Leukocyte-Adhesion Deficiency Syndrome

Positive, previously disclosed results from the global Phase 1/2 trial demonstrated genetic and phenotypic correction combined with hematologic stabilization extending out to 42 months after treatment with RP-L102 CRANBURY, N.J.--(BUSINESS WIRE)-- Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of genetic therapies for rare disorders with high unmet need, today announced that the European Medicines Agency (EMA) accepted the Marketing Authorization Application (MAA) for RP-L102, its lentiviral (LV) vector-based investigational gene therapy for Fanconi Anemia (FA), complementation group A, a rare genetic disorder caused by mutations in the FANCA gene affecting DNA repair and characterized by bone marrow failure (BMF), cancer predisposition, and congenital malformations. “The acceptance of the MAA for RP-L102 marks an important step forward in our goal of bringing this potential gene therapy treatment to patients impacted by this devastating childhood disorder. Currently, there are no existing options to potentially prevent BMF for patients with FA,” said Kinnari Patel, Pharm.D., MBA, President, Head of R&D and Chief Operating Officer, Rocket Pharma. “We are appreciative of the patients, their families, and researchers who helped reach this meaningful milestone and continue participating in the clinical development program. We look forward to partnering closely with the EMA throughout the review process to make RP-L102 available to patients with FA who are in need of new treatment options.” MAA acceptance was based on positive, previously disclosed data from the global RP-L102 Phase 1/2 clinical trial. RP-L102 demonstrated sustained genetic correction, comprehensive phenotypic correction, and hematologic stabilization. The safety pro highly favorable with no significant safety signals, and the treatment, administered without any cytotoxic conditioning, was well tolerated. There were no signs of bone marrow dysplasia, clonal dominance, or insertional mutagenesis related to RP-L102. In the absence of allogeneic hematopoietic stem cell transplant (HSCT), the primary cause of death among patients with FA is BMF, which typically occurs during the first decade of life. Although allogeneic transplants can cure the hematologic component of FA, they confer significant side effects and substantially increase the risk of solid organ malignancies, which have become the most frequent cause of FA-related death. The Biologics License Application (BLA) for FA remains on track for submission to the U.S. Food and Drug Administration (FDA) in the first half of 2024. About RP-L102 RP-L102 is an investigational gene therapy that contains autologous (patient-derived) hematopoietic stem cells that have been genetically modified with a lentiviral (LV) vector to contain a functional copy of the FANCA gene. Rocket holds FDA Regenerative Medicine Advanced Therapy (RMAT), Rare Pediatric Disease, and Fast Track designations in the U.S., PRIME and Advanced Therapy Medicinal Product (ATMP) designations in the EU, and Orphan Drug designation in both regions for the program. RP-L102 was in-licensed from the Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación Biomédica en Red de Enfermedades Raras and Instituto de Investigación Sanitaria Fundación Jiménez Díaz. About Fanconi Anemia Fanconi Anemia (FA) is a rare genetic disorder characterized by bone marrow failure (BMF), cancer predisposition, and congenital malformations. In the absence of allogeneic hematopoietic stem cell transplant (HSCT), the primary cause of death among patients with FA is BMF, which typically occurs during the first decade of life. Allogeneic HSCT, when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Both chemotherapy conditioning and graft-versus-host disease, a known complication of allogeneic HSCT, are associated with an increased risk of solid tumors, mainly squamous cell carcinomas of the head and neck region. Approximately 60-70% of patients with FA have a Fanconi Anemia complementation group A (FANCA) gene mutation, which encodes for a protein essential for DNA repair. Mutations in the FANCA gene lead to chromosomal breakage and increased sensitivity to oxidative and environmental stress. Increased sensitivity to DNA-alkylating agents such as mitomycin-C (MMC) or diepoxybutane (DEB) is a “gold standard” test for FA diagnosis. Somatic mosaicism occurs when there is a spontaneous correction of the mutated gene that can lead to stabilization or correction of a FA patient’s blood counts in the absence of any administered therapy. Somatic mosaicism, often referred to as “natural gene therapy” provides a strong rationale for the development of FA gene therapy because of the selective growth advantage of gene-corrected hematopoietic stem cells over FA cells. There is a high unmet medical need for patients with FA. About Rocket Pharmaceuticals, Inc. Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of investigational genetic therapies designed to correct the root cause of complex and rare disorders. Rocket’s innovative multi-platform approach allows us to design the optimal gene therapy for each indication, creating potentially transformative options that enable people living with devastating rare diseases to experience long and full lives. Rocket’s lentiviral (LV) vector-based hematology portfolio consists of late-stage programs for Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure (BMF) and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, and Pyruvate Kinase Deficiency (PKD), a monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. Our adeno-associated viral (AAV) vector-based cardiovascular portfolio includes a late-stage program for Danon Disease, a devastating heart failure condition resulting in thickening of the heart, an early-stage program in clinical trials for PKP2-arrhythmogenic cardiomyopathy (ACM), a life-threatening heart failure disease causing ventricular arrhythmias and sudden cardiac death, and a pre-clinical program targeting BAG3-associated dilated cardiomyopathy (DCM), a heart failure condition that causes enlarged ventricles. For more information about Rocket, please visit and follow us on LinkedIn, YouTube, and X. Rocket Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements concerning Rocket’s future expectations, plans and prospects that involve risks and uncertainties, as well as assumptions that, if they do not materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. All statements other than statements of historical facts contained in this release are forward-looking statements. You should not place reliance on these forward-looking statements, which often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “will give,” “estimate,” “seek,” “will,” “may,” “suggest” or similar terms, variations of such terms or the negative of those terms. These forward-looking statements include, but are not limited to, statements concerning Rocket’s expectations regarding the safety and effectiveness of product candidates that Rocket is developing to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Danon Disease (DD) and other diseases, the expected timing and data readouts of Rocket’s ongoing and planned clinical trials, the expected timing and outcome of Rocket’s regulatory interactions and planned submissions, Rocket’s plans for the advancement of its DD program, including its planned pivotal trial, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, Rocket’s ability to establish key collaborations and vendor relationships for its product candidates, Rocket’s ability to develop sales and marketing capabilities or enter into agreements with third parties to sell and market its product candidates and Rocket’s ability to expand its pipeline to target additional indications that are compatible with its gene therapy technologies. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket’s dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, unexpected expenditures, Rocket’s competitors’ activities, including decisions as to the timing of competing product launches, pricing and discounting, Rocket’s ability to develop, acquire and advance product candidates into, enroll a sufficient number of patients into, and successfully complete, clinical studies, Rocket’s ability to acquire additional businesses, form strategic alliances or create joint ventures and its ability to realize the benefit of such acquisitions, alliances or joint ventures, Rocket’s ability to obtain and enforce patents to protect its product candidates, and its ability to successfully defend against unforeseen third-party infringement claims, as well as those risks more fully discussed in the section entitled “Risk Factors” in Rocket’s Annual Report on Form 10-K for the year ended December 31, 2023, filed February 27, 2024 with the SEC and subsequent filings with the SEC including our Quarterly Reports on Form 10-Q. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. View source version on businesswire.com: Contacts Media Kevin Giordano media@rocketpharma.com Investors Brooks Rahmer investors@rocketpharma.com Source: Rocket Pharmaceuticals, Inc. View this news release online at:

Pictured: 3D rendering of human cells and DNA/iStock/iStock, anusorn nakdee 2023 was a banner year for cell and gene therapy, with seven FDA approvals, according to the Alliance for Regenerative Medicine. And the pace doesn’t appear to be slowing at all as the second quarter of this year gets underway. The advocacy group is anticipating an even bigger year for the CGT space in 2024, with a potential 17 approvals in the U.S. and EU combined, according to ARM’s annual Cell & Gene State of the Industry Briefing in January. “It seems like the FDA is really pushing forward with accelerated approvals for cell and gene therapies, and that’s quite encouraging to see,” Jack Allen, a senior research analyst at Baird, told BioSpace. “These can be quite expensive products to develop, and if we’re able to leverage abbreviated pathways to get them to market rapidly, I think that can really reignite enthusiasm for the space.” Allen noted that cell and gene therapy is somewhat de-risked by the fact that, in many instances, these treatments involve introducing the genetic sequence for a native functional protein. “I think there will be some bumps in the road as it relates to pressing forward rapidly with the technology,” he said, but “it seems like the FDA has buy-in and is willing to ride through some of those bumps.” Here, we take a closer look at six of the more notable cell and gene therapies approved during the past year—two of them under the FDA’s accelerated approval pathway—and preview some of the decisions on the horizon. Cell Therapies BMS’s Breyanzi Chronic lymphocytic leukemia and small lymphocytic leukemia On March 14, the FDA approved Bristol Myers Squibb’s Breyanzi as the first CAR T cell therapy for relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia. In the pivotal TRANSCEND 004 trial, Breyanzi elicited a complete response—something that is “basically unheard of” in patients with relapsed/refractory CLL, according to Rosanna Ricafort, vice president and head of late development hematology and cell therapy at BMS—in 20% of recipients, with responses lasting more than 35 months. The Big Picture In November 2023, the FDA launched an investigation into the “serious risk” of secondary malignancies in patients treated with BCMA- or CD19-directed autologous CAR T cell therapies. This led to the addition of a boxed warning to all six commercial CAR-T therapies at the time, including BMS’s Breyanzi. But industry leaders and the FDA itself have been supportive of CAR-T’s risk/benefit profile. Breyanzi’s approval in two more indications, along with the recommendation of FDA advisers to move Abecma and J&J’s Carvykti into earlier lines of treatment for multiple myeloma, have cemented this tone. Iovance’s Amtagvi Melanoma In one of the year’s most anticipated decisions, the FDA in February greenlit the first one-time cell therapy for a solid tumor, Iovance Biotherapeutics’ Amtagvi for unresectable or metastatic melanoma, under the accelerated approval pathway. Iovance is currently conducting a confirmatory study to verify the therapy’s benefit. The Big Picture Amtagvi is the first tumor-infiltrating lymphocytes (TIL) therapy, a treatment modality some experts say has advantages over CAR-T. While CAR Ts recognize only a small number of proteins on the surface of tumor cells, TILs can identify tumor targets derived from intra- or extracellular tumor proteins, Sammy Farah, CEO of Turnstone Biologics, told BioSpace. As of February 2023, there were more than 75 TIL immunotherapies in preclinical or clinical studies for various indications. Gene Therapies Orchard Therapeutics’ Lenmeldy Metachromatic leukodystrophy Last month, the FDA approved Orchard Therapeutics’ Lenmeldy as the first gene therapy for metachromatic leukodystrophy (MLD), a rare, degenerative disease characterized by loss of motor and cognitive function and early death. MLD is caused by a deficiency in the arylsulfatase-A (ARSA) gene, leading to a buildup of fatty substances in the cells. Lenmeldy is a single-dose infusion made from a patient’s own hematopoietic stem cells, which have been genetically modified to include functional copies of the ARSA gene. The Big Picture Lenmeldy joins a growing list of gene therapy firsts in pediatric diseases, including Sarepta’s Elevidys for Duchenne muscular dystrophy and bluebird bio’s Skysona for cerebral adrenoleukodystrophy. It is also the first FDA-approved treatment for MLD patients, “who previously had no treatment options beyond supportive and end-of-life care,” Orchard CEO Bobby Gaspar said in a statement. Vertex and CRISPR Therapeutics’ Casgevy Sickle cell disease, beta thalassemia Possibly the most celebrated approval of 2023 went to Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy, which in December became the first-ever CRISPR-based gene editing therapy in the U.S., for sickle-cell disease (SCD). Just one month later, Casgevy was also approved for transfusion-dependent beta thalassemia, more than two months ahead of its PDUFA date. The Big Picture Casgevy’s SCD approval came just over a decade after the publication of the Nobel Prize-winning CRISPR-Cas9 technology—a timeline many industry experts have deemed faster than what would normally be expected of a new modality. But CRISPR is not without its risks. Researchers have cited cell toxicity and genomic instability as potential side effects, which could potentially trigger tumor development. Scientists are now working to improve on the technology with new modalities, including base editing and epigenetic editing. Bluebird bio’s Lyfgenia Sickle-cell disease While the historic nature of Casgevy’s approval won the day, bluebird bio’s Lyfgenia, a lentiviral gene therapy, also got the FDA’s nod for SCD on Dec. 8, 2023. Treatment with Lyfgenia led to the complete resolution of vaso-occlusive events 6 to 18 months after infusion, making it another promising option for patients. The Big Picture Allen said Lyfgenia may have a couple of advantages in the SCD market. “Both [therapies] are incredibly transformative in that they effectively eliminate sickle-cell disease–induced pain crises. Lyfgenia I think is quite interesting in that there’s a longer durability of data . . . and they also have some data in stroke patients, which I think is going to be differentiating in the commercial marketplaces” given the prevalence of stroke in SCD. Lyfgenia also has the upper hand over Casgevy in terms of developing the infrastructure needed to deliver treatment to patients. Sarepta’s Elevidys Duchenne muscular dystrophy In one of 2023’s more controversial decisions, the FDA approved Sarepta Therapeutics’ Elevidys as the first gene therapy for Duchenne muscular dystrophy (DMD). Elevidys missed the primary functional endpoint in a randomized trial but won accelerated approval based on data showing it increased the expression of the micro-dystrophin protein—a biomarker the agency determined is “reasonably likely to predict clinical benefit” in DMD patients 4 to 5 years of age. The FDA’s green light followed an adcomm meeting where its advisers narrowly recommended the gene therapy for approval. Then, just four months after the approval, Elevidys failed a confirmatory trial. The Big Picture Elevidys’ approval kicked off a wave of momentum in the DMD space. In October 2023, the FDA authorized Santhera Pharmaceuticals’ Agamree, and just last month, Italfarmaco won approval for Duvyzat, the first nonsteroidal drug approved to treat patients with all genetic variants of the disease. On the Horizon Rocket’s Kresladi Leukocyte adhesion deficiency-I Rocket Pharmaceuticals had expected a decision on its gene therapy Kresladi, in development for the rare disease leukocyte adhesion deficiency-I, in March, but the FDA pushed the date back to June 30, 2024 in order to allow for more review time. BMS’s Breyanzi Follicular lymphoma and mantle cell lymphoma It’s a big year for BMS’s Breyanzi, as the company is expecting the FDA to decide on the CAR T cell therapy as a treatment for patients with relapsed or refractory follicular lymphoma on May 23 and for those with relapsed or refractory mantle cell lymphoma who have been treated with a Bruton tyrosine kinase inhibitor therapy on May 31. Pfizer’s Beqvez Hemophilia B After winning approval in Canada in January, Pfizer’s adeno-associated virus-based gene therapy fidanacogene elaparvovec—marketed as Beqvez in Canada—has a PDUFA date in the second quarter of 2024. Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.

Aaron Ondrey joins as Chief Financial Officer bringing seasoned leadership experience in financial management, strategic planning, commercial finance, and capital allocation Additional key appointments within existing corporate leadership team expand capabilities and expertise spanning early discovery through commercialization CRANBURY, N.J.--(BUSINESS WIRE)-- Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of genetic therapies for rare disorders with high unmet need, today announced the appointment of Aaron Ondrey, as Chief Financial Officer, and the further evolution of its corporate leadership team through key appointments with existing team members. These leadership announcements build on and expand Rocket’s preparedness for its planned transition to commercial stage and continued development of its pipeline. Aaron Ondrey joins Rocket as Chief Financial Officer, bringing more than 20 years of experience in financial management, strategic planning, commercial finance, capital allocation and mergers and acquisitions having held multiple finance leadership positions across the pharma and biotech industry. Mr. Ondrey most recently served as CFO of Mirati Therapeutics through the launch of KRAZATI® and the company’s acquisition by Bristol Myers Squibb in January 2024. He brings invaluable expertise to support Rocket’s commercial transition and growth trajectory, notably strong financial acumen and exceptional operational management capabilities. Prior to Mirati, Mr. Ondrey also held senior leadership positions at Arena Pharmaceuticals, Alexion Pharmaceuticals, and Regeneron Pharmaceuticals. The key appointments within Rocket’s existing corporate leadership team are as follows: Kinnari Patel, Pharm.D., MBA, has been appointed President, Head of R&D and Chief Operating Officer. Dr. Patel will be focused on R&D with oversight spanning research through late-stage development and manufacturing. In addition, she will continue in her capacity as COO, driving company operations aimed toward advancing the company’s key strategic priorities. Jonathan Schwartz, M.D., has been appointed Chief Medical & Gene Therapy Officer, with his remit spanning Research and Discovery as well as Clinical Development. Dr. Schwartz will bring deep and seasoned scientific and clinical thought leadership instrumental in continuing to develop and advance Rocket’s current and future pipeline. Mark White, MB.ChB, has been appointed General Manager, Commercial Affairs, leading the Medical Affairs, Marketing, Commercial Operations, and Value & Access functions. Dr. White’s extensive drug development and franchise leadership experience, combined with the benefit of bringing these functions together under his leadership, best positions Rocket for long-term success with highly complex therapies aimed at rare diseases. Martin Wilson. J.D., has been appointed General Counsel & Chief Corporate Officer, and will lead Legal, Compliance, and Corporate Development. This evolution creates a newly integrated team aimed at advancing Rocket’s corporate strategy, led by Mr. Wilson’s strong legal and strategic acumen and experience. “Today’s leadership announcements underscore Rocket’s preparedness as we transform from a clinical organization to a commercial stage gene therapy company, notably by expanding our financial expertise with the addition of seasoned finance leader, Aaron Ondrey as our Chief Financial Officer,” said Gaurav Shah, M.D., Chief Executive Officer, Rocket Pharma. “We are leveraging our team's deep talent and experience to optimally position Rocket for operational and commercial excellence and look forward to continuing our strong momentum as we advance our leading pipeline for patients living with rare cardiovascular and hematologic diseases." About Rocket Pharmaceuticals, Inc. Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of investigational genetic therapies designed to correct the root cause of complex and rare disorders. Rocket’s innovative multi-platform approach allows us to design the optimal gene therapy for each indication, creating potentially transformative options that enable people living with devastating rare diseases to experience long and full lives. Rocket’s lentiviral (LV) vector-based gene therapies target hematologic diseases and consist of late-stage programs for Fanconi Anemia, a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, and Pyruvate Kinase Deficiency (PKD), a monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. Our adeno-associated virus (AAV)-based cardiovascular portfolio includes a late-stage program for Danon Disease, a devastating heart failure condition resulting in thickening of the heart, an early-stage program in clinical trials for PKP2-arrhythmogenic cardiomyopathy (ACM), a life-threatening heart failure disease causing ventricular arrhythmias and sudden cardiac death, and a pre-clinical program targeting BAG3-associated dilated cardiomyopathy (DCM), a heart failure condition that causes enlarged ventricles. For more information about Rocket, please visit and follow us on LinkedIn, YouTube and X. Rocket Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements concerning Rocket’s future expectations, plans and prospects that involve risks and uncertainties, as well as assumptions that, if they do not materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. All statements other than statements of historical facts contained in this release are forward-looking statements. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. These forward-looking statements include, but are not limited to, statements concerning Rocket’s expectations regarding the safety and effectiveness of product candidates that Rocket is developing to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Danon Disease (DD) and other diseases, the expected timing and data readouts of Rocket’s ongoing and planned clinical trials, the expected timing and outcome of Rocket’s regulatory interactions and planned submissions, Rocket’s plans for the advancement of its DD program, including its planned pivotal trial, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, Rocket’s ability to establish key collaborations and vendor relationships for its product candidates, Rocket’s ability to develop sales and marketing capabilities or enter into agreements with third parties to sell and market its product candidates and Rocket’s ability to expand its pipeline to target additional indications that are compatible with its gene therapy technologies. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket’s dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, unexpected expenditures, Rocket’s competitors’ activities, including decisions as to the timing of competing product launches, pricing and discounting, Rocket’s ability to develop, acquire and advance product candidates into, enroll a sufficient number of patients into, and successfully complete, clinical studies, Rocket’s ability to acquire additional businesses, form strategic alliances or create joint ventures and its ability to realize the benefit of such acquisitions, alliances or joint ventures, Rocket’s ability to obtain and enforce patents to protect its product candidates, and its ability to successfully defend against unforeseen third-party infringement claims, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket’s Annual Report on Form 10-K for the year ended December 31, 2023, filed February 27, 2024 with the SEC and subsequent filings with the SEC including our Quarterly Reports on Form 10-Q. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.