Cell therapy

Eli Lilly in April continued a buyout streak involving the makers of “in vivo” cell therapies when it agreed to pay as much as $7 billion to acquire privately held biotechnology company Kelonia Therapeutics.

Lilly paid $3.25 billion up front for Kelonia and could eventually hand the startup’s shareholders another $3.75 billion if certain unspecified clinical, regulatory and sales milestones are met, it said at the time.

For Lilly, the acquisition furthers a push into what’s become a fast-advancing field of drug research. The cell therapies currently on the market involve “ex vivo” procedures, in which patient cells are extracted, genetically modified in a lab and then reinfused. Newer “in vivo” approaches are designed to alter immune cells without this complex and burdensome process, a workaround that could significantly broaden cell therapy’s reach.

In vivo cell therapy research remains early, with many programs currently only in preclinical or the first stage of human testing. Nonetheless, the concept’s potential has captured the attention of many large drugmakers. At least five have acquired biotech startups working on the technology over the last year or so. Lilly has bought two developers since February: Orna Therapeutics and now Kelonia.

Worth up to $2.4 billion, the Orna deal gave Lilly a preclinical program that’s shown promise in autoimmune disease, as well as a technology for manipulating cells “in vivo.” The Kelonia buyout hands Lilly another way of making these therapies; specially engineered viral particles that can get into cells and teach them how to make a new cancer-fighting receptor.

Kelonia’s most significant attempt at this approach is “KLN-1010,” a treatment in early-stage testing for multiple myeloma. The therapy is designed to help the body generate immune cells that target BCMA, a protein universally found on malignant cells.

According to Lilly, early data presented at a medical meeting last year provided “initial clinical validation” and “promising tolerability.” If successful in further testing, KLN-1010 would represent a “transformative advance” against the disease by “eliminating the complexities” of marketed cell therapies, Lilly added.

Available cell therapies “have meaningfully improved outcomes for patients with various cancers, but significant manufacturing, safety, and access barriers mean that only a fraction of eligible patients actually receive them,” said Jacob Van Naarden, head of Lilly’s oncology division as well as corporate business development, in the statement. “Kelonia's in vivo platform has the potential to change that by delivering rapid, durable responses in a far simpler, off-the-shelf format.”

While the upfront payment “appears full, we believe it is justified given the strength of the clinical data and the competitive dynamics in the space,” wrote RBC Capital Markets analyst Trung Huynh in a note to clients. AbbVie and Bristol Myers Squibb paid $2.1 billion and $1.5 billion, respectively, for companies that didn't have "comparable efficacy data" when they were acquired, he added.

The buyout "positions [Lilly] at the forefront of a potentially transformative technology with broad platform applicability beyond multiple myeloma," Huynh wrote.

Johnson & Johnson in July made its biggest investment yet in “in vivo” cell therapy, announcing a deal to work with, and potentially acquire, young biotechnology firm Sail Biomedicines at an agreed-upon price.

J&J paid $785 million up front initially, including a $465 million equity investment, to help advance Sail’s lead program as well as a technology the startup uses to reprogram immune cells inside the body. Dubbed SAIL-0839, that prospect is still in preclinical testing, and Sail hasn’t disclosed what diseases it will go after. Other therapeutic targets could be added to the deal over time, J&J said.

J&J also secured an exclusive option to acquire the startup for $2.58 billion in the future. Should it exercise that right, J&J would join an already large group of major drugmakers, among them Eli Lilly and Bristol Myers Squibb, to recently purchase an in vivo cell therapy developer.

CAR-T therapies are now a well-known form of cancer care. Engineered from a patient’s own cells, they’re able to durably wipe out certain malignancies when they work.

So far, though, the available CAR-T treatments are “ex vivo” therapies, which involve manipulating cells in a lab in a costly and burdensome process. They’re also still largely limited to a handful of blood cancers and other tumors, and usually involve a chemotherapy conditioning step that can be a barrier to broader use.

A new wave of drugmakers have responded with technologies designed to make the process far more convenient by effectively coaxing the body into making its own specialized, disease-hunting cells. These in vivo techniques could make cell therapy more widely accessible and be helpful treating autoimmune conditions, where a more convenient and less invasive approach could be particularly useful.

Large pharmaceutical companies have taken note, snapping up at least a half dozen startups working on in vivo technology since early last year. Many, like Sail, are working on would-be immune disease treatments.

For J&J, the deal is a way to build on an already-established presence in cell therapy. The company co-developed the multiple myeloma treatment Carvykti with Legend Biotech. It’s dabbled in other cell therapy approaches in the past, too, including through a partnership with Kelonia Therapeutics before that company was acquired by Lilly.

“Sail’s innovative platform represents an exciting new approach that seeks to harness the power of CAR-T therapy in a simpler, more scalable way,” said John Reed, J&J’s head of R&D, in the announcement.

Sail was formed through a 2023 merger of Senda Biosciences and Laronde, two companies backed by biotech creator Flagship Pioneering. That deal married work on “endless RNA” with research into "programmable nanoparticles" able to get into a variety of cells and tissues. Sail used those technologies to develop a pipeline of in vivo cell therapies. Four are in preclinical development.

“Our new class of medicines offers an innovative therapeutic horizon for patients and providers — powerful, accessible, and scalable products,” said John Mendlein, Sail’s executive chairman, in a statement.

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By the PPD™ clinical research business of Thermo Fisher Scientific

For many cell and gene therapies, the greatest challenge is no longer the science. It's finding enough patients to prove the science works.

What was once considered one of medicine's most ambitious frontiers is rapidly becoming clinical reality. Cell and gene therapies are creating new treatment possibilities for patients with rare diseases, inherited disorders and certain cancers.

Yet every breakthrough reveals another challenge.

The science behind these therapies continues to advance, but the systems responsible for testing, delivering and monitoring them are struggling to keep pace. For many developers, the greatest obstacle is no longer discovering a promising therapy. It is building a clinical development strategy capable of supporting treatments that are inherently more personalized, operationally demanding and data intensive than traditional medicines.

Conventional clinical trials were designed around large patient populations and standardized treatment pathways. Cell and gene therapy studies rarely have those advantages. Many enroll only a handful of participants, each representing a significant portion of the evidence base. Every screening decision, laboratory result and study visit carries disproportionate importance.

Finding eligible patients is often the first hurdle. These therapies frequently target rare diseases or highly specific genetic subtypes, leaving only a small number of potential participants worldwide. Even when patients are identified, complex eligibility requirements and specialized treatment pathways can narrow that population even further.

The operational demands continue after enrollment. Patients may require extensive biomarker testing, sophisticated laboratory support, specialized treatment centres and years of long term follow up after receiving therapy. Sites must coordinate multidisciplinary teams while managing complex logistics that stretch far beyond the traditional responsibilities of a clinical trial.

None of these challenges exist in isolation. A delay in laboratory testing can postpone treatment. Limited collection capacity can slow recruitment. Missing long term data from a single participant may influence how regulators interpret an entire program. Success increasingly depends on how well these individual components work together.

This has prompted a shift in how many organizations think about clinical development. Rather than viewing protocol design, patient recruitment, laboratory strategy and long term follow up as separate activities, developers are beginning to approach them as parts of one connected clinical ecosystem.

That broader perspective is also changing how evidence is generated. In rare diseases, natural history studies and patient registries often provide critical context for understanding disease progression and selecting meaningful endpoints. Biomarkers can help identify the patients most likely to benefit while patient and caregiver perspectives ensure that clinical outcomes reflect meaningful improvements in everyday life, not simply statistical significance.

Long term evidence has become equally important. Many gene therapies require years of continued monitoring to understand durability and identify delayed safety events. Designing studies that patients can realistically remain part of over time has become just as important as designing studies that answer scientific questions.

These developments reflect a broader evolution across precision medicine. As therapies become increasingly individualized, clinical development must become equally adaptable. Flexible trial designs, stronger operational coordination and more integrated evidence strategies will all play an important role in determining how quickly innovative therapies reach the patients who need them.

The future of cell and gene therapy will certainly be shaped by advances in biology. It will also be shaped by quieter innovations in trial design, patient engagement, evidence generation and clinical operations. Those may not attract the same headlines as a scientific breakthrough, but they will determine how many breakthroughs ultimately become accessible treatments.

Read the full white paper from the PPD™ clinical research business of Thermo Fisher Scientific to explore integrated clinical strategies for advancing cell and gene therapy development, from patient identification through long term follow up.

An experimental cancer cell therapy developed by Legend Biotech helped reduce or eliminate signs of disease in people with lymphoma enrolled in a clinical trial, sparking hopes the “in vivo” medicine might compete with personalized, marketed treatments like Novartis’ Kymriah.

At the higher of the two dose levels tested so far, all six people treated with the therapy, LB2501, responded. Five had no evidence of lymphoma lesions, according to trial details released ahead of a medical meeting in June.

Legend is one of many companies seeking to develop therapies that fight cancer by reprogramming immune cells inside the body. If successful, these therapies would sidestep an extensive, “ex vivo” process that involves extracting cells and modifying them in a lab.

Multiple Wall Street analysts praised the data, with RBC Capital Markets’ Leonid Timashev noting that a successful “in vivo” product could record blockbuster sales while “ex vivo” counterparts face “logistical bottlenecks” that limit their commercial potential.

Legend is already a prominent cell therapy player, having successfully developed the personalized multiple myeloma treatment Carvykti that it now sells with Johnson & Johnson. It’s now turning to “in vivo” work, an area that’s seen an explosion in venture investments as well as a string of recent drugmaker acquisitions.

With LB2501, Legend uses a modified virus to deliver into immune cells instructions to find and attack cells expressing the proteins CD19 and CD20. Those proteins are found on the surface of malignant B cells and are known targets in lymphoma. Importantly, the treatment doesn’t require a chemotherapy step to prepare the body for treatment, as other cell therapies do. 

The data reported at the European Hematology Association meeting in June came from a first-in-human trial conducted in China that’s testing LB2501 in people whose disease had progressed after at least two lines of treatment. An abstract posted ahead of that meeting involves results in 12 patients with large B cell lymphoma, follicular lymphoma or mantle cell lymphoma who received one of two tested doses.

No responses were observed at the lower dose, even though there was evidence of activity in five of the six recipients. At the higher dose, though, remissions — defined as a reduction or elimination of lymphoma lesions — were registered in all six recipients. Five had “complete” responses, Legend said.

Eight of the enrollees had an immune response called cytokine release syndrome that is often seen with cell therapies, but only one needed an intervention beyond basic symptomatic treatments for fever, pain or nausea. No patients had an immune response that affected the brain or nerves, another side effect associated with ex vivo cell therapies.

In his note, Timashev wrote further data, such as a six-month follow-up, will be necessary to see how Legend’s therapy stacks up against others, such as an experimental treatment from Lyell Immunopharma. But the news is nonetheless “exciting both for their clinical value of the product, and strategically, because it puts forth a credible second act for [Legend] beyond Carvykti.”

The most effective drug for Parkinson’s disease hasn’t changed in 50 years. But fresh research published in one of the country’s top scientific journals is helping build the case for a more cutting-edge approach that uses stem cells to restore important brain functions.

The second most common neurodegenerative illness, Parkinson’s is caused by the loss of certain nerve cells. These cells produce a chemical messenger, dopamine, that plays a crucial role regulating movement. Since the 1970s, a drug called levodopa, which the body converts into dopamine, has been the mainstay treatment for combating the tremors, slowness, stiffness and balance issues that come with Parkinson’s.

Levodopa doesn’t stop the disease, however, so scientists have spent decades trying to find a more permanent fix. The latest development in that search comes from two clinical trials testing stem cell-derived therapies transplanted into the brains of Parkinson’s patients.

The first of those trials, conducted at the Kyoto University Hospital in Japan, evaluated seven people who received what are essentially blank slate cells that can turn into dopamine-producing neurons. These cells were created using a technology pioneered at Kyoto University, where roughly 20 years ago, scientists discovered how to reset some adult human cells to act like stem cells.

The study’s main focus was safety. Results, published in April in the journal Nature, show no serious adverse events were reported, though researchers did identify 73 mild to moderate events. Importantly, there was no evidence the introduced cells started growing in an unchecked, tumor-like fashion — a major concern with stem cell implants.

The study also explored whether this therapy had any effect on patients’ disease. Two years post-treatment, the six participants who were evaluable had gotten better on a scale clinicians use to measure the severity of Parkinson’s motor symptoms. Researchers looked at what’s known as “on” time, when medications are adequately controlling these symptoms, as well as the opposite “off” time, and found scores improved an average of 36% and 20%, respectively.

Another test indicated that dopamine-producing cell activity had increased substantially. This was determined through a technique in which researchers strap a radioactive element to a molecule of levodopa and then use a PET scan to follow its path through the nervous system, somewhat like how a submarine tracks objects on a sonar display.

The second trial took place at sites throughout the U.S. and Canada, and employed a different kind of stem cell that comes from human embryos. It enrolled a total of 12 participants and followed them for a year post-transplant.

Similar to the Japan study, there were no deaths, serious adverse events or tumor-like tissue growth related to the introduced cells. Trial runners did report two serious events overall. One participant was hospitalized with COVID-19, while another had a seizure that was attributed to the surgical procedure.

The trial also saw improvements in “off” scores on that disease severity scale and positive results from the radioactive levodopa test.

The cell therapy tested, called bemdaneprocel, is being developed by Bayer subsidiary BlueRock Therapeutics, which back in August 2023 announced some of the trial data. The company expects to start a Phase 3 experiment before the end of June.

Hideyuki Okano, a stem-cell scientist at Keio University in Tokyo, argues more research is needed to confirm these types of cell therapies are effective against Parkinson’s.

Still, in an accompanying Nature editorial, he called the new trial results “encouraging” because they suggest treating Parkinson’s patients with donor cell transplants is likely safe. That both trials “proved to be safe, and hinted at possible efficacy, is an important step towards the establishment of this cell therapy for Parkinson’s disease in wider society,” he wrote.

Cell therapy for Parkinson’s isn’t a new idea. In 1989, a team led by neuroscientist Olle Lindvall performed the first cell transplantations for Parkinson’s patients. While the landmark study didn’t show a major therapeutic benefit, a few interesting signals encouraged the research community to keep exploring.

One ethical concern from that trial was that it used a relatively large amount of tissue derived from aborted fetuses. In the decades since, Parkinson’s and cell biology experts have made significant progress identifying other, less controversial sources of stem cells that can be scaled more easily.

A milestone of that work came in 2020, when the technique invented at Kyoto University was used to turn a Parkinson’s patient’s own skin cells into the early stages of dopamine-producing neurons, which were then implanted into his brain.

According to Okano, as of December, there were 115 clinical trials testing 83 products derived from “pluripotent” stem cells. And among those targeting central nervous system disorders, the ones for Parkinson’s disease are at a more advanced stage of development.

Further behind Bayer and BlueRock, Aspen Neuroscience, a San Diego-based biotechnology company, has a Parkinson’s therapy derived from patients’ own cells currently in early-stage human testing.

Almost a decade ago, brain drugmaker Acorda Therapeutics was having a banner year. Its multiple sclerosis medicine Ampyra brought in more money than ever in 2017, reaching nearly $550 million and accounting for more than 90% of the company’s net revenue. Then everything came crashing down.

By late 2018, U.S. courts had invalidated the key patents protecting Ampyra from generic competition. Sales subsequently plummeted. Acorda hoped to offset those declines with Inbrija, a new Parkinson’s disease drug given through a special inhaler. But mere months after Inbrija entered the market, its launch was derailed by the COVID-19 pandemic.

Inbrija did start to gain momentum as the pandemic abated, though the rebound came too late. Acorda was tapped on cash by 2024, and still owed bondholders hundreds of millions of dollars due at the end of the year. The company asked for more time to repay the debt, according to former CEO Ron Cohen. The response it got: “first see if you can find a buyer.”

Acorda did, in Merz Therapeutics. It went on to file for Chapter 11 bankruptcy in April 2024, which, Cohen said, was a tax-favorable way to transfer assets to Merz. The sale process was complete by that July.

After Acorda wound down, Cohen went looking for his next act. He found it in Oryon Cell Therapies, a startup that emerged from stealth in March with $42 million in funding. Oryon aims to treat Parkinson’s through the “autologous” process of extracting and reengineering a patient’s own cells to act a certain way. Specifically, it hopes to create neurons that can restore dopamine production and help improve movement control.

BioPharma Dive spoke to Cohen about lessons learned from the Acorda saga and why Oryon stood out amongst a handful of developers in the Parkinson’s cell therapy space. The following conversation has been edited and condensed for clarity.

BIOPHARMA DIVE: It’s not hard to find interesting science in today’s biotech ecosystem. What specifically drew you to Oryon?

RON COHEN: There’s something uniquely awful about diseases that affect the brain and the spinal cord. Not only do they interrupt you physically, but they eat away at who you are and what makes you a person. It’s just uniquely tragic for me. So I find a lot of meaning in trying to alleviate conditions in that spectrum.

I was looking for a technology that sang to me, data that I could believe in, that I had conviction in. I preferred to find somebody that already had funding. I was seeing a lot of seed-round-type companies. That's fine. But I've been there, done that. I paid my dues. If I can take my experience and apply it to an existing group with money, technology and proof-of-concept data, then I can contribute fully. This is what I found at Oryon.

I also liked how they were doing autologous cells. There's only one other company that's directly head to head on that score. Everyone else is doing donor cells. Of course, there is an advantage to donor cells, manufacturing, because you don't have to make the cells fresh for each new person getting them.

On the other hand, with autologous therapies, you don't have to give immune suppression for the first year. And you're not taking the risk that, over time, there may be low-grade immune effects. Again, that's all hypothetical and may turn out fine. But that was my calculus.

There are a handful of other developers working on cell therapies for Parkinson’s. How do you see Oryon as differentiated from them?

COHEN: I did a lot of diligence on the field, looked at the different players. What I liked about Oryon was, first of all, they had human data. And the data was credible to me. Even though it's not yet placebo-controlled, it was at least internally controlled. The first patients given Oryon’s therapy were all evaluated unilaterally, so at least you can compare one side of the brain to the other on the imaging and one side of the body to the other on the effect.

Aspen Neuroscience, which is the other autologous company, looks very nice. They're doing neural progenitor cells. They derive their [stem cells from a patient’s own] skin. I've had a skin biopsy. I don't want to have one again. I'm being a little glib.

So they take the cells, they drive them to become neuronal progenitors … . You put them in, they continue to divide, and then at some point they decide they're going to differentiate. And you trust that at least some will become the dopaminergic neurons you want.

My bias, from long years of drug development, is the more you know about what you're putting in, the more you know about dose, the more you know about specific characteristics … then when you see the results, you can calibrate. [With Oryon’s approach], I know how many of those cells I'm giving. I like that.

At least a couple companies — Aspen, Bayer’s Bluerock subsidiary — are significantly further along in development. How are you thinking about your own timelines?

COHEN: There are five or six companies working on this, some of them are ahead. What is it that would make me want to take the chance on Oryon? There were actually two things in terms of their data.

One was the unilateral testing. I looked at their data comparing one side to the other, and I thought: This all makes sense. The side that got the implant is controlling the other side of the body and showing the biggest change. The other side is showing some improvement, which I would have expected.

And then the second thing was they were doing imaging studies. The imaging was tracking functional results. Not all the patients responded exactly the same, which is good. If they did, I'd be wondering. That's not biology.

I looked at the whole thing, and I said there is a reasonable chance this could be best in class. We have a long way to go to prove that. We know in biotech that you never have all the information you need to make a decision. This was enough information for me to make the decision.

You see autologous as an advantage for Oryon. Had the company been focused on donor-derived cells, would you have found it as interesting an opportunity?

COHEN: This is retrospective, so take that for what it's worth. I think I would have looked at Aspen and thought: I like autologous, and the thing in favor of donor cells is the manufacturing. Now, that's not trivial. It's expensive to make these cells, and when you're doing it patient by patient, you don't have economies of scale the way you do with allogeneic.

Frankly, if it turned out that these patients were followed for several years, and allogeneics [showed similar] outcomes and were just as safe even with the immune suppression — if all that were true, then I would say it's cheaper to make the allogeneics, and probably they could then beat everyone on price and reimbursement.

But the bet I'm making is that [because of various immunological concerns], autologous really will have benefits. As part of my diligence, I talked to doctors in the field, many friends and colleagues who know Parkinson's. I called them up and said, “Hey, what do you think of this?” I didn't get a single one who didn't say, “Oh, if I can avoid immune suppression, then I will.”

Parkinson’s doesn’t have a great array of treatment options. And yet, cell therapy can be a lot to ask of a patient. What demand do you see for these kinds of medicines?

COHEN: I don't know, to tell you the truth.

I've done straw polling in my networks. I have 250 Parkinson's doctors in my database who I personally have interacted with over the last 10 years. There is an enormous receptivity to something like this, based on everything I've heard.

Even though the company's not public, just through the grapevine of the neurologists and neurosurgeons and other people in the academic world who are involved, we already have a few hundred people on the waiting list who called in and said, “Yeah, could you consider me for the trials?” I'm not surprised, because this disease sucks, and you can quote me on that.

Do you see this as a market where multiple cell therapy products can be successful?

COHEN: It doesn't matter what condition, there's virtually always space for multiple entries. There are over a million people with Parkinson's in the U.S. Tens of thousands of new cases in just the U.S. alone are diagnosed every year. You can get about an equal number or more for the E.U., and then Asia is astronomical. So there's going to potentially be a humongous demand.

The icing on the cake would be if the data show advantages to Oryon's approach. The jury is completely out on that. It's going to be a few years before we really know for sure.

If it turns out that there is an advantage, then we can enter the market as a fast follower with those advantages to talk about. If it turns out that no, we're entering the market in follow up, it won't be as big an opportunity for Oryon. But will it be a substantive market? Yes.

What lessons from your time at Acorda that you think will be helpful as you helm Oryon?

COHEN: I learned a lot about the Parkinson's market and the way the doctors think. It is true that this is a particular indication where the doctors tend to be slower on uptake of new drugs. One reason is that they tend to be more conservative. They're dealing with an older, frailer population. Comparing it to other neurologists in MS, they treat people in their 20s, and there's a different feel to it. They go, “Yeah, I'll try anything.”

Now, our insurance system also doesn't help, because any new branded therapy is going to be costly compared to generics. They have to go through hurdles with insurance and step edits and prior authorization.

My sense of that population is they will respond far more positively to something like this, because it's not just another symptomatic drug. This is biologically, if you will, turning back the clock, at least on the motor symptoms of the disease.

Late-stage studies are often expensive. How far do you expect Oryon’s funding to stretch before you have to raise more?

COHEN: In terms of recruiting and getting [the Phase 1/2 study] done, we should be able to get all the patients in before the end of 2026 and to have most of the follow up done and really talk to the FDA about Phase 3 by mid-2027, to then start Phase 3 in late 2027 or the first half of 2028.

I'm not going to commit to when we would raise money. But I will tell you, given my experience, I'm always raising money, even when I'm not raising money.

Once I have a core group in place that's handling the absolute key clinical, regulatory, manufacturing, and development issues and [working to] compress the timelines and make it more cost efficient, I'm going to be talking with investors just to prepare the way, just to get people interested.

When the time comes for the next round, that’s not when I'm going to start. I will have already started for months.

An experimental therapy from Allogene helped eliminate signs of cancer better than standard treatment in a Phase 3 trial in first-line large B-cell lymphoma, results suggesting the biotechnology company may have found a role to use donor-derived cell therapy against the deadly blood cancer.  

After 45 days of treatment, seven of the 12 patients given Allogene’s therapy in the study were negative for “minimal residual disease,” meaning that diagnostic tests could no longer detect signs of cancer. By comparison, only 2 of 12 placebo recipients hit that mark, a roughly 42-percentage-point difference that clears an important bar published literature has suggested is crucial for delaying a relapse. 

The results came from an early “futility” analysis Allogene disclosed in April. Allogene is enrolling 220 people in the study and expects to report in 2027 results showing whether treatment staved off cancer’s return. 

Allogene spun out of Pfizer’s cell therapy work in 2018 with plans to prove that donor-derived, or “allogeneic” cell therapies could prove a more convenient alternative to their personalized CAR-T counterparts. But like many of its peers, Allogene suffered several setbacks along the way. It’s lost most of its market value since going public. 

In 2024, though, Allogene came up with a new way to show allogeneic treatments might have an important role to play in lymphoma. Rather than position cema-cel in settings where CAR-T therapies like Breyanzi and Yescarta are available, it set its sights earlier, testing the treatment in people who are at risk of relapse after receiving a widely used drug regimen known as R-CHOP.

Allogene’s study results were an important early step towards validating the company’s choice. The therapy significantly exceeded the 25- to 30-point difference, compared to placebo, on minimal residual disease that investors and analysts had been looking for. The treatment also wasn’t associated with severe occurrences of the kind of immune or neurological side effects often associated with personalized cell therapies. 

Half of the patients in the cema-cel arm experienced neurological side effects such as headache and dizziness that were judged to be “low grade.” Two had mild infections, such as a urinary tract infection or COVID-19, according to Allogene.

“These interim data suggest that an off-the-shelf CAR-T may be able to intervene during that important window before clinical relapse to eliminate residual disease and make earlier intervention feasible in routine clinical practice,” Zachary Roberts, Allogene’s chief medical officer, said in a statement, calling the data “encouraging.”

Personalized, or autologous CAR-T treatments, are largely given at specialized centers. Allogene aims to show that its donor-derived treatment could be more accessible to those who receive care at community cancers. A third of study participants were infused at these centers, which “bodes well for broad adoption,” wrote William Blair analyst Sami Corwin in a client note.

Roger Song, an analyst at Jefferies, added in a separate note that cema-cel could become a $3 billion asset for Allogene “that is currently underappreciated.” Song has previously predicted that cema-cel could bring in peak global revenues of $1.1 billion per year.

Kyverna Therapeutics is seeking clearance of what could be the first marketed cell therapy for an autoimmune condition after the treatment succeeded in a pivotal trial in a progressive condition known as stiff person syndrome.

According to Kyverna, four months after treatment with its therapy miv-cel, Phase 2 study participants had a median 46% improvement from the trial’s start on a type of timed walking test. More than four-fifths had at least a 20% improvement, a threshold that’s believed to be “clinically meaningful,” Kyverna said in December. The therapy met its key secondary study goals as well.

Kyverna said there were no “high-grade” cases of the immune or neurological side effects associated with treatments like miv-cel. There were Grade 3 or 4 instances of neutropenia, or low counts of a kind of white blood cell, but Kyverna said they were “manageable.” The company began filing an application for U.S. approval in May. 

Kyverna has long been a front-runner in the race to transform the types of cell therapies originally developed for cancer into autoimmune disease treatments.

Originally formed to pursue so-called Treg cell therapy, the company changed direction and licensed a more conventional cell therapy technology that’s yielded what’s now known as miv-cel. Fueled by academic studies suggesting these therapies might rewire the immune systems of people with autoimmune disorders like lupus, it raised hundreds of millions of dollars in private and public funding. But mixed early results and growing competition tempered excitement about these treatments, depressing the share price of Kyverna and many of its peers. 

Kyverna swapped CEOs and, under a new leader, began developing miv-cel for stiff person syndrome, a disorder that causes intensifying muscle stiffness. While rare, the condition has less therapeutic competition than Kyverna’s other targets and, because of its fast progression, offered a quicker path to clinical results.  

Since then, Kyverna has begun clawing back some of its stock value and quickly completed enrollment in a registrational trial. Its goal in the 26-patient study was for miv-cel to help drive at least a 20% change on a timed, 25-foot walking test. Executives had pointed to case reports suggesting miv-cel could produce more powerful effects.

According to Leerink Partners analyst Thomas Smith, the fresh results are a “best-case scenario” for Kyverna, enabling the company to bring to market the first and only therapy for stiff person syndrome as well as, more broadly, the first approved cell therapy for an autoimmune disease.

In addition to clearing the important walking test threshold, miv-cel also helped many patients no longer need a walking device after 16 weeks and, so far, has freed all study participants from the immunotherapies typically used to treat their condition. 

“We believe this highlights miv-cel's potential to provide unprecedented clinical benefit, while significantly reducing or eliminating chronic treatment burden,” Smith wrote. 

Gilead Sciences in February deepened its investment in cell therapy, agreeing to acquire its longtime development partner Arcellx in a $7.8 billion deal centered around an experimental multiple myeloma treatment. 

Gilead already owned about 11.5% of Arcellx’s equity prior to the deal’s announcement. It then paid $115 per share for the rest of Arcellx’s stock. Arcellx stockholders could receive another $5 per share in future payouts, too, should the biotech’s top program, “anito-cel,” win approval and go on to generate $6 billion in cumulative net sales through the end of 2029. 

Gilead is best known for its HIV drugs. But it’s also long been a leader in cancer cell therapy, a way of modifying the body’s immune defenders to hunt and kill tumors. Through its $12 billion acquisition of Kite Pharma nearly a decade ago, the company acquired two blood cancer therapies now known as Yescarta and Tecartus. Those therapies are the centerpiece of a business that now brings in more than $1 billion annually and that Gilead has looked to as a way to diversify into oncology. 

Still, Gilead’s cell therapy business took years to ramp up, part of a broader struggle companies have had profitably selling complex treatments that take weeks to make and are largely administered at major institutions. And of late, sales have declined amid pressure from newer competitors.

Yet Gilead sees anito-cel potentially turning that business around. Arcellx medicine imbues T cells with the ability to fight multiple myeloma, a progressive cancer of the bone marrow. That therapy has already been submitted for U.S. approval based on study results showing a 96% response rate among recipients whose multiple myeloma had relapsed, or hadn’t responded to, at least three prior treatments. A decision is expected by Dec. 23. 

Effective, marketed cell therapies from Johnson & Johnson and Bristol Myers Squibb work similarly, as do a handful of “bispecific” antibody therapies. Gilead, for its part, said that anito-cel has demonstrated “deep and durable responses” with a “predictable and manageable safety profile,” which addresses “key challenges” associated with existing multiple myeloma cell therapies. The companies have been aiming to prove, for instance, that people who receive anito-cel have a lower risk of a cell therapy-related side effect called parkinsonism. 

Antio cel “could become a foundational treatment for multiple myeloma over time, including earlier lines of therapy,” said CEO Daniel O’Day, in a statement.

The therapy has “shown generally comparable efficacy” to Carvykti with the potential for a better safety, wrote RBC Capital Markets analyst Brian Abrahams, in a Monday note to clients. But Gilead and Arcellx are behind competitors in an area “where early entrenchment may be important. The “degree of market acceptance” for a cell therapy in the earliest lines of care is also “unclear,” he added.

Like some of its peers, Gilead has also invested in “in vivo” treatments that modify cells inside the body and are seen as more convenient alternatives to existing therapies. Gilead claimed that some Arcellx research could be useful there, in addition to helping produce “next-generation” cell therapies and bispecific antibodies.

Chinese biotechnology company Oricell Therapeutics in April banked more than $110 million in a “pre-IPO” venture funding to help it advance a portfolio of cell therapies for tough-to-treat solid tumors. 

Oricell’s lead program is being tested against advanced hepatocellular carcinoma, an aggressive liver cancer that most frequently occurs in people with chronic organ damage. That therapy, Ori-C101, has already completed early testing in humans and demonstrated what the company claims to be a “best-in-class efficacy and safety profile.” 

Most of the cell therapies that have reached market so far are used to treat blood malignancies. Solid tumors have proven trickier foes, however. These tumors often have cells expressing a variety of antigens, making them hard to target with a therapy aimed at only one. They also use a layer of immune-suppressing cells and other molecules as a protective shield against the body’s defenses.  

Oricell is relying on multiple approaches to help, among them a kind of “armored” technology that helps cell therapies fight through this immune-weakening barrier. Its lead program is also aimed at a protein, GPC3, that’s highly expressed on cancerous liver cells and largely not on healthy tissue. In a small study presented at the annual American Society of Clinical Oncology meeting in 2025, the company said six of 10 patients treated with its therapy responded to treatment, and nine achieved disease control. 

Oricell’s pipeline includes six other named drug prospects for other solid tumors and blood cancers. One, “OriCAR-017,” is in a Phase 1/2 trial in China for multiple myeloma. Results are expected later this year. Oricell is also working on “in vivo” CAR-T technology, an increasingly popular approach through which immune cells are engineered within a patient’s body.

“We are committed to delivering transformative therapies that offer real hope to cancer patients worldwide, positioning Oricell as a dominant force in the global immunotherapy arena,” Huanfeng Yang, Oricell’s CEO, said in a statement.

The Food and Drug Administration last year eased limitations it imposed around the complex cancer drugs known as CAR-T therapies, removing several onerous requirements as well as loosening restrictions on which facilities can provide treatment.

The FDA’s action applied to therapies made by Bristol Myers Squibb, Gilead Sciences, Johnson & Johnson and Novartis that are used to treat several types of blood cancer. Specifically, it removes so-called “Risk Evaluation and Mitigation Strategies” from the drugs’ labeling, which are used to help manage serious side effects of treatment.

According to the FDA, these REMS requirements are no longer necessary to ensure safe use of these CAR-T therapies as both physicians and hospitals are now well versed in managing the two syndromes most commonly associated with the drugs.

Since the FDA’s approval of Novartis’ Kymriah for leukemia in 2017, six more CAR-T therapies have reached market. These medicines are made from a patient’s own immune cells, extracted from the body and engineered in a lab to hunt down specific proteins found on the surface of malignant clones.

For some people with leukemia, lymphoma or multiple myeloma, they can prompt powerful responses and even long-lasting remission. But their administration also comes with notable risks, including a hyperactive immune response known as CRS and neurological toxicity dubbed ICANS.

When CAR-T therapies were new, physicians and the hospitals they worked at faced a learning curve handling these treatment-associated conditions, which require specific management and drugs to bring under control.

The REMS imposed by the FDA was designed to help mitigate these risks by requiring hospitals receive special certifications before they could administer treatment, and mandating specialized reporting of side effects to the agency.

“Given the established management guidelines and extensive experience of the medical hematology [and] oncology community in diagnosing and managing the risks of CRS and neurologic toxicities across products in the class of BCMA- and CD19-directed autologous CAR-T cell immunotherapies, FDA has determined that the safe and effective use of CAR-T cell immunotherapies for the indicated population can be assured without a REMS,” the agency said in a statement last June. BCMA and CD19 are the protein targets of the seven approved CAR-T therapies.

Reporting rates for CRS and ICANS have “remained stable,” the FDA added.

Alongside removal of the REMS, the regulator also reduced its requirement that patients remain nearby the facility they received treatment from one month to two weeks. And its limitation on how long patients must wait before they can drive or operate machinery again after treatment is lowered from two months to two weeks.

Removal of the REMS should lower the logistical hurdles patients face in receiving CAR-T treatment as well as the cost of administration, the Alliance for Regenerative Medicine, a trade group, said in a post to LinkedIn.

“We believe the reduction in CAR-T burden for patients and caregivers, enabled by FDA's new monitoring and driving requirements, will drive expansion of the U.S. cell therapy market,” Daina Graybosch, an analyst at Leerink Partners, wrote in note to clients.

In a statement, Bristol Myers, which sells the CAR-T therapies Abecma and Breyanzi, noted that only two in 10 eligible patients receive the treatments “due to the confluence of complex logistical and geographic barriers affecting patients and providers.”

The changes could help expand use of CAR-T from specialized medical institutions, where it’s most commonly given, to community health centers, Bristol Myers said.

Breyanzi, Kymriah and Gilead’s Yescarta and Tecartus are cleared to treat lymphoma, although Kymriah is more commonly used for leukemia, where it is also approved. Abecma and J&J’s Carvykti are used for multiple myeloma.

The most recently OK’d CAR-T treatment, Autolus Therapeutics’ Aucatzyl for lymphoma, was the first to be cleared without an initial REMS program.