2023-06-05 11:38:01 ET
Summary
- Agenus Inc. has existed for a long three decades, doing nothing much really.
- They have been producing very strong data from botensilimab lately.
- Agenus Inc. prospects could now change for the better.
My beef against Agenus Inc. ( AGEN ), as I noted in December, is that in its 28 long years, the company has done some promising research, but in its own pipeline, it has never approached much near the market. Many of its molecules have shown “promise” over the years, and botensilimab is the latest in that list of promising candidates. There are indications, though, that despite the 40% drop in prices in the last 6 months, this time, with botensilimab, it might be different.
Botensilimab is an Fc-enhanced CTLA-4 inhibitor which provides broader coverage of the molecule, increasing patient targeting by 40%, as well as increasing benefits for existing patients. Some of the benefits are T cell priming, Treg depletion, and T cell memory formation as well as improved safety. The company’s very long-tailed pipeline can be seen here . Botensilimab consists of a majority of the pipeline, as monotherapy or as combo therapy. Lead indications are Non-MSI-H-colorectal cancer, PD-1 r/r melanoma, Pancreatic cancer and cervical cancer.
If you have followed my coverage of Agenus, this is a R&D focused company with years of work in oncology. I covered the development of balstilimab, and how it has not fared well as monotherapy in 2nd line cervical cancer for various reasons. This molecule is still in the game, but focus is now more on Botensilimab, which has consistently produced good data, including from 9 cold and treatment-resistant tumors in a phase 1 trial, while avoiding known safety issues like hypophysitis, pneumonitis, or high-grade hepatitis of first generation CTLA-4 molecules.
Botensilimab has also shown superior ORR data compared to historical data in a number of tumors. In 70 evaluable patients with Non-MSI-H CRC, trial data showed 23% ORR vs 1-5% historical ORR. In 24 evaluable patients with ovarian cancer, the ORR numbers were 33% vs 3-10%. 13 evaluable patients with sarcoma had a 46% compared to 12-16% ORR in historical populations. In 8 evaluable patients with PD-((L))1 Refractory NSCLC, 50% ORR was observed vs. 6-13% ORR in the historical population.
In overall survival ((OS)) and also in Non-MSI-H CRC, botensilimab combined with balstilimab showed a much better OS than multiple other standard therapies. 12 month OS stood at 63% overall and 81% for patients with no liver mets, while for Regorafenib, 12 month OS was 24.3, and for TAS-102 it was 27%.
The company provides a detailed set of comparative data, which shows how well the bot/bal combo did in 2L Non-MSI-H CRC:
“This data highlights the deep and durable responses achieved with botensilimab and balstilimab in advanced MSS CRC, underscoring remarkable benefit for these patients who have failed standard of care or other investigative therapies,” said Agenus Chief Medical Officer Steven O’Day. “With over 300 patients enrolled to date, botensilimab alone and in combination with balstilimab have demonstrated durable clinical responses across nine cold and treatment-resistant cancers.”
Interestingly, two years ago, balstilimab went through some tough times after the FDA perfunctorily created a situation whereby Agenus was forced to withdraw its cervical cancer NDA for balstilimab monotherapy and discontinue trials. The drug has now managed to survive as a combo therapy with botensilimab, not only in cervical cancer, but also doing well in ovarian cancer. In March, they presented combo data from a phase 1b study in platinum-resistant or refractory ovarian cancer showing an overall response rate of 33%. 79% percent of these heavily pretreated patients had high-grade serous ovarian cancer, a form of disease “ generally thought to be unresponsive to immunotherapy,” and where historical response rates have varied between 3 and 10% only.
Agenus has four other companies spun off from its original core. These are:
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MiNK Therapeutics, a publicly traded developer of allogeneic iNKT cells with a pipeline of CAR & TCR iNKTs, cytokine engineering, bispecific engagers
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SaponiQx, an integrated vaccine platform whose QS-21 STIMULON adjuvant is a key component of GSK’s Shingrix, Mosquirix, and recently filed elderly RSV vaccine
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Agenus Biologics and Atlant Clinical, cGMP manufacturing facility and CRO serving the US and EU markets respectively
Financials
Agenus Inc. has a market cap of $558mn and a cash balance of $193mn. R&D expenses were $57mn for the three months ended March 31, while G&A expenses were $18mn. At that rate, they have fewer than 3 quarters of cash. Institutions hold a large percentage of the stake, while retail presence is also significant. Key holders are Deep Track Capital, State Street and so on. There are almost no insider transactions in the last 2 years, neither buys nor sells, except for three option exercises.
Bottomline
Agenus Inc. was founded in 1994 and in these 3 decades, it has been able to get approval for one of its assets through GSK. Its own pipeline has not done well. The 2021 PDUFA withdrawal was unfortunate, but it was also illustrative of how this company runs. It does a lot of work, but it never gets there.
This time, though, with botensilimab, things may actually be different. The results Agenus Inc. has published for botensilimab are really strong, and while the cross-trial comparisons they have put out will only matter insofar as they actually do a comparison trial with a standard of care in these indications, they are indicative of good things. I will not invest right now, but I will keep watching Agenus Inc.
For further details see:
Agenus: This Time May Be Different