Pan-RAS (Fog Pharma)

In-licensed potential best-in-class pan-RAS molecular glue ERAS-0015 and potential first-in-class pan-KRAS inhibitor ERAS-4001 with a goal of expanding treatment options across RAS-driven tumors Initiated SEACRAFT-2 registrational trial in patients with NRASm melanoma; randomized data for naporafenib plus trametinib vs. trametinib monotherapy expected in 2025 Robust balance sheet with cash, cash equivalents, and marketable securities of $460 million as of June 30, 2024 is expected to fund operations into H1 2027 SAN DIEGO, Aug. 12, 2024 (GLOBE NEWSWIRE) -- Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today provided business updates and reported financial results for the fiscal quarter ended June 30, 2024. “This second quarter 2024 was transformative for Erasca, driven by the successful in-licensing of a RAS-targeting franchise of potentially best-in-class and first-in-class molecules along with initiating our SEACRAFT-2 Phase 3 registrational trial for naporafenib; in addition, we strengthened our balance sheet and significantly extended our cash runway from multiple equity financings and prioritization decisions,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “Naporafenib plus trametinib has shown clinically meaningful and differentiated progression free survival and overall survival benefits across Phase 1 and 2 trials in patients with NRAS-mutant (NRASm) melanoma. We may also have the opportunity to expand treatment options for patients with various RAS Q61X solid tumors based on the initial Phase 1b combination data from SEACRAFT-1 expected in the fourth quarter of the year.” Dr. Lim continued, “Our bolstered pipeline includes an exciting RAS-targeting franchise, including a pan-RAS molecular glue ERAS-0015 and a pan-KRAS inhibitor ERAS-4001, that exhibit complementary RAS inhibitory mechanisms, differentiated preclinical profiles, and the potential to expand treatment options across RAS-driven tumors. We are well-positioned to continue advancing our pipeline through multiple catalysts and deliver on our mission to develop therapies that shut down RAS-driven cancers for the benefit of patients.” Research and Development (R&D) Highlights Initiated SEACRAFT-2 Pivotal Phase 3 Trial: In June 2024, Erasca announced the initiation of the global SEACRAFT-2 Phase 3 trial evaluating the pan-RAF inhibitor naporafenib in combination with the MEK inhibitor trametinib (MEKINIST®) in patients with NRASm melanoma. The two-stage design is expected to provide a randomized data readout of naporafenib plus trametinib against single agent trametinib in 2025 in Stage 1 and inform the randomized Phase 2 dose for the combination. In Stage 2, the trial is expected to compare the combination against physician’s choice of chemotherapy or a single agent MEK inhibitor using dual primary endpoints of progression free survival and overall survival for regulatory approval. Corporate Highlights In-Licensed Potential Best-in-Class and First-in-Class RAS-Targeting Franchise: In May 2024, Erasca announced exclusive license agreements for two preclinical RAS programs—a potential best-in-class pan-RAS molecular glue (ERAS-0015) and a potential first-in-class pan-KRAS inhibitor (ERAS-4001). ERAS-0015 and ERAS-4001 are potent, orally bioavailable molecules with complementary RAS inhibitory mechanisms that have the potential to address unmet needs in approximately 2.7 million patients who are diagnosed annually globally with RAS-mutant (RASm) tumors, of which over 2.2 million patients are diagnosed with KRAS-mutant (KRASm) tumors.Extended Cash Runway with $229 Million in Equity Financings: In March 2024, Erasca entered into a $45 million oversubscribed private placement financing led by high-quality new and existing healthcare-focused investors. Additionally, in May 2024, Erasca entered into a $184 million oversubscribed underwritten offering led by high-quality new and existing healthcare-focused investors. Together, these equity financings extended Erasca’s expected cash runway into the first half of 2027. Key Upcoming Milestones SEACRAFT-1: Phase 1b trial for naporafenib (pan-RAF inhibitor) plus trametinib in patients with RAS Q61X solid tumors Initial Phase 1b combination signal-seeking efficacy data in relevant tumor types expected to be reported in Q4 2024 SEACRAFT-2: Randomized pivotal Phase 3 trial for naporafenib plus trametinib in patients with NRASm melanoma Phase 3 Stage 1 randomized dose optimization data expected to be reported in 2025 AURORAS-1: Phase 1 trial for ERAS-0015 (pan-RAS molecular glue) in patients with RASm solid tumors IND filing expected in H1 2025Initial Phase 1 monotherapy data in relevant tumor types expected to be reported in 2026 BOREALIS-1: Phase 1 trial for ERAS-4001 (pan-KRAS inhibitor) in patients with KRASm solid tumors IND filing expected in Q1 2025Initial Phase 1 monotherapy data in relevant tumor types expected to be reported in 2026 Second Quarter 2024 Financial Results Cash Position: Cash, cash equivalents, and marketable securities were $460.2 million as of June 30, 2024, compared to $322.0 million as of December 31, 2023. In April 2024, Erasca completed a $45 million private placement, raising net proceeds of $43.6 million after deducting placement agent fees and expenses. In May 2024, Erasca completed a $184 million underwritten offering, raising net proceeds of $174.4 million after deducting underwriting discounts and commissions, and offering costs. Erasca expects its current cash, cash equivalents, and marketable securities balance of $460.2 million to fund operations into the first half of 2027. Research and Development (R&D) Expenses: R&D expenses were $33.0 million for the quarter ended June 30, 2024, compared to $26.2 million for the quarter ended June 30, 2023. The increase was primarily driven by an impairment charge on operating lease assets and property and equipment, and increases in expenses incurred in connection with clinical trials, preclinical studies, and discovery activities, personnel costs primarily due to termination benefits in connection with a reduction in force, facilities-related expenses and depreciation, and outsourced services and consulting fees. Erasca also recorded $22.5 million of in-process R&D expense during the quarter ended June 30, 2024 for upfront payments under Erasca’s ERAS-0015 and ERAS-4001 license agreements. General and Administrative (G&A) Expenses: G&A expenses were $12.3 million for the quarter ended June 30, 2024, compared to $9.8 million for the quarter ended June 30, 2023. The increase was primarily driven by an impairment charge on operating lease assets and property and equipment, and an increase in legal fees. Net Loss: Net loss was $63.2 million, or $(0.29) per basic and diluted share, for the quarter ended June 30, 2024, compared to $31.8 million, or $(0.21) per basic and diluted share, for the quarter ended June 30, 2023. About ErascaAt Erasca, our name is our mission: To erase cancer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of patients with cancer. We have assembled one of the deepest RAS/MAPK pathway-focused pipeline in the industry. We believe our team’s capabilities and experience, further guided by our scientific advisory board which includes the world’s leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer. Cautionary Note Regarding Forward-Looking Statements Erasca cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: our expectations regarding the potential therapeutic benefits of our product candidates, including naporafenib, ERAS-0015, and ERAS-4001; the planned advancement of our development pipeline, including the anticipated timing of data readouts for the SEACRAFT-1, SEACRAFT-2, AURORAS-1, and BOREALIS-1 trials; the anticipated timing of the IND filings for the AURORAS-1 and BOREALIS-1 trials; and our ability to successfully prioritize our pipeline portfolio to focus on existing programs that we believe have the highest probability of success. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: our approach to the discovery and development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; our assumptions about ERAS-0015’s or ERAS-4001’s development potential are based in large part on the preclinical data generated by the licensors and we may observe materially and adversely different results as we conduct our planned studies and trials; we only have one product candidate in clinical development and all of our other development efforts are in the preclinical or development stage; we have not completed any clinical trials of naporafenib and are reliant on data generated by Novartis in prior clinical trials conducted by it; our planned SEACRAFT trials may not support the registration of naporafenib; our assumptions around which programs may have a higher probability of success may not be accurate, and we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; potential delays in the commencement, enrollment, data readout, and completion of clinical trials and preclinical studies; our dependence on third parties in connection with manufacturing, research, and preclinical and clinical testing; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization, or may result in recalls or product liability claims; unfavorable results from preclinical studies or clinical trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results; the inability to realize any benefits from our current licenses, acquisitions, and collaborations, and any future licenses, acquisitions, or collaborations, and our ability to fulfill our obligations under such arrangements; regulatory developments in the United States and foreign countries; later developments with the FDA or EU health authorities may be inconsistent with the feedback received to date regarding our development plans and trial designs; our ability to obtain and maintain intellectual property protection for our product candidates and maintain our rights under intellectual property licenses; our ability to fund our operating plans with our current cash, cash equivalents, and marketable securities; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our annual report on Form 10-K for the year ended December 31, 2023, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Erasca, Inc.Selected Condensed Consolidated Balance Sheet Data(In thousands)(Unaudited) June 30, December 31, 2024 2023 Balance Sheet Data: Cash, cash equivalents, and marketable securities $460,248 $321,992 Working capital 393,112 294,520 Total assets 525,744 395,297 Accumulated deficit (704,231) (606,013)Total stockholders’ equity 451,087 316,686 Erasca, Inc.Condensed Consolidated Statements of Operations and Comprehensive Loss(In thousands, except share and per share amounts)(Unaudited) Three months ended June 30, Six months ended June 30, 2024 2023 2024 2023 Operating expenses: Research and development $33,032 $26,218 $61,606 $53,803 In-process research and development 22,500 — 22,500 — General and administrative 12,250 9,752 22,527 19,192 Total operating expenses 67,782 35,970 106,633 72,995 Loss from operations (67,782) (35,970) (106,633) (72,995)Other income (expense) Interest income 5,041 4,251 8,941 8,128 Other expense, net (460) (62) (526) (113)Total other income (expense), net 4,581 4,189 8,415 8,015 Net loss $(63,201) $(31,781) $(98,218) $(64,980)Net loss per share, basic and diluted $(0.29) $(0.21) $(0.53) $(0.43)Weighted-average shares of common stock used in computing net loss per share, basic and diluted 217,806,567 150,037,029 184,484,154 149,772,093 Other comprehensive income (loss): Unrealized gain (loss) on marketable securities, net 14 (279) (273) 248 Comprehensive loss $(63,187) $(32,060) $(98,491) $(64,732) MEKINIST® is a registered trademark owned by or licensed to Novartis AG, its subsidiaries, or affiliates. Contact:Joyce AllaireLifeSci Advisors, LLCjallaire@lifesciadvisors.com Source: Erasca, Inc.

Revolution Medicines headquarters in Redwood City, California. Credit: Tada Images via Shutterstock. Revolution Medicine plans to kickstart a Phase III trial following positive data from a first-in-human study of its investigational KRAS inhibitor RMC-6236 in pancreatic cancer patients. In an investor deck released yesterday [15 July], the company outlined updated data from the Phase I trial (NCT05379985) that outlined responses from 127 patients with pancreatic ductal carcinoma (PDAC) who received between a dose of RMC-6236 ranging from 160mg to 300mg. Median progression-free survival was 8.1 months in patients with the KRAS G12X mutation, and 7.6 months in those who broadly have RAS-mutant tumours. Among participants who had at least three prior treatment regimens, the median progression-free survival was 4.2 months. Out of the 127 participants, 96% suffered from side effects. The most common were rashes, diarrhoea, nausea, and mouth sores. Those adverse events were deemed severe or medically significant in 28% of patients. The company had previously presented early Phase I data, which covered 40 evaluable patients, at the European Society of Medical Oncology 2023 meeting in October. See Also: MHRA approves Pierre Fabre’s vibegron to treat OAB Rusan Pharma’s API Plant in Ankleshwar Receives US FDA GMP Approval The Redwood City, California-based company now plans on initiating a Phase III RASolute 302 trial in metastatic PDAC patients. The study will compare the 300mg dose of RMC-6236 to the investigator’s choice of standard chemotherapy among patients previously treated with two lines of therapy. According to Revolution, primary endpoint data is expected in 2026 and 2027. KRAS is a gene that provides instructions for making a protein called K-Ras, which is part of the RAS/MAPK pathway. It is the most frequently mutated oncogene, meaning KRAS has been a target investigated by cancer scientists for decades. There are currently only two approved KRAS inhibitors, Bristol Myers Squibb ’s (BMS) Krazati (adagrasib) and Amgen ’s Lumakras (sotorasib), both of which are KRAS G12C inhibitors indicated to treat NSCLC. Their US Food and Drug Administration (FDA) approvals were a breakthrough for the scientific community, with GlobalData forecasting sales of $1.63bn for Krazati and $787m for Lumakras in 2030. GlobalData is the parent company of Pharmaceutical Technology. In its 1Q earnings released in May, the company outlined plans to release data in H2 2024 to support the initiation of two pivotal studies in pancreatic cancer and NSCLC. Though KRAS G12C is a prominent mutation seen in lung cancer, certain malignancies such as pancreatic cancer most commonly have the G12D mutation in the KRAS gene. Therefore, there is a need for KRAS inhibitors that can treat other cancer types. GMC-6236 is part of the emerging innovation being seen in the KRAS space. Instead of targeting a specific mutation such as G12C, the drug is a multi-selective non-covalent inhibitor designed to treat patients with cancers driven by a wide range of common RAS mutations. Other companies advancing KRAS inhibitors include GenFleet Therapeutics, which is investigating the Phase III asset GFH925 , a KRAS G12C inhibitor for the treatment of patients with refractory metastatic colorectal cancer (CRC).