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Porter discusses regulatory compliance, ATMP sponsors, and Philadelphia’s Cellicon Valley.
Applied Clinical Trials: Since January 2020, the US Food and Drug Administration (FDA) has issued ten guidance documents for gene therapy program sponsors to align with the advances in research. How receptive have sponsors been to the various guidance and what are the key takeaways for companies in regard to maintaining regulatory compliance from these guidances?
Porter: Sponsors have been receptive to these guidances and, in fact, appreciate the clarity they can offer. One of the challenges in developing products in the cell and gene therapy space is working in a regulatory landscape that is constantly evolving with the advancement of these novel technologies. Sponsors face the challenge of designing development plans and timelines to meet moving targets with respect to CMC requirements, clinical trial endpoints and criteria for approval. This is particularly relevant for cell and gene therapies in the rare disease space, where, due to potential accelerated approval programs, sponsors could be moving to commercial manufacturing scale up in a short period of time. In addition to working within these guidelines, sponsors should maintain an open dialogue with FDA with regard to development plan, clinical trial design and manufacturing plans and procedures. This can help eliminate surprises from the agency that could result in clinical holds, which can derail development timelines, and/or require costly additional development work, including additional clinical trials or comparability studies.
ACT: As we move out of the pandemic, what issues specific to ATMP sponsors are coming to the surface?
Porter: The biggest issues we’re seeing for ATMP sponsors as we move out of the pandemic are related to manufacturing and financing. Securing manufacturing capacity is a challenge. There are limited manufacturers with the expertise and facilities to manufacture cell and gene therapy products. In addition, this type of manufacturing requires skilled operators, and manufacturers are facing the same labor challenges seen in the rest of the economy. Beyond limited capacity, there can also be several issues that can arise in the transition from lab-based manufacturing in early development stages to scaled up production. For sponsors, manufacturing setbacks can be expensive, and, especially for smaller start-ups and academic spinouts, can significantly derail development timelines. Meeting projected time to market can be critical for these companies with respect to securing continued financing.
ATMP sponsors are also facing capitalization challenges in early 2022. In 2021, the bull market for life sciences companies began to stall. After seeing several high-valuation IPOs in the space, such as Sana Biotechnology, Lyell Immunoharma and Caribou Biosciences, there has been a significant slowdown. Several cell and gene therapy clients we were working with in the confidential registration statement process have paused their IPO plans. Given the climate in the capital markets, competition in the private financing markets has also increased, making crossover and venture financing more difficult to secure. Given these challenges, ATMP sponsors are now implementing cost-saving strategies to extend cash runways, which can, among other strategies, include limiting development focus to one or two programs at a time.In addition, ATMP sponsors are looking for more creative financing alternatives, such as strategic collaborations with large pharma partners, royalty financing, venture debt and support from inside investors, to get them through until the markets rebound.
ACT: How is the local Cellicon Valley progressing? Milestones/achievements/messages?
Porter: Philadelphia’s Cellicon Valley continues to grow. As home to the University of Pennsylvania, Children’s Hospital of Philadelphia, & Jefferson Health, Philadelphia has seen the advancement of key cell and gene therapy leaders, such as Dr. Carl June and Dr. Jim Wilson. Philadelphia continues to grow as an innovation hub, with promising startup and spin-out companies (including those guided by Dr. June and Dr. Wilson) finding a home in the Philadelphia area. At present there are over 30 cell and gene therapy companies and 60 labs in the region, as well as big pharma presence from GlaxoSmithKline, Bristol Myers Squibb, Merck, Sanofi, and Johnson & Johnson. Since 2018, several cell and gene therapy companies headquartered in the Philadelphia area, such as Cabaletta Bio, Castle Creek Bio, Century Therapeutics, and Passage Bio, have completed successful IPOs, with six IPOs in 2020 alone.
A recent major addition to Cellicon Valley is Discovery Labs and the Center for Breakthrough Medicine (CBM). CBM is the first and largest single-point cell and gene therapy Contract Development and Manufacturing complex in the world, offering plasmid, viral vector and cell therapy manufacturing as well as process development, analytical development and testing services all on one site. In early 2022, CBM and the University of Pennsylvania’s Gene Therapy Program signed a landmark collaboration agreement, to combine Penn’s knowledge and expertise in the development of gene therapies with CBM’s manufacturing capacity and singular focus on advanced therapies. As cell and gene therapy manufacturing demand is expected to continue to outpace capacity, the Discovery Labs and CBM will help support the growth of Philadelphia’s cell and gene therapy companies.