As part of WuXi AppTec’s ongoing efforts to collaboratively foster new thinking and actionable approaches in advancing breakthroughs for patients, we have launched a new interview series in 2022 – “Delivering on the Promise of New Modalities” – so leading voices of R&D can share how their approaches are addressing the barriers standing in the way of breakthroughs.

Our next “Delivering on the Promise of New Modalities” interview series installment features Karen Kozarsky, Co-Founder & Chief Scientific Officer of SwanBio Therapeutics. As a gene therapy company advancing AAV-based therapies for the treatment of devastating, inherited neurological conditions, SwanBio Therapeutics recently announced their completion of $56 Million Series B Financing to advance novel gene therapies for neurological conditions. Earlier this year in July, they entered into a partnership with Purespring Therapeutics to license their proprietary in-vivo ‘gene therapy search engine’ to advance AAV-based gene therapies for use in neurological diseases.

We’re excited to have you with us, Karen! Congratulations on all of SwanBio’s success this past year. For drug discovery & development related to inherited neurological conditions, what are the challenges in developing therapeutic interventions and potential new modality solutions?

Karen: SwanBio Therapeutics is a gene therapy company aiming to bring life-changing treatments to people with devastating neurological conditions. We’re focused on these individuals and their families because of the historic challenges that have hampered advances in neurology.

One of the main barriers to progress in neurological R&D has been a lack of understanding about the mechanisms of diseases. Thanks to advancements in genetics, we are now better positioned than ever to identify, target and treat the root cause of disease.

In many cases, gene therapy is technically capable of addressing the genetic cause of disease, rather than just the symptoms, which holds great potential for patients who have been waiting for meaningful treatments. This is the case for adrenomyeloneuropathy (AMN), the disease SwanBio is initially targeting.

Once that root cause of disease is identified, the next challenge facing drug developers is delivering therapies in a targeted, efficient, and effective way.

What is your new modality or technological approach helping to address these challenges? How is it different from existing approaches?

Karen: In many cases, gene therapy is technically capable of addressing the root cause of disease. This is what SwanBio is focused on in AMN – a condition with no therapeutic options besides symptom management.

In developing a gene therapy that addresses the ABCD1 gene deficiency that causes AMN, we are aiming to address the downstream effects patients experience due to the gene deficiency, which affects the cells of the spinal cord and other tissues, manifesting as spastic paraparesis, and sensory ataxia. These effects lead to loss of mobility in adulthood, incontinence, debilitating pain, and sexual dysfunction, impairing quality of life.

To further address the challenges facing experimental gene therapies, we have curated a specific expertise in intrathecal delivery. Our method aims to achieve targeted biodistribution throughout the spinal cord, rather than relying on higher, systemic doses (and higher systemic exposure) others have explored for delivery to the CNS.

What are critical challenges in realizing the full potential of gene therapies? What could be the solutions in your opinion?

Karen: The success of gene therapies relies on solid manufacturing strategies. The critical importance of this function led us at SwanBio to take an incredibly intentional approach to manufacturing, establishing scalable, commercial-ready processes from the outset. We made a significant upfront investment in process development and optimization to eliminate the need for bridging during clinical development and to ideally minimize regulatory delays.

Another challenge facing drug development in any category is translating the success of preclinical research to the clinical setting. Naturally, we’ve seen this challenge in gene therapy as well. Our approach to overcoming this barrier has been to build the connections between efficacy and biodistribution to develop a strong patient dosing strategy. We look forward to executing this careful planning when we officially begin our Phase 1/2 clinical study and start dosing patients later this year.

What does global collaboration mean to your company?

Karen: At SwanBio, our initial focus is on rare, neurological diseases. A natural consequence of working in rare disease is that the number of clinicians who have true expertise and deep experience working with affected patients is limited, and widespread knowledge of diseases can also be rare. Rare expertise in rare disease means that true, global collaboration is critical to success. As a result, we started making connections and building relationships with centers and expert physicians around the world from the very beginning – even before SwanBio was technically founded. We have made a point to work with them closely from the onset, to understand the science and learn from their experiences spending a lot of time with patients.

This approach means that we look for expertise, without worrying about borders.

If we were to gather here again in 10 or 15 years’ time, what do you think we’re going to be talking about in terms of the landscape of gene therapy R&D?

Karen: My hope is that in 10-15 years, we will see a faster pace of gene therapy approvals – ultimately getting treatments to people in need much more quickly. This may require new partnership models or strategies to help gene therapy companies translate their early clinical successes into pivotal trials and eventually commercialized products.

I also hope that we’ll see greater manufacturing efficiencies and quality across the board. This evolution will require more knowledge sharing – the convergence of methods from groups who have become experts in gene therapy manufacturing, and who are willing to share their best practices for the greater good.

 

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Karen Kozarsky, PhD

Co-Founder & Chief Scientific Officer

Karen Kozarsky is the co-founder and CSO of SwanBio Therapeutics, a Philadelphia-based gene therapy company focused on bringing life-changing treatments to people with devastating neurological conditions. She leads the development of the company’s pipeline – therapies designed for intrathecal delivery to address targets in both the central and peripheral nervous systems.

Karen has 25+ years of experience in gene therapy, with a primary focus on adeno-associated virus (AAV) vectors. Her expertise includes evaluating potential therapeutic opportunities, identifying new areas, and developing products from the earliest preclinical stages through IND.

She has been involved in the development of multiple gene therapy products that are in clinical trials. Karen’s roles have included President of Vector BioPartners, Vice President of R&D at REGENXBIO Inc., and Head, Gene Therapy in the GlaxoSmithKline Biopharmaceutical Center of Excellence for Drug Discovery. Previously, she was a Research Assistant Professor at the University of Pennsylvania’s Institute for Human Gene Therapy, and completed postdoctoral fellowships at the University of Michigan in gene therapy and in immunology. She received a PhD in biology from the Massachusetts Institute of Technology and a BA in biology from Amherst College.

In 2021, Karen was recognized by the Philadelphia Business Journal as one of the year’s ‘Women of Distinction’ for her leadership and vision. Karen was named by the Alliance for Regenerative Medicine as the first co-Chair of the Gene Therapy Section to support policies to advance novel gene therapies, and has been a committee member for the American Society of Gene & Cell Therapy.