First Commercializations of Systemic Therapies as Backstop for CRISPR Investors

There is widespread consternation about the disconnect between recent clinical breakthroughs and the performance of CRISPR-related stocks.  I am highly confident that this will correct by mid-2027 at the latest when NTLA-2002 should become the first systemically administered CRISPR therapeutic to be commercialized.  It will demonstrate the high demand by patients and physicians for this revolution in medicine and commercial viability.

 

KOL enthusiasm

In 2017 at the iconic Paris ATTR Amyloidosis Meeting where Alnylam unveiled the biggest clinical breakthrough in RNAi, the eyes of key opinion leader Dr Julian Gillmore (UCL) lit up when going another step forward into the future, talking about the promise of one-dose CRISPR genome editing for the disease.  This was notable since he is essentially involved in all the key clinical programs in ATTR amyloidosis irrespective of modality, including TTR stabilizers and RNAi silencing.    

I noticed similar genuine enthusiasm at last year’s ACAAI meeting from hereditary angioedema (HAE) KOL Dr Banerji (Harvard) regarding NTLA-2002 after experiencing NTLA-2002 in her own patients.  Another seeing-is-believing moment was recently voiced by Prof Patel of UCL, an investigator in the VERVE-102 PCSK9 base editing trial:

 “This is reality; it’s not science fiction. We’re actually doing it. I’ve had patients of mine in the trial receive this one-and-done treatment, and it’s going to change the face of cholesterol management going forward.”

I have yet to see a single trial investigator or KOL who has deeply thought about the implications of one-time therapies in clinical development for the above diseases and discarded them as freakish or irresponsible as people invested in competing therapies like to do.

 

Patient enthusiasm

The same holds true for patients, that is the people whose voice should have the most weight in the discussion on the risk/benefits and ethics of genome editing. 

In a patient preference survey commissioned by Verve Therapeutics, one third already stated that a one-time genome editing treatment would be more appealing to them than daily pills or injectible drugs.  I expect this number to further increase as VERVE-102 makes its way through the clinic and first patients get treated commercially (word of mouth will be tremendous). 

Similarly, HAE patients confronted with NTLA-2002 look to it with hopes of allowing them to forget about their disease and not having to worry about getting repeat-administered drugs covered by insurance in perpetuity.  Accordingly, enrolment in the phase 3 HAELO trial is extraordinarily swift as patients are lining up for NTLA-2002 according to Intellia Therapeutics.

 

But what about payors?

Besides public acceptance of CRISPR genome editing, cost for these one-time therapies is often brought up as an argument against CRISPR.  Surely, they will be prohibitively expensive.  Why for example would anybody pay $2M for ATTR-drug NTLA-2001 when you can get the RNAi alternative for just $500k annually.  Sure, some people will rent the child booster from the rental car company at $20 a day, instead of buying one from a Walmart around the corner for the same price.

If anything, it is CRISPR Therapeutics that have the pricing power in most settings, including for mass markets like cholesterol lowering (--> VERVE-102).  The vastly superior outcomes in terms of morbidity and mortality projected for life-long LDL cholesterol lowering, especially when initiated early on, should more than compensate the $100k or so price tag I expect it to carry initially.  There is also a noticeable shift in the new US administration towards preventing rather than treating disease.  No better modality than genome editing for that as long as the delivery and gene target is safe.

In the words of Stanford’s genome editing scientist Matt Porteus at the 2025 Copenhagen CRISPR conference, the US insurance system is 'f*cked up', but with many eyes nowadays on how the insurance and PBM industry deals with access (see United Health) and the aforementioned inherent pricing power of (non-viral) genome editing, payors will not meaningfully stand in the way of these therapies.  Similarly, the new modality should run into open doors with Medicare and Medicaid who are most vested in the long-term outcomes of covered lives.

 

Momentum building

With NTLA-2002 likely wrapping up enrolment in Q3, we should see the first commercialization of the promising crop of systemically administered CRISPR drugs in mid-2027.  NTLA-2001 for ATTR-PN, BEAM-302 for AATD, VERVE-102 for heFH and high-risk ASCVD, and finally NTLA-2001 for ATTR-CM should follow in 2028/9.  When the sales numbers finally come in, even the longest naysaying hold-outs will have to admit defeat and CRISPR stocks should rebound.  This could be greatly catalyzed if that happens in a lower interest rate environment (Powell will be replaced in 2026).

But even before that, the steady stream of recent clinical successes (VERVE-102, urea cycle N=1 base editing, NTLA-2001 ATTR-PN data at PNS, BEAM-302 initial data) have led to increased broader interest in CRISPR with large social and traditional media accounts talking about the technology once again.  If industry validation is what you are looking for, with Regeneron and Eli Lilly having to make their respective NTLA-2001 and VERVE-102 opt-in decisions soon and share prices dangerously low, we could see ‘strategics’ stepping in.  The dam could break any day, in a positive way, for long-suffering investors.