Agenus Reports Fourth Quarter and Full Year 2023 Results
- Fast Track designation received for metastatic colorectal cancer patients not MSI-H/dMMR
- Phase 1 data showed 24% durable ORR in patients with non-active liver metastases
- Completed enrollment of Phase 2 trial with 230 patients
- Expansion opportunities in pancreas, lung, neoadjuvant CRC, and melanoma
- Financial results for 2023 with $156 million revenue and $257 million net loss
- $25 million milestone payment from BMS triggered by Phase 2 study commencement
- Active discussions for monetizing assets and potential cash proceeds of $100-200 million
- Cash balance of $76.1 million at the end of 2023
- Net loss of $257 million in 2023
- Significant cash burn with $224 million used in operations in 2023
- High research and development expenses of $234.6 million in 2023
- Negative net loss per share of $0.69 in 2023
Insights
The Fast Track designation by the FDA for BOT/BAL in metastatic, refractory colorectal cancer (CRC) is a pivotal development in oncology therapeutics. This status expedites the review of drugs intended to treat serious conditions with unmet medical needs. Given the durable Objective Response Rate (ORR) of 24% in non-active liver metastases (NLM) patients, this is a significant improvement compared to the standard 1% to 6.1% response rates. The 12-month overall survival (OS) rate of 74% is noteworthy, as median OS has not been reached, indicating potential for extended survival benefits.
The safety profile, with immune-related adverse events such as diarrhea and colitis, is consistent with the class effects of immunotherapies. The Grade 3 treatment-related adverse events in 14% of patients will require careful management but are within the expected range for such potent agents. The extension of BOT/BAL's application to other cancers like pancreatic, lung and melanoma suggests its potential as a versatile anti-cancer agent.
The financial implications of Agenus Inc.'s recent FDA Fast Track designation are multifaceted. The milestone payment of $25 million from BMS, triggered by the commencement of a Phase 2 study, bolsters the company's financial position. The revenue of $156 million against a net loss of $257 million for the full year 2023 reflects substantial investment in research and development, which is typical for biotech firms at this stage.
Active discussions to monetize non-strategic assets, royalty monetization and project financing could yield $100-200 million in cash proceeds, potentially improving the company's liquidity. The cash balance of $76.1 million, with anticipated funding through 2024, suggests a runway for ongoing clinical trials. However, investors should be cognizant of the high burn rate and the need for continued capital infusion to sustain long-term operations.
The oncology drug market is highly competitive, with a significant emphasis on innovation and drug efficacy. Agenus Inc.'s BOT/BAL combination therapy addresses a critical need in the refractory CRC market, especially for patients who have failed first and second-line treatments. The therapy's expansion into other cancer types indicates a strategic move to capture a larger share of the oncology market.
The company's strategic partnerships and the potential for co-development and co-commercialization deals could enhance market penetration and share. The anticipation of topline data from ongoing Phase 2 studies in the second half of 2024 will be a critical milestone for the company and could impact its market positioning significantly.
FDA Grants Fast Track designation for BOT/BAL in metastatic, refractory colorectal cancer (CRC) patients who have failed 1st and 2nd line standard of care treatments
Data from Phase 1 of BOT/BAL in refractory CRC showed durable ORR of
Clinical data sets path for expansion opportunities in pancreas, lung, neoadjuvant CRC, and melanoma
“In 2023, Agenus made significant advances across our BOT/BAL development program. Our first target indication is metastatic, refractory colorectal cancer that is not MSI-H/dMMR, for which we are focused on pursuing accelerated approval,” said Garo Armen, Ph.D., Chief Executive Officer. “We are also pursuing multiple strategies to capitalize the company through this important path in our efforts to bring BOT and BOT/BAL to the forefront of solid tumor cancer treatment. Our vision is to maximize BOT's utility to benefit patients in combination with other immune therapies as well as current standards of care for patients with both early and late-stage tumors.”
2023 Highlights on Botensilimab
Colorectal Cancer:
- Received Fast Track designation for patients with metastatic colorectal cancer that is not MSI-H/dMMR and who do not have liver metastases, and who were previously treated with standard combination chemotherapy, anti-VEGF and anti-EGFR if RAS wild type (“refractory MSS mCRC NLM”)
- Completed enrollment of patients with refractory MSS mCRC NLM in a Phase 1 (n=150) and randomized Phase 2 (n=230) in October 2023.
-
Clinical data reported by Agenus in October 2023 revealed:
-
Among the 70 efficacy evaluable ("EE") patients in the refractory MSS mCRC NLM treatment setting, a
24% RECIST v1.1 response rate was observed in those treated with the BOT/BAL combination. Based on literature review, the response rate in a similar population treated with standard of care therapies ranges from1% to6.1% 1, 2. -
The 12-month overall survival (OS) rate is
74% with median OS not yet reached. - Topline data from the ongoing Phase 2 study are expected in 2H 2024.
-
The most common safety observations are immune-related diarrhea and colitis, which are managed in accordance with standard therapies. Grade 3 treatment related diarrhea/colitis occurred in approximately
14% of patients.
-
Among the 70 efficacy evaluable ("EE") patients in the refractory MSS mCRC NLM treatment setting, a
Neoadjuvant CRC:
-
Clinical data presented at ASCO-GI January 2024:
- In an investigator sponsored trial (IST) led by Dr. Pashtoon Kasi at Weill-Cornell Medicine, patients diagnosed with resectable localized colon or rectal cancer were treated with one dose of BOT and two doses of BAL approximately 4 weeks prior to planned surgery. After surgery, pathologic analysis reported significant tumor shrinkage.
-
3/3 patients (
100% ) with MSI-H CRC experienced major pathological responses (>90% tumor shrinkage) in less than 4 weeks, while 6/9 (67% ) MSS CRC patients had tumor shrinkage of50% or more. - IST is expanding to 24 patients with an extended follow-up time (6-8 weeks); Agenus plans to prioritize neoadjuvant development and is evaluating study designs for subsequent pivotal trials.
2L Metastatic Pancreatic:
- In patients with metastatic pancreatic cancer who have failed or don’t respond to FOLFIRINOX (2L Pancreatic) and received treatment with BOT in combination with gemcitabine+nab-paclitaxel, significant tumor marker reductions were observed in 4 of 5 patients, all with liver metastases.
-
Two (2) of the 4 patients achieved PRs at 16 weeks (target lesion reductions of
47% (confirmed) and -37% (pending confirmation). Two other patients showed stable disease at their first 8-week scan with tumor reductions of -20% and -13% . - A Phase 2 randomized study is in progress, with preliminary data expected to be available mid-year.
CTLA-4/PD-1 Relapsed Refractory Advanced Melanoma (“2L+ Melanoma”):
-
Phase 1b expansion cohort in 2L+ Melanoma reported a
30% ORR and60% disease control rate (n=10; 2/8 BOT responses and 1/2 BOT/BAL responses); all patients had failed anti-PD-1 therapy and 8/10 had failed both anti-PD-1/CTLA-4 therapy. - In the Phase 2 study in 2L+ Melanoma, data from the fully enrolled BOT monotherapy arm and a cohort of patients on BOT/BAL (n=30) are anticipated in 2H2024.
Refractory Non-Small Cell Lung Cancer (NSCLC):
-
In the PD(L)-1 refractory cohort, a
56% ORR and an89% disease control rate were observed in patients treated with the BOT/BAL combination (n=9). - In a TKI-refractory cohort, 2 out of 7 patients experienced complete confirmed objective responses after treatment with BOT/BAL*.
Advanced Sarcomas:
-
Updated findings from a Phase 1b study of 41 efficacy evaluable patients treated with BOT/BAL showed durable responses with an ORR of
20% , a median response duration of 19.4 months (iRECIST), and a 6-month progression-free survival rate of40% . -
A higher ORR was observed by dose level, with
29% at 2 mg/kg BOT compared to15% at 1 mg/kg BOT.
Refractory Ovarian:
-
In a total of 24 evaluable patients treated with BOT/BAL, with a median of four prior lines of therapy, an overall response rate of
33% was observed. The disease control rate was67% and the median Duration of Response (DOR) was not yet reached.
Finance
-
$25 million -
Advancing in our discussions on monetizing non-strategic assets, royalty monetization, and project financing, with the potential to yield
$100 -200 million - Currently we are in active discussions with several potential biopharma partners for potential co-development and co-commercialization of BOT/BAL.
Fourth Quarter and Full Year 2023 Financial Results
For the year ended December 31, 2023, we recognized revenue of
We ended the year with a
| December 31, | |||||||||||||||
2023 |
2022 |
||||||||||||||
| Cash, cash equivalents and short-term investments | $ |
76,110 |
|
$ |
193,358 |
|
|||||||||
| Three months ended December 31, | Year ended December 31, | ||||||||||||||
2023 |
2022 |
2023 |
2022 |
||||||||||||
| Revenues, research and development | $ |
30,249 |
|
$ |
3,755 |
|
$ |
38,764 |
|
$ |
16,975 |
|
|||
| Revenues, non-cash royalty |
|
53,038 |
|
|
18,284 |
|
|
114,572 |
|
|
45,285 |
|
|||
| Revenues, royalty sales milestone |
|
- |
|
|
- |
|
|
- |
|
|
25,250 |
|
|||
| Revenues, other |
|
514 |
|
|
6,347 |
|
|
2,978 |
|
|
10,514 |
|
|||
| Total Revenue |
|
83,801 |
|
|
28,386 |
|
|
156,314 |
|
|
98,024 |
|
|||
| Research and development expenses |
|
66,723 |
|
|
53,279 |
|
|
234,569 |
|
|
186,691 |
|
|||
| General and administrative expenses |
|
21,177 |
|
|
25,036 |
|
|
78,739 |
|
|
81,007 |
|
|||
| Cost of service revenue |
|
260 |
|
|
7,693 |
|
|
3,111 |
|
|
10,568 |
|
|||
| Other income |
|
(193 |
) |
|
(3,918 |
) |
|
(2,663 |
) |
|
(10,944 |
) |
|||
| Non-cash interest expense |
|
44,574 |
|
|
18,326 |
|
|
100,551 |
|
|
62,955 |
|
|||
| (Gain) loss related to debt |
|
- |
|
|
1,937 |
|
|
- |
|
|
(782 |
) |
|||
| Non-cash contingent consideration fair value adjustment |
|
(158 |
) |
|
135 |
|
|
(556 |
) |
|
(815 |
) |
|||
| Net loss | $ |
(48,582 |
) |
$ |
(74,102 |
) |
$ |
(257,437 |
) |
$ |
(230,656 |
) |
|||
| Net loss per share attributable to Agenus Inc. common stockholders | $ |
(0.13 |
) |
$ |
(0.24 |
) |
$ |
(0.69 |
) |
$ |
(0.78 |
) |
|||
| Cash used in operations | $ |
40,590 |
|
$ |
47,338 |
|
$ |
224,202 |
|
$ |
175,373 |
|
|||
| Non-cash operating expenses | $ |
56,455 |
|
$ |
32,777 |
|
$ |
139,015 |
|
$ |
96,286 |
|
|||
Conference Call
Date: March 14th, 2024, 8:30 a.m. ET
To access dial-in numbers, please register here.
Conference ID: 73242
Webcast
A live webcast and replay of the conference call will be accessible on the company’s website at https://investor.agenusbio.com/events-and-presentations and via https://events.q4inc.com/attendee/678927380.
References
1 Prager et. al NEJM 2023
2 Grothey et al. Lancet 2013
* Investigator reported, subject to change
About Botensilimab
Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator (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 900 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 Agenus
Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a comprehensive pipeline of immunological agents. The company’s 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 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 a 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 Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission and available on our website at www.agenusbio.com. 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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Investors
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Source: Agenus Inc.
FAQ
What is the Fast Track designation received by Agenus for BOT/BAL?
What was the durable ORR observed in Phase 1 for patients with non-active liver metastases?
What were the financial results for Agenus in 2023?
What was the milestone payment triggered by the Phase 2 study commencement?
What was the cash balance of Agenus at the end of 2023?
