CRISPR Therapeutics creates gene-based medicines

Gene-Editing Genius

CRISPR (clustered regularly interspaced short palindromic repeats) has been making news about research and investment. Scientists learned that CRISPR, a naturally occurring gene-editing function of bacteria, has potential for treating genetic diseases. Now a number of companies are using gene-editing to try to cure illnesses caused by errors on a single gene. They include sickle cell disease, hemophilia and cystic fibrosis.

Swiss-based CRISPR Therapeutics, a biopharmaceutical company attempting to create transformative gene-based medicines for serious diseases, “has produced results that could not only make it a winner in single-gene disorders, but position it to tackle much more complex -- and profitable -- diseases in the years ahead,” according to Jason Hawthorne of The Motley Fool (https://www.fool.com/investing/2020/12/15/where-will-crispr-therapeutics-be-in-10-years/). CRISPR Therapeutics, a gene-editing company, attempts to develop gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a gene-editing technology that allows for precise, directed changes to genomic DNA. The company has a wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in London, United Kingdom.

CRISPR’s CTX001 is a potential drug to treat sickle cell disease and beta-thalassemia, disorders that affect the oxygen-carrying cells in the blood. After harvesting a patient's own cells from his or her own bone marrow, medical professionals use CTX001 to edit the gene responsible for red blood cell production and infuse the cells back into the body.  In 2015, CRISPR entered into a partnership with Vertex Pharmaceuticals to develop a number of treatments using this technology, receiving cash, equity and future royalties, while Vertex obtained the rights to market the treatments to be developed.

Thus far, the partnership “has produced outstanding results,” according to Hawthorne. At last year’s American Society of Hematology conference, the two companies reported on 10 patients treated with CTX001. All had been free of the problems associated with the diseases – “the need for transfusions in the case of beta-thalassemia, and pain crises for sickle cell disease,” Hawthorne explained. In 2021 there will be data on another 10 patients. Although the science has caused some excitement, the market is relatively small: approximately 300,000 people per year are born with sickle cell disease, and 60,000 with beta-thalassemia.

CRISPR and Vertex announced in December 2020 that The New England Journal of Medicine published an independently peer-reviewed article called “CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β Thalassemia.” The article includes detailed information on the first patient with transfusion-dependent beta thalassemia (TDT) enrolled in CLIMB-Thal-111 and the first patient with severe sickle cell disease (SCD) enrolled in CLIMB-SCD-121, at 18 and 15 months of follow-up, respectively, according to the companies .

Enrollment and dosing are ongoing in the clinical trials for CTX001. More than 20 patients have been dosed with CTX001 across both trials to date. Completion of enrollment in both trials is expected in 2021. Additionally, the first patient with TDT treated in CLIMB-Thal-111 recently completed two years of follow-up and has enrolled in the long-term follow-up trial, CTX001-131.

CRISPR Therapeutics is also enrolling participants in studies to test CAR-T therapies that utilize gene-editing to make immune systems able to recognize and attack specific kinds of cancer cells. In one example, CTX110 has demonstrated dose-dependent reduction in tumor sizes. Patients have had responses that last more than 3 months with positive top-line results from its ongoing Phase 1 CARBON trial assessing the safety and efficacy of several dose levels of CTX110. The company expects to report additional data from this trial in 2021.

CRISPR Therapeutics’ Phase 1 clinical trial assessing the safety and efficacy of several dose levels of CTX120, its wholly-owned allogeneic CAR-T investigational therapy targeting B-cell maturation antigen for the treatment of relapsed or refractory multiple myeloma, is ongoing. The Company expects to report top-line data from this trial in 2021.

CRISPR Therapeutics’ two independent Phase 1 clinical trials assessing the safety and efficacy of several dose levels of CTX130, its wholly-owned allogeneic CAR-T investigational therapy targeting CD70, for the treatment of both solid tumors and certain hematologic malignancies, are ongoing. The Company expects to report top-line data from these trials in 2021.

In addition, CRISPR Therapeutics has partnered with ViaCyte, a private company, to develop a treatment for Type 1 diabetes. The partners, who hope that gene-editing can protect ViaCyte's replacement pancreatic stem cells from the body's immune system, expect results from a phase 1/2 clinical trial of the treatment to be released in 2021.

CRISPR has established plans for research collaborations with Vertex on Duchenne muscular dystrophy, cystic fibrosis and other diseases. They are also exploring the idea of turning gene expression on or off. Researchers have wanted to use CRISPR to temporarily turn off the cell receptors to which a particular virus binds or to silence the genes responsible for high cholesterol production since CRISPR technology was discovered.

Now scientists are writing CRISPR "programs" to take actions on multiple genes at the same time. They can turn stem cells into neurons that make up the central nervous system, which could have implications for creating healthy cells to replace problem cells in people with Alzheimer's or ALS. Newly developed mRNA technology could be combined with CRISPR to change the way clinicians treat diseases.  

To advance its programs, CRISPR Therapeutics is building a new cell therapy manufacturing facility in Framingham, Massachusetts, as reported in Area Development (https://www.areadevelopment.com/newsItems/6-29-2020/crispr-therapeutics-framingham-massachusetts.shtml). According to Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics, “We look forward to building a state-of-the-art manufacturing facility, which will accelerate our programs and allow us to scale for commercial supply. We look forward to bringing our facility online rapidly. In addition to building out this internal manufacturing capacity, we will continue to work closely with our key manufacturing partners globally."

The company expects to hire about 100 full-time employees to work at the new facility, which will provide GMP manufacturing according to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) regulations and guidelines to support clinical supply and commercial product upon potential regulatory approval. The facility will help to produce the company’s therapeutics for hemoglobinopathies, oncology, regenerative medicine and rare diseases.