All right. Good morning, everyone, and thanks so much for making it out to the TD Cowen 46th Annual Healthcare Conference. I'm Steven Iannone. I'm here on the biotech team, and with us today is the management of PMV. As you'll hear, and as you no doubt know, and it goes the novel p53 or various we've got with the chief sir and of course, the CEO. We'll be hearing a presentation from them, and then if time, we're gonna take some questions. Yeah, take it away.
Great. Thank you so much, Steven. Present result today at Cowen Conference. As you may be aware, PMV Pharma was founded on the premise of harnessing the power of P53 to treat cancer. Our lead candidate, rezatapopt, is a first-in-class investigational P53 Y220C reactivator. P53 Y220C mutation has previously been considered an undruggable target, but it is found in around 2.9% of ovarian cancer patients as well as 1% across all solid tumors. As you may have seen, our phase 1 data that really provided that proof of concept was recently published in the New England Journal of Medicine. Currently, we are actively enrolling in our pivotal phase 2 PYNNACLE study where we will be going through the interim study results, which has demonstrated favorable efficacy and safety to date across multiple tumor types.
Based on the data that we are seeing, we are planning to submit an NDA submission in the first quarter of 2027, specifically in the platinum-resistant refractory ovarian cancer patient population. We have a strong balance sheet that enables us to have a cash runway through first quarter of 2027. Just to highlight the data that we're seeing so far, it's quite compelling. In our interim analysis set, across all cohorts, we are seeing a 34% overall response rate with a median duration of response of 7.6 months. In ovarian cancer, which is a strong and significant unmet medical need, we're seeing a strong response rate and benefit of an overall response rate of 46% with a median DOR of eight months.
This is what is going to drive us with that initial registrational opportunity that we will be pursuing in that platinum-resistant or refractory patient population in ovarian cancer. As you know, TP53 Y220C mutation presence leads to a worse prognosis. What we hope to deliver is having this opportunity to have a novel biomarker selected chemo alternative therapy for patients. What we'll be walking through today is the phase 2 interim data. We'll dive into the ovarian cancer cohort in more detail. We'll also walk you through our NDA submission strategy and what comes beyond our monotherapy program. Just to refresh you on our phase 2 study design, we are currently enrolling actively across the globe with 70 sites that have been activated so far.
Our patient population is aged at least 12 years of age, and they have locally advanced or metastatic solid tumors harboring that TP53 Y220C mutation. In addition, these patients are KRAS wild-type. These patients have received prior standard of care or are ineligible for appropriate standard of care. This is a basket trial of approximately 200 patients, and we're dosing patients at 2,000 milligrams QD with food. We have a total of 5 cohorts. Cohort 1 is ovarian cancer, where we are enrolling a total of 120 patients, and cohorts 2 through 5 has 18 patients each in lung, breast, endometrial, as well as all other solid tumors. Our primary endpoint is overall response rate per blinded independent central review, and we're looking at the data across all cohorts as well as the ovarian cancer cohort.
This study design enables us to accelerate development in key tumor types via a streamlined single-arm study design. Let's dive into the demographics and baseline characteristics across all cohorts. This is across 112 patients, where we have a median of 65 years of age in our patients. When you look at the demographics, about 73% of our patients are female. This is driven by the tumor types that we have enrolled, which is heavily weighted towards ovarian, breast, as well as endometrial. The ECOG performance status is well-balanced between ECOG performance zero and one. The prior lines of systemic therapy, there's about a median of 3 with a range of 1-10, which highlights the heavily pretreated patient population that we've enrolled so far. Let's dive into the ovarian cancer demographics and baseline characteristics.
In the 51 patients that we have in ovarian, the median age is 67, again, well balanced in ECOG performance status between zero and one, with a median of four prior lines of therapy with a range of 1-10. This further highlights that with three or more prior lines of therapy, we have 73% of our patients that are heavily pretreated. All of our patients have received platinum-based therapy, and around 78% have received prior bevacizumab. Around 60% of our patients have received prior PARP inhibitors. You look at platinum status at study entry, around 60% are platinum-resistant and 35% are platinum-refractory. Just to highlight, in many clinical trials, platinum-refractory patients are excluded, you can see here that these patients are included in our study.
When you look at platinum refractory and primary platinum refractory specifically, it's around 14%. This is a really tough to treat patient population that we're enrolling. When you look at the high-grade serous histology, it's around 96% of patients, so quite a few of our patients have this histology. We've observed responses across 8 different tumor types. When you look at the data across all of our cohorts, as mentioned earlier, we have a 34% response rate with a 7.6-month median duration of response. When you dive in more deeply into ovarian cancer, it's a 46% ORR with an eight-month median DOR. Of note, when you look at the post-data cutoff, in ovarian cancer specifically, we have reached a 50% response rate, where we observed two additional responses within these 48 patients that are part of this data cut.
Of note, in endometrial cancer, even though it's an early signal, we are seeing a 60% response rate. It's quite a compelling efficacy signal in a monotherapy setting that we are observing here. When you dive in a little bit more deeply into ovarian, we have looked at multiple subgroups. When you look across these different subgroups, what we're observing is a 40%-50% consistent ORR. It's quite compelling to see this. Let's dive into platinum-resistant and refractory. You can see here it's 48% and 44%. You look at prior therapies, you're still consistently seeing that 46%-52% response rate. With folate receptor alpha and positive and negative, you're also seeing a consistent response rate. In essence, it's a compelling efficacy that's observed regardless of prior treatment received in a heavily pretreated population.
In addition, of note, when you look at single agent non-platinum-based chemotherapy, we are clearly exceeding those ORRs with what we're observing here. Here you can see the compelling target lesion reduction that we have observed in the majority of patients. In teal, you can see the ovarian cancer patients that are represented, as well as the other tumor types that have observed responses, as well as the tumor lesion reduction. Here you can see that we have observed a rapid time to response that's very much consistent with precision oncology therapies. We've observed a median time to response of 1.3 months across all cohorts, as well as the ovarian cancer cohort. As noted earlier, the median duration of response is 7.6 months across all the cohorts and 8.0 months in ovarian.
Of note, 40% of our patients remain on treatment as of the data cut. Turning to the safety and tolerability profile, it's quite favorable. Most of our treatment-related adverse events were grade one and two in nature. What you typically see, when patients are treated with rezetapopt, there is nausea, fatigue, blood creatinine increase, as well as ALT increase. Lab abnormalities were manageable as well as monitorable, with most of the cases being transient and reversible. Of note, four patients did discontinue treatment due to treatment-related adverse events, which is a quite a low frequency. When you compare our experience to the phase 1 experience, we are now administering food for our patients when they are taking rezetapopt, and there has been a significant decrease in the incidence of GI treatment-related adverse events.
Here is our data from a ctDNA perspective, which supports the on-target activity that we're seeing. Basically, we are observing a 91% reduction in the TP53 Y220C VAF, which is quite a compelling story. With that now we'll transition to what comes next from an NDA submission perspective. As you can see, ovarian cancer is our lead indication. This has been informed by FDA feedback. We are actively enrolling in our ovarian cancer cohort. We have enrolled about 75 patients to date. As a result, we envision that we would have a primary analysis data set by the end of this year, which would then lead us to an NDA submission in the 1st quarter of 2027, thereby enabling a potential U.S. launch at the end of 2027. We will be seeking accelerated approval.
As mentioned earlier, we are enrolling a total of 120 patients, and this enables us to essentially fulfill what we would need from a post-approval requirement perspective, since that is required to convert to full approval ultimately. rezatapopt is well-positioned for success in ovarian cancer and beyond. What we offer is a biomarker-directed approach, we have convenient oral administration compared to what you see in the platinum-resistant ovarian cancer population from a treatment landscape perspective. In addition, we are a chemo alternative and our adverse events are quite manageable in comparison to what you see in the treatment landscape currently, mostly ADCs as well as chemotherapy. You may be curious as to how easy is TP53 Y220C from an identification perspective.
It is on all of the existing NGS panels that we've evaluated to date, most notably Foundation, Tempus, Caris, SOPHiA GENETICS, as well as MSK-IMPACT and MSK-ACCESS. Reimbursement of NGS testing is widely covered by Medicare and private insurance for qualifying patients. Patient identification has not been an issue for us during the clinical study, and we do not envision this being a challenge or barrier for commercialization. When you look at the second-line plus ovarian cancer potential, it offers a meaningful market potential. We have about 1,700 patients that are addressable second-line plus patients, and this results in a US market potential of about $350 million-$420 million, where globally you would expect to see around $520 million-$630 million.
We would also, beyond this, be positioning and further pursuing label expansion beyond ovarian cancer. As far as future opportunities to grow rezatapopt, we will of course be continuing to monitor our patients in the existing study across all of our cohorts, including endometrial as well as breast. We are also evaluating opportunities to look at rezatapopt in combination with other therapies. Currently, we are partnering with MD Anderson, where they are running an investigator-initiated study in heme malignancy in relapsed refractory AML/MDS in combination with azacitidine. Once this study reads out, there would be the potential to further evaluate newly diagnosed AML/MDS patients in combination with azacitidine and venetoclax. From a solid tumor perspective, we would be looking at combining with bevacizumab in the platinum-sensitive ovarian cancer space, which would enable us to go into earlier lines of therapy in ovarian cancer.
The other option that is on the table is pan-KRAS inhibitors in lung, pancreatic, and CRC. This enables us to capture that opportunity for those patients that are not currently being enrolled in phase 2, where they are KRAS mutated, since our patient population right now is KRAS wild-type. With that, I hope you could see that we have demonstrated compelling efficacy with our phase 2 interim analysis results, and we have a defined registrational path for rezatapopt, where we have observed a 46% ORR in ovarian cancer with a median DOR of eight months. This NDA submission is planned in the first quarter of 2027 in the PROC patient population. Currently, our cash runway will last us through the first quarter of 2027. With that, take any questions.
Thank you very much. Thanks so much for providing the update. Maybe before we begin, the publication in NEJM recently was really exciting. Anything you want to highlight from that, Deepika?
Yes. It's quite exciting to see how much interest and enthusiasm the investigators have for finally we're drugging TP53. I think it's been a target that's been the holy grail for a very long time, over 40 years now, since it's been identified. We're quite excited by the fact that New England Journal of Medicine has published our data from a phase one perspective, and it's very consistent with what we see in phase two, where we observed multiple responses across multiple tumor types. We're excited to bring forward all of that to phase two and what we're seeing here.
I think that one of the kind of key questions folks continue to have is about the market size in the second-line plus, you know, platinum-resistant ovarian. Maybe can you give us an update or remind us what % of patients progress off of platinum chemo. Then what potentially the incidence could be in the U.S. yearly. Then what the strategy is from expanding from the initial U.S. to potentially the EU and, you know, U.K. setting, which might see a little bit more uptake and opportunity?
Absolutely. When you look at the progression of patients from chemo in the platinum sensitive stage, typically it's around 80% of patients that ultimately progress to become platinum-resistant. When you look at our second-line plus patient population that's addressable from an ovarian cancer perspective, it's around 1,700 patients, of which 900 are in the U.S. That being said, it's, we see it as a compelling opportunity, as you saw, in the U.S. market potential as well as globally. We are, of course, focused on what we'll be pursuing as an NDA strategy in the U.S., but we will continue to engage with global health authorities around what would come next beyond that, especially with Europe and Asia.
Is that a plan to do independently, or would you partner?
I think all of the options are on the table. David?
Yeah, absolutely. I think we do have an opportunity in this very focused population and call point to commercialize on our, on our own. I think, you know, a recent example of a smallish biotech going to market, and particularly in the ovarian space, is Verastem. You know, there's a model there that is doing well. In addition, given the activity that we're seeing in PROC, you know, this is a compelling drug that if you have a bag, it's another, it's another therapy that you can put in that bag. You know, I think, we're looking at options moving forward, but they're there, so go it alone or in partnership with someone who already has that commercial infrastructure and a, and a lower cost of capital.
Makes sense. Given that you're already seeming to gear up towards the regulatory submission, how have any conversations with regulators happened? You know, any highlights from those if you have anything you wanna add?
Sure. Yeah.
Yes.
July of last year, right?
That's right. We interacted with the agency last year in the July timeframe. They were very supportive of the data that we have shared with them already to pursue the platinum-resistant refractory ovarian cancer population. We will be continuing to engage with them in the second half of this year as we get closer to that primary analysis population. We're quite excited.
Can we expect an update or, once the minutes come out from that?
Yes. I think in the second half of this year, we would be providing a data update around our progress as well as outcomes from health authority discussions.
Gotcha. Now, maybe remind us the 70 patients that have been enrolled, globally, what's the split between US and ex-US, in, yeah, in terms of sites?
Yeah. It's about half and half. It's about a pretty even split between the two. We have some patients coming out of Asia-Pacific as well.
In case anyone has questions, please do feel free to raise your hands.
That's great because it's a pretty clear story, so.
You mentioned the, a data update in Q, in H2, a conference that would be, you know, that you might, be thinking about.
Yeah. That's it. Go ahead.
Go ahead. It's just, you know, we do like presenting at medical congresses. Second half of this year, we look forward to that data update. You can probably guess what meetings we're looking at.
You've also had some pretty interesting efficacy initially in the endometrial setting. Can you tell us about any efforts that you've taken to increase enrollment across other tumor types, endometrial, breast as was mentioned as well, any others?
Yeah.
Yeah. It is a quite a compelling story we're seeing in this early data set. We continue to engage with our sites directly. Since TP53Y220C is widely identifiable from an NGS perspective, we're just continuing to increase awareness around rezatapopt, engaging with our sites, and just medical education that we're doing. Also, we are partnering with patient referral services as well.
In terms of the investigator-initiated trial in AML/MDS, can you maybe remind us what was the initial signal that you saw that motivated that and then kind of what the future of that might hold from a potential regulatory standpoint?
Sure. I think in the AML/MDS community, there's just such a high unmet medical need, especially when it comes to TP53 mutated patients. It was a lot of incoming interest from these physicians that are focused on heme malignancies because there's just not much left for patients, right? And especially when they're TP53 mutated, standard of care is not very effective. As a result, based on this incoming interest, we especially from MD Anderson, we decided to partner with them and have this investigator-initiated study get off the ground. They're quite excited. They continue to have such amazing interest across the globe in this study overall.
Remind us of the timeline on that, on the trial.
It's still early days. Since it's an investigator-initiated study, it kind of takes its course from a timeline perspective. We would be giving updates as soon as we have some interesting information to share as it progresses. Enrollment is continuing to progress.
Sure.
Yeah. really interesting presentation. Thank you. Just a quick question. Have you characterized CNS metastases in any of the patients that you've enrolled across all the tumor types? Have you looked at, like, CNS efficacy of rezatapopt?
It's a great question. Just to highlight, we have excluded primary CNS tumors given the limited blood-brain barrier penetration. We have looked at CNS metastases. Some of our patients do have it. I don't have the percentage offhand, but it does not necessarily confer a problem, so to speak, from a response perspective.
Okay.
Yeah.
Thank you.
In terms of the, you know, the results that came out first in September and were later presented at the triple meeting, from PYNNACLE, we also saw a slight increase in the response rates between, you know, the two data cuts and, you know, what could we see in terms of a continuing response? 'Cause your time to response is pretty fast, but, you know, the progression of a response from, like, you know, the depth of the partial responses, how is that informing what you might see in the future in terms of, you know, potentially getting better?
Yeah. I think we're already excited that we're post data cutoff at a 50% response rate, and I think what we'll tend to see is that increase in durability of response. We're also hoping for as we continue to follow patients. As noted earlier, we have about 40% of patients that continue on treatment after the data cutoff. I think we'll be informed by, hopefully, consistent ORR or maybe a little bit better, as well as continued information around the durability of response.
You know, Steven, I think, you know, something we can all look towards here, in terms of predicting the future is the biology behind P53. As Deepika said, there's, you know, there's more than 4 decades of that behind me. My co-founder, Arnold Levine, discovered P53 in 1979. That early response, that's at the first scan, six weeks, was actually expected because the mechanism of action of rezatapopt is to take that very large pool of mutant protein, in this case Y220C, which builds up over time in a cancer cell as the wild-type pathway, of course, is dysregulated. There's no autoregulatory loop between P53 and its degradation.
These mutant pools are huge, and we've demonstrated that rezatapopt directly engages that pool of protein and rapidly converts it to a wild-type form and restores wild-type p53 activity. That's a rapid early response biologically, and we're seeing the clinical consequences of that, and that's, you know, if you're a responder, the vast majority of them, we see that response at your first scan at six weeks.
Thanks for the reminder there. Then yep, please.
Can you just talk a little bit about, I know you talked about bev combo, but maybe just anything on chemo ADC immunotherapy combination opportunities?
Sure. Yes. We have recently generated some preclinical data in combination with bevacizumab, and what we saw was an additive effect, which really provides that further strength to the opportunity to then go into the clinic in combination with bevacizumab. I think there are opportunities to combine with any of the standard of care that is becoming available in the platinum-resistant setting. For this moment in time, we're most excited about combining with bevacizumab in that earlier line of therapy, specifically in the platinum-sensitive space.
That's right.
Maybe one minor one. There was a phase I study initially initiated recently, or I think planned for PK in combination with metformin, rosuvastatin, and a couple other agents. What's maybe the logic for that?
These are typically clinical pharmacology studies that we do to fulfill what FDA is requiring. Basically, CYP3A4 substrates and CYP2C8 inhibitors. Basically, we're doing a cocktail study. This is another opportunity for patients to have access to rezatapopt because this is being done in advanced cancer population. It really provides that opportunity for further access for patients as well.
All right. Oh, please.
Yeah. So my question is around, kind of, adoption of the testing. So I understand you are working with opportunities to drive adoption of p53 testing. Are there any other drivers that, you know, other drugs or maybe that would help you? What is the current situation with this testing? How many patients are tested at first-line versus second-line, and how you plan to improve that?
Based on our understanding, around 75% of ovarian cancer patients are actually tested prior to first line to understand their mutational profile. As far as testing, physicians that are Gyn Oncs and Med Oncs in this space are very much accustomed to testing patients in order to understand BRCA, HRD, and now with TP53. This is going to not be a barrier to adoption from our perspective. In addition, IHC is also being utilized, so biomarkers are not a stranger to the community. We expect this not to be a barrier at all.
Just to close out on it's, it's a great question. For us right now, since p53 has been on NGS panel since the beginning, since it had prognostic value, right now the educational push for it's not just a prognostic marker, but now it's therapeutically actionable, so making sure that gets out there, is really important for us. It's really not so much now a question of adoption of NGS, it's linking a hit to a drug.
All right. Well, with that, we're out of time. Let's thank management one more time for their participation.
Thank you.
Thank you, Steven.