Good afternoon, and welcome to our next fireside chat. I am Robert Burns, a Managing Director and Senior Biotech Analyst at H.C. Wainwright & Co. I am joined today by Pete DeMuth, the CSO of Elicio. Pete, thank you for joining us today.
Good to be here.
Why don't we start off from a high level perspective? For those who may be unfamiliar with Elicio, can you provide a brief overview of the company, its technology, and your pipeline?
Yeah, of course. Great place to start. Elicio Therapeutics is a clinical-stage cancer immunotherapy company. We're focused on immunotherapies that are directed specifically to the lymph nodes. We believe that the lymph nodes are a key site in our body which orchestrate the immune response against cancer. To date, it's been a challenge to get these immunotherapies to the cells that matter in the lymph nodes. You can see here we're doing that with a platform approach, which we call Amphiphile or AMP. This is a technology developed at Massachusetts Institute of Technology intended to direct immunotherapy specifically to lymph nodes and the immune cells that reside there. We have proof of concept from two completed phase I trials and a randomized phase II, which had a final analysis earlier this summer. We can talk certainly about that.
The lead candidate is our ELI-002, which is a KRAS specific immunotherapy designed to target the seven most common mutant forms of KRAS. We have some exciting data from the randomized phase II trial, as well as from a series of patients that were on that trial that then went on to receive subsequent therapy, including a checkpoint t hat had some notable radiographic responses in the metastatic setting. So, excited to talk more about that.
Awesome. Yeah, we are certainly going to dive into all those data sets. Why do not we level set and provide some historical context here? Obviously, cancer vaccines in the past have typically underperformed. Why have not they worked that well, and what is different about this current generation of cancer vaccines?
Yeah, there are two things that I would point to. The first one is just the technology has improved dramatically. Historically, cancer vaccines, especially the types that we work on, have had significant challenges in getting to the places where they can have their biological effect, the lymph nodes. There was a decade's worth of research done at MIT to study that, and then to develop this Amphiphile approach for lymph node targeted immunotherapy. What that does is get these agents directly to the immune cells, which then orchestrate the immune response against cancer. There is a potency challenge that needed to be overcome. The other thing that has been a challenge is the setting of disease.
We started out studying minimal residual disease, and we are now moving our way into metastatic disease. One of the things that has come alongside of that is checkpoint inhibition.
This is a tool that with the synergistic effect with a cancer vaccine, could become a very potent combination for future therapy in cancer.
Yeah. Building on that point, obviously we saw that Moderna announced results from its phase III INTerpath-001 trial, which evaluated the combination of its mRNA based individualized neoantigen vaccine plus KEYTRUDA in the adjuvant setting. That was for completely resected stage IIB to IV melanoma, and it met its primary endpoint of RFS.
Yep.
Separately, maybe a week later, we saw BioNTech on the flip side of that, announce that it halted its phase II, evaluating its mRNA based neoantigen vaccine as adjuvant in Stage 2, 3 colorectal cancer, who were ctDNA positive after R0 resection because of futility. While the full data sets have not been presented, maybe you could compare and contrast these divergent results and sort of hypothesize why we are seeing those opposite results.
Yeah. These are two very exciting readouts, and I think we can learn quite a bit from them. Firstly, melanoma is not CRC. I think on the spectrum of cancers that are thought to be sensitive to immunotherapy, melanoma is certainly at the far end, a place where you have abundant neoantigens, where the standard of care does involve immunotherapy already. So adding a vaccine to that checkpoint backbone therapy seems like a really good idea, and I think the data speaks for itself. The CRC setting is a little bit more challenging, perhaps a little bit more refractory to immunotherapy. The backbone standard therapy does not involve immunotherapy, so you're sort of building onto a foundation that does not yet exist.
I think it's important to note both of those approaches are personalized in nature, so they have some challenges with cost of goods, manufacturing time, complexity. They also target personalized, but not tumor driver or essential mutations most often. I think it remains to be seen. We'll see how the data plays out, but that could leave you open to escape mutations that would limit the durability of responses. Whereas what we're doing with our ELI-002 program is targeting a truncal driver mutation in KRAS-
Something that the tumor can't really get rid of and is essential for tumor progression. So we're certainly excited to see how we can do with an off-the-shelf approach, what has been done with Moderna and Merck.
Yeah.
Yeah, excited about that opportunity going forward.
Awesome. Thank you for that landscape perspective. Now let's sort of dive into what Elicio has demonstrated. You recently reported that three patients who progressed on ELI-002 7P in the AMPLIFY-7P trial, who then went on to receive a checkpoint plus chemo, had some pretty noticeable response rates. Maybe give us some historical context there and walk us through what you observed.
Yeah. These are three patients that completed ELI-002 treatments while on AMPLIFY-7P. They had progression while on therapy, but then went on to receive subsequent chemotherapy plus checkpoint inhibitor therapy with radiation. Rob, I think what you're alluding to is illustrated nicely in these tables where we know these active therapies that are the standard of care or have been experimentally evaluated in pancreas cancer have generated extremely low rates of complete response. A handful have been reported in the literature amongst many dozens of evaluated patients. It's known that these type of deep responses are very rare in this patient group.
What you're alluding to in our case series are three of three patients that were studied in this setting where they have completed ELI-002, had a metastatic recurrence, then received subsequent therapy, including checkpoint inhibition therapy, and all three of them achieved a complete radiographic and complete metabolic response, and that was accompanied by normalization of their tumor biomarkers. You can see one example here of a patient that had several paraesophageal lymph node recurrences that then had a complete response on radiography and PERCIST criteria.
This three of three, although it's a small patient series and needs to be confirmed in a prospective trial, certainly gives us an interesting signal, and we have extensive translational data to build around that hypothesis, showing tumor infiltration by KRAS or by T cells, KRAS T cells in the blood that persist through the subsequent therapy regimen that those patients received, and antigen spreading to other non-KRAS personalized tumor mutations that could contribute to anti-tumor T cell response.
Could you also discuss how these observations, particularly given how profound this initial observation is, how it has influenced your near-term clinical development strategy for ELI-002, as well as the trial design for the Plan N study evaluating ELI-002 7P in combination with the RAS inhibitor plus minus an anti-PD-1 agent?
Yeah, happy to do that. These data give us some confidence to move into the metastatic pancreas cancer space. We are doing that with a prospective phase I trial where we will have two cohorts. Those cohorts will receive ELI-002 in combination with a RAS inhibitor, and one will further receive a checkpoint inhibitor therapy. So, those are open label based on radiographic endpoints, things that could be read out relatively quickly, and the idea is to confirm and further evaluate the trends that we saw in those three patients from the case series that I just mentioned.
Okay. When do you think you are going to initiate this trial? More specifically, when you say RAS inhibitor, are we talking an allele-specific RAS inhibitor, or are we talking more about what we saw come out of Revolution Medicines not too long ago with its first landmark approval?
Yeah, it is a great question. This is a trial that we are planning to initiate in Q4 with readouts throughout Q1 and Q2. As I said, it is open label based on radiographic endpoints, so those can come relatively quickly as patients are enrolled onto the study. Your question about RAS inhibitors is a really good one. Obviously, Revolution Medicines has been approved in the second line. There are some benefits for using an approved agent for patient access and reimbursement, things like this, trial conduct. But we believe that ELI-002 could complement the class of RAS inhibitors, both Pan-RAS inhibitors as well as allele-specific inhibitors.
We are very excited to have those discussions and to see where we can go with this combination.
All right. Given the fact that you expect to initiate this trial in 4Q of this year, maybe talk to me a little bit about when you might see initial efficacy data from this trial, and what type of magnitude of clinical signal would you consider sufficient in order to advance this agent into later stage development and, well, more specifically, in that specific setting?
Yeah. There are a few things that we are looking for in this trial. As we said in that case series, we have three patients. Three patients had CR, three patients had multiple scans showing CR.
Two of those had duration of response more than nine months. There are a couple ways that I think this phase I trial could give us additional data that would build our confidence for moving forward. One would be to see an overall response rate that is trending in a direction that is better than what the standard of care is.
The second would be to see a rate of CR that is interesting beyond what's known from the historical benchmark, which as we know, is relatively low, one or two out of many series that include 40 to 50 patients.
Those would be the things that we'll look for. There's an opportunity to look for the translational correlates that we have seen in the case series that have also built our confidence, and I think with that data set, we would feel confident saying that we've validated the proof of concept for synergy between a RAS inhibitor and ELI-002 with a further evaluation of the contribution of a checkpoint inhibitor. The other thing, and perhaps one of your questions will lead us here, is just to note that what we know about RAS inhibitors from preclinical studies is that a lot of their activity does derive from an immunological mechanism of action. For example, RAS inhibition can alleviate the myeloid biology that suppresses the tumor microenvironment. It can lead to better antigen presentation.
Doing these sort of combinations with a therapy that generates T cells that then could take advantage of all those benefits of RAS inhibition seems like a really strong driving hypothesis, and checkpoint inhibition, as we know, can really potentially supplement that as well.
Now, from a mechanistic perspective, the science sounds sound there. I'm really looking forward to potential initial results early on in 2027. Why don't we shift gears a little bit now to the AMPLIFY-7P trial. You announced the results in June from the DFS primary endpoint from that randomized phase II portion. Maybe walk us through those results and highlight what you consider to be the most important takeaways from that data set.
Yeah, great question. I will just remind us of the key findings from our phase I study, which are shown on this slide. That was a single-arm study, but what allowed us to do was strongly correlate and consistently correlate the strength of the KRAS T cell response generated by ELI-002 and relapse-free and overall survival.
As we moved into phase II, we were interested to see that as well as the primary endpoint, which you mentioned. While the intention to treat primary endpoint for DFS improvement was not met, what we did find were a few very encouraging things. The first were the six-month and the 12-month DFS landmark analyses. These showed during that window where ELI-002 is being actively treated-
Given to patients, there was an apparent benefit over the observation standard of care.
Yeah.
That suggests that potentially additional dosing could maintain that benefit m ore long term. The second thing that we observed, and I will see if I can get this slide to go there, is again, this reconfirmation of the strength of KRAS-specific T cells correlated to DFS improvement.
You can see that here. It is an excellent validation, I think, of what we have seen in phase I. Certainly shows that ELI-002 induced KRAS-specific T cells can have an impact on DFS and we are looking forward to building off of that. Further analysis, including subgroups, pre-specified analyses are in preparation for sharing in a future medical conference or publication.
Perfect. You previously indicated that you are going to hold an end of phase II meeting with the FDA regarding phase III development of 002 or 7P. That announcement was prior to what you found in the metastatic setting. Talk to me a little bit about how you are thinking about these two settings in PDAC, as well as the IIT phase I neoadjuvant combination study.
Are you waiting for results from the phase I, the company-sponsored one that you are going to initiate in 4Q, as well as the IIT, before you engage with the FDA? Talk to me a little bit about the sequencing here.
Yeah. There's some interdependencies, of course. You're right, we will learn quite a bit from this phase I study. This'll be one of the first, the other being the neoadjuvant IIT study that you mentioned where we're combining ELI-002 with a checkpoint inhibitor concurrently
Yeah.
Instead of in series. We'll certainly be able to generate a lot of data and understanding from those studies that would then potentially inform our strategy in phase III.
There are some learnings that we would look to take forward in the design of the phase III. Certainly, our priority at the moment is to focus on this phase I prospective study, where we're studying 002 with RAS inhibition and checkpoint inhibitor therapy.
That will come quickly, relatively so at least, and that should give us additional learnings to design the phase III going forward.
Yeah. When we think about the phase III trial in the adjuvant setting, obviously, just based on the setting, it would take a considerably longer time to read out than it would in the metastatic setting. If you had to choose phase III development in metastatic versus phase III in adjuvant, obviously we're reading the tea leaves here.
Yeah.
The crystal ball. We're Miss Cleo-ing. But how are you thinking about those two settings from a phase III development perspective?
Yeah. I don't want to speculate, but I think the considerations that you've laid out are the right ones.
Right? We know that the metastatic pancreas cancer space is four to five times as large as the adjuvant/neoadjuvant space.
Yeah.
We know that the speed of trials is certainly an advantage in that setting, so getting to a registrational study and onto the market with a metastatic program is likely to be faster and require less capital resources.
Yeah.
I think we will certainly see and adapt as we get these different pieces of information, let it inform us, but you are thinking about it exactly in the way that we are.
Okay. When we think about that phase I metastatic trial, obviously you sort of alluded to that it sort of would be prudent to prioritize development with an FDA-approved Pan-RAS inhibitor. But obviously, when we look at the class overall of Pan-RAS inhibitors or Pan-KRAS, either/or-
It's extremely burgeoning. It's burgeoning to.
Absolutely.
A very significant degree.
Yes.
What characteristics are most appropriate or are most important to you when you're considering other optimal RAS inhibitors to potentially combine with ELI-002? Obviously, there's some next-gen approaches. Would breadth of KRAS coverage, depth and durability of pathway inhibition, safety, immune tolerability. Just give me a little bit how you're thinking about that.
Yeah. I think you've identified the key ones. Certainly, safety is important.
Yeah.
Right? We want to take that into account. Duration, depth of inhibition of the RAS pathway, I think is important. Allele-specific inhibition seems to, based on some of the early clinical data, maybe be safer but be subject to other escape mutations. Importantly for Pan-RAS or allele-specific RAS inhibition, the pathways that those tumors use to escape that therapeutic pressure are ones that could be overcome with an immunotherapy.
Specifically, amplification of the RAS pathway may allow you to get around a RAS inhibitor, but it will provide more antigen that would potentially be useful as a target for the immune response.
Yeah.
In the allele-specific case, if tumors mutate to a different mutant variant of RAS, having seven specificities of the immune response against all of those common mutation forms of RAS could give you a way to control potential escape mutations that otherwise would emerge in a RAS inhibitor only setting.
No, I completely agree with you there. One of the things that I find to be a strength within the data sets that we've seen so far with 002 is the safety profile associated with it. Obviously, when we think about the safety profile we've seen with some of the Pan-RAS inhibitors, they really do have some toxic side effects. But with the side effect profile we've seen with you guys, there really won't be that much overlap there.
Yeah.
It seems like it would be feasible, at least from a tolerability perspective. Give me your thoughts there.
Yeah, absolutely. I think this is one of the strong suits of ELI-002, and it's designed that way. A lymph node targeted immunotherapy restricts immune activation to the lymph nodes, and that can overcome some of the safety challenges that these types of therapies have had in the past. But I think this sets us up really well to combine with even some of the more toxic RAS inhibitors, and potentially to do therapy over the long term.
For example, in the metastatic setting, if patients can't endure RAS inhibitor therapy, continuing to dose with the ELI-002 would be a really attractive way to continue to give the immune system an ability to put pressure on the tumor and prevent recurrences.
Yeah. When we think about the prevalence of KRAS mutations and the alleles that 002 target, how are you thinking about the potential addressable patient population here and overall market opportunity? Because it's not just PDAC where this thing could be potentially applicable.
That's absolutely true. RAS is mutated in approximately one quarter of all human solid cancers.
The big three are pancreas cancer, colorectal cancer, non-small cell lung cancer. Together in the U.S. and the Europe, that's more than 500,000 patients per year. Then there are a number of other solid tumors that express KRAS.
Yeah.
As we said earlier, the metastatic patient group in the U.S. is about four to five times larger than the neoadjuvant, adjuvant patient group.
There are some features that make that attractive. But I think proof of concept in this area, in pancreas cancer, in a place where immunotherapy is thought to be not effective w ould give us a lot of confidence to move into these other areas where immunotherapy, for example, is part of the standard of care for non-small cell lung cancer.
Yeah.
To build onto that would potentially be even more favorable than doing it in pancreas cancer. I guess suffice to say, there's a big opportunity here for us to move into.
One of the things that I've definitely noted that people who are newer to the Elicio story might not realize was that at one point you also had a P53 and a BRAF vaccine. This technology is not just specific to KRAS, but you could apply it to other sorts of targets. Give me a sense as to where those programs are in development right now. Obviously, we'll talk about your cash runway in a little bit, but just
Yeah.
Give me a flavor as to the broad applicability of this platform.
Yeah. This was meant to be a modular platform, one that could address a variety of driver mutations. KRAS was an obvious choice for our first one. But you're right, we have programs that target mutated BRAF and mutated P53. Those are pre-clinically validated, and simply awaiting the right resourcing to bring them forward into the clinic.
Okay. Maybe remind us what your cash is as of end of Q2.
What that operational runway provides.
Yeah. We reported in our SEC filings, $23.5 million at the end of Q2. We did a $15 million registered direct in July. Together that gives us an operating runway into the first quarter of 2027.
Awesome. I certainly look forward to all the developments coming out of Elicio. Pete, thank you for joining us today.
Thanks, Rob.