Sagimet Biosciences Study update

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, Ascletis' phase III open label extension clinical trial of denifanstat in moderate to severe acne vulgaris that was conducted in China. We will also provide an update on Sagimet's planned U.S. phase III AURORA clinical trial of denifanstat, or DENI for short, for the treatment of moderate to severe acne. For today's presentation, I will provide a brief overview of Sagimet, highlighting our FASN inhibitor development programs and the significant market opportunity. Dr. Harper, an internationally recognized dermatologist and thought leader in acne and rosacea, will then review DENI's mechanism of action and the positive 52-week data from the phase III open label extension clinical trial of DENI 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 III AURORA clinical trial of DENI 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 deni 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 approximately 10 million suffering from moderate to severe acne. We believe that patients are underserved by the currently approved treatments. If approved for the treatment of acne, deni could be a convenient, once-daily oral medication and the first innovative oral treatment approved for acne in more than 40 years. With deni, we are now moving into a registrational U.S. phase III study, building upon the recent successful phase III clinical trial conducted by our licensed partner, Ascletis, for deni in moderate to severe acne in which deni met all primary and secondary endpoints.

We also have a second oral FASN inhibitor, TVB-3567, currently in phase I study. We are about to complete the single and ascending dose and the food effect portion of this phase I and are moving into the PD biomarker phase of the study. We anticipate starting a phase II dose-ranging proof of concept study with 3567 by the end of this year. Earlier today, we announced a $150 million financing, which further strengthens our balance sheet and extends our runway through the middle of 2029. As noted, we are planning to take deni into a phase III 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 II trial expected to start by the end of this year.

In addition and in parallel, we plan to advance a topical formulation FASN 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 of matter protection for deni to 2032 plus potential PTE extension to 2037. For both denifanstat and 3567, we are exploring pathways to extend protection into the 2040s. Next thing, 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 deni.

Annually, 5 million 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 deni 50 milligrams once daily, if approved, will be prescribed to treat patients with moderate to severe acne. As noted, we are also developing a topical FASN 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 FASN inhibitor such as deni 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 a very interesting molecule to us in dermatology and in the acne world in particular. I like that last slide where we break acne down into mild, moderate, and severe. That certainly is the case. 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 am 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 is one. Cutibacterium acnes, which is a bacteria involved in acne. That is 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 recently, we had nothing topically that would work for sebum at all. We now have clascoterone or WINLEVI, which can help topically. I will tell you that it is 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 and oral contraceptives. But those two right there are systemic anti-androgens. So we cannot use those in men at all.

The three that I have just talked about, the topical clascoterone, the oral contraceptives, and spironolactone, are all working through the same pathway. They are trying to block sebum by blocking androgen. The fourth option here, or the third oral, would be oral isotretinoin, a drug that is commonly known by the name of Accutane. It has 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 is 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. When we look at a drug like denifanstat, and I love that I get to call it deni today. We've decided that may shorten my presentation by a little bit. When we look at a drug like deni, it has a whole different mechanism of action here. That important role of sebum in acne, 80% of the sebum, of the lipid in sebum, comes through this de novo lipogenesis pathway. If we can look over on the right, we'll see FASN 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 stearic acid. Stearic acid in particular being pretty specific to sebum.