By Judy Ya-Hsuan Lin
Cancerous tumors create highly specific conditions in their growth environment that are not present in normal tissues. Their established specificity allows researchers to develop safer therapeutic strategies, in which the activation of medication would be turned toward the target tumor sites and away from the normal tissues. In other words, this safer drug delivery system greatly lowers the risks of systemic toxicity arising from an overreaction of the immune system that may affect not only the tumor but healthy cells.
Intelligent Drug Delivery System: Conditionally Active Biologics
BioAtla, a clinical-stage biotech company that operates from San-Diego, California, and Beijing, China. It has invented Conditionally Active Biologics (CAB), which is a pool of proteins, including monoclonal antibodies, enzymes, and other protein designed with functions dependent on changes in micro physiological conditions, such as pH level, oxidation, temperature, pressure, presence of certain ions, and hydrophobicity.
CAB proteins are designed to deliver their therapeutic payload and activate the immune response in specific and selected locations and conditions. The activation is designed to be reversible to repeatedly switch on and off when the CAB moves from cancerous to normal cellular microenvironment. One of BioAtla’s proprietary investigational CAB, Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody BA3071, combines with BeiGene’s anti-PD-1 antibody Tislelizumab together to treat solid tumors and hematologic cancers with lower toxicity risks.
The inhibition of immune checkpoints like anti-CTLA-4 and anti-PD-1 monoclonal antibodies demonstrates promising effects in patients with advanced-stage melanoma and other cancers. Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FCγR on macrophages through activating antibody-dependent macrophage-mediated killing T effector cells. A total of 16 potentially registration-enabling clinical trials will be conducted in China and globally, including twelve Phase 3 trials and four pivotal Phase 2 trials.
BA3071 is a novel, investigational CAB CTLA-4 inhibitor. CTLA-4 is an inhibitory receptor expressed on T cells, and its pathway is a key immune checkpoint pathway that provides a downregulating signal to T cells. However, such an inhibition leads to the immune attack of healthy cells, so the application of BioAtla’s proprietary CAB technology is the concomitant here to activate the binding to CTLA-4 receptor on T cells only in the tumor microenvironment.
Previously, existing treatments for solid tumors and hematologic cancers included surgery, chemotherapy, and radiation therapy. Although they remove cancerous cells, such treatments could accidentally destroy healthy cells. Medication accompanied by CAB could greatly avoid the possibility of sacrificing healthy cells while removing the malignant ones.
This month, BioAtla and Beigene revised their previous global co-development and commercialization agreement signed in April 2019 to a global licensing agreement. Under the amended terms, BeiGene holds an exclusive global license to BA3071 and is responsible for its global clinical development and commercialization. BioAtla, in recognition of its continuous development on novel monoclonal antibody and protein therapeutic product candidates, will receive a sum of $20 million upfront and milestone payments for attaining specific net sale goals. BioAtla will also be eligible to receive up to $249 million once developmental and regulatory milestones are achieved globally.
“We believe that our amended agreement with BeiGene will align and potentially accelerate the global development and potential commercialization of BA3071. BeiGene’s management of the global clinical trials of BA3071 in combination with BeiGene’s Tislelizumab may advance the prospects of new combination therapies for the treatment of several cancer indications,” stated Jay M. Short, Ph.D., Chairman, CEO and Co-Founder of BioAtla. “The expanded royalty rates also recognize the exceptional opportunity that CAB technology can provide for novel combination therapies.”
Editor: Rajaneesh K. Gopinath, Ph.D.
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