Opportunity for Enhancing Immunotherapeutic Drug Efficacy
The emergence of immuno-oncology drugs – therapeutics designed to spur engagement of the host immune system against cancer cells – has transformed the treatment of cancer. Since approval of the first immuno-oncology agent in 2011, 11 drugs have been approved in the U.S. to date and they have become the standard of care in a number of cancer types, including melanoma, lung and kidney cancers1. Hundreds of other compounds are in development.
These compounds encompass a wide range of therapeutic strategies, including checkpoint inhibitors, T-cell targeted immuno-modulators such as CART-T therapies, cancer vaccines, oncolytic viruses, and next generation, bi-specific antibodies. All these approaches rely on the presence of tumor antigens – proteins present on tumor cells that allow the immune system, and immuno-oncology agents to recognize and target these cells.
Despite the dramatic results generated by immuno-oncology therapies to date, they have produced sustained therapeutic benefit in only a subset of patients. For example, the average response rate to checkpoint inhibitors, across a range of tumors, is approximately 30 percent of patients. For CART-T therapy, initial response rates are high but many patients relapse.
Recent research suggests that one reason patients do not respond to immuno-oncology therapies is an insufficient number, or density, of tumor antigen targets. For example, the beneficial responses to checkpoint inhibitors directly correlate with high numbers of tumor mutations and a resulting increase in the number of tumor antigens2. In acute lymphoblastic leukemia patients treated with an experimental CAR-T therapy directed at CD22, there were significant response rates in those patients with high levels of CD22. Tumors in those patients, who had been treated with CAR-T therapy directed at another tumor antigen, CD19, had escaped immune recognition and destruction by downregulating CD193.
2 Yarchoan, et al., New England Journal of Medicine, 2017; Tumor Mutational Burden and Response Rate to PD-1 Inhibition.
3 Fry et al., Nature Medicine, 2018. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy.
Bryologyx’s lead program
The Bryologyx development program is focused initially on B-cell cancers. Based on the human safety data from previous clinical trials with bryostatin-1, and the company’s progress to date, Bryologyx is on a path to initiate clinical studies in late 2020 with bryostatin-1 in combination with an immuno-oncology drug. At the same time, the company is evaluating bryostatin-1’s potential in a range of solid tumors.
Bryostatin-analogs for HIV
One of the key challenges in treating HIV is the virus’ ability to remain latent in infected T-cells, and inaccessible to immune effectors or antiviral drugs, which are effective only when the virus is active. Latent infection remains a threat to patients throughout their lives and the singular barrier to curing the disease.