On May 13, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported business updates and announced financial results for the first quarter ended March 31, 2025 (Press release, Verastem, MAY 13, 2025, View Source [SID1234652992]).
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"In the first quarter of 2025, we continued to make progress with our pipeline programs by exercising our option early to license VS-7375 from our partner GenFleet Therapeutics, completing enrollment in the initial cohorts in our RAMP 205 clinical trial in first-line metastatic pancreatic cancer, and continuing enrollment in the triplet combination in our RAMP 203 clinical trial in advanced KRAS G12C mutant non-small cell lung cancer," said Dan Paterson, president and chief executive officer of Verastem Oncology. "With a strengthened financial position, we are looking forward to a transformational second quarter with the FDA approval and launch of AVMAPKI FAKZYNJA CO-PACK for KRAS-mutated recurrent low-grade serous ovarian cancer, our plans to initiate a Phase 1/2a study in the U.S. for VS-7375, our potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, in mid-2025, and share updated data for both VS-7375 and RAMP 205 at ASCO (Free ASCO Whitepaper)."
First Quarter 2025 and Recent Updates
Avutometinib and Defactinib Combination in Low-Grade Serous Ovarian Cancer (LGSOC)
Announced the U.S. Food and Drug Administration (FDA) approved AVMAPKI FAKZYNJA CO-PACK (avutometinib capsules; defactinib tablets) for the treatment of adult patients with KRAS-mutated recurrent LGSOC who have received prior systemic therapy on May 8, 2025, in advance of PDUFA action date of June 30, 2025.
Initiation of the commercial execution of the AVMAPKI FAKZYNJA CO-PACK launch in the U.S.
AVMAPKI FAKZYNJA CO-PACK is now available through a specialty distribution network in the U.S.
A support program for patients prescribed AVMAPKI FAKZYNJA CO-PACK, called Verastem Cares, is now available.
Submitted request for NCCN guideline inclusion.
Shared multiple oral and poster presentations at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 on April 25-30, highlighting the exploration of the mechanisms by which the Company’s FAK inhibitor increases the anti-tumor efficacy of avutometinib.
Multiple abstracts were selected for oral and poster presentations at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women’s Cancer on March 14-17 in Seattle. These presentations included an oral presentation of additional analyses from the Phase 2 RAMP 201 trial of avutometinib and defactinib combination with recurrent LGSOC and an oral presentation of interim results from a Phase 2 Investigator-Sponsored Trial evaluating avutometinib plus defactinib in advanced or recurrent gynecologic mesonephric cancer.
Key Milestones Expected for 2025:
Primary analysis from both the FRAME and RAMP 201 clinical trials anticipated to be published in H1 2025.
Complete enrollment for the international Phase 3 confirmatory RAMP 301 clinical trial for patients with recurrent LGSOC regardless of KRAS mutation status by the end of 2025.
Report initial data from the RAMP 201J Phase 2 clinical trial being conducted in Japan with JGOG in H2 2025.
Continue to advance the regulatory pathway in Japan and Europe.
RAMP 205: Avutometinib Plus Defactinib in Combination with Chemotherapy in First-Line Metastatic Pancreatic Cancer
Completed enrollment of 60 patients in the dose-level evaluation phase of RAMP 205 study in Q1; follow-up continues.
In March 2025, announced several updates to the trial, including the addition of a new dose level "0" to evaluate the doses of avutometinib and defactinib used in LGSOC and expanding all dose levels to 12 patients each, including six additional patients to dose level "1", where 5/6 patients reported an objective response (83% cORR) at the ASCO (Free ASCO Whitepaper) 2024 annual meeting.
Key Milestones Expected for 2025:
Plan to report additional data when ASCO (Free ASCO Whitepaper) abstracts are live on May 22, 2025.
Select the recommended Phase 2 Dose (RP2D) for trial expansion in H1 2025.
RAMP 203: Avutometinib Plus Defactinib in Combination with a KRAS G12C Inhibitor in Non-Small Cell Lung Cancer (NSCLC)
Completed enrollment in the KRAS G12C inhibitor prior-treated Stage 1 Part B doublet cohort in Q1 2025.
Completed enrollment in the planned dose level evaluation cohorts for the triplet combination in Q1 2025.
Key Milestones Expected for 2025:
Present an interim update of both doublet and triplet data at a medical meeting in H2 2025.
VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in Advanced Solid Tumors
Verastem announced in April 2025 that the FDA had cleared the Company’s Investigational New Drug (IND) application for VS-7375, enabling a Phase 1/2a trial in advanced solid tumors in the U.S.
Shared a presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2025, highlighting that VS-7375 was found to be more potent than other KRAS G12D inhibitors in preclinical models.
GenFleet announced on Feb. 28, 2025, that it had dosed the first patient in the Phase 2 portion of the trial in China.
Verastem announced on January 14, 2025, that it had exercised its option early to license GFH375 (VS-7375) from partner GenFleet Therapeutics. In addition, the Company announced preliminary clinical data from the Phase 1 dose-escalation study conducted by GenFleet in China. In the study, VS-7375 demonstrated oral bioavailability, with no DLTs across six dose levels, and partial responses were achieved among multiple patients with both pancreatic and lung cancers.
Key Milestones Expected for 2025:
Initiate a Phase 1/2a trial in the U.S. by mid-2025.
GenFleet to share clinical data from the Phase 1 study of VS-7375 in an oral presentation at ASCO (Free ASCO Whitepaper) on Monday, June 2, 2025.
Upcoming Presentations
ASCO Annual Meeting
The meeting will be held from May 30 to June 3, 2025, in Chicago, IL, and abstracts are under embargo until May 22, 2025, at 5:00 pm EDT.
Title: A First-in-Human Phase I/II Study of GFH375, a Highly Selective and Potent Oral KRAS G12D Inhibitor in Patients with KRAS G12D Mutant Advanced Solid Tumors
Abstract Number: 3013
Session: Rapid Oral Abstract Sessions: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Date/Time: Monday, June 2, 2025 from 8:00 am to 9:30 am CDT
Title: Avutometinib/defactinib and gemcitabine/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: Updated safety and efficacy of a phase 1b/2 study (RAMP 205)
Abstract Number: e16043
Accepted for inclusion in the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting Proceedings, Journal of Clinical Oncology supplement. The abstract is under embargo until May 22, and the Company will be reporting additional data then.
ESMO Gynaecological Cancers Congress 2025
The meeting will be held from June 19 to 21, 2025, in Vienna, Austria, and the abstract is under embargo until June 16, 2025.
Title: Blood ctDNA vs tumor tissue screening for the detection of KRAS mutations in low-grade serous ovarian cancer
Abstract Number: 276
Date/Time: Thursday, June 19, from 2:00 to 3:30 pm EDT
Corporate Updates
In April 2025, Verastem strengthened its balance sheet by raising gross proceeds of approximately $75 million in a private placement of 3.4 million shares of its common stock and 7.3 million pre-funded warrants to purchase 7.3 million shares of its common stock.
First Quarter 2025 Financial Results
Verastem Oncology ended the first quarter of 2025 with cash, cash equivalents and investments of $117.6 million. On a pro forma basis, taking into account the $75 million of gross proceeds raised in a private placement in April, cash and cash equivalents were $192.6 million as of March 31, 2025.
Total operating expenses for the three months ended March 31, 2025 (the "2025 Quarter") were $44.2 million, inclusive of $6.8 million of one-time charges, compared to $28.1 million for the three months ended March 31, 2024 (the "2024 Quarter").
Research & development expenses for the 2025 Quarter were $29.2 million, compared to $17.7 million for the 2024 Quarter. The increase of $11.5 million, or 65.0%, was primarily related to the option exercise fee related to the GenFleet G12D program, increased contract research organization costs, and increased drug substance and drug product costs.
Selling, general & administrative expenses for the 2025 Quarter were $15.0 million, compared to $10.4 million for the 2024 Quarter. The increase of $4.6 million, or 44.2%, was primarily related to additional costs in anticipation of a potential launch of avutometinib and defactinib in KRAS mt LGSOC, increased personnel costs, including non-cash stock compensation, and one-time financing costs associated with the note purchase agreement.
Net loss for the 2025 Quarter was $52.1 million, or $0.96 per share (basic and diluted), compared to $33.9 million, or $1.26 per share for the 2024 Quarter.
For the 2025 Quarter, non-GAAP adjusted net loss was $42.9 million, or $0.79 per share (diluted) compared to non-GAAP adjusted net loss of $26.2 million, or $0.98 per share (diluted), for the 2024 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 months ended March 31, 2025 and 2024 are included in the tables accompanying this press release after the unaudited condensed consolidated financial statements.
About AVMAPKI and FAKZYNJA Combination Therapy
AVMAPKI (avutometinib) inhibits MEK kinase activity while also blocking the compensatory reactivation of MEK by upstream RAF. RAF and MEK proteins are regulators of the RAS/RAF/MEK/ERK (MAPK) pathway. Blocking RAF and/or MEK activates FAK, a key mediator of drug resistance. FAKZYNJA (defactinib) is a FAK inhibitor and together, the avutometinib and defactinib combination was designed to provide a more complete blockade of the signaling that drives the growth and drug resistance of RAS/MAPK pathway-dependent tumors.
The U.S. Food and Drug Administration (FDA) approved AVMAPKI FAKZYNJA CO-PACK (avutometinib capsules; defactinib tablets) for the treatment of adult patients with KRAS-mutated recurrent LGSOC who have received prior systemic therapy on May 8, 2025. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Verastem is also evaluating avutometinib in combination with defactinib and other agents as a potential treatment for patients with advanced pancreatic cancer (RAMP 205; NCT05669482) and advanced KRAS G12C mutant non-small cell lung cancer (RAMP 203; NCT05074810). Avutometinib and defactinib are not approved by the FDA or any other regulatory authority, either in combination or with other therapies, for any of these investigative uses. Neither avutometinib nor defactinib are approved by the FDA or any other regulatory authority on a stand-alone basis for any use.
AVMAPKI FAKZYNJA CO-PACK U.S. Indication
Indication
AVMAPKI FAKZYNJA CO-PACK is indicated for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy.
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Important Safety Information
Warnings and Precautions
Ocular Toxicities: Ocular toxicities, including visual impairment and vitreoretinal disorders, occurred. Perform comprehensive ophthalmic evaluation at baseline, prior to cycle 2, every three cycles thereafter, and as clinically indicated. Withhold AVMAPKI FAKZYNJA CO-PACK for ocular toxicities until improvement at the same or reduced dose. Permanently discontinue AVMAPKI FAKZYNJA CO-PACK for any grade 4 toxicity.
Serious Skin Toxicities: Skin toxicities, including photosensitivity and severe cutaneous adverse reactions (SCARSs) occurred. Adhere to concomitant medications. Monitor for skin toxicities and interrupt, reduce or permanently discontinue AVMAPKI FAKZYNJA CO-PACK based on severity, tolerability and duration.
Hepatotoxicity: Monitor liver function tests prior to each cycle, on day 15 of the first 4 cycles, and as clinically indicated. Withhold, reduce or discontinue AVMAPKI FAKZYNJA CO-PACK based on severity and persistence of abnormality.
Rhabdomyolysis: Monitor creatine phosphokinase prior to the start of each cycle, on day 15 of the first four cycles, and as clinically indicated. If increased CPK occurs, evaluate patients for rhabdomyolysis or other causes. Withhold, reduce or permanently discontinue AVMAPKI FAKZYNJA CO-PACK based on severity and duration of the adverse reaction.
Embryo-Fetal Toxicity: AVMAPKI FAKZYNJA CO-PACK can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.
Adverse Reactions
The most common (≥ 25%) adverse reactions, including laboratory abnormalities, were increased creatine phosphokinase, nausea, fatigue, increased aspartate aminotransferase, rash, diarrhea, musculoskeletal pain, edema, decreased hemoglobin, increased alanine aminotransferase, vomiting, increased blood bilirubin, increased triglycerides, decreased lymphocyte count, abdominal pain, dyspepsia, dermatitis acneiform, vitreoretinal disorders, increased alkaline phosphatase, stomatitis, pruritus, visual impairment, decreased platelet count, constipation, dry skin, dyspnea, cough, urinary tract infection, and decreased neutrophil count.
Drug Interactions
Strong and moderate CYP3A4 inhibitors: Avoid concomitant use with AVMAPKI FAKZYNJA CO-PACK.
Strong and moderate CYP3A4 inducers: Avoid concomitant use with AVMAPKI FAKZYNJA CO-PACK.
Warfarin: Avoid concomitant use of AVMAPKI FAKZYNJA CO-PACK with warfarin and use an alternative to warfarin.
Gastric acid reducing agents: Avoid concomitant use of AVMAPKI FAKZYNJA CO-PACK with proton pump inhibitors (PPIs) or H2 receptor antagonists. If use of an acid-reducing agent cannot be avoided, administer FAKZYNJA 2 hours before or 2 hours after the administration of a locally acting antacid.
Use in Specific Populations
Lactation: Advise not to breastfeed.
Fertility: May impair fertility in males and females.
Click here for full Prescribing Information.
About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor
VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. Verastem announced in April 2025 that the U.S. Investigational New Drug (IND) application for VS-7375 was cleared and plans to initiate a Phase 1/2a clinical trial in mid-2025. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024.