CytomX

In 2017, CytomX entered into a strategic immuno-oncology collaboration with Amgen focused on research and development of T-cell-engaging bispecific therapeutics. The current lead program, CX-904, is a CytomX Probody T-cell-engaging bispecific designed to target the epidermal growth factor receptor (EGFR) on cancer cells and the CD3 receptor on T cells. EGFR is a highly validated oncology target expressed on multiple human cancer types. CytomX is leading early development and has advanced CX-904 into a Phase 1/1b clinical study. Amgen will lead later development and commercialization with global late-stage development costs shared between the two companies. CytomX is eligible to receive development, regulatory and commercial milestones for the EGFR program. Amgen will lead global commercial activities with CytomX able to opt into a profit share in the U.S. and receive tiered, double-digit royalties on net product sales outside of the U.S.

Amgen also receives exclusive worldwide rights to develop and commercialize up to three additional, undisclosed targets. CytomX will be eligible to receive additional upfront and milestone payments and high single-digit to mid-double digit royalty payments on any resulting products. CytomX also receives the rights from Amgen to an undisclosed preclinical T-cell-engaging bispecific program. Amgen is eligible to receive milestones and royalty payments on any resulting products from this CytomX program.

In 2020, CytomX entered into a strategic collaboration with Astellas to co-develop an undisclosed number of Probody T-cell-engaging bispecific therapeutics designed to target the CD3 receptor on T cells and select oncology targets within the tumor microenvironment.

CytomX is leading research and discovery activities, up to clinical candidate selection. Astellas will lead and fund preclinical and clinical development and commercialization activities with CytomX eligible to receive tiered from high-single digits to mid-teens royalties on net product sales outside of the U.S.

For a specified number of targets, prior to the initiation of the first pivotal clinical trial for a product directed toward such target, CytomX may exercise an option to co-fund a pre-determined portion of clinical development costs. For these products, CytomX is eligible to receive a pre-specified portion of profits in the United States and tiered low-double digit to mid-teen percentage royalties on net sales outside of the United States.  CytomX may later elect to co-commercialize in the United States the products directed toward such targets.

In 2014, CytomX and Bristol-Myers Squibb entered into a research collaboration and license agreement to discover, develop and commercialize novel therapies against multiple targets using CytomX’s proprietary Probody platform. Since then, Bristol-Myers Squibb has advanced two CTLA-4 Probody programs into the clinic with prioritization of BMS-986288, the non-fucosylated CTLA-4 Probody therapeutic into Phase 2 studies.

In March 2017, CytomX and Bristol-Myers Squibb expanded their 2014 collaboration to provide for the selection of additional oncology targets to enter into novel therapeutic discovery. Under this expanded agreement, Bristol-Myers Squibb made an upfront payment of $200 million to CytomX, and CytomX will also be eligible to receive future development, regulatory and sales milestone payments for each collaboration target, as well as tiered royalties on net sales of each product commercialized by Bristol-Myers Squibb.

In 2022, CytomX entered into a strategic collaboration with Regeneron to create conditionally-activated investigational bispecific cancer therapies utilizing CytomX’s Probody^® therapeutic platform and Regeneron’s Veloci-Bi^® bispecific antibody development platform.

The collaboration applies CytomX’s industry-leading masking strategies to develop bispecifics that remain inactive until activated by proteases in the tumor microenvironment. This technology has the potential to widen the therapeutic window and help minimize off-target effects for these next-generation T-cell engaging therapies, potentially addressing tumor types that have historically been unresponsive to immunotherapy.

Under the agreement, Regeneron and CytomX will collaborate on the discovery activities to identify and validate conditionally active bispecific antibodies. Regeneron will be responsible for funding preclinical and clinical development and commercialization activities. CytomX received an upfront payment of $30 million and will be eligible to receive future target nomination payments and preclinical, clinical, and commercial milestones of up to $2 billion. CytomX is also eligible to receive tiered global net sales royalties.

In 2023, CytomX entered into a strategic collaboration and licensing agreement to create investigational mRNA-based conditionally activated therapies for cancer and other diseases utilizing Moderna’s mRNA technologies and CytomX’s Probody^® therapeutic platform.

The research collaboration will leverage core scientific advances at Moderna and CytomX. Moderna’s mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases, and autoimmune diseases. CytomX’s Probody technology enables proteins to be activated locally in diseased tissue, while remaining masked in systemic circulation. These advances open up the strategy of encoding potent, masked biologics with mRNA, for the potential treatment of a wide range of diseases.

Under the terms of the agreement, CytomX will receive an upfront payment of $35 million, including $5 million of pre-paid research funding. CytomX will continue to receive research funding and is eligible to receive up to approximately $1.2 billion in future development, regulatory, and commercial milestone payments. CytomX is also eligible to receive tiered royalties on global net sales of any products that are commercialized under the agreement. Moderna and CytomX will collaborate on discovery and pre-clinical development and Moderna will lead clinical development and commercialization of therapeutics resulting from the agreement.