On February 2, 2023 Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported key strategic priorities and upcoming catalysts to support its lead compound RAF/MEK clamp avutometinib in RAS pathway-driven cancers (Press release, Verastem, FEB 2, 2023, View Source [SID1234626730]).

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"Building on the Breakthrough Therapy designation for the combination of avutometinib with defactinib in recurrent LGSOC and the positive results from the interim analysis of Part A of the RAMP 201 trial, we are working rapidly to bring forward the first U.S. Food and Drug Administration (FDA)-approved therapy for these patients who deserve better options," said Brian Stuglik, CEO of Verastem Oncology. "Further, we plan to efficiently advance our development program and provide early data read-outs with avutometinib combinations across other RAS pathway-driven cancers with high unmet need, including combinations in KRAS G12C mutant NSCLC and frontline metastatic pancreatic cancer. With the recently announced financing, we have strengthened our balance sheet and cash runway to deliver on these key initiatives."

2022 and Recent Accomplishments

Completed target enrollment in the RAMP 201 trial evaluating avutometinib + defactinib in recurrent LGSOC and reported positive interim data from Part A that included blinded independently confirmed response rates in both KRAS Mutant and KRAS wild-type tumors with a favorable safety and tolerability profile.
The combination of avutometinib and defactinib was selected as the go-forward treatment regimen for the recurrent LGSOC program.
In the KRAS G12C Mutant NSCLC program, the RAMP 203 trial, evaluating the combination of avutometinib with Amgen’s LUMAKRASTM (sotorasib), advanced to final dose level of 4 mg avutometinib with 960 mg of LUMAKRASTM and enrollment was initiated in the RAMP 204 trial of avutometinib with Mirati’s KRAZATI (adagrasib).
Initiated the RAMP 205 trial evaluating avutometinib and defactinib with standard of care chemotherapy in frontline metastatic pancreatic cancer.
Secured up to $150 Million in non-dilutive financing from Oxford Finance LLC and entered into a definitive agreement to sell up to approximately 2.1 million shares of its Series B Convertible Preferred Stock to affiliates of BVF Partners L.P. in a private placement to raise aggregate gross proceeds of up to approximately $60 million in two tranches. On January 27, 2023 Verastem Oncology closed on the initial tranche of 1.2 million shares of its Series B Convertible Preferred Stock (the "Preferred Stock") with gross proceeds of $30 million.
2023 Strategic Priorities

Initiate confirmatory study of avutometinib + defactinib in recurrent LGSOC upon agreement with the FDA on study design in support of filing for accelerated approval.
Advance KRAS G12C mutant NSCLC program with initial read-outs of the RAMP 203 and RAMP 204 trials evaluating avutometinib in combination with LUMAKRASTM (sotorasib) or KRAZATITM (adagrasib).
Determine recommended Phase 2 dose and complete enrollment of the initial Phase 2 expansion cohort of the RAMP 205 trial evaluating avutometinib and defactinib plus standard of care chemotherapy in frontline metastatic pancreatic cancer.
Progress signal-finding, investigator-initiated trial program of combinations with avutometinib in additional RAS pathway-driven cancers with high unmet need.
Anticipated 2023 Milestones and Catalysts

Q1-2023

Determine recommended Phase 2 dose for RAMP 203 trial (KRAS G12C NSCLC avutometinib + LUMAKRASTM (sotorasib)) combination trial.
Launch education campaign in LGSOC to differentiate LGSOC from high-grade ovarian cancer, highlight signs and symptoms and younger age at diagnosis.
Q2-2023

Present updated results of Part A of RAMP 201 trial (LGSOC avutometinib + defactinib) at a scientific medical conference.
Finalize confirmatory trial study design for recurrent LGSOC program.
Present updated results of investigator-sponsored trial of avutometinib and everolimus in KRAS-mutant NSCLC.
2H-2023

Initiate confirmatory study of avutometinib and defactinib in recurrent LGSOC.
Report initial read-out of safety and preliminary efficacy of the RAMP 203 trial (KRAS G12C NSCLC avutometinib + LUMAKRASTM (sotorasib)) combination trial.
Provide initial safety read-out and recommended dose of RAMP 204 (KRAS G12C NSCLC avutometinib + KRAZATITM (adagrasib)) combination trial.
Determine recommended Phase 2 dose and complete enrollment of the initial Phase 2 expansion cohort of RAMP 205 (frontline metastatic pancreatic cancer avutometinib and defactinib plus standard of care).
Financial Update

As of December 31, 2022, Verastem Oncology had preliminary unaudited cash and short-term investments of $87.9 million.

On January 24, 2023, Verastem Oncology announced that it had entered into a definitive agreement to sell up to approximately 2.1 million shares of Preferred Stock to affiliates of BVF Partners L.P. in a private placement to raise aggregate gross proceeds of up to approximately $60 million in two tranches, before deducting fees to the placement agent and other estimated offering expenses payable by Verastem Oncology. Verastem Oncology closed on the initial tranche of 1.2 million shares of Preferred Stock for a purchase price of $30 million on January 27, 2023.

Upon closing of the initial tranche of the private placement, Verastem Oncology achieved the Term B Milestone under the Oxford Loan and Security Agreement which will allow Verastem Oncology to draw an additional $15M in term loans ("Term B Loan").

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 in combination with defactinib in patients with recurrent LGSOC. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (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, Verastem Oncology 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.