Hi all, thank you for coming here today. I'd like to introduce you to the Tempest team. Today we have Steve Brady, Chief Executive Officer, Sam Whiting, Chief Medical Officer, and Nicolas Maestas , VP of Strategy and Finance. My name is Emily Spielman , and I'm an analyst with TD Cowen's Healthcare Investment Banking team, and I'm available after the presentation if you have any questions. I'll now pass it over to the Tempest team. Thank you for being here.
Thanks, Emily. Thank you for having us. Again, my name is Steve Brady. I'm the President and CEO of Tempest Therapeutics. To dispense with the legalities first, we are a publicly traded company, and I will most likely be making forward-looking statements, so please, do refer to our filings with the SEC. This is a great time to be talking about Tempest. It's our first time at the Cowen Conference. And why do I say it's a great time? Because the company is transitioning based on some new exciting data that we presented in the fall. We're transitioning into a late-stage company, and this is all being led by a program called TPST-1120, a PPAR Alpha antagonist. It's part of a diversified portfolio inside the company. We have three publicly announced programs, more inside research. We are an oncology-focused company.
Each of these programs, to our knowledge, are the leaders in the targeting their respective targets. The lion's share of the interest, right now from the buy side, and just generally everyone outside Tempest, is on this lead program TPST-1120, and that's what we're going to be talking about today in this abbreviated timeframe, but there's definitely more inside the company. There's a second clinical program called TPST-1495. It is in the prostaglandin pathway, which many of you know have been implicated in, as a potential cancer, you know, modulation pathway for many, many years. We presented some data at ASCO last year on this program, in solid tumors. Unlike TPST-1120, that has, you know, absolutely taken the lead and is expanding. You know, the more we look at data, TPST-1495 is focusing in its development.
We're going to be finishing up an endometrial arm this year, and we have some new interest externally that's not represented on this slide. It is on our pipeline slide, looking at FAP, which is, as you know, a cancer-adjacent indication. So more to come on 1495 in FAP, but for now, 1120 is really the story that's driving everyone's interest inside Tempest. So as I mentioned, it is a PPAR Alpha antagonist. You know this pathway, PPAR. There have been agonists in this space for many years: approved drugs, fenofibrates. This is the other side of the field. We are antagonizing PPAR Alpha to fight cancer. And why did we choose this target? It's multifold, and I want to say at the outset, this is one of those nice experiences in drug development. We've all worked on many targets and many programs over the years.
TPST-1120 is one of those rare instances, at least for me, where we had a hypothesis when we started the program. We thought we should look in certain places. We thought we should combine with certain other mechanisms of action. And all of that is coming together now as we're moving towards the first pivotal study, and we're steady, and we're sitting on the other side of multiple positive data sets. So it's really nice to see the hypothesis grounding into reality. So again, why were we interested in this target? Well, it was multifaceted. One, from the very beginning, we were looking at this as a way to combine both a targeted oncology therapy with an immune-mediated therapy. And why is that? Because the target is expressed both on multiple types of cancer, both solid tumors and heme indications, but also on immune-suppressive cells.
So we thought when we kicked this program, excuse me, this program, off, that we could target the cancer cells directly, but that we could also, for lack of a better term, reactivate or the classic phrase we all love for many years, make cold tumors hot, and have that dual mechanism of action, benefit cancer patients. Some of the data we just got in fall makes it look like that is indeed happening, which is very exciting. And there was also that mechanistic part. When I say that with other MOAs, because of the nature of the target expression and some genetic work that we had done in the past, we thought that it would be interesting to combine 1120 with not only a PD-1 axis antibody, but also with an antiangiogenic agent.
That's going to play out as well in the lead indication in first-line liver cancer that we are looking at right now and for which we released those data. Most of us in drug development look at the genetic expression of the target, and we have a large preclinical data set that are not in this presentation, but it's always good to look and see where your target is expressed. Three of our top indications, liver, kidney, and cholangio, all came out of very early screens that we did. Again, as I mentioned, and we're seeing signals in phase one and in the phase two in all three of those indications. What that shapes up for us with respect to this program is 1120 is emerging as a company within a single program.
And so we're fortunate that this is turning out the way it has. On that comment on immune mediation versus direct cellular targeting, the data here show a combination with a checkpoint inhibitor. But interestingly, on the right side, you see re-challenge with the tumors with no drug, and you see complete cure in the subset of the animals where we so there is clearly an immune-mediated aspect. We see that preclinically, but we also see that in the phase two data that we have as well. The other aspect of this pathway, which has been really interesting to people, we get a lot of questions about, and you know that there are companies targeting this exact target, are beta-catenin mutations. Beta-catenin mutations are relevant to PPAR Alpha targeting. Why? Because in patients with that mutation, it upregulates reliance on the target.
And so again, as part of the original preclinical logic for moving forward with the program, we were always interested in how this would look. And so we ran preclinical studies on it. And this was one of the more actually, when I first joined the company, anecdotally, I looked at these data. We all have wonderful preclinical combination data, as you can see in this beta-catenin HCC model, combining 1120 with a checkpoint inhibitor just crushed the tumors, and it was just long-term, not just control, but, you know, cure in these mice. And this was exciting before we went into liver patients who mutated or not for beta-catenin, but it really did support our original clinical plan. So like everyone else, we did a standard phase 1 dose escalation, mono and combo.
We were selected for a podium presentation at ASCO, when these data were released. And what was really interesting was this was at the during COVID. And as you know, a lot of the academic centers are where the HCC patients are seen. So we didn't have a lot of HCC patients in the phase 1 study. We had to wait to get our phase 2 data for that. But what we did see, if you look over here on the right side in the combination arm and on the left, this is the monotherapy. Given that this is Panc and CRC and some incredibly rough third and fourth line patients, we were pleased with this profile. What gets the most extension externally is on that right side where you see those four lines on the waterfall.
Three of those 4 patients are RCC patients, and those are all at the 2 highest doses. And so why were people interested in that going all the way back to the genetic expression of the target? RCC was 1 of our top 3 targets for PPAR Alpha. It also when we did, a meeting at this ASCO, when you talk to the KOLs, this target is highly relevant for RCC generally. So we were excited to see those data. And the reason we've included them in an abbreviated conversation like this is because we don't view 1120 as just a liver cancer opportunity. It is. Liver cancer is massive. It is an uncrowded space, and we think, you know, a phenomenal place for us to be right now. But, capital dependent, we would go beyond into RCC and other indications of interest.
Here's one of the exciting patients from that study. Very quickly, as you can see on the top, we had a long, long, durable, deep response in a heavily pretreated patient. We were the fourth line of therapy. But as you can see here, she had already been treated with nivolumab and Ipi and did not respond. And then when she got on 1120 plus Nivo, the same exact antibody, she had a deep response. This is one of the RCC patients, another RCC patient below. Very quickly, one of the other responses in this study was in a cholangiocarcinoma patient. Interesting for two reasons. One, or actually three reasons. One, if you look on the table on the bottom, you will see how heavily pretreated this patient was. I think we were the seventh therapy. Cholangio is a cold tumor.
It is not known to respond to checkpoint inhibitors. It is also one of the top expressors of our profile. Here you see when combined 1120 and Nivo, this patient responded into a PR as well, even after all of those therapies. So at the same time we were doing the phase 1, another rarity, we had an ongoing randomized phase 1b/2. The separation between that ASCO presentation I mentioned and these data were about 15 months, so it really accelerated the program. This, 1120, was put into a randomized study in collaboration with Roche where we were added on to the undisputed standard of care in first-line HCC, which is Roche's Atezo/Bev. It was 1120 plus Atezo/Bev versus Atezo/Bev randomized global study, 40 patients in the 1120 arm and 30 patients in the standard of care arm.
The data that we presented in the fall were wonderful. I mean, as you saw, I think we broke a Nasdaq record in 1 day. There was an incredibly positive reaction to these data. ORR, not in every indication or not in every cancer indication, ORR isn't necessarily, you know, a bellwether for the eventual regulatory endpoint. As Roche published in their phase 3 when they gained this first-line label, ORR was a predictor of OS. And as you can see in this case, we, you know, more than doubled the ORR of the control arm. Our PFS positive hazard ratio 0.7. OS in the control arm had been reached. We had not reached OS yet at this time, which is great because that is the regulatory endpoint for first-line liver cancer.
And then going back to those subpopulations of patients, we have more data on this. We were really excited to see that adding 1120 onto Atezo/Bev effectively made it indifferent to the immune status of the patient. Our ORR didn't change. That's one of the holy grails, right? We don't; no one wants to have PD-L1 positive only therapies, as we move forward in immunotherapy. And in this case, we were really pleased to see that. Could it be that it's that original hypothesis that it's a combination of direct cellular targeting, or is it that plus we were able to hit the immune suppressive cells and reignite the immune system, making a cold tumor hot? That's a Nature paper to figure that out at some point in the future. What we care about right now is that it's working and it looks indifferent.
And then also of excitement to a lot of people in the beta-catenin patients, the beta-catenin mutated patients that we were able to get data on, the ORR increases to 43% and we had 100% disease control rate. Again, makes a ton of sense based on the target and what beta-catenin does in those patients. So we were really excited about that. Again, the story all coming together, and supporting, obviously, moving into a pivotal study in this indication in the overall population. So at the time, we also released more data that are because we did not have our OS data.
When you look at the number of patients on the 1120 arm who were still on study and on treatment, and those patients who had passed between the two arms, it's a pretty dramatic difference, the control arm doing significantly worse than the 1120 arm. So this makes us, you know, optimistic when we get the next data cut, which we hope we'll have, all further OS data that we're excited about where everything was going. And I remind you, we put out, what I guess you could call a very top-line early data set from this study in April. Everything looked directionally correct towards what ended up being the October release. And as of the October release, everything's looking directionally correct for the final data release as well. Kaplan-Meier on the PFS, not on OS, because again, OS was not reached.
This is on our website if you want to get better quality, images. You see a nice clinically significant separation. To channel our CMO, if we would love to see this in the phase 3, it'd be wonderful. But again, this is an OS indication that we're going for when we do the pivotal study. The waterfalls put here quickly for the obviousness of the improvement that 1120 confers versus standard of care, the 30% versus 13%. What's really interesting coming up is when you layer this over the immune status and mutation status of the patients. This is that, you know, key just pausing again on from a success in phase 3 and also a commercial benefit. There are two populations everyone looks at in HCC, PD-L1 negative status and beta-catenin status.
Beta-catenin status, again, should confer a benefit like we saw preclinically and we're seeing in this data set. When you add 1120, that's anywhere from 20%-40% of HCC patients. And then the PD-L1 negative status of HCC patients is significant. I mean, some papers show north of 70% of the patients are PD-L1 negative. And as you remember in the data we just released, the standard of care's ORR drops down to 7% in those patients. So this, if 1120 replicates what we saw in these randomized phase 2 data, we're going to be indifferent to whether a patient is PD-L1 negative or positive, and we're going to benefit if they're beta-catenin mutant. So back to the waterfalls. As you can see here, this is the same, just an enlarged version of the control arm's waterfall.
On the bottom, what you have are the PD-L1 status of the patient and the immune phenotype of the tumor itself. No criticism of the control arm. I mean, this is, atezolizumab is a it's an immunotherapy. It's supposed to work better, in hotter patients or hotter tumors or PD-L1 positive patients. As you can see, the tumor reductions are, grouped around the hotter tumor types. But when you look at when you add 1120, we're just indifferent. We're indifferent to whether it's red or gray or blue or yellow. There's responses all over the place. Again, we think this is twofold, a combination of hitting the tumor directly because of the target, but also hitting PPAR Alpha expressed on immune suppressive cells, thereby allowing the immune system to do its job. We get a lot of questions about safety in our phase 1.
TPST-1120 looked wonderful. Knock on wood that that continues. One of the things that, we were pleased to see in the randomized phase two data is that replicated. Interestingly here on the bottom on the dose intensity chart, as you know, whenever you're adding a third drug or a second drug to a standard of care agent, regulatory agencies care about the intensity of the standard of care. Is adding your drug going to reduce the intensity of the standard of care? In this case, actually, Atezo/Bev, the use of Atezo/Bev intensity went up. Why is that? Well, we think our patients are doing better because of the combination. They were able to handle more drug. Still, great to see as we're going into all of our FDA and broader, global regulatory conversations. Important in any randomized study is where the arms balanced.
So obviously we have scoured these data. We and Roche both do the arms as balanced. It was they ran the phase 2. It was a successfully done randomized study. But what this slide shows when in these green boxes, if you're going to look at anything, any of these categories like ECOG 1, or sorry, ECOG status or other indicators, if anything, they favor the control arm. The 1120 arm actually did worse in terms of the patients that were allocated to it. So we still say generally balanced, but if you want to dig in on any of these, we're happy to follow up with that as well. So where are we now? We really, we released the data in fall. We are full steam ahead to starting a pivotal randomized phase 3. All the discussions with FDA and so forth are this year. These are strong data.
We're excited by them. Our default is obvious the path of highest likelihood of success and, probably least resistance with regulatory authorities is to just take the phase two and expand it. We are not going to preselect for PD-1 negative patients. We are not going to preselect for beta-catenin patients. We're going to capture as much of that as we can. But the 1120 triplet is winning in the overall population. And so that is the population we're planning to do the phase three in. We will definitely want to know how beta-catenin patients did and PD-1 negative patients did. And we'll have those data. We're going to collect those when we can. We are and have been open about conversations that we've been having with people other than Roche.
There is a strong argument out there, not held by Roche, but held by competitors that we should sub out atezo for a PD-1, as opposed to doing it with a PD-L1. Given the experience of FDA and other regulatory authorities with checkpoint inhibitors, PD-1, PD-L1 checkpoint inhibitors in HCC, we don't think that's controversial. But that could be one thing if that could be a deviation or a change in the plan. If a partner comes in and says, "I'm going to give you my wonderful PD-1," and there's a reason for us to do that, we're going to explore that. But the fastest, quickest way is obviously, excuse me, is obviously just to expand the phase 2 and keep going full speed ahead. Everyone probably knows this, but I think it bears pausing on for a second because this is rare. Liver is an enormous indication.
It's one of the few growing indications, unfortunately, for patients. The prognosis is still not very good. The high watermark that we saw with Roche's Atezo/Bev phase III median OS was 19 months. Not great for first-line indication. Also, from a commercial perspective, Roche's, I mean, liver, first-line liver is strangely uncrowded. Roche is the dominant player. If you talk to some of the KOLs, they'll say up to 70%+ of the market is a single therapy. So as we move forward with this triplet, we think, one, there's an opportunity to significantly move the needle for patients, but from a commercial perspective, there is an opportunity to take market share. As I mentioned, we don't have time to talk about the other programs. It's all eyes on 1120, right now, but we are interested in expanding beyond HCC into other indications, including heme.
There are other programs inside the company as well, but I am out of time. I want to thank the Cowen team again for the invitation and opportunity to present, and we're happy to follow up. Thank you.