Hello, everyone. Thank you so much for joining us at the Jefferies Global Healthcare Conference 2025. We're kind of winding the day down now, but it's my distinct honor and pleasure to be hosting PMV Pharmaceuticals. We're going to get a perspective today from the Chief Development Officer, Deepika Jalota. Deepika, welcome.
Thank you so much. It's a pleasure to be here.
Maybe we could just get directly into the story. Maybe before we get into the questions, can you just provide us an overview of PMV, the currently active programs, and where the company sits today?
Sure. PMV was created around 11 years ago by three gentlemen: David Mack, who's our CEO; Arnie Levine, who essentially discovered the role of p53; and Thomas Shenk, who's a world-renowned virologist. The company was formed around harnessing the power of p53. We've progressed through our phase I program, evaluating Rezatapopt, which is targeting the TP53 Y220C mutation in solid tumors. Based on our phase I data, we were able to progress into our phase II registrational study that is currently ongoing. We started enrolling last year, and enrollment is going quite well. We plan to complete enrollment by the end of this year. We do plan to have an interim analysis in the middle of this year, where we will be sharing data from approximately 50 patients that have had at least 18 weeks of follow-up, and of which about 20 of those patients will have ovarian cancer.
With that, we would progress to an NDA submission, hopefully by the end of next year.
Interesting.
There's a lot for us to look forward to with regards to the Pinnacle study.
Absolutely. Maybe taking a step back, you discussed the founders, the founding story of the company. What is the role of the p53 protein, and what are key approaches to targeting p53 mutations?
Sure. P53 protein is essentially a tumor suppressor that plays a crucial role in regulating the cell cycle and preventing cancer formation. Essentially, when this is operating as it should, what you have is P53 driving when there is damaged DNA cells and cell proliferation due to damaged DNA. Essentially, you will have P53 driving cell cycle arrest, apoptosis, as well as cell senescence. When P53 is mutated, it's no longer acting as a tumor suppressor in preventing cancer growth and proliferation of cells that create cancer. As a result, what we're doing is Rezatapopt is essentially serving as a small molecule that docks into that mutant protein that's formed when the tyrosine is substituted by cysteine.
That's the Y220C?
That's Y220C, exactly. What ends up happening is when the small molecule docks into that pocket that's formed with that mutant protein, it stabilizes into the wild-type conformation, and it enables it to do what it should as a guardian of the genome and have that downstream transcription and act as it should.
Maybe talk a little bit too about you have a very interesting approach, I find, where it's both kind of precision medicine, but also kind of broadly applicable across tumor types. Can you talk about how common the Y220C mutation is and kind of your interesting approach?
The Y220C mutation is present in approximately 1% across all solid tumors. When you look at ovarian cancer specifically, it has a frequency of about 3%. That is what drove us to design our basket study as it is, with five cohorts, where we are evaluating Rezatapopt in ovarian cancer, where we are looking at 42 patients there, and then 18 patients each in cohorts two through five, where we will be looking at breast cancer, lung cancer, endometrial cancer, as well as all other solid tumors.
You're in phase II, but you had a very interesting phase Ib across multiple solid tumors. Can you take us through and review kind of that data set, what made you really excited with it and spurred on development into this phase II?
Absolutely. We were able to show preliminary efficacy across six tumor types, and that includes ovarian cancer, breast cancer, small cell lung cancer, prostate, endometrial, as well as head and neck cancer. This gave us, basically resulted in a 38% confirmed overall response rate at the recommended phase II dose, which is 2,000 milligrams q.d. administered with food. In addition, we were able to observe a median DOR of seven months. Based on this data, it helped us go down the path of a basket study and evaluating a tumor-agnostic approach for Rezatapopt.
How was safety in that phase Ib?
Safety was it was well tolerated. Essentially, what we saw was primarily grade one and grade two treatment-related adverse events, and they were primarily GI toxicities that were mitigated with food. We see that reduction in GI toxicity, but there's a dual benefit in that when you administer Rezatapopt with food, you have a 40% increase in exposure. That dual benefit is there.
Is administration going to be with food in phase II?
That is correct.
Okay. Now, there was an interesting kind of finding in the phase Ib, and that at least it appeared that KRAS status impacted efficacy in the phase Ib. Can you talk a little bit through that, and then also kind of any mechanistic reasons behind this, or just it's idiosyncratic, and how does that impact the baseline characteristics decisions you made for the phase II?
What we observed in phase I is that when a patient had a KRAS mutation that was co-occurring with TP53 Y220C, we ended up seeing clinical activity, but it was not as durable or having the same depth of response as what we saw in patients that were KRAS wild type. As a result, in the phase II study, we decided to enroll patients that are KRAS wild type as well as being TP53 Y220C mutated. From a mechanistic perspective, as we all know, KRAS is an oncogenic driver mutation. When it is present and it is mutated, it really confers a worse prognosis in patients. When you look at some of the literature around colorectal cancer patients, when there are co-occurring TP53 mutations as well as KRAS mutations, there was an observation of this weakened anti-tumor immunity.
The mechanistic rationale behind what we observed in the phase I study is still being further elucidated, and we're working through that. That being said, this opens up the opportunity to have a combination approach with pan-KRAS inhibitors, and that is something we are currently evaluating to address these patients of extreme high unmet medical need.
Yes. And also, though, KRAS and both Y220C mutations. They're going to be picked up on a standard panel?
Absolutely. That's a great point. How we enroll our patients is through identification through local NGS testing that's already being performed at our study centers. KRAS is already on the panel, as well as TP53 Y220C. Patient identification has not been an issue for our phase II study or phase I because it's prolifically present in all of the different assays that are available from a sequencing perspective, such as Foundation Medicine, Caris, Tempus, and many others.
In terms of maybe I'm a little bit less familiar, but in clinical practice, it's very easy to use these panels to identify which drugs are going to be suitable for these patients.
That's correct. These reports do read out specifically what mutations the patient has. For example, if you look at the Foundation report, you will see when there are actionable mutations. For those targets where there are clinical trials available, they're also listing those. Keeping fingers crossed, if we do have an approval in the future, we will be listed as an actionable target.
Oh, interesting.
To that point, TP53 has already been watched by physicians because it confers a worse prognosis than those that are not TP53 mutated, so those that are wild type. As a result, it's already on the radar for physicians to keep an eye out for.
Okay. Very cool. Maybe before getting into the phase II, you had some alignment with the FDA in July of 2023 with regards to the phase II study design and the registrational path. Can you remind us what was discussed there, what was concluded, and how did that inform your phase II?
Absolutely. We discussed our study design, which we were able to get alignment on with regards to proceeding for potential registration in the future, as well as getting alignment on our recommended phase II dose, which everyone knows we all have to navigate Project Optimus, which we were effectively able to do with the agency.
Great. What are the important study features for phase II? You mentioned all the cohorts and the numbers, but there is a specific cohort that is going to be a little bit enriched. Maybe take us through why you are doing that.
Sure. As mentioned earlier, ovarian cancer is going to be a higher number of patients with 42. This is due to the frequency of the mutation in ovarian cancer patients at around 3%. These patients will have platinum-resistant or refractory disease, very high unmet medical need for these patients. With regards to the bar from which the lower bound of the 95% confidence interval has to exclude, it's 12% because that represents standard of care for these patients. Our phase II study is designed to target a 30% response rate. We look forward to sharing more data in the middle of this year.
Yeah, in the middle of it is.
It's very soon.
Very soon. Imminent or just very soon?
It's very soon.
Soon? Okay. Let's see. What is the phase II study power to show on ORR? Yeah, what power or yeah, and what powering overall? And then also maybe DOR kind of assumptions too.
Sure. For the ovarian cancer patient population, it is powered to show 85% to target that 30% overall response rate. We also have pre-specified another patient population, which is a tumor-agnostic cohort across the basket, and that is powered at 95%.
What response rate?
For 30% response.
Same response rate, different powerings.
Just based on the sample size because it's 42 patients for ovarian cancer. Exactly.
DOR assumptions? You had talked to the agency about kind of expectations there.
Right. The expectations from the agency are typically a median DOR of six months. And based on the phase I data, we were able to demonstrate a seven-month median DOR.
Okay. Great. How is enrollment proceeding for the phase II? You mentioned when interim are expected, but in terms of the breakdown, how many patients will be ovarian at the interim?
At the interim, we expect to share 50 patients across all cohorts with at least 18 weeks of follow-up, of which 20 of those patients will have ovarian cancer. From an enrollment perspective, enrollment is progressing according to our projections, where we will complete enrollment by the end of this year for those 114 patients.
Complete enrollment for all 114 patients by the end of the year. Can you talk us through also just NDA plans, final data plans? Any type of timelines would be helpful.
Absolutely. With regards to our study, as mentioned, we have two pre-specified populations: ovarian cancer cohort, as well as the basket for tumor-agnostic. With regards to the approach that we will be taking, we can go in either direction. When you look at tumor-agnostic approvals across the board from a precedence perspective, there have been nine approved to date, of which six started with an anchor indication and built their way towards a tumor-agnostic approach. It's really only the NTRAK gene fusion targeted agents that were able to get that initial tumor-agnostic approval from the start. That being said, most likely we will use ovarian cancer as that anchor indication to work our way towards tumor-agnostic label.
Interesting. So will that be an accelerated approval based on ovarian?
That's correct. It would be an accelerated approval. We would have to complete a post-approval commitment in order to transition to a full approval. What that could look like is something that we will be aligning with the FDA on. What we would anticipate is continuing enrollment in our existing study.
Yeah.
Continued follow-up would be sufficient.
Sorry, just to really clarify, what would be the catalyst to file for accelerated approval in ovarian, and what kind of data cut do you need when that's?
Right. The interim would not be serving as that final analysis. We would need to essentially have those 42 patients followed up for at least six months' durability of response. What that means is, if you do the math, we would end up having an NDA submission at the end of next year, and we would have final analysis data in probably the second half of next year.
Great. Great. Any other key takeaways on the phase II study we may have missed, or have we hit most of the main points?
I think we've hit most of the main points. I think from an enrollment perspective, as mentioned, patient identification has not been a challenge. We continue to enroll according to projections.
Great.
Quite excited about the interim.
In terms of you also mentioned potential use in combination with KRAS targeting agents. Any announcements or plans around or high-level thinking about those? Would that, could you potentially, would that be an investigator-led study, or is that something that you would consider internally?
We are evaluating all options. We have not announced anything formally yet, but these options are on the table as to whether it will be an investigator-initiated study or sponsored by PMV. That being said, we do have an ongoing study where MD Anderson is the sponsor. They are also working with MSK in the relapse refractory AML-MDS patient population. This study is currently ongoing, and we had announced the initiation of enrollment earlier this year.
What are the differences in that study compared to your phase II? Is it in combination with other drugs, different patient populations?
That's right. It is a different patient population, relapse refractory AML-MDS. It is in combination with azacitidine. It is approximately 25 patients that we're planning to enroll in that study, or I should say MD Anderson is planning to enroll.
Yeah. It's great that you have the interest from them.
Yeah, absolutely.
Awesome. Any other you had considered, you're always considering kind of new development candidates. Any thoughts, high-level thoughts about potential announcement of future INDs or anything of that nature?
We do have an undisclosed target that we're working on actively. It is currently in lead optimization. We are progressing that through preclinical development, and the hope is to have an IND in 2026 that we would be sharing further details on at a later time.
That's still on, I think you could, it's still on the p53 hypothesis overall.
It would be orthogonal to p53.
Oh, okay. Okay. Great. Fantastic. I guess kind of last question on my end. What is the company's current cash position, and kind of what does your runway support?
Our runway supports us until the end of next year, and we have approximately $165 million in cash. This will lead us to that NDA submission timeframe from a cash runway perspective.
After that, you'd probably need some additional support for launch, etc.
That's correct. Yes.
Okay. Great. Any other things high level? I'd be happy to open it up to questions if you'd want any, but I'm going to leave it for you for the last words on PMV.
We're truly addressing an unmet medical need. We're excited by what we've delivered from a phase I perspective and really looking forward to sharing our data for the phase II interim analysis. It's we're drugging p53, and that's been something that's been evasive for many years. It is something to look forward to.
We've definitely noticed just the excitement and the exceeding the enrollment that you previously, it was previously 30, now it's 50. We're really excited to see that these centers are excited to use a drug. I just want to say good luck before the data, and we'll see it soon enough. Thank you so much.
Thank you.