Good afternoon, everyone. Welcome to our 37th Annual Piper Sandler Healthcare Conference. It's day three of our conference. My name is Yaz Rahimi. I'm a Senior Biotech Analyst at Piper Sandler and a Covering Analyst on Pliant Therapeutics. Bernard, Chris, and Keith, thank you so much for traveling from the Bay Area to be with us. And also, congrats to the data this morning. So wonderful to get the news, but maybe a great place to start off would be if you could provide an update of the data introduced this morning for investors who may have missed it as they have been in meetings all day.
Absolutely. Maybe I can kick it off and Eric can provide additional data or detail. And for those here in the audience and listening in, the deck is on the website, and I will refer a couple of times maybe to some slides. I think for me, the key highlight from what we have, you know, generated out of this phase 1 study, albeit, you know, it's a very early study. It was meant as a safety study, limited number of patients, is the fact that we see a durable response, right? 15 months, median 15 months on treatment so far to date, with four responders. Responses are deep. We have one complete responder. This is in patients that have been heavily pretreated. This is basically kind of end of the line for them.
So they failed not just Pembro or, or other ICIs, but they actually also failed chemotherapy or other targeted therapies before. For example, the cholangiocarcinoma patient, which is actually as part of a Lynch syndrome, this patient has a complete response, has been on treatment for, I think now, about a year and a half. The patient itself, this is his fifth line of therapy. Went through four different lines before, continued to progress. Had colon cancer before as well, even underwent radiotherapy and seems to be a complete responder and kind of stays like that. So I think that to me is the key highlight of the data. Of course, there's much more in that data set, the fact that we can, it seems, predict response based on the interferon gamma response, after 14 days of, monotherapy.
Maybe Eric, you can provide additional details on some of the data that we have seen.
Yeah, I think the. I mean, Bernard alluded to it. The interferon gamma signal was really interesting because we saw it really as a distinguisher between responders and non-responders in our study. It was rapidly seen in the setting of initial 14-day monotherapy with 101095. It was also statistically significant compared to baseline. What's interesting about that is that we had also seen this preclinically in our animal models. That's what you would expect by really having an immune response in the tumor microenvironment. That was really exciting. Another really good point is that the drug was really well tolerated. We saw that the most frequent adverse event was rash, but that it was mild to moderate, and we only had one discontinuation due to rash. It was managed topically.
So, really great feedback from the investigators, from that perspective that they really see a therapy that can not only improve response but is well tolerated in, you know, combination with a drug that they use very often, right? Pembro.
And team, I know you had initially, you also had provided, an interim data readout. So help us sort of put into context the data from this morning versus the interim look. I think, Bernard, you alluded to sort of the longer time point. But if you could just maybe shed some more light on, sort of comparing and contrasting these readouts.
Yeah, we have one additional responder. So last time we disclosed data, we were three partial responders. Now we had one additional partial responder. And then one of the partial responders of last time turned into a complete responder. This was the cholangiocarcinoma patient. And then to your point, it's just the duration of time on treatment, and the duration of the ongoing response without any progression. And then to Eric's point, safety, right? The safety data set, of course, is now expanded because of, you know, the time we had. The interferon gamma data are new, as well as additional biomarker data that we have been analyzing. We only kind of disclosed the interferon gamma, but there's more to come, I would argue, and the plan is, you know, once we have the full data set to present at one of the upcoming conferences.
Okay. And team, you've also announced this morning that you're going to move the program forward. So maybe help investors understand what in the data set warrants advancing the program. And then what would the next steps look like for the program?
Yeah, for the next steps in terms of the program, we'll move on to part two of the study. So it'll still be a phase 1b study where we will evaluate 101095 and specific tumor types. So that's what we wanna do. We'll start with non-small cell lung carcinoma and then also explore other tumor types. Then we'll give more information as we just you know select these different tumor types. We also believe that the 1,000-milligram BID dose makes good sense to evaluate in this study as you know really in terms of whether we will still keep the monotherapy. We will still keep that because we wanna continue to explore this interferon gamma signal and also the effect on other biomarkers. Yeah, I mean, that's really what we'll be doing.
Then, yeah, the question is whether we have to include another dose.
Yeah.
in that part two or whether we want to, I would say defer that to a later stage of development, right? To fulfill our requirements for Project Optimus. So we wanna be really mindful of all these considerations.
How large of a cohort do you envision in the 1b portion of that sort of?
Yeah, it's, I mean, it's not a large footprint we're talking about. So it's something that, you know, we would easily execute.
Would you be in a position now that you've made a decision to move forward to next steps and, you have the dose and obviously continue if you wanted to go higher, could you get potential data in 2026? What would the timeline look like, post-start?
Yeah, we don't really have, I mean, formal guidance in terms of timing of data, but I anticipate, I mean, for sure in 2027, right? If we start in 2026, depending on the size of the cohort, I think that will be the determining factor. But 2027 we should have your data. Whether 2026, I don't know. Hard to say. Depends also on the design. Of course, all of this is still open label.
Okay.
So of course data are coming in as they come in.
I assume the type of cancers will be very much aligned with the current patient, like the split of the various types are gonna be the same as you just reported out, right? It's not. There's not a reason to enrich.
I mean, we will do a phase 1b study in non-small cell.
Yeah.
So that will be a given, kind of set of patients and then look at another mix of, of potential, tumors depending on, I mean, more data to be analyzed coming out of this specific trial to see, you know, why are we having certain responders and why are patients still progressing, under treatment. And that will define kind of the, the, the patient population or the indications that we will study in kind of a more of a mix type of cohort.
Then, team, big picture, like, does this now represent sort of a shift in the company's strategy as you're thinking about?
I mean, not really. I mean, we have always been an integrin platform company, right? So what is our strength? Our strength is on one hand is understanding the biology and having the chemistry to address integrin receptors, within different disease settings. Of course, we spend a lot of time in fibrosis.
Yeah.
We went into primary sclerosing cholangitis, PSC, oncology with these data. Obviously we're going to spend, you know, resources to moving forward to advancing this specific program, but at the same time, we have a number of additional earlier stage programs that we will be more public about in 2026, including, and there was a reference to that in the press release, specific targeted drug delivery to very specific cell types. For example, delivery of siRNA to muscle cells, to adipocytes. We have now in vivo data that support that, and, you know, needs to be confirmed in larger animal species, but we anticipate to kind of start disclosing those data in 2026 as well, so there is a platform and we will start to rebuild the pipeline that is, you know, minus the fibrosis asset, but with the oncology asset as the lead asset.
We have enough cash and Keith can talk about that. We will, you know, remain opportunistic as it relates to potential additional assets from outside that would fit our pipeline. But right now the focus is on the oncology program.
Okay. And team, who are some of the competitors in the space on the oncology side as we think about?
It's crowded and it's not.
Yeah.
I mean, of course the whole space of ICI refractory patients. So second line in non-small cell, for example, is crowded. If we look at any kind of the options today, if you look at PFS, it's at anywhere between three and five months. So we may have something that will do much better than that based on what we see today. But of course it needs to be confirmed. True competitors around the same mechanism, there are a couple of companies or number of companies focusing on bispecifics where TGF beta is being blocked together with something else like a PD1 or a PDL, VEGF, EGF, EGFR. So that's one specific space. And then the other one for me, actually, the true competitor from a mechanistic perspective as well as indication perspective is AbbVie. This is the original argenx compound and anti-GARP.
GARP and alpha v beta 8, one of our two targets that we address with the small molecule, are very close to each other. They, they basically work hand in hand in terms of activating TGF beta, which then leads to immune exclusion of the tumor. GARP kind of serves as a chaperone protein that offers latent TGF beta to the receptor. So their antibody basically blocks the conversion of TGF beta, by, alpha v beta 8. So very, very similar. They are currently in later stage development, in non-small cell, in, HCC as well as urothelial cancer. So I think definitely something to keep an eye on, see how that goes, and how we will compare to that. That's an antibody. We are a small molecule. I think I want to kind of reiterate the small molecule part of this, twice daily dosing, small molecule.
I think this is one of the reasons we see the efficacy that we see, but also stay away from the, you know, typical TGF-beta related toxicity. We have rash, but it's mild to moderate. We are aware of other programs addressing same target with an antibody that had much more rash. So I think we can kind of find a position where we have efficacy without running into some of the target-related toxicities because it's a small molecule and it gets much better penetration into the tumor.
Okay. Team, Bernard, you talked about the platform capability, right? And the emerging research that you just alluded to in terms of specific tissue delivery of large molecules such as siRNAs. So what else, just maybe talk to us the capabilities of the platform as you're gonna be sort of generating, you know, a rich pipeline from that?
So what do we have? I mean, we have still a number of small molecules preclinical that are kind of DC ready or already development candidates and that let's say a year from the clinic that we, you know, for good reasons decided to put on hold as we were moving forward with our IPF program, fibrosis program, to save, you know, resources. Those are available and basically can move into the clinic in different indications. I'm not going to disclose which ones, but these are molecules, small molecules against specific integrins that, you know, was based on certain biology, related to what I would consider relevant diseases, not necessarily fibrosis. Could also be oncology or other chronic indications. And then we have the siRNA delivery platform that we are moving forward where we're looking at muscle cell and adipocytes.
So you can kind of guess what potential indications that could be. We don't disclose the target genes of those siRNAs, but, you know, as we move forward, we will be more public about that.
And how soon could some of these programs enter the clinic or, or at least be IND already?
If we do, yeah, I think 2027 is a reasonable time to kind of move these things forward into the clinic. Yes.
Okay.
From a cash perspective, Keith can talk to that, you know.
Yeah, we're fortunate to be in a very strong position. So we, with our current plan, we have cash through 2028.
Wow.
So that gives us an ample runway past any phase 1b data that we expect to get. So we have a lot of flexibility with how we direct resources in that time period.
Okay, and in terms of enrichment of the pipeline or even being concurrently open, if there is potential opportunity.
Absolutely.
Of an asset. As you think about adding onto the pipeline, maybe investors or programs listing, what are therapeutic areas that you would be interested or are you basically agnostic to that?
We are relatively agnostic to that.
Okay.
Right? I think from a therapeutic perspective, I mean, therapy specific perspective, I mean, we don't have in-house cell therapy capability.
Yeah. Yeah.
Or CAR-T or anything like that. So we are very much a small molecule play. But now with the siRNAs, we are venturing into something that is quite different, but using a small molecule as a warhead to kind of deliver. So we are again relatively agnostic to indication, relatively agnostic into kind of, you know, kind of therapeutic modality as long as it's not kind of too far away from where we are today.
I think, I think also a lot of recognized sort of investors recognize the capability of Pliant in terms of a team of execution from a clinical perspective. Maybe like help us. Obviously it was pretty unfortunate, you know, for Bexo to have a safety signal, but when it comes to the team that you guys had built, you know, and to maybe sort of help us understand sort of how much of that group is maintained.
Yeah. We have maintained.
How do you gonna?
Yeah, we have maintained our development capabilities as much as possible. Of course, a phase 1b is a different thing than a global phase 2b and IPF.
Yeah. Yeah.
So we right-sized the company. I have gone through that. So it's a smaller company than what it used to be. But the core capabilities are there from a clinops and clinical perspective. We actually going to add more capabilities in terms of on the clinical oncology side as well as on the regulatory side as it relates to oncology because that's very specific. So we're going to bring those additional expertise in to support this program. But otherwise I think we still have a team that's very much first very motivated to move this forward. It's a program that we know, which has the advantage of something that you buy and you never know what's you know in some I'm not saying skeletons but you know due diligence will never be.
Yeah.
Due diligence will never be 100%.
Yeah.
This one we know, and so that gives comfort and people are extremely motivated to stay and to kind of really work on this, so all of that is in place. Of course, we also looked at our cash burn and making sure that we have sufficient runway, so we had to kind of right size the company.
Okay. Wonderful. Well, team, this is an exciting announcement. Obviously, you know, we are very much looking forward into next year, a new year, a new beginning, a new program, lots happening at Pliant, you know. Thank you again for being here with us and let's give a big applause to the Pliant team.
Thanks for having us.
Yeah.