Verastem Inc

Previous wording

We estimate the total annual incident addressable market opportunity forthe combination of avutometinib and defactinib to be approximately $300 million for KRAS mt and approximately $270 million KRAS wt populations, respectively. We estimate the total prevalent addressable market opportunity to be approximately $1.7 billion for KRAS mt and approximately $1.1 billion for KRAS wt populations, respectively. Our estimates of the patient population, pricing and revenue opportunities for its product candidates, including for KRAS mt and KRAS wt patients with LGSOC, are based on several internal and third-party estimates and assumptions, including, without limitation, internal forecasts, the median duration of treatment from initial interim clinical data and the assumed prices at which we can commercialize our product candidates. Specifically, our estimates of total addressable market opportunities are based on: (a) estimated annual incidence of KRAS mt and KRAS wt populations of approximately 500 and 1,000 patients, respectively, (b) estimated prevalence of KRAS mt and KRAS wt populations of approximately 2,800 and 4,200 patients, respectively, (c) the average duration of therapy as observed in Verastem clinical trials of 18 months and eight months for KRAS mt and KRAS wt populations, respectively, and (d) an estimated cost of therapy of $34,000 per month consistent with other recent oncology drug launches.

Current wording

We estimate the total annual incident addressable market opportunity forthe combination of avutometinib and defactinib to be approximately $300 million for KRAS mt and approximately $374 million for KRAS wt populations. We estimate the total prevalent addressable market opportunity to be approximately $1.7 billion for KRAS mt and approximately $1.6 billion for KRAS wt populations, respectively. Our estimates of the patient population, pricing and revenue opportunities for its product candidates, including for KRAS mt and KRAS wt patients with LGSOC, are based on several internal and third-party estimates and assumptions, including, without limitation, internal forecasts, the median duration of treatment from initial interim clinical data and the assumed prices at which we can commercialize our product candidates. Specifically, our estimates of total addressable market opportunities are based on: (a) estimated annual incidence of KRAS mt and KRAS wt populations of approximately 500 and 1,000 patients, respectively, (b) estimated prevalence of KRAS mt and KRAS wt populations of approximately 2,800 and 4,200 patients, respectively, (c) the average duration of therapy as observed in Verastem clinical trials of 18 months and 11 months for KRAS mt and KRAS wt populations, respectively, and (d) an estimated cost of therapy of $34,000 per month consistent with other recent oncology drug launches.

Previous wording

The average duration of therapy included in this calculation is based, in part, on the estimated duration of therapy for patients dosed with the combination of avutometinib and defactinib for the combined Parts A, B, and C in RAMP 201 as of the latest data cutoff in February 2024. Amongst 115 patients, 58 enrolled with KRAS mutated LGSOC and 57 had wild-type, or non-mutated, KRAS. The estimated median duration of therapy for all patients is nine months and the estimated mean duration of therapy is 14 months. For KRAS mt, the estimated median duration of therapy is 14 months and the estimated mean duration of therapy is 18 months with 31 patients still on treatment as of the data cutoff date. For KRAS wt, the estimated median duration of therapy is seven months and the estimated mean duration of therapy is 11 months with 12 patients still on treatment as of the data cutoff date.

Current wording

The average duration of therapy included in this calculation is based, in part, on the estimated duration of therapy for patients dosed with the combination of avutometinib and defactinib for the combined Parts A, B, and C in RAMP 201 as of the data cutoff as of June 30, 2024. Amongst 115 patients, 58 enrolled with KRAS mutated LGSOC and 57 had wild-type, or non-mutated, KRAS. The estimated mean duration of therapy for all patients is 14.5 months. For KRAS mt, the estimated mean duration of therapy is 18.3 months and for KRAS wt, the estimated mean duration of therapy is 10.7 months.

Previous wording

Estimated median duration of therapy was calculated using Kaplan-Meier methods. Estimated mean duration of therapy was calculated by projecting complete time on treatment for patients still on treatment by sampling from an exponential distribution conditional on the observed duration through the cutoff date.

Current wording

Estimated mean duration of therapy was calculated by projecting complete time on treatment for patients still on treatment by sampling from an exponential distribution conditional on the observed duration through the cutoff date.

Previous wording

In December 2023, we announced initiation of a Phase 3 trial, known as the RAMP 301 study, to evaluate the combination of avutometinib and defactinib for the treatment of patients with recurrent LGSOC. The RAMP 301 study is a randomized global trial, evaluating the efficacy and safety of avutometinib and defactinib versus standard chemotherapy or hormonal therapy in patients with recurrent LGSOC. RAMP 301 is intended to serve as the confirmatory study required by the FDA to potentially convert an accelerated approval for the combination of avutometinib and defactinib for the treatment of LGSOC to full approval. We also intend to initiate discussions with global regulatory authorities, including those in Europe and Japan, to determine the regulatory path with the objective of ultimately seeking approval for the combination in additional regions.

Current wording

In December 2023, we announced initiation of a Phase 3 trial, known as the RAMP 301 study, to evaluate the combination of avutometinib and defactinib for the treatment of patients with recurrent LGSOC. The RAMP 301 study is a randomized global trial, evaluating the efficacy and safety of avutometinib and defactinib versus standard chemotherapy or hormonal therapy in patients with recurrent LGSOC. RAMP 301 is intended to serve as the confirmatory study required by the FDA to potentially convert an accelerated approval for the combination of avutometinib and defactinib for the treatment of LGSOC to full approval. We also intend to initiate discussions with global regulatory authorities, including those in Europe and Japan, to determine the regulatory path with the objective of ultimately seeking approval for the combination in additional regions. For RAMP 301, we are currently enrolling patients with LGSOC regardless of KRAS mutation status across the United States, United Kingdom, European Union, Canada, and Australia, and we plan to complete enrollment by the end of 2025.

Previous wording

In September 2021, we entered into a clinical collaboration agreement with Amgen, Inc. (“Amgen”) to evaluate the combination of avutometinib with Amgen’s KRAS G12C inhibitor LUMAKRAS® (sotorasib) in a Phase 1/2 study entitled RAMP 203. The Phase 1/2 trial is evaluating the safety, tolerability and efficacy of avutometinib in combination with LUMAKRAS in patients with KRAS G12C NSCLC who have not been previously treated with a KRAS G12C inhibitor, as well as in patients who have progressed on a KRAS G12C inhibitor. The trial is building on preclinical data showing a deeper blockade of MAPK pathway signaling and enhanced anti-tumor efficacy with the combination of LUMAKRAS (KRAS G12C inhibition) and avutometinib (RAF/MEK inhibition) relative to either agent alone. The RAMP 203 study has progressed to the recommended Phase 2 dose of 4 mg avutometinib in combination with 960 mg of LUMAKRAS. RAMP 203 is currently enrolling patients in the dose expansion phase (Part B) for patients who are G12C inhibitor treatment naïve and for patients who have experienced disease progression on a prior G12C monotherapy. In October 2023, we announced initial safety and pharmacokinetics results, as well as preliminary efficacy results, from the RAMP 203 study which were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2023. These preliminary results showed a confirmed overall response rate (“ORR”) of 25% (3/12) across efficacy-evaluable patients and seen in both KRAS G12C inhibitor resistant (14.3%; 1/7) and naïve (40%; 2/5) patients. In January 2024, the FDA granted fast track designation for combination of avutometinib and LUMAKRAS 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. Based on stronger tumor regressions in KRAS G12C-mutant NSCLC preclinical models when a FAK inhibitor is added along with G12C inhibitor and avutometinib, defactinib is being added to the RAMP 203 study. We plan to provide data updates from the RAMP 203 study in the second half of 2024.

Current wording

In September 2021, we entered into a clinical collaboration agreement with Amgen, Inc. (“Amgen”) to evaluate the combination of avutometinib with Amgen’s KRAS G12C inhibitor LUMAKRAS® (sotorasib) in a Phase 1/2 study entitled RAMP 203. The Phase 1/2 trial began evaluating the safety, tolerability and efficacy of avutometinib in combination with LUMAKRAS in patients with KRAS G12C NSCLC who have not been previously treated with a KRAS G12C inhibitor, as well as in patients who have progressed on a KRAS G12C inhibitor. The trial built upon initial preclinical data showing enhanced anti-tumor efficacy with the combination of LUMAKRAS (KRAS G12C inhibition) and avutometinib (RAF/MEK inhibition) relative to either agent alone. In October 2023, we announced initial safety and pharmacokinetics results, as well as preliminary efficacy results, from the RAMP 203 study which were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2023. These preliminary results showed a confirmed ORR of 25% (3/12) across efficacy-evaluable patients and seen in both KRAS G12C inhibitor resistant (14.3%; 1/7) and naïve (40%; 2/5) patients. In January 2024, the FDA granted fast track designation for combination of avutometinib and LUMAKRAS 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. The RAMP 203 study has progressed to the recommended Phase 2 dose of 4 mg avutometinib in combination with 960 mg of LUMAKRAS for the doublet of avutometinib and LUMAKRAS. RAMP 203 is currently enrolling patients who have experienced disease progression on a KRAS G12C inhibitor in the dose expansion phase (Part B) and completed enrollment of patients without prior G12C treatment to the initial doublet dose expansion phase. Based on emerging data demonstrating improved tumor regressions in KRAS G12C-mutant NSCLC preclinical models when a FAK inhibitor is combined with a G12C inhibitor and avutometinib, defactinib was

Previous wording

In November 2021, we entered into a clinical collaboration agreement with Mirati Therapeutics, Inc. (“Mirati”) to evaluate the combination of avutometinib with Mirati’s KRAS G12C inhibitor KRAZATI® (adagrasib) in a Phase 1/2 trial entitled RAMP 204. The Phase 1/2 trial will evaluate the safety, tolerability and efficacy of avutometinib in combination with KRAZATI in patients with KRAS G12C NSCLC who have progressed on a KRAS G12C inhibitor. The trial will build on preclinical data showing a deeper blockade of MAPK pathway signaling resulting in enhanced anti-tumor efficacy with the combination of KRAZATI (KRAS G12C inhibition) and avutometinib (RAF/MEK inhibition) relative to either agent alone. The RAMP 204 study is open and enrolling. Dose escalation is ongoing. We plan to provide data updates from RAMP 204 in the second half of 2024.

Current wording

In November 2021, we entered into a clinical collaboration agreement with Mirati Therapeutics, Inc. (“Mirati”) to evaluate the combination of avutometinib with Mirati’s KRAS G12C inhibitor KRAZATI® (adagrasib) in a Phase 1/2 trial entitled RAMP 204. The Phase 1/2 trial will evaluate the safety, tolerability and efficacy of avutometinib in combination with KRAZATI in patients with KRAS G12C NSCLC who have progressed on a KRAS G12C inhibitor. The trial will build on preclinical data showing a deeper blockade of MAPK pathway signaling resulting in enhanced anti-tumor efficacy with the combination of KRAZATI (KRAS G12C inhibition) and avutometinib (RAF/MEK inhibition) relative to either agent alone. In the fourth quarter of 2024, after discussion with Bristol Myers Squibb Company, who completed an acquisition of Mirati in the first quarter of 2024, and the RAMP 204 steering committee, we decided to close the RAMP 204 study to further enrollment in order to prioritize the RAMP 203 study. No new safety signals were identified in the RAMP 204 study and closure to further enrollment is not related to safety findings. The RAMP 203 study will be prioritized primarily because it covers both patients who are G12Ci treatment naïve and progressed and importantly includes the triplet treatment approach.

Previous wording

205 is evaluating the safety, tolerability and efficacy of avutometinib and defactinib in combination with GEMZAR® (gemcitabine) and ABRAXANE® (Nab-paclitaxel) in patients with previously untreated metastatic adenocarcinoma of the pancreas. The RAMP 205 trial is evaluating whether combining avutometinib (to target mutant KRAS which is mutated in more than 90% of pancreatic adenocarcinomas) and defactinib (to reduce stromal density and adaptive resistance to avutometinib) to the standard GEMZAR/ABRAXANE regimen improves outcomes for patients with pancreatic adenocarcinoma. In August 2022, PanCAN agreed to provide us with an additional $0.5 million for the collection and translational analysis of patient samples. The RAMP 205 trial is open and enrolling. Combination dose evaluation is ongoing. As of a data cut of May 14, 2024, we reported patients receiving the combination of avutometinib and defactinib with gemcitabine and Nab-paclitaxel in dose level 1 cohort achieved a confirmed ORR of 83% (5/6), one dose-limiting toxicity was observed in the dose level 1 cohort, and the dose level was subsequently cleared after additional patients were enrolled. The initial interim results were presented at the American Society of Clinical Oncology Annual Meeting in June 2024.

Current wording

In May 2022, we received the first “Therapeutic Accelerator Award” from PanCAN for up to $3.8 million. The grant is supporting a Phase 1b/2 clinical trial of avutometinib in combination with defactinib entitled RAMP 205. RAMP 205 is evaluating the safety, tolerability and efficacy of avutometinib and defactinib in combination with GEMZAR® (gemcitabine) and ABRAXANE® (Nab-paclitaxel) in patients with previously untreated metastatic adenocarcinoma of the pancreas. The RAMP 205 trial is evaluating whether combining avutometinib (to target mutant KRAS which is mutated in more than 90% of pancreatic adenocarcinomas) and defactinib (to reduce stromal density and adaptive resistance to avutometinib) to the standard GEMZAR/ABRAXANE regimen improves outcomes for patients with pancreatic adenocarcinoma. In August 2022, PanCAN agreed to provide us with an additional $0.5 million for the collection and translational analysis of patient samples. The RAMP 205 trial is open and enrolling. Combination dose evaluation is ongoing. As of a data cut of May 14, 2024, we reported patients receiving the combination of avutometinib and defactinib with gemcitabine and Nab-paclitaxel in dose level 1 cohort achieved a confirmed ORR of 83% (5/6), one dose-limiting toxicity was observed in the dose level 1 cohort, and the dose level was subsequently cleared after additional patients were enrolled. The initial interim results were presented at the American Society of Clinical Oncology Annual Meeting in June 2024. We expect to report updated data from RAMP 205 study in the first quarter of 2025.

Previous wording

In August 2023, we entered into a collaboration and option agreement (the “GenFleet Agreement”) with GenFleet pursuant to which GenFleet granted us options toobtain exclusive development and commercialization rights worldwide outside of mainland China, Hong Kong, Macau, and Taiwan (the “GenFleet Territory”) for up to three oncology programs targeting RAS pathway driven cancers (the “GenFleet Options”). We may exercise our GenFleet Options on a program-by-program basis. The collaboration builds on the strengths of both companies in oncology small molecule drug development, enabling us to partner our clinical development and regulatory expertise with GenFleet’s accomplished discovery capabilities. This synergistic collaboration includes our experience and established network of collaborators, including scientific and clinical experts in RAS biology and RAS pathway-driven cancers and GenFleet’s accomplishments with its KRAS G12C inhibitor program. In December 2023, we announced the selection of an orally bioavailable, potent and selective small molecule KRAS G12D (ON/OFF) inhibitor entitled GFH375/VS-7375 with a potential best-in-class profile as the lead program from our collaboration with GenFleet. An investigational NDA by GenFleet in China for GFH375/VS-7375, was cleared in June 2024, following which GenFleet initiated a Phase 1/2 study in solid tumors with KRAS G12D mutation for GFH375/VS-7375 in China in June 2024. In July 2024, we announced that the first patient had been dosed in a Phase 1/2 trial in China, conducted by GenFleet, evaluating GFH375/VS-7375. The Phase 1 study is being conducted in approximately 20 hospitals in China and will evaluate the safety and efficacy of GFH375/VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The Phase 1 study will determine the recommended Phase 2 dose and then further evaluate in Phase 2 the efficacy and safety of GFH375/VS-7375 in patients with advanced solid tumors, such as pancreatic ductal adenocarcinoma, colorectal cancer and non-small cell lung cancer.

Current wording

In August 2023, we entered into a collaboration and option agreement (the “GenFleet Agreement”) with GenFleet pursuant to which GenFleet granted us options toobtain exclusive development and commercialization rights worldwide outside of mainland China, Hong Kong, Macau, and Taiwan (the “GenFleet Territory”) for up to three oncology programs targeting RAS pathway driven cancers (the “GenFleet Options”). We may exercise our GenFleet Options on a program-by-program basis. The collaboration builds on the strengths of both companies in oncology small molecule drug development, enabling us to partner our clinical development and regulatory expertise with GenFleet’s accomplished discovery capabilities. This synergistic collaboration includes our experience and established network of collaborators, including scientific and clinical experts in RAS biology and RAS pathway-driven cancers and GenFleet’s accomplishments with its KRAS G12C inhibitor program. In December 2023, we announced the selection of an orally bioavailable, potent and selective small molecule KRAS G12D (ON/OFF) inhibitor entitled VS-7375/GFH375 with a potential best-in-class profile as the lead program from our collaboration with GenFleet. An investigational new drug (“IND”) application by GenFleet in China for VS-7375/GFH375, was cleared in June 2024, following which GenFleet initiated a Phase 1/2 study in solid tumors with KRAS G12D mutation for VS-7375/GFH375 in China in June 2024. GenFleet has dosed several patients in the Phase/12 study in China evaluating VS-7375/GFH375 in patients with KRAS G12D-mutated advanced solid tumors which started in July 2024. The Phase 1 study is being conducted in approximately 20 hospitals in China and will evaluate the safety and efficacy of VS-7375/GFH375 in patients with advanced KRAS G12D mutant solid tumors. The Phase 1 study will determine the recommended Phase 2 dose and then

Previous wording

Our operations to date have been organizing and staffing our company, business planning, raising capital, identifying and acquiring potential product candidates, undertaking preclinical studies and clinical trials for our product candidates and initiating U.S. commercial operations following the approval of COPIKTRA through our ownership period ending in September 2020. We have financed our operations to date primarily through public offerings of our common stock and pre-funded warrants, offerings of convertible notes, sales of common stock under our at-the-market equity offering programs, our loan and security agreement executed with Hercules in March 2017, as amended, the upfront payments and milestone payments under our license and collaboration agreements with Sanofi, CSPC Pharmaceutical Group Limited (“CSPC”), and Yakult Honsha Co., Ltd. (“Yakult”), the upfront payment and milestone payments received under the Secura APA, the proceeds in connection with the private investment in public equity (the “PIPE”), and our Loan Agreement with Oxford, sales of Series B Convertible Preferred Stock. Additionally, from our U.S. commercial launch of COPIKTRA on September 24, 2018, through our ownership period ending in September 2020, we financed a portion of our operations through product revenue.

Current wording

Our operations to date have been organizing and staffing our company, business planning, raising capital, identifying and acquiring potential product candidates, undertaking preclinical studies and clinical trials for our product candidates and initiating U.S. commercial operations following the approval of COPIKTRA through our ownership period ending in September 2020. We have financed our operations to date primarily through public offerings of our common stock, pre-funded warrants, and warrants, offerings of convertible notes, sales of common stock under our at-the-market equity offering programs, our loan and security agreement executed with Hercules in March 2017, as amended, the upfront payments and milestone payments under our license and collaboration agreements with Sanofi, CSPC, and Yakult, the upfront payment and milestone payments received under the Secura APA, the proceeds in connection with the private investment in public equity (the “PIPE”), and our Loan Agreement with Oxford, sales of Series B Convertible Preferred Stock. Additionally, from our U.S. commercial launch of COPIKTRA on September 24, 2018, through our ownership period ending in September 2020, we financed a portion of our operations through product revenue.

Previous wording

proceeds of approximately $51.1 million from the sale of 13,333,334 shares of our common stock and accompany warrants to purchase up to 13,333,334 shares of our common stock and pre-funded warrants to purchase up to an aggregate of 5,000,000 shares of common stock and accompanying warrants to purchase up to 5,000,000 shares of our common stock. Refer toNote 16. Subsequent Events our unaudited condensed consolidated financial statements included in this quarterly report for additional details on the July 2024 Offering. In accordance with applicable accounting standards, we evaluated whether there are conditions and events, considered in the aggregate, that raise substantial doubt about our ability to continue as a going concern within 12 months after the date of the issuance of the consolidated financial statements. We anticipate operating losses may continue for the foreseeable future since we do not yet have regulatory approval to sell any of our product candidates, and we continue to incur operating costs to execute our strategic plan, including costs related to research and development of our product candidates and commercial readiness activities. As a result of the assessment in accordance with the applicable accounting standards, these conditions raise substantial doubt about our ability to continue as a going concern for 12 months after the date the condensed consolidated financial statements are issued.

Current wording

As of September 30, 2024, we had an accumulated deficit of $891.0 million. Our net loss was $24.0 million, $66.1 million, $20.0 million and $60.0 million for the three and nine months ended September 30, 2024 and 2023, respectively. As of September 30, 2024, we had cash, cash equivalents, and investments of $113.2 million. In accordance with applicable accounting standards, we evaluated whether there are conditions and events, considered in the aggregate, that raise substantial doubt about our ability to continue as a going concern within 12 months after the date of the issuance of the consolidated financial statements. We anticipate operating losses may continue for the foreseeable future since we do not yet have regulatory approval to sell any of our product candidates, and we continue to incur operating costs to execute our strategic plan, including costs related to research and development of our product candidates and commercial readiness activities. As a result of the assessment in accordance with the applicable accounting standards, these conditions raise substantial doubt about our ability to continue as a going concern for 12 months after the date the condensed consolidated financial statements are issued.

Previous wording

The critical accounting policies we identified in our most recent Annual Report on Form 10-K for the fiscal year ended December 31, 2023, related to revenue recognition, collaborative agreements, accrued and prepaid research and development expenses, and stock-based compensation. During the six months ended June 30, 2024, there were no material changes to our critical accounting policies.

Current wording

The critical accounting policies we identified in our most recent Annual Report on Form 10-K for the fiscal year ended December 31, 2023, related to revenue recognition, collaborative agreements, accrued and prepaid research and development expenses, and stock-based compensation. During the nine months ended September 30, 2024, there were no material changes to our critical accounting policies.

Previous wording

*Research and development expense.*Research and development expense for the 2024 Quarter was $18.1 million compared to $12.9 million for the 2023 Quarter. The $5.2 million increase from the 2023 Quarter to the 2024 Quarter was primarily driven by an increase of $2.6 million in contract research organization (“CRO”) costs, an increase of $1.1 million in consulting costs, an increase of $0.7 million in investigator fees, an increase of $0.4 million in personnel costs, including non-cash stock compensation and an increase of $0.4 million in clinical supply costs.

Current wording

*Research and development expense.*Research and development expense for the three months ended September 30, 2024 (the “2024 Quarter”) was $24.8 million compared to $13.9 million for the three months ended September 30, 2023 (the “2023 Quarter”). The $10.9 million increase from the 2023 Quarter to the 2024 Quarter was primarily driven by an increase of $4.8 million in contract research organization (“CRO”) costs, an increase of $1.8 million in consulting costs, an increase of $1.7 million in investigator fees, an increase of $1.0 million in milestone and upfront payments pursuant to the GenFleet Agreement, an increase of $0.6 million in clinical supply, an increase of $0.5 million in personnel costs, including non-cash stock compensation and an increase of $0.5 million in drug substance and drug product manufacturing costs.

Previous wording

Selling, general and administrative expense. Selling, general and administrative expense for the 2024 Quarter was $10.2 million compared to $7.4 million for the 2023 Quarter. The increase of $2.8 million from the 2023 Quarter to the 2024 Quarter primarily resulted from an increase of $2.1 million of costs in anticipation of potential launch of

Current wording

Selling, general and administrative expense. Selling, general and administrative expense for the 2024 Quarter was $12.3 million compared to $7.4 million for the 2023 Quarter. The increase of $4.9 million from the 2023 Quarter to the 2024 Quarter primarily resulted from $3.0 million in July 2024 Offering financing fees in the 2024 Period, an increase of $1.2 million in personnel costs, including non-cash stock compensation, and an increase of $0.7 million in cost in anticipation of potential launch of avutometinib and defactinib in LGSOC.

Previous wording

Other expense. Other expense for the 2024 Quarter and 2023 Quarter was less than $0.1 million. Other expense for the 2024 Quarter and 2023 Quarter was comprised of transaction losses due to changes in foreign currency exchange rates.

Current wording

Other expense. Other expense for the 2024 Quarter was $0.1 million compared to less than $0.1 million for the 2023 Quarter. Other expense for the 2024 Quarter and 2023 Quarter was comprised of transaction losses due to changes in foreign currency exchange rates.

Previous wording

*Interest income.*Interest income for the 2024 Quarter was $1.0 million compared to $1.1 million for the 2023 Quarter. The decrease of $0.1 million from the 2023 Quarter to the 2024 Quarter in interest income was primarily due to the decrease in investment balances on short term investments and cash equivalents during each respective quarter.

Current wording

*Interest income.*Interest income for the 2024 Quarter was $0.8 million compared to $2.2 million for the 2023 Quarter. The decrease of $1.4 million from the 2023 Quarter to the 2024 Quarter in interest income was primarily due to the decrease in investment balances on short term investments and cash equivalents during each respective quarter.

Previous wording

*Change in fair value of preferred stock tranche liability.*The change in fair value of the preferred stock tranche liability was $10.2 million income for the 2024 Quarter compared to $4.0 million expense for the 2023 Quarter. The change in fair value of preferred stock tranche liability was comprised of the mark-to-market adjustment related to the second tranche right issued as part of the Securities Purchase Agreement. The fair value of the preferred stock tranche liability decreased from $10.2 million at the beginning of the 2024 Quarter to $0.0 million at the end of the 2024 Quarter resulting in $10.2 million income in the 2024 Quarter. The fair value of the preferred stock tranche liability increased from $3.5 million at the beginning of the 2023 Quarter to $7.5 million at the end of the 2023 Quarter resulting in $4.0 million expense in the 2023 Quarter.

Current wording

*Change in fair value of preferred stock tranche liability.*The change in fair value of the preferred stock tranche liability was $0.0 million for the 2024 Quarter compared to $0.2 million income for the 2023 Quarter. The change in fair value of preferred stock tranche liability was comprised of the mark-to-market adjustment related to the second tranche right issued as part of the Securities Purchase Agreement. The fair value of the preferred stock tranche liability was $0.0 million at the beginning of the 2024 Quarter and expired in July 2024 resulting in no adjustment in the 2024 Quarter. The fair value of the preferred stock tranche liability decreased from $7.5 million at the beginning of the 2023 Quarter to $7.3 million at the end of the 2023 Quarter resulting in $0.2 million income in the 2023 Quarter.

Previous wording

*Sale of COPIKTRA license and related assets revenue.*Sale of COPIKTRA license and related assets revenue for the six months ended June 30, 2024 (the “2024 Period”) was $10.0 million compared to $0.0 million for the six months ended June 30, 2023 (the “2023 Period”). Sale of COPIKTRA license and related assets revenue for the 2024 Period was comprised of one sales milestone of $10.0 million due Secura achieving cumulative worldwide net sales of COPIKTRA exceeding $100.0 million during the 2024 Period. The $10.0 million milestone payment was received by us in July 2024.

Current wording

*Sale of COPIKTRA license and related assets revenue.*Sale of COPIKTRA license and related assets revenue for the nine months ended September 30, 2024 (the “2024 Period”) was $10.0 million compared to $0.0 million for the nine months ended September 30, 2023 (the “2023 Period”). Sale of COPIKTRA license and related assets revenue for the 2024 Period was comprised of one sales milestone of $10.0 million due upon Secura achieving cumulative worldwide net sales of COPIKTRA exceeding $100.0 million during the 2024 Period. The $10.0 million milestone payment was received by us in July 2024.

Previous wording

Research and development expense. Research and development expense for the 2024 Period was $35.8 million compared to $24.9 million for the 2023 Period. The $10.9 million increase from the 2023 Period to the 2024 Period was primarily driven by an increase of $4.2 million in CRO costs, an increase of $2.0 million in investigator fees, an increase of $1.9 million in consulting costs, an increase of $1.3 million in personnel costs, including non-cash stock compensation, an increase of $1.0 million in clinical supply costs and an increase of $0.5 million in other R&D costs.

Current wording

Research and development expense. Research and development expense for the 2024 Period was $60.5 million compared to $38.9 million for the 2023 Period. The $21.6 million increase from the 2023 Period to the 2024 Period was primarily driven by an increase of $8.9 million in CRO costs, an increase of $3.6 million in investigator fees, an increase of $3.6 million in consulting costs, an increase of $1.8 million in personnel costs, including non-cash stock compensation, an increase of $1.6 million in clinical supply costs, an increase of $1.0 million in milestone and upfront payments pursuant to the GenFleet Agreement, an increase of $0.5 million in IST expenses, and an increase of $0.6 million in other research and development costs.

Previous wording

The $8.7 million increase inavutometinib+ defactinib costs from the 2023 Period to the 2024 Period was primarily driven by an increase in RAMP 301 study costs, an increase in drug metabolism and pharmacokinetics costs, an increase in RAMP 205 study costs, and an increase consulting costs, partially offset by a decrease in RAMP 202 study costs. The $0.8 million increase in avutometinib and other combination costs from the 2023 Period to the 2024 Period was primarily driven by an increase in investigator payments. The $1.6 million decrease in avutometinib

Current wording

2024 Quarter remain classified within “avutometinib + other combinations” in the table above. The $17.2 million increase inavutometinib+ defactinib costs from the 2023 Period to the 2024 Period was primarily driven by an increase in RAMP 301 study costs, an increasein drug metabolism and pharmacokinetics costs, an increase in RAMP 201 study costs, an increase in consulting costs, an increase in RAMP 205 study costs, andinclusion of RAMP 203 study costs incurred within the 2024 Quarter within avutometinib+ defactinib, partially offset by a decrease in RAMP 202 study costs. The $1.5 million decrease in avutometinib manufacturing and non-clinical trial specific costs from the 2023 Period to the 2024 Period was primarily driven by a decrease in avutometinib drug substance costs. The $1.7 million increase in GenFleet costs from the 2023 Period to the 2024 Period was primarily driven $3.0 million development milestone payment made in 2024 Period compared to the $2.0 million upfront payment made in the 2023 Period pursuant to the GenFleet Agreement.

Previous wording

Selling, general and administrative expense. Selling, general and administrative expense for the 2024 Period was $20.6 million compared to $14.7 million for the 2023 Period. The increase of $5.9 million from the 2023 Period to the 2024 Period primarily resulted from an increase of $4.1 million in costs in anticipation of potential launch of avutometinib and defactinib in LGSOC, an increase of $2.4 million in personnel costs, including non-cash stock compensation, and partially offset by a decrease of $0.6 million of costs associated with financing activities in the 2023 Period.

Current wording

Selling, general and administrative expense. Selling, general and administrative expense for the 2024 Period was $32.8 million compared to $22.1 million for the 2023 Period. The increase of $10.7 million from the 2023 Period to the 2024 Period primarily resulted from an increase of $4.7 million in costs in anticipation of potential launch of avutometinib and defactinib in LGSOC, an increase of $3.6 million in personnel costs, including non-cash stock compensation, $3.0 million in July 2024 Offering financing fees in the 2024 Period, and partially offset by $0.6 million in financing fees for the Securities Purchase Agreement in the 2023 Period.

Previous wording

Other expense. Other expense for the 2024 Period was $0.1 million compared to other expense of less than $0.1 million in the 2023 Period. Other expense for the 2024 Period was comprised of transaction losses due to changes in foreign currency exchange rates. Other expense for the 2023 Period was comprised of a gain on the sale of fixed assets and transaction losses due to changes in foreign currency exchange rates.

Current wording

Other expense. Other expense for the 2024 Period and 2023 Period was $0.1 million. Other expense for the 2024 Period was comprised of transaction losses due to changes in foreign currency exchange rates. Other expense for the 2023 Period was comprised of transaction losses due to changes in foreign currency exchange rates partially offset by a gain on sale of fixed assets.

Previous wording

*Interest income.*Interest income for the 2024 Period was $2.4 million compared to $2.1 million for the 2023 Period. The increase of $0.3 million from the 2023 Period to the 2024 Period was primarily driven by an increase in investment balances on short term investments and cash equivalents during each respective period.

Current wording

*Interest income.*Interest income for the 2024 Period was $3.2 million compared to $4.3 million for the 2023 Period. The decrease of $1.1 million from the 2023 Period to the 2024 Period was primarily driven by an decrease in investment balances on short term investments and cash equivalents during each respective period.

Previous wording

*Interest expense.*Interest expense for the 2024 Period was $2.3 million compared to $1.9 million for the 2023 Period. The increase of $0.4 million from the 2023 Period to the 2024 Period was primarily driven additional interest expense in the 2024 Period pursuant to the Loan Agreement as a result of the additional $15.0 million debt drawdown on March 22, 2023.

Current wording

*Interest expense.*Interest expense for the 2024 Period was $3.4 million compared to $3.0 million for the 2023 Period. The increase of $0.4 million from the 2023 Period to the 2024 Period was primarily driven additional interest expense in the 2024 Period pursuant to the Loan Agreement as a result of the additional $15.0 million debt drawdown on March 22, 2023.

Previous wording

*Change in fair value of preferred stock tranche liability.*The change in fair value of the preferred stock tranche liability was $4.2 million income for the 2024 Period compared to $0.5 million expense for the 2023 Period. The change in fair value of preferred stock tranche liability was comprised of the mark-to-market adjustment related to the second tranche right issued as part of the Securities Purchase Agreement. The fair value of the preferred stock tranche liability decreased from $4.2 million at the beginning of the 2024 Period to $0.0 million at the end of the 2024 Period resulting in $4.2 million income in the 2024 Period. The fair value of the preferred stock tranche liability increased from $6.9 million upon issuance on January 24, 2023, to $7.5 million at the end of the 2023 Period resulting in $0.5 million expense in the 2023 Period.

Current wording

*Change in fair value of preferred stock tranche liability.*The change in fair value of the preferred stock tranche liability was $4.2 million income for the 2024 Period compared to $0.3 million expense for the 2023 Period. The change in fair value of preferred stock tranche liability was comprised of the mark-to-market adjustment related to the second tranche right issued as part of the Securities Purchase Agreement. The fair value of the preferred stock tranche liability decreased from $4.2 million at the beginning of the 2024 Period and expired in July 2024 resulting in $4.2 million income in the 2024 Period. The fair value of the preferred stock tranche liability increased from $6.9 million upon issuance on January 24, 2023, to $7.3 million at the end of the 2023 Period resulting in $0.3 million expense in the 2023 Period.

Previous wording

We have financed our operations to date primarily through public and private offerings of our common stock, common warrants and pre-funded warrants, offerings of convertible notes, sales of common stock under our at-the-market equity offering programs, our loan and security agreement executed with Hercules in March 2017, as amended, the upfront payments under our license and collaboration agreements with Sanofi, Yakult, and CSPC, the upfront payment under the Secura APA, the proceeds in connection with the PIPE, the Loan Agreement with Oxford, and the issuance of Series B Convertible Preferred Stock. With the commercial launch of COPIKTRA in the United States in September 2018 through our ownership period ending in September 2020, we financed a portion of our operations through product revenue. As of September 30, 2020, we have sold our COPIKTRA license and no longer sell COPIKTRA in the United States. We expect to finance a portion of our business through future potential milestones and royalties received pursuant to the Secura APA.

Current wording

upfront payment under the Secura APA, the proceeds in connection with the PIPE, the Loan Agreement with Oxford, and the issuance of Series B Convertible Preferred Stock. With the commercial launch of COPIKTRA in the United States in September 2018 through our ownership period ending in September 2020, we financed a portion of our operations through product revenue. As of September 30, 2020, we have sold our COPIKTRA license and no longer sell COPIKTRA in the United States. We expect to finance a portion of our business through future potential milestones and royalties received pursuant to the Secura APA.

Previous wording

As of June 30, 2024, we had $83.4 million of cash, cash equivalents, and investments. We primarily invest our cash, cash equivalents and investments in U.S. Government money market funds, U.S. government agency bonds, corporate bonds and commercial paper of publicly traded companies.

Current wording

As of September 30, 2024, we had $113.2 million of cash, cash equivalents, and investments. We primarily invest our cash, cash equivalents and investments in U.S. Government money market funds, U.S. government agency bonds, corporate bonds and commercial paper of publicly traded companies.

Previous wording

Operating activities. The use of cash in both periods resulted primarily from our net losses adjusted for non-cash charges and changes in the components of working capital. Our cash outflow from net losses adjusted for non-cash charges and adjustments was $43.4 million and $36.7 million for the 2024 Period and the 2023 Period, respectively. Non-cash charges and adjustments were primarily related to the changes in fair value of the preferred stock tranche liability and stock-based compensation expense in the 2024 Period and 2023 Period. Our cash outflow from operating activities due to changes in operating assets and liabilities was $12.5 million and $3.5 million for the 2024 Period and the 2023 Period, respectively. Cash outflow due to changes in operating assets and liabilities for the 2024 Period was primarily driven by an increase of $10.0 million of accounts receivable, $0.8 million of grant receivable, a decrease of $0.7 million of accrued expenses and other liabilities, a decrease of $0.5 million of accounts payable, and a decrease of $0.3 million of deferred liabilities, Cash outflow due to changes in operating assets and liabilities for the 2023 Period was primarily driven by a decrease of $1.6 million in accrued expenses and other liabilities, an increase of $1.5 million in prepaid expenses, other current assets and other assets and a decrease of $0.4 million in accounts payable. The increases in both periods in prepaid expenses, other current assets, and other asserts is exclusive of cash received from PanCAN and used on the RAMP 205 study. Cash used in operating activities was $55.9 million and $40.2 million for the 2024 Period and the 2023 Period, respectively.

Current wording

Operating activities. The use of cash in both periods resulted primarily from our net losses adjusted for non-cash charges and changes in the components of working capital. Our cash outflow from net losses adjusted for non-cash charges and adjustments was $78.7 million and $55.8 million for the 2024 Period and the 2023 Period, respectively. Non-cash charges and adjustments for the 2024 Period were primarily related to the changes in fair value of the preferred stock tranche liability, the change in fair value of warrant liability and stock-based compensation expense. Non-cash charges and adjustments for the 2023 Period were primarily related to stock-based compensation expenses. Our cash outflow from operating activities due to changes in operating assets and liabilities was $0.9 million and $1.0 million for the 2024 Period and the 2023 Period, respectively. Cash outflow due to changes in operating assets and liabilities for the 2024 Period was primarily driven by a decrease of $2.7 million of account payable, an increase of $1.9 million of prepaid expenses, other current assets and other assets, a decrease of $0.3 million of deferred liabilities, and an increase of $0.2 million of grant receivable partially offset by an increase of $4.2 million of accrued expenses and other liabilities. Cash outflow due to changes in operating assets and liabilities for the 2023 Period was primarily driven by an increase of $3.0 million in prepaid expenses, other current assets and other assets partially offset by an increase of $1.3 million in accrued expenses and other liabilities, an increase of $0.3 million in deferred liabilities and an increase of $0.2 million in accounts payable. The increases in both periods in prepaid expenses, other current assets, and other asserts is exclusive of cash received from PanCAN and used on the RAMP 205 study. Cash used in operating activities was $79.7 million and $56.8 million for the 2024 Period and the 2023 Period, respectively.

Previous wording

*Investing activities.*The cash provided by investing activities for the 2024 Period relates to maturities of investments of $60.0 million, partially offset by a purchase of property and equipment of less than $0.1 million. The cash used by investing activities for the 2023 Period primarily relates to the net maturities of investments of $13.2 million.

Current wording

*Investing activities.*The cash provided by investing activities for the 2024 Period relates to maturities of investments of $60.0 million, partially offset by a purchase of property and equipment of less than $0.1 million. The cash provided by investing activities for the 2023 Period relates to the net purchases of investments of $56.9 million.

Previous wording

Financing activities. The cash provided by financing activities for the 2024 Period represents $1.3 million of proceeds received from insurance premium financing and $0.2 million of proceeds received from exercise of stock options and our employee stock purchase plan, partially offset by $0.8 million of payments on insurance premium financing, $0.2 million of payments of deferred issuance costs, and $0.2 million of fees paid to the Lenders to amend our Loan Agreement with Oxford. The cash provided by financing activities for the 2023 Period primarily represents $91.9 million of proceeds from the public offering of common stock and pre-funded warrants, net of issuance costs, $28.1 million of proceeds received from issuance of Series B Convertible Preferred Stock, net of issuance costs, $14.9 million of proceeds received pursuant to the Loan Agreement, $1.4 million of proceeds received from insurance premium financing and less than $0.1 million of proceeds received related to our employee stock purchase plan, partially offset by $0.9 million of payments on insurance premium financing. Refer toNote 9. Notes Payable to our unaudited condensed consolidated financial statements included in this quarterly report for additional details on the finance agreement with AFCO related to insurance premium financing and the monthly payments of principal and interest related thereto;Note 7. Debt toour unaudited condensed consolidated financial statements included in this quarterly report for additional details on the Loan Agreement; andNote 10. Capital Stock to our unaudited condensed consolidated financial statements included in this quarterly report for additional details on the June 2023 Offering of common stock and pre-funded warrants, and the January 2023 offering of our Series B Convertible Preferred Stock.

Current wording

payments on insurance premium financing, and $0.2 million of fees paid to the Lenders to amend our Loan Agreement with Oxford. The cash provided by financing activities for the 2023 Period primarily represents $91.4 million of proceeds from our public offering in June 2023 of common stock and pre-funded warrants to purchase shares of our common stock, net of issuance costs, $28.1 million of proceeds received from issuance of Series B Convertible Preferred Stock, net of issuance costs, $14.9 million of proceeds received pursuant to the Loan Agreement, $1.4 million of proceeds received from insurance premium financing and $0.1 million of proceeds received related to our employee stock purchase plan, partially offset by $1.3 million of payments on insurance premium financing. Refer toNote 9. Notes Payable to our unaudited condensed consolidated financial statements included in this quarterly report for additional details on the finance agreement with AFCO related to insurance premium financing and the monthly payments of principal and interest related thereto;Note 7. Debt toour unaudited condensed consolidated financial statements included in this quarterly report for additional details on the Loan Agreement; andNote 10. Capital Stock to our unaudited condensed consolidated financial statements included in this quarterly report for additional details on the July 2024 Offering of common stock, pre-funded warrants, and warrants, June 2023 Offering of common stock and pre-funded warrants, and the January 2023 offering of our Series B Convertible Preferred Stock.