Tyra Biosciences, Inc. Common Stock Study result

Please go ahead. Thank you, operator, and good morning, everyone, and thank you for joining us.

I'm Todd Harris, CEO at Tyra Biosciences, and we are thrilled to be sharing with you the results that we're seeing in our SURF302 study evaluating oral dabogratinib in patients with intermediate-risk NMIBC. I'd like to begin by thanking the patients, their families who participated in this study, our investigators, study coordinators, employees, and our shareholders. None of this would be possible without you. Before we begin, I'd like to remind everyone that during today's presentation, we will be making forward-looking statements, including statements about our future clinical plans, data and strategy, and potential therapeutic benefits of dabogratinib. These statements are subject to risks and uncertainties that could cause actual results to differ material. Please refer to the slide and our SEC filings for cautionary language and a discussion of these risks.

We undertake no obligation to update these forward-looking statements except as required by law. I'm pleased to be joined by our Chief Medical Officer, Doug Warner, also Dr. Mark Silva from Greater Boston Urology, a community urologist out of Boston who's actually participated in both of our SURF302 and SURF303 studies. He's here to share his perspective on both the data and the impact of oral dabogratinib for his potential patients and practice. I'll share some market insights up front. Doug's going to be walking through the data, and we have other members of our team, including Alan as well. We are excited to share today that we believe we have a drug with dabogratinib.

At the 60 milligram dose, we are seeing the safety for chronic dosing, the clinical efficacy, and the convenience of an oral therapy that could truly shift the paradigm of treatment in this setting of intermediate-risk NMIBC. I've talked a lot about the patient journey in the past. Patients with intermediate-risk NMIBC suffer from multiple procedures, surgeries, and over-instrumentation. It is the key unmet need. For the first time with the data we're sharing today, we can envision a future where the procedural burden could be replaced with the convenience of a simple oral drug at home. This population, of which there are about 50,000 new patients seeking treatment every year, 70% of these patients actually opt out or forego an effective treatment that's been proven to reduce recurrence. That's a treatment involving induction and maintenance chemo, and it's in the guidelines.

Why are they opting out of or foregoing this effective treatment? It is because this is a disease that is not likely to progress, but is highly recurrent, and facing the choice between multiple catheterizations and procedures that would be required to maintain a disease-free status, most patients are simply waiting to recur, and when they do recur, undergoing a single operative procedure instead of the multiple catheterizations. When we look specifically at the largest population, the FGFR3-positive population, it is clear this is the population with the highest unmet need. Really meaningful data from Dr. Meeks at AUA this year highlighted that FGFR3-positive patients have a median recurrence-free survival of only 16 months, versus the broader population that is not FGFR3 having a median RFS of 40 months.

It is clear that this is a signal that is causing multiple and frequent recurrences, and by suppressing this signal, we have the opportunity to change the patient journey, bend the curve towards a longer disease-free survival. The evidence is already there. We have seen with intravesical and oral pan-FGFR inhibition that as long as FGFR3 is being suppressed, we can see 100% durability. But in all of these examples, when that FGFR3 suppression signal goes away, patients come off treatment, we see a high rate of recurrence that starts to happen right away. 3 of 4 evaluated patients in that TAR-210 phase II study actually came off of therapy and recurred within 3 months. 4 of 6 patients who had discontinued treatment have recurred within a year.

When we think about how can we maintain treatment and the broader pipeline, all of the approaches that are moving into phase III adjuvant studies require multiple urethral violations to be effective. This is continuing this paradigm where patients today are voting with their feet not to undergo treatment. With an oral drug in dabogratinib, we have the potential for chronic suppression, chronic dosing with the safety signal and the efficacy signal we are talking about today, that it could actually change the paradigm for these patients in maintaining a response and avoiding recurrence. The study that we designed to demonstrate this is our SURF302 study, and it is the data we will be sharing today. It is important to highlight that this is a marker lesion study. What does that mean? That means that at least one marker was left behind in the tumor and drug was given to identify which dose can we see that marker lesion shrink or disappear.

We actually, with the design of this study, have 2 studies in one. We allowed both patients with a single marker lesion, which is a really high predictor of adjuvant success, and this was the criteria that the one predecessor study, THOR-2, the criteria that they used. But we also looked at patients with multiple marker lesions, which could give an initial indication of dabogratinib's use in an ablative setting. We tested 2 doses, 50 and 60 milligrams. Both of these doses were chosen as potential doses to cover our IC50, which has an AUC of 2,500 nanogram times hour per mil.

We will highlight in the data today why that is important and why we think that we are seeing a great dose response between 50 and 60 milligrams. Finally, the endpoints. The primary endpoint was CR at 3 months. Because of the importance of the adjuvant signal when a lesion is shrinking greater than 50% and no new lesions are appearing, we also look at best overall response as a clear indicator that there is enough drug on board with a particular dose to shrink the tumor and to potentially have an effect in an adjuvant setting. What are we seeing? Initial data shows that when we look at the study with single marker lesions, we have 100% ORR at our 60-milligram dose.

Recall, this is an ablative signal-seeking study, so when we look at these single-marker lesions, and this was the way that the THOR-2 study was ran, we see 100% ORR, and we see a best overall response of 75% CR. This is exactly the benchmark we were hoping to see. THOR-2-like efficacy, but with a much-improved tolerability, which, as Doug walks through the data today, you will see. At 60 milligrams, we are seeing the safety signals that could support chronic dosing potential. All this comes together to highlight a very high probability of success in an adjuvant phase III. So 60 milligrams is the go-forward dose we are planning for an adjuvant phase III versus a placebo. What the data also show here, and we will highlight this, that with multiple marker lesions, the responses are not as strong.

When we think about the potential of using dabogratinib in an ablative setting, it is clear that potential more drug on board could be helpful for ablation, so we will be studying a 70-milligram dose expansion in SURF302 prior to considering whether we further expand this study towards lesions of all sizes in an ablative setting. To be clear, the biggest opportunity we are pursuing, where 85% of the market, we believe is in the adjuvant setting, and that is the phase III dose selection that we are moving forward with and talking about today at 60 milligrams. With that, let me hand it over to Doug to get into the study details.

Doug? Thank you, Todd. SURF302 enrolled a highly recurrent untreated population.

This is very consistent with the overall patient population in low-grade IR-NMIBC. This is an elderly group of patients, the vast majority of which had recurrent disease and had prior TURBTs up to 10. Interestingly enough, as Todd pointed out, this patient population, the majority did not receive intravesical chemotherapy. This patient population had a high tumor burden, with over a third of patients had greater than one marker lesion at baseline. In addition, total aggregate tumor size was 10 millimeters in a quarter of the patients. Overall, when we look at the safety data, dabogratinib showed favorable safety and tolerability that support chronic dosing in this indication. Adverse events were manageable. There was no clinically significant hyperphosphatemia, nail toxicity, or ocular toxicity. These are common toxicities that affect quality of life that are associated with pan-FGFR inhibitors.