Tenaya Therapeutics, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Thanks, Joseph, to you, and to the HCW team for inviting us.

Yeah. So we're really excited. The update that we did recently was actually a meaningful update from what we did at AHA last year, and we were already pretty pleased with what we had at AHA last year. Now with the benefit of more time, we now have data from six patients, seven patients worth of safety, six patients worth of efficacy data. And the good news is that all patients are seeing meaningful improvements in one or more measures of all the domains that we're looking at right now. So we're looking at circulating biomarkers. We're looking at hypertrophy, so that's that remodeling you talked about. Feel and function measured two different ways, New York Heart Class, KCCQ, and for feel and function, six-minute walk test and peak VO2.

Now we don't have all of that information in hand for all patients at one or two-year time points, but we have quite a bit. Overall, the totality of the data shows that patients are doing well on multiple measures. There's quite a bit of internal consistency. Any one measure might be strong here and weak there, but overall, it is unambiguous that there's a clinical effect that is happening, and it's because of TN-201. The levels of hypertrophy that we're seeing, the reductions, multiple measures of wall thickness and LVMI. 4 out of 6 patients had double-digit decreases in hypertrophy, and these are very sick patients, and that's being achieved on top of standard of care. 4 out of 6 patients also have improvements in KCCQ. That was the first time we reported that. 5 out of 6 have improvements in New York Heart Association Class.

2 out of 3 patients with a high dose cord have improvements in six-minute walk tests that are above what would be considered clinically meaningful. For the very first patient evaluable at the high dose for whom we have peak VO2, they also had an improvement in peak VO2 that is above what would be considered clinically meaningful. Small N, early days, but overall, circulating biomarkers, hypertrophy, feel, and function all moving in the right direction for the majority of the patients.

Yeah. It's a good question, and let's just as a reminder, taking a step back. We're talking about the MYBPC3 mutation. It's the leading genetic cause of hypertrophic cardiomyopathy. This accounts for 20% of all mutations. That's about 120,000 patients in the U.S. alone. This is a large indication, and that makes it interesting, I think, both for investors as well as for potential partners in the biopharma space. One thing that's also interesting is there's a lot of phenotypic heterogeneity. I mean that at the level of you have adults, adolescents, even neonatal infants. You have heterozygotes. You have homozygotes. You have patients with the obstructive form of the disease and the non-obstructive form of the disease. That leads to a lot of variability in terms of how these patients are presenting, different standard of care. Some have myectomies. Some have some kind of medications or the others.

You expect there's going to be a certain amount of variability, and I'm glad that across all that variability, right now, most of our data has been generated in fact, all of our data has been generated in non-obstructive adults. TN-201, we think, is going to be important for all forms of the disease. This is a data-rich study where we're finding the signals to figure out where does TN-201 work the best. Right now, all of our data is in non-obstructive adults, and we're glad to see that even within that segment, there's a lot of heterogeneity and all these patients seem to be doing well.

In terms of we think about regulatory alignment and future approvals, one thing that we'll just have to be mindful of is that the alignment that we may achieve may be different at different times for different subpopulations. What do I mean by that? How you measure an obstructive adult versus a non-obstructive adult would be different. Majority of the patients are non-obstructive, but it would be different. Similarly, how you would measure a child who is dying of their disease within the first days, weeks, or months of life, these are the homozygous neonatal infants, very rare, very severe. That would be a different endpoint. Those would be different. When we think about the data we're generating, all of this is giving confidence in the activity of TN-201, and we're still early in our journey to figure out where does TN-201 really work the best, in which population, and where do we want to go into pivotal studies first, second, third given the heterogeneity of the disease.