Peresolimab

Seismic's $121 million series B follows a $101 million series A round in 2022. Seismic Therapeutic has secured a series B of significant magnitude, with $121 million pitched in by new investor Amgen Ventures in a round aimed at pushing two immunology programs into the clinic. The series B was led by new investor Bessemer Venture Partners, with participation from Amgen Ventures and Codon Capital, Alexandria Venture Investments, Gaingels and GC&H. Existing investors Timothy A. Springer, Lightspeed Venture Partners, Polaris Partners, Boxer Capital, GV, Samsara BioCapital, and unnamed management members and founders also joined in. The funding round follows a $101 million series A round in 2022, bringing Seismic’s total capital raised to $222 million. “When we launched Seismic at the end of 2021, we had a bold idea of applying machine learning to biologics drug discovery for immunology,” Jo Viney, Ph.D., CEO of Seismic, told Fierce Biotech via email. “At the time, we were a pioneer because most drug developers were applying machine learning to small molecules and target discovery. Our approach is to use machine learning to optimize the therapeutic properties of novel biologics for autoimmune diseases.” Seismic was launched by the founders of Pandion Therapeutics—including Viney—after its $1.9 billion acquisition by Merck in 2021. The company started exploring machine learning in pan‑immunoglobulin (Ig) G protease sculpting (Sc) enzymes, which gave way to Seismic’s S-1117 program, and dual-cell bidirectional antibodies, which resulted in the company’s S-4321 program, according to Viney. The new money will be funneled toward advancing those two programs—both currently in preclinical development—through IND-enabling studies and phase 1 trials. Though Seismic hasn’t revealed specific indications for either program, CEO Viney shared insight on the therapeutic potential for each.   Seismic’s Ig sculpting enzymes are designed to reduce or eliminate pathogenic antibodies that cause a range of autoimmune diseases such as myasthenia gravis, and chronic inflammatory demyelinating polyneuropathy, Viney said. Meanwhile, S-4321 is made to simultaneously engage inhibitory receptors on T cells and antigen presenting cells to tackle the multiple cell types driving autoimmune disease processes. “We are binding to PD-1 as well as another inhibitory receptor—Fc gamma RIIb,” Viney explained. “So, we are addressing two different pathways with two cell types with a single molecule.” The therapeutic potential lies in major autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease, the CEO said. In theory, tackling two pathways should offer more opportunity than just going after one, like Eli Lilly is with its mid-stage PD-1 agonist peresolimab for rheumatoid arthritis. The series B will also be used to build out Seismic’s pipeline and expand its machine learning-enabled IMPACT platform by adding more methods to enhance biologics drug discovery. The Massachusetts-based biotech has evolved since its launch a few years ago, expanding from a 14-person staff to 47 employees, and still growing, according to Viney, who said the company is actively recruiting.

THURSDAY, May 18, 2023 -- Peresolimab, a humanized immunoglobulin G1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway, is efficacious for patients with rheumatoid arthritis , according to a study published in the May 18 issue of the New England Journal of Medicine . Jay Tuttle, Ph.D., from Eli Lilly in San Diego, and colleagues conducted a phase 2a trial involving adults with moderate-to-severe rheumatoid arthritis who had an inadequate response to, a loss of response to, or unacceptable side effects with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or to biologic or targeted synthetic DMARDs. Participants were randomly assigned to receive 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every four weeks in a 2:1:1 ratio. The researchers found that the change from baseline in the Disease Activity Score for 28 joints based on the C-reactive protein level was significantly greater in the 700-mg peresolimab group versus the placebo group at week 12 (least-squares mean change, −2.09 ± 0.18 versus −0.99 ± 0.26). With response to the percentages of patients with American College of Rheumatology 20 (ACR20) response, but not the ACR50 and ACR70 responses, the results favored the 700-mg dose over placebo. "Peresolimab is a humanized monoclonal antibody designed to stimulate PD-1, with the goal of suppressing T-cell activation," write the authors of an accompanying editorial. "This novel approach provides an exciting therapeutic mechanism for the treatment of rheumatoid arthritis and potentially other autoimmune diseases in which antigen-activated lymphocytes play a pathogenic role." The study was funded by Eli Lilly, the manufacturer of peresolimab. Abstract/Full Text (subscription or payment may be required) Editorial (subscription or payment may be required) Posted May 2023