Rocket Pharmaceuticals, Inc. Common Stock Status update

Meg, please begin. Thank you, and welcome to everyone joining us for today's Danon disease program update.

Today, we will share new phase I findings and preliminary phase II clinical observations for RP-A501, including the initial safety experience with the recalibrated dose. We will also review the pivotal study's definition of efficacy success and our plans to complete dosing, followed by an update on the Duchenne population and potential commercialization opportunity. You will hear from Chief Executive Officer, Dr. Gaurav Shah, our Chief Medical Officer, Dr. Syed Rizvi, and our Chief Commercial Officer, Sarbani Chaudhuri. We are also pleased to include perspectives from Dr. Eric Adler and Dr. Barry Greenberg, whose work has helped advance the understanding of Danon disease and the clinical evaluation of RP-A501. Following prepared remarks, we will move into Q&A with our management team, including Gaurav, Syed, Sarbani, and our Chief Science and Gene Therapy Officer, Dr. Jonathan Schwartz.

Before we begin today's discussion, this discussion includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements concern our development plans, clinical and regulatory milestones, population estimates, and potential commercial opportunity. They involve risks and uncertainties, and actual results may differ materially. Please review the disclaimer in today's presentation and the risk factors in our filings with the Securities and Exchange Commission. These statements speak only as of today, and Rocket undertakes no obligation to update them except as required by law. RP-A501 is investigational, and its safety and efficacy have not been established. The revenue estimates we will discuss are internal modeling scenarios subject to clinical success, regulatory approval, and commercial assumptions. With that, I would like to now turn the program over to Gaurav.

Thank you, Meg, and thank you to everyone for joining. Before turning to today's program update, I want to highlight the financing we just announced after market close. Under our new Hercules facility, we received an initial $35 million, which, together with our existing resources and based on our current operating plan, is expected to fund operations into the third quarter of 2028. Additional borrowings under the facility could also extend our cash runway into 2029, subject to applicable borrowing conditions and depending on the timing and amount of future draws and our operating expenditures. This additional financial capacity supports our focus on completing the RP-A501 pivotal program and advancing toward a potential BLA submission. Let's start with the bottom line up front.

First, today, we are sharing additional phase I data, both longer-term clinical observations and biopsy findings, which show evidence of disease reversal or stabilization through 36 months and up to seven years post-treatment with RP-A501. Second, preliminary clinical data from the initial four phase II patients who were treated before the recalibrated dose and immune regimen and did not receive C3 inhibitors further support the efficacy of RP-A501. These findings build on evidence of restored myocardial LAMP2 expression and changes in cardiac structure while extending our understanding of patients' clinical courses over several years. The original phase II experience included serious safety events, including the tragic loss of a patient in the cohort evaluating an immunomodulatory regimen containing a C3 inhibitor. Together with input from global external experts, we responded by recalibrating the dose and modifying the treatment protocol.

The third takeaway here today is that the first three patients treated under this final revised approach have completed the initial observation period without clinical or laboratory evidence of thrombotic microangiopathy, capillary leak syndrome, or other significant toxicities. These early observations are encouraging and follow-up continues. Syed will review the safety experience and the changes we have made. Number four, we have aligned now with the FDA on a pivotal efficacy population of 12 males receiving commercial-grade RP-A501 at the recalibrated dose. New today is that the efficacy target is at least seven patients meeting both the pre-specified responder criteria at 12 months, which are improvement from baseline to at least Grade 1 in myocardial LAMP2 protein expression, and a reduction of at least 10% from baseline in left ventricular mass index, or LVMi. This gives us a clearly defined responder analysis.

The first three patients count toward that population, leaving nine additional patients to be dosed. We expect to complete dosing by mid-2027, and I will discuss the pivotal design and our intended accelerated approval pathway later in the program. Finally, today, we will share new analyses that substantially strengthen our understanding of Danon epidemiology and the diagnosed patient population and reinforces our confidence in a potential $1 billion-plus global peak annual commercial opportunity in the initial indication in Danon males alone. We have already engaged with FDA in expansion to females, which would increase this market much further.

We conducted two comprehensive independent epidemiology analyses, one genotype-based and one phenotype-based, and both converge on approximately the same estimate, which is 10,000 to 11,000 people with Danon disease in the U.S. and more than 20,000 if you include Europe as well. Importantly, we have also identified, on a cumulative basis, more than 900 U.S. patients with a confirmed Danon disease diagnosis, establishing a patient-level baseline while highlighting a substantial diagnosis gap. Sarbani will take you through this evidence behind the findings, where these patients receive care, and how these insights provide a strong foundation for accelerating diagnosis as we move toward launch. To put both the clinical need and the opportunity in context, we first need to understand the disease itself from the underlying biology to its aggressive clinical course, and importantly, the limitations of current care.

For that, I am pleased to turn this over to Dr. Eric Adler, an internationally recognized cardiologist, expert in Danon disease, and academic founder of the Danon program alongside Rocket. Eric will take us through the biology of Danon, how the disease progresses, why patients remain underdiagnosed, the burden and limitations of heart transplant, and finally, why LAMP2 gene addition is so directly aligned with the underlying disease mechanism.

Well, thank you, Gaurav. As you know, I am a heart failure cardiologist who has cared for Danon patients and studied Danon in the clinic and laboratory for many years. I still remember the first Danon case I saw nearly 20 years ago and the hopeless feeling I felt staring at that hypertrophied heart and knowing there is that little I had to offer. How far we have come. Danon stands out among inherited cardiomyopathies for its near complete lifetime penetrance in males, early and aggressive cardiac course, multisystem involvement, and the potential to affect multiple members of the same family. Danon is caused by pathologic variants in LAMP2, which encodes lysosome-associated membrane protein 2. It is X-linked and can affect successive generations, but de novo variants also occur, and absent family history does not rule it out. A hallmark is severe thickening of the heart muscle.

Ejection fraction can remain relatively preserved despite substantial hypertrophy, myocardial injury, and electrical abnormalities. By the time it falls, the cardiomyopathy may already be advanced. Importantly, hypertrophy, and specifically cardiac mass measured by MRI, is a very important tool we have for prognosticating patients. We know that when the estimated LV mass is abnormal in patients with cardiomyopathy, their prognosis is worse than those with normal LV mass. The clinical course differs for Danon males and females. My focus today will be primarily on the males. In males, cardiomyopathy often begins in childhood or adolescence and progresses rapidly. By the time many inherited cardiomyopathies are only beginning to manifest, a young man with Danon may already have progressed to advanced heart failure, transplantation, or death by his early 20s. Females generally develop cardiac involvement later in a more heterogeneous course.

Emerging natural history data shows that the majority are clinically affected by their 30s, while a subset develop life-threatening heart failure at a younger age. Despite its severity, Danon remains significantly underdiagnosed. We know the clinical signals that should raise suspicion. A young patient, particularly a male, with unusual severe unexplained hypertrophy. EKG abnormalities including ventricular pre-excitation, elevated muscle or liver enzymes, or manifestations outside the heart are sometimes, but not always, present. In my opinion, any unexplained cardiac hypertrophy or dilation in a young person should warrant a genetic test. You may be saving their life as well as their family members. This is the best way to diagnose Danon as well as other genetic cardiac disorders. Unfortunately, genetic testing remains low in the broader community and findings across organ systems may not be connected. Essentially, any young person with cardiac hypertrophy should get an evaluation.

This can save lives for the patient, but their family members as well. In short, in my opinion, any unexplained cardiac hypertrophy or dilation in a young person should warrant a genetic test. You may be saving their life as well as their family members. This is the best way to diagnose Danon as well as other genetic cardiac disorders. Unfortunately, genetic testing remains low in the broader community, and findings across other organ systems may not be connected. Earlier diagnosis supports disease-specific cardiac care, timely planning for advanced heart failure and transplantation, and evaluation of potentially affected family members. In Danon, time matters because progression of heart failure can be remarkably rapid. Today, there is no approved disease-modifying therapy for Danon. Current care is largely supportive. Cardiac surveillance, arrhythmia treatment, including ICD, management of heart failure complications, and as disease advances, mechanical circulatory support and transplant evaluation.