Advanced Therapies Week 2025: Expanding the Scope of Gene Therapy

At Advanced Therapies Week 2025, the session titled “Expanding the Promise of Gene Therapy” brought together leading experts to discuss cutting-edge advancements, challenges, and future directions in gene therapy. The panel comprised industry leaders from pioneering companies working to broaden the accessibility, efficacy, and manufacturability of gene therapies for neurological, rare, monogenic, and larger patient populations. The presentations centered around innovations in AAV (adeno-associated virus) capsid engineering, universal payload strategies, clinical and manufacturing advancements, and scalable production platforms.

Dr. Jorge Santiago-Ortiz from Apertura Gene Therapy presented their receptor-targeted capsid engineering platform, which focuses on developing novel AAV vectors capable of crossing the blood-brain barrier (BBB) via the human transferrin receptor (TfR1). Their engineered capsids achieve broad CNS distribution through intravenous administration, overcoming challenges like antibody neutralization and manufacturability issues, thereby expanding patient access to gene therapies, especially for neurological disorders such as Parkinson’s and Alzheimer’s.

Dr. Nicole Paulk, founder of Siren Biotechnology, discussed the concept of a “universal payload” AAV platform designed to simplify and accelerate gene therapy development across multiple indications by maintaining a constant payload and delivery system. She highlighted their approach to using cytokine immunotherapies delivered via AAV, targeting brain cancers with local intratumoral delivery through convection-enhanced delivery (CED). Preclinical data demonstrated significant tumor reduction and survival benefits in animal models, with ongoing large animal safety studies and upcoming IND-enabling trials.

Dr. Kinnari Patel, COO of Rocket Pharmaceuticals, provided an overview of their integrated pipeline targeting rare monogenic diseases, focusing on pediatric populations for diseases like Fanconi anemia and Danon disease. Rocket emphasizes bringing manufacturing in-house to control quality and costs, enabling scalable production for broader disease applications. Their clinical data show promising efficacy and safety, with ongoing efforts to expand access through genetic testing initiatives and collaborations to improve patient diagnosis and treatment timelines.

Manny Otero, CTO at Lexeo Therapeutics, outlined their strategy of leveraging lessons from viral vaccine manufacturing to create scalable, robust AAV production using an SF9 insect cell platform. This approach aims to produce the large doses necessary for treating more prevalent diseases like Alzheimer’s and cardiomyopathies while maintaining product quality and regulatory compliance. Lexeo emphasizes strong CMC integration and partnerships with CDMOs to ensure process development aligns with commercial-scale manufacturing needs.

The ATW 2025 session concluded with a panel discussion addressing questions on delivery methods, capsid engineering, manufacturing platforms, and clinical trial strategies, underscoring the exciting potential and ongoing challenges in advancing gene therapy from rare diseases to larger patient populations with more accessible, efficacious, and manufacturable solutions.

Highlights from Advanced Therapies Week 2025

• Apertura Gene Therapy’s receptor-targeted AAV capsids efficiently cross the blood-brain barrier, enabling intravenous delivery for neurological diseases.
• Siren Biotechnology pioneers a universal AAV platform maintaining a fixed payload to accelerate development across multiple brain cancer indications.
• Rocket Pharmaceuticals integrates manufacturing and patient genetic testing to expand rare disease treatment access and improve clinical outcomes.
• Lexeo Therapeutics applies viral vaccine manufacturing lessons to scale AAV production via SF9 insect cell culture for larger patient populations.
• Intratumoral convection-enhanced delivery (CED) offers precise, MRI-guided gene therapy administration in brain cancers, enhancing safety and efficacy.
• Antibody evading AAV capsids are engineered to overcome neutralizing antibodies, broadening eligibility for gene therapies.
• Platform-centric approaches in gene therapy development promise to reduce costs and accelerate clinical translation across diverse diseases.

Key insights from Advanced Therapies Week 2025:

• Blood-Brain Barrier Targeting via Transferrin Receptor (TfR1): Apertura’s engineered AAV capsids exploit receptor-mediated transcytosis to cross the BBB, a significant hurdle in CNS gene therapy. This mechanism allows minimally invasive intravenous delivery, improving patient access and enabling treatment of widespread CNS disorders. The use of humanized animal models enhances translational relevance, addressing a key bottleneck in vector development. This approach exemplifies how mechanistic understanding of tissue targeting can optimize vector design.
• Antibody Evasion to Expand Patient Eligibility: Approximately 50% of the population harbors pre-existing neutralizing antibodies against common AAV serotypes. Apertura’s platform incorporates mutations that allow capsids to evade these antibodies without compromising manufacturability or tropism, which is crucial for expanding treatment to adult patients and improving clinical trial enrollment. This highlights the importance of engineering vectors not only for efficacy but also for immunological compatibility.
• Universal Payload Strategy to Streamline Development: Siren Biotechnology’s innovative approach of fixing the payload and delivery vector across multiple indications addresses the recurring challenge of bespoke payloads for every rare disease. By focusing on pleiotropic cytokines and transcription factors, this strategy enables a platform that drastically reduces preclinical and clinical development timelines, cost, and complexity. This paradigm shift could revolutionize gene therapy by transforming it into a scalable, modular treatment platform akin to monoclonal antibodies or checkpoint inhibitors in oncology.
• Clinical Translation of AAV Immunotherapies in Brain Cancers: Siren’s preclinical data demonstrate dramatic tumor reduction and survival benefits using locally delivered AAV cytokine therapies in xenograft mouse models and safety in large immunocompetent animals. The use of convection-enhanced delivery (CED) combined with MRI guidance ensures precise targeting within the brain, mitigating off-target effects and toxicity. This localized delivery approach may offer a safer alternative to systemic administration for CNS tumors, addressing a significant unmet clinical need.
• In-House Manufacturing and Scalability as a Strategic Advantage: Rocket Pharmaceuticals’ decision to internalize manufacturing capabilities reflects a growing recognition of the need for quality control, cost management, and innovation in gene therapy production. This vertical integration supports rapid iteration, scalability, and consistency, which are critical as gene therapies move from niche ultra-rare diseases to broader patient populations. Their success with X Volente and other pipelines underscores the benefits of controlling the entire development-to-production continuum.
• Leveraging Vaccine Manufacturing Expertise for Large-Scale AAV Production: Lexeo Therapeutics applies decades of viral vaccine production experience to AAV manufacturing, choosing an SF9 insect cell baculovirus system. This platform balances yield, cost of goods, robustness, and regulatory compliance, addressing the unique demands of producing millions of doses for common diseases. Their approach exemplifies how cross-industry knowledge can accelerate gene therapy scalability and commercial readiness, vital for reaching larger markets.
• Collaborative Ecosystem and Platform Models are Key to the Future: Across the presentations at ATW 2025, a shared theme is the importance of partnerships, between academia, biotech, pharma, CDMOs, and patient communities, to accelerate innovation and access. The move toward platform technologies, whether receptor-targeted capsids, universal payloads, or scalable manufacturing, aims to reduce redundancy, cost, and time to market. This collaborative, platform-centric vision is necessary to transition gene therapy from a niche, ultra-rare focus to a mainstream therapeutic modality impacting millions.

Speakers:

• Audrey Chang – Executive Director, WuXi Advanced Therapies (Chair)
• Jorge Santiago-Ortiz – Director, CMC, Apertura Gene Therapy
• Nicole Paulk – CEO, Siren Biotechnology
• Kinnari Patel – President & COO, Rocket Pharmaceuticals
• Manny Otero – CTO, Lexeo Therapeutics

Conclusion:

This Advanced Therapies Week 2025 session showcased how advances in capsid engineering, delivery strategies, payload design, manufacturing innovation, and collaborative frameworks are collectively pushing gene therapy toward broader applicability, improved patient access, and sustainable commercial models. The integration of mechanistic science with scalable manufacturing and clinical insight is paving the way for next-generation gene therapies that promise to transform the treatment landscape for rare and common diseases alike.