The Nobel Prize in Chemistry was awarded to two scientists, Emmanuelle Charpentier and Jennifer Doudna, for “the development of a method for genome editing” on Oct. 7. Their discovery, CRISPR-Cas9, is nature’s scissors. It’s a protein which can locate and then precisely cut DNA, generating new strands in its stead. If it sounds insane, it’s because it is.
The buffer time between a discovery and the awarding of a Nobel Prize is almost 30 years. However, it has been less than a decade since Doudna & Charpentier published their findings. This underscores its gross importance. In the next ten years, this Wild West might change the entire pharmaceutical industry. It also turns out there’s a way to bet on its future.
While it probably didn’t get a lot of love in your high school biology class, CRISPR is on the cutting edge of biology. CRISPR proteins (like Cas9 and CPF1) are the backbone of new diagnostics which can target specific parts of genetic code and change them. CRISPR-Cas9 is essentially version one and other CRISPRs are iterations discovered along the way. These systems have already been used to modify genes in living cells. In the years ahead, these systems will move from the lab to living organisms, potentially used to correct mutations in our genome — genetic disorders, cancer and other illnesses.
There are dozens of CRISPR stocks on markets today. We’re still in the early stages, with CRISPR currently used to create the treatments (ex-vivo, outside of the body). However, in the not-so-distant future, CRISPR might be the treatment (in-vivo, inside the body). Many CRISPR companies are starting with therapeutics for blood disorders like beta-thalassemia or sickle cell disease. However, there’s plenty more targets on the horizon.
Here’s a short-list of some of the public companies trying to bring this potentially world-changing technology to the public:
Editas Medicine ($EDIT)
Editas Medicine was founded by a group of CRISPR scientists in 2016. The most notable founder is Feng Zhang, who patented CRISPR-Cas9 after proving it worked in Mammalian cells. Zhang did not invent or discover CRISPR-Cas9 and did not receive credit from the Nobel committee. However, his patent filing made him & his associated partners at MIT & Harvard the first-to-the-post – setting up an extensive patent battle in the courts. This court decision could fundamentally alter the existing intellectual property landscape for all CRISPR companies and inventors. However, it was under Editas that Zhang and Doudna hoped — and failed — to create a single company to unify the scientists pivotal to its invention.
Editas’ lead indications are still in development and haven’t made it to clinical trials. However, the company is simultaneously creating in-vivo and ex-vivo treatments unlike their peers. It is possible their in-vivo treatment for several ocular disorders will be going to clinicals close in proximity to their ex-vivo treatments for blood disorders. Editas treatments include partnerships with companies such as AskBio, Bristol Myers and BlueRock Therapeutics in the future in order to target neurological and several cancer disorders.
Editas has also been quick to hone in on new CRISPR systems and proteins to advance their therapeutic backbone.
CRISPR Therapeutics ($CRSP)
CRISPR Therapeutics is a Swiss biopharma company founded by Charpentier in 2013. They went public in 2016. $CRSP’s current portfolio orientation focuses on blood disorders and cancer (immuno-oncology). The company has major strategic partnerships with Vertex, ViaCyte and Bayer.
Their first drug, CTX001, is for patients suffering from sickle cell disease or beta thalassemia. These two genetic blood disorders cause the blood cells to be shaped differently, which causes side effects, pain and even death. CTX001 is a treatment aimed to edit patients’ own blood stem cells by collecting them, editing them with CRISPR and then reinfusing them. CTX 001 is currently in a Phase 1/2 trial and being developed and commercialized in part with Vertex Pharmaceuticals ($VRTX).
Their cancer drug portfolio focuses on allogeneic CAR-T cell therapies. Allogeneic refers to the fact that the T Cells are sourced from a healthy donor and then manufactured to create hundreds of doses. They are currently conducting three clinical trials with the intent of creating a more potent and consistent treatment option for people with hematologic or solid tumors.
Assuming $CRSP finds success with these solutions, they also have plenty of additional indications on the horizon. This includes an ex-vivo treatment for Type I diabetes and four in-vivo (in body) treatments for genetic disorders.
Intellia Therapeutics ($NTLA)
Intellia Therapeutics was founded in 2014 by Doudna. $NTLA is also working on an ex-vivo treatment for sickle cell disease in collaboration with Novartis. OTQ923/HIX763 is currently in a Phase 1/2 trial.
However, Intellia has an edge over its collaborators in the in-vivo game. Intellia received permission to initiate a Phase 1 trial on Oct. 19 for a single-course gene therapy which could stop and reverse a rare inherited condition called transthyretin amyloidosis (ATTR). ATTR is caused by a mutation which results in the liver producing a protein called transthyretin (TTR). This protein builds up in the body and reduces life expectancy. There are at least 250,000 ATTR patients worldwide. The therapy, NTLA-2001, is being produced in collaboration with Regeneron. The company will begin dosing in the trial before the end of the year.
In the future, the company plans to begin trials for more genetic diseases (such as Hereditary Angioedema and Hemophilia A/B). They also plan to start an immuno-oncology program to target leukemia and solid tumors.
Beam Therapeutics ($BEAM)
Beam Therapeutics, which was founded in 2017 and went public in 2020, is the latest prominent CRISPR company to come to market. Beam is still purely building out their pipeline. They are likely still a year or two from starting clinical trials.
Like associated firms, their pipeline focuses on blood disorders, cancer and ocular targets. However, Beam’s long-term novelty might be in targeting liver diseases in-vivo with CRISPR.
Beam licenses many of the CRISPR patents from the IP holders such as the Broad Institute. Unlike the other three companies on this list, Beam was not founded by CRISPR’s inventors or core discoverers. Beam is an outlier in the existing ecosystem. They also don’t look to have any collaborators or co-developers for their drugs at this time.
There is no ideal timeline for investments like these. However, in the next ten years, it’s possible that an investment in any of these companies could kill the benchmark.
Header image: Britannica