In a joint statement after, Astellas Pharma and Sutro Biopharma, which is based in South San Francisco, is a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates, announced a worldwide, strategic collaboration and licensing agreement focused on the discovery and development of novel immunostimulatory antibody-drug conjugates (iADCs)

iADCs are a next-generation ADC modality designed for treating cancer and to boost anti-cancer activity, offering potential new options for patients who, today, do not respond to existing cancer immunotherapies.

The collaboration leverages the unique cancer-fighting potential of iADCs as a novel modality, enabled by Sutro’s ability to engineer complex conjugated antibodies, and Astellas’ global oncology R&D expertise.

“We are delighted to work with Astellas, a premier biopharmaceutical company with substantial expertise in immuno-oncology, on this novel modality,” explained William J. Newell, Sutro’s Chief Executive Officer.

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“iADCs hold promise well beyond the existing success of ADCs. Sutro’s unique conjugation technology enables dual conjugations that site-specifically incorporate a potent cytotoxin that can directly kill tumor cells together with an immunostimulatory component that has the potential to locally prime an immune response to the patient’s particular tumor cells. We look forward to collaboratively exploring the potential of this approach to treat cold tumors and bring new drug therapies to patients who do not respond to existing immunotherapies.”

“Astellas considers Immuno-Oncology as one of the Primary Focuses of its R&D strategy; our goal is to bring effective drugs to patients who do not respond to existing immune checkpoint inhibitors,” said Naoki Okamura, Chief Strategy Officer, at Astellas.

“Sutro is a leading company in the area of iADCs, a new modality, and has its own original iADC technologies. The strategic partnership with Sutro will help us expand our pipeline and widen the choice of cancer immunotherapies,” Okamura added.

Tumor microenvironment
A key challenge with cancer immunotherapies, including immune checkpoint inhibitors, is the tumor microenvironment within cold tumors creating barriers to immune cell infiltration and thus preventing the cure. This microenvironment is a protective “environment” surroubnding the cancer that is advantageous to its own survival, that is, helps to protect itself from the immune system and help facilitate its own growth and metastasis. [1] Understanding tumor immune microenvironments is critical for identifying immune modifiers of cancer progression and developing cancer immunotherapies.[1]

Despite dramatic breakthroughs, major obstacles remain in the field of immunotherapy in the treatment of cancer. For example, immune checkpoint inhibitors approved to date are efficacious as a monotherapy in only about 20% of cancer types, which vary widely.[2]

Strategic partnership
Based on the strategic partnership between Astelas and Sutro, researchers will engage in the development of iADCs, a next generation modality with the potential for effective and efficient approaches for treatment of cold tumors so as to bring new drug therapies to patients who do not respond to existing therapies. An iADC, which combines an antibody with a small molecule compound that induces immunogenic cell death.

Immunogenic cell death is cancer cell death through the “cancer immune cycle” by which cancer antigens released by chemotherapy are captured by dendritic cells and then presented to T cells activated to kill the cancer cells. in addition to an immune activating molecule, has the potential to boost the anti-cancer action.

This partnership will enable Astellas and Sutro to mutually leverage strengths in their respective fields to accelerate iADC development for three distinct biological targets. Sutro will engage in research and preclinical studies to identify candidate compounds and then Astellas will pursue clinical development.

Sutro has advanced technologies for linking drugs to antibodies and proprietary component parts, including candidate antibodies and linkable cytotoxins and immunostimulatory molecules. For development of iADCs, Astellas will utilize the strength of its global R&D and commercialization capabilities in the area of antibodies and the small molecular components. These iADCs may have the potential to provide new therapeutic options for treatment of cancers for which no broadly effective therapy is currently available.

Under the terms of the agreement, Sutro will receive an upfront cash payment of US $ 90 million to develop iADCs for three biological targets and may be eligible to receive up to US $ 422.5 million in development, regulatory and commercial milestones for each product candidate, and tiered royalties ranging from low double-digit to mid-teens on worldwide sales of any commercial products that may result from the collaboration, subject to Sutro’s cost and profit sharing option for the United States.

Sutro has the option to share in the costs and profits for developing and commercializing product candidates in the United States. If Sutro exercise this option for a particular product candidate, Astellas and Sutro will equally share the costs of such co-development and co-commercialization, with the resulting profits/losses from co-commercialization also shared equally in the United States.

Reference
[1] Ren X, Zhang L, Zhang Y, Li Z, Siemers N, Zhang Z. Insights Gained from Single-Cell Analysis of Immune Cells in the Tumor Microenvironment. Annu Rev Immunol. 2021 Apr 26;39:583-609. doi: 10.1146/annurev-immunol-110519-071134. Epub 2021 Feb 26. PMID: 33637019.
[2] Ventola CL. Cancer Immunotherapy, Part 3: Challenges and Future Trends. P T. 2017 Aug;42(8):514-521. PMID: 28781505; PMCID: PMC5521300.

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