− Pivotal Phase 3 BOSTON Study Underway –
Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage
pharmaceutical company, today reported financial results for the
second quarter 2017 and commented on recent accomplishments and
clinical development plans for its lead, novel, oral Selective
Inhibitor of Nuclear Export (SINE™) compound selinexor (KPT-330),
and other pipeline assets verdinexor (KPT-335), and KPT-9274, its
oral, dual inhibitor of p21-activated kinase 4 (PAK4) and
nicotinamide phosphoribosyltransferase (NAMPT).
“Our second quarter achievements marked
significant progress across several of our development programs,
and especially for selinexor,” said Michael G. Kauffman, MD, PhD,
Chief Executive Officer of Karyopharm. “At the 2017 European
Hematology Association (EHA) Annual Meeting, we reported updated
data from the Phase 2b SADAL study investigating selinexor in
patients with relapsed or refractory diffuse large B-cell lymphoma
(DLBCL). The overall response rate (ORR) increased to 33.3%
for the overall trial population with similar response rates in
patients with double- or triple-hit DLBCL, indicating clear
activity in this population which usually has a particularly poor
prognosis. As we move to the second half of the year, our
focus remains on execution of key later-stage trials in our lead
indications of multiple myeloma (MM), DLBCL and liposarcoma.
In myeloma, the pivotal Phase 3 BOSTON study is now underway.
The Phase 2b STORM study, for possible accelerated approval,
continues to enroll well with top-line data expected by April
2018. In liposarcoma, the Phase 2 portion of the blinded,
randomized Phase 2/3 SEAL study recently completed enrollment and
we look forward to reporting the hazard ratio for progression-free
survival (PFS) and providing an update regarding the planned
development path in this indication during September or October
2017.”
Second Quarter 2017 and Recent Events,
Highlights and Milestones:
Selinexor in Multiple Myeloma
- Pivotal Phase 3 BOSTON Study Initiated.
Karyopharm initiated the pivotal, randomized Phase 3 BOSTON
(Bortezomib, Selinexor and
dexamethasone) study, evaluating
once weekly selinexor 100mg in combination with the proteasome
inhibitor Velcade (bortezomib, once weekly) and dexamethasone
(SVd), compared to standard dose Velcade (twice weekly) and
low-dose dexamethasone (Vd) in patients with MM who have had one to
three prior lines of therapy. The primary endpoints of the
study are PFS and ORR. The BOSTON study is expected to enroll
approximately 360 patients at over 100 clinical sites
internationally. Karyopharm is projecting to complete
enrollment in 2018, with top-line data anticipated in 2019.
- Selinexor Named Among the “Top 5 Oncology R&D
Products Worldwide in 2022” by EvaluatePharma®. In
EvaluatePharma’s recent report, World Preview 2017, Outlook to
2022, selinexor was projected to be one of the top five selling
oncology research and development products worldwide in 2022, with
the potential to generate estimated revenues of $920 million in
worldwide annual sales and capture 0.5% of the worldwide oncology
market share in the same timeframe. This analysis is based on
EvaluatePharma’s coverage of the world’s 6,500 leading
pharmaceutical and biotech companies and highlights certain
important industry trends by therapy area.
- Ongoing Phase 2b STORM Study Expansion in Patients with
Penta-refractory MM. The Phase 2b STORM study, which
was recently expanded to include 122 additional patients with
penta-refractory MM, continues to enroll on track. Karyopharm
expects to report top-line data from the expanded cohort by April
2018, and, assuming a positive outcome, intends to use the data
from the expanded STORM study to support a request for accelerated
approval for selinexor in heavily pretreated MM.
- Ongoing Phase 1b/2 STOMP Study Evaluating Selinexor in
Combination with Several Key MM Drugs. Enrollment is
complete in the Phase 1b/2 STOMP arm evaluating selinexor in
combination with Velcade and low-dose dexamethasone (SVd) in
heavily pretreated patients with MM. The SVd arm of the STOMP
study enrolled 42 patients. Dose escalation is complete and
expansion is ongoing in the arms evaluating oral selinexor plus
immunomodulatory drug (IMID) combinations, including selinexor +
Revlimid® (lenalidomide) + dexamethasone (SRd), and selinexor +
Pomalyst® (pomalidomide) and dexamethasone (SPd). The Company
expects to report updated data on these convenient, all oral
regimens by year end 2017.
- New Study Arm Initiated in Phase 1b/2 STOMP Study
Evaluating Selinexor in Combination with Darzalex®
(daratumumab). Karyopharm has dosed
patients in a new Phase 1b/2 STOMP study arm designed to evaluate
selinexor in combination with the anti-CD38 monoclonal antibody
Darzalex and low-dose dexamethasone (SDd) in heavily pretreated
patients with MM. The SDd arm of the STOMP study is expected
to enroll up to 16 patients and the Company expects to report
top-line data in the first half of 2018.
Selinexor in Diffuse Large B-Cell Lymphoma
- Updated Data from Phase 2b SADAL Study in DLBCL
Presented at EHA 2017. At the 2017 EHA Annual
Meeting in June, an oral presentation was given that highlighted
updated data from the ongoing Phase 2b SADAL study evaluating
single-agent selinexor in patients with relapsed or refractory
DLBCL. This latest data demonstrated that selinexor achieved
an ORR of 33.3% and a duration of response (DOR) of >7 months in
the first 63 patients, as adjudicated by an independent central
radiological committee. Patients were randomized to one of
two single-agent selinexor arms, a higher dose arm of 100 mg twice
weekly and a lower dose arm of 60 mg twice weekly. The median
overall survival was 8 months for all patients, consistent with
published data in this population which has a very poor prognosis.
As of the data cutoff date, the median survival for the
responders had not been reached and was over 9 months. Most
responses occurred at the first response evaluation (~2
months). As of the data cutoff date, 9 of the 21 responding
patients remained on treatment, including 6 patients who had a
complete response (CR). Selinexor also showed robust,
single-agent activity against GCB and non-GCB subtypes of DLBCL. Of
the 32 patients with DLBCL of the GCB-subtype, 9 responded (4
patients with a CR, 5 patients with a partial response (PR)) for an
ORR of 28.1%. Of the 31 patients with DLBCL of the non-GCB
(or ABC)-subtype, 12 responded (5 patients with a CR, 7 patients
with a PR) for an ORR of 38.7%. Amongst the 14 patients with
"double-" or "triple-hit" DLBCL, the ORR was consistent with the
ORR across the SADAL patient population, indicating anti-cancer
activity in this population, which usually has a particularly poor
prognosis. Side effects were consistent with those previously
reported with selinexor, and no new safety signals were
identified. Importantly, side effects were reduced in the
60mg cohort in comparison with the 100mg cohort.In consultation
with the U.S. Food and Drug Administration (FDA), Karyopharm
amended the SADAL study, removing the 100mg arm and continuing
enrollment only in the 60mg twice weekly arm. The FDA has
agreed that the single-arm trial design appears appropriate for
accelerated approval in DLBCL, though eligibility for accelerated
approval will depend on the complete trial results and available
therapies at the time of regulatory action. The SADAL study
is expected to enroll up to a total of 130 patients in the 60mg
single-arm cohort and Karyopharm plans to report top-line results
in the second half of 2018.
Selinexor in Other Hematologic Malignancies
Published Phase 1 Data Demonstrating
Selinexor's Activity in Patients with Relapsed/Refractory
Non-Hodgkin’s Lymphoma (NHL) in the Journal Blood. A
paper describing results from the first in human Phase 1 clinical
study assessing safety and preliminary activity of selinexor in
patients with relapsed or refractory NHL was recently published in
the journal Blood. In the paper, authored by John Kuruvilla,
et al., titled “Selective inhibition of nuclear export with
selinexor in patients with non-Hodgkin's lymphoma,” Karyopharm
collaborators reported that selinexor was generally well
tolerated. Of the 70 evaluable patients, 22 (31%) achieved an
objective response (OR), including 4 CRs and 18 PRs, which were
observed across a spectrum of NHL subtypes, including DLBCL,
Richter's transformation, mantle cell lymphoma, follicular lymphoma
and chronic lymphocytic leukemia. All four CRs were in patients
with DLBCL, and two of the four patients are believed to have
remained relapse-free as of the publication date, greater than 3
years since initiation of single agent selinexor therapy.
Tumor biopsies showed decreases in cell signaling pathways, reduced
proliferation, nuclear localization of XPO1 cargos and increased
apoptosis after treatment. The most common grade 3-4 drug-related
AEs were thrombocytopenia (47%), neutropenia (32%), anemia (27%),
leukopenia (16%), fatigue (11%) and hyponatremia (10%). A maximum
tolerated dose was not defined, but the highest allowable dose was
~120 mg twice weekly. Based on both tolerability and
antitumor activity, the recommended Phase 2 dose of selinexor in
NHL is 35 mg/m2 (~60 mg) twice weekly.
Selinexor in Solid Tumors
- Ongoing Phase 2/3 SEAL Study in
Liposarcoma. Enrollment is now complete in the Phase
2 portion of the blinded, randomized Phase 2/3 SEAL study
evaluating single-agent selinexor versus placebo in patients with
advanced liposarcoma. Karyopharm expects to report the hazard
ratio for PFS from the Phase 2 portion of the SEAL study and
providing an update regarding the planned development path in this
indication during September or October 2017. The primary
endpoint of the SEAL study is PFS and both the trial design and
endpoints have been accepted by the FDA and the European Medicines
Agency.
- Oral Presentation Highlighting Efficacy, Safety and
Intratumoral Pharmacokinetic Data for Selinexor in Glioblastoma at
the 2017 World Federation of Neuro-Oncology Societies (WFNOS)
Meeting. Clinical data from a Phase 2 study
evaluating selinexor in patients with recurrent glioblastoma was
highlighted in an oral presentation at the 2017 WFNOS meeting by
Andrew Lassman, MD, Columbia University Medical Center. The data
demonstrated that oral selinexor achieved responses and sufficient
intratumoral penetration, with a manageable tolerability profile
when accompanied by standard supportive care. Importantly,
disease control rates using selinexor dosed at 80 mg once weekly
were as high or higher than those observed with more intensive
dosing, and tolerability was improved.
Verdinexor
- Signed Global License Agreement with Anivive
Lifesciences for Verdinexor for Animal Health
Applications. Karyopharm and Anivive, a
privately-held biotech company, executed a licensing agreement
under which Anivive licensed from Karyopharm exclusive worldwide
rights to research, develop and commercialize verdinexor for the
treatment of cancer in companion animals. Under the terms of
the agreement, Anivive made a one-time upfront payment of $1
million to Karyopharm. Anivive also agreed to pay up to an
additional $43.5 million based on technology transfer and
achievement of specified regulatory, clinical and commercial
milestones, assuming approval in both the U.S. and the European
Union. In addition, Anivive agreed to pay Karyopharm a low
double-digit royalty based on future net sales of verdinexor.
KPT-9274
- Preclinical Efficacy Highlighting KPT-9274’s
Anti-Cancer Activity in Dogs with Spontaneous Lymphomas Presented
as a Late-Breaking Poster at the American Association of Cancer
Research (AACR) 2017 Annual Meeting. At the AACR
2017 Annual Meeting in April, Karyopharm collaborator Cheryl London
of Tufts University presented a late-breaking poster highlighting
preclinical data demonstrating the activity and synergy of
KPT-9274, the Company’s oral dual inhibitor of PAK4/NAMPT, with
doxorubicin to treat dogs with lymphoma. KPT-9274 is
currently being evaluated in a Phase 1 safety and tolerability
study in patients with advanced solid malignancies (including
sarcoma, colon and lung cancer) or non-Hodgkin's lymphoma (NHL)
whose disease has relapsed after standard therapy(s).
Top-line data from this clinical study are expected later this
year.
Other Corporate and Clinical Developments
- Generated $52.3 Million in Equity
Financings. In April 2017, the Company sold
approximately 3.9 million shares of common stock in an underwritten
public offering at a price to the public of $10.25 per share,
resulting in net proceeds to the Company of approximately $37.9
million after deducting underwriting discounts and commissions and
other offering expenses, and sold approximately 1.3 million shares
under its ATM offering facility for net proceeds of approximately
$14.4 million.
Second Quarter 2017 Financial
Results
Cash, cash equivalents and investments as of
June 30, 2017, including restricted cash, totaled $181.2 million,
compared to $175.5 million as of December 31, 2016.
On April 28, 2017, Karyopharm completed an
underwritten public offering of 3,902,439 shares of its common
stock at a price to the public of $10.25 per share. The net
proceeds to Karyopharm from the offering, after deducting the
underwriting discounts and commissions and offering expenses, were
approximately $37.9 million. In addition, during April 2017,
the Company sold approximately 1.3 million shares under its ATM
offering facility for net proceeds of approximately $14.4
million.
For the quarter ended June 30, 2017, research
and development expense was $23.1 million compared to $24.6 million
for the quarter ended June 30, 2016. For the quarter ended
June 30, 2017, general and administrative expense was $6.6 million
compared to $6.0 million for the quarter ended June 30, 2016.
Karyopharm reported a net loss of $29.4 million,
or $0.64 per share, for the quarter ended June 30, 2017, compared
to a net loss of $30.2 million, or $0.84 per share, for the quarter
ended June 30, 2016. Net loss includes stock-based
compensation expense of $5.1 million and $6.4 million for the
quarters ended June 30, 2017 and June 30, 2016, respectively.
Financial Outlook
Karyopharm expects its operating cash burn,
including research and development and general and administrative
expenses, for the year ending December 31, 2017 to be in the range
of $90-95 million. Based on current operating plans,
Karyopharm expects that its existing cash and cash equivalents will
be sufficient to fund its research and development programs and
operations into 2019, including the continued clinical development
of selinexor in the Company’s lead indications with a focus on
filing for accelerated approvals for both MM and DLBCL during 2018,
and preparing a commercial infrastructure for the potential launch
of selinexor in North America and Western Europe.
Conference Call
Information:
Karyopharm will host a conference call today,
Tuesday, August 8, 2017, at 8:30 a.m. Eastern Time, to discuss the
second quarter 2017 financial results, recent accomplishments,
clinical developments and business plans. To access the
conference call, please dial (855)
437-4406 (US) or (484) 756-4292 (international) at
least five minutes prior to the start time and refer to conference
ID: 53128722. An audio recording of the call will be
available under “Events & Presentations” in the
“Investor” section of Karyopharm's website,
http://www.karyopharm.com, approximately two hours after the
event.
About Karyopharm
Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a
clinical-stage pharmaceutical company focused on the discovery and
development of novel first-in-class drugs directed against nuclear
transport and related targets for the treatment of cancer and other
major diseases. Karyopharm's SINE™ compounds function by binding
with and inhibiting the nuclear export protein XPO1 (or
CRM1). The Company's initial focus is on seeking regulatory
approval and commercialization of its lead drug candidate, oral
selinexor (KPT-330). To date, over 2,100 patients have been
treated with selinexor and it is currently being evaluated in
several mid- and later-phase clinical trials across multiple cancer
indications, including in multiple myeloma in a pivotal, randomized
Phase 3 study in combination with Velcade® (bortezomib) and
low-dose dexamethasone (BOSTON), in combination with low-dose
dexamethasone (STORM) and backbone therapies (STOMP), and in
diffuse large B-cell lymphoma (SADAL) and liposarcoma (SEAL), among
others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing
or currently planned, including multiple studies in combination
with one or more approved therapies in a variety of tumor types to
further inform the Company's clinical development priorities for
selinexor. In addition to single-agent and combination
activity against a variety of human cancers, SINE™ compounds have
also shown biological activity in models of neurodegeneration,
inflammation, autoimmune disease, certain viruses and
wound-healing. Karyopharm, which was founded by Dr. Sharon Shacham,
currently has five investigational programs in clinical or
preclinical development. For more information, please visit
www.karyopharm.com.
Forward-Looking Statements
This press release contains forward-looking
statements within the meaning of The Private Securities Litigation
Reform Act of 1995. Such forward-looking statements include those
regarding the therapeutic potential of and potential clinical
development plans for Karyopharm's drug candidates, including the
timing of initiation and enrollment of certain trials and of the
reporting of data from such trials, and Karyopharm’s financial
outlook and financial projections for Karyopharm. Such statements
are subject to numerous important factors, risks and uncertainties
that may cause actual events or results to differ materially from
Karyopharm’s current expectations. For example, there can be no
guarantee that any of Karyopharm's SINE™ compounds, including
selinexor (KPT-330) or KPT-9274, Karyopharm's first-in-class oral
dual inhibitor of PAK4 and NAMPT, or any other drug candidate that
Karyopharm is developing, will successfully complete necessary
preclinical and clinical development phases or that development of
any of Karyopharm's drug candidates will continue. Further, there
can be no guarantee that any positive developments in Karyopharm's
drug candidate portfolio will result in stock price appreciation.
Management's expectations and, therefore, any forward-looking
statements in this press release could also be affected by risks
and uncertainties relating to a number of other factors, including
the following: Karyopharm's results of clinical trials and
preclinical studies, including subsequent analysis of existing data
and new data received from ongoing and future studies; the content
and timing of decisions made by the FDA and other regulatory
authorities, investigational review boards at clinical trial sites
and publication review bodies, including with respect to the need
for additional clinical studies; Karyopharm's ability to obtain and
maintain requisite regulatory approvals and to enroll patients in
its clinical trials; unplanned cash requirements and expenditures;
development of drug candidates by Karyopharm's competitors for
diseases in which Karyopharm is currently developing its drug
candidates; and Karyopharm's ability to obtain, maintain and
enforce patent and other intellectual property protection for any
drug candidates it is developing. These and other risks are
described under the caption "Risk Factors" in Karyopharm's
Quarterly Report on Form 10-Q for the quarter ended March 31, 2017,
which was filed with the Securities and Exchange Commission (SEC)
on May 4, 2017, and in other filings that Karyopharm may make with
the SEC in the future. Any forward-looking statements contained in
this press release speak only as of the date hereof, and, except as
required by law, Karyopharm expressly disclaims any obligation to
update any forward-looking statements, whether as a result of new
information, future events or otherwise.
Velcade® is a registered trademark of Takeda
Pharmaceutical Company LimitedRevlimid® and Pomalyst® are
registered trademarks of Celgene CorporationDarzalex® is a
registered trademark of Janssen Biotech, Inc.EvaluatePharma® World
Preview 2017, Outlook to 2022 is copyrighted by Evaluate Ltd.
CONDENSED CONSOLIDATED BALANCE
SHEETS |
(unaudited) |
(in thousands, except share and per share
amounts) |
|
|
|
|
June 30, 2017 |
|
|
December 31, 2016 |
|
Assets |
|
|
|
|
|
|
|
Current assets: |
|
|
|
|
|
|
|
Cash and
cash equivalents |
$ |
55,381 |
|
|
$ |
49,663 |
|
Short-term investments |
|
88,073 |
|
|
|
79,889 |
|
Restricted cash |
|
200 |
|
|
|
— |
|
Prepaid
expenses and other current assets |
|
2,070 |
|
|
|
2,084 |
|
Total
current assets |
|
145,724 |
|
|
|
131,636 |
|
Property and equipment,
net |
|
2,473 |
|
|
|
2,836 |
|
Long-term
investments |
|
37,269 |
|
|
|
45,434 |
|
Restricted cash |
|
284 |
|
|
|
479 |
|
Total
assets |
$ |
185,750 |
|
|
$ |
180,385 |
|
Liabilities and
stockholders’ equity |
|
|
|
|
|
|
|
Current
liabilities: |
|
|
|
|
|
|
|
Accounts
payable |
$ |
3,247 |
|
|
$ |
4,751 |
|
Accrued
expenses |
|
12,876 |
|
|
|
11,362 |
|
Deferred
revenue |
|
1,025 |
|
|
|
— |
|
Deferred
rent |
|
292 |
|
|
|
280 |
|
Other
current liabilities |
|
80 |
|
|
|
83 |
|
Total
current liabilities |
|
17,520 |
|
|
|
16,476 |
|
Deferred rent, net of
current portion |
|
1,516 |
|
|
|
1,666 |
|
Total
liabilities |
|
19,036 |
|
|
|
18,142 |
|
Stockholders’
equity: |
|
|
Preferred
stock, $0.0001 par value; 5,000,000 shares authorized; none issued
and outstanding |
|
— |
|
|
|
— |
|
Common
stock, $0.0001 par value; 100,000,000 shares authorized; 47,123,208
and 41,887,829 shares issued and outstanding at June 30, 2017 and
December 31, 2016, respectively |
|
5 |
|
|
|
4 |
|
Additional paid-in capital |
|
592,534 |
|
|
|
528,617 |
|
Accumulated other comprehensive loss |
|
(165 |
) |
|
|
(274 |
) |
Accumulated deficit |
|
(425,660 |
) |
|
|
(366,104 |
) |
Total
stockholders’ equity |
|
166,714 |
|
|
|
162,243 |
|
Total
liabilities and stockholders’ equity |
$ |
185,750 |
|
|
$ |
180,385 |
|
|
|
|
|
|
|
|
|
Karyopharm Therapeutics Inc. |
CONDENSED CONSOLIDATED STATEMENTS OF
OPERATIONS |
(unaudited) |
(in thousands, except share and per share
amounts) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended,
June 30, |
|
Six Months Ended
June 30, |
|
|
2017 |
|
2016 |
|
2017 |
|
2016 |
Contract and grant
revenue |
|
$ |
3 |
|
|
$ |
59 |
|
|
$ |
71 |
|
|
$ |
59 |
|
Operating
expenses: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Research
and development |
|
|
23,120 |
|
|
|
24,579 |
|
|
|
47,203 |
|
|
|
46,374 |
|
General
and administrative |
|
|
6,635 |
|
|
|
5,956 |
|
|
|
12,899 |
|
|
|
11,510 |
|
Total
operating expenses |
|
|
29,755 |
|
|
|
30,535 |
|
|
|
60,102 |
|
|
|
57,884 |
|
Loss from
operations |
|
|
(29,752 |
) |
|
|
(30,476 |
) |
|
|
(60,031 |
) |
|
|
(57,825 |
) |
Other income
(expense): |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Interest
income |
|
|
412 |
|
|
|
329 |
|
|
|
812 |
|
|
|
615 |
|
Other
expense |
|
|
(29 |
) |
|
|
(11 |
) |
|
|
(44 |
) |
|
|
(7 |
) |
Total
other income, net |
|
|
383 |
|
|
|
318 |
|
|
|
768 |
|
|
|
608 |
|
Loss before income
taxes |
|
|
(29,369 |
) |
|
|
(30,158 |
) |
|
|
(59,263 |
) |
|
|
(57,217 |
) |
Provision for income
taxes |
|
|
(18 |
) |
|
|
— |
|
|
|
(41 |
) |
|
|
— |
|
Net loss |
|
$ |
(29,387 |
) |
|
$ |
(30,158 |
) |
|
$ |
(59,304 |
) |
|
$ |
(57,217 |
) |
Net loss per
share—basic and diluted |
|
$ |
(0.64 |
) |
|
$ |
(0.84 |
) |
|
$ |
(1.35 |
) |
|
$ |
(1.59 |
) |
Weighted-average number
of common shares outstanding used in net loss per share—basic and
diluted |
|
|
45,831,239 |
|
|
|
35,956,470 |
|
|
|
43,873,892 |
|
|
|
35,917,486 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Contacts:
Michelle Carroll
(212) 600-1902
michelle@argotpartners.com
Media:
Eliza Schleifstein
(917) 763-8106
eliza@argotpartners.com
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