Agenus Announces End-of-Phase-2 Meeting Outcomes and Topline Interim Phase 2 Data for BOT/BAL in MSS Colorectal Cancer
Agenus Inc. (NASDAQ: AGEN) announced outcomes from its end-of-Phase 2 meeting with the FDA for its immunotherapy combination, botensilimab (BOT) and balstilimab (BAL), in treating relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC). Key points include:
1. Agreement on dosing regimen: 75mg BOT every 6 weeks (up to 4 doses) with 240mg BAL every 2 weeks (up to 2 years).
2. Interim Phase 2 data shows 19.4% ORR and 90% 6-month survival rate for BOT 75mg/BAL combination.
3. FDA advised against Accelerated Approval submission.
4. FDA recommended including a BOT monotherapy arm in Phase 3 study.
5. Agenus plans further FDA discussions as Phase 2 data matures.
6. European regulatory discussions scheduled for Q3 2024.
- Agreement reached with FDA on Phase 3 dosing regimen for BOT/BAL combination
- Preliminary Phase 2 data shows 19.4% ORR and 90% 6-month survival rate for BOT 75mg/BAL combination
- Phase 2 data trends consistent with promising Phase 1 results
- Strategic meeting with European agency scheduled for Q3 2024 to explore additional regulatory opportunities
- Ongoing development of BOT/BAL in earlier lines of CRC and other tumor types
- FDA advised against submission for Accelerated Approval
- FDA recommended inclusion of BOT monotherapy arm in Phase 3 study, potentially increasing study complexity and costs
- Lower ORR (19.4%) in Phase 2 compared to Phase 1 (23%) for MSS mCRC patients without active liver metastases
The interim Phase 2 data on the BOT/BAL combination marks a significant step in the treatment of microsatellite stable colorectal cancer (MSS CRC). Notably, the dosing regimen agreed upon with the FDA, featuring 75mg BOT every 6 weeks and 240mg BAL every 2 weeks, is a promising approach for relapsed/refractory MSS CRC, particularly for patients without active liver metastases. The objective response rate (ORR) of 19.4% and the 90% 6-month survival rate are indeed encouraging, aligning closely with the previous Phase 1 data.
However, the FDA's discouragement for accelerated approval indicates a need for more substantial evidence correlating the ORR to an overall survival benefit. This guidance may slow the approval process but also ensures that only treatments with clear and significant benefits reach patients. The inclusion of a BOT monotherapy arm in the Phase 3 trial is a strategic decision. It could provide additional insights into the efficacy of BOT alone versus its combination with BAL.
For MSS colorectal cancer, which lacks effective therapeutic options, this development is a beacon of hope. Yet, investors should temper their optimism with the understanding that further substantial evidence is necessary to secure FDA approval.
From a financial perspective, the outcomes presented at the end-of-Phase 2 meeting for Agenus' BOT/BAL combination are a mixed bag. On one hand, the positive interim data and the structured pathway towards a Phase 3 trial offer a clearer road to potential future revenue. However, the FDA's reluctance to consider accelerated approval based on the current data is a setback. This stance implies a longer timeline for any financial returns, as the Phase 3 trials will need to provide more definitive proof of survival benefits.
Currently, the 19.4% ORR and a 90% 6-month survival rate are promising, but investors should be cautious regarding the uncertain timeline and the significant costs associated with conducting extensive Phase 3 trials. Additionally, the market should consider the competitive landscape of MSS CRC treatments and how BOT/BAL will position itself against existing and upcoming therapies.
The strategic meeting scheduled with the European agency signifies potential expansion into the European market, which could be a vital revenue stream. However, similar regulatory challenges can be expected there, potentially mirroring the FDA’s cautious approach.
- Agreement reached with the FDA on Phase 3 dose for the BOT/BAL combination
- Accelerated approval pathway discouraged by FDA
-
Preliminary Phase 2 data tracks with Phase 1 BOT/BAL clinical activity in MSS mCRC (ORR ~
19.4% and90% alive at 6 months) - Strategic meeting with the European agency scheduled for Q3 2024 to explore additional regulatory opportunities
Key Outcomes of the EOP2 Meeting:
- Dosing Regimen: Agenus gained agreement on the proposed BOT/BAL combination dosing regimen of 75mg BOT once every 6 weeks for up to 4 doses in combination with 240mg BAL once every 2 weeks for up to 2 years.
-
Randomized Phase 2 Interim Data: Topline interim data suggest best activity seen at 75 mg BOT/240mg BAL combination (ORR
19.4% ; 6-month survival rate of90% ; data continues to mature). - Accelerated Approval: FDA advised against submission of these results in support of an Accelerated Approval based on their view that objective response rates may not translate to survival benefit.
- Phase 3 Protocol Design: The FDA recommended the inclusion of a BOT monotherapy arm at Agenus’ discretion in the Phase 3 study.
Dr. Steven O’Day, Agenus’ Chief Medical Officer, stated, “Based on the high level of enthusiasm from significant numbers of global clinical experts and the promising clinical activity we have seen in the Phase 1 and 2 studies, our commitment to seek all possible pathways to make BOT/BAL available to patients is unwavering. This includes exploring opportunities to partner in the
Agenus previously disclosed data from the Phase 1 trial, which showed an overall response rate (ORR) of
Topline interim data (below) from the Phase 2 trial are showing trends consistent with the Phase 1 study, including an ORR of
Topline Interim Phase 2 Data |
|||||
|
BOT + BAL 75 mg (n= 62) |
BOT+BAL 150 mg (n=61) |
BOT 75 mg (n=38) |
BOT 150 mg (n=40) |
SOC (n=33) |
ORR %
( n/nn |
19.4* (10.4, 31.4) 12/62 |
8.2 (2.7, 18.1) 5/61 |
0 (0.0, 9.3) 0/38 |
7.5 (1.6, 20.4) 3/40 |
0 (0.0, 10.6) 0/33 |
Follow-Up (m) Mean (SD) Range |
9.5 (2.77) 1.2, 15.7 |
9.1 (3.25) 0.1, 16.6 |
7.8 (4.37) 0.2, 14.8 |
8.2 (4.53) 0.7, 17.1 |
5.5 (5.30) 0.0, 13.0 |
*Pending confirmation of two additional responses in 75mg BOT + BAL arm. No responses are pending confirmation in other arms. |
These results are particularly meaningful, as the landscape of MSS colorectal cancer treatment has seen little advancement leaving a significant gap in effective therapies for patients.
“MSS colorectal cancer, representing approximately
In addition to the progress in the
Other areas of BOT/BAL clinical development:
Agenus continues to pursue opportunities for BOT/BAL development in earlier lines of CRC and other tumor types where BOT/BAL has demonstrated clinical activity, such as lung, melanoma, and pancreatic cancers. The company expects to present data from some of these programs at future medical congresses, including BOT/BAL in sarcoma at European Society for Medical Oncology (ESMO) in September 2024.
About Botensilimab
Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.
Approximately 1100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.
About Colorectal Cancer
Colorectal cancer (CRC) is the second leading cause of cancer death in
About Agenus
Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission is to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in
Forward-Looking Statements
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2023, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.
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