Tyra Biosciences, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Wow. Are we going all the way back to the beginning on this story here?

Yes. Sure. Look, Tyra's a company that's focused on precision medicine, and we make our own drugs.

We have an in-house SNÅP Chemistry platform. It's structure-based drug design. And we made dabogratinib from scratch, something we kicked off nearly seven years ago.

We've come a long way. And absolutely thrilled today to be sharing the first proof of concept of a potential oral FGFR3 selective drug in the intermediate-risk MIBC setting. This is part of our broader strategy that we're moving forward with dabogratinib. We're pursuing two urothelial indications, MIBC. We're pursuing upper tract urothelial, a rare disease with a similar lesion type in the urothelial lining, but in the kidney and the ureter. And we're pursuing growth disorders, including starting with achondroplasia. What's so meaningful about the data today is this is where the majority of the patients are with unmet need that could benefit from a drug like this. This will be our biggest indication.

For the first time, we're showing this proof of concept that with dabogratinib, we have a drug at 60 milligrams that could support chronic dosing to suppress FGFR3 orally, that has the activity we were hoping to see in terms of, we did a marker lesion study and in terms of seeing the activity with those lesions shrinking, and that has the convenience of an oral. Really underline that last point, which is so important because it's a competitive space, but all of the competitors are continuing a paradigm of urethral violation in order to get their therapy in. Patients are already voting with their feet today. 70% are opting out of an effective maintenance adjuvant treatment via induction maintenance chemo.

Despite that reducing their recurrence risk by 44%, 70% of patients say, "I would rather wait to recur than have all these catheterizations." An oral for the first time gives this patient population the hope and promise that they could control their disease with a simple at-home daily pill, and it's a complete game changer. The data we shared today shows proof of concept and a high likelihood of success as we move into phase III, which is the next step. We're going to be aligning with FDA. I think worthy of talking about that because we now have really a set of data that I would say is strongest in the space for predicting our potential success in phase III, let alone predicting what I think would be a very successful commercial product, potentially first in line. This is a $5 billion-plus market opportunity.

I would say the profile we have is leading the way as the likely first-line choice for physicians when they think about what really moves the needle for their patients that are over-instrumented and overburdened.

Yeah. And just to underscore that point, we asked in our physician survey, and we shared some of this data, about what the highest unmet need is in this patient population.

And the number one, 75% of physicians said it is the procedural burden, it is the repeat catheterizations. That is the unmet need. It is over-instrumentation and procedures. These lesions can get cut out, but the process of cutting it out, that surgical burden is high. And yes, you can catheterize and put chemo in there and see lesions disappear, but it is how can you get to an outcome with something that is not so burdensome on the patient? And that is really the vision and the goal for dabogratinib. What we were able to show, this was a really important study that we designed. We wanted to get to an answer quickly. We wanted to get an answer of what is a sufficient dose that we could use in the adjuvant setting to keep tumors from coming back.

To answer that question, we had physicians leave a marker lesion or lesions behind in the tumor. We had them take drug for 3 months or longer, and we evaluated, did the tumor shrink 50% or more or disappear? And when we looked across all the patients, we had two doses 50 milligrams and 60 milligrams.

And we evaluated both those that shrank completely and those that shrank 50% or more. We saw a clear dose response. At 60 milligrams, 79% of patients had a response. That means that their tumor was shrinking either 50% or more, or the tumor was gone. We had a 54% CR rate initially, but then migrating, sorry, 57%, migrating to 64% because those PRs start converting to CRs as we follow these patients. And that is really an extraordinary outcome, and it is the overall response that really matters in this adjuvant setting. Now, one of the things in the expectations going into this data set were around how would we compare with the only other oral that has attempted this. That study was a study called THOR-2.

It was oral erdafitinib. It was done at a single dose. It was done with marker lesions, but only one marker lesion was left behind. We actually evaluated patients both with one marker lesion and multiple marker lesions. What we saw was that when we looked at the patients with the single marker lesion, so the comparable study, there we actually have 100% ORR and a 75% CR rate. That is exactly in line with what THOR-2 was showing at a similar timeframe. That gives us the strong signal that we are suppressing FGFR3. With the oral, we are getting the best possible outcome that can be seen. You cannot beat 100% ORR. That now allows us to anchor on the dose as at a go-forward dose in the adjuvant setting.