CGT Manufacturing Resolution #1: Brace For Continued — But Nuanced — Investments In Manufacturing & Infrastructure

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

In early December, I invited Katy Spink, COO and managing partner of Dark Horse Consulting, to sit down with me for a discussion on her expectations and predictions for CGT manufacturing paradigms in the new year. But because cross-industry collaboration, face-to-face communication, and transparency are critical in this burgeoning industry (and, let’s be honest, can be a lot of fun), Katy and I were also joined by a small group of CGT manufacturing experts from different companies across the industry.

Our conversation ultimately outlined five best practices — or, more fittingly, New Year’s Resolutions — that companies should embrace in 2022 that will (incrementally) help us define and achieve manufacturing maturity in the future.

In the first of this five-part article, Spink dives into resolution #1, encouraging companies to celebrate the surge of investments in the CGT manufacturing space — albeit with a few small caveats.

 

There comes a time when any industry faces an inflection point. Excitement over a new class of therapy builds; investments and acquisitions are pursued; service providers hustle to build up their capacity and expertise in the new arena; and biotech companies’ pipelines expand at seemingly alarming rates. At a certain point, however, that growth either levels out or tapers off.

I’m delighted to inform you — if you weren’t already aware — that we have not yet reached the leveling or the tapering off period in the CGT industry. This is especially true if we look at the sheer number of investments in manufacturing infrastructure made in 2021 — a trend that Spink expects will continue into 2022.

“I have seen no signs of these investments leveling off,” she qualified. “There’s still a lot of money flowing into CGT manufacturing from investors. In fact, I think we’re just at the cusp of the tech and tools gold rush that will fuel tremendous improvements in the maturity and efficiency of CGT manufacturing.”  

This is a striking departure from the industry’s earliest days, during which the small market size made common raw materials and tools (e.g., cytokines and low adhesion flasks) difficult, if not impossible to source without paying a premium for custom development. It wasn’t until 10 years ago the tides began to turn with the advent of positive clinical data and increased investor attention. However, while vendor interest followed suit, the industry accelerated much more quickly than the supporting manufacturing and technological infrastructure could be established.

This continues to be a familiar story today, given increasingly broad industry investment in CGT development and ongoing COVID-19 vaccine/therapeutic development. Long CDMO lead times have certainly been one of the most common impetuses for bringing CGT manufacturing in-house. But we also can’t overlook the growing appreciation for and acknowledgement that manufacturing is one of the biggest factors that can disrupt a development program. In turn, the most sophisticated investors have become more knowledgeable and accepting of the fact that a greater portion of funding needs to be allotted to manufacturing — and perhaps even in-house capacity — earlier in the development paradigm.

“It used to be the case that, 10 to 15 years ago, investors didn’t inquire after your manufacturing,” Spink explained. “They were most interested in your clinical protocol and proof of concept data. But not only are preclinical companies raising larger rounds today, high-profile CMC challenges hamstringing development have made investors more open to companies using funding to control their CMC destinies earlier.” 

Though there is a lot of investment and capacity expansion in the space as a whole, we can’t overlook one big wrinkle in this otherwise rosy outlook: supply chain shortages and delays have also been throwing companies and their timelines for a loop. (O, where art thou, single-use technology?) This raises the important question of whether these ongoing delays could dissuade investment or cause lasting harm to the explosive CGT sector as a whole.    

As you might expect, the answer is a bit more nuanced than cut-and-dried. On the one hand, Spink is optimistic that biotechs, outsourcing partners, and tech providers as a whole will continue to receive financial support for manufacturing advancements, despite the stymied supply chain. However, this doesn’t mean that supply chain constrictions won’t be a significant foe to individual companies on a case-by-case basis.

“A biotech typically raises money to get to a certain milestone,” Spink clarified. “But if a supply chain delay means that milestone will now take an extra year, you won’t necessarily have enough money to reach that inflection point in your development program. The severity of this situation will ultimately depend on the investors’ reactions and the individual company’s financial status and needs. So, from an individual company standpoint, these supply chain issues could be problematic to their growth. But I don’t see these supply chain issues causing a significant retraction in the industry, because they’re not rooted in systemic scientific, safety, or regulatory-related questions or issues.”

I particularly liked this quote from Spink because it accomplishes two important things. On the one hand, it showcases some of the nuances that CGT companies could face on the supply chain, manufacturing, and funding side of things. But on the other hand, subtly tucked into the quote is another important best practice for companies — and that’s to take care when selecting investors.

Though the CMC challenges in this industry have encouraged investors to become increasingly well-versed in the manufacturing realm, the level of sophistication can run the gamut. It behooves a company to make sure that potential manufacturing and supply chain risks are well-understood by investors so they will be willing to support what needs to be done if and when the going gets tough.  

 

Looking to add another resolution to your list? Click here to figure out what else you may be missing.

Further Reading:

• For more on investment trends and securing adequate funding for CGT manufacturing, check out this previous Cell & Gene Collaborative article featuring two executives from VC firm, Syncona.