LEXINGTON, Mass.—Using antibodies to fight cancer continues to be an attractive area of therapeutic research but, as with all things, making a good thing better never hurts. And Agenus Inc. might just have come upon a way to do that, according to a study published in Cancer Cell recently, titled “Selective FcγR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens.” The study describes a novel discovery made by Agenus that may enhance the immune activity of cancer-fighting antibodies, including those targeting CTLA-4. Agenus has applied this discovery to its proprietary next-generation anti-CTLA-4 antibody (AGEN1181), which is on track for Investigational New Drug (IND) filing in the second half of this year with the U.S. Food and Drug Administration.
The preclinical study reports on a unique mechanism discovered by Agenus that can significantly improve the biological and immunological activity of certain cancer-fighting antibodies, such as those targeting CTLA-4 and TIGIT.
As noted by Agenus, “These findings provide the foundation for developing ‘next-gen’ antibodies designed to improve performance and expand clinical benefit.” Agenus has already employed this novel discovery to make next-gen monospecific and bispecific antibodies, with not only the AGEN1181 filing on the way, but also more IND filings between this year and early next year.
“We have discovered a new mechanism involving a key portion of antibodies that modulates biological function and cancer fighting abilities,” said Dr. Jeremy Waight, principal scientist at Agenus and lead author of the study. “Based on our discovery, we can modify this region, known as the Fc region, to significantly improve an antibody’s biological activity, by improving its immunological activity. We have already applied this discovery to our next-generation anti-CTLA-4 antibody, as well as other monospecific and bispecific antibodies in our preclinical pipeline, and observed dramatic improvement in immune responses and antitumor activity.”
Specifically, the research team demonstrated that a change in the Fc region can significantly improve the cross-talk between two immune cell types, such as antigen-presenting cells and T cells. This modification in the Fc region is said to increase both the duration and strength of interactions between the immune cells—a necessary interaction to launch the most effective attack possible against tumors.
“These findings are at the core of our next-generation antibody programs, which have moved at an incredible speed from the drawing boards to being clinic-ready in about 15 months, a testament to our strategy built on innovation and speed,” noted Dr. Alex Duncan, Agenus’ chief technology officer and head of research. “These findings provide a foundation for developing best-in-class antibodies optimized to improve response rates and durability of response for patients with cancer.”
Agenus is a clinical-stage immuno-oncology company focused on the discovery and development of therapies that engage the body’s immune system to fight cancer. The company’s vision is to expand the patient populations benefiting from cancer immunotherapy by pursuing a number of combination approaches that leverage a broad repertoire of antibody therapeutics and proprietary cancer vaccine platforms. To this end, Agenus has at its disposal a suite of antibody discovery platforms and a GMP manufacturing facility with the capacity to support early-phase clinical programs.
As a spokesperson for Agenus tells DDNews, “We have several clinical trials ongoing. Our pipeline is advancing. We delivered five INDs in 18 months, advanced our lead anti-CTLA-4 and anti-PD-1 antibody programs, treated more than 100 patients (with the data presented at this year’s American Society of Clinical Oncology meeting) and expanded the proprietary combination into a Phase 2 BLA path trial in 2L cervical cancer (a disease with no effective treatments).
“We have delivered on our partnered programs (Incyte is advancing GITR and OX40 in the clinic and will have TIM-3 and LAG-3 in the clinic this year). This year, we will deliver six INDs, including a novel anti-CTLA-4 antibody and first-in-class tumor microenvironment conditioning bispecific antibodies.”