All right. I'd like to welcome everyone to the Piper Sandler Healthcare Conference. My name's Biren Amin. I'm the Managing Director here at Piper Sandler. I'd like to introduce our next company. We have Elevation Oncology and their CEO, Joseph Ferra, with us. So welcome, Joe, to the Piper Sandler Healthcare Conference. Maybe to start off, I guess, you know, maybe give us a brief overview of, you know, the company's pipeline and, you know, some of the key events anticipated over the next, you know, 12 months. Yeah, for sure. And thank you, Biren. Thank you to the Piper team for hosting us. Always enjoyed this conference. I really appreciate the opportunity to be a part of it. As you mentioned, Elevation Oncology, our focus is developing selective cancer therapies that are focused on meeting unmet needs in oncology. And in particular, we are leveraging our expertise and what we believe are rapid advancements in ADC technology to develop better oncology therapeutics that meet significant unmet needs in the current landscape. Our lead program, EO-3021, is a Claudin 18.2 antibody-drug conjugate. When we recognized Claudin 18.2 as a target many years ago, we saw it as a unique target that was particularly suited to an ADC approach. 'Cause Claudin 18.2 in normal healthy tissue is limited to expression in the gastric mucosa. But in GI tumors in particular, Claudin 18.2 is known to be overexpressed, presenting an opportunity with a targeted cytotoxic like an ADC to have improved outcomes versus other standard of care agents. And in addition, because of all the advancements in the ADC technology, we saw an opportunity to leverage that technology for a more stable ADC that could limit payload-associated toxicities and maximize the overall potential of the program. We in-licensed EO-3021 in 2022, and we have worldwide rights outside of Greater China. And EO-3021 is utilizing MMAE as a payload. And because of that site-specific conjugation, we're able to minimize payload-associated toxicities that have plagued other types of conjugation approaches, more traditional cysteine-based approaches. With that, and the data that we showed in August earlier this year supported all that, where we showed robust and compelling anti-tumor activity. A safety profile, which was incredibly supportive of what we thought the site-specific conjugation would give us: limited heme, liver tox, no evidence of peripheral neuropathy, no evidence of neutropenia, an overall profile that not only puts us in a great position to have potential best-in-class Claudin 18.2 ADC as a monotherapy, but also puts us in a position for it to be the more combineable Claudin 18.2 ADC. As the field moves towards combination approaches, as is often the case in oncology, we think we have a particular opportunity, versus the competition for leveraging that efficacy and safety profile for a more combineable agent that can combine with other opportunities across the spectrum when we think about lines of therapy. You had phase one data that reported out this past summer. Can you maybe give us an overview of what was reported with this program, and you know, I guess what we should expect on the next data update? Yeah, for sure. So as you mentioned, in August of this year, a few months ago, we reported the initial data from our phase one dose escalation. And in that data, we reported a 43.8% overall response rate in a Claudin 18.2 enriched patient population. And we also had a safety profile that, as I mentioned, had limited heme, liver tox, and no peripheral neuropathy, no neutropenia, all AEs that have plagued other agents. With that profile, it incredibly encouraged us in our path forward for the program, both as a single agent and in combination. And as a single agent, we moved into the expansion portion of the phase one and expect to report additional data from that phase one trial in the first half of 2025. In addition, we laid out that across lines of therapy, we're moving into combination approaches of 3021, combining with ramucirumab in the second line and combining with dostarlimab, a PD-1 inhibitor, in the first line, and expect to move into enrolling first patients in those combination approaches by the end of the year. We've layered in multiple different approaches as we move forward on 3021 'cause we've been highly encouraged by the data that we reported and highly excited about how that data has supported all the initial hypotheses we had around the program. You have a cutoff of 2 plus, 3 plus greater than 20%. So is that something that we should expect in terms of more patients being evaluated at that cutoff on the next update? And I guess, what does, you know, durability look like in your view, given that's, you know, also, I think, an important consideration from a clinical standpoint? Yeah. So, more than a few things there. First, from a, you know, we as a field, as a company and as a field, we're learning a lot about Claudin 18.2 expression. And I'm sure we'll talk about Astellas' zolbetuximab program, which we are glad to see was the first approved Claudin 18.2 targeted agent, although it's a monoclonal antibody in combination with chemo, limited to the first line and the highest expressors. But thanks to Astellas and other programs, we're learning a lot about what Claudin 18.2 expression looks like. And in gastric and GEJ cancers in particular, how we can ensure that we're focusing on those patients that are more likely to respond to a targeted cytotoxic like 3021. And in the data that we reported in August, we utilized a Claudin 18.2 enriched subset based on cutoff of 20%, 2 plus, 3 plus, as you said. At 20%, 2 plus, 3 plus, we're capturing 60% of the advanced metastatic gastric and GEJ market. So an incredible amount, sizable opportunity. And you couple that with a significant unmet need because the current agents leave a lot of room, a lot of room for improvement, gives us a meaningful opportunity to capitalize on that, not just as a field with leveraging Claudin 18.2, but as a company 'cause we believe 3021 is potentially best in class. And then as we think about the next data update, of course, you know, we're gonna continue to show that 3021 has that potential best-in-class opportunity. And that's three components, as is always the case: efficacy, safety, and durability. And on the efficacy side, 3021 has already proven that it's robust and compelling anti-tumor activity that is highly relevant for, in the phase one study, these heavily pretreated patients. On the safety side, as I mentioned, continuing to see that that safety profile puts us in a position of potential best-in-class for a differentiated safety profile that, in addition to a monotherapy approach, also puts us, keeps us, continue to give us a lot of opportunity on the combination side will be important. And durability with current agents, although it looks different depending on the line of therapy you're looking at, we think all that puts us in an opportunity to really think about having improved durability around standard of care because, as we all know in oncology, often it is the case that durability is what clinicians really wanna look to, to be able to say that they have an agent that's differentiated. The phase one data that you've reported, you know, you highlighted that the safety profile looks really good as it relates to no heme tox. You've got minimal peripheral neuropathy. Sure. You know, talk to us what the drivers of that are. Like, what's leading to the improved safety profile compared to some of your competitors that are targeting, you know, Claudin 18.2, with their ADC assets? Yeah. And if you take the field and bifurcate it for just a moment, we are utilizing MMAE as a payload. Other Claudin 18.2 ADCs are using Topo as a payload. If we take the landscape of MMAE-associated MMAE payload agents that are out there, the majority of them are using more traditional cysteine-based conjugation, which has been currently used, very well known, but is also known to be less stable, leading to more free payload, more free MMAE, resulting in MMAE-associated toxicities that could really limit their overall clinical utility. In our case, we're using site-specific conjugation to glutamine, to two specific glutamines, resulting in a very specific homogeneous DAR of 2, a more stable linker, and a limited amount of MMAE that dissociates from the ADC, which ultimately should limit the MMA-associated toxicities of the drug, which is exactly as supported in the data that we reported so far. That overall gives us a huge amount of advantage over the other MMA-associated agents that are out there. The Topo agents, while some of them have shown a really compelling overall profile, Topo as a payload has a significant amount of heme tox. And as we all know, in addition to the issues that it has itself, once you start combining with other potential agents, especially as you think about combining with agents that are standard of care in gastric and GEJ cancer in the first line and second line, that high-level heme tox will just limit the ability to combine over time. And that's another reason why we think we have a unique opportunity with EO-3021 as the more combineable ADC for improved patient outcomes. DAR of 2, what doses have you evaluated? And, you know, what are your, like, go-forward doses, moving forward? Yep. So we in the dose escalation started at one mg per kg, and we titrated up from there. In the expansion portion of the trial, which we are in now, we are evaluating two and two and a half mg per kg as our go-forward doses. And we can continue to enroll patients at those two doses for the foreseeable future. And then, as it relates to safety, you know, Claudin 18.2 is well expressed on the GI, and many companies have faced, you know, GI-related events. How do you minimize for GI-related tox with 3021? Yes. And you may remember, and others may remember, that our partner CSPC reported initial data, a couple of years ago at ASCO. And their initial data showed, as expected, GI, GI, adverse events. What we did in our phase one is we implemented anti-emetic treatment, pretreatment, as well as to mitigate potential nausea and vomiting, which is known to be on-target, off-tumor toxicity with Claudin 18.2. It's known across the class. And in the data that we reported in August, that pretreatment with the anti-emetics significantly reduced the amount of vomiting that patients experience, which just helps to improve the overall profile of having a drug that is very tolerable for patients and that gives us an opportunity for thinking about further development. Got it. So let's say next update we get, you know, response rate similar to what you've previously reported or in that neighborhood, encouraging duration of response, minimal toxicity. What are the next steps for the program, after that update? Would you go into a phase two trial, or could you go into a potential pivotal, like study? Yep. So all great questions. So even currently, as well, at least as we said, by the end of the year, we're moving into dose escalation for the combination approaches for 3021, and we're gonna continue to move that forward in parallel with monotherapy. Once we get to the first half of 2025 update, I think even beyond that update, a big part of the path forward is gonna continue to be continuing to execute on the expansion portion of the trial in monotherapy and driving forward the combination approach. As you mentioned, ultimately, we need to think about how we're gonna make the move towards registration. We think the move towards registration looks different depending on the line of therapy. In particular, for example, in second-line gastric and GEJ cancer, the current standard of care is ramucirumab plus paclitaxel, which we see an opportunity for combining 3021 with ramucirumab and removing the chemo portion of that combo and having a potentially new standard of care with a targeted cytotoxic that has a similar mechanism of action to paclitaxel. There you know current standard of care is 30 with RAMPAC is a 30% response rate. Durability is around four months. Significant amount of opportunity to improve on that for those patients that are in the second-line setting. In the first-line setting, of course, immunotherapy plus chemo is the mainstay. Response rates are in the 50-60% range, and PFS is in the seven to nine months range. And there we see an opportunity for combining 3021 with something like dostarlimab, which we announced the agreement with GSK to evaluate 3021 with dostarlimab and think about leveraging that MMAE is known to induce immunogenic cell death. And is there a synergistic approach that we could take advantage of in combining with PD-1 inhibitors? We also think in the first line, because of that opportunity that safety profile that we have, we have an opportunity to think about combining with a complementary chemo agent in the first line for even more improved patient outcomes, an opportunity that other agents potentially may not have. So that gives us a lot of opportunity in the second line and in the first line. And how we think about moving the walk towards registration is gonna look slightly different between the two, as is always the case based on the line of therapy. But we look forward to reporting further data that continues to support that that path forward makes a lot of sense. A combination approach, initiating with second line with ramucirumab, first line with PD-1. Correct. Potentially first line with the cytotoxic agent? Cytotoxic agent, we think we have the opportunity to. That's not part of the plans initially. Right. Initially, we're gonna look at 3021 plus dostarlimab. But as we think further down the road and we continue to generate data that support that this safety profile continues to show what it currently has shown, we think there is an opportunity for thinking about adding chemo to that first-line approach for even improved patient outcomes in the first-line setting. When would you make that decision? Is it after you've seen the combination data with PD-1, or would you look at potentially initiating a combination with the chemotoxic before that? TBD. I think we need to do more work on monotherapy. We need to do more work first with the combo with dostarlimab and understand that based on the overall profile and see what the right timing of it, but scientifically and clinically speaking, there certainly is a lot of rationale to think about adding chemo onto the regimen as long as you think about it in terms of a complementary chemo approach. The combination would be evaluated primarily in gastric and GEJ, or would it be other tumor types? We, as a company, made the decision a while ago, although we all know, and as we've talked about, Claudin 18.2 is known to be expressed in a range of solid tumors. We made the decision as a company to focus on gastric GEJ, not just because of the initial clinical validation, but also because, we, as a company, think that is the area where there's the most significant amount of unmet need and the opportunity that an agent like 3021 had a significant opportunity to capitalize on that for improved patient outcomes. Down the line, is there a potential to evaluate esophageal, for example, or pancreatic? We enrolled. Those patients were allowed to be enrolled in the dose escalation portion of the phase one, but again, we focused on gastric and GEJ early on as a company. Certainly, there is an opportunity in esophageal and pancreatic overall for the agent, but we, in our immediate plans and our near to medium term, are gonna remain focused on gastric and GEJ. Got it. And then so you had mentioned Astellas. Astellas, you know, was zolbetuximab approved in certain parts of the world, for gastric GEJ. How does your program compare to that? Mm-hmm. You know, you talk a little bit about the expression levels where you're hitting a, you know, much wider target. But beyond that, you know, the benefits of ADC versus a antibody approach. Yeah. Yeah. And so we were incredibly pleased to see zolbetuximab approved. And as we all know, we're here to develop better, better outcomes for patients. And an agent like a targeted Claudin 18.2 monoclonal antibody like zolbetuximab was a huge step forward, not just for patients, but also as the field, as we continue to show that 18.2 as a target was an opportunity for improving those patient outcomes. And we, as a company, are benefiting from that, especially when in an area where we know that testing is gonna be important in identifying those patients that are more likely to respond. Zolbetuximab is a naked monoclonal antibody and is in combination with chemo in the first-line setting only. And in addition, zolbetuximab's approval is limited to the highest expressors of Claudin 18.2, so those that are expressed in 75%, 2 plus, 3 plus in the first-line setting. So at that cutoff, they're limited to about 35%-40% of the patient population, still leaving a significant amount of room for some patients that are in that expression level below that, that still have limited treatments and are not applicable to zolbetuximab. But we think it's an incredible first approval for the field and an area where we think an ADC approach, because you're delivering as a targeted cytotoxic, can quickly leapfrog something like a naked monoclonal antibody for overall better outcomes. And we look forward to 3021 continuing to show that it's one of them. Got it. And then I guess, you know, so this asset came from CSPC in China. They're running a trial in China. Do you collaborate with them in terms of data sharing? And would we get any updates from the China trial that would inform on the US program over the next year or so? Yeah. So, typical arrangement, we are constantly speaking with CSPC on a regular basis, and we certainly share clinical updates with them as they do with us. And we, as a company, continue to be very confident that the data we're showing and that we did show in August and will continue to show is certainly supportive of what the drug can do overall, regardless of the patient population. But CSP and the CS themselves are their own company, and they certainly have different requirements when it comes to disclosing data. And at this point in time, they haven't shared publicly any plans to share additional data from their program, which they call SYSA1801. But you're getting that read-through on a real-time basis that potentially informs you of decisions here. Yep. And that can certainly help us continue to make the best decisions we can for 3021 as we think about the path forward. Great, and then you've got a second program, you know, targeting HER3. Can you talk a little bit about, you know, this asset. Mm-hmm. Why target HER3 with an ADC approach? Yeah, for sure. And as I said in the beginning, we are very bullish on the fact that advancements in ADC technologies gives us an opportunity to develop ADCs these days that can resurrect some targets that previously just did not leverage good patient outcomes. We think HER3 is one of them. And Daiichi Sankyo has already shown that a HER ADC approach with HER3 certainly has legs and certainly can be meaningful. But we see a further opportunity for a differentiated HER3 ADC. And in April at AACR, we presented a poster which had a tool program, a tool molecule utilizing our former lead program, seribantumab, traditional cysteine-based conjugation, and a DAR of 4, and showed how in preclinical models that resulted in anti-tumor effect that was incredibly meaningful and differentiated. And we think there's an opportunity for driving a program like that forward. Most of the field is focused on topo as a payload, and in that poster, we used MMAE payload. Though we haven't named a development candidate for the HER3 ADC as of yet, we said we're gonna do so by the end of the year. We look forward to moving forward a clinical candidate towards the clinic that will take advantage of the fact that most of the field is limited to topo and that we see an opportunity for a differentiated ADC that has really improved outcomes relative to the field. Is it a site-specific conjugation? Are you using similar technology from CSPC, or is it a different? We haven't said specifically, but obviously, we are incredibly bullish on site-specific conjugation overall vis-à-vis our 3021 program. And we named development when we named the development candidate again by, as we said, by the end of this year, so relatively soon. We look forward to how we think that ADC approach that we're utilizing there can lead to better outcomes overall. And so you named the development candidate. I assume then at that point, you would initiate IND-enabling studies. Correct. How long would that take, before you're able to file an IND? Yeah. And we certainly haven't given any specific guidance on that to date, but typically, you can expect an IND is about 12 to 18 months, from when you name a development candidate. And that's probably a typical timeframe that's gonna be relevant here as well. So I guess in the 2026 timeframe is probably, like, a reasonable scenario. Yes. For an IND. And so I guess from a phase one standpoint, like, what solid tumors overexpress HER3, where you would potentially evaluate this program? Yes. And Daiichi Sankyo has done a lot of breast cancer, non-small cell lung cancer, pancreatic cancer. Significant HER3 as a target is known to be significantly expressed across a range of solid tumors, with those three being sort of top of the list. And a clinical development program for that type of approach can be very robust because there's a lot of opportunity and a lot of wood to chop in those markets. Over the next 12 months, you've got, you know, a development candidate too that'll be named shortly, initiation of the combination with 3021. We've got monotherapy data first half next year. I guess, could we add combination data by year-end 2025 in that list? We haven't said specifically. We look forward to talking more about the timing of combination data once we start enrolling patients in the trial. But, you know, as we said when we started the phase one dose escalation and monotherapy, that a first update once you start enrolling patients, general timeframe is 12-18 months from when you start. So certainly, we look forward to disclosing combination data as quickly as it's relevant. Great. Thanks, Joe, for attending the Piper Sandler Conference. It's great to have you. Thank you, Biren. Thank you. Appreciate everyone for joining, and thank you again to the Piper team. Good morning, everyone. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler, and thank you for joining us this year. This is the company's 36th, but my 21st or, no, 20th. We skipped one year Healthcare Conference. Pleased to have you all here for this momentous occasion. Before I begin, I am required to point out certain disclosures regarding the relationship between Piper and Tempest, our next presenting company, which are posted at the back of the room and also at the registration desk. Tempest is developing amezalpat for first-line liver cancer. The company shared some really impressive data in combination with Tecentriq and Avastin. We'll obviously focus much of our presentation on that today. I'm pleased to be joined by my good friend Steve Brady, CEO, and also Sam Whiting, PhD, Chief Medical Officer. Thanks, guys, for being with us today. Thank you for having us. Thank you. So amezalpat, or what used to be TPST-1120, targets PPAR-alpha. Maybe you guys can start off by describing the biology around this target and how it's working. Yeah, I can take that. So, PPAR-alpha, the target of the drug, is a transcription factor that is involved in regulating the metabolism of fats as a source of energy. The cells in the body use a variety of sources, materials for energy, glucose being a classic one. Fats are interesting because in the setting of cancer, our starting hypothesis was that the metabolism of fats is important to some tumors as a source of energy to grow, proliferate, and metastasize in the body. So part of their dangerous biology of cancer involves metabolism of fats. Then, secondarily, or actually not really secondarily, equally important, there is a component of the immune system, what are called immune suppressor cells, that also preferentially metabolize fats as a source of energy. And that's in contrast to immune effector cells, the killer immune cells, which are metabolizing glucose.