Tag: Academic research

PHOENIX, AZ — In my fifth year attending the Cell and Gene Meeting on the Mesa, I’ve seen a handful of trends trudge forward, stop dead in their tracks, and, in some cases, reverse course. 

Two years ago, cell and gene therapy (CGT) seemed like an untapped oil reserve waiting to power a new medical era. Casgevy, the first approved CRISPR medicine, had launched a new commercial era for gene editing, while CGT poster child CAR T-cell therapy was just one month shy of its seventh anniversary on the market, with seven approved therapies to match. All seven CAR T-cell therapies, along with Casgevy, were autologous.

An entire cell therapy industry formed around the autologous model, spawning and attracting a supersaturation of contract development and manufacturing organizations (CDMOs). To get a piece of the cell therapy commercialization pie, some CDMOs took up niches in preclinical development or clinical trial production at the requisite Current Good Manufacturing Practice (cGMP) standards. Other CDMOs specialized in the digital infrastructure needed to track cells on their “vein-to-vein” journey, and a select few even ventured into the realm of developing instruments for customers to bring production in-house. 

Few cell manufacturing concepts attracted as much attention as Cellares, touting a new generation of CDMOs—an automated “Industry 4.0” CDMO model dubbed “intelligent development and manufacturing organization” (IDMO). Co-founder and CEO Fabian Gerlinghaus preached that the platform would be an autologous cell therapy “kingmaker.” That claim didn’t seem overconfident after Cellares bolstered its position in April 2024, signing a deal worth up to $380 million with Bristol Myers Squibb (BMS) to manufacture selected CAR T-cell therapies globally. 

On the genetic medicine side, a few dozen gene therapies had been approved, and in vivo gene editing appeared imminent. Novartis’s Zolgensma, the standout, had generated roughly $1.2–1.4 billion annually since 2021 and had treated several thousand patients globally, while Sarepta’s Elevidys ramped much faster, from $200 million in 2023 to $821 million in 2024 and $899 million in 2025. 

However, between 2024 and 2026, there have been major setbacks across CGT. Elevidys was poised to surpass Zolgensma, but safety concerns and label restrictions halted its growth in 2025 after three Sarepta gene therapy-induced acute liver failure deaths. In August 2026, BMS walked away from the manufacturing deal, claiming Cellares’s offering failed to meet “the necessary requirements to make commercial Breyanzi.” 

Yet the tone at the 2026 Cell and Gene Meeting on the Mesa was anything but woeful or beaten down. Instead of personalizing every CGT, commercialization is pushing developers to broaden the patient pool for each program. These caught my eye at the Alliance for Regenerative Medicine (ARM) annual meeting.  

Searching for the sweet spot 

Jodi Cook, PhD, CEO of Skylark Bio, is a gene therapy veteran. She has been to all fifteen Cell and Gene Therapy Meeting on the Mesa conferences and told Inside Precision Medicine a pragmatic field is emerging. “The industry exploded on new money for a while,” Cook said. “Money was flowing everywhere, not just into gene therapy, and then it stopped. Now, we’re back to being mission-focused with sound business fundamentals to drive products forward.” 

Instead of raising successive rounds around incremental milestones, Cook believes that companies need enough capital to reach the clinic and compelling data to unlock the next investment. “Now, it’s more like you raise one large round of funding to get into first-in-human trials,” Cook said. “That makes it increasingly important to establish the commercial opportunity much earlier.” 

According to Cook, Skylark, a clinical-stage gene therapy company targeting inherited hearing loss and CNS disorders, prioritized commercialization and de-risking from the outset, advancing preclinical studies from mice to NHPs and then minipigs, whose inner ears closely approximate human size. “I tell my investors that we’ve de-risked everything we can externally,” said Cook. “Now the risk that’s left is execution, and I can control that.” Cook added, “All of the preclinical work and science line up. If you get it into the right cells, which we are, that should, over time, improve these children’s hearing, we did everything we could.” 

Skylark’s lead program illustrates one way to balance precision with scale. It targets GJB2-associated hearing loss, which accounts for 15% to 30% of all inherited hearing impairment. But rather than developing treatments for individual mutations, Skylark delivers a functional copy of the entire GJB2 gene. “There are multiple different mutations within the GJB2 gene,” Cook said. “We’re replacing the whole gene, so we don’t have to slice and dice to personalize it to you.” 

Skylark is applying the “doing more with less” approach throughout the pipeline. While each program requires a tailored payload, promoter, and regulatory elements, Cook is pushing for Skylark to get as close as possible to a “plug-and-play” model, reusing its capsid, manufacturing process, and much of its analytical infrastructure. That reuse could compress development timelines: what took three and a half years for Skylark’s first indication took about 18 months for its second. 

The goal, Cook said, is to finally make good on a longstanding gene therapy promise: “The business model can work if you can reuse or reapply the platform instead of doing something completely different for every individual.” 

The “other kind” of optogenetics 

One striking, out-of-the-box example of broadening a single gene therapy’s clinical applicability came from Nanoscope Therapeutics’ gene therapy solution to restore vision. Inherited retinal dystrophies (IRDs) are a diverse group of progressive genetic eye disorders characterized by the dysfunction and degeneration of photoreceptors (rods and cones) and the retinal pigment epithelium (RPE). Nanoscope’s strategy, however, has nothing to do with correcting the underlying congenital mutations that cause blindness. “If you don’t have functional photoreceptors, it may not matter which disease caused it, and there are dozens of them,” Samarendra Mohanty, PhD, Nanoscope’s president, CSO, and co-founder, said to Inside Precision Medicine. 

Nanoscope’s MOGENRY (sonpiretigene isteparvovec) delivers an engineered chimeric multi-characteristic opsin (MCO) to surviving bipolar cells that critically transduce light-gated photoreceptor activity. COO Paul Hallen said, “We’re essentially hijacking the bipolar cells to make them de facto photoreceptors. If your photoreceptors are dying and your bipolar cells remain intact, and there are roughly 10 million of them, that creates an opportunity.” 

To do so, Nanoscope doesn’t insert functional human opsins but rather a synthesized, Frankenstein-esque opsin that is far from naturally occurring or human. “There is no single molecule or opsin in nature that is broadband-sensitive, fast, and highly sensitive,” said Jared Stephens, Nanoscope’s vice president of strategy and business development. 

The MCO combines components derived from two algae and a sea anemone to respond rapidly across ordinary ambient light, making it suitable for restoring real-world vision without blur. “Here, we’re expressing a protein that is not only non-mammalian but derived from three different non-mammalian organisms,” Mohanty added. “This may be the most synthetic protein or gene sequence ever expressed in a human.” 

Nanoscope and other vision-loss companies call their tech optogenetics, which was intriguing after the 2026 Nobel Prize in Physiology or Medicine announcement. Mohanty mentioned Nanoscope’s optogenetic approach but, unprovoked, clarified the differences between their MCO and the work of newly minted Nobel laureates Karl Deisseroth, MD, PhD, Peter Hegemann, PhD, and Georg Nagel, PhD. 

“In optogenetics research, if you’re trying to probe 100 different types of cells in the brain, the goal has primarily been to stimulate each with a single wavelength of light,” Mohanty said. “You want zero crosstalk: blue responds to blue, green to green, red to red, etc. Our goal was the opposite.” 

Regardless, regulators are seeing the broad potential of Nanoscope’s MCOs. The PMDA—Japan’s FDA equivalent—recently accepted MOGENRY for priority review for IRDs, supported by data in retinitis pigmentosa and Stargardt disease. 

But what about gene editing? 

For Allen Reine, MD, CEO of Prime Medicine, the key to CGT is to nail down differentiated products and platforms. “I don’t think we want to be another company simply doing another PCSK9 therapy,” said Reine. “Are we solving a problem that others can’t by doing that? Probably not. The question is, where is prime editing differentiated, and where is it a unique approach to solving a problem?” 

The answer for Reine lies in addressing an unmet need with a differentiated therapy/approach that will make a meaningful difference to patients. “We have to check those boxes,” said Reine, who was an investor for 15 years before coming onto the operational side. “If all of those things are true, then there is likely a commercial opportunity. Then what we’re doing is good for patients and good for investors. When those two things align, that’s a great place for a company to be.” 

Reine thinks their Wilson’s disease program qualifies, and on day 1 of the conference, Prime Medicine announced the first dose of PM577a, an investigational in vivo prime editor for H1069Q-mutated Wilson disease, in its global Phase I/II study. 

Prime’s Alpha-1 Antitrypsin Deficiency (AATD) program trails close behind. Even though it’s a competitive space, Prime’s AATD program meets Reine’s criteria, who explained, “With alpha-1, it’s a competitive space, in part because the vast majority—95%, maybe 98%—of patients have one mutation. That makes it a very attractive target for gene-editing and RNA-editing therapies.” 

Reine expects clinical results for the Wilson and AATD liver programs in 2027, which will prove useful for advancing programs targeting other cell types. Prime has shown promising preclinical data in various tissues and indications, including the lung and cystic fibrosis, which Reine believes is highly translatable and profitable. “I strongly believe we can ultimately show that there are good business models behind these therapies in many cases,” said Reine. “That’s where we’re going to see important inflection points. To me, that means more dollars flowing into the space, more dollars being spent on programs and drugs that ultimately get to patients, and more patients who can potentially be cured of disease.” 

Automated autologous cell therapies  

Though disappointed in BMS’ withdrawal from Cellares’ manufacturing agreement, Gerlinghaus believes the company will stay on course. “Losing BMS was a setback, but BMS does not define the company,” Gerlinghaus told Inside Precision Medicine. Two weeks before the termination and reduction in force became public, he was visiting customers nationwide. Their response, he said, ranged from “We’re with you. This doesn’t change things for us” to asking whether Cellares could accelerate existing projects or take on additional trials. “One decision from one customer doesn’t change the vote of confidence we’ve gotten from a dozen other customers in the industry.” 

Cellares has since leaned harder into a portfolio strategy, more than doubling its customer base since the beginning of the year and aiming to build a portfolio of 30 to 40 active autologous ex vivo programs. “I don’t see us slowing down. I actually see us accelerating,” Gerlinghaus said. The main consequence of losing BMS, he argued, is timing: “It’ll just take about a year longer to get to commercial manufacturing than it otherwise would have.” 

There are successes for Cellares to report, including being one of eight companies picked for the FDA PreCheck program, which received over eighty applications. Similar to TSA PreCheck, the selection provides accelerated facility inspections for new domestic human drug and biological product manufacturing facilities ahead of commercial launch. Cellares was chosen alongside Eli Lilly, Regeneron, Amneal, Fujifilm Biotechnologies, Kriya Therapeutics, and Kyowa Kirin. 

The setback also tempered some of Gerlinghaus’ swagger. Asked whether he still stood by his previous description of Cellares as a potential “kingmaker,” Gerlinghaus replied: “As I get older, I get more humble.” After years of seemingly uninterrupted milestones, he acknowledged, “Now we’ve had a setback. But show me one company that never had a setback.” 

No company, field, product, or market has ever grown without setbacks. The key is to stay afloat until the stars align for a breakthrough. 

In Part 2 of this two-part series, Tim Hunt, CEO of the Alliance for Regenerative Medicine (ARM), and Karim Mikhail, the new director at the Center for Biologics Evaluation and Research (CBER), explain existing and developing frameworks for growing a sustainable cell and gene therapy industry.

The post Reporter’s Notebook: Cell and Gene Therapy’s Success Lies Beyond the Bespoke (Part 1) appeared first on Inside Precision Medicine.