On May 9, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported business updates and reported financial results for the first quarter ended March 31, 2024 (Press release, Verastem, MAY 9, 2024, View Source [SID1234643042]).

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"In the first quarter of 2024, we received FDA Orphan Drug Designation for avutometinib and defactinib combination in recurrent low-grade serous ovarian cancer, which recognizes this rare cancer as different and distinct from other forms of ovarian cancer and reinforces the need for new treatment options," said Dan Paterson, president and chief executive officer of Verastem Oncology. "We look forward to starting our planned rolling NDA submission and sharing topline data for avutometinib and defactinib combination in recurrent low-grade serous ovarian cancer. We also plan to announce initial data from the RAMP 205 trial in first-line metastatic pancreatic cancer at ASCO (Free ASCO Whitepaper) and plan to provide updates across our other clinical programs in the second half of 2024."

First Quarter 2024 and Recent Updates

Avutometinib and Defactinib Combination in Low-Grade Serous Ovarian Cancer (LGSOC)

Enrollment and site activations are underway in the U.S., Australia, and the UK, for the 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.
Granted Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for avutometinib alone or in combination with defactinib for the treatment of all patients with recurrent LGSOC, in March 2024.
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 included 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 focal adhesion kinase (FAK) inhibitor in recurrent LGSOC as well as a trials-in-progress poster about the Phase 3 RAMP 301 trial.
Plan to announce updated topline data from the RAMP 201 trial in LGSOC to coincide with the start of our planned rolling New Drug Application (NDA) submission for Accelerated Approval for the avutometinib and defactinib combination in recurrent LGSOC in Q2 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.
Avutometinib in Combination with KRAS G12C Inhibitors in Non-Small Cell Lung Cancer (NSCLC)

Verastem Oncology announced today it has received Fast Track Designation from the FDA for avutometinib in combination with Mirati’s (BMS) G12C inhibitor, KRAZATI (adagrasib) for the treatment of patients with KRAS G12C-mutated metastatic NSCLC who have received at least one prior systemic therapy and have not been previously treated with a KRAS G12C inhibitor, in April 2024.
Verastem Oncology announced today it has received Fast Track Designation from the FDA for the combination of avutometinib plus defactinib with Amgen’s G12C inhibitor, LUMAKRAS (sotorasib) for the treatment of patients with KRAS G12C-mutated metastatic NSCLC who have received at least one prior systemic therapy, in April 2024.
The FDA granted Fast Track Designation 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.
Data updates from patients with KRAS G12C-mutant NSCLC in the Phase 1/2 RAMP 203 trial evaluating avutometinib plus defactinib and sotorasib are planned for H2 2024.
Data from patients with KRAS G12C-mutant NSCLC in the Phase 1/2 RAMP 204 trial evaluating avutometinib and adagrasib are planned for H2 2024.
Avutometinib and Defactinib Combination in First-Line Metastatic Pancreatic Cancer

Verastem Oncology reported the acceptance of an abstract that will include initial safety and efficacy results from the RAMP 205 trial of avutometinib and defactinib in combination with current standard of care gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
GFH375 (VS-7375): Oral KRAS G12D (ON/OFF) Inhibitor

GenFleet Therapeutics investigational new drug (IND) application for GFH375 (VS-7375) was submitted in China and accepted for review. Expect to begin a Phase 1 trial in China in H2 2024.
Discovery/lead optimization continues for second and third programs with GenFleet collaboration.
Upcoming Presentations

Verastem Oncology reported the acceptance of an abstract for poster presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting being held from May 31 to June 4, 2024, in Chicago, IL.

Title: Avutometinib/defactinib and gemcitabine/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: Initial safety and efficacy of phase 1b/2 study (RAMP 205).
Abstract Number: 4140
Date/Time: Saturday, June 1, 2024, 1:30 to 4:30 pm CDT
Corporate Updates

Strengthened the executive leadership team with the appointment of John Hayslip, M.D., to chief medical officer in April 2024.
First Quarter 2024 Financial Results

Verastem Oncology ended the first quarter of 2024 with cash, cash equivalents and investments of $110.1 million.

Total operating expenses for the three months ended March 31, 2024 (the "2024 Quarter") were $28.1 million, compared to $19.3 million for the three months ended March 31, 2023 (the "2023 Quarter").

Research & development expenses for the 2024 Quarter were $17.7 million, compared to $12.0 million for the 2023 Quarter. The increase of $5.7 million, or 47.5%, was primarily related to increased contract research organization costs, increased investigator fees and increased personnel costs, including non-cash stock compensation.

Selling, general & administrative expenses for the 2024 Quarter were $10.4 million, compared to $7.3 million for the 2023 Quarter. The increase of $3.1 million, or 42.5%, was primarily related to additional costs in anticipation of a potential launch of avutometinib and defactinib in LGSOC, increased personnel costs, including non-cash stock compensation, and increased consulting and professional fees.

Net loss for the 2024 Quarter was $33.9 million, or $1.26 per share (basic and diluted), compared to $15.7 million, or $0.94 per share (basic and diluted, each as adjusted for the Company’s reverse stock split) for the 2023 Quarter.

For the 2024 Quarter, non-GAAP adjusted net loss was $26.2 million, or $0.98 per share (diluted) compared to non-GAAP adjusted net loss of $17.8 million, or $1.07 per share (diluted, as adjusted for the Company’s reverse stock split), for the 2023 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, 2024 and 2023 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 of the investigational combination of avutometinib and defactinib, a selective 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. 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 avutometinib in RAS/MAPK driven tumors as part of its Raf And Mek Program or RAMP. RAMP 301 (NCT06072781) is an international 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. The 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, is supported by the PanCAN Therapeutic Accelerator Award.

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. Upon approval of the investigational new drug (IND) application in China (which is currently under review), 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.