Clustered regularly interspaced short palindromic repeat (CRISPR) therapies are one of the most potentially powerful and transformative technologies in human history. No CRISPR-based therapeutics have yet been indicated for the treatment of human diseases, but three leading companies are racing to bring CRISPR therapies to the clinic.
The three leading gene-editing companies looking at commercialising CRISPR-based therapeutics are CRISPR Therapeutics, Intellia Therapeutics, and Editas Medicine. Key statistics for each of these companies are highlighted in Figure 1.
Figure 1: Key Statistics for Leading CRISPR-Based Therapeutic Companies and Agents in Clinical Development.
CRISPR Therapeutics has the largest market cap of the three, at $10.9B, with a clinical development program that is more advanced than those of Intellia and Editas. CRISPR Therapeutics has already published promising data on the use of CRISPR in β-thalassemia and sickle cell disease in the New England Journal of Medicine. The company has also initiated early stage clinical trials for its immuno-oncology program, which is based on the development of allogeneic chimeric antigen receptor T (CAR-T) cells targeting well-characterised targets in haematological malignancies, such as CD19+ and B cell maturation agent. The development of allogeneic CAR-T cells may circumvent issues with manufacturing and the costs associated with autologous CAR-T cells, which have already demonstrated impressive durable responses in patients with haematological malignancies. Furthermore, CRISPR Therapeutics was co-founded by Dr Emmanuelle Charpentier, joint winner of the Nobel Prize in Chemistry 2020 for CRISPR-Cas9, whose expertise will further support the successful direction of the company’s R&D programs.
Likewise, Dr Jennifer A. Doudna, the other joint winner of the Nobel Prize in Chemistry 2020, co-founded Intellia. Intellia’s approaches to clinical development can be separated into an in vivo and ex vivo approach. In vivo describes the introduction of the CRISPR technology into the patient directly via an intravenous route of administration, while ex vivo describes the removal of stem cells for gene editing followed by the re-introduction of these repaired cells into the patient. Intellia’s NTLA-2001 uses an in vivo approach to tackle a rare hereditary disorder, transthyretin amyloidosis, for which only chronic treatment options are currently available. Similar to CRISPR Therapeutics, Intellia is also considering sickle cell disease as a target indication, but the company is slightly behind CRISPR in terms of clinical development, potentially indicating a future second to market disadvantage. Intellia has established high profile collaborations with Regeneron and Novartis, which will boost its ability to navigate a successful route to market and provide the company with the necessary infrastructure and experience in drug development and commercialisation.
Editas Medicine has the smallest market cap of the three, and currently only has a single agent in clinical development: EDIT-101. Unlike the other companies, Editas is focusing on ocular diseases, specifically Leber Congenital Amaurosis, indicating the potential to monopolise this space. Dr Fen Zhang, Editas’ co-founder, is an expert in optogenetics and a pioneer in the application for CRISPR-Cas9 system in human cells, both of which represent key strengths for achieving Editas’ vision.
Each company has overlapping and distinct target indications, and all three are targeting haematological disorders and developing an immuno-oncology program, either in the clinical or pre-clinical stages. This suggests potential future competition, but also indicates that each company has room to carve out and monopolise distinct markets. CRISPR Therapeutics has a head start in terms of its clinical development and raising capital, and represents a safe choice for investors as a result. However, each of these companies produce little to no current revenue, and current expectations are contingent on favourable results from upcoming clinical trials, which are still in the early stages of development.
Despite this, the potential for CRISPR technology is huge. Blockbuster oncology drugs have the potential to prolong life by months to years, while CRISPR-based therapeutics represent a potential cure and could therefore prolong life by decades. Future challenges in this space include how to develop a fair pricing strategy, the logistics of offering broad access to the neediest populations in underserved markets (such as sickle cell patients in Africa), and potential unfamiliar adverse events associated with this novel modality of therapy. However, the potential upside for patients and long-term investors is huge. While CRISPR-based therapies are currently still in development, they will inevitably transform the lives of patients and the shape of the industry if they are brought to market.