Gene editing medicines

07 - 08 November 2024 09:00 - 17:00 Online Free Watch online
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This meeting will explore the innovations that are transforming the future of gene editing medicines.

Just 12 years after the discovery of CRISPR/Cas9, the first gene editing medicines have been approved and many more are in clinical development. This meeting will explore the innovations that are transforming gene editing medicines and their impact on patient health.

The potential applications of gene editing technologies for treating diseases are beginning to be realised. The science underpinning gene editing medicines continues to develop at a rapid pace, and clinical applications are growing. However, challenges in terms of manufacturing, scale-up, regulation, equitable access, health economics and safety make the widespread roll-out of these medicines difficult. 

This two-day conference will discuss recent advances, future priorities, and the wider social and economic context for the application of gene editing approaches in a healthcare setting.

Transforming our future conferences

This conference forms part of the Royal Society's industry-focused Transforming our future series. These unique meetings feature cutting-edge science and bring together experts from industry, academia, healthcare settings, funding bodies, the wider scientific community and government to explore and address key scientific and technical challenges of the coming decade.

Organisers

  • Steve Rees

    Steve Rees

    Steve Rees is Senior Vice-President of Discovery Sciences at AstraZeneca with responsibility for the discovery of novel drug candidates, using multiple therapeutic modalities, for projects for all AstraZeneca therapy areas. Prior to his current appointment Steve held positions of increasing responsibility at AstraZeneca including leadership of the Discovery Biology and Screening Sciences and Sample Management departments. He has served as Chair of the European Laboratory Research and Innovation Group, Chair of the European Council of the Society of Laboratory Automation and Screening and as Industry Trustee of the British Pharmacological Society and is a member of  the Royal Society Science, Industry and Translation Committee. Steve was awarded an OBE by Her Majesty the Queen in 2021 for services to science and the COVID19 response.

  • Laura Sepp-Lorenzino

    Laura Sepp-Lorenzino

    Laura Sepp-Lorenzino, Ph.D. joined Intellia Therapeutics in 2019 as Chief Scientific Officer and is responsible for Research and Early Development. Intellia is harnessing CRISPR-based technologies to revolutionize the future of medicine. Laura previously held leadership positions at Vertex, Alnylam and Merck. She serves on the Board of Directors of Taysha Gene Therapies and the Alliance for Regenerative Medicine, and on the Scientific Advisory Boards for Thermo Fisher Scientific, the U.K. Nucleic Acid Therapies and Arsenal Capital Partners. She received her professional degree in Biochemistry from the University of Buenos Aires, Argentina, and both her M.S. and Ph.D. in Biochemistry from New York University.

  • Professor Robin Ali

    Professor Robin Ali

    Professor Robin Ali is Professor of Human Molecular Genetics at King’s College London and Director of KCL Centre for Gene Therapy and Regenerative Medicine. He is also Director of the KCL Gene Therapy Vector Facility. Robin is a Fellow of the Academy of Medical Sciences, NIHR Senior Investigator (Emeritus) and a recent past President of the European Society of Gene & Cell Therapy. The focus of his research is the development of gene and cell therapy for the treatment of retinal disorders; he is a founder and former Chief Scientific Officer of MeiraGTx PLC, a Nasdaq-listed clinical-stage gene therapy company. Robin Ali and members of his team have received numerous prizes for their work on developing new treatments for retinal degeneration, including the €1M Champalimaud Vison Award.

    Robin has published over 200 peer-reviewed papers with landmark papers and preclinical therapeutic proof-of-concept studies for many different ocular disorders. As chief investigator, he established the world’s first clinical trial of gene therapy for retinopathy and his group is now developing a first-in-human clinical trial of transplantation of ES-derived cone photoreceptors for the treatment of macular degeneration. 

  • Professor Waseem Qasim

    Professor Waseem Qasim

    Waseem Qasim is Professor of Cell and Gene Therapy at UCL Great Ormond Street (GOS) Institute of Child Health in London. He has led ‘bench-to-bedside’ development of new treatments that use emerging genome editing strategies to reprogram immune cells to treat cancers. Clinical studies at GOS were the first to show the potential of donor T cell modified, initially using TALENs and then CRISPR/Cas9 and, most recently, ‘base editing’ technology. Similar approaches are now being developed to repair genes inside living cells to help children with inherited blood or immune disorders, and these developments are setting the scene for a new generation of genetic medicines.

  • Robin Lovell-Badge

    Professor Robin Lovell-Badge FRS

    Robin Lovell-Badge obtained his PhD at University College London in 1978 and was a postdoc in Cambridge, both with Martin Evans. After an EMBO fellowship in Paris he established his independent laboratory in 1982 at the MRC Mammalian Development Unit, UCL, directed by Anne McLaren. In 1988 he moved to the MRC National Institute for Medical Research, which was incorporated into the Francis Crick Institute in 2015. In 1990, his lab discovered Sry, the Y-linked sex determining gene and the Sox gene family. Major themes of his past and current work include sex determination, development of the gonads, nervous system and pituitary, and the biology of stem cells within these systems. He is also very active in both public engagement and policy work. He has a strong interest in the prospects for applications of human genome editing and was on the organising committee for the three international Summits held on this, including as chair for the 2023 meeting.

Schedule

09:00-09:05 Welcome and opening remarks
Steve Rees

Steve Rees

AstraZeneca

09:05-09:25 CRISPR/Cas9-based in vivo gene editing for transthyretin amyloidosis
Professor Julian Gillmore

Professor Julian Gillmore

UCL

09:25-09:30 Q&A

Chair

Steve Rees

Steve Rees

AstraZeneca

09:30-09:35 Introduction to Session 1
Steve Rees

Steve Rees

AstraZeneca

09:35-09:55 CRISPR on Drugs: Pharmacological Enhancement of Genome Editing

The CRISPR-Cas9 system is a transformative tool for genome engineering, yet achieving efficient gene insertion and repair remains a critical challenge, particularly in slowly dividing cells. At AstraZeneca, we have focused on enhancing targeted gene integration through the application of small molecules that modulate double-strand break repair pathways. Employing a two-inhibitor strategy (2i), we significantly boost the outcomes of nuclease-dependent editing, increasing both precision and efficiency in gene repair. Using engineered proprietary nucleases encapsulated in lipid nanoparticles (LNP) and a novel AAV vector configuration, we have demonstrated effective in vivo gene repair in an animal model of homozygous familial hypercholesterolemia, highlighting the potential for therapeutic interventions.

Marcello Maresca

Marcello Maresca

AstraZeneca

09:55-10:15 Genetic engineering of hematopoietic stem cells to treat human disease: state-of-the-art and future perspective

Genetic engineering of hematopoietic stem cells (HSC) with lentiviral vectors has been providing substantial benefit to growing numbers of patients affected by primary immunodeficiencies, hemoglobinopathies and storage disorders. Long-term follow up shows stable hematopoietic reconstitution by high numbers of corrected HSC without signs of clonal expansion or exhaustion. Precise engineering by gene editing may further improve the reach and safety of HSC gene therapy by achieving in situ gene correction or targeted transgene integration. Homology-driven editing, however, remains limiting in long-term HSC and the genetic outcome at target sites heterogenous and, for some by-products, potentially genotoxic. Template delivery by Integrase-defective lentiviral vectors rather than AAV6 and the use of lipid nanoparticles instead of electroporation may increase safety and efficiency of the procedure. Coupling selection for the intended edit and purging adverse outcomes may provide a preferred path towards clinical application of this currently unique modality enabling long-range edits. On the other hand, the emergence of base and prime editors that bypass the requirement for DNA double-strand breaks (DSB) allows editing single/few mutant nucleotides with limited activation of DNA damage response. We have shown, however, that DSBs are significantly lowered but not abrogated. Moreover, the expression of constitutive deaminase domains within the editors may impact the mutagenic load of treated cells. While these potentially genotoxic outcomes can be mitigated by optimizing expression and culture conditions, they should be better investigated and monitored in emerging clinical applications. Overall, our work should advance HSC gene therapy by a combination of transformative approaches leveraging on precision genetic engineering while alleviating the morbidity of the procedure, broadening application to several diseases and patients worldwide.

Luigi Naldini

Luigi Naldini

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget)

10:15-10:30 Q&A

Chair

Laura Sepp-Lorenzino

Laura Sepp-Lorenzino

Intellia Therapeutics

11:00-11:05 Introduction to Session 2
Laura Sepp-Lorenzino

Laura Sepp-Lorenzino

Intellia Therapeutics

11:05-11:20 Multiplexed CRISPR-based cell engineering to generate persistent allogeneic solutions and improved function in solid tumors

Cell therapies have shown great success in treating hematologic malignancies, but their widespread use has been limited by high cost and failures of autologous manufacturing and poor efficacy in solid tumors. To generate durable "off-the-shelf" allogeneic products with activity in immunosuppressive indications, multiple edits will likely be required; however, multiplex editing can cause concerns related to genotoxicity. To overcome these limitations, we developed a highly efficient multiplexed editing strategy combining CRISPR SpyCas9 cleavage for targeted integration of the CAR/TCR and Nme2Cas9 base editor for any additional knock out (KO) edits. A lipid nanoparticle platform was applied to maintain high cell viability and expansion. This strategy was deployed to generate allogeneic T cells avoiding host T and NK cell rejection and carrying further edits to improve activity in solid tumors. Engineered T cells showed high chromosomal integrity, early memory phenotype, high expansion, and functional activity in vitro and in vivo.

Dr Birgit Schultes

Dr Birgit Schultes

Intellia Therapeutics

11:20-11:35 Programming permanent gene repression by epigenetic editing

Epigenome editing is emerging as a powerful new strategy to silence gene expression without altering the primary DNA sequence. In this context, we and others have previously demonstrated that transient delivery of Engineered Transcriptional Repressors (ETRs) can result in efficient, long-term, stable, and specific epigenetic silencing of endogenous genes in both human and mouse cells, and more recently, in vivo in mice. ETRs are chimeric proteins consisting of a programmable DNA-binding domain, such as CRISPR-Cas9 or ZFPs, fused to one or more effector domains derived from naturally occurring epigenetic repressors. During my talk, I will present our efforts to refine and characterize this technology, focusing on its in vivo and ex vivo applications for the treatment of monogenic and acquired diseases.

Professor Angelo Lombardo

Professor Angelo Lombardo

San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) & Vita-Salute San Raffaele University

11:35-11:50 Delivery of genome editing tool kits in engineered lentivirus-derived particles

The invention of CRISPR/Cas gene editing tools offers hope for the development of drugs treating genetic defects directly in patients. However, delivering such tools to specific cells and organs remains a key challenge. Inspired by retroviruses' ability to carry integrase proteins into cell nuclei of infected cells, we engineered HIV-1-derived lentivirus-derived nanoparticles (LVNPs) to deliver transposases, designer nucleases, and RNA-guided endonucleases into cells. Recently, we demonstrated successful targeted DNA cleavage in cells treated with LVNPs loaded with SpCas9/guide RNA ribonucleoproteins (RNPs) and achieved gene editing via homology-directed repair, using reverse-transcribed DNA from co-packaged vector RNA as a template. The LVNP platform also supports base and prime editing, and pseudotyping enables cell-specific gene editing and adapted use in primary cells. Early in vivo evidence of LVNP-directed gene editing in the mouse retina fuels hope that LVNPs can be further developed and produced in large scale for therapeutic applications.

Professor Jacob Giehm Mikkelsen

Professor Jacob Giehm Mikkelsen

Aarhus University

11:50-12:05 Promise of AAV-mediated gene delivery as a disease-modifying therapy

The potential of recombinant adeno-associated viral vectors as a therapeutic modality for genetic diseases continues to show promise. There is demonstrable evidence of clinical efficacy and durability of effect that persists for multiple years following a single treatment in a growing number of indications. However, there are safety challenges with high doses indicating the need for more potent and tissue-tropic viral vectors. Host immune responses to the administered vector and expressed neo-transgene product require mitigation such as the tacit use of immunosuppressive regimens. Judicious selection of transgene expression cassette design is yet another important consideration for an optimal clinical outcome. Lessons learned are providing a clearer path to deploying this emerging technology platform for use in the next wave of diseases with particular emphasis on those with high unmet need.

Dr Seng H. Cheng

Dr Seng H. Cheng

Alexion, AstraZeneca Rare Disease

12:05-12:20 Lipid nanoparticles are enabling gene therapies

Lipid nanoparticles (LNPs) represent an advanced drug delivery system that is now enabling gene therapies. LNPs are critical to enabling the function of nucleic acids which are unable to access their target sites, the internal compartment of cells. The first-ever approved RNA interference therapeutic, Onpattro, was designed to deliver short interfering RNA to the liver to treat hereditary transthyretin amyloidosis. Further advancements of these systems through optimization of the LNP have enabled their use in the messenger RNA vaccines commercialized by Pfizer/BioNTech and Moderna. Most recently, LNPs have been applied to enable in vivo gene editing, protein replacement and to establish passive immunity. While substantial advancements have resulted in several medicines for liver diseases and vaccines, the critical barrier to treating or even curing disease is the ability to deliver nucleic acids to their target site in a precise manner to non-liver tissues.

Dr Jayesh Kulkarni

Dr Jayesh Kulkarni

NanoVation Therapeutics (NTx)

12:25-12:40 Q&A

Chair

Robin Lovell-Badge

Professor Robin Lovell-Badge FRS

The Francis Crick Institute

13:45-13:50 Introduction to panel
Professor Robin Lovell-Badge FRS

Professor Robin Lovell-Badge FRS

The Francis Crick Institute

13:50-15:00 Panellists
Sharmila Nikapota

Sharmila Nikapota

Cure EB Founder Trustee

Alyssa

Alyssa

Great Ormond Street Hospital Patient

Roanna Maharaj

Roanna Maharaj

PPV Thalassaemia Representative

Chair

Professor Waseem Qasim

Professor Waseem Qasim

UCL Great Ormond Street Institute of Child Health

15:30-15:35 Introduction to session 3
Professor Waseem Qasim

Professor Waseem Qasim

UCL Great Ormond Street Institute of Child Health

15:35-15:55 Precise gene correction for Primary Immunodeficiency Diseases

Inborn errors of immunity (IEIs) are monogenic disorders of immunity that causes significant morbidity or early mortality. Hematopoietic stem cell transplant can be life-saving but are limited by graft rejection, graft failure, graft-versus-host disease or a lack of suitably HLA-matched donors. Gene therapy using a patient’s own stem cells could mitigate these problems. The earliest stem cell gene therapy clinical trials using oncoretroviral vectors to insert therapeutic transgenes inadvertently activated nearby oncogenes and caused leukemias. Improved lentivectors used currently integrate in actively transcribed genes and can cause aberrant fusion transcripts.  Next-gen targeted gene editing tools like base editing provides precision and efficacy that should address random integration concerns and importantly, restores physiological gene expression. Preclinical base editing studies of a CYBB mutation in patient HSPCs confirming highly specific and efficient mutation repair supported our clinical gene therapy trial using BE HSPCs for treatment of Chronic Granulomatous Disease.  Our goal is to provide efficacy and safety data from treated patients to support extending the approach to other IEIs. 

Suk See De Ravin

Suk See De Ravin

National Institutes of Health

15:55-16:15 Hacking T cells to fight leukaemia

Most patients with leukaemia can be successfully treated with chemotherapy, but if the disease relapses and becomes ‘hard-to-treat’, we can now offer alternative approaches that harness powerful immune effects. T-cells, a critical group of white blood cells that protect us from infections, can be collected and reprogrammed to hunt down and eradicate certain types of blood cancer. Recently, genome editing technologies, including CRISRP/Cas9 and Base editing, have been used to simultaneously ‘hack’ multiple genes in T cells from healthy donors so that they can be pre-manufactured and used to treat different types of leukaemia without the need for any matching. These evolving gene-edited medicines offer powerful new therapies that are being tested in carefully designed clinical trials in children and adults.

Professor Waseem Qasim

Professor Waseem Qasim

UCL Great Ormond Street Institute of Child Health

16:15-16:35 Therapeutic gene editing for cardiovascular and metabolic diseases: from the leading cause of death to N-of-1 disorders

Inborn errors of metabolism (IEMs) are rare, devastating disorders arising from pathogenic variants in genes encoding enzymes of key biochemical pathways. The liver plays an important role in the pathogenesis of over 150 IEMs, often failing to metabolize a toxic metabolite that can injure secondary organs, such as brain. Liver transplantation is sometimes employed; however, its utility is limited by scarcity of donors and lifelong risk of post-transplant complications. We aim to establish a protocol for the rapid development of personalized, liver-directed editing therapies for hepatic IEMs. We envision a platform regulatory framework where IND-enabling studies for a “leader” hepatic IEM editing therapy also support programs for varied “follower” indications. The leader and follower therapies will differ only in patient-variant-specific guide RNA sequences. A platform regulatory approach is essential to develop therapies in time to meaningfully improve outcomes in this patient cohort who suffer significant early morbidity and mortality.

Professor Kiran Musunuru

Professor Kiran Musunuru

University of Pennsylvania

16:35-16:50 Q&A

Chair

Laura Sepp-Lorenzino

Laura Sepp-Lorenzino

Intellia Therapeutics

09:00-09:05 Welcome and opening remarks
Professor Robin Ali

Professor Robin Ali

King's College London

09:05-09:25 CRISPR Cures For All: an Actionable Path

Gene editing, a Nobel-prize winning technology for repairing genetic changes that cause disease, is the basis of a medicine for sickle cell disease. This landmark achievement raises the question: can gene editing be used for thousands of other severe diseases caused by single mutations? In a research lab the answer is a firm "yes" - but what about in the clinic? A path to "CRISPR Cures For All" exists. Making it real will take innovation and courage.

Fyodor Urnov

Fyodor Urnov

University of California, Berkeley

09:25-09:30 Q&A

Chair

Professor Robin Ali

Professor Robin Ali

King's College London

09:30-09:35 Introduction to session 1
Professor Robin Ali

Professor Robin Ali

King's College London

09:35-09:55 Innovation and challenges in CMC (Chemistry, Manufacturing and Controls) with new technology platforms – The gene and cell therapy case

Cell and gene therapies have revolutionized the treatment of various diseases, especially genetic disorders and certain cancers. Compared to traditional therapies, they offer targeted treatment by addressing diseases at the genetic level, long-lasting effects, personalization using the patient's own cells, and the potential to treat previously untreatable conditions. Traditional therapies such as small molecules and biologics, have well-defined CMC deliverables, well-established manufacturing processes and cost structures, allowing for predictable production scales and pricing. Cell and gene therapies often involve complex and individualized manufacturing processes that can lead to significant variability in yield, production timelines and costs. Cell and gene therapies also face unique challenges in scalability, quality controls, regulatory compliance, and supply chain logistics. Innovating manufacturing solutions, such as automation, standardization and advanced bioprocessing technologies, is essential. Continued investment in manufacturing capabilities and cost-effective strategies is crucial for integrating these groundbreaking therapies into standard healthcare practices.

 
Dafni Bika

Dafni Bika

AstraZeneca

09:55-10:15 Commercialising advanced cell & gene therapies - Challenges and opportunities

Commercialising Advanced Cell & Gene Therapy (ACGT) products poses several additional challenges for manufacturers. While these personalised therapies offer transformational outcomes, they are also more complex to deliver and often require new systems to be put in place, e.g. cold chain logistics, cell orchestration and scheduling platforms for autologous CART therapies. Improvements in the training and communication of the CAR T work force are essential for the delivery of CAR T therapy.  Patient management will increasingly be shared by different healthcare providers and new patient pathways are therefore needed to identify and refer of patients to treatment centres. ACGT products require long-term real world evidence collection through registries for safety and this may afford an opportunity to collect data for other purposes, e.g. establishing fair value. Expansion of existing capabilities like apheresis is required and has significantly lagged demand. Where-ever possible, simplified and standardised processes should be followed, taking into account that manufacturers must operate globally. Like other products with transformational outcomes, these therapies typically have accelerated approval based upon single-arm studies. This leads to greater uncertainty in appraising value and price, which is further exacerbated by most being one-time administered products. The NHS, as a single national provider of healthcare, has a significant advantage in addressing some of these challenges. Collaboration with all stakeholders, including industry, will be the key. An example of where this has worked well is the Advanced Therapy Treatment Centre (ATTC) network.

Christopher Vann

Christopher Vann

Autolus Ltd

10:15-10:35 Overcoming manufacturing and regulatory challenges in multicomponent gene editing technologies

Gene editing technologies present unique and complex manufacturing challenges. As multicomponent products, gene editing therapies require the precise integration of multiple biological elements, such as guide RNAs, nucleases, and delivery systems, each of which must meet stringent quality and safety standards. This complexity intensifies the difficulty of manufacturing these therapies, especially at small scales. The lack of appropriate small-scale manufacturing solutions creates a critical bottleneck, leading to inefficiencies, higher costs, and longer development timelines. This presentation will explore the dual challenges of manufacturing and regulation in gene editing, with a focus on the multicomponent nature of these products and the urgent need for new technologies and regulatory pathways. Addressing these issues is essential to unlocking the full potential of gene editing and accelerating the development of life-changing therapies.

Vanessa Almendro Navarro

Vanessa Almendro Navarro

Danaher

10:35-10:50 Q&A

Chair

Robin Lovell-Badge

Professor Robin Lovell-Badge FRS

The Francis Crick Institute

11:20-11:25 Introduction to session 2
Professor Robin Lovell-Badge FRS

Professor Robin Lovell-Badge FRS

The Francis Crick Institute

11:25-11:45 Cell and Genetic therapies: global regulatory strategies and lessons learned

Vertex invests in scientific innovation to create transformative medicines for people with serious diseases with a focus on specialty markets.  Cell and genetic therapies require a different approach to drug development including robust data packages and early and often engagement with regulators. This presentation will review global regulatory strategies and lessons learned on the journey to approval.

Stephanie Krogmeier

Stephanie Krogmeier

Vertex Pharmaceuticals

11:45-12:05 Ensuring safety in genome editing: Innovations in detecting and mitigating off-target effects

In recent years, several gene- and base-editing approaches have been developed for the treatment of congenital and acquired diseases. Some of these have been successfully translated into the clinic, and the first CRISPR-based drug has been approved. Before gene-edited products can be administered to patients, it is essential to thoroughly evaluate the genome of the edited cells, as genome editing carries risks of unintended off-target effects and significant on-target aberrations. This presentation will review the methods used to assess off-target effects, with a focus on CAST-Seq, an assay we have developed to detect both on- and off-target effects, including chromosomal rearrangements, in clinically relevant cell types ex vivo and in vivo. I will show how detailed analysis of collateral damage in cells edited with CRISPR-Cas nucleases, nickases or base editors has provided insights into the underlying mechanisms. Lastly, I will discuss strategies to reduce the risk of genotoxicity and improve the safety of these emerging therapeutic approaches.

Professor Toni Cathomen

Professor Toni Cathomen

University of Freiburg

12:05-12:25 Precision medicine and HTA: An overview of the barriers and solutions in evaluating Advanced Therapy Medicinal Products (ATMPs)

The number of ATMPs being assessed by NICE is likely to increase in the coming years. This presentation will provide an overview of the experience NICE has had to date with ATMPs and the crucial role the organisation plays in assessing the clinical and cost-effectiveness of these technologies. 

John Spoors

John Spoors

NICE

12:25-12:40 Q&A

Chair

Professor Robin Ali

Professor Robin Ali

King's College London

14:45-15:05 Regulation and encouraging innovation in Gene and ATMPs

As the UK’s medicines regulator, MHRA’s role is to strike a balance between enabling ground-breaking scientific advancements and safeguarding public health. Gene and ATMP medicines generally represent a significant innovation, offering potential cures for previously untreatable conditions. Our robust regulatory approach involves rigorous evaluation of the safety, efficacy, and quality implications, and we work closely with industry, healthcare professionals, and the wider public to ensure that gene editing medicines meet the highest standards of safety and quality. Acknowledging the evolving needs of the sector and the challenges of regulating such personalised medicines, we are taking proactive steps to enable innovation without compromising patient safety. Looking forward, we are committed to evolving our regulatory framework to adapt to the fast-paced developments in Gene and ATMPs, ensuring that innovative medicines reach patients in a timely and safe manner.

Julian Beach

Julian Beach

MHRA

13:40-13:45 Introduction to session 3
Professor Robin Ali

Professor Robin Ali

King's College London

13:45-14:05 What makes a successful commercial genetic medicine?

Over the past decade, we have seen the advancement of genetic therapies for numerous human diseases. There have been many successes but equally many failures. Intriguingly, there have been programmes that have shown clinical efficacy but have not been able to achieve either regulatory or commercial success. In this talk I will examine why some programmes even for ultra rare diseases, such metachromatic leukodystrophy, have been able to successfully secure access for patients and will also speculate on the reasons for the difficulties other programmes have faced. The criteria for success are multi factorial and include not only the commercial and economic landscape and value proposition and an understanding of the patient need, but also some of the manufacturing requirements needed to bring these complex biological medicines into the commercial arena. An understanding of these factors may help future products navigate their way through this evolving ecosystem and ultimately deliver the promise of these transformational medicines to patients in need.

Professor Bobby Gaspar

Professor Bobby Gaspar

Orchard Therapeutics, UCL

14:05-14:25 Economic aspects of access to gene therapies for ultra-rare diseases: an impossible riddle

Is it ethical to deny life-saving treatment from a child affected by a rare disease simply because it is too expensive? Or is it ethical to spend a fortune saving “only” one life when the same amount of money could improve the health of many others? This is not a new dilemma but the recent development of (hopefully curative) gene therapies for life-threatening ultra-rare diseases has brought this discussion to a new level. In July 2023, Fondazione Telethon became the first not-for-profit organization to be marketing the authorization holder of an ATMP in Europe. Fondazione Telethon could, for example, pave the way for a different commercialization model of ATMPs for ultra-rare diseases where profit does not play a role. However, this model can only be complementary to the standard pharmaceutical development - not alternative to it.

Stefano Benvenuti

Stefano Benvenuti

Fondazione Telethon

14:25-14:45 Effective clinical development to enable patient access for gene editing therapies

Gene editing therapies have the potential to revolutionise the treatment of genetic disorders, but the path to patient access and reimbursement has challenges. These challenges result from uncertainties around patient need, clinical value, and the disease, reimbursement, and commercial landscapes. Effective clinical development of gene editing therapies requires a patient-centric approach and early collaboration across various stakeholders, both internal and external. This talk will examine how these challenges can be mitigated earlier in the product lifecycle by adopting a “new” clinical development mindset and how this approach differs from traditional development.

Dr Benit Maru

Dr Benit Maru

SSI Strategy

15:05-15:20 Q&A

Chair

Steve Rees

Steve Rees

AstraZeneca

15:50-15:55 Introduction to panel
Steve Rees

Steve Rees

AstraZeneca

15:55-16:30 Panellists
Fyodor Urnov

Fyodor Urnov

University of California, Berkeley

Suk See De Ravin

Suk See De Ravin

National Institutes of Health

John Spoors

John Spoors

NICE

Dr Birgit Schultes

Dr Birgit Schultes

Intellia Therapeutics