Sagimet Biosciences Inc. Series A Common Stock Study update

Greetings, and welcome to the Sagimet Biosciences key opinion leader call. At this time, I'll participants are an elicit-only mode, and a question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded and will be available for the replay on the investor section of the Sagimet website following today's call. Before we begin, I would like to remind our listeners that our comments today will include some forward-looking statements. These statements include statements regarding the presentation of the data from our clinical trials, our clinical development plans, and related and anticipated development milestones, as well as Sagimet's cash and financial resources, financing, and partnering plans, expected cash runway, and related and anticipated development milestones. These statements involve a number of risks and uncertainties, which are outlined in the press release for this event and on slide 2 of this presentation. Actual events or results may differ materially from those projected in the forward-looking statements, which contain known and unknown risks, uncertainties, and other factors that may cause actual results or performance to differ materially from those projected. I would now like to turn the conference over to your host, Dave Happel. Thank you. You may now begin.

Thank you, Tara, and good morning, afternoon, everyone. We are delighted to have you join us today. During today's call, we plan to review the positive 52-week data from our licensed partner, Askleptos' phase 3 open label extension clinical trial of Denny Fanstat in moderate to severe acne, vulgaris, that was conducted in China. We will also provide an update on Sagimet's planned U.S. phase 3 Aurora clinical trial of Denny Fanstat, or Denny for short, for the treatment of moderate to severe acne. For today's presentation, I will provide a brief overview of Sagimet, highlighting our facet inhibitor development programs, and the significant market opportunities. Dr. Harper, an internationally recognized dermatologist and thought leader in acne and rosacea, will then review Denny's mechanism of action and the positive 52-week data from the phase 3 open label extension clinical trial of Denny in moderate to severe acne, vulgaris. Dr. Andreas Grauer, our chief medical officer, will then discuss our planned clinical development programs focusing on our U.S. phase 3 Aurora clinical trial of Denny for the treatment of moderate to severe acne, followed by a Q&A session with our panel. We are delighted to have with us today Dr. Julie Harper, a board-certified dermatologist practicing in Birmingham, Alabama; Dr.

Harper is the founding director and past president of the American Acne and Rosacea Society, a fellow of the American Academy of Dermatology and recently served on the AAD's Acne Work Group, and was also the former president of the Alabama Dermatological Society. As we get started today, next slide, please. As we get started today, I'll take a moment to give you a quick company snapshot. In April of 2026, we announced a strategic decision to advance Denny into moderate to severe acne where we see a significant opportunity to make this product with its novel mechanism of action available to patients and families living with acne. Acne impacts about 50 million people in the U.S., with an approximately 10 million suffering from moderate to severe acne, and we believe that patients are underserved by the currently approved treatments. If approved for the treatment of acne, Denny could be a convenient once-daily oral medication and the first innovative oral treatment approved for acne in more than 40 years. With Denny, we are now moving into a registrational U.S. phase 3 study building upon the recent successful phase 3 clinical trial conducted by our licensed partner, Askleptos. For Denny in moderate to severe acne, in which Denny met all primary and secondary endpoints.

We also have a second oral facet inhibitor, TVB, 3567, currently in phase 1 study. We are about to complete the single and ascending dose and the food effect portion of this phase 1, and are moving into the PD biomarker phase of the study. We anticipate starting a phase 2 dose ranging proof-of-concept study with 3567 by the end of this year. Also, earlier today, we announced a 150 million dollar financing, which further strengthens our balance sheet and extends our runway through the middle of 2029. As noted, we are planning to take Denny into a phase 3 trial in moderate to severe acne with patient screening expected to begin next month in October. Enrollment of the first patient is expected shortly thereafter. We also plan to continue the development of 3567 with a phase 2 trial expected to start by the end of this year. In addition, and in parallel, we plan to advance a topical formulation facet inhibitor into IND submission. As we move forward, we have the fundamentals in place to support the execution of our programs: our IP is strong, with composition and matter protection for Denny to 2032, plus potential PTE extension to 2037, and for both Denny Fanstat and 3567, we are exploring pathways to extend protection into the 2040s.

Next, I'm going to walk you through the acne landscape. Next slide, please. The global acne market is significant. Forecasted to reach 20 billion globally by 2034. Currently, within the U.S., as noted, there are approximately 50 million people with acne on an annual basis, of which approximately 10 million or more have moderate to severe acne. The target patient population for Denny. Annually, 5 to 6 million moderate to severe acne patients are actively seeking professional treatment, generally in the dermatology setting. Underscoring this potentially large underserved population largely due to the fact that currently available treatments have profiles that potentially limit their effectiveness to treat moderate to severe acne. Next slide, please. In mild disease, treatment consists primarily of topical agents, alone or in fixed-dose combinations. At the end of the spectrum, severe cystic acne is treated with oral isotretinoin, an effective option with significant prescribing limitations under the FDA-required iPledge REMS program. For patients with moderate to severe acne, dermatologists will typically add oral treatments to topical agents. These oral treatments are typically tetracycline-class antibiotics, which can have undesirable side effects and raise concerns about long-term antibiotic resistance with overuse. Across the treatment spectrum, skincare routines are deployed routinely to address dryness and irritation associated with acne therapies.

We anticipate that Denny, 50 milligrams once daily if approved, will be prescribed to treat patients with moderate to severe acne and, as noted, we are also developing a topical facet inhibitor, which we anticipate could be used to treat more mild to severe forms of acne. I will now invite Dr. Harper to share her thoughts on the therapeutic space, including the potential role of an oral facet inhibitor, such as Denny in the treatment of moderate to severe acne. Dr. Harper? Great. Thank you, Dave.

And thank you for the opportunity to be part of this again. This is the very interesting molecule to us in dermatology and in the acne world in particular. And I like that last slide where we break acne down into mild, moderate, and severe. That certainly is the case, but I will tell you regardless of the severity of acne, we are always trying, when we have that patient sitting in front of us in a clinical setting, like I'm in right now, we are always trying to target as many of these four drivers or pathogenic factors in acne as we can. So we have follicular, hyperproliferation, so plugging of the follicle, that's one. Cuteobacterium acnes, which is a bacteria involved in acne, that's another one of our key drivers. Inflammation is a third, and then the fourth and probably historically the hardest one to target is this increased sebum and really a change in composition of sebum. It is historically the hard one for us to target. Until very, very recently, we had nothing topically that would work for sebum at all. We now have Clascodaron or Wenlevy, which can help topically. I will tell you that it's slow and it has to be used twice a day.

And it is topical. Now, we can do some things orally, that will address sebum as well. Some of those were on the last slide. So that would include things like spironolactone in oral contraceptives. But those two right there are systemic antiandrogens. So we cannot use those in men at all. The three that I've just talked about, the topical Clascodaron, the oral contraceptives, and spironolactone, are all working through the same pathway. They're trying to block sebum by blocking androgen. The fourth option here or the third oral would be oral isotretinoin, a drug that's commonly known by the name of Accutane, been around for a long time, since 1982, and it really is FDA-approved for severe nodulocystic and scarring acne. So we reserve it for the most severe patients with acne. The other group of people who can benefit from oral isotretinoin are people who have just been really resistant to other treatments. So it is not often put in as a first-line treatment. So often it's going to be a rescue treatment in someone who has not responded well to other treatments. The way isotretinoin works is also different. It causes really just cell death of the sebaceous gland.

And so when we look at a drug like Denny Fanstat, and I love that I get to call it Denny today, we've decided that may shorten my presentation by a little bit. But when we look at a drug like Denny, it has a whole different mechanism of action here. So that important role of sebum in acne: 80 percent of the sebum, of the lipid in sebum, comes through this de novo lipogenesis pathway. So if we can look over on the right, we'll see facet in there that's fatty acid synthase. That's the enzyme in this pathway that's toward the end before we get the formation of palmitate and sapientic acid. Sapientic acid, in particular, being pretty specific to sebum. But if we can take Denny and put a big X over that facet in right there, it is a fatty acid synthase inhibitor. So it is going to block the end game there. It's going to help block sapientic acid and palmitate and therefore block lipid synthesis. And there's some things about this that I think are really unique and I'll try to call those out to you when we actually look at the clinical results with this.

So where do we really. Well, certainly sebum, but probably also should be anti-inflammatory. And then I would add, just as an acne thought leader, that I think it also stands to reason that if you decrease oil enough, oil or sebum is the food source for C acne, so you will probably indirectly have an impact on C acnes. And we're also learning more and more about the fact that it's changes in sebum that might really promote some of this follicular hyperkeratinization. When we look at lesions in a little bit, we're going to look at inflammatory lesions and then non-inflammatory lesions or comedones. Those comedones are going to come from that follicular hyperkeratinization. So we want to see if with a drug like Denny, which is really targeting sebum and inflammation, can we have an impact even on the follicular hyperkeratinization. So kind of watch for that as we go through. Okay, so we already have some data of course in the lab we have data that Denny Fanstat would have an impact on sebum reducing sebum. We also have some data from a phase one oncology clinical trial. Now, this was not a study for acne.

The dosages used here are higher than you're going to see in the acne studies. But still, what we see is when people are on this medication, they have measurements of sebum, lipids from the forehead, subutates were placed on the forehead, and then we were able to see both the quantity and the type of lipid that are present. Look at the graph at the bottom there. On the y-axis, we're looking at that sapientic acid in triglycerides. So one of the fatty acid chains in triglyceride. And then across the x-axis, we're looking at time. So we see people at day one, day two, there's not really any change here. By day eight, we're starting to see a decrease in sapientic acid. And by day 15, a big decrease. And in fact, it's more than 90 percent reduced from baseline. And it doesn't bump right back up. This stays low throughout the entire study. And we go out here to day 93. So we do have some evidence that this works. Now, let's talk about working in acne, not just specifically for sebum, but we're trying to treat acne. So let's look at that. There's a lot of information on this slide.

And I like to divide slides up. Okay, so vertically, we're going to look at the left half first. You'll see that vertical line. It's not really at the halfway mark. But hang with me on this. So on the left, we're looking at the phase three clinical trials with Denny. So these are the ones that were performed by Askletis. That's the sagimis licensed partner in China. So this study was done in China. 480 patients with moderate to severe acne. Right there, what that means on an IgA scale, investigators global assessment, I'm going to go ahead and tell you the numbers. I'm sure you already know these. A zero would be clear, no acne. A one would be almost clear, a two would be mild, a three would be moderate, and a four would be severe. Now, even to be severe here, there's a limit on severity. You can only have up to two nodules on the face. So there are people with way more severe acne than that that would still not qualify for this. So we're looking at the threes and the fours with a limit on how many nodules a patient could have. This is a very well-designed study.

It is double-blinded. It is multicenter, placebo-controlled, randomized one-to-one. So 480 people come into the study, 240 in the Denny arm, 240 in the placebo arm. The Denny dose here is 50 milligrams qd. Now, always in our studies for acne, we're looking at the same primary endpoints. And our endpoint time is going to be 12 weeks. And so at 12 weeks, we want to know how many of those people who started out as threes and fours are now zeros and ones. So it's treatment success is not just who got a little bit better. It's who got all the way down to clear or almost clear. That's one of the two primary endpoints. The other primary endpoint is lesion count reduction. So we're going to count both inflamed lesions. We're going to count comedones, which are the smaller blackheads and whiteheads. We're going to add that together and look at total lesion count. So the two things we're looking at are global assessment, which is like from an arm's length, that's the way that we're assessing that. And then we'll look at lesion count as well. To the right of that vertical line, this is the exciting new part.

This is the open label extension. So anytime we have a new drug like this, we need 52 weeks of safety data. And some people will start over and do a 52-week open label study. Others will do a 50-week open label extension right on the tail of that. We don't need 480 people now in this. We need 240. So it will be basically the first two 40, first come first serve. But we want about equal numbers to come in from the Denny arm, from phase three trial, and from the placebo arm. So we're going to filter in about half and half from those two. And then extend the study for an additional 40 weeks. You will notice now that there's no control group here. And that's really because these are safety studies. So we want everyone exposed to the drug so that we get all of the safety information that we can have. But we also don't mind a little bit of efficacy data here too. And that's the exciting thing I get to show us today. I think maybe for the first time, we're going to get to see what the efficacy looks like at the end of the 12 weeks as well.