The Hidden Catalysts in Medical Innovation

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Beyond scientific conundra, a major concern associated with most of these novel therapies is their accessibility. This is an issue inherent to personalized medicine. While much more precise, potent and sparing for the patient, it involves significantly more resources. As in the case of autologous cell therapies, an entire team of scientists may be engaged to work on the modification of the cells of a single patient. In fact, a record was recently broken with the price of Orchard Therapeutics' (a subsidiary of Kyowa Kirin) Lenmeldy gene therapy drug set at $4.25 million. 'The pricing really reflects the profound impact HSC gene therapies can have—helping transform a fatal, devastating disease into something that may be addressed with a one-time treatment. It also recognizes the significant investment required to bring such innovative, personalized treatments to market for an ultra-rare disease,' Kyowa Kirin North America's President, Steve Schaefer explained. Whereas these are certainly valid points, the question of accessibility remains to be solved.

As mentioned, specifically in the CAR T-cells space, costs can be tempered via the allogeneic card, which allows for the production of multiple doses from a single manufacturing run. Yet, solutions do exist for autologous therapies, which can have important advantages in certain cases. Service providers, like Contract Development and Manufacturing Organizations (CDMOS), can have a key role to play here. Cellares' CEO & Co-founder, Fabian Gerlinghaus, emphasized the degree of the scalability problem: 'About 20% of patients are dying on the waitlist even though they are eligible for approved cell therapies because the industry is unable to meet patient demand.' Cellares has developed a manufacturing platform, called Cell Shuttle, which, Gerlinghaus claims, successfully integrates and automates the entire cell therapy manufacturing process into one place. 'It encapsulates the functionality of approximately 100 benchtop instruments in a single, compact machine,' Gerlinghaus said, adding that this 'reduces labor and space requirements by 90%. The other key difference is that the Cell Shuttle can process 16 cell therapy processes simultaneously.' Gerlinghaus anticipates that the Cell Shuttles will be able to meet worldwide demand for cell therapies in the future.

Cellares is an example of how contract service providers can play a critical role in supporting the work of biopharma companies. Another such illustration comes from Nucleus Radiopharma, a CDMO operating in the space of radiopharmaceuticals. Highly promising, such therapies rely on low-energy isotopes that integrate cancer-targeting molecules. Perhaps counterintuitively, radiopharmaceuticals can allow for precise tumor treatment while minimizing damage to surrounding tissues. 'The potential in this field is significant, especially for conditions like neuroendocrine tumors and prostate cancer, where targeted radiotherapy could have a transformative impact,' Theodore Leondaridis, the Global Oncology Head of Pierre Fabre Group shared with us. The company is considering its entry into this space, as the sector is attracting more and more attention, as exemplified by recent news about Astrazeneca's pending $2.4 billion acquisition of Fusion Pharmaceuticals, known for developing next generation radioconjugates. But for all their prospects, radiopharmaceuticals have an Achilles' heel - manufacturing and logistics. Nucleus Radiopharma's CEO, Charles Conroy, told us that the industry is particularly challenging 'due to the short half-life of isotopes, which complicates logistics similar to shipping ice without refrigeration.' To address this, the CDMO is establishing multiple production sites across the U.S. 'We are strategically situating our facilities near major medical centers to expedite the transfer of

isotopes and drugs into patient studies and eventual commercial use,' Conroy said. But while infrastructural issues persist, Conroy is optimistic that the large investments that the sector is attracting will solve these.

The increased relevance of contract service providers is a general trend in life sciences driven as much by economic considerations, as by new challenges that come along with scientific advancements. 'The shift from small molecules to large molecules and biologics marks a significant evolution in healthcare. This transition necessitates specialized expertise in areas like cell and gene therapy, where CDMOS excel,' observed William Humphries, the CEO of Alcami Corporation. To respond to this new reality, global service providers are expanding and/or profiling their activities. 'We have broadened our service scope by acquiring CELLFORCURE from Novartis, a state-of-the-art cell and gene therapy manufacturing unit. This acquisition allows us to offer a more comprehensive range of CDMO activities, extending our expertise from small molecules to cell and gene therapy,' the CEO of the French-based SEQENS, Pierre Luzeau, told us.

Crucially, more than meeting new demands, service providers are also proactive innovators. A telling illustration comes from Codexis, which offers engineered enzymes to its various clients. One of its platforms, ECO Synthesis, is designed to address the scalability and sustainability challenges that have characterized the RNA synthesis space. Particularly the latter is a topic that has received little media attention but, as we are told, conventional RNA synthesis is heavily reliant on environmentally detrimental solvents. 'ECO Synthesis operates in water, dramatically reducing the carbon footprint and eliminating the need for large-scale, expensive containment facilities. This innovation not only promises a more sustainable approach but also significantly reduces capital investment requirements, enabling the production of SIRNA at scales previously deemed,' the CEO of Codexis, Stephen Dilly noted. Innovations of this sort are likely to prove as the key differentiator in the space of contract service providers in the years to come.

TREVOR P. CASTOR | PRESIDENT & CEO, APHIOS CORPORATION Zindol highlights our platform's capacity to offer natural, effective treatments with fewer side effects, addressing significant needs in areas like hyperemesis in pregnancy and post-operative care and versatility for improving quality of life. KEVIN ALI | CEO, ORGANON Achieving a women's health moonshot is within our collective reach. I'm energized by the positive trends I see across scientific discovery, focused government attention and private sector that are turning this future into our present.