Category Archives: Gene therapy

- Proof of Concept Data for New GTx-mAb Platform to Be Featured at ASGCT Along With Presentations From Multiple Programs -

- Company to Host Webcast on May 13 at 8:15 a.m. ET -

BEDFORD, Mass., April 28, 2021 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a clinical-stage genetic medicines company, announced today a new approach to its AAVHSC platform that delivers one-time gene therapy to produce antibodies throughout the body. Preclinical data that demonstrated proof of principle for this GTx-mAb platform is the subject of an upcoming presentation, alongside other digital and oral presentations from the Companys in vivo gene therapy and gene editing programs, that will be featured at the virtual American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting May 11 - 13, 2021.

We are excited to unveil our GTx-mAb platform and preclinical data targeting complement protein 5 with a one-time treatment, stated Arthur Tzianabos, Ph.D., President and Chief Executive Officer of Homology Medicines. These data demonstrated that our AAVHSCs delivered vectors at a high efficiency to the liver and secrete antibodies throughout the body, which resulted in sustained expression levels consistent with C5 antibody therapeutics in a humanized murine model. Importantly, this proof of concept for our approach unlocks the potential for a one-time treatment that leverages the liver to produce fully functional antibodies and the expansion of our pipeline to address diseases with larger patient populations.

Albert Seymour, Ph.D., Chief Scientific Officer, added, We also look forward to sharing new data across our genetic medicines pipeline programs, including PKU and Hunter syndrome, which support our plans to advance these two programs into the clinic this year. These data further demonstrated that our AAVHSCs efficiently transduced the liver and reached relevant tissues, including crossing the blood-brain and peripheral-nerve barriers with a single I.V. administration. Additionally, we plan to highlight advancements from our capsid characterizations and our internal GMP manufacturing process and platform, including an oral presentation showing the impact of novel formulations on capsid stability.

Homology management plans to host a conference call and webcast on May 13, 2021, at 8:15 a.m. ET to discuss the new GTx-mAb platform and ASGCT data highlighting the Companys human hematopoietic stem cell-derived adeno-associated virus vector (AAVHSC) platform and pipeline.

Homologys digital and oral presentations include:

In Vivo AAVHSC PlatformTransducing the Liver as an Antibody Factory Using AAVHSCsTuesday, May 11; 8:00 - 10:00 a.m.Abstract #: 336

Functional Characterization of AAVHSCs Compared to AAV Serotypes: Activation of Cellular Pathways In Vitro and In Vivo Transduction PropertiesTuesday, May 11; 8:00 - 10:00 a.m.Abstract #: 304

Wildtype AAV2 Rep Protein Produces Higher Titer AAVHSC Vectors with Improved Packaging Profiles Compared to Clade F Associated Chimeric RepTuesday, May 11; 8:00 - 10:00 a.m. Abstract #: 804

In Vivo, Nuclease-Free Gene Editing for PKUInvestigational Genetic Medicine Approaches for Phenylketonuria (PKU)Tuesday, May 11; 8:00 - 10:00 a.m.Abstract #: 405

In Vivo Gene Therapy for Hunter Syndrome Long-Term Expression of HMI-203: Investigational Gene Therapy Candidate for Mucopolysaccharidosis Type II (MPS II), or Hunter SyndromeTuesday, May 11; 8:00 - 10:00 a.m.Abstract #: 507

Scalable Manufacturing Oral PresentationNext Generation AAV Drug Products: Enhanced Stability & Clinical Ease for High Titer PreparationsTuesday, May 11; 6:45 - 7:00 p.m.Abstract #: 27

In Vivo Gene Therapy for MLD Oral PresentationGene Therapy Candidate for Metachromatic Leukodystrophy (MLD): Summary of Preclinical In Vivo Data Following an Intravenous Delivery of HMI-202Thursday, May 13; 5:30 - 5:45 p.m.Abstract #: 159

The abstracts are available on the ASGCT website.

About Homology Medicines, Inc. Homology Medicines, Inc. is a clinical-stage genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homologys proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicines in vivo either through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases. The Companys intellectual property covers its family of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visit http://www.homologymedicines.com.

Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; the potential of our gene therapy and gene editing platforms; our plans and timing for the release of additional preclinical and clinical data; our beliefs regarding our manufacturing capabilities; our position as a leader in the development of genetic medicines; and our participation in upcoming presentations and conferences. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies and clinical trials, and on general economic conditions; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the capabilities of our manufacturing facility; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property and significant costs as a result of operating as a public company. These and other important factors discussed under the caption Risk Factors in our Annual Report on Form 10-K for the year ended December 31, 2020 and our other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Company ContactsTheresa McNeelyChief Communications Officer and Patient Advocatetmcneely@homologymedicines.com781-301-7277

Media Contact:Marisa CitranoSenior Corporate Communications Associatemcitrano@homologymedicines.com617-335-2841

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Homology Medicines Announces New Approach to Leverage AAVHSC Platform by Delivering One-Time In Vivo Gene Therapy to Produce Antibodies in Humanized...

DocWire News recently sat down with Shephard Mpofu, M.D., SVP, Chief Medical Officer, Novartis Gene Therapies,to discuss important data for Zolgensma (onasemnogene abeparvovec-xioi) for patients with spinal muscular atrophy (SMA), a rare neurological condition and a leading genetic cause of infant death. See what Dr. Mpofu had to say.

DocWire News: Can you detail for us the highlights of the research that was presented at the 2021 MDA Virtual Clinical & Scientific Conference on Zolgensma for the treatment of spinal muscular atrophy (SMA)?

Dr. Shephard Mpofu: Thank you very much. Zolgensma is the only gene therapy for spinal muscular atrophy and the only spinal muscular atrophy treatment designed to directly address the genetic cause of the disease by really replacing the function of the missing or non-working survival motor neuron gene, SMN one, with a single one-time dose. It remains one of the most critical, transformative, essential, gene therapies that provides a lifetime benefit. At the virtual meeting, we presented a number of data, new Zolgensma data that really demonstrate age-appropriate development in children with spinal muscular atrophy. When used early, we also have real-world evidence that shows benefit in all children and durability five years post treatment, and importantly, how newborn screening enables a better outcome for a majority of these SMA kids.

DocWire News: How were these studies conducted?

Dr. Shephard Mpofu: Thank you very much. So we presented the pre-symptomatic study on patients with SMN one or two pick-up copies. Respectively, these fall into type one SMA and type two SMA. And we saw remarkable results where children were able to eat without any feeding tubes. And these children achieved age-appropriate milestones like sitting, standing and walking. Specifically, when we look at the two co-PI cohort, 80% of those patients achieved the primary efficacy endpoint, which was to sit for at least 30 seconds. And it was clear that the majority of those children achieved these milestones, which fall within the World Health Organizations window for normal development. A third of these children were also able to stand and a third were able to walk. None of these children had any events in terms of needing ventilator support. Neither was there any feed chipping that was required and no serious adverse events.

When we move onto the patients with three copies, we also had remarkable achievement in more than 53% of children achieving the primary endpoint of being able to stand for at least three seconds. And 40% of kids in this study were walking independently and it has happened in the copy two cohort. These kids achieve these milestones in keeping with the World Health Organizations development, milestone windows. Importantly, these results are unprecedented because when you look at kids with this type of disease in the natural history progression, these kids usually succumb to morbidity and mortality within two years. So seeing such a result provides the transformative, innovative impact of Zolgensma in spinal muscular atrophy.

DocWire News: Did any of these results surprise you?

Dr. Shephard Mpofu: These results add further weight and evidence to some of the studies weve done in different types of SMA, in symptomatic SMA, in multiple studies, across regions of Europe and the United States of America. And whats remarkable is that the benefit risk remains consistent across the trials and the transformative efficacy of a one-time essential treatment remains consistent across the various SMA types.

DocWire News: How big of a problem is SMA in America and is it often overlooked in your view?

Dr. Shephard Mpofu: SMA remains one of the most critical conditions that is occurring in about one in 10,000 children. This disease robs children of the ability to have any motor activity and children end up being unable to eat, to breathe or swallow and have a profound morbidity of requiring ventilation support and failure to thrive. Its severe, debilitating, irreversible neuromuscular loss and death is a consequence. In the United States, there has been a fantastic improvement across multiple states with newborn screening and education by various advocacy groups. And were starting to see an improvement in diagnosis, which is also something we picked up in our real-world evidence data and from our registry, where it was very clear that kids who have been diagnosed by newborn screening compared to those that are diagnosed by clinical diagnosis are treated early, and importantly, do very well on Zolgensma without requiring any other SMA therapies.

DocWire News: Whats the overall impact you think this therapy can have in the fight against SMA?

Dr. Shephard Mpofu: This therapy is transformative in that it addresses the root cause of the genetic disease in SMA by replacing the missing survival motor neuron one gene. And this is only done as a one-off treatment and provides a lifetime of benefits. It also reduces the burden that happens with other therapies of having to go to a hospital multiple times and also the burden thats around adherence in taking something daily.

DocWire News: Closing thoughts/remarks?

Dr. Shephard Mpofu: I just want to finish by saying that Zolgensma has constantly across multiple studies demonstrated the transformative efficacy in really showing age appropriate improvement in children with spinal muscular atrophy in most of the studies that we have done across the different types of SMA.

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Dr. Shephard Mpofu, Chief Medical Officer, Novartis Gene Therapies, Discusses Treatment for Children with Spinal Muscular Atrophy - DocWire News

CPhI Japan, the first large pharma event to trade in 2021, played host to 7214 attendees at the exhibition and a further 7204 virtual users from across the globe. The event, a key marker for the strength of the regional industry, has rebounded quickly with some 216 exhibitors searching for pharma partners. In fact, such has been the demand, CPhI Japan Connect the events digital platform for international audiences will remain open until the end of May.

Hosted at the Big Sight Exhibition Centre in Tokyo, the countrys cell and gene therapy sector, the expanding domestic R&D pipeline and renewed digital innovation were highlighted by experts as key growth areas in 2021.

The feedback on the ground was that the chance to meet again with industry professionals has really stimulated some extremely active discussions. From API producers and packaging to advanced therapies, the event played host to a really active couple of days that has reinvigorated growth and partnerships in Japan over the next year, commented Silvia Forroova, Brand Director Pharma at CPhI Japan.

Attendees highlighted the return of the event and its success as a key moment for renewed pharma growth in Japan. In fact, Japan (7.15) ranked second only to the United States in the most recent Annual CPhI Pharma Index, scoring extremely highly across innovation (7.34), API quality (7.78), finished dose manufacturing (8.13) as well as biologics manufacturing (7.20).

In one session, the strength of the countrys advanced therapy market was discussed in Trends in Cell and Gene Therapy presented by Ly Nguyen-Jatkoe of Informa Pharma Intelligence with rapid growth expected over the next 2-3 years.

In total, Japans largest pharma trade event saw an extremely strong industry turnout with 216 exhibitors from across the full spectrum of pharmaceutical supply chain.

Laura Murina, Brand Manager at CPhI Japan added, the great strength of CPhI events is that we bring everyone together and adopting a hybrid approach to CPhI Japan has been a great success empowering partnerships, international as well as domestic, and keeping vital connections and trends following across the industry.

Beyond the exhibition, the CPhI Japan Conference featured keynote insights, including a detailed appraisal of the dynamic R&D pipeline from Ian Haydock, Editor-In-Chief, Asia Pacific Informa Intelligence. Additionally, Timothy Pang and Caroline Zhang of Informa Pharma Intelligence presented analysis of Chinas growing pharma market; with Angela Irony of Maccabi Healthcare, Omer Dror of Lynx MD and Amir Trabelsi of GENOOX reviewing the latest digital health trends.

Finally, the Japan Pharmaceutical Traders Association delivered the CPhI Japan 2021 Symposium, discussing the supply of APIs in Japan and how to manage change especially relevant in a post Covid period as well as an overview of the Japanese regulatory system and recent proposals for improvement.

Event organisers are already looking ahead to CPhI Japan 2022, which will take place at the Big Sight Exhibition in Tokyo (20-22 April), with numbers expected to near double to 15,000 attendees and 400 exhibitors. The event will be co-located alongside ICSE (contact services), P-MEC (pharmaceutical machinery & lab equipment), bioLIVE (biopharmaceuticals), InnoPack (packaging & drug delivery systems), NEX (natural extract), and FDF (finished dose drugs).

-ENDS-

Notes to editors

About CPhI

CPhI drives growth and innovation at every step of the global pharmaceutical supply chain from drug discovery to finished dosage. Through exhibitions, conferences and online communities, CPhI brings together more than 100,000 pharmaceutical professionals each year to network, identify business opportunities and expand the global market. CPhI hosts events in Europe, Korea, China, India, Japan, South East Asia, North America, and the Middle East and Africa. Co-locating with ICSE for contract services; P-MEC for machinery, equipment & technology; InnoPack for pharmaceutical packaging; bioLIVE for biopharma; Finished Dosage Formulation for every aspect of the finished dosage supply chain; and NEX for natural extract products, applications and solutions. CPhI provides an online buyer and supplier directory at CPhI-Online.com.

For more information visithttps://www.cphi.com

About Informa Markets

Informa Markets creates platforms for industries and specialist markets to trade, innovate and grow. Our portfolio is comprised of more than 550 international B2B events and brands in markets including Healthcare & Pharmaceuticals, Infrastructure, Construction & Real Estate, Fashion & Apparel, Hospitality, Food & Beverage, and Health & Nutrition, among others. We provide customers and partners around the globe with opportunities to engage, experience and do business through face-to-face exhibitions, specialist digital content and actionable data solutions. As the worlds leading exhibitions organizer, we bring a diverse range of specialist markets to life, unlocking opportunities and helping them to thrive 365 days of the year.

For more information, please visit http://www.informamarkets.com.

The Informa Markets annual schedule of Pharmaceutical events include: CPhI Japan (14-16 April, 2021 at the Big Sight Exhibition Centre Tokyo, Japan); CPhI Discover (17 - 28 May 2021,Digital); CPhI South East Asia (4-6 August, 2021 at Challenger 2, IMPACT, Muang Thong Thani, Thailand); CPhI North America (10 August - 12 August, 2021 at Pennsylvania Convention Centre Philadelphia, USA); CPhI Korea (11-13 August 2021), COEX Seoul, Korea); CPhI, ICSE, P-MEC, FDF, InnoPack Worldwide, BioProduction (09 November 11 November 2021 at Fiera Milano, Milan); CPhI Middle East & Africa (26-28 September, 2021 at theRiyadh International Convention & Exhibition Center, Riyadh, Saudi Arabia); Pharmapack Europe 2021 (13-14 October, 2021 at the Paris Expo, Porte de Versailles Paris, France); CPhI & P-MEC India (24-26 November 2021 at the India Expo Mart, Greater Noida, Delhi NCR Delhi, India); CPhI & P-MEC China (Dec. 16 to 18, 2021 at SNIEC Shanghai, China)

For media enquiries, please contact:

Alex Heeley or Abdul Khalifeh

De Facto Communications

T: +44 (0) 203 735 8168

E:a.heeley@defacto.co.uk/a.khalifeh@defacto.co.uk

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CPhI Japan celebrates return, as cell & gene therapies and digital innovation highlighted - PharmiWeb.com

EDITOR: As a native Auroran, it saddens me to have to unsubscribe to my local paper due to the editor being a completely brainwashed idiot. I have stomached Editor Dave Perrys mainstream COVID-19 propaganda for a year as a way to stay balanced and listen to what the government is shoving down our throats.

But Perrys recent column about vaccine passports takes it a step too far. If he wants to take an experimental gene-altering technology to his vein, go for it.

For Perry to believe that those of us (not Republicans either, I am a lifelong liberty loving dem) who dont believe in big pharma should be shunned from normal activities in society makes him nothing short of an idiot totalitarian.

Perry needs to keep his stupid beliefs to himself and do his job as a journalist. Cover the adverse events happening to the rest of the lemming vaxxed herd. Or dont, and let those of us left with common sense take over when their gene-therapy turns out like most other ideas of big healthcare disaster.

Emory, via [emailprotected]

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LETTER: Dimwit Dave Perry needs real therapy not COVID-19 gene therapy - Sentinel Colorado

CRANBURY, N.J.--(BUSINESS WIRE)--Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders, today announces clinical data presentations at the upcoming 24thAmerican Society of Gene and Cell Therapy (ASGCT) Annual Meeting taking place May 11-14, 2021. Investigators will review new data from Rockets Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), and Fanconi Anemia (FA) gene therapy programs in oral and poster presentations.

Details for oral presentations are as follows:

Title: A Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Interim ResultsSession: Genetic Blood and Immune DisordersPresenter: Donald Kohn, M.D., Professor of Microbiology, Immunology and Molecular Genetics, Pediatrics (Hematology/Oncology), Molecular and Medical Pharmacology, and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los AngelesDate: Tuesday May 11, 2021Time: 6:15-6:30 p.m. EDTLocation: Room 7Abstract number: 39

Title: Lentiviral Mediated Gene Therapy for Pyruvate Kinase Deficiency: Updated Results of a Global Phase 1 Study for Adult and Pediatric PatientsSession: Gene Therapies for HemoglobinopathiesPresenter: Jos Luis Lpez Lorenzo, M.D., Hospital Universitario Fundacin Jimnez Daz, Madrid, SpainDate: Wednesday May 12, 2021Time: 6:45-7:00 p.m. EDTLocation: Room 7Abstract number: 83

Title: Gene Therapy in Fanconi Anemia: Current Strategies to Enable the Correction of HSCsSession: International Focus on Stem Cell Gene Therapy Presenter: Juan A. Bueren, Ph.D., Head of the Hematopoietic Innovative Therapies Division at the Centro de Investigaciones Energticas, Medioambientales y Tecnolgicas (CIEMAT) in Spain / CIBER-Rare Diseases / IIS-Fundacin Jimnez DazDate: Thursday, May 13, 2021Time: 10:00-10:45 a.m. EDTLocation: Room 7Abstract number: 36

Select results from Dr. Buerens presentation will also be highlighted by Paula Rio, Ph.D. Details for this Invited Presentation are as follows:

Title: Gene Therapy in Fanconi Anemia: Current Strategies to Enable the Correction of HSCsSession: International Focus on Stem Cell Gene TherapyPresenter: Paula Ro, Ph.D., Senior Researcher, Hematopoietic Innovative Therapies Division at CIEMAT in Spain / CIBER-Rare Diseases / IIS-Fundacin Jimnez DazDate: Thursday May 13, 2021Time: 10:00-11:45 a.m. EDT

Details for poster presentation are as follows:

Title: Gene Therapy for Fanconi Anemia [Group A]: Preliminary Results of Ongoing RP-L102 Clinical TrialsSession: Hematologic and Immunologic DiseasesPresenter: Agnieszka Czechowicz, M.D., Ph.D., Assistant Professor of Pediatrics, Division of Stem Cell Transplantation, Stanford University School of MedicineDate: Tuesday, May 11, 2021Time: 8:00-10:00 a.m. EDTLocation: Digital GalleryAbstract number: 697

Abstracts for the presentations can be found online at: https://annualmeeting.asgct.org/

About Leukocyte Adhesion Deficiency-I

Severe Leukocyte Adhesion Deficiency-I (LAD-I) is a rare, autosomal recessive pediatric disease caused by mutations in the ITGB2 gene encoding for the beta-2 integrin component CD18. CD18 is a key protein that facilitates leukocyte adhesion and extravasation from blood vessels to combat infections. As a result, children with severe LAD-I are often affected immediately after birth. During infancy, they suffer from recurrent life-threatening bacterial and fungal infections that respond poorly to antibiotics and require frequent hospitalizations. Children who survive infancy experience recurrent severe infections including pneumonia, gingival ulcers, necrotic skin ulcers, and septicemia. Without a successful bone marrow transplant, mortality in patients with severe LAD-I is 60-75% prior to the age of 2 and survival beyond the age of 5 is uncommon. There is a high unmet medical need for patients with severe LAD-I.

Rockets LAD-I research is made possible by a grant from the California Institute for Regenerative Medicine (Grant Number CLIN2-11480). The contents of this press release are solely the responsibility of Rocket and do not necessarily represent the official views of CIRM or any other agency of the State of California.

About Pyruvate Kinase Deficiency

Pyruvate kinase deficiency (PKD) is a rare, monogenic red blood cell disorder resulting from a mutation in the PKLR gene encoding for the pyruvate kinase enzyme, a key component of the red blood cell glycolytic pathway. Mutations in the PKLR gene result in increased red cell destruction and the disorder ranges from mild to life-threatening anemia. PKD has an estimated prevalence of 3,000 to 8,000 patients in the United States and the European Union. Children are the most commonly and severely affected subgroup of patients. Currently available treatments include splenectomy and red blood cell transfusions, which are associated with immune defects and chronic iron overload.

RP-L301 was in-licensed from the Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT), Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER) and Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz (IIS-FJD).

About Fanconi Anemia

Fanconi Anemia (FA) is a rare pediatric disease characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life. Allogeneic hematopoietic stem cell transplantation (HSCT), when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Graft-versus-host disease, a known complication of allogeneic HSCT, is 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. Mutation in the FANCA gene leads 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 patients 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.

About Rocket Pharmaceuticals, Inc.

Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is advancing an integrated and sustainable pipeline of genetic therapies that correct the root cause of complex and rare childhood disorders. The Companys platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket's clinical programs using lentiviral vector (LVV)-based gene therapy are for the treatment of Fanconi Anemia (FA), 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, Pyruvate Kinase Deficiency (PKD), a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia, and Infantile Malignant Osteopetrosis (IMO), a bone marrow-derived disorder. Rockets first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon disease, a devastating, pediatric heart failure condition. For more information about Rocket, please visit http://www.rocketpharma.com.

Rocket Cautionary Statement Regarding Forward-Looking Statements

Various statements in this release concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding its guidance for 2021 in light of COVID-19, the safety, effectiveness and timing of product candidates that Rocket may develop, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis (IMO) and Danon Disease, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. 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. 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 ability to monitor the impact of COVID-19 on its business operations and take steps to ensure the safety of patients, families and employees, the interest from patients and families for participation in each of Rockets ongoing trials, our expectations regarding the delays and impact of COVID-19 on clinical sites, patient enrollment, trial timelines and data readouts, our expectations regarding our drug supply for our ongoing and anticipated trials, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rocket's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, 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, 2020, filed March 1, 2021 with the SEC. 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.

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Rocket Pharmaceuticals Announces Upcoming Clinical Data Presentations at the 24th Annual Meeting of the American Society of Gene and Cell Therapy -...

Worldwide License to AAV sL65 Capsid, Novel Liver-Targeting Capsid, to Support Development of CANbridge Gene Therapy Programs for Fabry disease, Pompe disease and Options for two Additional Indications

Option to Exclusive License for LB-001, Investigational Gene Editing Treatment for Methylmalonic Acidemia, in Greater China

BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- CANbridge Pharmaceuticals, Inc., a biopharmaceutical company developing and commercializing innovative drugs to treat rare diseases and rare cancers in China and globally, announced that it has entered into a strategic collaboration and licensing agreement with LogicBio Therapeutics, Inc. (Nasdaq: LOGC), a clinical-stage genetic medicine company pioneering gene delivery and gene editing platforms to address rare and serious diseases, from infancy through adulthood. The agreement includes a worldwide license to develop, manufacture and commercialize gene therapy candidates for treatments for Fabry and Pompe diseases, based on LogicBios adeno-associated virus (AAV) sL65, the first capsid produced from the LogicBio sAAVy platform. The agreement also includes options for the development of AAV sL65-based treatments for two additional indications. AAV sL65 has unique liver-targeting properties, the potential to overcome limited potency and immunogenicity issues, and is more efficient to manufacture, potentially resulting in higher yields, making it a valuable strategic addition to the CANbridges gene therapy program.

CANbridge is also granted an option to an exclusive license for LB-001, an investigational in-vivo gene editing technology based on GeneRide platform for the potential treatment of methylmalonic acidemia (MMA), in Greater China (China, Taiwan, Hong Kong and Macau).

Under the terms of the agreement, LogicBio is eligible to receive an upfront payment of $10 million for the exclusive worldwide license to support the development of two gene therapy candidates for Fabry and Pompe diseases. In addition, the agreement grants options for two additional undisclosed gene therapy programs, based on AAV sL65, and an option to an exclusive license for LB-001 in Greater China. Upon exercising the option for LB-001, CANbridge would assume responsibility and costs for all future development in the territory, including regulatory and commercial activities and, potentially, manufacturing. The agreement also includes payments, including opt-in fees triggered upon the exercise of these options, as well as clinical, regulatory, and commercial milestone payments for up to $581 million, and up to double-digit royalties on net sales.

This important agreement advances our three-prong strategy to build CANbridges next-generation rare disease treatment pipeline: In-house research capability, as supported by the recent opening of our CANbridge rare disease research facility, in Massachusetts; collaborative academic research agreements, such as the two we have with the Horae Gene Therapy Center, at the University of Massachusetts Medical School; and partnerships with innovative biotechnology companies, said James Xue, Ph.D., Founder, Chairman and CEO of CANbridge Pharmaceuticals, Inc. LogicBios cutting-edge capsid and gene editing technologies, which have the potential to address the limitations of existing therapies, supplies a vital component to the CANbridge long-term rare disease capability.

About LogicBio Therapeutics, Inc.

LogicBio Therapeutics is a clinical-stage genetic medicine company pioneering gene delivery and gene editing platforms to address rare and serious diseases from infancy through adulthood. The companys proprietary GeneRide platform is a new approach to precise gene insertion that harnesses a cells natural DNA repair process leading to durable therapeutic protein expression levels. LogicBios cutting-edge sAAVyTM capsid development platform is designed to support development of treatments in a broad range of indications and tissues. The company is based in Lexington, MA. For more information, visit https://www.logicbio.com/.

About CANbridge Pharmaceuticals Inc.

CANbridge Pharmaceuticals Inc. is a biopharmaceutical company accelerating development and commercialization of treatments for orphan diseases and rare cancers to address unmet medical needs.

CANbridge has a global partnership with WuXi Biologics to develop and commercialize proprietary therapeutics for the treatment of rare genetic diseases. In greater China, where it is a recognized leader in rare diseases, CANbridge has an exclusive licensing agreement to commercialize Hunterase, an enzyme replacement therapy for the treatment of Hunter syndrome (also known as mucopolysaccharidosis type II), developed by GC Pharma and marketed in more than 11 countries worldwide. CANbridge also has a collaborative agreement with the Horae Gene Therapy Center at UMass Medical School for the research and development of gene therapies to treat rare genetic diseases.

For more on CANbridge Pharmaceuticals Inc., please go to: http://www.canbridgepharma.com

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CANbridge Pharmaceuticals Announces Strategic Collaboration with LogicBio Therapeutics and Licenses to Gene Delivery and Editing Platforms - BioSpace

NEW YORK As CRISPR researchers develop new and better ways to edit the genome while leaving as few unintended consequences as possible behind, a team led by scientists at the University of California, San Francisco and MIT has developed a method that would create completely reversible gene edits.

In a recent study in Cell, UCSF's Luke Gilbert, MIT's Jonathan Weissman, and their colleagues described their method, called CRISPRoff a programmable epigenome editor consisting of a single dead Cas9 fusion protein that establishes DNA methylation and repressive histone modifications. This transient CRISPRoff expression initiates highly specific repression of genes and DNA methylation that's maintained through cell division and differentiation of stem cells to neurons. In their experiments, they found that the epigenome editing was highly specific, with minimal off-target editing.

In order to reverse this effect, the researchers then engineered a switch they called CRISPRon, through which they used Cas9-mediated gene editing to inactivate DNMT1 the main DNA methylation maintenance enzyme in mammalian cells in cells where they had previously silenced specific genes. Post-DNMT1 knockout, 60 percent to 80 percent of cells demonstrated reactivated gene expression. Similarly, treatment of cells with a small-molecule inhibitor of DNMT1 showed reactivated expression of genes that had previously been silenced, demonstrating that depletion of DNA methylation was sufficient to reverse CRISPRoff-mediated gene silencing.

"If you want to fix a pathogenic mutation, then CRISPR is really enabling. But we felt that for many applications, you may not want to permanently mutate the genome," Gilbert said, explaining the method's genesis. "So, we were searching for ways to turn gene expression off or on, without manipulating the sequence of the genome and just manipulating the transcripts that are produced by a cell."

Medically, he noted, there could be many applications where patients might feel more comfortable with using genome editing if they know that their genes won't be permanently changed, in part based on the concept that gene therapy has already been in use for a variety of applications for more than a decade.

Gilbert further noted that while he, Weissman, and many other CRISPR researchers have been working with tools such as CRISPR interference (CRISPRi) that can downregulate gene expression rather than turning it off entirely, these tools are more awkward to work with from a therapeutic standpoint. While a regular CRISPR-Cas system uses a Cas nuclease to latch onto a gene a mutate it in some fashion to turn it off, CRISPRi uses deactivated Cas9, resulting in RNA-directed transcriptional control of the target region. In other words, it functions "almost like normal transcription factors within a cell, where you constitutively express proteins to target the gene, and then that turns the gene on or off," Gilbert explained. "One of the advantages of Cas9 is you can express it briefly and it'll make a change to the genome that's permanent, and carry it out for a long time. We were looking for ways to basically leverage the strengths of Cas9's permanence and durability, but also leverage this epigenetic editing feature of not having to permanently mutate a gene."

The dead Cas9 works as a programmable DNA binding element rather than as a programmable nuclease, Weissman added.

In terms of therapeutic applications for human beings, the technology has a lot of possible uses, the researchers believe. Before there was an Ebola vaccine, for example, they were working on CRISPRoff as a way to confer programable immunity for anyone who might be affected by the disease.

"If you have a virus where you know the receptor, you could use CRISPRoff to turn gene expression off," Gilbert said. For Ebola that receptor is a protein called NPC1. "We know if you turn NPC1 off in the liver, you're immune to Ebola. But you don't want to permanently mutate NPC1 because you cause cholesterol processing defects and lysosomal storage disorder phenotypes," he added. The idea they had, therefore, was to deliver CRISPRoff to the liver of healthcare workers traveling to Ebola hotspots so that they'd be completely immune to the disease while working with patients.

"And when they left the Ebola hotspot, to avoid detrimental effects of mutating or permanently silencing NPC1, then you could redeliver CRISPRon to restore gene expression and therefore not have any detrimental phenotypes from permanently losing that gene function," Gilbert added.

He further noted that the technology could even be used to modulate pain response. If someone were planning to have surgery, or recovering from an injury, CRISPRoff could be administered to shut down pain receptors for a short time. Once the patient recovered, the pain receptors could be turned back on. It would also help people avoid opioid pain killers.

Another example, according to Weissman, would be in the area of oncology. Cancer studies often reveal the presence of genes or gene mutations that lead to resistance to chemotherapy or radiotherapy. CRISPR is now being considered as a possible addition to some late-stage cancer patients' therapies as a way to knock out resistance genes and reawaken therapeutic response.

In May 2019, Christiana Care's Health System's Gene Editing Institute was preparing to file an investigational new drug application with the US Food and Drug Administration for a clinical trial protocol that would use CRISPR genome editing to improve the efficacy of chemotherapy for KRAS-positive non-small-cell lung cancer (NSCLC) patients. The protocol involved using CRISPR-Cas9 gene editing to knock down NRF2 in order to render patients more sensitive to chemotherapeutic agents.

Under a scenario using CRISPRoff, that gene's expression may only be off for the time it takes to administer the necessary cancer treatment. "You can imagine turning on or off genes in your intestine or in your blood stem cells," Weissman said. "The cells are more sensitive to radiation. But then after you have the radiotherapy, [the cells could return] to normal states so you don't have to worry about the long-term consequences of turning off the gene."

Weissman noted there may be some instances where CRISPRon isn't needed to turn gene expression back on. While conducting their experiments, the researchers noted that the gene silencing in certain loci would decay over a period of days or weeks, depending on the cell cycle turnover rate.

"If that can be tuned, we can now come in [with] one type of treatment and over the period of, say, weeks or months, it would naturally restore and you don't have to come in with the second," Weissman said.

That rate of decay would depend on the tissue in question and the dynamics of tissue turnover "will dictate how long these program changes last," Gilbert added. "In post-mitotic cells like muscle or neuron, these methyl marks in non-replicating cells may last for years and years. So, it depends on the cell type."

There are still many elements to CRISPRoff that have to be worked out and refined before it can be used in the clinic. As with any CRISPR system meant to be used as a therapy, delivery into the right cells at the right time is currently the principal challenge, Gilbert said. The researchers are also working on making the CRISPRoff complex smaller, and capable of targeting more than one loci at once, Weissman added.

But there's already been clear interest in commercializing the technology, he said. Both he and Gilbert, as well as a few other researchers who authored the paper, have already filed for patents on CRISPRoff and CRISPRon.

Indeed, Weissman said, the technology could have applications in cell therapy, and could even aid in the development of so-called off-the-shelf allogeneic CAR-T cells. The current procedure for making CAR Ts is expensive and time-consuming because it involves harvesting an individual's cells, engineering them, and re-administering them as a treatment. As of now, allogeneic CAR Ts could cause life-threatening graft-versus-host disease, and could be rejected by the host immune system.

Using CRISPRoff, however, Weissman envisions being able to edit allogeneic CAR Ts in ways that would camouflage them from an individual's immune system, while also adding safety controls that would allow a physician to turn the CAR Ts off, if needed. "It could make it a much more accessible treatment," he said. "You could have a safer and more universal cell therapy, and you can then do much more complicated engineering because you only have to do it once for many patients, as opposed to trying to do this complicated engineering in a bespoke way for each patient."

Overall, he added, what the study really shows is that cutting DNA and then repairing it is quite difficult. And while researchers have gotten better at avoiding off-target effects, so-called on-target off-targets unintended consequences of on-targets editing such as DNA damage response, large indels, and even chromothripsis, can still do damage to the genome.

"So, when you don't have to do that, therapeutically, there are lot of advantages," Weissman said. "Things like base editor and prime editor are examples of this, and we see CRISPRoff as a complement to this, which allows you to do epigenome editing from beginning to end, and to do it in a clean and controlled way."

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CRISPRoff Reversible Epigenome Editing Method Could Enable Safer, More Precise Therapeutics - GenomeWeb

Espaol

The genes in your bodys cells play an important role in your health indeed, a defective gene or genes can make you sick.

Recognizing this, scientists have been working for decades on ways to modify genes or replace faulty genes with healthy ones to treat, cure or prevent a disease or medical condition.

Now this research on gene therapy is finally paying off. Since August 2017, the U.S. Food and Drug Administration has approved three gene therapy products, the first of their kind.

Two of them reprogram a patients own cells to attack a deadly cancer, and the most recent approved product targets a disease caused by mutations in a specific gene.

What is the relationship between cells and genes?f

Cells are the basic building blocks of all living things; the human body is composed of trillions of them. Within our cells there are thousands of genes that provide the information for the production of specific proteins and enzymes that make muscles, bones, and blood, which in turn support most of our bodys functions, such as digestion, making energy, and growing.

Sometimes the whole or part of a gene is defective or missing from birth, or a gene can change or mutate during adult life. Any of these variations can disrupt how proteins are made, which can contribute to health problems or diseases.

In gene therapy, scientists can do one of several things depending on the problem that is present. They can replace a gene that causes a medical problem with one that doesnt, add genes to help the body to fight or treat disease, or turn off genes that are causing problems.

In order to insert new genes directly into cells, scientists use a vehicle called a vector which is genetically engineered to deliver the gene.

Viruses, for example, have a natural ability to deliver genetic material into cells, and therefore, can be used as vectors. Before a virus can be used to carry therapeutic genes into human cells, however, it is modified to remove its ability to cause an infectious disease.

Gene therapy can be used to modify cells inside or outside the body. When its done inside the body, a doctor will inject the vector carrying the gene directly into the part of the body that has defective cells.

In gene therapy that is used to modify cells outside of the body, blood, bone marrow, or another tissue can be taken from a patient, and specific types of cells can be separated out in the lab. The vector containing the desired gene is introduced into these cells. The cells are left, to multiply in the laboratory, and are then injected back into the patient, where they continue to multiply and eventually produce the desired effect.

Before a company can market a gene therapy product for use in humans, the gene therapy product has to be tested for safety and effectiveness so that FDA scientists can consider whether the risks of the therapy are acceptable in light of the benefits.

Gene therapy holds the promise to transform medicine and create options for patients who are living with difficult, and even incurable, diseases. As scientists continue to make great strides in this therapy, FDA is committed to helping speed up development by prompt review of groundbreaking treatments that have the potential to save lives.

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What Is Gene Therapy? How Does It Work? | FDA

Ever since the dawn of mankind, diseases have plagued humans over the ages. Years of innovations and advancements in science has provided us with a deeper understanding of how diseases work. This has led to lower mortality rates and longer lifespans. But there are some diseases that just cannot be cured using traditional medicine or surgery. Gene therapy is an experimental technique that caters to patients with such diseases.

Gene therapy is a technique which involves the replacement of defective genes with healthy ones in order to treat genetic disorders. It is an artificial method that introduces DNA into the cells of the human body. The first gene therapy was successfully accomplished in the year 1989.

The simple process of gene therapy is shown in the figure below:

In the figure, the cell with the defective gene is injected with a normal gene which helps in the normal functioning of the cell. This technique is employed mainly to fight against the diseases in the human body and also to treat genetic disorders. The damaged proteins are replaced in the cell by the insertion of DNA into that cell. Generally, improper protein production in the cell leads to diseases. These diseases are treated using a gene therapy technique. For example, cancer cells contain faulty cells which are different from the normal cells and have defective proteins. Hence, if these proteins are not replaced, this disease would prove to be fatal.

Basically, there are two types of gene therapy

This type usually occurs in the somatic cells of human body. This is related to a single person and the only person who has the damaged cells will be replaced with healthy cells. In this method, therapeutic genes are transferred into the somatic cells or the stem cells of the human body. This technique is considered as the best and safest method of gene therapy.

It occurs in the germline cells of the human body. Generally, this method is adopted to treat the genetic, disease causing-variations of genes which are passed from the parents to their children. The process involves introducing a healthy DNA into the cells responsible for producing reproductive cells, eggs or sperms. Germline gene therapy is not legal in many places as the risks outweigh the rewards.

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Gene Therapy - Discover How It Works Its Types And ...

Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein.

A gene that is inserted directly into a cell usually does not function. Instead, a carrier called a vector is genetically engineered to deliver the gene. Certain viruses are often used as vectors because they can deliver the new gene by infecting the cell. The viruses are modified so they can't cause disease when used in people. Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome.

The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient's cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the treatment is successful, the new gene delivered by the vector will make a functioning protein.

Researchers must overcome many technical challenges before gene therapy will be a practical approach to treating disease. For example, scientists must find better ways to deliver genes and target them to particular cells. They must also ensure that new genes are precisely controlled by the body.

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How does gene therapy work?: MedlinePlus Genetics