Pyramid Biosciences

Apr 18, 2023

News provided by Share this article Share this article GQ1010 demonstrated greater tumor growth inhibition and more potent cytotoxicity than DS-1062 across several preclinical models GQ1010 in combination with anti-PD1 also showed synergistic in vivo tumor growth inhibition superior to DS-1062 plus anti-PD1 Differentiated preclinical safety profile of GQ1010 suggests potential for a wider therapeutic index and improved combinability compared to more advanced TROP2 ADCs BRIDGEWATER, N.J., April 18, 2023 /PRNewswire/ -- Pyramid Biosciences, Inc., a privately-held, clinical-stage biotechnology company focused on developing transformative medicines for patients with cancer, and its partner GeneQuantum Healthcare (Suzhou) Co. Ltd, a privately-held biotechnology company based in China, announced data at the American Association for Cancer Research (AACR) Annual Meeting 2023 highlighting the preclinical efficacy and safety profile of GQ1010, a potential best-in-class antibody drug conjugate (ADC) targeting trophoblast cell surface antigen 2 (TROP2), across several in vitro and in vivo models. The poster presentation highlights several preclinical studies which showcase the differentiating attributes of GQ1010. Specifically, in a mouse syngeneic MC38 colon cancer model, the combination of GQ1010 plus anti-PD-1 therapy showed compelling synergistic tumor growth inhibition, which was superior to DS-1062 plus anti-PD-1. In this study, the GQ1010 combination reported 5 of 6 animals achieved a complete response, compared to zero of 6 animals with the DS-1062 combination. In addition, GQ1010 showed more potent in vitro cytotoxicity and a superior bystander effect versus DS-1062, and increased in vivo tumor growth inhibition with GQ1010 monotherapy compared head-to-head with either DS-1062 or TRODELVY® across multiple cancer models. Safety findings with GQ1010 in a non-human primate (NHP) study indicated a differentiated profile and highest non-severe toxic dose (HNSTD) of greater than 30 mg/kg, which may translate to a wider therapeutic window in human studies relative to more advanced TROP2 ADCs in development. Plasma stability studies showed 98% retention of drug-to-antibody ratio (DAR) for GQ1010, attributable to its unique, irreversible cleavable linker chemistry. "These preclinical findings are driven by GQ1010's unique ADC design, which utilizes site-specific enzymatic conjugation technology and a novel linker-payload which confer potent cytotoxicity and better stability in the plasma," said Qin Gang, Ph.D., CEO of GeneQuantum Healthcare. "The preclinical differentiation seen with GQ1010 provides further validation of the capabilities of the GeneQuantum platform to produce best-in-class bioconjugates, as was also observed in a Phase 1a study of the HER2-directed ADC, GQ1001." "TROP2 is a highly validated target in oncology, and TROP2-directed therapies are an important potential treatment option for a large number of cancers," remarked Brian Lestini, MD PhD, CEO of Pyramid Biosciences. "However, despite the TROP2 agents currently approved or in development, there remains significant unmet need for therapies that improve efficacy while reducing the potential for serious toxicities and optimizing therapeutic index and combinability. Preclinical data demonstrates the potential for GQ1010's unique ADC chemistry to provide a superior, best-in-class clinical profile and improve patient outcomes. Based on this preclinical data, we are excited to be moving GQ1010 into clinical development." The AACR annual meeting poster presentation details are as follows: Title: Preclinical characterization of GQ1010, a next generation Trop2 ADC with the best-in-class potential against diverse Trop2 positive solid tumors First Author: Yajun Sun Abstract #: 1549 About TROP2 TROP2 is a cell surface glycoprotein that is highly expressed in a variety of tumors including breast, lung, pancreatic, ovarian, and prostate cancer, and plays a role in tumor cell proliferation. Currently TRODELVY® (Gilead) is the only approved TROP2 ADC, with indications in triple-negative breast cancer, hormone-receptor positive breast cancer, and urothelial cancer. Clinical data have also been previously reported for TROP2 ADCs in development by Daiichi-Sankyo and Merck & Co. About Pyramid Biosciences, Inc. Founded in 2015, Pyramid Biosciences, Inc. is a clinical stage biotechnology company dedicated to developing transformative medicines for patients with cancer. Pyramid focuses on programs that target clinically validated mechanisms and with potential best-in-class properties that can address areas of high unmet need in cancer. Pyramid is currently conducting a global Phase 1/2 clinical trial of its lead oncology program PBI-200, a highly CNS penetrant next-generation NTRK inhibitor, in patients with NTRK-fusion driven cancers including primary and metastatic brain tumors. For more information, please visit www.pyramidbio.com . Pyramid Biosciences Media Inquiries: Laura DiCaprio