Dr. Sean McCarthy, CEO and Chairman of CytomX Therapeutics shared insights into the company's journey, platform technology, partnerships, and long-term vision. CytomX Therapeutics has established itself as a pioneer in localized biologic therapies, particularly in the field of oncology. Their proprietary Probody® therapeutics are designed to outsmart cancer by exploiting the unique conditions of the tumor microenvironment by localizing treatment in the tumor and limiting activity in healthy tissue. This approach aims to maximize therapeutic efficacy while minimizing side effects and enable new combinations of drugs previously not possible due to toxicities. 

The ProBody Platform: Unleashing the Potential 

CytomX Therapeutics pioneered the field of protease-based localized therapeutics, an idea ahead of its time. By engineering therapeutic antibodies with a masked approach, they enable conditional activation of biologic therapeutic candidates within the tumor microenvironment, while minimizing drug activity in healthy tissues, thereby broadening or creating a therapeutic window for safer and more potent treatments. Protease biology's role in cancer development has led to innovative strategies for enhancing efficacy while mitigating systemic toxicities.  

CytomX Therapeutics has utilized its multi-modality Probody platform to build a promising pipeline of potential first-in-class and best-in-class therapeutics that encompasses seven novel product candidates, three of which are currently in Phase 2 clinical studies across multiple cancer indications. These include the and praluzatamab ravtansine (CX-2009, targeting CD166), the Probody immune checkpoint inhibitors pacmilimab (CX-072, targeting PD-L1) and BMS-986249 (targeting CTLA-4), and the T-cell-engaging bispecific antibody CX-904 (targeting EGFR on tumor cells and the CD3 receptor on T cells. 

Diverse Application of the ProBody Platform 

CX-2029: A First-in-Class Conditionally Activated ADC Targeting CD71, the Transferrin Receptor 

• CD71, a transferring receptor, presents both tumor tissues and normal structures, making targeted therapy challenging. CytomX's masked ADC, CX2029, demonstrates promising results, including deep and durable responses in squamous esophageal cancer patients, offering the potential for this challenging disease. 

CX-2051: An EpCAM-directed Conditionally Activated ADC 

• A wholly owned asset, CX2051 is a masked ADC targeting EpCam, a highly expressed protein on various tumors. With an optimized design and a new payload, this program aims to break through in the solid tumor domain, potentially revolutionizing cancer therapy.  

CX-904: A Conditionally Activated T-Cell-Engaging Bispecific Antibody Targeting EGFR 

• The team successfully applies the platform to T-cell engagers, a field traditionally challenging in solid tumors. By masking both EGFR and CD3 binding arms, CX904 demonstrates improved maximum tolerated doses, extended pharmacokinetics, and potent antitumor activity, signifying significant potential. 

CX-801: An Interferon Alpha-2b Probody Cytokine 

• Unveiling a dual masking strategy, CytomX plans to transform interferon alpha 2B into a potent immunotherapy that maintains antitumor activity within the tumor while minimizing systemic side effects. This wholly-owned program holds promise for enhanced cancer immunotherapy. 

Strategic Collaborations 

CytomX Therapeutics has been actively engaging with industry giants like Amgen, Astellis, Regeneron, and Moderna. Through strategic partnerships and asset codevelopmen, this demonstrates the depth and breadth of their science, expanding their reach and impact. 

Pioneering Tomorrow's Cancer Therapies 

CytomX Therapeutics’s dedication to advancing the ProBody platform underscores its commitment to transforming cancer therapy. Through innovative strategies like targeted ADCs, T cell engagers, and immune modulation, the company is addressing the limitations of current treatments. Collaborations with industry giants and a robust pipeline position CytomX at the forefront of oncology innovation, promising a future of more effective and less toxic cancer treatments. 

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