The FDA has granted a Fast Track designation to the combination of balstilimab, a PD-1 inhibitor, and zalifrelimab, a CTLA-inhibitor, for the treatment of patients with relapsed or refractory metastatic cervical cancer reports Agenus. Fast Track Designation is supposed to only be granted by the FDA for products that are intended for the treatment of serious or life-threatening diseases or conditions, which demonstrate the potential of the drug to address unmet needs. This designation is a positive signal to the market, and patients, and offers the opportunity for Agenus to interact frequently with the FDA to discuss the drug’s development plan and ensure collection of appropriate data required to support the drug’s approval, as well as eligibility for rolling submission of a Biologic Licensing Application (BLA).
Cervical cancer is represented as a malignant tumor of the cervix, the lowermost part of the uterus that can be prevented by PAP smear screening, and an HPV vaccination. There can be few symptoms, and, in a few cases, there may be irregular bleeding or pain. Treatments range from surgery and radiation to chemotherapy. Researchers in this field are hoping that immunotherapy offers a possible gateway to improve on the results chemotherapy offers patients. Investigators are hopeful that they can build on the initial success with the PD-1 inhibitor pembrolizumab (Keytruda).
13,800 new cases will be diagnosed, while over 4,200 will die in American this year.
Fast Track Designation for Agenus’ Experimental Drugs
The FDA awarded this designation based on comprehensive data that supports the potential for both balstilimab and zalifrelimab to address a significant unmet medical need. This designation can help accelerate the approval of the drug for commercialization.
Balstilimab and Zalifrelimab Background
Both Balstilimab and Zalifrelimab are proprietary experimental drugs in the Agenus pipeline.
Zalifrelimab (AGEN1884) is an anti-CTLA4 antibody, designated to inhibit CTLA-4 and restore anti-tumor immunity. CTLA-4 (cytotoxic T-lymphocyte antigen-4) is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market. For example, in 2018, the Nobel Prize in Medicine was awarded for the establishment of CTLA-4 as a cancer immunotherapy target. Agenus has applied these scientific findings to create a therapy designated to treat cancer—AGEN1884. It is a fully-humanized monoclonal antibody that activates the immune system to destroy cancer cells by blocking the interaction between CTLA-4 and its binding partners CD80 and CD86.
Zalifrelimab is in clinical trials as a monotherapy and in combination with their PD-1 (AGEN2034 or Balstilimab) in an ongoing Phase I/2 open-label, multi-arm trial to investigate the safety, tolerability, pharmacokinetics, biological and clinical activity of this regimen in patients with metastatic or locally advanced solid tumors including refractory cervical cancer. The investigational product was initially developed by the Ludwig Cancer Institute, and in 2014, they and Agenus entered into a development deal.
PD-1 (programmed cell death protein 1) is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market. In 2018, the Novel Prize in Medicine was awarded for the establishment of PD-1 as a cancer immunotherapy target. Agenus has applied these scientific principles to create a therapy designed to treat cancer called AGEN2034 (Balstilimab). It is a novel, fully human monoclonal immunoglobulin G4 (IgG3) designed to block PD-1 from interacting with its ligands PD-L1 and PD-L2. This experimental drug is clinically active in patients with advanced or refractory cancer. For example, Agenus’ PD-1 is in clinical trials as a monotherapy and a combination with their CTLA-4 (Zalifrelimab) in an ongoing Phase I/2, open-label, multi-arm trial to investigate the safety, tolerability, pharmacokinetics, biological and clinical activity of this regimen in patients with metastatic or locally advanced solid tumors including refractory cervical cancer.
Positive Data Basis for Award
Agenus reported updated data from a pre-planned interim analysis revealing the robust and durable activity of the two drugs in patients with relapsed or refractory metastatic cervical cancer. This data demonstrates 26.5% objective response rates (ORR) (4Crs, 5Prs, 8SD), which are durable (median not yet reached) in all-comer, non-biomarker selected population of patients with refractory cervical cancer who have failed prior platinum chemotherapy with or without bevacizumab.
Filing a BLA in 2020
Agenus stated in its press release that the company expects to file 2 BLAs for accelerated approval of the combination of both balstilimab and zalifrelimab in 2020 for metastatic cervical cancer.
The Company: Agenus
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 combination approaches that leverage a broad repertoire of antibody therapeutics, adoptive cell therapies (through its AgenTus Therapeutics subsidiary), and proprietary cancer vaccine platforms. The company is equipped with a suite of antibody discovery platforms and a state-of-the-art GMP manufacturing facility with the capacity to support clinical programs. Agenus is headquartered in Lexington, MA.
Publicly traded (AGEN), the company’s share price, $2.52, leaves it with a market capitalization of $346.2 million. The company incurs losses over $100 million on $150 of projected revenue. For a thorough overview, see the firm’s most recent SEC disclosures.