Newsletter · · Ashutosh Agarwal

Casgevy Sales Jump 151 Percent While CRISPR Therapeutics Still Loses Money - Biotech Pipeline: Gene/Cell, Neuro & Tools - Week of August 23, 2026

Biotech pipeline newsletter for the week of August 23, 2026. Casgevy sales rose 151 percent year over year, yet CRISPR Therapeutics still posted a quarterly loss as Vertex keeps most of the profit, while a Stanford lab and AI-designed edits point to the next generation of gene therapies and the Alzheimer's debate reopens.

Biotech Pipeline: Gene/Cell, Neuro & Tools

Week of August 23, 2026: Casgevy Sales Jump 151 Percent While CRISPR Therapeutics Still Loses Money

After a couple of weeks dominated by an FDA rejection and a loud "we're losing to China" alarm, this week the conversation came back down to earth, and, honestly, back to the part that decides whether any of this makes money. The most useful discussion of the week was a plain-spoken tour of the first CRISPR medicine's actual finances: sales are climbing fast, and the company that invented it is still losing money. It's a perfect snapshot of where gene editing really sits: the science works, the demand is real, and the economics are still a slog. Elsewhere, a Stanford scientist walked through how artificial intelligence and a new class of "no-cutting" editing tools are quietly changing what these therapies can do, and the Alzheimer's conversation split into two camps that don't usually share a stage. Here's the week.

TL;DR

  • Gene editing's flagship drug is selling fast, and its inventor still isn't profitable. Casgevy, the first approved CRISPR medicine, booked $76 million in the second quarter, up 151% from a year earlier. But CRISPR Therapeutics keeps only about $10 million of that after a profit-split with Vertex, still posted a $90 million quarterly loss, and just took on $600 million of debt. (Brew Markets, Aug 19)
  • The next leap in editing is about adding genes, not just cutting them. A Stanford lab is building tools that insert a healthy gene without slicing the DNA at all, and using AI to design the edits, one system already finds a working fix for a patient's specific mutation by testing just four options. (ASGCT Podcast Network, Aug 18)
  • Two very different Alzheimer's camps spoke this week. A Mount Sinai neurologist laid out the mainstream diagnostic playbook behind the new amyloid drugs, while a separate podcast made the contrarian case that infections help drive the disease, a debate the field has quietly reopened. (Keeping Current CME, Aug 20; Gladden Longevity, Aug 20)

What's new

The story of the week: Casgevy is selling well, and CRISPR Therapeutics still loses money. Prompted by a listener question, the hosts of Brew Markets did something the sector rarely does out loud, they added up the actual dollars behind the first approved CRISPR medicine, and the picture was sobering in a very specific way.

Start with the good news. Casgevy, a one-time treatment for sickle cell disease and a related inherited blood disorder, is clearly in demand. The way it works is almost science-fiction made routine: doctors take a patient's own stem cells, use CRISPR (think of it as molecular scissors that find one exact spot in your DNA) to flip a genetic switch so the body makes a healthier form of hemoglobin, then put the cells back. It was first approved by the FDA in 2023, is now cleared in 39 countries, and earlier this year was expanded to children as young as two. Sales are ramping hard: $116 million for all of 2025, then $43 million in the first quarter of 2026, then $76 million in the second quarter, that last figure up 78% from the prior quarter and up 151% from a year earlier.

Here's the catch, and it's the whole point. CRISPR Therapeutics doesn't actually sell Casgevy. Back in 2015 it partnered with the much larger Vertex Pharmaceuticals, a company worth about $130 billion, versus CRISPR Therapeutics at roughly $5 billion, and Vertex now runs the entire commercial operation and keeps the larger share of the profits, split 60-40 in Vertex's favor. So of that headline $76 million, the host explained, CRISPR Therapeutics "only brings in about $10 million" after costs. Meanwhile the company posted a $90 million net loss for the quarter (an improvement, at least, from a loss of more than $200 million a year earlier), and it is still burning cash even with about $2.4 billion in the bank. The market has noticed: the stock is down 75% from its 2021 high, and in July it dropped more than 12% in a single day on news it was taking on $600 million of new debt to keep funding research. As the host put it, it's hard to borrow that much and get a warm reception "if you're not super high conviction yet that the path to profit and cash flow is going to be there to service that debt."

"Casgevy is generating revenue today, but the company has several other experimental therapies in human trials." The bet, in other words, isn't the one drug that works, it's everything behind it.

That pipeline is the real reason to own the stock, and it's broad: experimental programs in autoimmune diseases, blood cancers, high cholesterol, high blood pressure, and type 1 diabetes, some in-house and some partnered. And CRISPR Therapeutics isn't alone, because the underlying tool was invented by academics and isn't locked up by one patent, plenty of companies can use it. The hosts flagged Intellia (NTLA), worth about $1.5 billion, which they noted "just had a successful phase three trial"; Beam Therapeutics (BEAM) at about $2.5 billion, known for a diversified pipeline; and the much smaller Caribou Biosciences. For what it's worth, the Street is still mostly optimistic: of about 22 analysts covering CRISPR Therapeutics, 13 rate it a buy or strong buy, the rest a hold, and none a sell. (Brew Markets, Aug 19)

The second story: the next generation of editing is about writing genes in, not cutting them out. On the American Society of Gene & Cell Therapy's podcast, Stanford scientist Le Cong gave the clearest explanation heard this year of where the technology is actually heading, and why today's tools, for all their power, only solve half the problem.

His starting point: CRISPR/Cas9 and the older "zinc finger" tools are brilliant at breaking a gene, cutting it so it stops working. But a lot of genetic disease is the opposite problem, a gene that's missing or broken and needs to be restored. Cong's lab is building a fix for that. Instead of slicing the DNA, they use a "dead" version of Cas9, one that can't cut, but still works like a GPS to find the right address in the genome, and attach a small protein borrowed from bacteria-infecting viruses that can splice in a fresh, correct copy of a gene. "There's not a shortcut," he said of the broader field's decade-plus grind, but the direction is clear: from a single pair of scissors toward a whole toolbox, including the increasingly celebrated "base editing" and "prime editing" methods that rewrite DNA letters without a clean cut. (ASGCT Podcast Network, Aug 18)

The AI part is where it gets genuinely practical. Designing a good edit used to mean lab technicians screening 10 or 20 candidate "guides" (the piece that steers the editor to the right spot) and hoping one worked. Cong's lab trained software on years of real experimental data to predict the good ones in advance. One tool, built by a graduate student for a compact editor called Cas12, ranks the best guides and is right about 80% of the time. A second, built with Stanford's Dr. Matthew Porteus, a scientific co-founder of CRISPR Therapeutics, goes further: trained on roughly a decade of lab data, it can find a working repair for a patient's specific mutation by testing just four options, with the top guide correcting the error more than half the time. That's the difference between a boutique, one-off science project and something you could imagine scaling to many patients. Cong pointed to the widely reported "Baby KJ" case, a custom gene edit built for a single infant, as proof the approach can already reach a real patient. (ASGCT Podcast Network, Aug 18)

On Alzheimer's, the diagnostic playbook behind the new drugs. In a teaching session for physicians, Mount Sinai neurologist Dr. Ana Pereira walked through how doctors now confirm Alzheimer's before prescribing the new amyloid-clearing drugs, and her comments are a clean summary of where that launch actually stands. She named the two approved medicines, lecanemab (Leqembi) and donanemab (Kisunla), said they "very robustly remove amyloid from the brains," and put the benefit plainly: they're "predicted to slow progression by about 30%." Before starting a patient, she said, you confirm the disease with an amyloid PET scan or a spinal-fluid test, and you check whether the patient carries the APOE gene variant that raises the risk of ARIA, the brain swelling and micro-bleeding that is the main safety worry with these drugs. To track whether the drug is working, she prefers a PET scan before and after; the spinal-fluid version changes too slowly to be useful for monitoring. She also flagged the direction of travel that matters commercially: a simple blood test measuring a marker called p-tau217 is moving into the picture, with a dedicated session to follow. (Keeping Current CME, Aug 20)

One thing worth naming plainly: that session was an educational program supported by a grant from Eli Lilly, which makes Kisunla. It's a legitimate clinical teaching format, but the sponsorship is context a reader should have.

And the contrarian Alzheimer's view: what if infections help drive the disease? On a longevity-focused podcast, a researcher from the Alzheimer's Pathobiome Initiative, a global consortium, made the case that microbes are an under-appreciated "accelerant" of Alzheimer's, not just innocent bystanders. The evidence they marshaled: a study found active organisms in roughly half of brain plaques, many of them oral bacteria (the gum-disease bug Porphyromonas gingivalis) or a respiratory bacterium, plus a long-standing link to herpes viruses. The idea has real history, a 1998 US study found viable bacteria in the plaques of Alzheimer's brains but not in healthy controls, and it's getting fresh money: the National Institute on Aging has put up a $49 million grant to study a drug that targets the gum bacterium's toxic machinery. (Gladden Longevity, Aug 20)

The most intriguing wrinkle ties the two Alzheimer's camps together rather than pitting them apart: the guest argued that amyloid, the very stuff the new drugs strip out of the brain, may itself be part of the immune system's defense against infection, produced in response to invading microbes. If that's even partly right, it complicates the clean story that "amyloid is the problem, so remove it." They also flagged why women are hit harder, two-thirds of Alzheimer's patients are women, citing a Kaiser Permanente study of 500,000 women that linked any form of hormone replacement to a 50% lower rate of dementia. It's an early, debated area, and this was a wellness podcast rather than a clinical one, but the science is being funded seriously enough to take note. (Gladden Longevity, Aug 20)

The debate

Is CRISPR Therapeutics a bargain or a value trap? The Casgevy math frames the bull and bear cases better than any analyst note. The bull case: a real, approved, accelerating product; a fortress balance sheet of $2.4 billion; a broad pipeline aimed at far bigger markets than sickle cell (cholesterol, blood pressure, diabetes); and a stock already down 75% from its peak, so a lot of disappointment is priced in. The bear case: the company keeps only about $10 million of every $76 million its flagship drug earns, it's still losing $90 million a quarter, and it just borrowed $600 million, a move that, as the hosts noted, tends to spook equity investors precisely because it signals the path to profit isn't yet obvious. Both are true at once. This is a company whose present is a thin-margin junior partner and whose value lives almost entirely in trials that haven't paid off yet. The listener's instinct, "beaten down from its all-time high," interesting pipeline, captures the appeal and the risk in one breath. (Brew Markets, Aug 19)

Amyloid orthodoxy vs. the infection hypothesis. For the first time in a while, both sides of the "what actually causes Alzheimer's" argument showed up in the same week. The mainstream case, laid out in the Mount Sinai teaching session, is confident and operational: the disease is now defined biologically by amyloid and tau, the approved drugs clear amyloid and slow decline by roughly 30%, and the whole diagnostic apparatus (PET, spinal fluid, and soon a blood test) exists to select and monitor those patients. The challenger case, from the pathobiome researchers, doesn't deny amyloid matters; it argues amyloid may be a response to infection, which would make clearing it necessary but not sufficient. Notably, nobody this week argued the two views are irreconcilable, and the fact that the National Institute on Aging is funding an anti-microbial Alzheimer's drug to the tune of $49 million suggests the establishment isn't dismissing the idea either. (Keeping Current CME, Aug 20; Gladden Longevity, Aug 20)

Read-throughs and names in play

  • CRISPR Therapeutics (CRSP), the marquee name, priced for the pipeline. The near-term reality is a low-margin royalty-like sliver of Casgevy and ongoing losses; the entire thesis rests on the next wave of trials working. Watch for data from the non-sickle-cell programs and any sign the $600 million debt raise buys enough runway to reach them. (Brew Markets, Aug 19)
  • Vertex (VRTX), the quiet winner of the Casgevy story. The week's numbers are a reminder that the Casgevy partner keeps the larger 60% of profits and runs the commercial machine, so the sales ramp (up 151% year over year) accrues disproportionately to Vertex, not the company whose name is on the science. It remains the more defensive way to own the sickle-cell franchise. (Brew Markets, Aug 19)
  • Intellia (NTLA) and Beam (BEAM), the peers, one with fresh momentum. The hosts singled out Intellia as having "just had a successful phase three trial," the kind of clinical win the whole in-vivo editing group needs, while Beam was framed on the strength of a diversified pipeline. Both are far smaller than Vertex and, like CRISPR Therapeutics, are stories about future data, not current cash. (Brew Markets, Aug 19)
  • The editing frontier (base/prime editing, gene-insertion tools), read-through to the whole toolbox. Cong's point that the field is moving from "cutting" toward "inserting and correcting," accelerated by AI-designed edits, is the structural bull case for the next generation of programs, and a reminder that today's approved products use yesterday's tools. His nod to Matthew Porteus, a CRISPR Therapeutics co-founder, ties the academic frontier straight back to the listed names. (ASGCT Podcast Network, Aug 18)
  • The Alzheimer's diagnostics chain (PET, spinal fluid, blood tests), the launch's real gating factor. Pereira's workflow shows that every amyloid-drug prescription runs through a confirmatory scan or test first, and that a p-tau217 blood test is coming. That demand pull-through for diagnostics is the practical read-through for anyone playing the Leqembi/Kisunla launch, even though no diagnostics or tools company was named this week. (Keeping Current CME, Aug 20)
  • Beyond the three lanes, an FDA-process contrast worth a note. On a separate podcast, Celcuity CEO Brian Sullivan described winning a first approval for a breast-cancer drug (gedatolisib) it had licensed from Pfizer after Pfizer shelved it, using the FDA's rolling "real-time oncology review" and calling the agency "very tough" but "very collaborative." It's outside our gene-editing/neuro/tools universe, but after recent weeks of FDA-rejection headlines, it's a useful reminder that the same agency can still be a constructive partner when the data are strong. (Business of Biotech, Aug 17)

What changed

Last week was about a regulator saying no and two operators warning about China. This week the temperature dropped and the focus shifted back to fundamentals, the unglamorous but decisive question of whether gene editing can actually make money, answered with hard numbers for the one product that's furthest along. The answer, for now: the drug sells, the inventor doesn't profit, and the value is all in the pipeline. Alzheimer's coverage also shifted in character, away from launch metrics (patient starts, insurance coverage, IV-versus-injection) and toward the underlying biology and diagnostics, plus a genuine re-airing of the infection hypothesis. Nothing this week overturned last week; it filled in the money-and-mechanism layer beneath it.