Initiated confirmatory Phase 3 RAMP 301 trial
evaluating avutometinib and defactinib combination in recurrent
low-grade serous ovarian cancer; on track to submit rolling NDA for
accelerated approval in H1 2024; preparations underway for
potential commercial launch in 2025
Granted FDA Fast Track designation for
avutometinib and sotorasib combination for the treatment of KRAS
G12C-mutant non-small cell lung cancer
Announced oral KRAS G12D inhibitor GFH375
(VS-7375) as lead program in discovery and development
collaboration with GenFleet Therapeutics
Multiple data readouts evaluating combination
therapies in low-grade serous ovarian cancer, non-small cell lung
cancer and pancreatic cancer anticipated in 2024
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today reported financial results for the three months and full year
ended December 31, 2023, and highlighted recent progress.
“In 2023, we made significant progress toward expanding the
opportunities for avutometinib combination therapies across
RAS/MAPK driven cancers and I am extremely proud of the team’s
accomplishments,” said Dan Paterson, president and chief executive
officer of Verastem Oncology. “2024 is expected to be a pivotal
year with the planned NDA submission for our avutometinib and
defactinib combination in recurrent LGSOC, and multiple clinical
data readouts across our programs including initial data from the
RAMP 205 trial in metastatic pancreatic cancer and data from the
combination with G12C inhibitors in NSCLC. We look forward to
continuing to deliver results across our programs.”
Fourth Quarter 2023 and Recent Highlights
Avutometinib and Defactinib Combination in Low-Grade Serous
Ovarian Cancer (LGSOC)
- Initiated international confirmatory Phase 3 RAMP 301 trial
evaluating the avutometinib and defactinib combination versus
standard of care chemotherapy or hormonal therapy for the treatment
of recurrent LGSOC in December 2023 to support potential full
approval.
- Reported results of a planned subgroup analysis of Part A of
the Phase 2 RAMP 201 trial evaluating avutometinib and defactinib
combination in recurrent LGSOC, which demonstrated promising
efficacy in patients regardless of number and class of prior
therapies including after poor response to prior therapy at the
Annual Global Meeting of the International Gynecologic Cancer
Society meeting in November 2023.
- Launched patient and healthcare professional programs,
including Let’s Talk About LGSOC, to support clinicians in the
diagnosis and management of LGSOC and provide information and
resources to patients.
- Received Orphan Drug Designation from the U.S. Food and Drug
Administration (FDA) in March 2024 for avutometinib alone or in
combination with defactinib for the treatment of all patients with
recurrent LGSOC.
Verastem anticipates the following milestones for avutometinib
and defactinib combination in LGSOC in 2024:
- On track to submit a rolling New Drug Application (NDA) for
Accelerated Approval for the avutometinib and defactinib
combination in LGSOC in H1 2024. Preparations for a potential U.S.
commercial launch in 2025 are ongoing and plans to initiate
discussions with European and Japanese regulatory authorities to
address patient needs outside the U.S. continue to advance.
- Plan to announce updated topline data from RAMP 201 trial in
LGSOC in H1 2024.
Avutometinib in Combination with KRAS G12C Inhibitors in
Non-Small Cell Lung Cancer (NSCLC)
- Received Fast Track designation from the FDA for avutometinib,
in combination with Amgen’s G12C inhibitor, LUMAKRAS™ (sotorasib),
for the treatment of patients with KRAS G12C-mutant metastatic
NSCLC who have received at least one prior systemic therapy and
have not been previously treated with a KRAS G12C inhibitor, in
January 2024.
- Presented initial results from Phase 1/2 RAMP 203 trial
evaluating the efficacy and safety of avutometinib and sotorasib in
patients with KRAS G12C-mutant NSCLC who have or have not been
previously treated with a KRAS G12C inhibitor at the AACR-NCI-EORTC
International Conference on Molecular Targets and Cancer
Therapeutics in October 2023. The confirmed objective rate of
response (ORR) was 25% with responses observed in both KRAS G12C
inhibitor resistant and naïve patients, and a recommended Phase 2
dose was selected.
- Added defactinib to RAMP 203 trial of avutometinib with
sotorasib based on stronger tumor regressions in KRAS G12C-mutant
NSCLC preclinical models when FAKi is added along with G12Ci +
avutometinib.
Verastem anticipates the following milestones for avutometinib
in combination with KRAS G12C inhibitors in 2024:
- Data updates from patients with KRAS G12C-mutant NSCLC in the
Phase 1/2 RAMP 203 trial evaluating avutometinib and sotorasib and
the Phase 1/2 RAMP 204 trial evaluating avutometinib and adagrasib
are planned for mid-2024.
Avutometinib and Defactinib Combination in Frontline
Metastatic Pancreatic Cancer
- Plan to present initial safety and efficacy results from RAMP
205 trial of avutometinib and defactinib in combination with
current standard of care gemcitabine and nab-paclitaxel in
frontline metastatic pancreatic cancer in H1 2024.
GFH375 (VS-7375): Oral KRAS G12D (ON/OFF) Inhibitor
- Completed investigational new drug (IND)-enabling studies for
oral KRAS G12D (ON/OFF) inhibitor GFH375 (VS-7375), the lead
program in the collaboration with GenFleet Therapeutics
(“GenFleet”).
- GenFleet is expected to submit an IND application for GFH375
(VS-7375) in China in H1 2024 with plans to begin a Phase 1 trial
in H2 2024. Discovery/lead optimization continues for second and
third programs.
Upcoming Presentations
Verastem previously announced the acceptance of multiple
abstracts for presentation at upcoming medical conferences:
- Multiple abstracts were selected for oral and poster
presentations at the Society of Gynecologic Oncology (SGO) 2024
Annual Meeting on Women’s Cancer on March 16-18 in San Diego. These
presentations will include a late-breaking oral presentation on a
planned subgroup analysis of Part A of the Phase 2 RAMP 201 trial
of avutometinib and defactinib combination of heavily pretreated
patients with LGSOC and a plenary oral presentation of preclinical
efficacy data of avutometinib in combination with a FAK inhibitor
in recurrent LGSOC as well as a trials-in-progress poster about the
Phase 3 RAMP 301 trial. See press release here.
- Five preclinical data abstracts were accepted for poster
presentation at the American Association for Cancer Research (AACR)
Annual Meeting 2024 on April 5-10 in San Diego. These presentations
will highlight anti-tumor efficacy data of GFH375 (VS-7375), data
on RAF/MEK clamp avutometinib and FAK inhibition in pancreatic
ductal adenocarcinoma models supporting the ongoing RAMP 205 trial,
and avutometinib and a FAK inhibitor combination in cutaneous
melanoma models to overcome resistance to BRAF and MEK inhibitors,
resistance to immunotherapy, and brain metastasis. See press
release here.
Corporate Updates
- Strengthened the executive leadership team with appointments of
Mike Crowther to Chief Commercial and Business Strategy Officer and
the promotion of Dan Calkins to Chief Financial Officer in October
2023.
Fourth Quarter 2023 Financial Results
Verastem Oncology ended the fourth quarter of 2023 with cash,
cash equivalents and investments of $137.1 million.
Total operating expenses for the three months ended December 31,
2023 (the “2023 Quarter”) were $31.1 million, compared to $16.8
million for the three months ended December 31, 2022 (the “2022
Quarter”).
Research & development expenses for the 2023 Quarter were
$22.5 million, compared to $10.7 million for the 2022 Quarter. The
increase of $11.8 million, or 110.3%, primarily resulted from
increased contract research organization costs, increased drug
substance and drug product costs, and increased personnel costs,
including non-cash stock compensation.
Selling, general & administrative expenses for the 2023
Quarter were $8.6 million, compared to $6.1 million for the 2022
Quarter. The increase of $2.5 million, or 41.0%, was primarily
related to increased personnel costs, including non-cash stock
compensation, increased consulting and professional fees, and
additional costs in anticipation of a potential launch of
avutometinib and defactinib in LGSOC.
Net loss for the 2023 Quarter was $27.4 million, or $1.02 per
share (basic and diluted), compared to a net loss of $16.8 million,
or $0.99 per share (basic and diluted, each as adjusted for the
Company’s reverse stock split), for the 2022 Quarter.
For the 2023 Quarter, non-GAAP adjusted net loss was $29.6
million, or $1.10 per share (diluted), compared to non-GAAP
adjusted net loss of $15.4 million, or $0.90 per share (diluted, as
adjusted for the Company’s reverse stock split), for the 2022
Quarter. Please refer to the GAAP to Non-GAAP Reconciliation
attached to this press release.
Full-Year 2023 Financial Results
Total operating expenses for the year ended December 31, 2023
(the “2023 Period”) were $92.1 million, compared to $75.5 million
for the year ended December 31, 222 (the “2022 Period”).
Research & development expenses for the 2023 Period were
$61.4 million, compared to $50.6 million for the 2022 Period. The
increase of $10.8 million, or 21.3%, was primarily related to
increases in contract research organization costs, the $2.0 million
upfront payment made to GenFleet pursuant to the collaboration and
option agreement, and increased personnel costs, including non-cash
stock compensation.
Selling, general & administrative expenses for the 2023
Period were $30.7 million, compared to $25.0 million for the 2022
Period. The increase of $5.7 million, or 22.8%, was primarily
related to increased personnel costs, including non-cash stock
compensation, additional costs in anticipation of a potential
launch of avutometinib and defactinib in LGSOC, and increased
consulting and professional fees.
Net loss for the 2023 Period was $87.4 million, or $3.96 per
share (basic and diluted, each as adjusted for the Company’s
reverse stock split), compared to $73.8 million, or $4.57 per share
(basic and diluted, each as adjusted for the Company’s reverse
stock split) for the 2022 Period.
For the 2023 Period, non-GAAP adjusted net loss was $85.2
million, or $3.86 per share (diluted, as adjusted for the Company’s
reverse stock split), compared to non-GAAP adjusted net loss of
$67.4 million, or $4.18 per share (diluted, as adjusted for the
Company’s reverse stock split), for the 2022 Period. 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 months and
year ended December 31, 2023 and 2022 are included in the tables
accompanying this press release after the unaudited condensed
consolidated financial statements.
About the Avutometinib and Defactinib Combination
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/MAPK
pathway inhibition. In contrast to currently available MEK-only
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
MEK-only inhibitors. The U.S. Food and Drug Administration (FDA)
granted Breakthrough Therapy designation for the combination of
Verastem Oncology’s investigational RAF/MEK clamp avutometinib,
with defactinib, a selective FAK inhibitor, for the treatment of
all patients with recurrent LGSOC regardless of KRAS status after
one or more prior lines of therapy, including platinum-based
chemotherapy. Avutometinib alone or in combination with defactinib
was also granted Orphan Drug Designation by the FDA for the
treatment of LGSOC.
Verastem Oncology is currently conducting clinical trials with
its RAF/MEK clamp avutometinib in RAS/MAPK driven tumors as part of
its (Raf And Mek Program). RAMP 301
(NCT06072781) is a Phase 3 confirmatory trial evaluating the
combination of avutometinib and defactinib versus standard
chemotherapy or hormonal therapy for the treatment of recurrent
LGSOC. RAMP 201 (NCT04625270) is a Phase 2 registration-directed
trial of avutometinib in combination with defactinib in patients
with recurrent LGSOC and enrollment has been completed in each of
the dose optimization and expansion phases and the low-dose
evaluation.
Verastem Oncology has established clinical collaborations with
Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) in combination
with avutometinib and defactinib and KRAZATI™ (adagrasib) in
combination with avutometinib in KRAS G12C mutant NSCLC as part of
the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials,
respectively. Supported by the “Therapeutic Accelerator Award”
received from PanCAN, Verastem Oncology is conducting RAMP 205
(NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib
and defactinib with gemcitabine/nab-paclitaxel in patients with
front-line metastatic pancreatic cancer.
About GFH375 (VS-7375)
GFH375 (VS-7375) is a potential best-in-class, potent and
selective oral KRAS G12D (ON/OFF) inhibitor, identified as the lead
program from the Verastem Oncology discovery and development
collaboration with GenFleet Therapeutics. GenFleet plans to submit
an IND in China for GFH375 (VS-7375) in the first half of 2024, and
upon approval GenFleet is expected to initiate a Phase 1 trial in
China in the second half of 2024. The collaboration includes three
discovery programs, the first being the KRAS G12D inhibitor, and
will provide Verastem Oncology with exclusive options to obtain
licenses to each of the three compounds in the collaboration after
successful completion of pre-determined milestones in Phase 1
trials. The licenses would give Verastem Oncology development and
commercialization rights outside of the GenFleet territories of
mainland China, Hong Kong, Macau, and Taiwan.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a late-stage development
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 FAK inhibition. For more information, please
visit www.verastem.com and follow us on LinkedIn.
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 expected outcome and benefits of the
collaboration with GenFleet, the potential clinical value of
various of its clinical trials, the timing of commencing and
completing trials, including topline data reports, interactions
with regulators, the potential for and timing of commercialization
of product candidates 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. Forward-looking statements are not
guarantees of future performance and are 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, LUMAKRAS™ and others; the
uncertainties inherent in research and development, such as
negative or unexpected results of clinical trials, the occurrence
or timing of applications for our product candidates that may be
filed with regulatory authorities in any jurisdictions; whether and
when regulatory authorities in any jurisdictions may approve any
such applications that may be filed for our product candidates,
and, if approved, whether our product candidates will be
commercially successful in such jurisdictions; 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 trial design, labeling and other matters that
could affect the timing, 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 cause adverse safety events and/or unexpected
concerns may arise from additional data or analysis, or result in
unmanageable safety profiles as compared to their levels of
efficacy; that our product candidates may experience manufacturing
or supply interruptions or failures; that any of our third party
contract research organizations, contract manufacturing
organizations, clinical sites, or contractors, among others, who we
rely on fail to fully perform; that we face substantial
competition, which may result in others developing or
commercializing products before or more successfully than we do
which could result in reduced market share or market potential for
our product candidates; 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, including as a result of conducting
additional studies; that we may not have sufficient cash to fund
our contemplated operations; that we may not attract and retain
high quality personnel; that we or Chugai Pharmaceutical Co., Ltd.
will fail to fully perform under the avutometinib license
agreement; that our target market for our product candidates might
be smaller than we are presently estimating; that Secura Bio, Inc.
will fail to fully perform under the asset purchase agreement with
Secura Bio, Inc., including in relation to milestone payments; that
we will not see a return on investment on the payments we have and
may continue to make pursuant to the collaboration and option
agreement with GenFleet or that GenFleet will fail to fully perform
under the agreement; 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 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, 2023 as filed with the Securities
and Exchange Commission (SEC) on March 14, 2024 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.
Verastem Oncology
Condensed Consolidated Balance Sheets (in thousands)
(unaudited)
December 31, 2023
December 31, 2022
Cash, cash equivalents, &
investments
$
137,129
$
87,894
Accounts receivable, net
—
31
Prepaid expenses and other current
assets
6,553
4,945
Property and equipment, net
37
92
Right-of-use asset, net
1,171
1,789
Restricted cash and other assets
4,828
299
Total assets
$
149,718
$
95,050
Current Liabilities
$
26,380
$
21,663
Long term debt
40,086
24,526
Lease liability, long-term
530
1,470
Preferred stock tranche liability
4,189
—
Convertible preferred stock
21,159
—
Stockholders’ equity
57,374
47,391
Total liabilities, convertible
preferred stock and stockholders’ equity
$
149,718
$
95,050
Verastem Oncology Condensed
Consolidated Statements of Operations (in thousands, except per
share amounts) (unaudited)
Three months ended December
31,
Year ended December
31,
2023
2022
2023
2022
Revenue:
Sale of COPIKTRA license and related
assets revenue
$
—
$
—
$
—
$
2,596
Total revenue
—
—
—
2,596
Operating expenses:
Research and development
22,502
10,740
61,356
50,558
Selling, general and administrative
8,637
6,106
30,728
24,975
Total operating expenses
31,139
16,846
92,084
75,533
Loss from operations
(31,139)
(16,846)
(92,084)
(72,937)
Other income (expense)
(49)
(7)
(109)
47
Interest income
1,869
769
6,214
1,215
Interest expense
(1,120)
(724)
(4,139)
(2,137)
Change in fair value of preferred stock
tranche liability
3,071
—
2,751
—
Net loss
$
(27,368)
$
(16,808)
$
(87,367)
$
(73,812)
Net loss per share—basic and diluted
$
(1.02)
$
(0.99)(1)
$
(3.96)(1)
$
(4.57)(1)
Weighted average common shares outstanding
used in computing:
Net loss per share – basic and diluted
26,808
17,042(1)
22,054(1)
16,138(1)
(1) Amounts have been retroactively restated to reflect the
1-for-12 reverse stock split effected on May 31, 2023
Verastem Oncology
Reconciliation of GAAP to Non-GAAP Financial Information (in
thousands, except per share amounts) (unaudited)
Three months ended December
31,
Year ended December
31,
2023
2022
2023
2022
Net loss reconciliation
Net loss (GAAP basis)
$
(27,368)
$
(16,808)
$
(87,367)
$
(73,812)
Adjust:
Stock-based compensation expense
1,598
1,287
5,860
6,047
Non-cash interest, net
(837)
(3)
(1,132)
228
Change in fair value of preferred stock
tranche liability
(3,071)
—
(2,751)
—
Severance and other
113
109
199
109
Adjusted net loss (non-GAAP
basis)
$
(29,565)
$
(15,415)
$
(85,191)
$
(67,428)
Reconciliation of net loss per
share
Net loss per share – diluted (GAAP
Basis)
$
(1.02)
$
(0.99)(1)
$
(3.96)(1)
$
(4.57)(1)
Adjust per diluted share:
Stock-based compensation expense
0.06
0.09(1)
0.26(1)
0.38(1)
Non-cash interest, net
(0.03)
—(1)
(0.05)(1)
0.01(1)
Change in fair value of preferred stock
tranche liability
(0.11)
—
(0.12)(1)
—
Severance and other
—
—
0.01(1)
0.01(1)
Adjusted net loss per share –
diluted (non-GAAP basis)
$
(1.10)
$
(0.90)(1)
$
(3.86)(1)
$
(4.18)(1)
Weighted average common shares outstanding
used in computing net loss per share—diluted
26,808
17,042(1)
22,054(1)
16,138(1)
(1) Amounts have been retroactively restated to reflect the
1-for-12 reverse stock split effected on May 31, 2023
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240314845611/en/
For Investor and Media Inquiries: Julissa Viana Vice
President, Corporate Communications and Investor Relations
investors@verastem.com or media@verastem.com
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