Gene therapy is one of the hottest, most eye-opening areas in the life sciences right now. Its earliest victories happened more than 30 years ago, but, since then, gene therapy has struggled to build momentum — until now.
Ashanthi DeSilva owes her life to that early success.
She was born with adenosine deaminase (ADA) deficiency, a rare and fatal genetic disorder that at the time was called the “bubble boy” disease for a young boy who suffered from it and ultimately died from it in 1984. In 1990, four year-old DeSilva became the first patient to have a gene inserted into her cells. It saved her life. DeSilva now works to empower rare disease patient communities.
Since the DeSilva breakthrough in 1990, the gene therapy quest has faced many setbacks, which at times halted advances. The popularity of the technique has recently picked up again, with advances using adeno-associated virus (AAV) vectors and CRISPR technology.
CipherBio PRO Insights
CipherBio PRO looks at gene therapy companies that received funding in 2019, 2020 and 2021 Q1. CipherBio data shows 90 companies, 280+ investors, 200+ indications, 300+ scientific approaches and over $20B in invested capital. Additionally, these companies are separated by respective clinical phases (updated quarterly, Q1 2021).
With just over 70 of these companies still in the preclinical stage, the next wave of gene therapy treatments is being discovered in hopes of advancing through clinical trials and toward approval, the closest being two companies in phase 3 trials.
As expected, the top two indication groups were genetic and rare diseases as gene therapy allows the companies to “fix” the disease causing gene. Next up, following these indications: neurological disorders, cancers, metabolic diseases and eye diseases, all of which have recently gained traction in the gene therapy field as they target a greater patient population.
For eye diseases especially, gene therapy as a treatment is rapidly growing in popularity with 13 companies in clinical trials and $964M in investments. Recent research has shown the eye to be an attractive target for gene therapy because the therapeutic can be delivered locally (to the site of the disease), and the eye is an immune-privileged organ, meaning the therapeutic will not produce an inflammatory immune response.
*Image figures exclude IPO and Acquisitions for Gene Therapy
The biggest deal in the gene therapy ophthalmology field goes to Gyroscope Therapeutics, which filed for a $100M IPO in April 2021, less than a month after raising a $148M series C led by Forbion. Gyroscope is in a phase 2 trial for its lead candidate for patients with age-related macular degeneration who secondarily develop geographic atrophy.
The second biggest ophthalmology investment belonged to Cambridge, Massachusetts-based Generation Bio, which went public in June 2020 with a $230M IPO just six months after raising a $110M series C led by T. Rowe Price. Generation Bio’s work is in preclinical development in two disease areas, liver and retinal. It has eye disease product candidates for Leber congenital amaurosis, Stargardt macular degeneration and wet macular degeneration.
While gene therapy rapidly expands across indication fields with new advances for arenas like ophthalmology and metabolic disorders, are these companies’ scientific approaches advancing, too?
CRISPR has become a hot topic in the life science community, with the potential for the gene editing technique to revolutionize the development of gene therapies. Yet with this advancement in the field, only about 10% of the 87 companies use CRISPR technology, all in preclinical trials except for two, Caribou Biosciences and Graphite Bio. Caribou Biosciences is conducting a phase 1 trial for relapsed/refractory B cell non-Hodgkin’s lymphoma, and Graphite Bio is beginning a phase 1/2 trial for sickle cell disease.
Comparatively, nearly half of the companies use adeno-associated virus (AAV) vectors. With two FDA approved AAV-mediated gene therapies on the market and decades of research behind the method, AAV vectors are non-pathogenic and safely altered to not cause DNA damage. Spark Therapeutics developed Luxturna for rare inherited retinal dystrophy, and in 2017 it became the first FDA approved AAV-mediated gene therapy. Novartis in 2019 developed the second AAV therapy to be FDA approved — Zolgensma for spinal muscular atrophy.
Despite this popularity of AAV vectors, there are limitations, many to do with the AAV manufacturing that includes a low yield, time intensive and difficult process. To help combat these limitations came the emergence of manufacturing companies like Resilience, a California-based company that had the biggest investment round with an $800M Series B led by ARCH Venture Partners and 8VC. Ten of the companies are these manufacturers that recently have been known to partner or be acquired by gene therapy companies as seen in Charles River Laboratories $875M acquisition of Cognate Biosciences, a CDMO partner for cell and gene therapy products.
So, despite its limitations, AAV continues to dominate the field both in numbers and investments.
With $1.7 billion in investment rounds already raised in 2021, gene therapy is on the rise, and the technique extending to new disease realms beyond genetic disorders.
A limited number of gene therapy treatments are on the market worldwide, with only a few having received FDA approval. However, the FDA predicted that by 2025 it will receive an astonishing 200 investigational new drug applications per year and approve 10 to 20 cell and gene therapy products per year.
This is hope for a lot of patients — and it all started with four-year-old Ashanthi DeSilva.