Crescendo Biologics Ltd (Crescendo), a clinical stage immuno-oncology company developing novel, targeted T cell enhancing therapeutics, today announces a new translational science collaboration with The Institute of Cancer Research, London, one of the world’s most influential cancer research organisations. Working together, Crescendo and The Institute of Cancer Research (ICR) will further characterise the non-clinical pharmacology of CB307, Crescendo’s first-in-class lead programme.

CB307 is a novel, half-life extended PSMA x CD137 bispecific currently in a Phase 1 clinical study. It is designed for the conditional and durable activation and expansion of tumour-specific T cell populations, exclusively within the tumour microenvironment. The alliance with the ICR will drive valuable mechanistic insights into the pharmacology of CB307 in both in vitro and in vivo settings. It will include studies on patient-derived prostate cancer tissues to extend the understanding of PSMA and CD137 co-localisation and their influence on CB307-mediated T cell enhancement.

Professor Johann de Bono, Regius Professor of Cancer Research and Head of the Division of Clinical Studies at the ICR, commented: “We are very pleased to have initiated this important work with the team at Crescendo. Next generation immunotherapies could offer much-needed new treatment options to patients with castration-resistant prostate cancer, as well as other cancer types with high prevalence. We expect this collaboration to provide meaningful additional insights into the mechanisms and activity of CB307 in a variety of relevant settings.”

Dr Andrew Pierce, VP Translational Biology at Crescendo, added: “The ICR is a world-renowned research institution, and we are very excited to have the opportunity to collaborate with Professor de Bono and his team to further explore the immunobiology of PSMA and CD137, including their co-localisation in tumour tissue. The results of these translational studies will be of great importance in understanding the profile of CB307, especially when placed alongside the clinical results as they continue to emerge from our ongoing clinical programme.”

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About Crescendo Biologics

Crescendo Biologics is a private, clinical stage immuno-oncology company developing novel, targeted T cell enhancing Humabody® therapeutics.

Leading its proprietary pipeline, Crescendo Biologics has developed CB307, a novel half-life extended CD137 x PSMA Humabody® for the selective activation of tumour-specific T cells exclusively within the tumour microenvironment. CB307 is designed to achieve a longer lasting anti-cancer effect whilst avoiding systemic toxicity, and the clinical programme for CB307 is underway in patients with PSMA positive solid tumours.

The Company’s ability to develop multi-functional Humabody® therapeutics is based on its unique, patent protected, transgenic mouse platform generating 100% human VH domain building blocks (Humabody® VH). These robust molecules can be configured to engage therapeutic targets in such a way that they deliver novel biology and superior bio-distribution. This results in larger therapeutic windows compared to conventional IgG approaches. Humabody®-based formats can also be applied across a range of non-cancer indications.

Beyond Crescendo’s proprietary pipeline, the Company has a global, multi-target discovery and development collaboration with Takeda; a clinical development partnership with Cancer Research UK; and an exclusive, worldwide licensing agreement with Zai Lab, the product candidate of which is in a Phase 1 clinical trial.

Crescendo Biologics is located in Cambridge, UK, and is backed by blue-chip investors including Sofinnova Partners, Andera Partners, IP Group, Takeda Ventures, Quan Capital and Astellas.

For more information, please visit www.crescendobiologics.com and follow @HUMABODY.

About CB307

CB307 is a novel, half-life extended PSMA x CD137 bispecific currently in a Phase 1 clinical study. It is designed for the conditional and durable activation and expansion of tumour-specific T cell populations, exclusively within the tumour microenvironment.

The mechanism of conditional activation and expansion of T cells by CB307 is predicated on the presence of, and monovalent binding to, prostate-specific membrane antigen (PSMA) on tumour cells. This is expected to limit the activation and expansion of tumour-specific T cells to the tumour microenvironment. Cross-linking by CB307 between PSMA on the tumour cell and CD137 on the T cell then provides the necessary signal for T cells to proliferate and survive, generating a broad and durable anti-tumour response. In addition, CB307 contains no Fc region, further limiting its ability to exert off-target or out of tumour effects.

The half-life of CB307 has been extended through binding to human serum albumin, and the duration of half-life has been selected to optimize its extended biological effect while allowing quick systemic clearance.

CB307 is currently being studied in the POTENTIA trial, evaluating the safety and efficacy of CB307 in patients with advanced and/or metastatic PSMA-positive solid tumours. For more information about the POTENTIA trial, please visit the clinicaltrials.gov record at NCT04839991.

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