ITEM
1. | FINANCIAL
STATEMENTS |
LIPOCINE
INC. AND SUBSIDIARIES
Condensed
Consolidated Balance Sheets
(Unaudited)
See
accompanying notes to unaudited condensed consolidated financial statements
LIPOCINE
INC. AND SUBSIDIARIES
Condensed
Consolidated Statements of Operations and Comprehensive Loss
(Unaudited)
See
accompanying notes to unaudited condensed consolidated financial statements
LIPOCINE
INC. AND SUBSIDIARIES
Condensed
Consolidated Statements of Changes in Stockholders’ Equity
For
the Three Months Ended March 31, 2022 and 2021
(Unaudited)
See
accompanying notes to unaudited condensed consolidated financial statements
LIPOCINE
INC. AND SUBSIDIARIES
Condensed
Consolidated Statements of Cash Flows
(Unaudited)
See
accompanying notes to unaudited condensed consolidated financial statements
LIPOCINE
INC.
Notes
to Condensed Consolidated Financial Statements
(Unaudited)
(1) Basis of Presentation
The
accompanying unaudited condensed consolidated financial statements included herein have been prepared by Lipocine Inc. (“Lipocine”
or the “Company”) in accordance with the rules and regulations of the United States Securities and Exchange Commission (“SEC”).
The unaudited condensed consolidated financial statements are comprised of the financial statements of Lipocine and its subsidiaries,
collectively referred to as the Company. In management’s opinion, the interim financial data presented includes all adjustments
(consisting solely of normal recurring items) necessary for fair presentation. All intercompany accounts and transactions have been eliminated.
Certain information required by U.S. generally accepted accounting principles has been condensed or omitted in accordance with rules
and regulations of the SEC. Operating results for the three months ended March 31, 2022 are not necessarily indicative of the results
that may be expected for any future period or for the year ending December 31, 2022.
These
unaudited condensed consolidated financial statements should be read in conjunction with the Company’s audited consolidated financial
statements and the notes thereto for the year ended December 31, 2021.
The
preparation of the unaudited condensed consolidated financial statements requires management to make estimates and assumptions relating
to reporting of the assets and liabilities and the disclosure of contingent assets and liabilities to prepare these condensed consolidated
financial statements and the reported amounts of revenues and expenses during the reporting period in conformity with U.S. generally
accepted accounting principles. Actual results could differ from these estimates.
The
Company believes that its existing capital resources, together with interest thereon, will be sufficient to meet its projected operating
requirements through at least March 31, 2023 which includes an on-going clinical study for LPCN 1148, compliance with regulatory requirements
and on-going litigation activities. The Company has based this estimate on assumptions that may prove to be wrong, and the Company could
utilize its available capital resources sooner than it currently expects if additional activities are performed by the Company including
clinical studies for LPCN 1148, LPCN 1144, LPCN 1111, LPCN 1107 and neuroactive steroids (“NAS”) including LPCN 1544 and
LPCN 2101. While the Company believes it has sufficient liquidity and capital resources to fund our projected operating requirements
through at least March 31, 2023, the Company will need to raise additional capital at some point through the equity or debt markets or
via out-licensing activities, before or after March 31, 2023, to support its operations. If the Company is unsuccessful in raising additional
capital, its ability to continue as a going concern will become a risk. Further, the Company’s operating plan may change, and the
Company may need additional funds to meet operational needs and capital requirements for product development, regulatory compliance and
clinical trial activities sooner than planned. In addition, the Company’s capital resources may be consumed more rapidly if it
pursues additional clinical studies for LPCN 1148, LPCN 1144, LPCN 1111, LPCN 1107, and NAS including LPCN 1154 and LPCN 2101. Conversely,
the Company’s capital resources could last longer if it reduces expenses, reduces the number of activities currently contemplated
under our operating plan, if it terminates, modifies the design or suspends on-going clinical studies, or if it terminates or settles
any on-going litigation activities.
(2) Revenue
The
Company generates most of its revenue from license and royalty arrangements. At inception of each contract, the Company identifies the
goods and services that have been promised to the customer and each of those that represent a distinct performance obligation, determines
the transaction price including any variable consideration, allocates the transaction price to the distinct performance obligations and
determines whether control transfers to the customer at a point in time or over time. Variable consideration is included in the transaction
price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur when
the uncertainty associated with the variable consideration is subsequently resolved. The Company reassess its reserves for variable consideration
at each reporting date and makes adjustments, if necessary, which may affect revenue and earnings in periods in which any such changes
become known.
See
Note 8 for a description of the license agreement with Antares Pharma, Inc. See Note 12 for a description of the agreement with Spriaso.
License
Fees. For distinct license performance obligations, upfront license fees are recognized when the Company satisfies the underlying
performance obligation. This generally occurs upon transfer of the right to use the Company’s licensed technology to the customer.
In addition, license arrangements may include contingent milestone payments, which are due following achievement by our licensee of specified
sales or regulatory milestones and the licensee and/or Company will fulfill its performance obligation prior to achievement of these
milestones. Because of the uncertainty of the milestone achievement, and/or the dependence on sales of our licensee, variable consideration
for contingent milestones is fully constrained and is not recognized as revenue until the milestone is achieved by our licensee, to the
extent collectability is reasonably certain.
Royalties.
Royalties revenue consists of sales-based and minimum royalties earned under licenses agreements for our products. Performance obligations
under these licenses, which consist of the right to use the Company’s proprietary technology, are satisfied at a point in time
corresponding with delivery of the underlying technology rights to the licensee, which is generally upon transfer of the licensed technology/product
to the customer. Sales-based royalties revenue represents variable consideration under the license agreements and is recognized in the
period a customer sells products incorporating the Company’s licensed technologies/products. The Company estimates sales-based
royalties revenue earned but unpaid at each reporting period using information provided by the licensee. The Company’s license
arrangements may also provide for minimum royalties, which the Company recognizes upon the satisfaction of the underlying performance
obligation, which generally occurs with delivery of the underlying technology rights to the licensee. Sales-based and minimum royalties
are generally due within 45 days after the end of each quarter in which they are earned.
Contract
Assets
Contract
assets consist of minimum royalty revenue earned in relation to the license agreement but not yet payable based on the terms of the contract.
The contract asset as of March 31, 2022 is related to the Antares License Agreement.
Revenue
Concentration
A
major customer is considered to be one that comprises more than 10% of the Company’s total revenues. There was no revenue recognized
for either the three months ended March 31, 2022, or March 31, 2021.
(3) Earnings (Loss) per Share
Basic
earnings (loss) per share is calculated by dividing net income (loss) available to common shareholders by the weighted average number
of common shares outstanding during the period. Diluted earnings (loss) per share is based on the weighted average number of common shares
outstanding plus, where applicable, the additional potential common shares that would have been outstanding related to dilutive options,
warrants and, unvested restricted stock units to the extent such shares are dilutive.
The
following table sets forth the computation of basic and diluted earnings (loss) per share of common stock for the three months ended
March 31, 2022 and 2021:
Schedule of Computation of Basic and Diluted Earnings (loss) Per Share of Common Stock
| |
Three
Months Ended March 31, | |
| |
2022 | | |
2021 | |
Basic
loss per share attributable to common stock: | |
| | | |
| | |
Numerator | |
| | | |
| | |
Net
loss | |
$ | (3,487,781 | ) | |
$ | (3,368,082 | ) |
| |
| | | |
| | |
Denominator | |
| | | |
| | |
Weighted
avg. common shares outstanding | |
| 88,309,628 | | |
| 81,881,392 | |
| |
| | | |
| | |
Basic
loss per share attributable to common stock | |
$ | (0.04 | ) | |
$ | (0.04 | ) |
| |
| | | |
| | |
Diluted
loss per share attributable to common stock: | |
| | | |
| | |
Numerator | |
| | | |
| | |
Net
loss | |
$ | (3,487,781 | ) | |
$ | (3,368,082 | ) |
Denominator | |
| | | |
| | |
Weighted
avg. common shares outstanding | |
| 88,309,628 | | |
| 81,881,392 | |
| |
| | | |
| | |
Diluted
loss per share attributable to common stock | |
$ | (0.04 | ) | |
$ | (0.04 | ) |
The
computation of diluted loss per share for the three months ended March 31, 2022 and 2021 does not include the following stock options
and warrants to purchase shares or unvested restricted stock units in the computation of diluted loss per share because these instruments
were antidilutive:
Schedule of Anti-dilutive Securities Excluded from Computation of Earnings Per Share
| |
March
31, | |
| |
2022 | | |
2021 | |
Stock
options | |
| 4,229,739 | | |
| 3,849,790 | |
Warrants | |
| 1,934,366 | | |
| 1,934,366 | |
(4) Marketable Investment Securities
The
Company has classified its marketable investment securities as available-for-sale securities, all of which are debt securities. These
securities are carried at fair value with unrealized holding gains and losses, net of the related tax effect, included in accumulated
other comprehensive income (loss) in stockholders’ equity until realized. Gains and losses on investment security transactions
are reported on the specific-identification method. Dividend income is recognized on the ex-dividend date and interest income is recognized
on an accrual basis. The amortized cost, gross unrealized holding gains, gross unrealized holding losses, and fair value for available-for-sale
securities by major security type and class of security as of March 31, 2022, and December 31, 2021, were as follows:
Schedule of Available-for-Sale Securities
March
31, 2022 | |
Amortized
Cost | | |
Gross
unrealized holding gains | | |
Gross
unrealized holding losses | | |
Aggregate
fair value | |
| |
| | |
| | |
| | |
| |
Government
treasury bills | |
$ | 9,525,107 | | |
$ | - | | |
$ | (44,622 | ) | |
| 9,480,485 | |
Corporate
bonds, notes and commercial paper | |
| 26,808,608 | | |
| - | | |
| (22,794 | ) | |
| 26,785,814 | |
| |
| | | |
| | | |
| | | |
| | |
| |
$ | 36,333,715 | | |
$ | - | | |
$ | (67,416 | ) | |
$ | 36,266,299 | |
December
31, 2021 | |
Amortized
Cost | | |
Gross
unrealized holding gains | | |
Gross
unrealized holding losses | | |
Aggregate
fair value | |
| |
| | |
| | |
| | |
| |
Government
treasury bills | |
$ | 5,526,122 | | |
$ | - | | |
$ | (10,202 | ) | |
$ | 5,515,920 | |
Corporate
bonds, notes and commercial paper | |
| 38,181,099 | | |
| - | | |
| (7,814 | ) | |
| 38,173,285 | |
| |
| | | |
| | | |
| | | |
| | |
| |
$ | 43,707,221 | | |
$ | - | | |
$ | (18,016 | ) | |
$ | 43,689,205 | |
Maturities
of debt securities classified as available-for-sale securities as of March 31, 2022, are as follows:
Schedule of Maturities of Debt Securities Classified as Available-for-sale Securities
March
31, 2022 | |
Amortized
Cost | | |
Aggregate
fair value | |
Due
within one year | |
$ | 36,333,715 | | |
$ | 36,266,299 | |
Due
after one year through two years | |
| - | | |
| - | |
| |
$ | 36,333,715 | | |
$ | 36,266,299 | |
There
were no sales of marketable investment securities during the three months ended March 31, 2022, and 2021 and therefore no realized gains
or losses. Additionally, $25.2 million and $450,000 of marketable investment securities matured during the three months ended March 31,
2022, and 2021, respectively. The Company determined there were no other-than-temporary impairments for the three months ended March
31, 2022, and 2021.
(5) Fair Value
The
Company utilizes valuation techniques that maximize the use of observable inputs and minimize the use of unobservable inputs to the extent
possible. The Company determines fair value based on assumptions that market participants would use in pricing an asset or liability
in the principal or most advantageous market. When considering market participant assumptions in fair value measurements, the following
fair value hierarchy distinguishes between observable and unobservable inputs, which are categorized in one of the following levels:
|
● |
Level
1 Inputs: Quoted prices for identical instruments in active markets. |
|
|
|
|
● |
Level
2 Inputs: Quoted prices for similar instruments in active markets, quoted prices for identical or similar instruments in markets
that are not active, and model-derived valuation in which all significant inputs and significant value drivers are observable in
active markets. |
|
|
|
|
● |
Level
3 Inputs: Valuations derived from valuation techniques in which one or more significant inputs or significant value drivers are unobservable.
|
All
of the Company’s financial instruments are valued using quoted prices in active markets or based on other observable inputs. For
accrued interest income, prepaid and other current assets, accounts payable, and accrued expenses, the carrying amounts approximate fair
value because of the short maturity of these instruments. The following table presents the placement in the fair value hierarchy of assets
and liabilities that are measured at fair value on a recurring basis as of March 31, 2022 and December 31, 2021:
Schedule of Fair Value, Assets Measured on Recurring Basis
| |
| | |
Fair
value measurements at reporting date using | |
| |
March
31, 2022 | | |
Level
1 inputs | | |
Level
2 inputs | | |
Level
3 inputs | |
| |
| | |
| | |
| | |
| |
Assets: | |
| | | |
| | | |
| | | |
| | |
Cash
equivalents - money market funds | |
$ | 4,933,293 | | |
$ | 4,933,293 | | |
$ | - | | |
$ | - | |
Government
treasury bills | |
| 9,480,485 | | |
| 9,480,485 | | |
| - | | |
| - | |
Commercial
paper | |
| 14,744,099 | | |
| - | | |
| 14,744,099 | | |
| - | |
Corporate
bonds and notes | |
| 12,041,715 | | |
| - | | |
| 12,041,715 | | |
| - | |
| |
| | | |
| | | |
| | | |
| | |
| |
$ | 41,199,592 | | |
$ | 14,413,778 | | |
$ | 26,785,814 | | |
$ | - | |
Liabilities: | |
| | | |
| | | |
| | | |
| | |
Warrant
liability | |
$ | 1,173,785 | | |
| - | | |
| - | | |
$ | 1,173,785 | |
| |
$ | 42,373,377 | | |
$ | 14,413,778 | | |
$ | 26,785,814 | | |
$ | 1,173,785 | |
| |
| | |
Fair
value measurements at reporting date using | |
| |
December
31, 2021 | | |
Level
1 inputs | | |
Level
2 inputs | | |
Level
3 inputs | |
| |
| | |
| | |
| | |
| |
Assets: | |
| | | |
| | | |
| | | |
| | |
Cash
equivalents - money market funds | |
$ | 2,089,751 | | |
$ | 2,089,751 | | |
$ | - | | |
$ | - | |
Government
treasury bills | |
| 5,515,920 | | |
| 5,515,920 | | |
| - | | |
| - | |
Commercial
paper | |
| 15,385,634 | | |
| - | | |
| 15,385,634 | | |
| - | |
Corporate
bonds and notes | |
| 22,787,651 | | |
| - | | |
| 22,787,651 | | |
| - | |
| |
| | | |
| | | |
| | | |
| | |
| |
$ | 45,778,956 | | |
$ | 7,605,671 | | |
$ | 38,173,285 | | |
$ | - | |
Liabilities: | |
| | | |
| | | |
| | | |
| | |
Warrant
liability | |
$ | 795,796 | | |
| - | | |
| - | | |
$ | 795,796 | |
| |
$ | 46,574,752 | | |
$ | 7,605,671 | | |
$ | 38,173,285 | | |
$ | 795,796 | |
The
following methods and assumptions were used to determine the fair value of each class of assets and liabilities recorded at fair value
in the balance sheets:
Cash
equivalents: Cash equivalents primarily consist of highly-rated money market funds and treasury bills with original maturities to the
Company of three months or less and are purchased daily at par value with specified yield rates. Cash equivalents related to money market
funds and treasury bills are classified within Level 1 of the fair value hierarchy because they are valued using quoted market prices
or broker or dealer quotations for similar assets.
Corporate
bonds, notes, and commercial paper: The Company uses a third-party pricing service to value these investments. Corporate bonds, notes
and commercial paper are classified within Level 2 of the fair value hierarchy because they are valued using broker/dealer quotes, bids
and offers, benchmark yields and credit spreads and other observable inputs.
Warrant
liability: The warrant liability (which relates to warrants to purchase shares of common stock)
is marked-to-market each reporting period with the change in fair value recorded to other income (expense) in the accompanying statements
of operations until the warrants are exercised, expire or other facts and circumstances lead the warrant liability to be reclassified
to stockholders’ equity. The fair value of the warrant liability is estimated using a Black-Scholes option-pricing model. The significant
assumptions used in preparing the option pricing model for valuing the warrant liability as of March 31, 2022, include (i) volatility
of 100%, (ii) risk free interest rate of 2.64%, (iii) strike price of $0.50, (iv) fair value of common stock of $1.38, and (v) expected
life of 2.63 years. The significant assumptions used in preparing the option pricing model for valuing the warrant liability as of December
31, 2021, include (i) volatility of 100%, (ii) risk free interest rate of 0.97%, (iii) strike price of $0.50, (iv) fair value of common
stock of $0.99, and (v) expected life of 2.88 years.
The
Company’s accounting policy is to recognize transfers between levels of the fair value hierarchy on the date of the event or change
in circumstances that caused the transfer. There were no transfers into or out of Level 1, Level 2, or Level 3 for the three months ended
March 31, 2022.
(6) Loan and Security Agreements
Silicon
Valley Bank Loan
On
January 5, 2018, the Company entered into a Loan and Security Agreement (the “Loan and Security Agreement”) with Silicon
Valley Bank (“SVB”) pursuant to which SVB agreed to lend the Company $10.0 million. The principal borrowed under the Loan
and Security Agreement bears interest at a rate equal to the Prime Rate, as reported in the money rates section of The Wall Street Journal
or any successor publication representing the rate of interest per annum then in effect, plus one percent per annum (4.5% as of March
31, 2022), which interest is payable monthly. Additionally on April 1, 2020, the Company entered into a Deferral Agreement with SVB.
Under the Deferral Agreement, principal repayments were deferred by six months and the Company was only required to make monthly interest
payments. The loan matures on June 1, 2022. Previously, the Company only made monthly interest payments until December 31, 2018, following
which the Company also made equal monthly payments of principal and interest until the signing of the Deferral Agreement. The Company
will also be required to pay an additional final payment at maturity equal to $650,000 (the “Final Payment Charge”). The
Final Payment Charge will be due on the scheduled maturity date and as of March 31, 2022, approximately $649,000 has been recognized
as an increase to the principal balance with a corresponding charge to interest expense with the remaining final payment charge to be
recognized over the term of the facility using the effective interest method. At its option, the Company may prepay all amounts owed
under the Loan and Security Agreement (including all accrued and unpaid interest and the Final Payment Charge).
In
connection with the Loan and Security Agreement, the Company granted to SVB a security interest in substantially all of the Company’s
assets now owned or hereafter acquired, excluding intellectual property and certain other assets. In addition, as TLANDO was not approved
by the United States Food and Drug Administration (“FDA”) prior to May 31, 2018, the Company maintained $5.0 million of cash
collateral at SVB as required under the Loan and Security Agreement until such time as TLANDO is approved by the FDA. However, on February
16, 2021, the Company amended the Loan and Security Agreement with SVB to, among other things, remove the financial trigger and financial
trigger release event provisions requiring the Company to maintain a minimum cash collateral value and collateral pledge thereof.
While
any amounts are outstanding under the Loan and Security Agreement, the Company is subject to a number of affirmative and negative covenants,
including covenants regarding dispositions of property, business combinations or acquisitions, incurrence of additional indebtedness
and transactions with affiliates, among other customary covenants. The credit facility also includes events of default, the occurrence
and continuation of which could cause interest to be charged at the rate that is otherwise applicable plus 5.0% and would provide SVB,
as collateral agent, with the right to exercise remedies against the Company and the collateral securing the credit facility, including
foreclosure against the property securing the credit facilities, including its cash. These events of default include, among other things,
any failure by the Company to pay principal or interest due under the credit facility, a breach of certain covenants under the credit
facility, the Company’s insolvency, a material adverse change, and one or more judgments against the Company in an amount greater
than $100,000 individually or in the aggregate.
Future
maturities of principal payments on the Loan and Security Agreement as of March 31, 2022, are as follows:
Schedule
of Future Maturities of Principal Payments
Years
Ending December 31, | |
Amount (in
thousands) | |
2022 | |
$ | 833 | |
Thereafter | |
| — | |
| |
$ | 833 | |
(7) Income Taxes
The
tax provision for interim periods is determined using an estimate of the Company’s effective tax rate for the full year adjusted
for discrete items, if any, that are taken into account in the relevant period. Each quarter the Company updates its estimate of the
annual effective tax rate, and if the estimated tax rate changes, the Company makes a cumulative adjustment.
At
March 31, 2022 and December 31, 2021, the Company had a full valuation allowance against its deferred tax assets, net of expected reversals
of existing deferred tax liabilities, as it believes it is more likely than not that these benefits will not be realized.
(8) Contractual Agreements
On
March 29, 2012, the Company terminated its collaborative agreement with Solvay Pharmaceuticals, Inc. (later acquired by Abbott Products,
Inc.) for TLANDO. As part of the termination, the Company reacquired the rights to the intellectual property from Abbott. All obligations
under the prior license agreement have been completed except that Lipocine will owe Abbott a perpetual 1% royalty on our licensee’s
net sales of TLANDO. Such royalties are limited to $1.0 million in the first two calendar years following product launch, after which
period there is not a cap on royalties and no maximum aggregate amount. If generic versions of any such product are introduced, then
royalties are reduced by 50%. The Company did not incur any royalties during the three months ended March 31, 2022, and 2021.
On
October 14, 2021, the Company entered into a license agreement (“License Agreement”) with Antares Pharma, Inc. (“Antares”)
pursuant to which the Company granted to Antares an exclusive, royalty-bearing, sublicensable right and license to develop and commercialize,
upon final approval of TLANDO® from the U.S. Food and Drug Administration (“FDA”), the Company’s TLANDO product
with respect to testosterone replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone,
as indicated in NDA No. 208088, treatment of Klinefelter syndrome, and pediatric indications relating to testosterone replacement therapy
in males for conditions associated with a deficiency or absence of endogenous testosterone (the “Field”), in each case within
the United States. The Antares License Agreement also provides Antares with an option, exercisable on or before March 31, 2022, to license
TLANDO XR, the Company’s potential once-daily oral product candidate for testosterone replacement therapy. On April 1, 2022, the
Company entered into the First Amendment to the License Agreement (the “Amendment”), pursuant to which the License Agreement
was amended to extend the deadline by which Antares shall exercise its option to license TLANDO XR to June 30, 2022. As consideration
for the Company agreeing to enter into the Amendment, in April 2022 Antares paid the Company a non-refundable cash fee of $500,000 which
will be creditable toward the license fee agreed to in the License Agreement of $4 million. Upon execution of the Antares License Agreement,
Antares paid to the Company an initial payment of $11.0 million. Antares will also make additional payments of $5.0 million to the Company
on each of January 1, 2025, and January 1, 2026, provided that certain conditions are satisfied. The Company is also eligible to receive
milestone payments of up to $160.0 million in the aggregate, depending on the achievement of certain sales milestones in a single calendar
year with respect to all products licensed by Antares under the Antares License Agreement. In addition, upon commercialization, the Company
will receive tiered royalty payments at rates ranging from percentages in the mid-teens to up to 20% of net sales of TLANDO in the United
States, subject to certain minimum royalty obligations. If Antares exercises its option to license TLANDO XR, the Company will be entitled
to an additional payment of $3.5 million, as well as development milestone payments of up to $35.0 million in the aggregate and tiered
royalty payments at rates ranging from percentages in the mid-teens to 20% of net sales of TLANDO XR in the United States. The Company
retains development and commercialization rights in the rest of the world, and with respect to applications outside of the Field inside
or outside the United States. Antares will also purchase certain existing inventory of licensed products from the Company, subject to
testing and acceptance procedures. Finally, pursuant to the terms of the Antares License Agreement, Antares is generally responsible
for expenses relating to the development (including the conduct of any clinical trials) and commercialization of licensed products in
the Field in the United States, while the Company is generally responsible for expenses relating to development activities outside of
the Field and/or the United States. The Company did not recognize any revenue under the Antares Licensing Agreement during either the
three months ended March 31, 2022, or March 31, 2021.
| (c) | Contract
Research and Development |
The
Company has entered into agreements with various contract organizations that conduct preclinical, clinical, analytical and manufacturing
development work on behalf of the Company as well as a number of independent contractors and primarily clinical researchers who serve
as advisors to the Company. The Company incurred expenses of $1.0 million and $837,000, respectively, for the three months ended March
31, 2022 and 2021 under these agreements and has recorded these expenses in research and development expenses.
(9) Leases
The
Company has a non-cancelable operating lease for office space and laboratory facilities in Salt Lake City, Utah. The term of the lease
has been extended through February 28, 2023.
Future
minimum lease payments under non-cancelable operating leases as of March 31, 2022 are:
Schedule of Future Minimum Rental Payments for Operating Leases
| |
Operating | |
| |
leases | |
Quarter
ending March 31: | |
| | |
2022 | |
$ | 257,729 | |
2023 | |
| 57,273 | |
| |
| | |
Total
minimum lease payments | |
$ | 315,002 | |
The
Company’s rent expense was $84,000 and $83,000 for each of the three months ended March 31, 2022 and 2021, respectively.
(10) Stockholders’ Equity
| (a) | Issuance
of Common Stock |
On
January 28, 2021, the Company completed a public offering of securities registered under an effective registration statement filed pursuant
to the Securities Act of 1933, as amended (“January 2021 Offering”). The gross proceeds from the January 2021 Offering were
approximately $28.7 million, before deducting underwriter fees and other offering expenses of $1.9 million. In the January 2021 Offering,
the Company sold 16,428,571 shares of its common stock.
On
February 27, 2020, the Company completed a registered direct offering of securities registered under an effective registration statement
filed pursuant to the Securities Act of 1933, as amended (“February 2020 Offering”). The gross proceeds from the February
2020 Offering were approximately $6.0 million, before deducting placement agent fees and other offering expenses of $347,000. In the
February 2020 Offering, the Company sold 10,084,034 Class A Units at an offering price of $0.595 per unit, with each Class A Unit consisting
of one share of its common stock and one-half of a common warrant to purchase one share of common stock at an exercise price of $0.53
per share of common stock. Additionally, the common stock warrants were immediately exercisable and expire on February 27, 2025. By their
terms, however, the common stock warrants cannot be exercised at any time that the common stock warrant holder would beneficially own,
after such exercise, more than 4.99% (or, at the election of the holder, 9.99%) of the shares of common stock then outstanding after
giving effect to such exercise.
On
November 18, 2019, the Company completed a public offering of securities registered under an effective registration statement filed pursuant
to the Securities Act of 1933, as amended (“November 2019 Offering”). The gross proceeds from the November 2019 Offering
were approximately $6.0 million, before deducting placement agent fees and other offering expenses of $404,000. In the November 2019
Offering, the Company sold (i) 10,450,000 Class A Units, with each Class A Unit consisted of one share of its common stock and a common
warrant to purchase one share of its common stock, and (ii) 1,550,000 Class B Units, with each Class B Unit consisting of one pre-funded
warrant to purchase one share of its common stock and a common warrant to purchase one share of its common stock, at a price of $0.50
per Class A Unit and $0.4999 per Class B Unit. The pre-funded warrants, which were exercised for common stock in December 2019, were
issued in lieu of common stock in order to ensure the purchaser did not exceed certain beneficial ownership limitations. The pre-funded
warrants were immediately exercisable at an exercise price of $.0001 per share, subject to adjustment. Additionally, the common stock
warrants were immediately exercisable at an exercise price of $0.50 per share, subject to adjustment, and expire on November 17, 2024.
By their terms, however, neither the pre-funded warrants nor the common stock warrants can be exercised at any time that the pre-funded
warrant holder or the common stock warrant holder would beneficially own, after such exercise, more than 4.99% (or, at the election of
the holder, 9.99%) of the shares of common stock then outstanding after giving effect to such exercise. On the date of the November 2019
Offering, the Company allocated approximately $768,000 and $4.8 million to common stock/additional paid-in capital and warrant liability,
respectively.
On
March 6, 2017, the Company entered into the Sales Agreement with Cantor Fitzgerald & Co. (“Cantor”) pursuant to which
the Company may issue and sell, from time to time, shares of its common stock having an aggregate offering price of up to the amount
the Company registered on an effective registration statement pursuant to which the offering is being made. The Company currently has
registered up to $50.0 million for sale under the Sales Agreement, pursuant to the Registration Statement on Form S-3 (File No. 333-250072)
through Cantor as the Company’s sales agent. Cantor may sell the Company’s common stock by any method permitted by law deemed
to be an “at the market offering” as defined in Rule 415(a)(4) of the Securities Act, including sales made directly on or
through the Nasdaq Capital Market or any other existing trade market for our common stock, in negotiated transactions at market prices
prevailing at the time of sale or at prices related to prevailing market prices, or any other method permitted by law. Cantor uses its
commercially reasonable efforts consistent with its normal trading and sales practices and applicable law and regulations to sell these
shares. The Company pays Cantor 3.0% of the aggregate gross proceeds from each sale of shares under the Sales Agreement. In addition,
the Company has also provided Cantor with customary indemnification rights.
The
shares of the Company’s common stock sold under the Sales Agreement are sold and issued pursuant to the Registration Statement
on Form S-3 (File No. 333-250072) (the “Form S-3”), which was previously declared effective by the Securities and Exchange
Commission, and the related prospectus and one or more prospectus supplements.
The
Company is not obligated to make any sales of its common stock under the Sales Agreement. The offering of common stock pursuant to the
Sales Agreement will terminate upon the termination of the Sales Agreement as permitted therein. The Company and Cantor may each terminate
the Sales Agreement at any time upon ten days’ prior notice.
As
of March 31, 2022, we had sold an aggregate of 15,023,073 shares at a weighted-average sales price of $2.19 per share under the ATM for
aggregate gross proceeds of $32.9 million and net proceeds of $31.7 million, after deducting sales agent commission and discounts and
our other offering costs. During the three months ended March 31, 2022, the Company did not sell any shares of our common stock pursuant
to the Sales Agreement. During the three months ended March 31, 2021, the Company sold 1,811,238 shares of our common stock pursuant
to the Sales Agreement at a weighted-average sales price of $1.95 per share, resulting in net proceeds of approximately $3.4 million
under the Sales Agreement, which is net of $112,000 in expenses. As of March 31, 2022, the Company had $41.2 million available for sale
under the Sales Agreement.
On
November 13, 2015, the Company and American Stock Transfer & Trust Company, LLC, as Rights Agent, entered into a Rights Agreement.
Also on November 12, 2015, the board of directors of the Company authorized and the Company declared a dividend of one preferred stock
purchase right (each a “Right” and collectively, the “Rights”) for each outstanding share of common stock of
the Company. The dividend was payable to stockholders of record as of the close of business on November 30, 2015 and entitles the registered
holder to purchase from the Company one one-thousandth of a fully paid non-assessable share of Series A Junior Participating Preferred
Stock of the Company at a price of $63.96 per one-thousandth share (the “Purchase Price”). The Rights will generally become
exercisable upon the earlier to occur of (i) 10 business days following a public announcement that a person or group of affiliated or
associated persons has become an Acquiring Person (as defined below) or (ii) 10 business days (or such later date as may be determined
by action of the board of directors prior to such time as any person or group of affiliated or associated persons becomes an Acquiring
Person) following the commencement of, or announcement of an intention to make, a tender offer or exchange offer the consummation of
which would result in the beneficial ownership by a person or group of 15% or more of the outstanding common stock of the Company. Except
in certain situations, a person or group of affiliated or associated persons becomes an “Acquiring Person” upon acquiring
beneficial ownership of 15% or more of the outstanding shares of common stock of the Company.
In
general, in the event a person becomes an Acquiring Person, then each Right not owned by such Acquiring Person will entitle its holder
to purchase from the Company, at the Right’s then current exercise price, in lieu of shares of Series A Junior Participating Preferred
Stock, common stock of the Company with a market value of twice the Purchase Price. In addition, if after any person has become an Acquiring
Person, (a) the Company is acquired in a merger or other business combination, or (b) 50% or more of the Company’s assets, or assets
accounting for 50% or more of its earning power, are sold, leased, exchanged or otherwise transferred (in one or more transactions),
proper provision shall be made so that each holder of a Right (other than the Acquiring Person, its affiliates and associates and certain
transferees thereof, whose Rights became void) shall thereafter have the right to purchase from the acquiring corporation, for the Purchase
Price, that number of shares of common stock of the acquiring corporation which at the time of such transaction would have a market value
of twice the Purchase Price.
The
Company will be entitled to redeem the Rights at $0.001 per Right at any time prior to the time an Acquiring Person becomes such. The
terms of the Rights are set forth in the Rights Agreement, which is summarized in the Company’s Current Report on Form 8-K dated
November 13, 2015. The rights plan was originally set to expire on November 12, 2018; however, on November 5, 2018 our Board of Directors
approved an Amended and Restated Rights Agreement pursuant to which the expiration date was extended to November 5, 2021, and again on
November 1, 2021, the Company adopted a Second Amended and Restated Rights Agreement pursuant to which the expiration date was extended
to November 1, 2024, unless the rights are earlier redeemed or exchanged by the Company.
The
Company recognizes stock-based compensation expense for grants of stock option awards, restricted stock units and restricted stock under
the Company’s Incentive Plan to employees, nonemployees and nonemployee members of the Company’s board of directors based
on the grant-date fair value of those awards. The grant-date fair value of an award is generally recognized as compensation expense over
the award’s requisite service period. In addition, the Company has granted performance-based stock option awards and restricted
stock units, which vest based upon the Company satisfying certain performance conditions. Potential compensation cost, measured on the
grant date, related to these performance options will be recognized only if, and when, the Company estimates that these options or units
will vest, which is based on whether the Company considers the performance conditions to be probable of attainment. The Company’s
estimates of the number of performance-based options or units that will vest will be revised, if necessary, in subsequent periods.
The
Company uses the Black-Scholes model to compute the estimated fair value of stock option awards. Using this model, fair value is calculated
based on assumptions with respect to (i) expected volatility of the Company’s common stock price, (ii) the periods of time over
which employees and members of the board of directors are expected to hold their options prior to exercise (expected term), (iii) expected
dividend yield on the Common Stock, and (iv) risk-free interest rates. Stock-based compensation expense also includes an estimate, which
is made at the time of grant, of the number of awards that are expected to be forfeited. This estimate is revised, if necessary, in subsequent
periods if actual forfeitures differ from those estimates. Stock-based compensation cost that has been expensed in the statements of
operations amounted to approximately $171,000 and $148,000, respectively, for the three months ended March 31, 2022 and 2021 and
is allocated as follows:
Schedule of Employee Service Share-based Compensation, Allocation of Recognized Period Costs
| |
Three
Months Ended
March 31, | |
| |
2022 | | |
2021 | |
| |
| | |
| |
Research
and development | |
$ | 79,652 | | |
$ | 66,887 | |
General
and administrative | |
| 91,376 | | |
| 80,679 | |
| |
| | | |
| | |
| |
$ | 171,028 | | |
$ | 147,566 | |
The
Company issued 332,500 and 310,000 stock options, respectively, during the three months ended March 31, 2022 and 2021.
Key
assumptions used in the determination of the fair value of stock options granted are as follows:
Expected
Term: The expected term represents the period that the stock-based awards are expected to be outstanding. Due to limited historical
experience of similar awards, the expected term was estimated using the simplified method in accordance with the provisions of Staff
Accounting Bulletin (“SAB”) No. 107, Share-Based Payment, for awards with stated or implied service periods. The simplified
method defines the expected term as the average of the contractual term and the vesting period of the stock option. For awards with performance
conditions, and that have the contractual term to satisfy the performance condition, the contractual term was used.
Risk-Free
Interest Rate: The risk-free interest rate used was based on the implied yield currently available on U.S. Treasury issues with an
equivalent remaining term.
Expected
Dividend: The expected dividend assumption is based on management’s current expectation about the Company’s anticipated
dividend policy. The Company does not anticipate declaring dividends in the foreseeable future.
Expected
Volatility: The volatility factor is based solely on the Company’s trading history.
For
options granted during the three months ended March 31, 2022 and 2021, the Company calculated the fair value of each option grant on
the respective dates of grant using the following weighted average assumptions:
Schedule of Key Assumption of Fair Value of Stock Options Granted
| |
2022 | | |
2021 | |
Expected
term | |
| 5.85
years | | |
| 5.85
years | |
Risk-free
interest rate | |
| 1.41 | % | |
| 0.47 | % |
Expected
dividend yield | |
| 0.00 | % | |
| 0.00 | % |
Expected
volatility | |
| 102.43 | % | |
| 100.96 | % |
FASB
ASC 718, Stock Compensation, requires the Company to recognize compensation expense for the portion of options that are expected
to vest. Therefore, the Company applied estimated forfeiture rates that were derived from historical employee termination behavior. If
the actual number of forfeitures differs from those estimated by management, additional adjustments to compensation expense may be required
in future periods.
As
of March 31, 2022, there was $1.2 million of total unrecognized compensation cost related to unvested share-based compensation arrangements
granted under the Company’s stock option plan. That cost is expected to be recognized over a weighted average period of 2.23 years
and will be adjusted for subsequent changes in estimated forfeitures.
In
April 2014, the board of directors adopted the 2014 Stock and Incentive Plan (“2014 Plan”) subject to shareholder approval
which was received in June 2014. The 2014 Plan provides for the granting of nonqualified and incentive stock options, stock appreciation
rights, restricted stock units, restricted stock and dividend equivalents. The 2014 Plan has been amended and restated several times
to increase the authorized number of shares of common stock of the Company issuable under all awards granted under the 2014 Plan. The
board of directors, on an option-by-option basis, determines the number of shares, exercise price, term, and vesting period for options
granted. Options granted generally have a ten-year contractual life. The Company issues shares of common stock upon the exercise of options
with the source of those shares of common stock being either newly issued shares or shares held in treasury. An aggregate of 5,721,906
shares are authorized for issuance under the 2014 Plan, with 1,062,651 shares remaining available for grant as of March 31, 2022.
A
summary of stock option activity is as follows:
Schedule of Stock Option Activity
| |
Outstanding
stock options | |
| |
Number
of shares | | |
Weighted
average exercise price | |
Balance
at December 31, 2021 | |
| 4,551,205 | | |
$ | 2.82 | |
Options
granted | |
| 332,500 | | |
| 1.09 | |
Options
exercised | |
| (208,274 | ) | |
| 0.99 | |
Options
forfeited | |
| (445,692 | ) | |
| 1.16 | |
Balance
at March 31, 2022 | |
| 4,229,739 | | |
| 2.94 | |
| |
| | | |
| | |
Options
exercisable at March 31, 2022 | |
| 2,796,497 | | |
| 3.87 | |
The
following table summarizes information about stock options outstanding and exercisable at March 31, 2022:
Schedule of Share-based Compensation of Stock Options Outstanding and Exercisable
Options
outstanding | | |
Options
exercisable | |
Number
outstanding | | |
Weighted
average remaining contractual life (Years) | | |
Weighted
average exercise price | | |
Aggregate
intrinsic value | | |
Number
exercisable | | |
Weighted
average remaining contractual life (Years) | | |
Weighted
average exercise price | | |
Aggregate
intrinsic value | |
| | | |
| | | |
| | | |
| | | |
| | | |
| | | |
| | | |
| | |
| 4,229,739 | | |
| 5.97 | | |
$ | 2.94 | | |
$ | 666,686 | | |
| 2,796,497 | | |
| 4.30 | | |
$ | 3.87 | | |
$ | 330,331 | |
The
intrinsic value for stock options is defined as the difference between the current market value and the exercise price. There were 208,274
and 4,584 stock options exercised during the three months ended March 31, 2022, and March 31, 2021, respectively.
The
Company accounts for its common stock warrants under ASC 480, Distinguishing Liabilities from Equity, which requires any financial
instrument, other than an outstanding share, that, at inception, embodies an obligation to repurchase the issuer’s equity shares,
or is indexed to such an obligation, and requires or may require the issuer to settle the obligation by transferring assets, to be classified
as a liability. In accordance with ASC 480, the Company’s outstanding warrants from the November 2019 Offering are classified as
a liability. The liability is adjusted to fair value at each reporting period, with the changes in fair value recognized as gain (loss)
on change in fair value of warrant liability in the Company’s consolidated statements of operations. The warrants issued in the
November 2019 Offering allow the warrant holder, if certain change in control events occur, the option to receive an amount of cash equal
to the value of the warrants as determined in accordance with the Black-Scholes option pricing model with certain defined assumptions
upon a fundamental transaction.
As
of March 31, 2022, the Company had 1,094,030 common stock warrants outstanding from the November 2019 Offering to purchase an equal number
of shares of common stock. The fair value of these warrants on March 31, 2022, and on December 31, 2021. was determined using the Black-Scholes
option pricing model with the following Level 3 inputs (as defined in the November 2019 Offering):
Schedule of Fair Value of Warrants
| |
March
31, 2022 | | |
December
31, 2021 | |
Expected
life in years | |
| 2.63 | | |
| 2.88 | |
Risk-free
interest rate | |
| 2.64 | % | |
| 0.97 | % |
Dividend
yield | |
| — | | |
| — | |
Volatility | |
| 100.00 | % | |
| 100.00 | % |
Stock
price | |
$ | 1.38 | | |
$ | 0.99 | |
During
the three months ended March 31, 2022, and March 31, 2021, the Company recorded a non-cash loss of approximately $378,000 and $195,000,
respectively, from the change in fair value of the November 2019 Offering warrants. The following table is a reconciliation of the warrant
liability measured at fair value using level 3 inputs:
Schedule of Reconciliation of Warrant Liability
| |
Warrant
Liability | |
Balance
at December 31, 2021 | |
$ | 795,796 | |
Settlement
of liability on warrant exercise | |
| - | |
Change
in fair value of common stock warrants | |
| 377,989 | |
Balance
at March 31, 2022 | |
$ | 1,173,785 | |
Additionally,
in the February 2020 Offering, the Company issued 5,042,017 common stock warrants, however, because these warrants do not provide the
warrant holder the option to put the warrant back to the Company, the warrants are classified as equity. As of March 31, 2022, and March
31, 2021, there were 840,336 warrants outstanding that were issued in conjunction with the February 2020 Offering.
There
were no common stock warrants exercised during the three months ended March 31, 2022. During the three months ended March 31, 2021, 10,000
common stock warrants to purchase one share of our common stock were exercised, resulting in proceeds of approximately $5,000 in the
three months ended March 31, 2021.
The
following table summarizes information about common stock warrants outstanding at March 31, 2022:
Schedule of Number of Weighted Average Exercise Price
Warrants
outstanding | |
Number
exercisable | | |
Weighted
average remaining contractual life (Years) | | |
Weighted
average exercise price | | |
Aggregate
intrinsic value | |
| | | |
| | | |
| | | |
| | |
| 1,934,366 | | |
| 2.75 | | |
$ | 0.51 | | |
$ | 1,657,688 | |
(11) Commitments and Contingencies
Litigation
The
Company is involved in various lawsuits, claims and other legal matters from time to time that arise in the ordinary course of conducting
business. The Company records a liability when a particular contingency is probable and estimable.
On
April 2, 2019, the Company filed a lawsuit against Clarus in the United States District Court for the District of Delaware alleging that
Clarus’s JATENZO® product infringes six of Lipocine’s issued U.S. patents: 9,034,858; 9,205,057; 9,480,690; 9,757,390;
6,569,463; and 6,923,988. However, on February 11, 2020, the Company voluntarily dismissed allegations of patent infringement for expired
U.S. Patent Nos. 6,569,463 and 6,923,988 in an effort to streamline the issues and associated costs for dispute. Clarus answered the
complaint and asserted counterclaims of non-infringement and invalidity. The Company answered Clarus’s counterclaims on April 29,
2019. The Court held a scheduling conference on August 15, 2019, a claim construction hearing on February 11, 2020, and a summary judgment
hearing on January 15, 2021. In May 2021, the Court granted Clarus’ motion for Summary Judgment, finding the asserted claims of
Lipocine’s U.S. patents 9,034,858; 9,205,057; 9,480,690; and 9,757,390 invalid for failure to satisfy the written description requirement
of 35 U.S.C. § 112. Clarus still had remaining claims before the Court. On July 13, 2021, the Company entered into the Global Agreement
with Clarus which resolved all outstanding claims of this litigation as well as the on-going United States Patent and Trademark Office
(“USPTO”) Interference No. 106,128 between the parties. Under the terms of the Global Agreement, the Company agreed to pay
Clarus $4.0 million payable as follows: $2.5 million immediately, $1.0 million on July 13, 2022 and $500,000 on July 13, 2023. On April
29, 2022, the Company agreed to an amendment to Section 3.1 of the Global Agreement, pursuant to which the Company agreed to pay Clarus
$1,250,000 in May 2022, with no additional payments required thereafter. No future royalties are owing from either party. On July 15,
2021, the Court dismissed with prejudice the Company’s claims and Clarus’ counterclaims.
On
November 14, 2019, the Company and certain of our officers were named as defendants in a purported shareholder class action lawsuit,
Solomon Abady v. Lipocine Inc. et al., 2:19-cv-00906-PMW, filed in the United District Court for the District of Utah. The complaint
alleges that the defendants made false and/or misleading statements and/or failed to disclose that the Company’s filing of the
NDA for TLANDO to the FDA contained deficiencies and as a result the defendants’ statements about our business and operations were
false and misleading and/or lacked a reasonable basis in violation of federal securities laws. The lawsuit seeks certification as a class
action (for a purported class of purchasers of the Company’s securities from March 27, 2019 through November 8, 2019), compensatory
damages in an unspecified amount, and unspecified equitable or injunctive relief. The Company has insurance that covers claims of this
nature. The retention amount payable by us under our policy is $1.25 million. The Company filed a motion to dismiss this class action
lawsuit on July 24, 2020. In response, the plaintiffs filed their response to the motion to dismiss the class action lawsuit on September
22, 2020, and the Company filed its reply to the motion to dismiss on October 22, 2020. A hearing on the motion to dismiss occurred on
January 12, 2022. The Company intends to vigorously defend ourselves against these allegations and have not recorded a liability related
to this shareholder class action lawsuit as the outcome is not probable nor can an estimate be made of loss, if any.
On
March 13, 2020, the Company filed U.S. patent application serial number 16/818,779 (the “Lipocine ‘779 Application”)
with the USPTO. On October 16 and November 3, 2020, the Company filed suggestions for interference with the USPTO requesting that a patent
interference be declared between the Lipocine ‘779 Application and US patent application serial number 16/656,178 to Clarus Therapeutics,
Inc. (the “Clarus ‘178 Application”). Pursuant to our request, the Patent Trial and Appeal Board (“PTAB”)
at the USPTO declared the interference on January 4, 2021 to ultimately determine, as between the Company and Clarus, who is entitled
to the claimed subject matter. The interference number is 106,128, and we were initially declared Senior Party. A conference call with
the PTAB was held on January 25, 2021 to discuss proposed motions. On February 1, 2021, the PTAB issued an order authorizing certain
motions and setting the schedule for the preliminary motions phase. On July 13, 2021, the Company entered into the Global Agreement with
Clarus to resolve interference No. 106,128 among other items. On July 26, 2021, the PTAB granted the Company’s request for adverse
judgment in interference No. 106,128 in accordance with the Global Agreement.
Beyond
Solomon Abady v. Lipocine Inc. et al., 2:19-cv-00906-PM
matter, management does not currently believe that any other matter, individually or in the aggregate, will have a material adverse effect
on our financial condition, liquidity or results of operations.
Guarantees
and Indemnifications
In
the ordinary course of business, the Company enters into agreements, such as lease agreements, licensing agreements, clinical trial agreements,
and certain services agreements, containing standard guarantee and / or indemnification provisions. Additionally, the Company has indemnified
its directors and officers to the maximum extent permitted under the laws of the State of Delaware.
(12) Agreement with Spriaso, LLC
The
Company has a license and a services agreement with Spriaso, a related-party that is majority-owned by certain current and former directors
of Lipocine Inc. and their affiliates. Under the license agreement, the Company assigned and transferred to Spriaso all of the Company’s
rights, title and interest in its intellectual property to develop products for the cough and cold field. In addition, Spriaso received
all rights and obligations under the Company’s product development agreement with a third-party. In exchange, the Company will
receive a royalty of 20 percent of the net proceeds received by Spriaso, up to a maximum of $10.0 million. Spriaso also granted back
to the Company an exclusive license to such intellectual property to develop products outside of the cough and cold field. The Company
also agreed to continue providing up to 10 percent of the services of certain employees to Spriaso for a period of time. The agreement
to provide services expired in 2021; however, it may be extended upon written agreement of Spriaso and the Company. The Company did not
receive any reimbursements from Spriaso for the three months ended March 31, 2022 and 2021, respectively. Additionally, during the three
months ended March 31, 2022 and 2021, the Company did not receive any royalty revenue from Spriaso. Spriaso filed its first NDA and as
an affiliated entity of the Company, it used up the one-time waiver for user fees for a small business submitting its first human drug
application to the FDA. Spriaso is considered a variable interest entity under the FASB ASC Topic 810-10, Consolidations, however the
Company is not the primary beneficiary and has therefore not consolidated Spriaso.
(13) Recent Accounting Pronouncements
Accounting
Pronouncements Issued Not Yet Adopted
In
2016, the FASB issued Accounting Standards Update (“ASU”) 2016-13, Measurement of Credit Losses on Financial Instruments
(“ASU 2016-13”). This standard replaces the incurred loss impairment methodology in current GAAP with a methodology that
reflects expected credit losses on instruments within its scope, including trade receivables, and requires entities to measure all expected
credit losses for financial assets held at the reporting date based on historical experience, current conditions and reasonable and supportable
forecasts. The original effective date for ASU 2016-13 was for annual and interim periods beginning after December 15, 2019.
However,
in October 2019, the FASB issued ASU 2019-10, Financial Instruments - Credit Losses, Derivatives and Hedging, and Leases: Effective
Dates, which deferred the effective date of ASU 2016-13 for certain entities, including those that are eligible to be smaller reporting
companies. A company’s determination about whether it is eligible for the deferral is a one-time assessment as of November
15, 2019, based on its most recent determination of its small reporting company eligibility as of the last business day of the most recently
completed second quarter. Based on this determination, the Company qualifies as a smaller reporting entity and is therefore eligible
for the deferral of adoption of ASU 2016-13, resulting in a new effective date of January 1, 2023. The Company has historically not had
credit losses on financial instruments and is currently evaluating the impact the adoption of ASU 2016-13 will have on its consolidated
financial statements.
(14) Subsequent Events
Amendment
to Antares License Agreement
The
Antares License Agreement provides Antares with an option, exercisable on or before March 31, 2022, to license TLANDO XR, the Company’s
potential once-daily oral product candidate for testosterone replacement therapy. On April 1, 2022, the Company entered into the First
Amendment to the License Agreement (the “Amendment”) with Antares, pursuant to which the License Agreement was amended to
extend the deadline by which Antares shall exercise its option to license TLANDO XR to June 30, 2022. As consideration for the Company
agreeing to enter into the Amendment, in April 2022 Antares paid the Company a non-refundable cash fee of $500,000 which will be creditable
toward the license fee agreed to in the License Agreement of $4 million. If Antares exercises its option to license TLANDO XR, the Company
will be entitled to additional upfront payments in 2022 totaling $3.5 million, as well as development milestone payments of up to $35.0
million in the aggregate, and tiered royalty payments at rates ranging from percentages in the mid-teens to 20% of net sales of TLANDO
XR in the United States.
Amendment
to Global Agreement with Clarus
On
April 29, 2022, the Company entered into an amendment to the Global Agreement with Clarus, pursuant to which installment payment provisions
and amounts of Section 3.1 of the Global Agreement were amended. The terms of the original Agreement provided for the Company to make
two installment payments to Clarus: $1,000,000 on or before the twelve-month anniversary of the Global Agreement, and $500,000 on or
before the twenty-four-month anniversary of the Agreement. Under the terms of the amendment, the Company will make one payment of $1,250,000
in May 2022, and no additional payments thereafter. All remaining provisions of the Global Agreement remain unchanged.
ITEM
2. | MANAGEMENT’S
DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS |
The
following discussion of our financial condition and results of operations should be read in conjunction with our unaudited condensed
consolidated financial statements and the related notes thereto and other financial information included elsewhere in this report. For
additional context with which to understand our financial condition and results of operations, see the management’s discussion
and analysis included in our Form 10-K, filed with the SEC on March 9, 2022 as well as the financial statements and related notes contained
therein.
As
used in the discussion below, “we,” “our,” and “us” refers to Lipocine.
Forward-Looking
Statements
This
section and other parts of this report contain forward-looking statements within the meaning of Section 27A of the Securities Act of
1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, that involve risks and uncertainties. Forward-looking
statements provide current expectations of future events based on certain assumptions and include any statement that does not directly
relate to any historical or current fact. Forward-looking statements may refer to such matters as products, product benefits, pre-clinical
and clinical development timelines, clinical and regulatory expectations and plans, expected responses to regulatory actions, anticipated
financial performance, future revenues or earnings, business prospects, projected ventures, new products and services, anticipated market
performance, expected research and development and other expenses, future expectations for liquidity and capital resources needs and
similar matters. Such words as “may”, “will”, “expect”, “continue”, “estimate”,
“project”, and “intend” and similar terms and expressions are intended to identify forward looking statements.
Forward-looking statements are not guarantees of future performance and our actual results may differ significantly from the results
discussed in the forward-looking statements. Factors that might cause such differences include, but are not limited to, those discussed
in Part II, Item 1A (Risk Factors) of this Form 10-Q, or in Part I, Item 1A (Risk Factors) of our Form 10-K filed with the SEC on March
9, 2022. Except as required by applicable law, we assume no obligation to revise or update any forward-looking statements for any reason.
Overview
of Our Business
We
are a clinical-stage biopharmaceutical company focused on neuroendocrine and metabolic disorders using our proprietary oral drug delivery
technology. Our proprietary delivery technologies are designed to improve patient compliance and safety through orally available treatment
options. Our primary development programs are based on oral delivery solutions for poorly bioavailable drugs. We have a portfolio of
differentiated innovative product candidates that target high unmet needs for neurological and psychiatric CNS disorders, liver diseases,
and hormone supplementation for men and women.
We
entered into a license agreement for the development and commercialization our product candidate, TLANDO®, an oral testosterone replacement
therapy (“TRT”) comprised of testosterone undecanoate (“TU”). TLANDO is a registered trademark assigned to Antares.
On October 14, 2021, we entered into a license agreement (the “Antares License Agreement”) with Antares Pharma, Inc. (“Antares”
or our “Licensee”), pursuant to which we granted to Antares an exclusive, royalty-bearing, sublicensable right and license
to develop and commercialize, upon final approval of TLANDO from the United States Food and Drug Administration (“FDA”),
the TLANDO product for TRT in the U.S. Any FDA required post-marketing studies will also be the responsibility of our licensee, Antares.
On March 28, 2022, Antares received approval from the FDA for TLANDO as a TRT in adult males for conditions associated with a deficiency
of endogenous testosterone, also known as hypogonadism.
Additional
pipeline candidates include: LPCN 1148 comprising a novel prodrug of testosterone, testosterone laurate (“TL”), for the management
of decompensated cirrhosis; LPCN 1144, an oral prodrug of androgen receptor modulator for the treatment of non-cirrhotic non-alcoholic
steatohepatitis (“NASH”) which has completed phase 2 testing; LPCN 1111 (TLANDO® XR), a next generation oral TRT product
comprised of testosterone tridecanoate (“TT”) with the potential for once daily dosing which has completed Phase 2 testing;
; LPCN 1107, potentially the first oral hydroxy progesterone caproate (“HPC”) product indicated for the prevention of recurrent
preterm birth (“PTB”), which has completed a dose finding clinical study in pregnant women and has been granted orphan drug
designation by the FDA; and neuroactive steroids (NAS) including LPCN 1154 for postpartum depression (PPD) and LPCN 2101 for epilepsy.
The
following chart summarizes the status of our product candidate development programs:
To
date, we have funded our operations primarily through the sale of equity securities, debt and convertible debt and through up-front payments,
research funding and royalty and milestone payments from our license and collaboration arrangements. We have not generated any revenues
from product sales and we do not expect to generate revenue other than TLANDO royalties and license fees from product sales by Antares
unless and until we obtain regulatory approval of our product candidates.
We
have incurred losses in most years since our inception. As of March 31, 2022, we had an accumulated deficit of $176.2 million. Income
and losses fluctuate year to year, primarily depending on the nature and timing of research and development occurring on our product
candidates. Our net loss was $3.5 million for the three months ended March 31, 2022, compared to $3.4 million for the three months ended
March 31, 2021. Substantially all of our operating losses resulted from expenses incurred in connection with our product candidate development
programs, our research activities and general and administrative costs associated with our operations.
We
expect to continue to incur significant expenses and operating losses for the foreseeable future as we:
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conduct
further development of our other product candidates, including LPCN 1148, LPCN 1144, LPCN 1111, LPCN 1107, LPCN 1154 and LPCN 2101; |
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continue
our research efforts; |
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research
new products or new uses for our existing products; |
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maintain,
expand and protect our intellectual property portfolio; and |
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provide
general and administrative support for our operations. |
To
fund future long-term operations, including the potential commercialization of any of our product candidates, we will need to raise additional
capital. The amount and timing of future funding requirements will depend on many factors, including capital market conditions, the commercial
success of TLANDO, regulatory requirements related to our other product development programs, the timing and results of our ongoing development
efforts, the potential expansion of our current development programs, potential new development programs, our ability to license our
products to third parties, the pursuit of various potential commercial activities and strategies associated with our development programs
and related general and administrative support. We anticipate that we will seek to fund our operations through public or private equity
or debt financings or other sources, such as potential license, partnering and collaboration agreements. We cannot be certain that anticipated
additional financing will be available to us on favorable terms, in amounts sufficient to fund our operations, or at all. Although we
have previously been successful in obtaining financing through public and private equity securities offerings and our license and collaboration
agreements, there can be no assurance that we will be able to do so in the future.
Corporate
Strategy
Our
goal is to become a leading biopharmaceutical company focused on applying our proprietary drug delivery technology for the development
of pharmaceutical products focusing on neuroendocrine and metabolic disorders. The key components of our strategy are to:
Build
a diversified multi-asset pipeline of novel therapies. We intend to employ a value-driven strategy based on our proprietary technology
platform to identify and develop product candidates for neuroendocrine and metabolic disorders including Central Nervous System (CNS)
disorders and end stage diseases such as decompensated cirrhosis. We intend to focus on product candidates that we believe are differentiated,
have attractive profiles, and address a clear unmet medical need that we can advance quickly and efficiently into late-stage development.
Advance
LPCN 1148, a unique prodrug of androgen receptor agonist to manage end stage (decompensated) liver cirrhosis disease. We believe
LPCN 1148, a novel prodrug of testosterone, could address a significant unmet medical need in patients with decompensated liver cirrhosis
accompanied with muscle disorder such as secondary sarcopenia. Sarcopenia in male cirrhotic patients is known to be independently associated
with poor outcomes including quality of life, increased decompensation events such as hepatic encephalopathy, increased hospital admissions,
and increased mortality rate. We believe LPCN 1148 may be eligible for an orphan drug designation. Enrollment in a multi-center placebo-controlled
phase 2 trial is currently ongoing.
Support
our licensee in commercialization of our licensed oral TRT option. We believe the TRT market needs a differentiated, convenient oral
option. We have exclusively licensed rights to TLANDO to Antares for commercialization of TLANDO in the US. We plan to support our licensee’s
efforts to effectively enable the availability of TLANDO to patients in a timely manner, in addition to receiving milestone and royalty
payments associated with TLANDO commercialization as agreed to in the Antares License Agreement.
Develop
partnership(s) to continue the advancement of pipeline assets. We continuously strive to prioritize our resources in seeking co-development
partnerships of our pipeline assets. We currently plan to explore partnering of LPCN 1144, our candidate for treatment of non-cirrhotic
NASH, LPCN 1107, our candidate for prevention of pre-term birth, and LPCN 1111, a once-a-day therapy candidate for TRT.
Our
Product Candidates
Our
pipeline of clinical candidates including LPCN 1148, an androgen therapy for the management of cirrhosis, LPCN 1144, an oral androgen
therapy for the treatment of non-cirrhotic NASH, LPCN 1111, a next-generation potential once daily oral TRT, LPCN 1107, an oral therapy
for the prevention of PTB, and NAS including LPCN 1154 for postpartum depression (PPD) and LPCN 2101 for epilepsy. We will continue to
explore other product candidates targeting indications with a significant unmet need.
Our
products are based on our proprietary Lip’ral drug delivery technology platform. Lip’ral based TLANDO was approved in
March 2022. Lip’ral technology is a patented technology based on lipidic compositions which form an optimal dispersed phase
in the gastrointestinal environment for improved absorption of insoluble drugs. The drug loaded dispersed phase presents the solubilized
drug efficiently at the absorption site (gastrointestinal tract membrane) thus improving the absorption process and making the drug less
dependent on physiological variables such as dilution, gastro-intestinal pH, and food effects for absorption. Lip’ral based formulation
enables improved solubilization and higher drug-loading capacity, which can lead to improved bioavailability, reduced dose, faster and
more consistent absorption, reduced variability, reduced sensitivity to food effects, improved patient compliance, and targeted lymphatic
delivery where appropriate.
Our
Development Pipeline
LPCN
1148: Oral Product Candidate for the Management of Decompensated Cirrhosis
We
are currently evaluating LPCN 1148 comprising testosterone laurate (TL) for the management of decompensated cirrhosis. We believe LPCN
1148 targets unmet needs for cirrhosis subjects including improvement in the quality of life of patients while on the liver transplant
waiting list, prevention or reduction in the occurrence of new decompensation events, and improvement in post liver transplant survival,
including outcomes and costs.
We
are currently conducting a Phase 2 POC study (NCT04874350) in male cirrhotic subjects to evaluate the therapeutic potential of LPCN 1148
for the management of sarcopenia. The ongoing Phase 2 POC study is a prospective, multi-center, randomized, placebo-controlled study
in male sarcopenic cirrhotic patients. Subjects will be randomized 1:1 to one of two arms. The treatment arm is an oral dose of LPCN
1148, and the second arm is a matching placebo. The primary endpoint is change in skeletal muscle index at week 24 with key secondary
endpoints including change in liver frailty index, rates of breakthrough hepatic encephalopathy, and number of waitlist events, including
all-cause mortality. Total treatment is expected to be 52 weeks. We currently expect enrollment in the Phase 2 study to be complete by
the end of the third quarter of 2022 and top-line 24-week results by the end of the first quarter of 2023.
Possible
outcomes of interest from the Phase 2 study include
clinical outcomes such as overall survival and new decompensation events (including hepatic encephalopathy and/or ascites occurrences),
rates of survival to transplant, rates of hospitalizations, infections, etc., muscle changes such as muscle mass, body composition, myosteatosis
(muscle fat), functional capacity changes such as liver frailty index (LFI), patient reported outcomes (PROs), and biochemical markers
including hematocrit for anemia status, albumin, creatinine/kidney function, etc.
Disease
Overview – Cirrhosis
There
are over 2 million cases of cirrhosis worldwide, with over 500,000 people living with decompensated cirrhosis in the U.S. and nonalcoholic
fatty liver disease is the most rapidly increasing indication for liver transplant. 62% of those on the liver transplant (“LT”)
waitlist are male. The economic burden (approximately $812,500/transplant) is high and continues to increase. Each year about half of
the approximately 17,000 people in U.S. on the LT waitlist undergo transplant, while nearly 3,000 patients either die or are removed
from the list because they were “too sick to transplant.”
Liver
cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands. Cirrhotic patients typically
have a years-long silent, asymptomatic phase (compensated cirrhosis) until decreasing liver function and increasing portal pressure move
the patient into the symptomatic phase (decompensated cirrhosis). Transition to decompensated cirrhosis is marked by clinical events
including ascites, encephalopathy, jaundice, and/or variceal hemorrhage. Decompensated subjects survive on average less than 2 years.
Common causes of liver cirrhosis include alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), chronic hepatitis B and C,
primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and cryptogenic.
Common
complications in cirrhotic patients may include: compromised liver function, portal hypertension, varices in GI tract with internal bleeding,
edema, ascites, hepatic encephalopathy, compromised immunity with post-transplant acute rejection risk, high sodium levels, increased
bilirubin, low albumin level, insulin resistance with impaired peripheral uptake of glucose, depression, accelerated muscle disorder
in the form of sarcopenia, myosteotosis, and frailty with compromised energetics, bone diseases (e.g., osteoporosis), high alkaline phosphatase
(ALP), cachexia, malnutrition, weight loss (>5%), symptoms of hypogonadism such as abnormal hair distribution, anemia, sexual dysfunction,
testicular atrophy, muscle wasting, fatigue, osteoporosis, gynecomastia, inflammation with elevated cytokines, and infection risk leading
to hospital admissions and possibly death.
Hepatic
encephalopathy (“HE”), a significant decompensation event in patient with cirrhosis, is a brain dysfunction caused by liver
insufficiency and/or portal systemic shunting. Because the damaged liver cannot function normally (as in cirrhosis), neurotoxins such
as ammonia are inadequately removed from systemic circulation and travel to the brain, where they affect neurotransmission. This can
cause episodes of HE, which may present as alterations in consciousness, cognition, and behavior that range from minimal to severe. Overt
HE occurs in 30% to 40% of patients with cirrhosis at some point during the clinical course of their disease. As the burden of chronic
liver disease and cirrhosis is increasing, the frequency of HE is also increasing.
Muscle
Disorders and Cirrhosis
Muscle
disorders secondary to cirrhosis could be manifested in the form of several inter-related characteristics such as sarcopenia, myosteotosis,
and frailty impacting muscle mass, strength, quality, and function. Chronic inflammation and oxidative stress have also been reported
to accelerate muscle wasting. Muscle also plays a significant compensatory role in detoxifying ammonia, a neurotoxin and a myotoxin implicated
in precipitation of HE in cirrhosis patients.
Sarcopenia
and associated frailty affect up to 70% of cirrhotic men and are a leading cause of patients being removed from the LT wait list. Due
to the lack of available organs and aging demographics of those on the waitlist, patients that do receive a transplant are “increasingly
being described as frail”. The presence of sarcopenia or frailty is associated with increased risk of hospitalization and hepatic
decompensation, a two-fold increase in waitlist mortality, poor post-transplant outcomes, and reportedly is equivalent to adding 9-10
points to the Model for End-Stage Liver Disease (MELD) score.
Sarcopenia
is typically associated with body composition changes with decreased muscle mass and/or low skeletal muscle index. Change in one or more
of appendicular lean mass, total lean mass, fat mass, high VAT (visceral adipose tissue), waist circumference, weight, and/or BMI are
notable features. Myosteotosis (fat infiltration in muscles) is indicative of poor muscle quality. Frailty is a state of low energetics
accompanied with low physical performance/mobility probably because of poor muscle strength/function and is assessed via various measures
such as decreased gait speed, weak hand grip; slow rising from a chair, balance, isometric knee extension peak torque or a composite
measure such as liver frailty index (LFI).
Reportedly,
as shown in the figure below, muscle disorder such as sarcopenia and myosteotosis in cirrhosis could be a clinically meaningful predictor
of survival and mortality with lower survival in cirrhotic patients with accompanying muscle disorders.
Montano-Loza,
J Cachexia Sarcopenia Muscle. 2016 May; 7(2): 126–135
Muscle
Disorders and Mortality in Liver Cirrhosis
Sarcopenia
develops in the majority of male cirrhosis patients. The main mechanisms associated with sarcopenia and decompensated cirrhosis include
a catabolic state, progressive immobility, imbalance between muscle breakdown and formation, and hormonal changes. Patients are typically
diagnosed with decompensated cirrhosis upon development of cirrhotic symptoms (e.g., jaundice, HE), and the diagnosis is confirmed via
various liver function/imaging tests (e.g., MELD score, liver biopsy, CT scan). A variety of clinical evaluations for muscle mass, strength,
and function are typically used to diagnose sarcopenia. Sarcopenia in cirrhosis also correlates with decompensation events, particularly
HE (sarcopenia is about 2-fold more prevalent in overt HE patients than those without overt HE). Notably, low testosterone in males is
associated with sarcopenia, severity of cirrhosis, and mortality.
Reportedly,
as shown in figure below, sarcopenia is a predictor for increased mortality in cirrhosis (about 2-fold higher compared to no sarcopenia).
Tantai
et al. J. Hepatol. 2022, 76, 588–599
Reportedly,
as shown in figure below, pre transplant sarcopenia in liver cirrhosis often produces poor post-transplant outcomes with higher mortality
rates. Longer post-transplant hospitalization and rehabilitation can be demanding on the individual, both physically and financially.
Englesbe
et al. J Am Coll Surg. 2010 Aug;211(2):271-8
Myosteatosis
in cirrhosis
Myosteatosis,
fat infiltration in muscles, has been found in many cirrhotic patients undergoing liver transplant evaluation, and studies have associated
it with more complications and poor survival. Myosteatosis is characteristically associated with liver steatosis in NAFLD, resulting
from ectopic fat accumulation in skeletal muscle. Myosteatosis may affect many individuals who do not meet the anthropometric criteria
for sarcopenia or obesity. The accumulation of excess fat in extramyocellular compartments is mostly pathologic. It can be defined as
intramuscular (between muscle fibers) or intermuscular (between muscle fascicles) and is associated with lower muscle function and strength,
muscle atrophy, and physical disabilities.
Frailty
and cirrhosis
Frailty
is a state of low energetics accompanied with low physical performance/mobility, usually as a result of poor muscle strength/function
and its presence is assessed via various measures such as decreased gait speed, weak hand grip, slow rising from a chair, poor balance,
low isometric knee extension peak torque or a composite measure such as liver frailty index (LFI).
Reportedly,
as shown in figure below, frailty predicts LT waitlist mortality among outpatients with cirrhosis regardless of the MELD score.
Lai
et al. Am J Transplant. 2014 Aug;14(8):1870-9
The
presence of frailty is associated with increased waitlist death/delisting
Moreover,
it has also been reported, as shown in figure below, that there is a higher incidence of waitlist mortality as the frailty worsened.
Lai
et al. J Hepatol. 2020 Sep;73(3):575-581.
Trajectory
of liver frailty and mortality
Currently,
there are no FDA approved drugs to treat secondary sarcopenia in cirrhosis. We believe we are the only clinical-stage company
pursuing decompensation in sarcopenic cirrhotic patients, and no regulatory precedent currently exists for the approval of decompensation
or sarcopenia-targeted therapies. We believe LPCN 1148 has the potential to aid the management of decompensation events in male sarcopenic
cirrhotic patients through the following possible mechanisms of action: myo-augmentation (impact muscle mass and/or quality and/or function)
via myostatin inhibition, myosteatosis reduction, anti-catabolic effect, changes in body composition (increase lean mass and/or reduce
fat mass) and slowing muscle autophagy; inducing hepato-effective actions with improved key liver injury markers; increase protein synthesis;
improve anemia, induce immunomodulation with improvement of immuno-dysregulation, and lower infection rates; anti-inflammatory/antioxidant
effects by lowering undesirable cytokines such as IL-1, IL-6, and TNF-α; and improve mitochondrial function.(1)
| (1) | Ref:
Leise. Mayo Clin Proc. 2014.; Hudson. Eur J Gastroenterol. 2019.; Bajaj. Clin Gastroenterol
Hepatol. 2017.; Bohra. World J Gastroenterol. 2020.; Carey, Hepatology, 2019; Sinclair, Ailment
Pharmacol Ther, 2016; Lai, Am J Transplant, 2014; Montano-Loza, Clin Transl Gastroenterol,
2015; Kahn, Clin Transp, 2018; Montano-Loza, J Cach, Sarco, and Musc, 2016. |
LPCN
1144: An Oral Prodrug of Bioidentical Testosterone Product Candidate for the Treatment of NASH
We
are currently evaluating LPCN 1144, an oral prodrug of bioidentical testosterone comprised of TU, for the treatment of non-cirrhotic
NASH.
Disease
Overview – NASH
NASH
is a more advanced state of non-alcoholic fatty liver disease (“NAFLD”) and can progress to a cirrhotic liver or liver failure,
require liver transplant, and can result in hepatocellular carcinoma/ liver cancer, and death. Progression of NASH to end stage liver
disease will soon surpass all other causes of liver failure requiring liver transplantation. Importantly, beyond these critical conditions,
NASH and NAFLD patients additionally suffer heightened cardiovascular risk and, in fact, die more frequently from cardiovascular events
than from liver disease. NAFLD/NASH is becoming more common due to its strong correlation with obesity and metabolic syndrome, including
components of metabolic syndrome such as diabetes, cardiovascular disease and high blood pressure. Twenty to thirty percent of the U.S.
population is estimated to suffer from NAFLD and fifteen to twenty percent of this group progresses to NASH, which is a substantially
large population that lacks an effective therapy. NASH is a silent killer that affects millions in the U.S. Diagnoses have been on the
rise and are expected to increase dramatically in the next decade. Approximately 50% of NASH patients are in adult males. In men, especially
with comorbidities associated with NAFLD/NASH, testosterone deficiency has been associated with an increased visceral adipose tissue
and insulin resistance, which could be factors contributing to NAFLD/NASH. There is currently no approved therapy for the treatment of
NASH although there are several drug candidates currently under development with many clinical failures to date.
The
critical pathophysiologic mechanisms underlying the development and progression of NASH include reduced ability to handle lipids, increased
insulin resistance, injury to hepatocytes and liver fibrosis in response to hepatocyte injury. NASH patients have an excessive accumulation
of fat in the liver resulting primarily from a caloric intake above and beyond energy needs. A healthy liver contains less than 5% fat,
but a liver in someone with NASH can contain more than 20% fat. This abnormal liver fat contributes to the progression to NASH, a liver
necro-inflammatory state that can lead to scarring, also known as fibrosis, and, for some, can progress to cirrhosis and liver failure.
Markers
of Liver Cell Death
Alanine
aminotransferase (“ALT”) is an enzyme that is produced in liver cells and is naturally found in the blood of healthy individuals.
In liver disease, liver cells are damaged and, as a consequence, ALT is released into the blood, increasing ALT levels above the normal
range. Physicians routinely test blood levels of ALT to monitor the health of a patient’s liver. ALT level is a clinically important
biochemical marker of the severity of liver inflammation and ongoing liver disease. Elevated levels of ALT represent general markers
of liver cell death and inflammation without regard to any specific mechanism. Aspartate aminotransferase (“AST”) is a second
enzyme found in the blood that is produced in the liver and routinely measured by physicians along with ALT. As with ALT, AST is often
elevated in liver disease and, like ALT, is considered an overall marker of liver inflammation.
Diagnosis
Most
people with NASH are asymptomatic and their disease is often discovered incidentally following a liver imaging procedure, such as an
ultrasound, prescribed for other reasons or as part of an investigation for elevated liver enzymes. Once suspected clinically, a liver
biopsy is required to definitively diagnose NASH, which necessitates the joint presence of steatosis, ballooning and lobular inflammation.
Once pathologically confirmed, the severity of NAFLD and NASH is determined using the histologically validated NAFLD activity score,
which grades disease activity on a scale of 0 to 8. The NAFLD activity score is the sum of the individual scores for steatosis (0 to
3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) but does not include a score for fibrosis. Fibrosis staging
(F0-F4) relies on the NASH CRN classification (F0 = no fibrosis; F1 = perisinusoidal or portal/periportal fibrosis (not both); F2 = both
perisinusoidal and portal/periportal fibrosis; F3 = bridging fibrosis; F4 = cirrhosis).
Histological
diagnosis remains the gold standard for assessment of NASH and fibrosis. However, given that liver biopsy is associated with risks of
pain, bleeding and other morbidity, as well as significant cost, the procedure is not practical for general patient screening. Several
non-invasive tools such as clinical risk scores and imaging techniques are increasingly used to assess potential NASH patients. Clinical
risk scores such as the NAFLD fibrosis score, Fibrosis-4 index, the Enhanced Liver Fibrosis score and vibration-controlled transient
elastography (“VCTE”), have been validated and are increasingly used. These tools have an excellent negative predictive value
and an acceptable positive predictive value for detection of advanced (≥ F3) fibrosis and are increasingly used in clinical settings.
Extensive efforts are also under way to develop non-invasive means to identify patients with NAS ≥ 4 or fibrosis ≥ F2 without a
liver biopsy. In draft guidance, the FDA encouraged sponsors to identify biochemical or noninvasive imaging biomarkers that, once characterized
and agreed by the FDA, could replace liver biopsies for patient selection and efficacy assessment in clinical trials.
We
expect that the validation and subsequent adoption of these new tools will result in an increase in the diagnosis and treatment rates
for NASH in the future.
Current
Status
We
have recently completed the LiFT Phase 2 clinical study in biopsy-confirmed non-cirrhotic NASH subjects. The LiFT clinical
study was a prospective, multi-center, randomized, double-blind, placebo-controlled multiple-arm study in biopsy-confirmed hypogonadal
and eugonadal male NASH subjects with grade F1-F3 fibrosis and a target NAFLD Activity Score ≥ 4 with a 36-week treatment period.
The LiFT clinical study enrolled 56 biopsy confirmed NASH male subjects. Subjects were randomized 1:1:1 to one of three arms (Treatment
A is a twice daily oral dose of 142 mg testosterone equivalent, Treatment B is a twice daily oral dose of 142 mg testosterone equivalent
formulated with 217 mg of d-alpha tocopherol equivalent, and the third arm is twice daily matching placebo).
The
primary endpoint of the LiFT clinical study was change in hepatic fat fraction via MRI-PDFF and exploratory liver fat/marker end
points post 12 weeks of treatment. Additionally, key secondary endpoints post 36 weeks of treatment included assessment of histological
change for NASH resolution and/or fibrosis improvement (biopsy) as well as liver fat data (MRI-PDFF). The LiFT clinical study
was not powered to assess statistical significance of any of the secondary endpoints. Other important endpoints included the following:
change in liver injury markers, anthropomorphic measurements, lipids, insulin resistance and inflammatory/fibrosis markers; as well as
patient reported outcomes.
Additionally,
subjects have access to LPCN 1144 through an open label extension (“OLE”) study. The extension study will enable the collection
of additional data on LPCN 1144 for up to a total of 72 weeks of therapy, as well as data for 36 weeks of therapy for those subjects
on placebo in the LiFT study. The OLE has been completed and we expect topline results from the study in May 2022.
Treatments
with LPCN 1144 post 12 weeks of treatment resulted in robust liver fat reduction, assessed by MRI-PDFF, and showed improvement of liver
injury markers with no observed tolerability issues.
Liver
biopsies were performed at baseline (“BL”) and after 36 weeks of treatment (“EOS”). Prespecified biopsy analyses
included NASH Clinical Research Network (“CRN”) scoring as well as a continuous paired (“Paired Technique”) and
digital technique (“Digital Technique-Fibronest”). All biopsy analyses were performed on the same slides and the reads for
the three techniques were done independently. Analysis sets included the NASH Resolution Set (all subjects that have BL and EOS biopsy
with NASH at BL [NAS ≥4 with lobular inflammation score ≥ 1 and hepatocyte ballooning score ≥1 at BL] (n=37)), the Biopsy Set
(all subjects with baseline and EOS biopsies (n=44)), and the Safety Set (all randomized subjects (n=56)).
Both
LPCN 1144 treatment arms met with statistical significance the pre-specified accelerated approval regulatory endpoint of NASH resolution
with no worsening of fibrosis based on NASH CRN scoring. Additionally, both treatment arms showed substantial improvement of the observed
NASH activity in steatosis, inflammation, and ballooning.
Key
results from the LiFT clinical study are presented in the following tables and figures:
In
both treatment arms, substantial reductions in markers of liver injury compared to placebo were observed post four weeks of treatment
and were sustained through EOS. Using all available Safety Set data, ALT decreased up to a mean of 23.4 U/L at EOS from all group mean
baseline of 51.5 U/L and AST decreased up to a mean of 13.3 U/L at EOS from all group mean baseline of 31.9 U/L.
Positive
effects in appendicular lean mass and whole-body fat mass, an indicator of overall tissue quality, based on dual-energy X-ray absorptiometry
scans, were noted in both LPCN 1144 treatment arms.
Finding
on liver injury marker and positive effects on body composition can be seen in the following table:
During
the 36 weeks of treatment, LPCN 1144 was well tolerated with an overall safety profile comparable to placebo.
In
November 2021, the FDA granted Fast Track Designation to LPCN 1144 as a treatment for non-cirrhotic NASH. The Fast Track program is designed
to accelerate the development and expedite the review of products, such as LPCN 1144, which are intended to treat serious diseases and
for which there is an unmet medical need.
We
had a written only response from FDA for a LPCN 1144 Type C meeting with the FDA in January 2022 to discuss the development path forward
with LPCN 1144. The FDA acknowledged that the NDA submission of LPCN 1144 would be via 505(b)2 regulatory pathway and agreed that no
additional non-clinical studies are needed to support an NDA submission. The FDA recommended to request an end-of-phase 2 (EOP2) meeting.
The FDA acknowledged that in the LiFT study subjects achieved improvements in key components associated with NASH histopathology
after 36-weeks of treatment with LPCN 1144 in adult males and agreed that the proposed multicomponent primary surrogate endpoint is acceptable
for seeking approval under the accelerated approval pathway. The FDA also recommended either conducting a separate dose–ranging
study prior to phase 3 or evaluating multiple doses in phase 3. The FDA agreed that the proposed primary multicomponent surrogate endpoint,
NASH resolution with no worsening of fibrosis, is acceptable for seeking approval under the accelerated approval pathway and the FDA
recommended a phase 3 trial with a study duration of 72 weeks. The FDA has requested that Lipocine submit an updated Phase 3 protocol
for FDA feedback on the study design and we have requested an EOP2 meeting to discuss the phase 3 and confirmatory trial designs.
We
are exploring the possibility of licensing LPCN 1144 to a third party, although no licensing agreement has been entered into by the Company.
No assurance can be given that any license agreement will be completed, or, if an agreement is completed, that such an agreement would
be on acceptable terms.
TLANDO:
An Oral Product Candidate for Testosterone Replacement Therapy
As
previously described, under the Antares License Agreement, we granted to Antares an exclusive, royalty-bearing, sublicensable right and
license to develop and commercialize, upon final approval of TLANDO from the FDA, our TLANDO product for TRT in the U.S. On December
8, 2020, the FDA provided tentative approval for TLANDO as a TRT in adult males for conditions associated with a deficiency of endogenous
testosterone, also known as hypogonadism. The FDA provided final approval of TLANDO on March 28, 2022. Any FDA requirement to conduct
certain post-marketing studies will be the responsibility of our licensee, Antares.
Proof-of-concept
for TLANDO was initially established in 2006, and subsequently TLANDO was licensed in 2009 to Solvay Pharmaceuticals, Inc. which was
then acquired by Abbott Products, Inc. (“Abbott”). Following a portfolio review associated with the spin-off of AbbVie Inc.
by Abbott in 2011, the rights to TLANDO were reacquired by us. All obligations under the prior license agreement have been completed
except that Lipocine will owe Abbott a perpetual 1% royalty on net sales. Such royalties are limited to $1 million in the first two calendar
years following product launch, after which period there is not a cap on royalties and no maximum aggregate amount. If generic versions
of any such product are introduced, then royalties are reduced by 50%.
Under
the Pediatric Research Equity Act (“PREA”), since TLANDO received full FDA approval, under the Antares Licensing Agreement,
Antares will need to address the PREA requirement to assess the safety and effectiveness of TLANDO in pediatric patients. The FDA may
also require certain post-marketing studies to be conducted which will also be the responsibility of our licensee, Antares.
Upon
execution of the Antares License Agreement, Antares paid to us an initial payment of $11.0 million. Antares will also make additional
payments of $5.0 million to us on each of January 1, 2025, and January 1, 2026, provided that certain conditions are satisfied. We are
also eligible to receive milestone payments of up to $160.0 million in the aggregate, depending on the achievement of certain sales milestones
in a single calendar year with respect to all products licensed by Antares under the Antares License Agreement. In addition, upon commercialization,
we will receive tiered royalty payments at rates ranging from percentages in the mid-teens to up to 20% of net sales of TLANDO in the
United States, subject to certain minimum royalty obligations. Further, on October 14, 2021, we assigned our Manufacturing Agreement,
dated August 27, 2013, by and between the Company and Encap Drug Delivery (the “Manufacturing Agreement”) to Antares as part
of the Antares License Agreement.
We
are exploring the possibility of licensing LPCN 1021 (known as TLANDO in the United States) to third parties outside the United States,
although no licensing agreement has been entered into by the Company. If and when an agreement is made with a partner, such arrangement
would likely be contingent upon obtaining acceptable cost of goods by securing an agreement with a new manufacturer in addition to obtaining
local regulatory approval. No assurance can be given that any license agreement will be completed, or, if an agreement is completed,
that such an agreement would be on terms favorable to us.
LPCN
1111: A Next-Generation Long-Acting Oral Product Candidate for TRT
LPCN
1111: is a next-generation, novel ester prodrug of testosterone comprised of testosterone tridecanoate (TT) which uses the proprietary
delivery technology to enhance solubility and improve systemic absorption. We completed a Phase 2b dose finding study in hypogonadal
men in the third quarter of 2016. The primary objectives of the Phase 2b clinical study were to determine the starting Phase 3 dose of
LPCN 1111 along with safety and tolerability of LPCN 1111 and its metabolites following oral administration of single and multiple doses
in hypogonadal men. Good dose-response relationship was observed over the tested dose range in the Phase 2b study. Additionally, the
target Phase 3 dose met primary and secondary end points. Overall, LPCN 1111 was well tolerated with no drug-related severe or serious
adverse events reported in the Phase 2b study.
In
February 2018 we had a meeting with the FDA to discuss these pre-clinical results and to discuss the Phase 3 clinical study and path
forward for LPCN 1111. Based on the results of the FDA meeting and additional pre-clinical studies conducted after the FDA meeting, we
have proposed a Phase 3 protocol for LPCN 1111 and have solicited FDA feedback. Based on initial FDA feedback, we expect the Phase 3
clinical trial design to follow the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(“ICH”) guidelines and we expect the trial will include at least a three-month efficacy treatment period and a one-year safety
component for approximately 100 subjects. We are currently seeking further clarification from FDA with respect to the total subject LPCN
1111 exposure information needed for an NDA filing. We continue to refine the Phase 3 protocol and plan to request FDA approval of the
protocol once it is finalized. Additionally, the FDA previously requested that a food effect and a phlebotomy study be completed, and
that ambulatory blood pressure monitoring (“ABPM”) be included as part of the Phase 3 clinical study. We are currently transferring
the manufacturing of LPCN 1111 to a third-party contract manufacturer and scaling up the formulation after which we anticipate the next
steps in developing LPCN 1111 may be to conduct a food effect/phlebotomy study with LPCN 1111. Under the terms of the Antares License
Agreement, Antares has been granted an option to license LPCN 1111, exercisable on or before March 31, 2022, for further development
and, should LPCN 1111 receive FDA approval, commercialization. On April 1, 2022, the Company entered into the First Amendment to the
License Agreement (the “Amendment”), pursuant to which the License Agreement was amended to extend the deadline by which
Antares shall exercise its option to license LPCN 1111 to June 30, 2022. As consideration for the Company agreeing to enter into the
Amendment, Antares paid the Company a non-refundable cash fee of $500,000 in April 2022.If Antares exercises its option to license LPCN
1111, we will be entitled to an additional payment of $3.5 million, as well as development milestone payments of up to $35.0 million
in the aggregate and tiered royalty payments at rates ranging from percentages in the mid-teens to 20% of net sales of LPCN 1111 in the
United States. We are currently in the process of scaling up manufacturing production of clinical supplies for a Phase 3 clinical trial.
LPCN
1107: An Oral Product Candidate for the Prevention of Preterm Birth
We
believe LPCN 1107 has the potential to become the first oral hydroxyprogesterone caproate (“HPC”) product indicated for the
reduction of risk of PTB (delivery less than 37 weeks) in women with singleton pregnancy who have a history of singleton spontaneous
PTB. Prevention of PTB is a significant unmet need as approximately 11.7% of all U.S. pregnancies result in PTB, a leading cause of neonatal
mortality and morbidity.
Current
Status
We
have completed a multi-dose PK dose selection study in pregnant women. The objective of the multi-dose PK selection study was to assess
HPC blood levels in order to identify the appropriate LPCN 1107 Phase 3 dose. The multi-dose PK dose selection study was an open-label,
four-period, four-treatment, randomized, single and multiple dose PK study in pregnant women with three dose levels of LPCN 1107 and
the IM HPC (Makena®). The study enrolled 12 healthy pregnant women (average age of 27 years) with a gestational age of approximately
16 to 19 weeks. Subjects received three dose levels of LPCN 1107 (400 mg BID, 600 mg BID, or 800 mg BID) in a randomized, crossover manner
during the first three treatment periods and then received five weekly injections of HPC during the fourth treatment period. During each
of the LPCN 1107 treatment periods, subjects received a single dose of LPCN 1107 on Day 1 followed by twice daily administration from
Day 2 to Day 8. Following completion of the three LPCN 1107 treatment periods and a washout period, all subjects received five weekly
injections of HPC. Results from this study demonstrated that average steady state HPC levels (Cavg0-24) were comparable or higher for
all three LPCN 1107 doses than for injectable HPC. Additionally, HPC levels as a function of daily dose were linear for the three LPCN
1107 doses. Also, unlike the injectable HPC, steady state exposure was achieved for all three LPCN 1107 doses within seven days.
A
traditional PK/PD based Phase 2 clinical study in the intended patient population is not expected to be required prior to entering into
Phase 3. Therefore, based on the results of our multi-dose PK study we had an End-of-Phase 2 meeting and subsequent guidance meetings
with the FDA to define a pivotal Phase 2b/3 development plan for LPCN 1107. However, these discussions will need to be updated based
on recent developments with Covis’ Makena®. We plan to resume our interactions with the FDA to discuss our pivotal clinical
trial design and better understand next steps to advance LPCN 1107
We
are exploring the possibility of licensing LPCN 1107 to a third party, although no licensing agreement has been entered into by the Company.
No assurance can be given that any license agreement will be completed, or, if an agreement is completed, that such an agreement would
be on acceptable terms.
The
FDA has granted orphan drug designation to LPCN 1107 based on a major contribution to patient care. Orphan designation qualifies Lipocine
for various development incentives, including tax credits for qualified clinical testing, and a waiver of the prescription drug user
fee when we file our NDA.
Recent
Competition Update
On
October 5, 2020, the FDA’s Center for Drug Evaluation and Research (“CDER”) proposed that Makena be withdrawn from
the market because the PROLONG trial failed to verify the clinical benefit of Makena and concluded that the available evidence does not
show Makena is effective for its approved use.
CDER
issued AMAG Pharmaceuticals, the NDA holder at the time, a Notice of Opportunity for Hearing to withdraw approval of Makena, for which
AMAG Pharmaceuticals responded by requesting a hearing and providing detail on the company’s position, recognizing clinicians’
decade-long use of Makena’s treatment and the public health implications of withdrawing approval. The FDA Commissioner has recently
granted Covis a public hearing although the date of that hearing is not publicly known. During this time, Makena and the approved generics
of Makena will remain on the market until the FDA makes a final decision about these products.
Currently,
Makena and the approved generics of Makena are the only products approved for the prevention of recurrent preterm birth.
The
FDA also indicated that it intends to hold a meeting with experts in obstetrics, neonatal care, and clinical trial design to discuss
how to facilitate development of effective and safe therapies to treat preterm birth.
Oral
NAS Programs for CNS Disorders
Some
preferred endogenous or naturally occurring NAS present in central nervous system (CNS) act as positive allosteric modulators (PAM) of
the GABAA receptor, the major biological target of the inhibitory neurotransmitter γ-aminobutyric acid (GABAA).
To improve oral delivery of these modulators, several synthetic NAS derivatives of endogenous GABAA receptor PAMs, have been
developed for therapeutic use in the past few decades.
We
believe through utilization of our proprietary technology we may have the ability to enable effective oral delivery of endogenous GABAA
receptor PAMs which historically had been challenging to deliver orally as they were deemed to be not orally bioavailable. We believe
these endogenous GABAA receptor PAMs provide opportunity as a differentiated NAS for treatment of various CNS disorders via
the preferred and convenient oral route.
LPCN
1154: Product Candidate for PPD
We
are currently evaluating LPCN 1154 comprising an endogenous NAS for PPD. FDA has cleared LPCN 1154 IND (investigational new drug) application
to conduct a phase 2 study in PPD. We have completed a PK study with LPCN 1154 post oral administration in which we believe clinically
relevant levels of the active were observed. We are currently conducting a food effect PK study.
PPD
PPD
(Postpartum depression), a type of major depressive disorder with onset either during pregnancy or within four weeks of delivery, refers
to depression persisting up to 12 months after childbirth. PPD can be clinically segmented by the severity of symptoms and presence of
a comorbidity, including epilepsy. Approximately 1 in 9 mothers suffers from PPD in the United States alone; this equates to approximately
500,000 women being affected by PPD annually.
Disease
Overview - PPD
|
● |
PPD
is distinct from the “baby blues,” a condition that affects up to 70% of all new mother’s experience; “baby
blues” tend to be short-lived emotional conditions that do not interfere with daily activities. |
|
|
|
|
● |
Symptoms
of PPD include hallmarks of major depression, including, but not limited to, sadness, depressed mood, loss of interest, change in
appetite, insomnia, sleeping too much, fatigue, difficulty thinking/concentrating, excessive crying, fear of harming the baby/oneself,
and/or thoughts of death or suicide. |
|
|
|
|
● |
During
pregnancy, levels of endogenous NAS increase considerably along with levels of progesterone; however, they drop sharply postpartum.
It has been hypothesized that the rapid perinatal decrease in circulating levels of endogenous NASs may be involved in the development
of PPD. The first and only approved treatment option for PPD is an injectable containing endogenous NAS. |
|
● |
Depression
may persist long after child delivery. Additionally, approximately 40% of women relapse in subsequent pregnancies or on other occasions. |
|
|
|
|
● |
Psychiatric
comorbidities are common in patients with epilepsy. Patients with epilepsy are at high risk for major depressive disorders and PPD.
Reported PPD rates are higher among women with epilepsy than the general population. |
Associated
Risk Factors
|
● |
Genetic:
family history and/or previous experience of depression or other mood disorders |
|
|
|
|
● |
Physiological:
rapid changes in sex hormones, stress hormones, and thyroid hormone levels during and after delivery |
|
|
|
|
● |
Environmental:
stressful life events, changes in relationships at home and at work, and/or lack of familial support |
Unmet
medical need
Approximately,
1 in 9 mothers suffer from PPD in the United States alone, which equates to approximately 500,000 women affected by PPD annually. We
believe there is considerable unmet need within women with PPD due to lack of convenient and fast-acting oral therapies. Selective Serotonin
Reuptake Inhibitors (SSRIs) have been the traditional first-line choice for women with severe PPD requiring weeks for onset of efficacy;
therefore, a need for a faster onset of action remains a significant unmet need in treating PPD, especially in women with epilepsy risk
wherein psychiatric comorbidity is common and PPD rates are higher than the general population.
Injectable
brexanolone (ZulressoTM, Sage Therapeutics) became the first FDA-approved treatment for postpartum depression. However, numerous factors
limit the utilization of injectable brexanolone such as method of administration, cost, and safety concerns. Administration of injectable
brexanolone requires a 60-hour continuous infusion in a supervised medical setting, a demanding ask for a mother with a newborn. Besides
associated privacy concerns and social stigma, hospitalization may also require separation of the mother and child for a few days, which
may be difficult to the already strained mother-infant bond and may present breast feeding challenges. Moreover, the pharmacotherapy
costs coupled with hospitalization/childcare costs limits its accessibility and affordability to women most in need of the therapy. Finally,
due to concerns about the safety of injectable ZulressoTM including excessive sedation or loss of consciousness, Zulresso has a Black
Box Warning in its label and is only available through a restricted distribution program (REMS), and sites need significant time to become
treatment ready.
We
believe the need for a convenient, at-home treatment with faster onset of action which could offer privacy and affordability, independent
of socio-economic status, for women with PPD is a significant unmet need. LPCN 1154 targets this unmet need with affordable NAS.
LPCN
2101: NAS for epilepsy
We
are currently evaluating an additional NAS candidate, LPCN 2101, for women with epilepsy (“WWE”). We have completed a pre-clinical
study for LPCN 2101. We plan to file an IND with the U.S. FDA for LPCN 2101 to conduct a proof-of-concept study for the evaluation
of safety, tolerability, and efficacy in adult female subjects of childbearing age diagnosed with epilepsy.
Disease
Overview - Epilepsy
Epilepsy
is defined by the 1) occurrence of at least two unprovoked seizures more than 24 hours apart, 2) occurrence of one unprovoked seizure
and a probability of further seizures occurring over the next 10 years, and/or 3) diagnosis of an epilepsy syndrome. Patients with epilepsy
are more likely to be comorbid with other conditions, including depression and anxiety.
Patients
with epilepsy have increased risk of mortality due to direct effects of seizures (e.g., status epilepticus, car accidents) and indirect
effects of seizures (e.g., suicide, cardiovascular effects.)
Epilepsy
is a disorder of the brain that causes seizures, affecting the physical, mental, and social well-being of persons, and is associated
with a 2 to 3 times greater mortality rate compared with the general population. About 60-65% of epilepsy is idiopathic and about 30%
of patients are refractory (i.e., epilepsy not well managed with currently available antiepileptic drugs (“AEDs”)). Epilepsy
is the most common neurological disorder during pregnancy.
It
is estimated that approximately 900,000 CB age women suffers from active epilepsy in the U.S. Women of CB age with epilepsy face many
additional challenges due to hormonal influences on seizure activity and endocrine function throughout the different phases of their
reproductive cycles. Elevated estrogen or decreased progesterone levels can exacerbate seizure frequency. Often, these women experience
hormonal and endogenous NAS imbalances, coupled with fluctuations in the blood levels of AEDs that impact control of seizures, efficacy
of oral contraceptives, any coexisting anxiety and/or depression and any associated sleep impairment. Epileptic patients are 5-20 times
more likely to develop depression.
Clinical
segmentation can be categorized by epilepsy type, comorbidities and patient subgroups. Categorization of focal epilepsy, generalized
epilepsy, combined focal and generalized epilepsy, and unknown epilepsy can guide the choice of AED. Special patient subgroups, including
WWE of CB age and elderly patients, require special care and management of epilepsy. Comorbidities such as depression and anxiety may
be co-treated with therapies that do not aggravate seizures and have no drug interaction with the AED used for epilepsy. While lowest
effective dose and monotherapy are preferred, management of patients with epilepsy is focused on controlling seizures, avoiding adverse
events, and maintaining quality of life. Despite a wide range of AEDs available, about 30 % of all people with epilepsy still fail to
respond to treatment effectively. Women with epilepsy face specific challenges throughout their lifespan because of seizures, AEDs,
and hormonal fluctuations.
Women
with epilepsy were once counseled to avoid pregnancy, but epilepsy is no longer considered a contraindication to pregnancy. Caregivers
for WWE in the preconception phase either intending to start a family (planning pregnancy) or using contraception to prevent an unplanned
pregnancy face significant challenges to balance seizure control efficacy with the selection and dosage of AEDs and AED-related risks
such as, among other risks, fetal-neonatal toxicity, contraception failure, and psychiatric side effects.
Several
AEDs are known to have teratogenic effects on the developing fetus (converging evidence from registry studies indicates that teratogenic
risks are highest with valproate, followed by carbamazepine and topiramate). Other commonly prescribed AEDs, including older generation
agents, such as phenobarbital and phenytoin, have been associated with higher risks as compared with lamotrigine, levetiracetam, clonazepam
and gabapentin (Vajda et al., 2014; Voinescu and Pennell, 2015). Moreover, risks associated with AEDs is considerable early in pregnancy;
therefore, it is necessary that WWE of CB age undergo counselling, monitoring, and adjustment to the most appropriate AED prior to becoming
pregnant. It is preferable WWE of CB age discuss seizure control with their doctor for at least 6 months before conception and, if possible,
cease AED therapy or use the lowest effective dose of a single anticonvulsant according to the type of epilepsy and the fetal toxicity
of the AED. Anxiety, depression, lack of adherence to AED, and/or contraception failure may be experienced by women who are worried about
unplanned pregnancy or are late in confirming pregnancy, planned or unplanned. AEDs can reduce the efficacy of oral contraceptives, compounding
this problem.
Complex,
multidirectional interactions between female hormones, seizures, and AEDs exist. Most hormones act as NAS and can thus modulate brain
excitability. Any changes in endogenous or exogenous hormone levels can affect the occurrence of seizures, either directly or via PK
interactions that modify the plasma levels of AEDs (Harden, 2008). The PK interactions between oral contraceptives and AEDs are bidirectional
(Johnston and Crawford, 2014). The efficacy of hormonal contraception may be diminished for women taking CYP-P450 enzyme inducing AEDs.
Epilepsy is not a medical condition in which contraceptives are contraindicated. Contraceptive failure, possibly related to AEDs, may
be responsible for up to one in four unplanned pregnancies in WWE (-12.5% of all WWE pregnancies), vs a rate of 1% in healthy women.
Unmet
need to treat WWE in CB age
It
is estimated that approximately 900,000 CB age women suffer from active epilepsy in the U.S. Women of CB age with epilepsy face many
additional challenges such as hormonal influences on seizure activity and endocrine function throughout the different phases of their
reproductive cycles, and approximately 30% of patients with epilepsy cannot be efficiently controlled with available AEDs making consideration
of newer pharmacological treatment development options important.
Managing
uncontrolled seizures in WWE of CB age is the primary aim during preconception, pregnancy, and postpartum phases. Therefore, uncompromised
AED efficacy with acceptable variability and less or no drug-drug interactions achieved with lowest possible monotherapy dose to address
fetal toxicity concerns, remain highly unmet needs. Moreover, control of seizures including prevention of breakthrough seizures is critical
when planning for pregnancy and also during pregnancy, as it can also lead to undesired falls or auto-accidents and compromise freedom
to drive.
Select
AEDs have the potential to induce contraception failures, reproductive hormone imbalance, anxiety, and depression. There remains an unmet
need for an AED without the aforementioned downsides, with no to low fetal-neonatal toxicity and without any breast-feeding concerns
as well as potential to treat associated comorbidities.
While
over 30 molecules have been approved for the treatment of epilepsy in the U.S., no epilepsy drug has been specifically approved for WWE
of CB age. We believe our endogenous NASs as GABAA PAMs, while targeting the goal of seizure control, also have the potential
for additional benefits in psychiatric disorders comorbidities (e.g., anxiety and/or depression), and sleep impairment. Moreover, these
oral endogenous NAS could potentially address some of the fetal toxicity concerns related to unplanned or planned pregnancy in WWE. (2)
| (2) | Ref:
S.Bangar et al. Functional Neurology 2016; 31(3): 127-134; Reimers et al. Seizure. 2015 May;28:66-70. |
Financial
Operations Overview
Revenue
To
date, we have not generated any revenues from product sales and do not expect to generate revenue other than TLANDO royalties and licensing
fees until one of our product candidates receives approval from the FDA. Revenues to date have been generated substantially from license
fees, royalty and milestone payments and research support from our licensees. Since our inception through March 31, 2022, we have generated
$44.2 million in revenue under our various license and collaboration arrangements and from government grants. We may never generate revenues
from any of our clinical or preclinical development programs other than TLANDO as we may never succeed in obtaining regulatory approval
or commercializing any of these product candidates.
Research
and Development Expenses
Research
and development expenses consist primarily of salaries, benefits, stock-based compensation and related personnel costs, fees paid to
external service providers such as contract research organizations and contract manufacturing organizations, contractual obligations
for clinical development, clinical sites, manufacturing and scale-up for clinical trials, formulation of clinical drug supplies, and
expenses associated with regulatory submissions. Research and development expenses also include an allocation of indirect costs, such
as those for facilities, office expense, travel, and depreciation of equipment based on the ratio of direct labor hours for research
and development personnel to total direct labor hours for all personnel. We expense research and development expenses as incurred. Since
our inception, we have spent approximately $132.5 million in research and development expenses through March 31, 2022.
We
expect to continue to incur significant costs as we develop our other product candidates, including the ongoing Phase 2 POC study in
male cirrhotic subjects with LPCN 1148.
In
general, the cost of clinical trials may vary significantly over the life of a project as a result of uncertainties in clinical development,
including, among others:
|
● |
the
number of sites included in the trials; |
|
|
|
|
● |
the
length of time required to enroll suitable subjects; |
|
|
|
|
● |
the
duration of subject follow-ups; |
|
|
|
|
● |
the
length of time required to collect, analyze and report trial results; |
|
|
|
|
● |
the
cost, timing and outcome of regulatory review; and |
|
|
|
|
● |
potential
changes by the FDA in clinical trial and NDA filing requirements for testosterone replacement therapies. |
A
change of outcome for any of these variables with respect to the development of our product development candidates could mean a substantial
change in the costs and timing associated with these efforts, could require us to raise additional capital, and may require us to reduce
operations.
Given
the stage of clinical development and the significant risks and uncertainties inherent in the clinical development, manufacturing and
regulatory approval process, we are unable to estimate with any certainty the time or cost to complete the development of LPCN 1148,
LPCN 1144, LPCN 1111 (TLANDO XR), LPCN 1107, LPCN 1154, LPCN 2101, and other product candidates. Clinical development timelines, the
probability of success and development costs can differ materially from expectations and results from our clinical trials may not be
favorable. If we are successful in progressing LPCN 1148, LPCN 1111, LPCN 1144, LPCN 1107, NAS including LPCN 1154 and LPCN 2101, or
other product candidates into later stage development, we will require additional capital. The amount and timing of our future research
and development expenses for these product candidates will depend on the preclinical and clinical success of both our current development
activities and potential development of new product candidates, as well as ongoing assessments of the commercial potential of such activities.
Summary
of Research and Development Expense
We
are conducting on-going clinical and regulatory activities with most of our product candidates. Additionally, we incur costs for our
other research programs. The following table summarizes our research and development expenses:
| |
Three Months Ended March 31, | |
| |
2022 | | |
2021 | |
External service provider costs: | |
| | | |
| | |
LPCN 1148 | |
$ | 431,170 | | |
$ | - | |
LPCN 1154 | |
| 254,247 | | |
| 7,430 | |
LPCN 1111 | |
| 152,329 | | |
| - | |
LPCN 1144 | |
| 84,549 | | |
| 763,230 | |
LPCN 1107 | |
| 42,161 | | |
| 1,000 | |
TLANDO | |
| - | | |
| 86,724 | |
Total external service provider costs | |
| 964,456 | | |
| 858,384 | |
Internal personnel costs | |
| 694,721 | | |
| 570,266 | |
Other research and development costs | |
| 228,776 | | |
| 151,890 | |
Total research and development | |
$ | 1,887,953 | | |
$ | 1,580,540 | |
We
expect research and development expenses to increase in the future as we complete on-going clinical studies, including the Phase 2 POC
study in male cirrhotic subjects with LPCN 1148, as we conduct future clinical studies, including when and if we conduct Phase 2 clinical
studies with our product candidates and Phase 3 clinical studies with LPCN 1144, LPCN 1111, and LPCN 1107. However, if we are unable
to raise additional capital, we may need to reduce research and development expenses in order to extend our ability to continue as a
going concern.
General
and Administrative Expenses
General
and administrative expenses consist primarily of salaries and related benefits, including stock-based compensation related to our executive,
finance, business development, and support functions. Other general and administrative expenses include rent and utilities, travel expenses,
professional fees for auditing, tax and legal services.
General
and administrative expenses also include expenses for the cost of preparing, filling and prosecuting patent applications and maintaining,
enforcing and defending intellectual property-related claims, including our on-going patent interference and patent infringement lawsuits
against Clarus.
We
expect that general and administrative expenses will increase in the future as we mature as a public company including legal and consulting
fees, accounting and audit fees, director fees, increased directors’ and officers’ insurance premiums, fees for investor
relations services and enhanced business and accounting systems, litigation costs, professional fees and other costs. If we are unable
to raise additional capital, we may need to reduce general and administrative expenses in order to extend our ability to continue as
a going concern.
Other
Expense (Income)
Other
expense (income) consists primarily of interest income earned on our cash, cash equivalents and marketable investment securities and
interest expense incurred on our outstanding Loan and Security Agreement and losses (gains) on our warrant liability.
Results
of Operations
Comparison
of the Three Months Ended March 31, 2022 and 2021
The
following table summarizes our results of operations for the three months ended March 31, 2022 and 2021:
| |
Three
Months Ended March 31, | | |
| |
| |
2022 | | |
2021 | | |
Variance | |
Research
and development expenses | |
$ | 1,887,953 | | |
$ | 1,580,540 | | |
$ | 307,413 | |
General
and administrative expenses | |
| 1,243,687 | | |
| 1,533,953 | | |
| (290,266 | ) |
Interest
and investment income | |
| 41,576 | | |
| 10,649 | | |
| 30,927 | |
Interest
expense | |
| 19,529 | | |
| 68,973 | | |
| (49,444 | ) |
Unrealized
loss on warrant liability | |
| 377,988 | | |
| 195,065 | | |
| 182,923 | |
Income
tax expense | |
| 200 | | |
| 200 | | |
| - | |
Research
and Development Expenses
The increase in research and
development expenses during the three months ended March 31, 2022, as compared to the three months ended March 31, 2021 consisted of
$431,000 in contract research organization expense related to our ongoing Phase 2 clinical study for LPCN 1148, an increase of $288,000
for PK and food effect studies for LPCN 1107 and LPCN 1154, an increase of $152,000 in manufacturing scale up for LPCN 1111, an increase
of $125,000 in personnel expenses and an increase of $77,000 in other R&D costs. These increases were offset by a decrease
of $679,000 in contract research organization expense and outside consulting costs related to the completion of our LPCN 1144 LiFT
Phase 2 clinical study in NASH subjects and a decrease of $87,000 in costs associated with TLANDO.
General
and Administrative Expenses
The
decrease in general and administrative expenses during the three months ended March 31, 2022 was primarily due to a $474,000 decrease
in legal costs due to less activity in 2022 as compared to 2021 with the July 2021 settlement of the lawsuit filed against Clarus Therapeutics
Inc. for patent infringement and a decrease of $22,000 in personnel costs. These decreases were offset by an increase of $65,000 in professional
fees related to the recruitment of additional directors to our Board, a $64,0000 increase in various consulting services, an increase
of $35,000 for proxy solicitation services, $26,000 increase in corporate insurance expenses, and a $16,000 decrease in other general
and administrative costs.
Interest
and Investment Income
The
increase in interest and investment income during the three months ended March 31, 2022 was due to higher interest rates in 2022 compared
to 2021.
Interest
Expense
The
decrease in interest expense during the three months ended March 31, 2022, was due to a decrease in interest expense on our Loan and
Security Agreement with SVB as a result of lower principal balances in 2022 compared to 2021.
Loss
on Warrant Liability
We
recorded a loss of $378,000 and $195,000, respectively, on warrant liability during the three months ended March 31, 2022, and 2021 related
to the change in the fair value of outstanding common stock warrants issued in the November 2019 Offering. The loss in 2022 and 2021
was mainly attributable to an increase in the value of warrants outstanding as of March 31, as compared to December 31, in both 2022
and 2021 due to an increase in our stock price. There were zero and 10,000 common stock warrants from the November 2019 Offering exercised
during the three months ended March 31, 2022, and March 31, 2021, respectively. The warrants are classified as a liability due to a provision
contained within the warrant agreement which allows the warrant holder the option to elect to receive an amount of cash equal to the
value of the warrants as determined in accordance with the Black-Scholes option pricing model with certain defined assumptions upon a
change of control. The warrant liability will continue to fluctuate in the future based on inputs to the Black-Scholes model including
our current stock price, the remaining life of the warrants, the volatility of our stock price, the risk-free interest rate and the number
of common stock warrants outstanding.
Liquidity
and Capital Resources
Since
our inception, our operations have been primarily financed through sales of our equity securities, debt and payments received under our
license and collaboration arrangements. We have devoted our resources to funding research and development programs, including discovery
research, preclinical and clinical development activities. We have incurred operating losses in most years since our inception and we
expect to continue to incur operating losses into the foreseeable future as we advance clinical development of LPCN 1148, LPCN 1111,
LPCN 1144, LPCN 1107, NAS including LPCN 1154 and LPCN 2101, and any other product candidate, including continued research efforts.
As
of March 31, 2022, we had $42.0 million of unrestricted cash, cash equivalents and marketable investment securities compared to $46.6
million at December 31, 2021.
On
January 28, 2021, we completed a public offering of securities registered under an effective registration statement filed pursuant to
the Securities Act of 1933, as amended (“January 2021 Offering”). The gross proceeds from the January 2021 Offering were
approximately $28.7 million, before deducting underwriter fees and other offering expenses of $1.9 million. In the January 2021 Offering,
we sold 16,428,571 shares of our common stock.
On
January 5, 2018, we entered into the Loan and Security Agreement with SVB pursuant to which SVB agreed to lend us $10.0 million. The
principal borrowed under the Loan and Security Agreement bears interest at a rate equal to the Prime Rate, as reported in money rates
section of The Wall Street Journal or any successor publication representing the rate of interest per annum then in effect, plus one
percent per annum, which interest is payable monthly. Additionally on April 1, 2020, we entered into a Deferral Agreement with SVB. Under
the Deferral Agreement, principal repayments were deferred by six months and we were only required to make monthly interest payments
during the deferral period. The Loan matures on June 1, 2022. Previously, we were only required to make monthly interest payments until
December 31, 2018, following which we also made equal monthly payments of principal and interest until the signing of the Deferral Agreement.
We will also be required to pay an additional final payment at maturity equal to $650,000 (the “Final Payment Charge”). At
our option, we may prepay all amounts owed under the Loan and Security Agreement (including all accrued and unpaid interest and the Final
Payment Charge). In connection with the Loan and Security Agreement, we granted to SVB a security interest in substantially all of our
assets now owned or hereafter acquired, excluding intellectual property and certain other assets. In addition, as TLANDO was not approved
by the FDA by May 31, 2018, we were required to maintain $5.0 million of cash collateral at SVB until such time as TLANDO is approved
by the FDA. However, on February 16, 2021, we amended the Loan and Security Agreement with SVB to, among other things, remove the financial
trigger and financial trigger release event provisions requiring us to maintain a minimum cash collateral value and collateral pledge
thereof. While any amounts are outstanding under the Loan and Security Agreement, we are subject to a number of affirmative and negative
covenants, including covenants regarding dispositions of property, business combinations or acquisitions, incurrence of additional indebtedness
and transactions with affiliates, among other customary covenants. The credit facility also includes events of default, the occurrence
and continuation of which could cause interest to be charged at the rate that is otherwise applicable plus 5.0% and would provide SVB,
as collateral agent, with the right to exercise remedies against us and the collateral securing the credit facility, including foreclosure
against the property securing the credit facilities, including our cash. These events of default include, among other things, any failure
by us to pay principal or interest due under the credit facility, a breach of certain covenants under the credit facility, the Company’s
insolvency, a material adverse change, and one or more judgments against us in an amount greater than $100,000 individually or in the
aggregate.
On
March 6, 2017, we entered into the Sales Agreement with Cantor pursuant to which we may issue and sell, from time to time, shares of
our common stock having an aggregate offering price of up to the amount we have registered on an effective registration statement pursuant
to which the offering is being made. We currently have registered up to $50.0 million for sale under the Sales Agreement, pursuant to
our Registration Statement on Form S-3 (File No. 333-250072), through Cantor as our sales agent. Cantor may sell our common stock by
any method permitted by law deemed to be an “at the market offering” as defined in Rule 415(a)(4) of the Securities Act,
including sales made directly on or through the NASDAQ Capital Market or any other existing trade market for our common stock, in negotiated
transactions at market prices prevailing at the time of sale or at prices related to prevailing market prices, or any other method permitted
by law. Cantor uses its commercially reasonable efforts consistent with its normal trading and sales practices and applicable law and
regulations to sell these shares. We pay Cantor 3.0% of the aggregate gross proceeds from each sale of shares under the Sales Agreement.
We have also provided Cantor with customary indemnification rights.
The
shares of our common stock sold under the Sales Agreement are sold and issued pursuant to our Registration Statement on Form S-3 (File
No. 333-250072) (the “Form S-3”), which was previously declared effective by the Securities and Exchange Commission, and
the related prospectus and one or more prospectus supplements.
We
are not obligated to make any sales of our common stock under the 2020 Sales Agreement. The offering of our common stock pursuant to
the 2020 Sales Agreement will terminate upon the termination of the 2020 Sales Agreement as permitted therein. We and Cantor may each
terminate the 2020 Sales Agreement at any time upon ten days’ prior notice.
We
did not sell any shares of our common stock pursuant to the Sales Agreement during the three months ended March 31, 2022. During the
three months ended March 31, 2021, we sold 1,811,238 shares of our common stock resulting in net proceeds of approximately $3.4 million
under the Sales Agreement which is net of $112,000 in expenses consisting of commissions paid to Cantor in connection with these sales
and other offering and accounting costs. As of March 31, 2022, we had $41.2 million available for sale under the Sales Agreement.
We
believe that our existing capital resources, together with interest thereon, will be sufficient to meet our projected operating requirements
through at least March 31, 2023 which includes an on-going clinical study for LPCN 1148, research and development activities and compliance
with regulatory requirements. We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available
capital resources sooner than we currently expect if additional activities are performed by us including new clinical studies for LPCN
1111, LPCN 1144, LPCN 1107 and NASs. While we believe we have sufficient liquidity and capital resources to fund our projected operating
requirements through at least March 31, 2023, we will need to raise additional capital at some point through the equity or debt markets
or through out-licensing activities, either before or after March 31, 2023, to support our operations. If we are unsuccessful in raising
additional capital, our ability to continue as a going concern will be limited. Further, our operating plan may change, and we may need
additional funds to meet operational needs and capital requirements for product development, regulatory compliance and clinical trial
activities sooner than planned. In addition, our capital resources may be consumed more rapidly if we pursue additional clinical studies
for LPCN 1111, LPCN 1144, LPCN 1107 and NASs including LPCN 1154 and LPCN 2101. Conversely, our capital resources could last longer if
we reduce expenses, reduce the number of activities currently contemplated under our operating plan or if we terminate or suspend on-going
clinical studies or intellectual property litigation, or if we terminate or settle any on-going litigation activities. We can raise capital
pursuant to the Sales Agreement when not restricted due to terms of previous financings but may choose not to issue common stock if our
market price is too low to justify such sales in our discretion. In addition, as of March 31, 2022, we have 5,223,779 unissued and unreserved
shares available for issuance. Without sufficient shares available for issuance, our ability to raise capital through sales of equity,
including under the Sales Agreement, is limited. While we are seeking shareholder approval of an amendment to our Amended and Restated
Certificate of Incorporation of the Company to increase the number of authorized shares of common stock, there is no guarantee that we
will obtain such approval. We rely on our authorized but unissued shares of common stock to raise capital from time to time to fund the
development of our pipeline and advance product candidates to stages that allow for out licensing, allow us to remain independent and
maintain business flexibility, and create value for our shareholders. Without sufficient authorized but unissued shares of common stock,
we will be limited in our ability to raise capital, which could have an adverse impact on our liquidity and ability to operate our business.
If we are unable to effectively raise capital, including through the sale of capital stock or other equity securities, our business and
financial condition will be adversely affected. There are numerous risks and uncertainties associated with the development and, subject
to approval by the FDA, commercialization of our product candidates. There are also numerous risks and uncertainties impacting our ability
to enter into collaborations with third parties to participate in the development and potential commercialization of our product candidates.
We are unable to precisely estimate the amounts of increased capital outlays and operating expenditures associated with our anticipated
or unanticipated clinical studies and ongoing development and pre-commercialization efforts. All of these factors affect our need for
additional capital resources. To fund future operations, we will need to ultimately raise additional capital and our requirements will
depend on many factors, including the following:
|
●
|
the
scope, rate of progress, results and cost of our clinical studies, preclinical testing and other related activities for all of our
product candidates, including LPCN 1148, LPCN 1111, LPCN 1144, LPCN 1107 and neuroactive steroids including LPCN 1154 and LPCN 2101; |
|
|
|
|
● |
the
cost of manufacturing clinical supplies and establishing commercial supplies of our product candidates and any products that we may
develop; |
|
● |
the
cost and timing of establishing sales, marketing and distribution capabilities, if any; |
|
|
|
|
● |
the
terms and timing of any collaborative, licensing and other arrangements that we may establish; |
|
|
|
|
● |
the
number and characteristics of product candidates that we pursue; |
|
|
|
|
● |
the
cost, timing and outcomes of regulatory approvals; |
|
|
|
|
● |
the
timing, receipt and amount of sales, profit sharing, milestones or royalties, if any, from our potential products; |
|
|
|
|
● |
the
cost of preparing, filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; |
|
|
|
|
● |
the
extent to which we acquire or invest in businesses, products or technologies, although we currently have no commitments or agreements
relating to any of these types of transactions; and |
|
|
|
|
● |
the
extent to which we grow significantly in the number of employees or the scope of our operations. |
Funding
may not be available to us on favorable terms, or at all. Also, market conditions may prevent us from accessing the debt and equity capital
markets, including sales of our common stock through the Sales Agreement. If we are unable to obtain adequate financing when needed,
we may have to delay, reduce the scope of or suspend one or more of our clinical studies, research and development programs or, if any
of our product candidates receive approval from the FDA, commercialization efforts. We may seek to raise any necessary additional capital
through a combination of public or private equity offerings, including the Sales Agreement, debt financings, collaborations, strategic
alliances, licensing arrangements and other marketing and distribution arrangements. These arrangements may not be available to us or
available on terms favorable to us. To the extent that we raise additional capital through marketing and distribution arrangements, other
collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our product
candidates, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us.
If we do raise additional capital through public or private equity offerings, the ownership interest of our existing stockholders will
be diluted, and the terms of these securities may include liquidation or other preferences, warrants or other terms that adversely affect
our stockholders’ rights or further complicate raising additional capital in the future. If we raise additional capital through
debt financing, we may be subject to covenants limiting or restricting our ability to take specific actions, such as incurring additional
debt, making capital expenditures or declaring dividends. If we are unable, for any reason, to raise needed capital, we will have to
reduce costs, delay research and development programs, liquidate assets, dispose of rights, commercialize products or product candidates
earlier than planned or on less favorable terms than desired or reduce or cease operations.
Sources
and Uses of Cash
The
following table provides a summary of our cash flows for the three months ended March 31, 2022, and 2021:
| |
Three
Months Ended March 31, | |
| |
2022 | | |
2021 | |
Cash
used in operating activities | |
$ | (3,885,402 | ) | |
$ | (4,061,774 | ) |
Cash
provided by (used in) investing | |
| 7,295,427 | | |
| (33,994,221 | ) |
Cash
provided by financing activities | |
| (627,346 | ) | |
| 29,440,207 | |
Net
Cash From Operating Activities
During
the three months ended March 31, 2022, and 2021, net cash used in operating activities was $3.9 million and $4.1 million, respectively.
Net
cash used in operating activities during the three months ended March 31, 2022, and 2021 was primarily attributable to cash outlays
to support ongoing operations, including research and development expenses and general and administrative expenses. During 2022 we performed
activities related mainly to the following: Phase 2 POC study in male cirrhotic subjects with LPCN 1148, PK and food effect studies with
LPCN 1154 and LPCN 1107, and manufacturing scale up with LPCN 1111. During 2021 we primarily performed activities related to the LPCN
1144 LiFT Phase 2 paired biopsy clinical study.
Net
Cash From Investing Activities
During
the three months ended March 31, 2022, net cash provided by investing activities was $7.3 million compared to net cash used in investing
activities of $34.0 million during the three months ended March 31, 2021.
Net
cash provided by investing activities during the three months ended March 31, 2022, was primarily the result of the net maturities of
marketable investment securities of $7.3 million. Net cash used in investing activities during the three months ended March 31, 2021
was primarily the result of purchasing marketable investment securities, net, of $34.4 million. There were $27,000 in capital expenditures
during the three months ended March 31, 2022, and no capital expenditures during the three months ended March 31, 2021.
Net
Cash From Financing Activities
During
the three months ended March 31, 2022, net cash used in financing activities was $627,000 and during the three months ended March 31,
2021, net cash provided by financing activities was $29.4 million.
Net
cash used in financing activities during the three months ended March 31, 2022, was due to $833,000 in debt principal repayments under
the SVB Loan and Security Agreement, offset by $206,000 cash provided by proceeds from stock option exercises. Net cash provided by financing
activities during the three months ended March 31, 2021, was attributable to the net proceeds from the sale of 16,428,571 shares of common
stock pursuant to January 2021 Offering resulting in net proceeds of $26.8 million and $3.4 million in proceeds from the sale of 1,811,238
shares of common stock pursuant to the ATM, offset by $833,000 in debt principal repayments.
Contractual
Commitments and Contingencies
Long-Term
Debt Obligations and Interest on Debt
On
January 5, 2018, we entered into a Loan and Security Agreement with SVB pursuant to which SVB agreed to lend us $10.0 million. The principal
borrowed under the Loan and Security Agreement bears interest at a rate equal to the Prime Rate plus one percent per annum, which interest
is payable monthly. The loan matures on June 1, 2022 and we are required to make equal monthly payments of principal and interest for
the remaining term of the loan beginning on November 1, 2020 although there was a principal deferment period of six months beginning
on April 1, 2020 due to COVID-19. We will also be required to pay the Final Payment Charge at maturity.
Purchase
Obligations
We
enter into contracts and issue purchase orders in the normal course of business with clinical research organizations for clinical trials
and clinical and commercial supply manufacturing and with vendors for preclinical research studies, research supplies and other services
and products for operating purposes. These contracts generally provide for termination on notice and are cancellable obligations.
Operating
Leases
In
August 2004, we entered into an agreement to lease our facility in Salt Lake City, Utah consisting of office and laboratory space which
serves as our corporate headquarters. On January 24, 2022, we modified and extended the lease through February 28, 2023.
Critical
Accounting Policies and Significant Judgments and Estimates
Our
management’s discussion and analysis of our financial condition and results of operations is based on our financial statements
which we have prepared in accordance with U.S. generally accepted accounting principles. In preparing our financial statements, we are
required to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets
and liabilities at the date of the financial statements and the reported amounts of revenues and expenses during the reporting periods.
Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances,
the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent
from other sources. Actual results may differ from these estimates under different assumptions or conditions. There have been no significant
and material changes in our critical accounting policies during the three months ended March 31, 2022, as compared to those disclosed
in “Management’s Discussion and Analysis of Financial Condition and Results of Operations-Critical Accounting Policies and
Significant Judgments and Estimates” in our Form 10-K filed March 9, 2022.
New
Accounting Standards
Refer
to Note 12, in “Notes to Unaudited Condensed Consolidated Financial Statements” for a discussion of accounting standards
not yet adopted.
Off-Balance
Sheet Arrangements
None.