Biotech Roundtable: Who will bring the next CRISPR drug to market?

CRISPR gene editing technology has been heralded as a revolutionary breakthrough in drug development, enabling scientists to potentially cure genetic diseases by modifying the genes that cause them.

The technology grabbed headlines last fall when the FDA approved the first CRISPR product for the US market, Casgevy, a gene therapy for the treatment of sickle cell disease developed by Vertex Pharmaceuticals (VRTX) and CRISPR Therapeutics (NASDAQ:CRSP). Both stocks saw strong run-ups ahead of regulatory approvals in the US and EU, further stoking investor interest in the technology.

Despite the fanfare, questions remain about this emerging field of drug development and its future.

Last week, Seeking Alpha explored whether CRISPR was overhyped and which companies looked particularly attractive in the space. This week, we look at:

• Which company is most likely to bring the next CRISPR product to market?
• Are there similar technologies that investors should be looking at as well?

To answer these questions, we reached out to Seeking Alpha biotech analysts Stephen Ayers, Edmund Ingham and Terry Chrisomalis to see what they had had to say about this intriguing technology and the companies that are working in it.

Which company do you think will be the next to bring a CRISPR product to market?

Stephen Ayers: I believe Intellia Therapeutics (NTLA), alongside Regeneron Pharmaceuticals (REGN), is leading with NTLA-2001 for ATTR amyloidosis with cardiomyopathy. This rare, severe disease could see a breakthrough with NTLA-2001, heralded by the FDA's recent agreement for a pivotal study. This therapy, leveraging CRISPR for in vivo gene editing, could offer a one-off treatment, positioning it as a potential first for this condition.

Edmund Ingham: It may be some time before a second CRISPR-based drug is approved, which is part of the reason why the market isn’t buying CRISPR companies’ shares as aggressively as it might be, given how effective the approach can be. There are many biotech companies developing gene therapies using CRISPR -- Editas Medicine (EDIT), Caribou Biosciences (CRBU), Intellia Therapeutics (NTLA), Beam Therapeutics (BEAM), and, of course, CRISPR Therapeutics (CRSP) and its partner, Vertex Pharmaceuticals (VRTX). Few programs have progressed into pivotal studies as yet, however, so I think we may be looking at a 3-5 year timeline before we see another approval, which could come in the cell therapy space, targeting oncology, or in sickle cell disease or thalassemia, the two indications in which CRISPR Therapeutics / Vertex’s Casgevy is approved.

Terry Chrisomalis: I believe that the next company to bring a CRISPR drug to market will be Editas Medicine (EDIT) with reni-cel, also known as EDIT-301. The reason being is because of the FDA Accelerated Approval pathway it was afforded. Editas is currently testing the use of this CRISPR candidate in an ongoing phase1/2/3 study for the treatment of patients with severe sickle cell disease, or SCD. It is on track to report clinical data at two different times this year, mid-2024 and by year-end 2024. The basis for my belief that this may be the next CRISPR drug to come to market would be because the FDA came into alignment with Editas that the phase 1/2/3 study will be allowed to support a Biologics License Application filing for reni-cel for this severe SCD patient population.

Are there similar technologies that investors should be looking at instead of or in addition to CRISPR?

Stephen Ayers: CRISPR stands out in genome editing. Yet, alternatives like zinc finger nucleases, or ZFNs, and TALENs exist, each with distinct pros and cons. ZFNs, employed by entities such as Sangamo Therapeutics (SGMO), boast a longer history in clinical trials. Their track record is solid, though precision may lag. Meanwhile, RNA editing technologies offer a novel approach. They modify RNA, bypassing DNA alterations. This method promises a reversible, possibly safer avenue for gene regulation.

Edmund Ingham: As important as the CRISPR gene editing mechanism is, there are arguably other forms of gene editing that may work as well as CRISPR in certain diseases. Antisense oligonucleotides, for example, RNA-interference, base editing, messenger-RNA, CAR-T cell therapy for hematological and solid tumor cancers. CRISPR scores highly in terms of versatility, limiting “off target” toxicity, and allowing genes to self-repair naturally, for example, but as drug delivery technology improves, we may find that the space opens up and CRISPR becomes only one of several different approaches that may effectively treat genetic diseases.

Arguably, the most important developments are being made within drug delivery -- if you can find a way to get your RNA payload to the desired cell, without it being broken up on its journey, for example, then you may be able to treat many different types of disease using this approach, as opposed to using CRISPR technology.

Terry Chrisomalis: CRISPR is in a class of its own, but there might be a type of technology close to it which might be gene therapy. The intended goal of this technology is to provide patients with the proper gene to avoid disease altogether. Having said that, this class of medicine is highly ideal when the target of choice is straightforward and the genetic material can properly fit into a vector for delivery. The downside is that there is a limit on the number of genes that can be packaged into a vector to deliver the proper gene so that the correct protein can be made. This is where CRISPR would shine and thus why it is a technology to keep an eye on.

Still, gene therapy is closely similar in terms of being able to get the correct copy of a gene inserted to make the right functional protein. There are several gene therapy developers that have done well making advancements in using gene therapy to treat a variety of disorders. For instance, Novartis (NVS) has already received approval for Zolgensma to treat patients with spinal muscular atrophy. Biogen (BIIB) has already received FDA approval for Spinraza to treat this very same patient population. Bottom-line, I believe that gene therapy is a similar type of technology that investors should be watching closely like CRISPR.