On November 3, 2022 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported financial results for the three months ended September 30, 2022, and highlighted recent progress (Press release, Verastem, NOV 3, 2022, View Source [SID1234623043]).

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"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.