Pierre Socha
Something truly extraordinary happenedexactly 10 years ago. Emily had been diagnosed with acute lymphoblastic leukaemia, had relapsed twice and as thecancerbecame resistant to all treatments, she was given only a few more weeks to live. She was five years old. As a last resort, her parents enrolled her in a clinical trial at Philadelphia’s Children Hospital what would make her the first paediatric patient in the world to receive CAR T-cell therapy.It was her last shot. It was an experimental therapy.
The T-cell therapy worked, and Emily remains cancer-free to this day.
Cell and gene therapies represent a phenomenal new treatment modality for clinicians and patients.
Advances in cell and gene therapy (CGT) offer the potential to transform medicine, as they offer the promise of treating, and, in some cases, curing diseases that until recently were considered intractable. The breadth of medical applications spans from rare and devastating diseases like ALS that have few, or no, treatment options, to more prevalent conditions like heart failure, type-1 diabetes, Parkinson’s, Alzheimer’s, and many cancers.
However, they present a unique delivery challenge in that each patient requires not only a personalised treatment, but also a unique manufacturing process that begins with each individual patient’s cells. The manufacturing and logistics of getting the treatment to patients at scale, and at affordable prices, creates a manufacturing bottleneck that many of the big players have failed to address.
This is where new approaches have begun to fill the gap, developing new technologies that can decrease the bottleneck and turn CGT into a viable option for the future of medicine. For example, the London and New Jersey-based start-up Ori Biotech has developed a proprietary, flexible manufacturing programme that automates cell and gene manufacturing to increase throughput, improve quality and decrease costs to enable patient access to this new generation of life saving treatments. Its technology has been recognised by investors in the space, as Ori recently raised over $100 million in Series B funding to help launch its platform.
Ori Biotech’s rapid ascent didn’t happen in a vacuum. The synthetic biology industry as a whole is thriving and 2021 was a year of records and breakthroughs. CRISPR gene-editing technology was deployed in vivo in human patients for the first time with extremely encouraging interim Phase 1 results. CAR-T treatments Yescarta (Gilead) and Breyanzi (Bristol-Myers Squibb) have also significantly outperformed second line standard of care for large B-cell lymphoma, the most common type of non-Hodgkin’s lymphoma.Thisleads us to believe that CAR-Ts and CGTs will rapidly become first-line therapies in immuno-oncology. Studies are also suggesting that responses from allogene-edited CAR-T cells are in line with that of autologous CAR-Ts, which was long suspected but remained to be demonstrated.
Another paradigm being challenged is that one cannot reverse damage that has already occurred. The conventional wisdom is that with degenerative conditions the journey is a one-way street and therapies can only prevent further damage. There are now several notable examples of howthat is not true. Possibly the most exciting research results relate to a type-1 diabetes patient who lived with the condition for 40 years and saw “cure-like results” after 90 days of receiving a one-off treatment of stem cells derived B-cells. This also shows the potential of cell and gene therapies for complex, polygenic diseases – again, a space that was thought to be out of reach. We can now replace the lost cells, restore function and reverse at least the symptoms of degenerative conditions.
Not surprisingly, the regenerative medicine sector had a record-breaking year with $23.1B raised, of which gene therapy and cell immuno-oncology took the lion’s share, each attracting north of $10B in new funding, largely driven by venture capital. A record 26 companies IPO-ed last year, nearly double the previous record of 14.
2021was also the second-best year on record for the number of new products approved by regulators (6), and the best year for cell-based immune-oncology with three new CAR-T therapies approved across US, Europe and China. Itwas also an important year for breakthrough therapy and RMAT designation aimed at expediting patient access to regenerative medicine. Seven programmes were awarded the designation, pushing the total to 68 since 2017. And we’re on the cusp of an even larger rollout, with more than 2,600 trials ongoing worldwide, equally split between industry-sponsored research and academic sponsored trials.More than 9,900 cell therapy trials are currently recruiting.
It is no longer a question of if distributed manufacturing of CGT will emerge, but when and how prevalent it will become. This revolution in accessibility of new treatment modalities is also triggering new business models and we believe that the value chain will look nothing like today. For instance, leading academic centres such as MD Anderson or University College London, are rapidly repositioning downstream.
It is easy to forget that most approved cell and gene therapies originated from university-affiliated research centres before being licensed to big pharma. By using solutions such as Ori they retain control of manufacturing and delivery, and morph into therapy developers cum providers, potentially leaving big pharmaceuticalsand centralised contract manufacturers out of the equation – unless they, in turn, adapt.
We expect the industry to look profoundly different in years to come, withnew actors playing a central role in making life changing treatments available to millions of patients worldwide.
Thank you, Emily.
