Checkpoint blockade therapies are based on the principle of removing the “brakes” of the immune system, in order to use the power of the body’s immune system to fight cancer faster and more effectively.
BA3071 is part of BioAtla’s conditionally active biologic (CAB) proprietary technology, which is based on the creation of compounds that can be activated or inactivated under specific physiological conditions.
In the case of BA3071, the anti-CTLA-4 antibody has been designed to become active and block the CTLA-4 receptor found on the surface of immune T-cells — boosting the body’s immune response against cancer cells — only when it reaches the tumor. With this strategy, the risk is greatly reduced for systemic toxicity arising from an overreaction of the immune system that may affect not only the tumor, but healthy tissues as well. Using this approach in combination with other checkpoint inhibitors, such as BeiGene’s tislelizumab, is considered much safer for patients.
Tislelizumab (BGB-A317) is an investigational anti-PD-1 checkpoint blockade antibody that has been designed to minimize binding to the Fc-gamma receptor found on the surface of macrophages (immune cells responsible for removing dead cells and debris from tissues), thereby impairing macrophages from wrongly engulfing the activated T-cells.
“BioAtla has developed an exciting proprietary protein discovery and expression platform to generate CABs, which in turn have been applied to BA3071, a novel, investigational CTLA-4 inhibitor that is designed to be conditionally activated in the tumor microenvironment,” Lai Wang, a senior vice president at BeiGene, said in a press release.
“The unique nature of BA3071 provides an exciting opportunity to combine this CTLA-4 antibody with our anti-PD-1 antibody, tislelizumab. We look forward to working with BioAtla through proof-of-concept, followed by global development of this potentially unique cancer therapy as a single agent or in combination with other therapies,” Wang added.
Under the terms of the agreement, BioAtla will co-develop BA3071 to meet predefined goals, while BeiGene will be responsible for leading the development and commercialization of the product candidate, as well as for filing global regulatory documentation. BeiGene will co-own an exclusive license with BioAtla to develop and produce the product candidate worldwide, as well as hold an exclusive license to commercialize the product on a global scale.
BeiGene will provide financial support to cover development, manufacturing and commercialization costs of the product candidate in Asia (except Japan), Australia, and New Zealand, and will share all costs, commercial profits, and losses with BioAtla in other parts of the world.
BioAtla will receive a sum of $20 million upfront, as well as milestone payments for attaining specific goals defined a priori. The company will also be eligible to receive up to $249 million once developmental and regulatory milestones are achieved globally, and once commercial milestones are attained within the BeiGene territory, including tiered royalties on product sales.
“We believe that our collaboration with BeiGene will accelerate the global development and potential commercialization of BA3071 and advance the prospects and potential of safer and more effective combination therapies for the treatment of several cancer indications,” said Jay M. Short, PhD, chairman, CEO, and co-founder of BioAtla. “The application of BioAtla’s CAB technology to CTLA-4 inhibition may offer greater potency and safety, thereby improving this important cancer therapy and expanding its potential applications.”
BioAtla is planning to file an investigational new drug (IND) application for BA3071 to the U.S. Food and Drug Administration later this year. Once the IND is cleared, the company is planning to launch a multi-center, open-label Phase 1/2 clinical trial to assess the safety and efficacy of BA3071 alone, or in combination with BeiGene’s tislelizumab.