Crescendo Biologics presents preclinical data on lead clinical candidate CB307 and unveils its first ‘2 in 1’ immune cell engager CB699 at AACR 2024

Crescendo Biologics presents preclinical data on lead clinical candidate CB307 and unveils its first ‘2 in 1’ immune cell engager CB699 at AACR 2024

• Preclinical data demonstrate strong rationale for ongoing Phase 1b POTENTIA trial investigating conditional CD137 (4-1BB) agonist CB307 as monotherapy and in combination with pembrolizumab in patients with prostate cancer
  • Simultaneous publication in prestigious Clinical Cancer Research journal, including research generated through successful collaboration with The Institute of Cancer Research, London
• Crescendo also debuts CB699, a mesothelin-directed, CD137 and CD40 dual agonist demonstrating tumour-targeted activation of T, NK, and B lymphocytes

Cambridge, UK, 10 April 2024 – Crescendo Biologics Ltd (Crescendo), a clinical stage immuno-oncology company developing novel, targeted immune cell enhancing therapeutics, has presented preclinical data at the 2024 American Association for Cancer Research (AACR) Annual Meeting on its two leading programmes:

• Clinical programme CB307 a ‘1st and only’ in class CD137 (4-1BB) x PSMA bispecific for end-stage prostate cancer patients
• First ‘2 in 1’ immune cell engager CB699, a mesothelin (MSLN) directed molecule designed to target both CD40 and CD137

These programmes are derived from Crescendo’s proprietary Humabody® V_H platform which is associated with superior tumour penetration compared to traditional antibodies.

Theodora Harold, CEO at Crescendo Biologics, commented: “Crescendo employs a tumour-targeted approach to directing immune cell activation against cancer. The data from our two lead programmes highlight the potential of immuno-oncology therapies that are potent and long-lasting, yet well-tolerated by patients.

“The pharmacology data we have shared on CB307, underpins its clinical development in PSMA+ metastatic castration-resistant prostate cancer (mCRPC), which continues at pace in our ongoing Phase 1b trial. CB699 is a pipeline programme which has excited us with its potential and I am delighted that we have been able to share our early research at this year’s conference. These preclinical findings support this candidate’s progression into clinical development, and we look forward to providing further insights as the programme matures.”

Abstract #5313: CB307: A dual targeting costimulatory Humabody® V_H therapeutic for treating PSMA-positive tumours
The functional activity of CB307, a first-in-class CD137 x PSMA bispecific Humabody®, designed to achieve a longer lasting anti-cancer effect whilst avoiding systemic toxicity, was assessed in preclinical models.

The details of this research have also been published in Clinical Cancer Research, a journal of the AACR. The paper, ‘CB307: A dual targeting costimulatory Humabody® V_H therapeutic for treating PSMA-positive tumours’, co-authored by Crescendo scientists and Regius Professor of Cancer Research, Johann de Bono from The Institute of Cancer Research, London, reports:

• CB307 demonstrated effective activation of both T and NK cells via the co-stimulatory receptor CD137 in a PSMA-dependent manner
• Its combination with PD-(L)1 inhibitors showed supra-additive anti-tumour activity, which is retained even in absence of tumour PD-L1 expression, potentially enabling a wider patient population to benefit from checkpoint inhibitor therapies
• Although prostate cancer has been considered an ‘immunologically cold’ tumour type, the data revealed co-localisation of CD137 and PSMA in metastatic prostate cancer lesions, supporting the use of CB307 in mCRPC
  
  

Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, comments: “The data shared at AACR and published in Clinical Cancer Research support this novel candidate’s (CB307) clinical evaluation in PSMA+ mCRPC, both as a monotherapy and in combination settings.”

Abstract #5302: CB699: A novel mesothelin-binding Humabody® CD40 and CD137 dual-agonist for enhancing immune cell responses against MSLN+ tumours
Derived from the Humabody® V_H platform, CB699 is Crescendo’s first candidate in a novel class of tumour antigen-directed CD40 and CD137 dual agonists, designed to enhance the anti-tumour activity of multiple immune cell types. CB699 is a half-life extended CD40 x CD137 x MSLN trispecific molecule. The preclinical studies support Crescendo’s progression of the candidate towards clinical development:

• Pharmacokinetic data including preclinical dose range finding and half-life of CB699 support clinical development;
• The results demonstrated CB699’s ability to conditionally enhance both T cell and antigen-presenting cell (APC) signalling axes, providing a comprehensive anti-cancer immune response; and
• The trispecific format was able to drive conditional CD40 agonism in the presence of either CD137+ or MSLN+ cells, and similarly, conditional CD137 agonism in the presence of either CD40+ or MSLN+ cells, potentially providing a potent yet safe way to target heterogeneous tumours
  
  

Both abstracts are available on the AACR website and the posters are available on the Crescendo website under Posters & Publications.

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About CB307
CB307 is Crescendo’s lead clinical candidate, a first-in-class, half-life extended, CD137 x PSMA bispecific Humabody®, designed to deliver a safer and more durable anti-cancer response.

CB307 conditionally activates only tumour-specific T cells, exclusively within the tumour microenvironment, using the CD137 co-stimulatory mechanism. Its unique format enables potent, tumour-specific killing, while avoiding systemic toxicity and can be applied to a broad range of PSMA+ cancer indications to address a large unmet medical need.

Clinical development of CB307 is on track with the Phase 1b POTENTIA trial ongoing in adult patients with PSMA+ metastatic castration-resistant prostate cancer (mCRPC). POTENTIA (NCT04839991) is an open-label, dose escalation and cohort expansion study to assess the safety, tolerability and preliminary efficacy of CB307 as a monotherapy and in combination with pembrolizumab (KEYTRUDA®).

About CB699
CB699, a half-life extended CD40 x CD137 x mesothelin (MSLN) trispecific molecule, is the second candidate in Crescendo’s proprietary pipeline of novel, targeted immune-cell-enhancing therapeutics, derived from its Humabody® V_H platform. CB699 aims at enhancing immune cell activity against MSLN+ tumours, using both immune cell and APC signalling axes.

About Crescendo Biologics
Crescendo Biologics is a private, clinical-stage immuno-oncology company developing novel, targeted immune cell-enhancing therapeutics derived from its proprietary Humabody® V_H platform. Beyond Crescendo’s proprietary pipeline, the Company has global, multi-target discovery and development collaborations with Takeda and BioNTech, and an exclusive worldwide licensing agreement with Zai Lab. Located in Cambridge, UK, Crescendo is backed by blue-chip investors including Sofinnova Partners, Andera Partners, IP Group, BioNTech, Takeda, Quan Capital and Kreos Capital. Visit www.crescendobiologics.com and follow on LinkedIn and X (Twitter).