Managing Editor’s Note: Tomorrow morning at 10 a.m. ET, Jeff is sitting down with Wall Street legend Whitney Tilson to reveal the details behind the artificial intelligence “super chip” that could shake up the entire AI sector…
Jeff’s also got his eye on a handful of stocks that could dethrone the Magnificent 7 once this tiny firm’s AI super chip goes mainstream.
He’s kicking things off at 10 a.m. tomorrow. You can go here to automatically sign up to attend.
After yesterday’s Bleeding Edge – $256 Million Worth of Spit, it feels right to share a very recent example of what real personalized medicine looks like.
It’s not some far-off medical technology that will happen years into the future. It’s actually happening right now, it’s incredible, it’s just that it’s not happening at scale yet.
A perfect example is a study published yesterday in Nature: World First: ultra-powerful CRISPR treatment trialed in person.
The study outlines how a genetic editing derivative of CRISPR was used to treat an 18-year-old with a rare immune disorder caused by genetic mutations using an approach called “prime editing.”
The company behind the work is Prime Medicine (PRME), a genetic editing startup that went public in October 2022 – the first year of the biotech winter. Talk about bad timing. Not surprisingly, it’s had a tough run of it since then, despite incredible progress.
Stock Chart of Prime Medicine | Source: Bloomberg
While the stock chart won’t show it, what Prime Medicine has accomplished with its prime editing is just amazing.
Prime Medicine targeted chronic granulomatous disease (CGD) – a rare immune system disorder caused by specific unwanted genetic mutations.
The underlying mutations related to CGD disable a variety of immune cells, thus weakening the human immune system. This genetic disease severely weakens the immune system against bacteria and fungi, often resulting in debilitating and often fatal infections.
This is precisely the power and promise of genetic editing technology. When the underlying cause of a genetic disease and its unwanted mutations are well understood, genetic editing therapies can be developed to correct/edit the unwanted mutations.
This is why the work of Regeneron (through its acquisition of 23andMe), Syntensor, and Simplify Genomics is so important.
The faster we connect those dots between the unwanted mutations and the diseases, the faster we can develop precision therapies to save lives and cure all diseases caused by genetic mutations.
Chronic granulomatous disease was a great first target for Prime Medicine to test its prime editing technology because its mutations are well understood. The most common form of CGD can be corrected by simply inserting two deleted letters into the DNA sequence – something prime editing is tailored to do.
Prime Medicine’s approach for CGD is ex vivo, which means the patient’s blood stem cells are taken out of the body, edited in a laboratory, and then reinjected back into the patient. This, by definition, is personalized and precision medicine.
The individual patient’s DNA is “corrected” outside of the body and then returned to the body to replace the “old” cells immediately after the patient has undergone chemotherapy to kill off any of the remaining stem cells with the unwanted mutation.
Ex vivo approaches to genetic editing are much more expensive than in vivo therapies, which are simply injected into the patient. The best approach to genetic editing depends on, among other things, the disease itself, efficacy of the therapy, any toxicity, and, of course, costs.
In the case of Prime Medicine’s therapy for CGD, PM359, the patient was given a single dose of the therapy via an IV after the chemotherapy was complete.
The efficacy of the therapy was measured by monitoring dihydrorhodamine (DHR) positivity as a proxy for the healthy functioning of neutrophils – an important type of white blood cell critical for fighting infections. CGD’s genetic mutations disable these immune cells, these neutrophils, which is why, as I mentioned above, patients with the disorder are so prone to severe infections.
But here’s where it gets incredible…
A common diagnostic criterion for CGD is, as we might expect, markedly low-level DHR positivity. Less than 20% raises concerns for elevated risk of infection, while those with less than 10% DHR positivity are noted as at significant risk of CGD-related infection.
But by day 15 after the injection of the modified cells, the patient who received Prime Medicine’s therapy had 58% DHR positivity. By day 30, that number increased to 66%.
At these levels, there is a strong indication that the patient could be cured for life. But, of course, Prime Medicine still needs to track the patient closely through the six-month and one-year marks. But I’d be willing to bet that DHR positivity levels will be even higher.
I’d like to take a step back and highlight how incredible this is:
Sounds incredible. And it is!
And yet, the stock is down 20% on the news, and it announced that it is restructuring its business.
Sadly, Prime Medicine will not develop its cure for CGD any further. The reality is that, as a small biotech company, it just doesn’t have the capital to do so for a market so small. Somewhere between every 100,000 and 200,000 births in the U.S. occur with the CGD mutation.
Because CGD is potentially fatal, this is a perfect example of why sequencing an infant’s genome can be lifesaving. Identifying a potential fatal genetic disease before symptoms present can literally be the difference between life and death.
Prime Medicine needs to find a larger biotech or pharmaceutical company to take PM359 through trials.
As for its restructuring, it will focus on developing its in vivo programs for the treatment of Wilson’s Disease and AATD, which are two of the largest liver diseases caused by genetic mutations.
They are good therapeutic targets because the genetic mutations are well understood, and the in vivo approach is far less expensive to push through clinical trials.
But even despite the lower cost of trials and the significantly larger markets for these therapies, Prime Medicine is still going to need to raise a lot more capital to get it through the next couple of years.
In fact, in March, it filed for a potential $125 million secondary offering, which it has not raised yet. I’m sure the management team was hoping that the incredible news on PM359 would have sent the stock much higher, presenting a higher valuation to raise additional capital.
The early filings for secondary offerings are often a sign that a company has good news on the way, but in a biotech bear market, even fantastic news won’t get the bull charging.
Jeff
The Bleeding Edge is the only free newsletter that delivers daily insights and information from the high-tech world as well as topics and trends relevant to investments.
The Bleeding Edge is the only free newsletter that delivers daily insights and information from the high-tech world as well as topics and trends relevant to investments.
