Temozolomide

Naporafenib is a potential first-in-class and best-in-class pan-RAF inhibitor for multiple RAS/MAPK pathway-driven tumors and has been dosed in over 500 patients to date Favorable mOS and mPFS demonstrated in pooled analysis of Phase 1b and Phase 2 trials in NRASm melanoma Randomized Stage 1 readout for naporafenib plus trametinib vs. trametinib monotherapy expected in 2025 SAN DIEGO, June 18, 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 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 NRAS-mutant (NRASm) melanoma. Naporafenib is a potential first-in-class and best-in-class pan-RAF inhibitor that has been dosed in over 500 patients to date and is being developed to treat multiple types of RAS/MAPK pathway-driven tumors. “NRASm melanoma is an aggressive disease with no approved targeted therapies, underscoring the high unmet need for these patients. We are pleased to announce the initiation of our SEACRAFT-2 pivotal Phase 3 trial, which has a two-stage design. Importantly, Stage 1 is expected to provide a randomized data readout of naporafenib plus trametinib against single agent trametinib in 2025 and will inform the randomized Phase 2 dose (RP2D) for the combination,” said Shannon R. Morris, M.D., Ph.D., Erasca’s chief medical officer. “Stage 2, which incorporates feedback from the United States Food and Drug Administration (FDA) and European health authorities, is designed for regulatory approval and will compare the combination against physician’s choice of chemotherapy or a single agent MEK inhibitor using dual primary endpoints of progression free survival (PFS) and overall survival (OS).” A pooled analysis of the Phase 1b and Phase 2 trials of patients with NRASm melanoma dosed with naporafenib in combination with trametinib showed a median OS (mOS) of 13.0 and 14.1 months and a median PFS (mPFS) of 5.1 and 4.9 months at two doses of the combination, respectively. The pooled dataset at each dose compares favorably relative to historical benchmarks. About SEACRAFT-2 SEACRAFT-2 is a randomized, pivotal Phase 3 trial evaluating the clinical efficacy of naporafenib in combination with trametinib (MEKINIST®) compared to physician’s choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) in the post-immunotherapy setting in patients with NRAS-mutant metastatic melanoma. A randomized Stage 1 readout for naporafenib plus trametinib compared to trametinib alone is expected in 2025. About Naporafenib Naporafenib (formerly LXH254) is a potent and selective pan-RAF inhibitor, with a potential first-in-class and best-in-class profile. Naporafenib has been dosed in over 500 patients to date, whereby safety, tolerability, pharmacokinetics, and pharmacodynamics have been established in both monotherapy and select combinations. Clinical proof-of-concept (PoC) has been established for the combination with trametinib for patients with NRAS-mutant (NRASm) melanoma, which includes NRAS Q61X melanoma, and preliminary clinical PoC has been established for the combination with trametinib for patients with RAS Q61X in non-small cell lung cancer (NSCLC). Erasca plans to focus initially on advancing and securing regulatory approval for naporafenib plus trametinib in NRASm melanoma as part of the SEACRAFT-2 pivotal Phase 3 trial and in RAS Q61X solid tumors as part of the ongoing SEACRAFT-1 Phase 1b trial, respectively. Erasca is also exploring additional combinations of naporafenib with other proprietary therapeutic agents in our pipeline. Naporafenib has received Fast Track Designation from the United States Food and Drug Administration (FDA) for patients with advanced NRASm melanoma. About Erasca At 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 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; the planned advancement of our development pipeline, including the anticipated timing of the Stage 1 data readout for the SEACRAFT-2 trial, and other upcoming development milestones. 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; the analysis of pooled Phase 1 and Phase 2 naporafenib plus trametinib data covers two clinical trials with different designs and inclusion criteria, which cannot be directly compared, and therefore may not be a reliable indicator of mOS data; due to differences between trial designs and subject characteristics, comparing data across different trials may not be a reliable indicator of data; results from preclinical studies or early clinical trials, including the clinical trial results discussed in this press release, not necessarily being predictive of future results; unfavorable results from preclinical studies or clinical trials; 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; 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 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, 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; the inability to realize any benefits from our current licenses, collaborations, acquisitions, and collaborations, and any future licenses, acquisitions, or collaborations, and our ability to fulfill our obligations under such arrangements; our ability to obtain and maintain intellectual property protection for our product candidates; regulatory developments in the United States and foreign countries; Fast Track Designation may not lead to a faster development or regulatory review or approval process, and does not increase the likelihood that our product candidates will receive marketing approval; 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. MEKINIST® is a registered trademark owned by or licensed to Novartis AG, its subsidiaries, or affiliates. Contact: Joyce Allaire LifeSci Advisors, LLC jallaire@lifesciadvisors.com Source: Erasca, Inc.

140 patients have been recruited at sites in Spain, Italy, France and United Kingdom. The open readout of the trial is expected by late 2024. Laminar aims to submit regulatory filings or conditional marketing authorization by early 2025. PALMA DE MALLORCA, Spain, June 11, 2024 /PRNewswire/ -- Laminar Pharmaceuticals S.A., a clinical-stage biotechnological company developing novel therapies to treat diverse pathologies with unmet clinical needs, is pleased to announce the recruitment of patients for the CLINGLIO (NCT04250922) study has been closed after 140 adult patients have been successfully enrolled. The CLINGLIO study is a multinational, phase 2b/3, randomized, placebo-controlled, double-blind clinical trial evaluating idroxioleic acid in combination with Standard of Care (combined tumour resection and chemoradiotherapy) for the treatment of newly diagnosed glioblastoma patients. The CLINGLIO trial, funded by a European Commission Grant (H2020) is being carried out in 21 hospitals in Spain, Italy, France, and United Kingdom. The investigational study drug, idroxioleic acid (LAM561, sodium; 2-OHOA) is a synthetic fatty acid with a novel therapeutic approach, administrated orally to treat this devastating type of cancer. "We are pleased to announce that the pivotal phase 2b/3 trial recruitment is completed, as this means that the results and outcome of the trial will be soon available," said Adrian McNicholl, Chief of Clinical Operations at Laminar Pharmaceuticals. The trial is expected to reach the trigger event for interim analysis in July 2024, which would provide an unblinded readout the last quarter of this year. "If idroxioleic acid is able to show compelling evidence demonstrating significant progression free survival benefit with overall survival, it could imply the first addition to the Standard of Care for glioblastoma patients since the approval of Temozolomide in 2005, 19 years ago." These unblinded results will be submitted for EMA evaluation for Conditional Marketing Authorization in early 2025, and the trial will continue until final analysis of survival in 2026. Pablo Escribá, CEO of Laminar Pharmaceuticals, said: "The completion of the recruitment is a huge milestone in our clinical trial and in the development of this potential new therapy for glioblastoma patients. We are excited about the possibility of offering a new treatment available for this fatal disease, which has some of the clearer unmet needs across the oncology field". The CLINGLIO trial, which was initiated in December 2019, has enrolled 140 participants across 4 countries in Europe. Those patients were randomized 1:1 versus placebo. Idroxioleic acid or placebo is added to Standard of Care, and continued for as long as the tumour does not progress. Idroxioleic acid has shown a favorable safety profile in pre-clinical and clinical trials so far. Additionally, no safety concerns were raised by an Independent Data Monitoring Committee (IDMC) who recommended "continue without modifications" after unblinded reviews of the available safety and efficacy data. The trial will continue until the final analysis of overall survival. The CLINGLIO trial is considered pivotal in that results showing significant clinical benefit could be sufficient for a request for conditional marketing authorization in the EU late this year; and potential full marketing authorization in 2026, for which enabling pre-submission interactions with the EMA have been initiated. About Laminar Pharmaceuticals S.A. Laminar Pharmaceuticals S.A. (Laminar) is a Spanish biotechnological company created in 2006, committed to translational health research, for the rational design and development of drugs to treat oncological and other pathologies in the form of synthetic fatty acids considered "First-in-class Health Solutions" and based on a novel technology, the Melitherapy (MLT or Membrane Lipid Therapy). Laminar controls all the processes, from the rational design of the molecules to the clinical trials that lead up to the launch of a new drug, with constant investment in R&D and high-quality standards. It is currently headquartered in Mallorca (Spain) with a subsidiary in Massachusetts (USA). About Glioblastoma Glioblastoma is the most common primary malignant brain tumour and accounts for nearly 50 percent of all gliomas and approximately 25 percent of all primary brain and CNS malignant tumours. The incidence of GBM in Europe is currently above 25,000 new cases each year, rising to over 100,000 cases per year worldwide. The prognosis for Glioblastoma patients is very poor, with a median survival time of about 14.5 months despite optimum chemo-radiation treatment. About 15% of patients survive two years after diagnosis and ca. 4% survive for five or more years. In this scenario, there is a desperate need for novel treatment alternatives that provide safe and more efficacious clinical outcomes. About idroxioleic acid Idroxioleic acid (LAM561; 2-hydroxyoleic acid (2-OHOA)) is a synthetic derivative of oleic acid and Laminar's most advanced R&D product, which is taken orally. This drug alters the composition of the plasma membrane in cancer cells, reducing the activity of membrane-associated signaling proteins that are known to promote tumour growth and affecting tumours in the brain. LAM561 is in the process of completing its last clinical development phase in adults and has shown promising preliminary clinical activity in the treatment of aggressive high-grade glioblastoma. SOURCE Laminar Pharmaceuticals, S.A.