Agenus Inc. (AGEN) Earnings Call Transcript & Summary

So with the current trials that are ongoing, we chose to do Phase II trials that are randomized, dose finding as well as able to differentiate between the single-agent activity versus multi-agent activity. And so it's a very well-designed trial that accommodates the regulatory agency's newest paradigm. And as you know, the FDA is now very much zeroed in on these items, contribution of elements and the right dose. And so this trial is designed to do that. But it also has a reference arm, the standard of care arm. And that's also very important because even though we have shown significant activity in our trial in the 20s versus low single-digit activity with the standard of care in response rates. But to show that in a randomized setting is important, and this trial will do that. Now depending on how compelling the results are and depending on what the agency thinks about that, we may go and see if we can have the ability to bring these products to patients as soon as possible because the KOLs that we've spoken to at major places like Dana Farber, MSK, MD Anderson, UCSD, UCSF and all of that, Europe are very interested in bringing this product to their patients. So we will work responsibly with the regulators around the world, including the FDA, to make sure that if there's an avenue to bring the trial results through completion, while we do expanded Phase III trials in third line as well as first-line patients, and those would be ongoing, of course, at the time of our request. Then we may have an early window -- may have an early window for registration. But nonetheless, we are very adamant about doing not just third-line patients, which -- in CRC, which target about 8,000 in the U.S. alone, but also first-line patients, which are approximately 80,000 in the U.S. So there's no reason for us not to pursue these strategies simultaneously, and we will.

Great. And maybe like you've already noted melanoma as well as pancreatic as other clinical priorities. But maybe zooming out it at a higher level, you've evaluated, I think, 9 tumor types across for botensilimab. So how are you thinking about clinical development in some other areas where you've generated interesting to such as sarcomas or non-small cell lung cancer anywhere basically.

As we've launched these Phase II trials in colorectal pancreas and melanoma, the Phase I trial remains open in other subtypes. And I would say the most excitement we have right now is non-small cell lung cancer, obviously, sarcomas, ovarian cancer that we've reported data on but also other GU tumors, as well as other GI tumors. So that trial is going to stay open and expanding cohorts to really see where these others. But we haven't limited this Phase I trial to any 1 disease type. We have 9 tumors that have shown a response already 9 different tumor types, and we'll continue to expand.

Great. Great. And before we move on to some other aspects of your company any key near-term milestones or data sets that you would highlight for botensilimab?

Well, it's as Steven mentioned, the campaign started with ESMO GI. We had a late breaker opening session at ESMO GI. And that was the first time we displayed the data that quickly followed with a substantial number of KOL meetings at ESMO in Paris, followed by SITC, a plenary session at SITC followed by a sarcoma session in Vancouver and followed by most recently, ASCO GI in San Francisco. So this has been a campaign where it's been back to back additional data disclosures, more mature data disclosures. And I'm very confident that you'll see more of that in the first half of this year, for sure, and ongoing, of course. Now in addition to that, we have other programs that are in earlier stages of development, with some very exciting data that we expect to disclose this year as well. They include our CD137 molecule, which has been a problem child for the industry because of toxicity and/or lack of activity by others. We have a very, very impressive molecule that has shown no toxicity so far. And we've gone through the dose escalation process. And now we're in combination trials with botensilimab. And we have a myeloid antibody -- that's a very, very exciting target as well. Many years ago, we had licensed 1 of those to Merck and ILT4, but we have our own ILT2, which we believe is even more impressive than what we have licensed to Merck and Merck is very, very diligently pursuing. It's in Phase III trials, and it's grown more activity in multiple cancers than any other agent that I know besides what botensilimab. So those are very exciting developments that are coming down the pike, and we will see data on those as the year unfolds.

Excellent. Yes. And regarding CD137, as you had mentioned, it has been a bit of a problem child, so to speak. But I guess, what do you think you or anyone really needs to demonstrate for this target in order to convince the feel that this is something that could be real.

Yes. I think the agonist antibodies have struggled, right? Obviously, the inhibitory antibodies, CTLA-4, PD-1, LAG-3, TIM-3, the exhaustion markers. But to really agonize T cells has had toxicity issues. It's had a struggle, but the concept is really good. If you could push T cells and NK cells into that early activated state, particularly if they have memory, you're going to do well. So what I'm excited about our CD137 it's been designed just like botensilimab is designed specifically to fix a biologic problem. This has been designed not with Fc-enhancement but through the -- a unique epitope that when this engages the Fc co-engagement with the Fc gamma receptor is very activating in a tumor microenvironment, not a liver environment. So we looked at this preclinically. And so far, we will have more data this year, but we've already shown that this monospecific therapy has not shown liver talks. So we're excited to show more. But if we can have an agonistic antibody that really gooses T cells and NK cells, as we block the checkpoint inhibitory signals that's safe in combination, it will be a major step for the field, but more to be determined, but we are combining this agonist antibody CD137 with our botensilimab now in melanoma, and we expect to complete that cohort in the first half of this year. So we're moving forward, both as a single agent and combination with the agonist. And then I would just say the ILT2 story. Merck has done -- we obviously built the ILT4 molecule, a pure myeloid checkpoint, what's differentiating first-in-class with our molecule of ILT2 is, number one, it's more enriched in the myeloid cells than ILT4. So we think it may be better as a myeloid checkpoint, but it also has lymphoid checkpoint properties that ILT4 doesn't have. So we're going to be activating T and NK cells at the same time that we're switching the myeloid element. So it's multifunctional and it's in human Phase I right now, and we're escalating. So we do have a tool chest of combinations that can be incredibly effective as we move forward, and we look forward to showing more data this year.

Perfect. Great. And you guys have touched upon this a bit as well, but like business development has been pretty like active area for you guys. How are you guys thinking about that on a go-forward basis?

Very important point, Charles a very important point. And many years ago, when we started our antibody exploits, we didn't have much resources, both in terms of company resources, capabilities and people resources. So we ended up licensing things, for example, ILT4 is an example of that to Merck. On terms that if we knew how the product was performing today, would certainly look for more attractive terms for us. But it started then. And then subsequently, we licensed some of our first-generation compounds for pretty impressive amounts of cash. And then, of course, we did the Gilead transaction and the BMS transaction. Most recently, when the BMS transaction was done it was $200 million upfront for preclinical product and made the headlines because it was the largest such transaction of its category at the time. And the reason I think we were successful in doing all of these things is because of what Dr. O’Day mentioned. There are certain attributes that are designed into these molecules. It's not just a target. For example, pursuing targets like TIGIT, like OX40, like CTLA-4 is somewhat of a generic process I mean anybody can develop and anybody to target a well-known molecule. But in our case, because of our internal capabilities, we've done, I think, an exemplary spectacular job of science and designing molecules that not just do 1 thing, but multiple things, for example, with botensilimab, it not binds to CTLA-4, but as Dr. O’Day said, it primes these cells. It actives these cells. It does many of these things, it causes memory response. It down regulates regulatory T cells. So it's all done in 1 molecule as much as possible. But in spite of that, the immune system and the cancer is a tug-of-war. And the immune system is really the body's military to win that tug-of-war. And so to do that, I think it's simplistic to think that only a sync single agent is going to be able to do it. So that's, hence, our activities with multiple components of that immunological army. That's part of the strategy of the company. Now having said all of this, in the last 9 years, we have brought in over $800 million of upfront cash with transactions that we've done. And while the grace of some superior force, these transactions have been done with molecules that are outside of the current state of the art, next-gen molecules that we have in our portfolio. for which we have complete control of right now. And so going forward, in terms of transactions, we will be selective. So it's not just the amount of money that you receive. Is it the right partner that's going to be driving these things to the finish line in a way that is substantial, along with us. It requires the right partner. It requires us to participate in a control infection in the development of that compound. And it also requires us to be able to have a lion's share of the economics. So those are the new criteria. And with each and every transaction, we've made steady progress towards this objective, more control, more of the economics or more significant share of the economics and, of course, choosing the partner very carefully.

Perfect. And with that, we should probably wrap up. But Garo and Steve, I want to say thank you very much again for joining us here today, and I hope you enjoy the rest of the conference.

Thank you very much.

Thank you all.