By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1
It’s no secret that the cell and gene therapy sector suffered some setbacks as a result of Covid-19. But with 2022 in full swing, here are four things to keep your eyes on that will be important this year in the world of cell and gene therapy.
The Year of RNA Therapeutics
Thanks to the messenger RNA (mRNA) Covid-19 vaccines, RNA research is mainstream news. Unlike conventional cell engineering, which uses DNA to modify cells irreversibly, RNA cell therapies tend to be safer because they have predictable lives within the body, and they extend beyond oncology from autoimmune to respiratory disorders. To date, several new candidates will enter the clinic for the first time in 2022, as there are hundreds of RNA therapies in the pipeline. The most common modalities in development (i.e. preclinical through preregistration) are RNA interference (RNAi), antisense oglinucliotides, and mRNA. Companies like Cartesian Therapeutics focus on development and manufacturing of RNA therapies that treat a number of diseases. On Cell & Gene: The Podcast, two of my guests, Cartesian’s CEO Dr. Murat Kalayoglu and CSO Dr. Michael Singer explained the cell and gene therapy sector's advancements in RNA cell therapy and the why behind the company’s decision to build its own wholly-owned GMP manufacturing facility and why RNA has advantages over other cell therapies respectively. Solving the RNA delivery problem will remain a challenge in 2022, but RNA will only gain more and more traction as the year goes on.
Good News from OTAT Regarding Rare Disease Trials
During a webinar held last month, Office of Tissues and Advanced Therapies (OTAT) Director Wilson Bryan explained that the organization plans to institute new processes to expedite its reviews of new cell and gene therapies, because it has learned that clinical trials for gene therapy products do not have to enroll huge numbers of patients. Bryan stated that many recently approved gene therapies “are life-savings products and they all got approved based on a single arm study because they had large effect sizes. That is one of the things that have been proven, if there is a large effect size, the clinical trials do not have to be big. We can do clinical trials in small populations.” Time will tell if OTAT indeed expedites trial reviews, but the near-term looks promising.
Get Manufacturing Right
Start early. I can’t emphasize this enough. I wrote an article for Life Science Leader’s Outlook issue, and in it, I interviewed André Choulika, CEO at Cellectis, and Michael Mehler, director, global site operations, at Immatics. Choulika provided perspectives for gene therapy, and Mehler provided me with the same for cell therapy. When we discussed manufacturing specifically, Choulika stated, “When you are addressing rare genetic disorders or relapsed/unresponsive cancers, there will be no one “quick fix” that can be applied to a multitude of disorders and patient sub-populations. To consistently reproduce high-quality batches, companies will need to have specific requirements of the modified cells and the key starting materials needed for gene editing.
We believe that bringing manufacturing in-house could contribute to eliminating some of the risks for inconsistencies among treatments, ensuring that lead times are met so patients are never waiting for their treatments, and improving adaptability, as each disease targeted by advanced therapeutics may require great innovation at the level of our manufacturing capabilities. Importantly, having our manufacturing in-house means that we can rapidly “version” promising therapeutic candidates as we monitor clinical responses, leading to the best possible product at registrational filing.
As Mehler explained, “flexibility and adaptability are critical when transitioning a cell therapy from research to early clinical manufacturing. Many companies will be faced with the decision to either build their own manufacturing facility or utilize a centralized approach. Also, implementing a GMP mindset from the earliest point of the project will help ease the transition from research to early clinical and commercial manufacturing. However, to achieve significant cost savings, the sector must move from the manual ad-hoc hospital labs, where the early therapies have been delivered, to scaled-up and far more automated processes that are faster and more reliable. A key to this new approach will be dedicated facilities and extensive process automation that removes bottlenecks.”
For a whole host of reasons, not all biotechs will build their own in-house manufacturing facility. But as Mehler stated, adopting and implementing the GMP mindset is critical to commercializing a therapy. So, too, is researching and partnering early, as in pre-clinical early, with manufacturers to reach the commercialization goal.
Talent Hiring and Retention
The cell and gene sector has suffered some serious talent poaching in years past. Stiff competition for top talent remains even as the field continues to explode with opportunities. Yet there are only so many qualified candidates to fill the sector’s various roles. I’ve talked to countless biotech leaders who state that keeping talented people on their teams has been difficult, especially in manufacturing. Indeed, the increased demand for skilled personnel in the CGT industry has become a significant obstacle for cell and gene therapy companies, with manufacturing reported as the skill area of greatest concern. Salary and perks will always matter, but the company’s mission, vision, as well as a genuine commitment to diversity and inclusion had better stand out. Covid-19 has taught us many things, and the company you keep in your professional life is one of them.