Agenus (AGEN) reported its Q1 2024 earnings, highlighting significant progress in its botensilimab (BOT) and balstilimab (BAL) program, particularly in relapsed/refractory microsatellite stable (MSS) colorectal cancer (CRC). The company also announced a $100 million royalty financing agreement with Ligand Pharmaceuticals to support the program's development and commercialization readiness.
BOT/BAL Program Update
Chief Medical Officer Dr. Steven O'Day emphasized the potential of BOT/BAL in poorly immunogenic tumors, which often do not respond to established immuno-oncology therapies. In a Phase 1b cohort of 77 relapsed/refractory MSS CRC patients without active liver metastases, the combination of botensilimab and balstilimab demonstrated a confirmed overall response rate (ORR) of 23% and a median overall survival (mOS) of 21.2 months, with almost 14 months of median follow-up. The 12-month overall survival estimate was 71%, and the 18-month overall survival estimate was 62%. These results contrast sharply with standard-of-care therapies in this setting, which typically yield ORRs of 1% to 6% and mOS of 12 months or less.
"These data, which continue to mature, stand in stark contrast to standard-of-care therapies in this treatment setting with overall response rates of 1% to 6% and a median overall survival of 12 months or less," said Dr. O'Day.
The most common adverse events observed were immune-related diarrhea and colitis, managed with standard therapies. Grade 3 or greater treatment-related diarrhea/colitis occurred in approximately 16% of patients.
Agenus completed enrollment in a randomized global Phase 2 trial with 234 metastatic CRC patients (MSS without active liver metastases) in November 2023. Initial data from a March data cut demonstrated consistency with the Phase 1 results. The company plans to present more mature results at a scientific meeting in the second half of 2024.
Regulatory and Commercialization Strategy
Agenus anticipates submitting a Biologics License Application (BLA) to the FDA by the end of the year, supported by data from the Phase 2 trial, the expanded Phase 1 cohort, and real-world evidence. An FDA meeting is planned for July 2024 to gain alignment on the filing and the design of a confirmatory Phase 3 trial, which is expected to commence this year.
Chief Commercial Officer Robin Taylor noted that the company is preparing for the launch of BOT/BAL, with a focus on supply chain readiness and building a commercial team. Market research indicates significant anticipation for BOT/BAL among GI oncologists.
Financial Position
Agenus reported a cash and cash equivalent balance of $52.9 million at the end of Q1 2024. The $100 million royalty financing agreement with Ligand Pharmaceuticals, consisting of an initial $75 million investment with an option for an additional $25 million, strengthens the company's financial position. The company is also exploring additional capital infusion mechanisms.
Expansion into Earlier Lines of Therapy
Several investigator-sponsored trials (ISTs) are evaluating BOT/BAL in earlier lines of therapy for colorectal cancer. The NEST trial at Cornell showed major pathologic responses in six out of nine MS-stable colorectal patients treated in a neoadjuvant setting, including two pathologic complete responses. The FOLFOX 3B regimen trial at City of Hope is investigating BOT/BAL combined with standard-of-care FOLFOX plus bevacizumab in first-line metastatic or FOLFOX-rechallenged metastatic patients.
Other Pipeline Programs
Agenus is also following maturing Phase 2 trials with BOT or BOT/BAL in refractory melanoma and second-line metastatic pancreatic cancer. Updates on these data are expected in the second half of 2024.
Forward-Looking Statements
Agenus anticipates securing up to $200 million in cash infusion by midyear and releasing promising Phase 1 and 2 data in melanoma, lung cancer, sarcoma, and pancreatic cancer in the second half of the year.
