Combination Trials with Avutometinib
(VS-6766) Ongoing as Part of Development Program Designed to
Maximize Potential Across RAS Pathway-Driven Tumors
Company Confirms Q4 FDA Meeting Based on
Encouraging Results to Date in Ongoing RAMP 201 Trial of
Avutometinib (VS-6766) ± Defactinib in Low-Grade Serous Ovarian
Cancer
RAMP Trials with Avutometinib (VS-6766)
Combinations in KRAS G12C Mutant NSCLC and Frontline Metastatic
Pancreatic Cancer on Track
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today reported financial results for the three months ended
September 30, 2022, and highlighted recent progress.
“In the third quarter, we provided an overall update regarding
our RAMP program with RAF/MEK clamp avutometinib (VS-6766),
including the encouraging interim results of the RAMP 201 trial
that are the basis for advancing our discussions with the FDA
regarding the go forward treatment regimen selection and regulatory
path forward. Building on our breakthrough therapy designation, our
efforts are focused on rapidly advancing this program to make a
difference for patients in this highly recurrent,
chemotherapy-resistant cancer where no treatments are specifically
approved and limited other treatment options are available,” said
Brian Stuglik, CEO of Verastem Oncology. “Based on the response
results and safety profile seen to date in the RAMP 201 trial, we
are looking forward to the results of our broader development
program which is aimed at maximizing combinations with avutometinib
(VS-6766) across RAS pathway-driven tumors, including KRAS G12C
mutant non-small cell lung cancer, frontline metastatic pancreatic
cancer and KRAS mutant colorectal cancer.”
Second Quarter 2022 and Recent Highlights
Low Grade Serous Ovarian Cancer (LGSOC)
- Verastem recently conducted a second planned interim analysis
of the ongoing RAMP 201 trial among patients with recurrent LGSOC.
Based on the results, including independently confirmed responses
and no new safety signals, the Company has confirmed a meeting with
the U.S. Food and Drug Administration (FDA) by the end of the year
to review the data set, to discuss the go forward treatment regimen
selection and align on requirements to initiate a New Drug
Application submission. The Company will provide an update after
the upcoming meeting with the FDA.
- Since the first interim analysis announced in June, the trial
has been continuing with all four cohorts (avutometinib (VS-6766) ±
defactinib in KRAS mutant and KRAS wild type patient populations)
with full enrollment based on the study protocol expected by the
end of the year.
KRAS Mutant Non-Small Cell Lung Cancer (NSCLC) Combination
Studies
- The RAMP 203 Phase 1/2 trial to evaluate the safety,
tolerability and efficacy of avutometinib (VS-6766) in combination
with Amgen’s KRAS G12C inhibitor LUMAKRASTM (sotorasib) in patients
with KRAS G12C mutant NSCLC, has advanced to Cohort 2 of 4 mg
avutometinib (VS-6766) in combination with 960 mg of LUMAKRASTM.
Initial safety results are expected by the end of the year.
- The RAMP 204 Phase 1/2 trial of avutometinib (VS-6766) and
Mirati’s adagrasib, which will determine the maximum tolerated dose
and recommended Phase 2 dose for the combination and evaluate the
safety, tolerability and efficacy of the combination in patients
who have progressed on a KRAS G12C inhibitor, is open and
enrolling.
- The RAMP 203 and 204 studies will investigate the potential
benefits of a more complete vertical blockade of the RAS pathway as
acquired resistance to KRAS G12C inhibitors in patients occurs
predominantly through additional mutations in the RAS pathway, many
of which could be addressed with a downstream inhibitor such as
avutometinib (VS-6766).
- Results of the ongoing investigator-initiated trial of
avutometinib (VS-6766) and everolimus in KRAS-mutant NSCLC are
anticipated in the first half of 2023.
- In a planned analysis of the Part A data from the RAMP 202
trial among patients with KRAS G12V and non G12V KRAS NSCLC treated
with the combination of avutometinib (VS-6766) and defactinib, no
subtype was identified for further clinical evaluation of
avutometinib (VS-6766) with defactinib in this trial. Verastem
plans to present the Part A results of RAMP 202 at an upcoming
medical congress.
Frontline Metastatic Pancreatic Cancer
- The Company announced plans to open the RAMP 205 Phase 1b/2
clinical trial of avutometinib (VS-6766) with defactinib in
addition to standard of care chemotherapy
(gemcitabine/nab-paclitaxel) in frontline metastatic pancreatic
cancer in the fourth quarter of this year. The trial, in
partnership with the Pancreatic Cancer Action Network (PanCAN) will
evaluate whether blockade of KRAS signaling, which is mutated in
more than 90% of pancreatic cancer tumors, along with chemotherapy
and reduction of stromal density, will improve outcomes for
patients with pancreatic cancer.
Corporate Updates
- Avutometinib has been accepted as the International
Nonproprietary Name (INN) and United States Adopted Name (USAN) for
VS-6766.
- Intermittent dosing intellectual property for both avutometinib
(VS-6766) alone (previously announced) and in combination with
defactinib was recently allowed, extending patent coverage up to
2038 and 2040, respectively.
- Anil Kapur, the Executive Vice President, Corporate Strategy
and Chief Commercial Officer at Geron Corporation, was appointed to
the Company’s Board of Directors, effective October 20, 2022.
Third Quarter 2022 Financial Results
Verastem Oncology ended the three months ended September 30,
2022 (2022 Quarter) with cash, cash equivalents and investments of
$104.0 million. Total operating expenses for the 2022 Quarter were
$17.7 million, compared to $14.8 million for the three months ended
September 30, 2021 (2021 Quarter).
Research and development expenses for the 2022 Quarter were
$11.3 million, compared to $9.3 million for the 2021 Quarter. The
increase of $2.0 million, or 21.5%, primarily resulted from an
increase in drug product and drug substance costs, consulting
costs, clinical supply costs, pre-clinical costs, and personnel
costs, including non-cash stock-based compensation.
Selling, general and administrative expenses for the 2022
Quarter were $6.4 million, compared to $5.5 million for the 2021
Quarter. The increase of $0.9 million, or 16.4%, primarily resulted
from an increase in commercial costs, and consulting and
professional costs.
Net loss for the 2022 Quarter was $18.1 million, or $0.09 per
share (basic and diluted), compared to net loss of $22.8 million,
or $0.13 per share (basic and diluted), for the 2021 Quarter.
For the 2022 Quarter, non-GAAP adjusted net loss was $16.6
million, or $0.08 per share (diluted), compared to non-GAAP
adjusted net loss of $12.8 million, or $0.07 per share (diluted),
for the 2021 Quarter. Please refer to the GAAP to Non-GAAP
Reconciliation attached to this press release.
Use of Non-GAAP Financial Measures
To supplement Verastem Oncology’s condensed consolidated
financial statements, which are prepared and presented in
accordance with generally accepted accounting principles in the
United States (GAAP), the Company uses the following non-GAAP
financial measures in this press release: non-GAAP adjusted net
loss and non-GAAP net loss per share. These non-GAAP financial
measures exclude certain amounts or expenses from the corresponding
financial measures determined in accordance with GAAP. Management
believes this non-GAAP information is useful for investors, taken
in conjunction with the Company’s GAAP financial statements,
because it provides greater transparency and period-over-period
comparability with respect to the Company’s operating performance
and can enhance investors’ ability to identify operating trends in
the Company’s business. Management uses these measures, among other
factors, to assess and analyze operational results and trends and
to make financial and operational decisions. Non-GAAP information
is not prepared under a comprehensive set of accounting rules and
should only be used to supplement an understanding of the Company’s
operating results as reported under GAAP, not in isolation or as a
substitute for, or superior to, financial information prepared and
presented in accordance with GAAP. In addition, these non-GAAP
financial measures are unlikely to be comparable with non-GAAP
information provided by other companies. The determination of the
amounts that are excluded from non-GAAP financial measures is a
matter of management judgment and depends upon, among other
factors, the nature of the underlying expense or income amounts.
Reconciliations between these non-GAAP financial measures and the
most comparable GAAP financial measures for the three and nine
months ended September 30, 2022, and 2021 are included in the
tables accompanying this press release after the unaudited
condensed consolidated financial statements.
About Avutometinib (VS-6766)
Avutometinib is a RAF/MEK clamp that induces inactive complexes
of MEK with ARAF, BRAF and CRAF potentially creating a more
complete and durable anti-tumor response through maximal RAS
pathway inhibition. Avutometinib is currently in late-stage
development.
In contrast to other MEK inhibitors, avutometinib blocks both
MEK kinase activity and the ability of RAF to phosphorylate MEK.
This unique mechanism allows avutometinib to block MEK signaling
without the compensatory activation of MEK that appears to limit
the efficacy of other inhibitors. The U.S. Food and Drug
Administration granted Breakthrough Therapy designation for the
combination of Verastem Oncology’s investigational RAF/MEK clamp
avutometinib, with defactinib, its FAK inhibitor, for the treatment
of all patients with recurrent low-grade serous ovarian cancer
(LGSOC) regardless of KRAS status after one or more prior lines of
therapy, including platinum-based chemotherapy.
Verastem Oncology is currently conducting clinical trials with
its RAF/MEK clamp avutometinib in RAS-driven tumors as part of its
(Raf And Mek Program). RAMP 201 is a
registration-directed trial of avutometinib alone and in
combination with defactinib in patients with recurrent LGSOC.
Verastem Oncology has established clinical collaborations with
Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) and adagrasib in
combination with avutometinib in KRAS G12C mutant NSCLC as part of
the RAMP 203 and RAMP 204 trials, respectively. As part of the
“Therapeutic Accelerator Award” Verastem Oncology received from
PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical
trial evaluating avutometinib and defactinib with
gemcitabine/nab-paclitaxel in patients with front-line metastatic
pancreatic cancer.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a development-stage
biopharmaceutical company committed to the development and
commercialization of new medicines to improve the lives of patients
diagnosed with cancer. Our pipeline is focused on novel small
molecule drugs that inhibit critical signaling pathways in cancer
that promote cancer cell survival and tumor growth, including
RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition. For
more information, please visit www.verastem.com.
Forward-Looking Statements Notice
This press release includes forward-looking statements about
Verastem Oncology’s strategy, future plans and prospects, including
statements related to the potential clinical value of various of
its clinical trials, the timing of commencing and completing
trials, including topline data reports, interactions with
regulators and potential for additional development programs
involving Verastem Oncology’s lead compound. The words
"anticipate," "believe," "estimate," "expect," "intend," "may,"
"plan," "predict," "project," "target," "potential," "will,"
"would," "could," "should," "continue," “can,” “promising” and
similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. Each forward-looking statement is subject
to risks and uncertainties that could cause actual results to
differ materially from those expressed or implied in such
statement.
Applicable risks and uncertainties include the risks and
uncertainties, among other things, regarding: the success in the
development and potential commercialization of our product
candidates, including avutometinib in combination with other
compounds, including defactinib, LUMAKRASTM and others; the
occurrence of adverse safety events and/or unexpected concerns that
may arise from additional data or analysis or result in
unmanageable safety profiles as compared to their levels of
efficacy; our ability to obtain, maintain and enforce patent and
other intellectual property protection for our product candidates;
the scope, timing, and outcome of any legal proceedings; decisions
by regulatory authorities regarding labeling and other matters that
could affect the availability or commercial potential of our
product candidates; whether preclinical testing of our product
candidates and preliminary or interim data from clinical trials
will be predictive of the results or success of ongoing or later
clinical trials; that the timing, scope and rate of reimbursement
for our product candidates is uncertain; that third-party payors
(including government agencies) may not reimburse; that there may
be competitive developments affecting our product candidates; that
data may not be available when expected; that enrollment of
clinical trials may take longer than expected; that our product
candidates will experience manufacturing or supply interruptions or
failures; that we will be unable to successfully initiate or
complete the clinical development and eventual commercialization of
our product candidates; that the development and commercialization
of our product candidates will take longer or cost more than
planned; that we or Chugai Pharmaceutical Co., Ltd. will fail to
fully perform under the avutometinib license agreement; that we or
our other collaboration partners may fail to perform under our
collaboration agreements; that we may not have sufficient cash to
fund our contemplated operations; that we may be unable to obtain
adequate financing in the future through product licensing,
co-promotional arrangements, public or private equity, debt
financing or otherwise; that Secura Bio, Inc. will achieve the
milestones that result in payments to us under our asset purchase
agreement with Secura Bio, Inc.; that we will be unable to execute
on our partnering strategies for avutometinib in combination with
other compounds; that we will not pursue or submit regulatory
filings for our product candidates; and that our product candidates
will not receive regulatory approval, become commercially
successful products, or result in new treatment options being
offered to patients.
Other risks and uncertainties include those identified under the
heading “Risk Factors” in the Company’s Annual Report on Form 10-K
for the year ended December 31, 2021 as filed with the Securities
and Exchange Commission (SEC) on March 28, 2022 and in any
subsequent filings with the SEC. The forward-looking statements
contained in this press release reflect Verastem Oncology’s views
as of the date hereof, and the Company does not assume and
specifically disclaims any obligation to update any forward-looking
statements whether as a result of new information, future events or
otherwise, except as required by law.
References
1 Verastem Oncology Press Release. Verastem Oncology Receives
Breakthrough Therapy Designation for VS-6766 with Defactinib in
Recurrent Low-Grade Serous Ovarian Cancer. May 24, 2021. Available
at:
https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-receives-breakthrough-therapy-designation-vs.
Accessed March 2022.
Verastem Oncology
Condensed Consolidated Balance
Sheets
(in thousands)
(unaudited)
September 30,
December 31,
2022
2021
Cash, cash equivalents, &
investments
$
103,976
$
100,256
Accounts receivable, net
74
516
Prepaid expenses and other current
assets
4,709
4,968
Property and equipment, net
121
210
Right-of-use asset, net
1,927
2,302
Restricted cash and other assets
288
410
Total assets
$
111,095
$
108,662
Current Liabilities
$
21,873
$
18,590
Convertible senior notes
268
249
Long term debt
24,399
—
Lease Liability, long-term
1,682
2,264
Stockholders’ equity
62,873
87,559
Total liabilities and stockholders’
equity
$
111,095
$
108,662
Verastem Oncology
Condensed Consolidated
Statements of Operations
(in thousands, except per share
amounts)
(unaudited)
Three months ended September
30,
Nine months ended September
30,
2022
2021
2022
2021
Revenue:
Sale of COPIKTRA license and related
assets revenue
$
—
$
—
$
2,596
$
902
Transition services revenue
—
2
—
606
Total revenue
—
2
2,596
1,508
Operating expenses:
Research and development
11,288
9,325
39,818
27,951
Selling, general and administrative
6,421
5,523
18,869
18,455
Total operating expenses
17,709
14,848
58,687
46,406
Loss from operations
(17,709
)
(14,846
)
(56,091
)
(44,898
)
Other income
20
—
54
—
Interest income
316
40
446
141
Interest expense
(717
)
(7,980
)
(1,413
)
(9,962
)
Net loss
$
(18,090
)
$
(22,786
)
$
(57,004
)
$
(54,719
)
Net loss per share—basic and diluted
$
(0.09
)
$
(0.13
)
$
(0.30
)
$
(0.31
)
Weighted average common shares outstanding
used in computing:
Net loss per share – basic and diluted
197,151
179,861
189,999
174,524
Verastem Oncology
Reconciliation of GAAP to
Non-GAAP Financial Information
(in thousands, except per share
amounts)
(unaudited)
Three months ended September
30,
Nine months ended September
30,
2022
2021
2022
2021
Net loss reconciliation
Net loss (GAAP basis)
$
(18,090
)
$
(22,786
)
$
(57,004
)
$
(54,719
)
Adjust:
Stock-based compensation expense
1,356
1,987
4,760
6,137
Non-cash interest, net
120
7,959
231
9,287
Severance and Other
—
40
—
40
Adjusted net loss (non-GAAP
basis)
$
(16,614
)
$
(12,800
)
$
(52,013
)
$
(39,255
)
Reconciliation of net loss per
Share
Net loss per share – diluted (GAAP
Basis)
(0.09
)
(0.13
)
(0.30
)
(0.31
)
Adjust per diluted share:
Stock-based compensation expense
0.01
0.01
0.02
0.04
Non-cash interest, net
—
0.05
—
0.05
Severance and Other
—
—
—
—
Adjusted net loss per share –
diluted
(non-GAAP basis)
$
(0.08
)
$
(0.07
)
$
(0.28
)
$
(0.22
)
Weighted average common shares outstanding
used in computing net loss per share—diluted
197,151
179,861
189,999
174,524
View source
version on businesswire.com: https://www.businesswire.com/news/home/20221103005859/en/
Investors: Dan Calkins +1 781-469-1694 Investor Relations
dcalkins@verastem.com Nate LiaBraaten +1 212-600-1902
nate@argotpartners.com Media: Lisa Buffington Corporate
Communications +1 781-292-4205 lbuffington@verastem.com
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