Good morning, and thanks for joining us to have a conversation with Joseph Ferra, CEO of Elevation Oncology. Elevation Oncology is a clinical-stage biotechnology company focused on developing antibody-drug conjugates and monoclonal antibodies for cancer therapy. So to discuss the company's strategy and some of the clinical milestones that they plan to achieve in 2024 and beyond, I welcome Joseph to this discussion. Joe, glad to see you here, and thanks for accepting our invitation and joining us in this conversation with our audience here. So to start off, can you give us a little bit of a background on Elevation Oncology itself, and also your lead molecule, EO-3021, and it's which is an ADC that is targeting Claudin 18.2, and the reasons for choosing Claudin 18.2 as a target? Yeah, sure. Well, so first of all, thank you for the invitation to present at the conference, to be included in the conference, and, as always, the continued support from you, RK, and from the entire H.C. Wainwright team. And thank you to all of you for joining today. So, Elevation Oncology, we have found a very specific and very broad way of looking at selective cancer therapies as a way of building a differentiated oncology pipeline. We all know that oncology has a significant unmet need across a range of solid and heme malignancies, and there is always an opportunity for improving upon current standard of care, as well as an opportunity to improve, think about new targets that could be meaningful for better outcomes for patients. Claudin 18.2 was a target that we, early on as a company, identified as an emerging target in oncology that was gonna have an opportunity for improving standard of care for patients. When we first started looking at Claudin 18.2, we were actually very modality agnostic. We, as a company, were not wedded to any specific type of approach when it came to other programs we looked at and the way our lens, the way we look in oncology, 'cause we think it's important to have a target-specific approach that, based on the target, based on the tumors that we're looking at, what is the best opportunity based on the technology available and based on what we think is gonna be important for that target in having better outcomes for patients? When we started looking at Claudin 18.2 as a target, we quickly got to an ADC, an antibody-drug conjugate, as an optimal opportunity and quickly becoming potentially the standard of care in treatment for tumors that express Claudin 18.2. And this was largely driven by two things. First, Claudin 18.2 was emerging, and we thought an ADC would be an opportunity for delivering a targeted cytotoxic that could have an opportunity in a broader range of expression than many other modalities we're looking at, including potentially naked monoclonal antibodies. Two, we were highly impressed by all the advancements in ADC technology that we all, as an industry, are continuing to benefit from, and by extension, the patients will benefit from as well, and that these advancements in technology were just giving us a toolkit for designing better ADCs and a better opportunity for, again, delivering a targeted, a cytotoxic in a targeted way, staying away from those cells that, of course, that are healthy, that we would rather not touch with a chemotherapeutic, and those cells that we wanna kill with a targeted cytotoxic. When we looked at the landscape of ADCs at the time, we moved towards what we're calling EO-3021. We in-licensed rights to 3021 from a Chinese company, CSPC. We honed in on this program because it was differentiated thanks to its site-specific conjugation. Now, this is an approach that is part of this advancements in technology around ADCs, giving us an opportunity, we believe at the time, an opportunity to minimize payload, in this case, the payload is MMAE, payload-associated toxicities, and maximize the overall opportunity for the program, and we're pleased to see that even in the initial data that we reported last month from our phase 1, that that data supported exactly that differentiation across multiple points, which we'll talk more about, but that movement towards ADC for Claudin 18.2 set us on a path as a company towards utilizing those advancements in ADC, ADC technologies, developing a lot of in-house expertise around ADCs, and leveraging that for a differentiated, as I said before, selective cancer therapy pipeline. And that's also representative in that our second program, which we started talking about earlier this year, which is an ADC targeted to HER3, another target that is well-validated with across multiple approaches, including an ADC approach, and that we think that in the advancements in ADC technology give us an opportunity to think about a differentiated HER3 ADC. And we've said that we're gonna name a development candidate from our HER3 ADC later this year. Very good, so as you said, EO-3021 is in a phase one clinical study, which includes not only dose escalation, but also expansion portions. Can you please discuss the design of that study? Yeah, for sure. So, as I mentioned, as you hinted at, RK, we presented initial data from our phase 1 for EO-3021 last month, and a few takeaways from that data overall was, first, it showed that we have an active agent with a differentiated safety and tolerability profile and a potential best-in-class Claudin 18.2. The second key takeaway is that we were fortunate that even in this initial data set, we could see an initial trends in expression, Claudin 18.2 expression, that could lead us towards the future development of the program and ensuring that we're focusing on those patients that are more likely to respond to a, to an agent like EO-3021. And the third part is we set out a vision for the program going forward, exploring EO-3021, not just in monotherapy, but also in combination approaches, thinking about different lines of therapy and moving it to gastric GEJ for EO-3021 across lines of therapy. Moving forward from here, we've also said that we're moving to the expansion portion of the phase 1 in monotherapy, focusing on two doses, 2 and 2.5 mg per kg, and we've started moving into the expansion portion of the phase 1, going forward. We've also said that by the end of the year, we're going to start enrollment in the combination approaches of EO-3021. Now, we think that our approach with EO-3021, thanks to the site-specific conjugation, gives us an opportunity to be the more combinable Claudin 18.2 ADC. And earlier this year, we announced clinical supply agreements with both Eli Lilly and GSK, where we're gonna be exploring combinations of EO-3021 with ramucirumab and dostarlimab, respectively, as we think about moving into combination approaches, both in second-line gastric GEJ cancer and first-line gastric GEJ cancer. So, when you released the data in August, you know, from that data, we saw that Claudin 18.2 expression is very important, you know, for EO-3021 to be efficacious, right? Because, you know, it had a promising ORR in the patients that expressed Claudin 18.2, but not as much in the non-expressers. So, based on the differentiated data, you know, it looks like you're going to use the biomarker in selecting the next phase of the clinical development. So, how would you incorporate that? You know, at what stages would you incorporate that? Is it just more in the selection or also throughout the progression of the disease, watching the expression of Claudin 18.2 through as the disease progresses? Yep. Yep. So, very good question. So we, in the data that we presented last month, we had approximately a 43% overall response rate in a Claudin 18.2 enriched population within gastric GEJ cancer. That is part of the evolution of the understanding of the target, and as I said in my earlier comments, that the understanding of Claudin 18.2 as a target is evolving rapidly, both by us as a company, but also as a field. One thing that we have learned for sure is that expression matters, as expected, and that in our data, we were fortunate that even early on in this initial data, we could see a trend in that those patients that expressed Claudin 18.2 above a IHC benchmark of 20%, 2+, 3+, saw that 43% overall response rate, but also that those patients whose tumors expressed below the 20%, 2+, 3+, we saw a 0% cutoff. That's a pretty stark contrast in terms of thinking about a cutoff that could give us a trend towards focusing on those patients that are more likely to respond, versus those patients who are less likely to respond. We, as a field, and we as a company, have also learned a lot in the past few months about the expression curve for Claudin 18.2, in that it's very U-shaped. You have 20%-30% of patients on the left end of the curve, which are expected to be non-expressers to very low expressers. On the opposite ends of the curve, you have 30%-40%, which are considered very high expressers. In the middle, you have about 20%-30% of those that are low to medium and/or heterogeneous expressers of Claudin 18.2 across their tumors. At a cut-off of 20%, 2+, 3+, we know we're looking at 60% of the opportunity for gastric GEJ cancers in improving the standard of care for those patients. As we think about the future development of EO-3021, we've said in the expansion portion of the trial, we're gonna implement prospective testing. As I said, as we mentioned from the cut-off that we just said, what's one thing that is very clear, that we wanna make sure we're focusing on those patients that are more likely to respond. So implementing a prospective cut-off gives us an opportunity, even in the expansion portion of the trial, which is happening now, of making sure that we're enrolling those patients that are more likely to respond. We think the evolution of understanding the expression of what the ultimate optimal cut-off is, is still gonna evolve with time. It's gonna evolve for our program. It's gonna evolve from other programs. But all of that is sort of understanding in real time, based on real-world data that we're generating and that other companies are generating, so that we can maximize the opportunity for Claudin 18.2 ADC. So in the current study, you have the dose escalation portion. Are we going to see additional data from that part of the study? And in terms of the expansion, you know, how, what's the expansion going to be like in terms of patients? And you know, you said you're planning to, you know, you're enrolling patients there, so how many? What's the enrollment status at this point? Yeah. So we have said that we moved into the expansion portion of the phase one in monotherapy for EO-3021. We, as a company, made the decision a while ago, given the unmet need in gastric and GEJ tumors, of focusing on gastric and GEJ, even though there certainly is an opportunity for Claudin 18.2 ADC across other tumors. But we think it's important for us to focus both in single agent and in combination in gastric and GEJ for EO-3021. As part of the expansion portion, we've said that the additional data, the next data opportunity to share clinical data is gonna be in the first half of 2025, and we expect that first half of 2025 data to include additional data, additional patients from the ongoing phase one in monotherapy, including now the expansion portion of the trial. So Claudin 18.2, just like any other target, you know, does have some safety issues around it. But I believe EO-3021 is differentiated from the other clinical candidates that are targeting Claudin 18.2. What's the differentiation there, especially in terms of the safety? And, you know, what sort of safety data have you seen so far? Yeah. Yeah, for sure. The safety and tolerability of EO-3021 certainly is a key part of our differentiation and our potential best-in-class. You know, the efficacy that we reported certainly is competitive relative to the field, but you add on top of that, the overall profile, including safety and tolerability, really gives us an opportunity to think more broadly and have a potential best-in-class Claudin 18.2 ADC. That all stems from the site-specific conjugation and having a more stable ADC construct that gives us an opportunity to deliver the cytotoxic to the tumor where it matters and not in other places where we don't want it to matter. The safety and tolerability profile for EO-3021, really, first, for Claudin 18.2 as a target, Claudin 18.2 in healthy tissue largely is expressed in the gastric mucosa, so nausea and vomiting are known on-target, off-tumor toxicities for Claudin 18.2-directed agent, ADC or otherwise. We, as a company, hope to mitigate that in our phase 1 by having pre-treatment with antiemetic treatment, and that actually, in our data, alleviated the significant portion of the vomiting that patients experience with a Claudin 18.2-directed therapy. The other aspect of safety and tolerability is around the payload, and as I said, with the site-specific conjugation, we hope to minimize the MMA-associated toxicities, and we did exactly that. We had minimal MMAE-associated toxicities in the data that we shared, but we also had no evidence of peripheral neuropathy or neutropenia, two very well-known toxicities associated with MMAE that have plagued more traditional ADC constructs, and opportunities for having a better overall profile for, with an MMAE payload stems from those two AEs alone. So given that profile, it puts us in a position to have not only a better profile from a single agent, but also a better, more combinable agent. There are other Claudin 18.2 ADCs that do have some of those toxicities, and certainly, they have an opportunity to be drugs, but their safety and tolerability profile, we think, will limit their clinical utility overall. So, Joe, you alluded to two potential molecules that you want to combine with EO-3021 when you start your combination studies. What's the rationale behind the choice of those two? Yeah. So, we think about it in terms of different lines of therapy. So in second line, the standard of care is Lilly's ramucirumab plus paclitaxel, and there we see an opportunity of replacing chemo, paclitaxel, with a targeted cytotoxic, like EO-3021. So there, the opportunity in second line is thinking about replacing chemo and having a more targeted cytotoxic for a better, more tolerable approach in second-line gastric GEJ cancer. First-line combination with dostarlimab, a PD-1 inhibitor, there is a lot of opportunity to think about synergy between an MMAE payload and opportunity for immunogenic cell death. So we think not only is PD-1 clearly a part of the standard of care within gastric first-line gastric GEJ cancer, but there we see an opportunity for improving upon the current standard of care. Also, relative to the safety profile and the profile of EO-3021, we also could see an opportunity to thinking about combining EO-3021 with chemotherapy in the first line, so thinking about a triplet combination, EO-3021, plus a PD-1 inhibitor, like dostarlimab, as well as a chemo approach as well. That isn't a type of approach that is available to us in EO-3021, largely because of that site-specific conjugation and that more favorable safety and tolerability profile relative to the field. So then let's talk for a couple minutes on your second molecule, the HER3 ADC, that you plan to unveil, you know, in the coming months. So at AACR, you did present some of the data talking about the strong anti-tumor activity in xenograft models. From there, what's the plan in terms of developing the HER3 ADC, and you know, how quickly can we get to the clinic? And, you know, what is the combination that you're looking at, you know, that you're trying to do better? Yeah. Yeah, for sure. So as I said, as we've continued to say as a company, we think the advancements in ADC technologies are gonna give us an opportunity as a company, but also as an industry, of rethinking about targets that previously just were challenging from a drug development standpoint. We certainly think HER3 is one of them, and that's been validated by other approaches with other ADCs. But the field, for the most part, is dominated by topo payload ADCs within HER3. At AACR, we had a representative preclinical proof-of-concept molecule, where we used our prior lead program, seribantumab, HER3 naked monoclonal antibody, plus traditional cysteine-based conjugation, plus an MMA payload and a DAR of 4. And so how that could have an opportunity for having activity and differentiated activity in a range of HER3-dependent models. As we think about the program, we certainly think there are ways of differentiating relative to the field. For having a HER3 ADC, that is gonna be very meaningful, both complementary, in some cases, better than what is currently in development. There is no HER3 ADC approved currently, and that option is not available to patients, and HER3 is known to be expressed in a range of solid tumors. So there, we see an opportunity for a differentiated approach. We plan to name a development candidate by the end of the year, and of course, with that, moving that program into IND-enabling studies. But haven't given any further timelines relative to the program beyond naming a development candidate in the coming months. So, you know, 30 years ago, we all saw the magic bullet, you know, paper that came out, starting to talk about ADC as an idea. And especially in the last couple of years, ADC seems to be the keyword. Yeah ... you know, for many industry players. When you talk to industry folks at this point, what is exciting them, you know, that suddenly changed, Mm-hmm ... over the last two years? And where do you think, you know, Elevation can be a strong player? Yeah. Yeah, so for sure. So it's, it stems from, you know, I think, or, you know, as with many technologies in our industry, early on, ADCs got a bad rap, and a lot of that came down to the intersection between efficacy and tolerability. And thanks to the advancements in the technologies, we just have an opportunity to develop more better ADCs. And an ADC also has three parts. It has an antibody, it has a linker, and it has a payload. So it gives you a really good construct for tailoring a drug towards what you want to achieve. We, as a company at Elevation Oncology, we're not wedded to any specific technology, and we see that as a competitive advantage for us, in that we have this knowledge around ADC, ADC construct, across a range of different targets, and have the ability to think about, both for EO-3021 as a program, for our HER3 ADC, and further programs after that, about tailoring the best ADC technology relative to the target that we wanna go after and what we're trying to solve. We think an ADC approach is going to be quickly gonna become the primary approach across a range of solid tumors, and we look forward to leveraging our expertise to doing more of that, so that we can have better outcomes for patients across a range of solid tumors. So in closing, you know, what's your current cash position, and what sort of runway can you get from that? Yep. So we, as of June, we have approximately $110 million in cash. Current cash runway is into 2026. So we are very fortunate to be very well capitalized as we continue to move EO-3021 forward in the phase I, as well as moving into combination, moving the HER3 ADC forward, and doing that in a way that we can have additional data in the first half of 2025, and think about a cash position that gives us the opportunity to execute across all of this. Thank you, Joe. Thanks for joining us, and good luck. Thank you. Appreciate it.