SHOC2

ERAS-0015 and ERAS-4001 showed robust anti-tumor activity as monotherapy and combination therapy First-in-class examples of direct SHOC2 binders and modulators of SMP complex assembly identified with potential to block oncogenic RAS/MAPK pathway signaling SAN DIEGO, April 29, 2025 (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 presented new preclinical data reinforcing the best-in-class profiles of Erasca’s RAS-targeting franchise at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, Illinois. The Company also presented potential first-in-class examples of direct SHOC2 binders and modulators of SMP complex assembly, representing a new approach to block oncogenic RAS/MAPK pathway signaling. The posters are available online at Erasca.com/science/#presentations. “We were pleased to present new preclinical data at this year’s AACR meeting further solidifying our understanding of the properties that support the best-in-class potential of our pan-RAS molecular glue ERAS-0015 and the best-in-class/first-in-class potential of our pan-KRAS inhibitor ERAS-4001. We also showcased our research capabilities with, to our knowledge, the first identification of direct SHOC2 binders targeting the RAS/MAPK pathway in collaboration with our scientific advisory board member Pablo Rodriguez-Viciana,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “Importantly, these data reinforce the favorable pharmacokinetic properties that allow for robust anti-tumor activity at significantly lower doses of ERAS-0015 versus the leading pan-RAS molecular glue in development, as well as the potential expanded therapeutic index of ERAS-4001 through selective targeting of key KRAS mutations. We are excited to achieve our goal of advancing development of both RAS-targeting compounds in the clinic this year.” Poster Presentation Highlights Abstract 390 – ERAS-0015 is a pan-RAS molecular glue with best-in-class potential in RAS mutant solid tumors ERAS-0015 demonstrated favorable pharmacokinetic properties including longer residence time and greater tissue exposure that led to robust anti-tumor activity alone and in combination at doses lower than the leading pan-RAS molecular glue in development. ERAS-0015 is a pan-RAS molecular glue designed to shut down pathogenic signaling mediated by mutant and wildtype RAS by targeting RAS in the GTP-bound state. 8-21-fold greater cyclophilin A (CypA) binding for ERAS-0015 vs. pan-RAS molecular glue comparator RMC-6236 ERAS-0015 dose-dependently formed a ternary complex with active state RAS and CypA, which blocks formation of additional downstream effector complexes Potent inhibition of proliferation with ERAS-0015 across a panel of cell lines spanning diverse tumor tissues and RAS mutations Preferential drug distribution into tumor tissues Promising monotherapy and combination activity across multiple RAS mutant models Abstract 4367 – ERAS-4001 is a pan-KRAS inhibitor with robust anti-tumor activity in KRAS altered solid tumors ERAS-4001 potentially has an expanded therapeutic index relative to pan-RAS inhibitors by selectively targeting both mutant and wildtype KRAS, leading to significant tumor growth inhibition alone and in combination. Selectively targeting both wildtype (WT) and oncogenic KRAS may address resistance mechanisms to mutant-selective KRAS inhibitors that are driven by WT KRAS activity. A potential first-in-class pan-KRAS inhibitor, ERAS-4001 is a novel, highly potent pan-KRAS inhibitor that blocks mutant and WT KRAS, potentially offering improved tolerability relative to pan-RAS inhibitors by sparing NRAS and HRAS. ERAS-4001 selectively inhibited KRAS mutant enzymes and WT KRAS over WT HRAS and NRAS ERAS-4001 inhibited 3D cell viability and proliferation in 13 G12X mutant and one wildtype KRAS amplified cell lines across indications with single digit nanomolar IC50s Dose-dependent tumor growth inhibition and significant antitumor efficacy with ERAS-4001 monotherapy in KRAS mutant xenograft models Robust tumor growth inhibition with ERAS-4001 plus anti-PD-1 or cetuximab in KRAS mutant models Promising antitumor monotherapy and combination activity across multiple KRAS mutant models Abstract 3152 – Identification and characterization of inhibitors of SHOC2-MRAS-PP1C complex assembly Identified inhibitors of SMP complex assembly via SHOC2 engagement, representing a potential new approach to attenuate RAS/MAPK pathway signaling. Genetic ablation or protein degradation of SHOC2 can sensitize RAS-driven cells to RAS/MAPK pathway inhibitors and prevent adaptive resistance. Identified two lead series that bind selectively to SHOC2 with low nanomolar affinity, interfere with SMP complex assembly, and inhibit the SMP complex’s phosphatase activity To our knowledge, these compounds represent the first examples of direct modulators of the SMP complex Further optimization of SHOC2 binders for protein-protein inhibitors (PPIs) and degrader modalities is ongoing 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 patients with cancer. We have assembled one of the deepest RAS/MAPK pathway-focused pipelines 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 and early-stage development projects, including ERAS-0015, ERAS-4001, and our SHOC2 binding project; and our ability to achieve our goal of initiating the clinical development of ERAS-0015 and ERAS-4001 this year. 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 development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; results from preclinical studies not necessarily being predictive of future results; 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; unfavorable results from preclinical studies or clinical trials; 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; 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, 2024, 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. Contact: Joyce Allaire LifeSci Advisors, LLC jallaire@lifesciadvisors.com Source: Erasca, Inc. Source: Erasca, Inc.

A small Northwestern University spinout attempting to develop a twist on biologics has pulled together a $30 million Series A. The startup, named Grove Biopharma, weathered the pandemic and, after more than a year of fundraising, pushed through the difficult financing environment in a bid to prove its platform can hit intracellular disease targets and potentially open up a new field of medicines. To get to this point, Grove had to rightsize its original ambition of raising a $50 million Series A, CEO Geoffrey Duyk said in an interview. The funding environment has been particularly difficult for startups like Grove that are attempting to create new platforms. Risk-averse investors have mostly concentrated their bets on clinical-stage assets or pipelines on the cusp of human trials. Duyk has seen both sides of the coin, having worked in R&D at Millennium and Exelixis in the 1990s and early 2000s before spending two decades on the investing side. “This is obviously the most challenging environment I’ve seen in my entire career,” Duyk said, “and I’ve been through many, many cycles.” The Series A, albeit smaller than planned, does come with industry validation via Eli Lilly, which took part in the DCVC Bio-led round. Grove previously raised about $8 million in seed funding, Duyk said. The nimble startup, which has about a dozen employees, is also part of the burgeoning Chicago biotech scene . Grove was incubated by local investor Portal Innovations, and it is housed in the same West Loop building as the Chan Zuckerberg Biohub Chicago. The startup’s platform seeks to make synthetic biomolecules that can go after intracellular targets. Whereas the industry has traditionally thought of materials as delivery mechanisms, Grove wants to flip the switch on that thinking. “It’s not just new drugs. It’s not just a new molecule. It’s a new way to develop drugs,” scientific founder and Northwestern professor Nathan Gianneschi said in an interview. “This is turning that around and saying, ‘Well, no, the material itself is the drug.'” Gianneschi and Duyk co-founded Grove in 2020 alongside chief technology officer Paul Bertin. Duyk called it a “three-men-in-a-garage” type of startup after it spun out from the university lab. “Nathan was asking some interesting questions: What if you rethought what a protein was? Instead of a protein being a linear polymer of amino acids, what if you made it a branch of polymer peptides?” Duyk said. Grove’s molecules look like little trees, hence the company’s name, according to Gianneschi. He and his team discovered a fully synthetic molecule that incorporated the critical features of an antibody but could also get inside a cell, Duyk said. “It was like a little bit of a dream to begin with, that you could mimic proteins using polymer chemistry,” Gianneschi said. Its first clinical attempt will be in prostate cancer with a molecule that goes after AR-V7, an androgen receptor splice variant. That said, the startup will likely need more financing to get into the first human trial, Duyk said. Grove’s other oncology programs include work in SHOC2, the MYC/WDR5 interaction, and the MYC transactivation domain. Its in-house R&D engine is also exploring neurodegenerative diseases by way of tau pathology and the Keap1-Nrf2 pathway. Grove is hopeful that its platform can lead to medicines that are delivered via IV, under-the-skin injections or even topicals, Duyk said. Work has yet to be done to see if they can be made available orally, he added. The company also plans to seek biopharma partnerships, saying its platform can be applied in multiple areas, including degraders. “We can use our molecules to do the equivalent of ADCs,” Duyk said. “We can use our molecules to do the equivalent of radiopharmaceuticals, so there’s a lot of interest in pursuing that.” Editor’s note: This story was updated to correct the AR-V7 program is in prostate cancer, not pancreatic.

Nitpicker/Shutterstock Bristol Myers Squibb entered two separate research collaboration and licensing deals, one with San Francisco-based SyntheX and the second with London’s Autolus Therapeutics. This first partnership will leverage SyntheX’s ToRNeDO platform for protein degradation. The platform discovers molecular glue-based protein degraders using pre-specified E3 ligases and neosubstrates. Molecular glue degraders are compounds that organize interactions between a target protein and an E3 ubiquitin ligase, which causes the degradation of the target protein. Ubiquitin attaches to obsolete proteins, signaling to cells that it’s time for them to be disposed of by breaking them down into their component molecules. BMS is paying upfront cash and an investment in the company. SyntheX is eligible for up to $550 million in performance-based milestones. It is also eligible for royalties based on worldwide net sales of any subsequent commercial products. Maria Soloveychik, Ph.D., SyntheX’s co-founder and CEO said the company looks forward to combining its ToRNeDO platform with BMS's clinical development expertise as "we work to discover and deliver the next-generation of TPD therapies for patients in need.” The company’s pipeline focuses on oncology and includes STX100 targeting RAD51; STX200 targeting RAF1; STX300 targeting KRASG122X, STX400 targeting NRas; STX500 targeting Cbl-b and STX600 targeting Shoc2. All are in preclinical development. SyntheX’s investors include BMS, SOSV, OMX/Ventures, MorganNoble, Oriza Ventures and 8VC. The Autolus Therapeutics agreement provides BMS with access to Autolus’ RQR8 safety switch, which BMS can then incorporate into specific cell therapies for cancer indications. Toxic side effects, such as cytokine release syndrome and brain toxicity, are common in cell therapies. In these types of cell therapies, such as CAR-T, T-cells are genetically engineered to respond to specific cancer antigens and their epitopes. They are then infused back into the patient, where they become a living therapy, producing more T-cells to attack the cancer cells. But they can grow too fast or too much, which causes severe side effects. Safety switches, such as Autolus’ RQR8, are a way of limiting these side effects by placing limits on T-cell production. “Safety switches are critical to the future of our field of advanced cell therapies,” said Martin Pule, Autolus’ CSO in a prepared statement. “They allow us to develop approaches that are designed to significantly improve patient outcomes, whilst at the same time incorporating the potential to reduce the risk of severe adverse side effects from the treatment.” Autolus’ proprietary RQR8 switched is administered with Genetech and Biogen’s Rituxan (rituximab). Rituxan is approved to treat non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis and pemphigus vulgaris. Once dosed, rituximab binds to the engineered CD20 epitopes on the surface of the cell therapy and triggers selective cell death. RQR8 is a 136-amino-acid epitope-based marker/suicide gene. A suicide gene is genetically coded so that it selectively destroys transferred T cells when facing unacceptable levels of toxicity, a common severe side effect of CAR-T and cell therapies. Specifically, RQR8 is for T-cells and combines target epitopes from both CD34 and CD20 antigens, which allows selection from a clinically approved CliniMACS CD34 system (Miltenyi), a medical device system designed to enrich CD34+ targets. Binding with rituximab, it selectively deletes transgene-expressing cells.