VYNE Guggenheim 3rd Annual Healthcare Innovation Conference

Happy to. Thanks for having us. I appreciate it. Rebecca Frey, I'm the Chief Executive Officer of Yarrow. We put the company together in 2025. This was incubated inside RTW Investments with the intention of acquiring a first-in-class anti-TSHR asset for the treatment of both Graves' disease and TED. We spent a lot of time in 2025 pursuing the asset and also preparing to launch the company, pursuing financing, et cetera. We also, in that context, we pursued a reverse merger as part of our financing, so we have since completed a reverse merger with VYNE Therapeutics that closed in July. We have raised a total of roughly a little bit north of $350 million across our PIPE and a subsequent follow-on financing that we did in September to fund our programs going forward. We also have recently launched a phase II study in Graves' disease.

Our core thesis is that blocking TSHR with a monoclonal antibody is the most direct way to shut down the disease process in both Graves' disease and thyroid eye disease. If we are successful, this could be the first mechanistic approach to actually have a significant benefit in both Graves' and thyroid eye disease, and we have the most advanced TSHR program currently across both those indications. Our strategy has been to generate clinical data across both indications. Presently, we're doing this through a combined phase IIa/IIb study in Graves' that we've initiated in the U.S., while our partner GenSci is continuing to run a phase I-B study in TED in China.

Got it. We anticipate having data from both our Graves' phase IIa and the GenSci TED phase I-B in the second half of 2027.

Those are our major upcoming catalysts.

I'll just start by saying I think this is a really exciting time because the field is opening up in terms of really starting to figure out biologically what's going on and how to tackle these diseases, which have very significant unmet needs. I myself have Graves' disease, so very passionate about that. The underlying biology is pretty well characterized. Both Graves' and TED are diseases that are driven by autoantibodies. Those autoantibodies bind to the TSH receptor, which is expressed on the thyroid and also in the eye. When they bind to the receptor, they overstimulate it. That overstimulation drives the dysregulation of thyroid hormones, and in the eye, also drives the local immune response. That's essentially the disease pathology, and it's a polyclonal disease, so patients can develop a wide range of different isotypes of antibodies that are directed to the TSH receptor.

Conceptually, you can go after the receptor or you can perhaps go after the antibodies. What we believe is that because the disease is purely driven through that receptor location, that by intervening at that point, you have the most direct and efficient way to actually stop the disease process in its tracks, which is what you ultimately want to do from a clinical perspective. We have phase I single-dose data. There's also phase I data that's been generated with another TSHR antibody called K1-70, and across those datasets, you see consistently that this has that potential in terms of even with the single dose, you see a very rapid and deep suppression of signaling at the receptor that's reflective of effectively blocking and interrupting that disease process in a meaningful way.

Very much so. First of all, I think that we saw the full data set on the FcRns in TED last week, and I think it was obviously alerting and raises some questions, right, about how do you really tackle TED. But the other end of this is that you have the IGF-1R class, which is very limited by safety issues, but they are highly efficacious, and they work by indirectly inhibiting receptor signaling. For us, we see that as validation that if we block TSHR in the eye, which is essentially what is done indirectly by an IGF-1R inhibitor, we have the potential to see improvements in clinical measures of disease. I think that is what is nice about TSHR is it is applicable to both diseases, whereas IGF-1R, A, is limited by toxicity, and B, does not really apply to the thyroid.

GenSci is conducting a two-part study in patients with TED in China. These are moderate to severe patients with active TED. The first part of the study, which we have shared the top-line data from, was a single ascending dose study. It is a first-in-human study that went directly into the patient population, and they looked at five different doses of YB-101 versus placebo in an escalating fashion, and obviously evaluated safety and PKPD and efficacy. I think first and foremost, it was informative in that we saw very good safety. There are no dose-limiting toxicities associated with blocking TSHR in this way. The main difference from placebo from a safety perspective is only in the context of thyroid hormones, and we can talk about that.

Yeah. You see very rapid reversal of thyroid hormones with a single dose.

Within the first two to three days, you see T4 and T3 declining, and within the first five days, you see TSH increasing after a single dose. That is really a new paradigm because if you look at the little bit of data we have with FcRns on thyroid hormones, for example, TSH takes many, many weeks, if not months, to improve. This is the first approach that has the ability to very rapidly reverse the balance of the thyroid hormones. Even though it is a first-in-human study, we did also look at effects of this approach on proptosis, which is the primary efficacy measure that you would look at in TED, and it is a small sample size, so provide those caveats.