2nd Patient with Chronic Granulomatous Disease Successfully Treated with Prime Editing

Prime editing researchers are so excited about the technology that sponsor Prime Medicine is unable to control the newsflow on their CGD trial.  As happened 3 weeks ago at the ASGCT where news of a first patient successfully treated with PM359 leaked, Prime Medicine co-founder Dr. David Liu just dropped (23:00min mark) that a second subject has been treated…with even greater efficacy.

 

90% gene correction efficacy

As was detailed in a subsequent press release by Prime Medicine, the first patient saw a 66% correction of the GT deletion in the mutated NCF1 gene in hematopoietic stem cells that had been treated with prime editing ex vivo.  Importantly, neutrophil (day 14) and platelet (day 19) engraftment occurred extremely fast following transplantation compared to prior experiences with Cas9 nuclease (e.g. Casgevy, ~30 days) and similar to base editing (Beam Therapeutics sickle cell program).  This indicates that non-double-strand DNA cleavage methods are preferable for ex vivo HSC editing from that perspective alone.

Following a company re-organization where Prime Medicine announced it would not further pursue PM359 in favor of commercially more attractive genetic disease in the liver, the future of that program seemed in limbo.  However, with a second patient now treated, and at remarkable 90% gene correction efficacy according to David Liu, it now looks like Prime Medicine will complete the first patient cohort and seek ways to monetize the priority review voucher potential (PRV) of that program.  PRVs have recently sold for ~$150M a piece and provide a critical incentive for the development of treatments for rare pediatric diseases.

The PRV incentive was highlighted by David Liu, the intention to complete the first cohort confirmed in a fireside chat yesterday at Jefferies by the new CEO Allan Reine.  Considering the rarity of this form of CGD (~1 in 600,000 births), I would not be surprised if the new FDA granted PM359 early approval after this cohort considering that HSC gene editing is now well established.

 

Update on arbitration with Beam Therapeutics

Clinical results with CGD and preclinical data from Prime Medicine’s in vivo liver programs show that, with optimization and know-how, prime editing efficacies can be as high as with the simpler, but somewhat dirtier Cas9 nuclease and base editing.  This makes them the preferred CRISPR editing modality for virtually all indications and has led to a conflict with Beam Therapeutics as they see their lead alpha-1-antitrypsin (AATD) base editing program under threat.

Previously, I had viewed Beam Therapeutics to have the upper-hand with regard to correcting the Z allele as this, as a single transition application, would seem to fall within its exclusive field of use of prime editing under their agreement with Prime Medicine.  Allan Reine, however, hinted at Jefferies that the edit Prime Medicine is pursuing is aimed at restoring the wildtype amino acid…not necessarily wildtype DNA.  This could mean that Prime Medicine’s strategy is to replace the AAG lysine codon in the 342 Z allele to GAA glutamic acid, instead of GAG as Beam Therapeutics is doing.  This would involve two, not a single transition and thus arguably fall outside the scope of Beam’s exclusive field 😊.

Disclosure: I am long Prime Medicine with about 7% of my portfolio allocated.  Given yesterday’s bullish regulatory (FDA CBER listening session), legal, and clinical developments and the basic premise that prime editing is the preferred CRISPR modalities in the foreseeable future, I am looking to add to my position.  Hard to believe a company controlling such a monumental technology can go bankrupt as the markets seem to price in.