Rocket Pharmaceuticals, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Josh, thanks for having me, having us. Rocket is a gene therapy company. We are focused on rare genetic cardiomyopathies. We have three in the clinic, one representing each of the big buckets of genetic cardiomyopathies, which are hypertrophic, represented by Danon disease, arrhythmogenic, demonstrated by PKP2, and dilated, demonstrated by BAG3. We try to find assets that have a very clear mechanism of action, where we target the protein of interest in the cell of interest, and in which there's a high unmet need, and where we believe that we can see clinical results in a timeframe that makes sense for regulatory reasons. That's been our philosophy since day one. We actually started the company as an ex vivo lenti company, and we still have those programs, including the recently approved KRESLADI for severe LAD-I, a Fanconi anemia program, and a PKD program.

We've shifted our focus to cardiomyopathies in the last few years to really be able to prioritize and use our resources most wisely, but we continue to seek opportunities to partner out the LV assets. We will be launching KRESLADI in the fourth quarter of this year for those patients who want access to it. In general, we have a pipeline underneath these six programs that's deep and equally exciting. We're very excited about the next 9 to 12 months, as there are numerous catalysts coming up.

Well, we don't want to be the most expensive out there. But the reality, the truth is that the cost of non-therapy is pretty vast and pretty large, and even the numbers that are out there for other approved gene therapy products are lower than the actual cost of treating an LAD-I patient over the course of a lifetime. So we'll be announcing that at some point in the coming months, but in expected line with other gene therapies.

Okay on the ex vivo lenti side.

Yeah. There's almost an inverse correlation between the number of patients out there and the devastating-ness of a disease, right? So yes, Danon is very devastating. It's probably one of the most aggressive cardiomyopathies out there. Also the one where we can demonstrate clean, clear benefit in the single-arm trial, which we're working on right now for a pivotal trial. Danon, I would say we continue to say at least 15,000 patients in the U.S. and Europe. The next most devastating is likely BAG3, which is a dilated cardiomyopathy. It's a bigger market. We haven't come out with the actual numbers or epidemiology in that. And PKP2 is, of course, can be fatal with sudden cardiac deaths.

There are more than 50,000 patients with PKP2 in the U.S. and Europe, but that's a disease that's heterogeneous and where we need to be very smart about trial design so we can win if it works.

Yeah. Unfortunately for AAV, there are no preclinical models that mimic the safety we see in humans. There's just no TMA model, there's no even platelets in the LFTs, and mice and NHPs and pigs tend to not fluctuate too much with AAV. We have to learn this in the real world and sometimes the hard way. In terms of the dose, we have now treated 3 patients with the revised regimen and the recalibrated dose of 3.8 E13 vector genomes per kilogram successfully, safely. These patients tolerate the therapy well. It's been a journey, right? Last several years, you learn so much from each patient. Even in phase I when we'd begun, when we first started with patient 1001, he got some steroids but nothing else, and he wouldn't take his steroids, and it took a while to sort of stabilize him.

He did not have TMA. But I can say even that patient who is 7 years out is working full time, and he's living a normal life in his mid-20s, which would be unexpected with anything else, right? So wherever we are in Danon, I think that the long-term path to success is about the positive benefit risk. I think on the safety side, I feel we've solved it with this recalibrated dose and this regimen. Obviously, we'll need to treat more patients to see for sure. I think that with AAVs for heart, this mid to low upper E13 range seems like the Goldilocks zone. We're in the same place with PKP2. We have not announced our BAG3 dose, but you can understand it's in that range as well. And that gets around some of the more common TMA and liver issues that are seen in the 1 E14 range.

Yeah. The only time we have seen TMA in the setting of Danon disease was in phase I, where we were well above 1 E14 in one patient. In Danon at this dose, in a couple of patients, one of them had another complement activating mutation called CUL4B, so we don't know exactly what happened there. Another patient got sort of the higher end of the dose, and also had recent prior infections. It could be that all three of those patients had issues that we're going to screen out anyway with new patients. Having said that, the dose range in which we saw clear efficacy in phase I was anywhere between around 4 E13 up to 1.1 E14.