EVOLVE-104

Poster Presentations Spotlight Differentiated Therapeutic Profile and Precision Therapeutic Strategy for Lead Development Candidate EVOLVE104 as Program Advances Toward Clinic for Solid Tumors EVOLVE Platform Development Showcased with CD20-Targeted EVOLVE205 for Hematologic Tumors BRANFORD, Conn., Nov. 11, 2024 (GLOBE NEWSWIRE) -- EvolveImmune Therapeutics, an immuno-oncology company developing first-in-category, multifunctional biotherapeutics to overcome the therapeutic challenges of cancer cell resistance to current immune therapy agents, today announced that new preclinical and translational data highlighting EVOLVE, the company’s novel costimulatory T cell engager platform, were presented at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). Two poster presentations reported the latest preclinical results for the company’s lead development candidate, EVOLVE104, which is being developed for the treatment of solid tumors. In a separate oral presentation, EvolveImmune introduced a new program, EVOLVE205, which exemplifies the expanded potential of the EVOLVE platform to next-generation T cell engager formats. The EVOLVE platform uniquely unleashes potent, selective and integrated CD2 T cell co-stimulation, which amplifies and sustains the tumor killing capacity of these T cells. This approach bypasses low tumor immunogenicity, conditionally activates adaptive immunity and reduces T cell dysfunction to overcome therapeutic challenges in solid and hematologic tumors. By pairing its distinctive co-stimulation strategy with EvolveImmune’s deep insights in cancer cell biology, EVOLVE enables the discovery and development of first-in-category precision immuno-oncology agents with an enhanced likelihood of clinical success. Highlights from the company’s SITC presentations are as follows: EVOLVE104: One poster presentation (abstract #1326) detailed EvolveImmune’s precision therapeutic strategy for its lead development candidate, EVOLVE104, a novel multi-functional T cell engager with integrated CD2 co-stimulation which conditionally targets ULBP2/5/6. Researchers evaluated ULBP2/5/6 RNA and immunohistochemistry analyses across a range of solid tumor types and lines of therapy to pinpoint cancers enriched for its expression and most likely to respond to EVOLVE104 therapy. While ULBP2/5/6 expression is low and restricted in normal human tissues, it is highly expressed in malignancies with squamous pathology and select other cancers such as non-small cell lung cancer (NSCLC), head and neck cancers and muscle-invasive bladder cancer, is retained in the metastatic setting, and is maintained following relapse from standard of care therapies. Squamous cell cancers showed elevated immune infiltration compared to adenocarcinomas, and an enhanced proportion of CD2+ tumor-infiltrating lymphocytes (TILs) compared to other costimulatory receptors. Taken together these findings highlight bladder cancer, NSCLC, and head and neck cancers as among the malignancies most likely to respond to EVOLVE104, even following relapse or recurrence, and support the company’s strategy of targeting these indications in planned clinical studies. EvolveImmune continues to progress its chemistry, manufacturing, and control (CMC) activities for EVOLVE104, with the goal of advancing the program into the clinic in 2025. In a second poster presentation (abstract #1339), researchers highlighted the emerging favorable preclinical pharmacokinetic and toxicity profile for EVOLVE104. While differences in the tissue expression of cynomolgus ULBPs were detected, EVOLVE104 binds with similar affinities to human and cynomolgus T cells and sustained in vivo T cell engagement of EVOLVE104 was confirmed. No safety or tolerability findings were identified, including no overt cytokine excursions even at supra-pharmacologic exposures, and no evidence for non-specific T cell activation was observed. These results support the favorable developability of EVOLVE104. EVOLVE205: In an oral presentation (abstract #1137), researchers highlighted the discovery of EVOLVE205, a highly potent CD20-targeted CD2 co-stimulatory T cell engager designed in a 2:1 bispecific format. Presented data demonstrated EVOLVE205’s ability to drive stronger in vitro tumor killing activity compared to clinical benchmarks such as glofitamab without exaggerating cytokine release, and significant improvement in an in vivo efficacy model. The company’s optimization of EVOLVE205 offers a compelling example of its ability to expand the potential of the EVOLVE platform by applying integrated CD2 co-stimulation to next-generation T cell engager formats. “The EvolveImmune team has made impressive progress to accelerate their pipeline development and to extend the potential applications of the EVOLVE technology. EVOLVE104 is an exciting new and differentiated T cell engager because it has a unique cancer target and incorporates CD2 co-stimulation to amplify anti-tumor T cell responses. I was particularly encouraged by the new data presented at this meeting which identify potentially responsive patient populations to EVOLVE104 and have important implications for expedited clinical development,” said Mario Sznol, M.D., co-Leader of the Cancer Immunology Program and Leader of the Melanoma/Renal Cancer Translational Research Team at Yale Cancer Center, and a member of EvolveImmune’s scientific advisory board. “There are substantial unmet needs in the cancer immunotherapy field that could be addressed by EVOLVE104 and EvolveImmune’s emerging pipeline molecules, and I look forward to their rapid deployment into the clinic.” “These presentations at the SITC conference provide an excellent snapshot of the rapid progress we have made to advance our EVOLVE technology, and the exciting therapeutic potential of our lead program, EVOLVE104,” said Jay Fine, Ph.D., president of research and development at EvolveImmune. “EVOLVE104 continues to demonstrate a distinctly differentiated profile in preclinical and translational studies, which our team is committed to building upon. We are eager to translate these findings to the clinic and look forward to initiating first-in-human trials in 2025.”Additional information on the 39th Annual Meeting of SITC is available through the conference website at: https://www.sitcancer.org/2024/home About EvolveImmune Therapeutics EvolveImmune Therapeutics, Inc. is an immunotherapy platform company developing first-in-category, multifunctional biotherapeutics designed to overcome cancer-driven immunodeficiency in a range of solid tumors and hematological cancers. First-in-human clinical trials are anticipated in 2025. The company is supported by a syndicate of top-tier life science industry investors including Pfizer Ventures, Solasta Ventures, Bristol Myers Squibb, Takeda Ventures, Inc., Yonjin Ventures and Elm Street Ventures. For more information, please visit: www.evolveimmune.com

AbbVie, already a leader in the T cell engager field with Epkinly and a Phase 3 program, is further digging into the field with a new discovery collaboration with EvolveImmune Therapeutics. The Chicago pharmaceutical company will pay EvolveImmune $65 million in upfront payments and equity, and it could dish out up to $1.4 billion in biobucks and fees if it elects to license the programs. The tie-up will focus on solid tumors and hematologic malignancies. The partnership is further validation of the R&D at EvolveImmune, which has raised about $72 million to date from VC investors as well as Bristol Myers Squibb and the corporate venture arms of Pfizer and Takeda. “There’s a next generation of T cell engagers, which we’re part of, that can bend the curve on treating patients,” EvolveImmune CEO Stephen Bloch told Endpoints News . He said the industry is “just at the beginning of that wave.” The deal arrives amid a week stacked with TCE-related deals and partnerships. GSK announced it’s paying $300 million upfront to buy an oncology T cell engager from Chimagen that it plans to study in lupus next year, and Genmab lined up a partnership with Revitope Oncology in solid tumors. Earlier this year, Merck paid $700 million for a Curon asset , Candid Therapeutics raised $370 million and Clasp Therapeutics nabbed $150 million. AbbVie is no stranger to T cell engagers. With Genmab, it markets the lymphoma treatment Epkinly. And in June, it also entered Phase 3 with another TCE, named ABBV-383. The money from AbbVie will help EvolveImmune get its lead internal program, named EVOLVE-104, into the clinic by the middle of next year, according to Bloch. The company likely won’t raise another private funding round before that Phase 1 but is open to additional financing in the future, he said. EvolveImmune has built a co-stimulatory molecule into its programs, which activates CD2, to improve durability. Bloch said T cell engagement through CD3 alone is “not enough” and leads to exhaustion and dysfunction of the T cells. “It’s a system, rather than folks who are thinking about multiple therapies or exogenous or multiple antibodies, to try to get to the same place,” Bloch said. Putting T cell engagers in studies for patients with autoimmune diseases has also become a focus in recent deals. Bloch said the company has a CD20 program that could be applied in autoimmune indications but will likely wait to see how other autoimmune TCEs read out in 2025. He’s not ruling out partnerships on the autoimmune front, though. “There’s a lot of competition,” he said, “and there’s also a lot of watching and seeing.” The startup, which has nearly 40 employees, previously did CRISPR/Cas9 discovery work in the CAR-T space. “The CAR-Ts obviously are incredibly important, but the T cell engagers open up cancer therapies to a much broader set of patients who may not be at academic medical centers,” Bloch said. He also pointed to the “very, very high” costs of administering CAR-Ts to patients.