7:59 am
DISCUSSING STRATEGIES TO SOLVE THE ADVERSE CLINICAL EFFECTS OF LARGE DOSES FOR MUSCULAR TARGETS

8:00 am Morning Refreshments

8:30 am Chair’s Opening Remarks

8:45 am A Clinician’s Perspective: Gene Therapy for X-Linked Myotubular Myopathy

  • Perry Shieh Professor of Neurology & Pediatrics, University of California Los Angeles & Principal Investigator for ASPIRO, Astellas Gene Therapies

Synopsis

  • -X-Linked Myotubular Myopathy (XLMTM): Burden of disease
  • Gene therapy and efficacy outcomes
  • Safety profile and liver toxicity

9:15 am Panel Discussion: The Race for A Cure: Field Update of Muscular Disorders Gene Therapy Programs

  • Anh Nguyen Head of Limb Girdle Muscular Dystrophy, AskBio
  • Carl Morris Chief Scientific Officer, Solid Biosciences Inc.
  • Perry Shieh Professor of Neurology & Pediatrics, University of California Los Angeles & Principal Investigator for ASPIRO, Astellas Gene Therapies
  • Teji Singh Head of Clinical Development, Sarepta Therapeutics
  • Sharon Hesterlee Chief Research Officer, Muscular Dystrophy Association

Synopsis

  • Addressing older patient populations & introducing even larger doses
  • Clinicians managing the adverse effects: myocarditis and liver toxicity
  • Discussing predisposition to adverse side effects

10:00 am Structured Networking

10:45 am Morning Break

ASSESSING THERAPEUTIC EFFICACY & SAFETY IN MUSCULAR DISORDERS

11:00 am Investigating Clinical Data & Improving Monitoring with Novel Assays

Synopsis

  • Anti-capsid and anti-transgene antibody characterization with novel multiplex assays
  • Isotyping of anti-capsid antibodies
  • Domain mapping of anti-transgene protein antibodies

11:30 am Analytical Tools to Improve Empty/Full Ratio in Initial Stages of AAV Process Development

Synopsis

  • Empty AAV capsids are known contributors of immunogenicity in gene therapy products
  • Reducing them below 10% during downstream process is difficult if empty capsids constitute vast majority of total AAV produced in harvest. The solution is further optimization of harvest production
  • Determining the factors that improve empty/full ratio is possible already at the initial stages of upstream process development, with utilization of at-line HPLC system that measures E/F ratio directly in harvest samples. The same tool can be used for in-process control, to track the AAV production in samples collected during manufacturing runs
  • Described HPLC analytics is suitable for wide variety of samples, which allows easy link-up of upstream with downstream process development, and overall more holistic approach to AAV bioprocess

12:00 pm Utilizing Preclinical Models to Demonstrate Efficacy & Durability for Muscular Disorders

  • Marla Weetall Senior Vice President, Pharmacology & Biomarkers, PTC Therapeutics

Synopsis

  • Challenges in mouse models of DMD and in measuring dystrophin
  • Use of corticosteroids in mouse models of DMD and in the clinic
  • Measuring dystrophin increases in mouse models of DMD and in the clinic

12:30 pm Lunch & Networking

1:26 pm
EXPLORING NOVEL IN VITRO & IN VIVO PRECLINICAL ANIMAL MODELS OF MUSCULAR DISORDERS

1:30 pm Utilizing Multiple Animal Models to Evaluate Therapeutic Efficacy

Synopsis

  • Gene therapy studies in small animal models
  • Functional efficacy evaluations
  • Utility of canine models for further evaluation

2:00 pm Accessing Contractility of 3D iPSC-derived Engineered Muscle Tissues at High-throughput Using a Novel, Label-free Method

  • Greg Luerman Vice President, Research & Partnerships, Curi Bio

Synopsis

Overview of the technology, along with application examples across various use cases, including:

  • Skeletal muscle applications that can achieve tetanic contractions and fatigability, as well as stain positively for muscle specific markers, including fast myosin and desmin.
  • Disease models generated from iPSCs – including patients with rare diseases such as muscular dystrophy – and tested on the platform

2:15 pm Utilizing In Vitro 3D Muscle Bundles to Assess the Functionality of AAV Therapeutics for Duchenne Muscular Dystrophy (DMD)

Synopsis

  • Reproducible assay to test gene therapy candidates in DMD-patient derived cells
  • Repair of truncated dystrophin at the sarcolemma of DMD-treated myotubes
  • Structural restoration of the DAPC complex in DMD myotubes treated with an AAV-mediated exon skipping

2:45 pm Afternoon Break

NAVIGATING REGULATORY & MANUFACTURING CHALLENGES FOR MUSCULAR DISORDERS

3:15 pm Development of a Manufacturing Process: AT132’s CMC Journey

  • Chris Lorenz Senior Vice President, Technical Operations, Astellas Gene Therapies

Synopsis

  • Covering the scale up challenges and considerations for entering a late phase trial
  • Walking through the strategies, and considerations for AT132 as a case study

3:45 pm Guidance for AAV Process Development Based on Cost Modeling

Synopsis

  • Production of adeno-associated virus (AAV) and other viral vectors used for gene therapy faces challenges due to high manufacturing costs and compressed process development timelines compared to traditional biopharmaceuticals
  • Many process development activities may be undertaken to reduce manufacturing costs, but these costs are often not directly related to the process improvements being considered
  • In this work, process and cost models were built for AAV production and analyzed to assess the holistic impact of common process development objectives such as DNA digestion on the manufacturing costs
  • The insights from these analyses provide guidance for prioritization of various process development objectives

4:15 pm Panel Discussion: Overcoming Manufacturing Challenges with Advancing Programs

  • Chris Lorenz Senior Vice President, Technical Operations, Astellas Gene Therapies
  • Ratish Krishnan Associate Director, Novel Modalities, Millipore Sigma
  • Sharon Hesterlee Chief Research Officer, Muscular Dystrophy Association

Synopsis

  • Discussing the additional potency assays requested by regulators
  • Debating the affect of quality on efficacy
  • Approaching later programs and ensuring quality scale up and avoiding bottlenecks with large doses required for high muscle mass

4:45 pm Chairs Closing Remarks

5:00 pm Scientific Poster Session

Synopsis

At the first in-person Gene Therapy for Muscular Disorders event, maximize your networking opportunities by sharing your research and exploring your peers posters to improve your understanding of the field and make new connections.

6:00 pm End of Conference Day One