Astellas and Sutro Unite to Overcome Checkpoint Inhibitor Limitations with iADCs

Tokyo-based Astellas Pharma and South San Francisco-based Sutro Biopharma have inked a global collaboration and licensing deal aimed at the discovery and development of novel immunostimulatory antibody-drug conjugates (iADCs).

iADCs are considered a next-generation modality designed to overcome limitations of current immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors like Merck’s Keytruda (pembrolizumab). According to the two companies, the first-generation immune checkpoint inhibitors work well by themselves in only about 20% of cancer types.

The new approach combines an antibody with a small molecule drug that causes immunogenic cell death with an immune-activating molecule.

Under the terms of the deal, Sutro and Astellas will work to develop iADCs for three distinct biological targets. Sutro will perform research and preclinical assays to identify candidate compounds, while Astellas will take over clinical development. Sutro’s expertise is in antibody-drug conjugates and Astellas will leverage its global R&D and commercialization capabilities in the antibody and small molecule arena.

Astellas is paying Sutro $90 million upfront. Sutro is eligible for $422.5 million in development, regulatory and commercial milestones for each product candidate. Sutro will also be up for tiered royalties ranging from low double-digit to mid-teens on global sales. In addition, Sutro has an option to share in the costs and profits for developing and commercializing candidates in the U.S. If Sutro chooses this option, the two companies will equally split the costs of the co-development and co-commercialization.

“We are delighted to work with Astellas, a premier biopharmaceutical company with substantial expertise in immuno-oncology, on this novel modality,” William J. Newell, Sutro’s chief executive officer, said. “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.”

On Monday, Astellas announced that the U.S. Food and Drug Administration had placed a clinical hold on its FORTIS Phase I/II trial of AT845 in adults with late-onset Pompe disease. The hold was based on a serious adverse event of peripheral sensory neuropathy in one of the trial participants. AT845 is an adeno-associated virus (AAV) gene replacement therapy.

Meanwhile, Sutro's pipeline includes ADCs for ovarian cancer, endometrial cancer, non-small cell lung cancer (NSCLC), non-gynecological cancers, lymphoma and multiple myeloma, a bispecific ADC for NSCLC and esophageal cancer, cytokines for advanced or metastatic solid tumors and a 24-valent conjugate vaccine for invasive pneumococcal disease.

Sutro has numerous partnerships with companies including Bristol Myers Squibb, EMD Serono, Merck KGaA, BioNova and VaxCyte.

Of Tuesday’s deal, Astellas Chief Strategy Officer Naoki Okamura said, “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. Sutro is a leading company around 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.”