Good day, and welcome to the Rocket Pharmaceuticals Investor Conference Call to discuss the FDA approval of KRESLADI, RP-L201, a lentiviral vector-based gene therapy for patients with severe leukocyte adhesion deficiency type I or LAD-I. As a reminder, today's call is being recorded. I'd now like to turn the call over to Meg Dodge, Senior Vice President of External Affairs. Meg, please begin.
Thank you, operator, and hello to everyone who joined today's call. Earlier, Rocket Pharmaceuticals announced that the U.S. Food and Drug Administration has granted accelerated approval to KRESLADI, a gene therapy for the treatment of pediatric patients with severe leukocyte adhesion deficiency type I. KRESLADI represents the first and only gene therapy approved for severe LAD-I, and this milestone marks the first commercial product approval in Rocket's history. On today's call, you will hear from Dr. Gaurav Shah, Chief Executive Officer, Dr. Jonathan Schwartz, Chief Science and Gene Therapy Officer, and Sarbani Chaudhuri, Chief Commercial Officer. Following prepared remarks, we will open the call for questions, and joining the Q&A will be Martin Wilson, Chief Corporate Officer and Principal Financial Officer.
Before we begin, I would like to remind listeners that today's call will be making forward-looking statements as within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are based on our current expectations and assumptions and are subject to risks and uncertainties that could cause actual results to differ materially from those described in such forward-looking statements.
Forward-looking statements on this call may include, among other things, statements regarding the timing and execution of commercialization activities for KRESLADI, expected patient identification and treatment timelines, anticipated launch readiness, manufacturing and treatment center preparedness, projected financial runway, potential monetization of a rare pediatric disease priority review voucher, and the continued development of our pipeline programs. Important factors that may affect future results are described in Rocket's filings with the U.S. Securities and Exchange Commission, including our most recent annual report on Form 10-K. These forward-looking statements speak only as of today's date, and Rocket undertakes no obligation to update them except as required by law. With that, I'll turn the call over to Gaurav.
Thank you, Meg. Today marks an important milestone for Rocket Pharmaceuticals and, most importantly, for patients and families affected by severe leukocyte adhesion deficiency I. I'm excited to share that the FDA has granted accelerated approval to KRESLADI, the first gene therapy approved for this devastating pediatric disease. This milestone is meaningful for three reasons. First, it addresses a devastating ultra-rare pediatric disease characterized by recurrent life-threatening infections and high early childhood mortality without definitive treatment. Second, it demonstrates Rocket's ability to execute across the full continuum of gene therapy development, from clinical research and complex manufacturing to regulatory approval. Third, the approval makes Rocket eligible for a Rare Pediatric Disease Priority Review Voucher, which represents a potential source of meaningful non-dilutive capital to support advancement of our broader pipeline. Importantly, this approval also positions Rocket to leverage our gene therapy expertise across additional rare disease programs.
Severe LAD-I is an ultra-rare inborn error of immunity, formerly known as primary immunodeficiency, caused by mutations in the ITGB2 gene that impair normal immune function. The disease is characterized by an inability of white blood cells to effectively migrate from the bloodstream into tissues to fight infection and support wound healing. As a result, affected children experience recurrent severe bacterial and fungal infections beginning early in life, often requiring frequent and prolonged hospitalization. Despite supportive care, these infections and related complications can become life-threatening. In the absence of definitive corrective therapy, severe LAD-I is associated with a very high risk of mortality in early childhood.
Historically, the standard definitive treatment option for severe LAD-I has been allogeneic hematopoietic stem cell transplantation, a complex endeavor associated with frequent and clinically meaningful risks, including graft failure and graft- versus- host- disease, which are documented even in the most recent medical literature. Allogeneic transplant is further limited by donor availability. Today's approval reflects the dedication of patients and families, our clinical investigators, advocacy partners, regulatory reviewers, and the Rocket team. It also represents an important step in Rocket's evolution into a commercial stage gene therapy company. With that, I will now turn the call over to Jonathan to review the clinical data supporting the approval.
Thank you, Gaurav. KRESLADI is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of pediatric patients with severe LAD-I due to biallelic variants in the ITGB2 gene who do not have an available human leukocyte antigen-matched sibling donor for allogeneic hematopoietic stem cell transplant. In LAD-I, ITGB2 mutations lead to deficient or absent expression of the CD18 protein on white blood cells. As a result, children with severe LAD-I experience recurrent and often life-threatening infections beginning early in life, and historically face a high risk of mortality in early childhood in the absence of definitive corrective therapy. Following treatment with KRESLADI, which is administered as a one-time intravenous infusion following myeloablative conditioning, functional copies of the ITGB2 gene are introduced into autologous hematopoietic stem cells, leading to expression of functional CD18 that forms CD18-CD11 heterodimers, enabling leukocyte adhesion to endothelial surfaces and extravasation into tissues.
This indication was approved under the FDA's accelerated approval pathway based on increases in neutrophil CD18 and CD11a surface expression, biomarkers indicating restored beta-2 integrin activity and leukocyte function. The approval is supported by data from an open-label, single-arm international clinical study evaluating a one-time infusion of gene-modified autologous hematopoietic stem cells in pediatric patients with severe LAD-I. The clinical study evaluated survival without allogeneic transplant and biomarker restoration of neutrophil CD18 and CD11a expression, which served as the basis for accelerated approval. Following infusion, neutrophil CD11a expression increased in all treated patients, as did CD18 expression in all patients in whom it was severely reduced, each exceeding pre-specified response criteria and sustained over extended follow-up. All patients are alive and none have required an allogeneic transplant, with follow-up of 3.6-5.7 years after treatment.
Measures of gene marking, including vector copy number in peripheral blood cells, have remained stable over time, supporting durable engraftment of gene-corrected hematopoietic stem cells. Supportive clinical observations during follow-up include substantial reductions in infection-related complications and hospitalizations relative to the pretreatment period. Integration site analyses to date demonstrate highly polyclonal gene marking without evidence of clonal dominance, consistent with the expected safety profile of lentiviral gene therapy. As described in the prescribing information, key risks include serious infections, veno-occlusive disease, delayed or failed engraftment, hypersensitivity reactions, and the potential for lentiviral insertional oncogenesis requiring long-term monitoring.
Consistent with the accelerated approval framework, continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory clinical trials. Rocket will continue long-term follow-up of treated patients and additional post-marketing data collection to further characterize long-term outcomes. With that, I will now turn the call over to Sarbani to discuss our commercialization approach.
Thank you, Jonathan. The approval of KRESLADI represents an important milestone both for patients and for Rocket's evolution into a commercial stage organization. Our commercialization approach begins with the patient. Severe LAD-I is a devastating pediatric disease associated with high early childhood mortality and a substantial burden on families and healthcare systems. Severe LAD-I is an ultra-rare condition. Approximately 25 children are estimated to be born with LAD-I each year in the U.S., with roughly 2/3 having the severe form of the disease. In practice, treatment volumes are influenced by factors such as diagnosis timing, referral pathway, transplant status, and the complexity of delivering an individualized ex vivo gene therapy. As a result, we expect the number of patients treated annually to remain in the single-digit range, including in the years following launch.
Accordingly, our approach emphasizes discipline and dependable delivery, comprehensive patient support, and step-by scaling as we bring this therapy to market. The sequencing of our launch is deliberate and focused on execution excellence consistent with the specialized requirements of ex vivo gene therapy administration. We anticipate commercial availability and initiation of patient enrollment beginning in the fourth quarter of 2026. This timeline reflects the operational requirements associated with delivering an ex vivo gene therapy. Key launch readiness activities include ensuring product supply readiness with external manufacturing partners, establishing coordinated vein-to-vein treatment processes, and onboarding a limited number of highly experienced qualified treatment centers. Given the complexity of treatment and the vulnerability of this pediatric patient population, KRESLADI will initially be available at a limited number of specialized centers to support operational excellence and patient safety during early commercialization.
We are working closely with leading immunologists, transplant physicians, patient advocacy organizations, and payer stakeholders to support early diagnosis, referral pathways, and access planning. We intend to provide guidance on pricing and access considerations as we approach commercial launch, consistent with the timing typically observed for therapies addressing ultra-rare diseases. From stem cell collection to infusion, the treatment journey spans approximately four to five months. As a result, we expect first patient infusions and therefore initial product revenue to occur in 2027. Our focus is to ensure that once a patient enters the treatment pathway, the entire vein-to-vein process is coordinated, predictable, and optimized for successful outcomes. With that, I will now turn the call back to Gaurav.
As Sarbani outlined, our launch approach is deliberately phased to ensure operational excellence and patient safety. Our approach to launching KRESLADI is intentionally disciplined. Ex vivo gene therapy requires a coordinated ecosystem involving manufacturing partners, specialized treatment centers, and payer processes. We made a deliberate decision to sequence certain commercialization investments following regulatory clarity and alignment on final commercial specifications. This approach ensures that when patients begin treatment, the full treatment pathway is operational, coordinated, and reliable. Our focus is on building a highly reliable treatment ecosystem from the outset, which we believe is critical to long-term commercial success. Given the ultra-rare nature of severe LAD-I, KRESLADI is not expected to be a significant near-term revenue driver. However, the importance of this approval extends well beyond near-term revenue. We believe KRESLADI creates value for Rocket on several levels.
First, it delivers the first approved gene therapy for children with severe LAD-I. Second, it demonstrates Rocket's ability to successfully execute complex gene therapy development across clinical, manufacturing, regulatory, and commercial functions. Third, the approval makes Rocket eligible for a rare pediatric disease priority review voucher, a PRV, representing a potential source of meaningful non-dilutive capital to support advancement of our broader pipeline. As of December 31st, 2025, Rocket reported cash, cash equivalents, and investments of approximately $188.9 million. Based on our current plans, we expect this capital to fund operations into the second quarter of 2027, and potentially into 2028 with monetization of the PRV or other non-dilutive sources of capital.
As stated in our earlier press release announcing this approval, we intend to evaluate strategic options for monetization of the voucher with the objective of enhancing financial flexibility and supporting advancement of our pipeline. As we move forward, key value drivers for Rocket will include commercial launch execution, continued clinical progress across our AAV programs, and strategic capital management. We will provide further updates on commercialization progress and platform milestones in the quarters ahead. Before moving to questions, I want to again thank the patients and families who participated in the clinical trial, our investigators and advocacy partners, our regulatory and agency colleagues, and the entire Rocket team. Their dedication made this milestone possible. Together, we are working toward delivering new treatment options for patients with serious and life-threatening rare diseases. Operator, please open the line for questions.
Thank you. Ladies and gentlemen, the floor is now open for questions. If you wish to join the queue to ask a question at this time, please press star one on your telephone keypad. We do ask, if listening on speakerphone this morning, that you pick up your handset while asking your question to provide optimal sound quality. Once again, please press star one on your telephone keypad at this time if you wish to join the queue to ask a question. Please hold a moment while we poll for questions. The first question this morning is coming from Andrew Tsai from Jefferies. Andrew, your line is live. Please go ahead.
Hi. Good morning. Big congratulations on the execution and approval. It's exciting times. You're planning to launch in Q4. Maybe describe the gating steps you need to accomplish or address before you're ready to launch. Secondly, as we await your pricing disclosure, are there any kind of drug precedents or comps you'd mention to the extent you're willing to share? Any bookends could be interesting to hear. Thank you.
Hi, Andrew. Thanks for the question. The critical requirements prior to patient enrollment to make sure that we deliver seamless treatment with something as complicated as ex vivo gene therapy requires a few steps, as you mentioned. First, product supply and readiness with external manufacturing partners. Second, vein-to-vein operational infrastructure. Third, the onboarding of select few qualified treatment centers. We've also been engaging with payers to ensure reimbursement. Those are the steps that are in between now and access for patients. In terms of other analogs, as you mentioned, we're not providing pricing guidance just yet, but the other analogs with ex vivo monogenic diseases that are in the market are reasonable analogs and precedents. Thank you.
Thank you. Bigger picture, how does this approval maybe embolden you to pursue other rare diseases in a similar manner? Single arm, you know, pivotal phase II type studies, you know, and similar in size. You're kinda doing this for Danon, and can we expect this to be the case for PKP2, BAG3, and maybe your other future programs? Thank you.
Yeah, thanks. We are going to shift our focus in development. We have shifted our focus to monogenic cardiovascular conditions, many of which are rare, like Danon and like PKP2. There will be more. This PRV certainly helps us invest in those programs with a bold mindset, as you mentioned. Also Danon itself comes with the PRV, so some of these diseases may also have their own PRVs. PRVs have been a great program to help companies like Rocket advance the broader pipeline.
Great. Congrats again.
Thank you. Your next question is coming from Patrick Dolezal from LifeSci Capital. Patrick, your line is live. Please go ahead.
Hi. Passing on my congratulations as well, and thanks for taking the questions. Just on the point of the PRV received today, could you provide a little more implications, a little more context for the implications of cash runway there? Is there sort of a certain go or no-go amount that you're looking for? I guess the second question is how might the cash burn be impacted by commercialization activities related to KRESLADI? Thanks.
Great. Thanks, Patrick. The PRV sale, with regards to PRV sale, we are in active discussions and engaging with external parties, as we speak. More on that as soon as we have more information. In terms of the cash runway, without speculating on what the price will be, we anticipate the cash runway to be extended into early 2028. In terms of KRESLADI commercial efforts, we are going to execute what we would call a minimal viable launch. Meaning we will make the product available to patients and physicians who deem it something, a good option for those patients. We are not actively otherwise marketing or putting a lot of money into commercial efforts for KRESLADI. We are instead going to focus those commercial efforts into expanding the Danon commercial setup and the other cardiovascular programs.
Super helpful. Thank you. Congrats again.
Thank you. Your next question is coming from Josh Schimmer from Cantor. Josh, your line is live. Please go ahead. Josh, please check to see if your line may be muted. You can please proceed with your question at this time.
Thank you. Yep, thanks. Did not realize I was muted. Thanks for taking the questions, and congrats on the approval. Three quick ones. First, maybe semantics, but, Gaurav, you said the indicated KRESLADI is eligible for a PRV. When do you actually get the PRV? What actually has to happen to go from actual eligibility to in hand? That's number one. Number two, do you still plan on exploring, perhaps less severe patients? I think you'd indicated that at one point that might have been a consideration for KRESLADI. Number three, for the side effects listed on the package insert, just confirming that you did not see any of those in the clinical trial. Those are only theoretical based on the mechanism of intervention. Thank you.
Thanks, Josh. I should clarify that with the approval, we have the PRV in hand, so that's an important clarification. Thanks for raising it. In terms of the moderate patient population, this may be part of our lifecycle management, but right now we are focused on severe LAD-I patients. For the third question, I'll pass it to Jon.
Thanks for the question and good morning, Josh. Most of the serious adverse events that were identified in the pivotal study were infections which occurred during the post-conditioning neutropenia period, and these are fully resolved. One patient did experience veno-occlusive disease, and then the full set of side effects are available in the prescribing information as well as in the New England Journal publication from 2025. I would emphasize that we did not identify any instances of engraftment failure, nor did we identify any instances of delayed neutrophil or platelet engraftment. We did not observe any hypersensitivity reactions, and very importantly, there was no evidence for insertional oncogenesis. The integration site analyses at all time points for all patients indicated a very highly polyclonal integration site patterns.
Okay. Thank you very much.
Thank you. Your next question is coming from Mani Foroohar from Leerink. Mani, your line is live. Please go ahead.
Hi. Good morning. This is Lili Nsongo, on for Mani. Thanks for taking our question. Can you remind us the estimated size of the addressable market given the approval in patient with no HLA-matched donor sibling. Additionally, you mentioned a patient journey of four to five months. What are the rate-limiting steps to that, and what should we expect this to look like at a steady state? Thank you.
I will answer the addressable market question, and I'll pass the second part of your question to Sarbani. On the addressable market, there are, we estimate, about 25 patients born with LAD type I in the U.S. every year. Two-thirds of them are severe. Half of them will get a transplant, and about a quarter would have an HLA-matched sibling donor transplant. You can see just from this math that we anticipate single-digit numbers even long term in terms of treatments, but we'll be able to provide more guidance as we get closer to the actual launch. In terms of the vein to vein time and aspects of that, I will ask Sarbani to address that.
Thank you, Gaurav. To clarify, we had mentioned that our vein-to-vein time is around four to five months. It is in the range of what we would expect with an ex vivo gene therapy, and it's primarily driven by the individualized patient collection, manufacturing to infusion, and the time it takes for our manufacturing to happen as well as the release of the final drug product. Of course, in the beginning it is a little bit more unpredictable because we have to see about the time it takes for payer access, but over time, we expect this to be in the four- to five-month range from the time a patient is enrolled to the time they actually get infused with drug.
Thank you.
Thank you. Your next question is coming from Jason Zemansky from Bank of America. Jason, your line is live. Please go ahead.
Morning. Congrats on the milestone and thanks for taking our question. Appreciate that most of the treatment will happen in the United States. Curious about the pathway for non-U.S. patients, simply because if we're talking about single-digit number of patients treated, you know, what does the inflow from Europe or other markets look like? Thank you so much.
Thanks, Jason. Our focus right now is the U.S. market, and we have not made specific plans beyond that at the moment, and if we do, we'll update everybody. Thanks, Jason.
Thank you. Your next question is coming from Tara Bancroft from TD Cowen. Tara, your line is live. Please go ahead.
Hi. Good morning and congrats. I'm curious, based on the FDA communications that you've had and received, what's your level of confidence that the long-term follow-up from this trial would suffice for this post-marketing requirement that's labeled by the language in the label? Or do you think there will be another confirmatory trial that would have to start, and if so, what would that look like and a potential timeline? Thanks.
Thanks, Tara. The FDA guidance on the path to full approval is very clear with regard to the clinical program. It is further follow-up of the current ongoing clinical study as well as evaluation of a subset of patients in the post-marketing registry. In other words, patients who are actually treated in the real world, a subset of those. There is no new clinical trial required at all, and that's very clear in the post-marketing requirements. Thank you.
Thank you. Your next question is coming from Yun Zhong from Wedbush Securities. Yun, your line is live. Please go ahead.
Hi. Good morning. Thank you very much for taking the questions and congratulations on the approval. I understand that you're not going to actively market this product, but anything that you think that you could potentially learn from bluebird's experience given that the lentiviral gene therapy launch and commercialization was, maybe a little disappointing, as compared to expectation? Thank you very much.
I'll ask Sarbani Chaudhuri to address that.
Thank you, Gaurav. As we stated, we are operating already under the assumption that this is an ultra-rare patient population at birth, and our go-to-market model is optimized for that. We are both being efficient in our commercialization approach as well as in our manufacturing approach. We're starting with realistic expectations and having realistic expectations on how we get this to market in the most efficient way.
Great. Thank you.
Thank you. Your next question is coming from Tessa Romero from JP Morgan. Tessa, your line is live. Please go ahead.
Hi, team. This is [Miriam] on for Tess. Thanks for taking our question, and congrats on the news. Just one question from us. What is the right way to think about the amount of data the FDA would wanna see from treated patients in the ongoing clinical study and post-marketing registry to adjust Accelerated Approval to a traditional approval? Thank you.
Jonathan?
Thanks for the question. The level of data that the FDA will require from post-marketing patients is really data that's going to be available through what would be considered routine clinical management from our treating physicians and the primary immunodeficiency experts that would be referring patients into the study. Largely, this would include things like survival, transplant status, and the flow cytometry results on the white blood cells indicating CD11 and CD18 levels, which is something that would be conducted in patients with severe LAD-I. So it's not some extraordinary requirement. It's very consistent with the way the expert immunodeficiency clinicians will manage the patients.
Okay, that's helpful. If I may ask additional one, how is resumption of patient dosing and Danon tracking timing-wise? Any updates on that?
Yeah. Thanks for the question. I think you asked about Danon, and I couldn't hear quite clearly, but Danon patient tracking is on course to begin first half of 2026. Thank you.
Thank you. Your next question is from Mike Ulz from Morgan Stanley. Mike, your line is live. Please go ahead.
Thanks. Good morning, and congratulations on the approval as well. Maybe just a quick one on the launch plans. Can you maybe give a little more color on the number of specialty centers you plan to target to have online maybe by the end of this year, and then how that could evolve as the launch progresses in the outer years? Thanks.
Sarbani?
Thank you. As you mentioned earlier, we plan to activate a very small number of highly specialized treatment centers, and given that it's an ultra-rare disease. At this point, we cannot give specific numbers, but our hope is we have a handful of them activated by the time we're ready for launch, which is in Q4. Then over time, we will evaluate if we need more centers. Then in terms of the question of where these patients are, the good part and why we feel we can have a very efficient commercialization approach is these patients are primarily in about the 40+ PIDTC specialist centers across the country. Largely, I would say all the patients that will come to any qualified treatment center will be coming from these specialty centers, and they have very good peer-to-peer networks. Thank you.
Great. Thank you.
Thank you. Before we close today's call, just a final reminder, if anyone would like to join queue, please press star one on your keypad at this time. Once again, please press star one if you wish to join queues to ask a question at this time. There are no further questions in queue. Ladies and gentlemen, this concludes today's conference call. Thank you all for participating. You may now disconnect and have a great day.