Above the noise: CGT developers focus on access to better treatments amid immunology boom

Sometimes a little hype is a good thing.

The dealmaking and investment frenzy in immunology and inflammation (I&I), fueled by a demand for novel treatments to serve a growing patient population, has helped the pharma industry ride out market rough patches, as companies eye a global I&I market poised to more than double by 2032.

It’s enthusiasm well spent for the estimated 50 million people in the U.S. alone who are affected by autoimmune diseases — an umbrella term that, depending on which source you consult, consists of somewhere between 80-150 different chronic conditions characterized by immune cells that attack the host tissues they are supposed to protect.

Autoimmune diseases are universally difficult to diagnose, and accuracy is further complicated by symptoms that vary drastically from one person to another, even within the same disease. While there are affordable treatments — including modern, targeted biologics such as tumor necrosis factor blockers and interleukin inhibitors — prolonged use of immunosuppressive therapies carries risks of potentially serious side effects and drug resistance. The standard course of care largely exists to control flare-ups and manage symptoms to prevent further damage to the body and organs — there is still no cure for any autoimmune disease.

“People look at autoimmune diseases as non-malignant diseases, but in fact, people living with these diseases face a range of progressive, debilitating symptoms that  are lifelong and require chronic immunosuppressive therapy. These diseases profoundly impact quality of life and can lead to life-threatening organ problems and ultimately, death,” says Rosanna Ricafort, vice president, senior global program lead for hematology and cell therapy at Bristol Myers Squibb.

The urgency of this unmet need has not evaded the CGT sector, which has not so quietly executed a ‘strategic pivot’ into autoimmune disease. Facing a saturated market in hematological cancers, developers with B-cell targeting therapies originally designed to detect and kill cancer cells have recognized the potential of these assets to clear the autoreactive B cells that are the problematic hallmark of many autoimmune diseases.

“Think of it as a cache reset on an internet browser,” says John (Bobby) Goulding, MPhil, Ph.D., director of immunology & cell based immunotherapy at Fate Therapeutics. “Not a total replacement of the immune system, but a precision elimination of those autoreactive populations of cells that could potentially never come back.”

In 2022, a now-landmark German research study led by Georg Schett, MD, professor and vice president of research at the Friedrich-Alexander University of Erlangen-Nuremberg, lit the space on fire. In the five-person study, lupus patients who were refractory to multiple immunosuppressive drugs experienced disease remission within three months of treatment with a CD19 CAR-T cell therapy and maintained drug-free remission during an eight-month follow-up.

“That dataset came out and people’s eyes were really opened to the fact that there are a lot of other B-cell driven pathologies that are hugely debilitating or in some cases, even life-threatening. And it became apparent that CD19 targeting CAR-T cells could be very useful in these areas of unmet need,” says Goulding.

When the CGT field pivots, it pivots hard. American Society of Gene & Cell Therapy’s (ASGCT) clinical trials finder is currently tracking just under 100 early- to mid-stage global CGT trials, almost half of which are in lupus indications. An industry report from biotech analysts at William Blair detailed over 30 companies pursuing the development of an engineered cell therapy for the treatment of autoimmune diseases in over a dozen disease areas.

While CGTs could offer a true turning point for the treatment of intractable autoimmune diseases, the shift into broader patient populations could also be a turning point for the CGT field. But even as companies begin to share promising clinical data, the field is acutely aware that it must get beyond the scientific fanfare.

“I can see people are excited, but how are they going to succeed unless that excitement translates to patients receiving and benefiting from treatment?” asks Ali Pashazadeh, MD, founder and CEO of Treehill Partners.

Venturing outside the realm of hematological malignancies, CGT developers must now confront lower risk tolerance and higher patient expectations. Not only must companies prove long-term durability and impeccable safety, but they must contend with a familiar foe — commercial viability.

“CGTs have known weaknesses in manufacturing, scalability, affordability, development timelines and, ultimately, navigating the end market. Moving into the autoimmune disease space, you’re now taking the same hurdles that you have in oncology and transposing that to an incredibly crowded market with significant generic footprint. So it is even more imperative to understand your commercial market very early on,” says Pashazadeh.

As they look to scale to new heights, CGT drug developers are starting with the end in mind, zeroing in on how to make therapies affordable and accessible. From efforts to overhaul manufacturing for existing autologous therapies to explorations of allogeneic platforms and novel therapeutic designs, the CGT field is raising the bar.

Science meets commercial reality

With seven commercialized CAR-T cell therapies on the U.S. market and the first launch now more than seven years in the rearview, the CAR-T modality has established itself as an important tool for fighting hematological malignancies. Since the historic first approval of Novartis’ Kymriah for B-cell precursor acute lymphoblastic leukemia in 2017, more than 30,000 patients with blood cancers have been treated with CAR-T cell therapies. And although the treatment is not without side effects or durability challenges, its use is backed by over a decade of clinical and real-world follow-up data on efficacy and toxicities.

In cancer, CAR-Ts are often used after B-cell targeting monoclonal antibodies (mAbs) have failed. B-cell targeting mAbs are also commonly used in the treatment of autoimmune disease, and, like in cancer, some patients become refractory or relapse following mAb therapy. This is often attributed to incomplete B-cell eradication from tissues in the body.

By targeting the CD19 protein expressed on the surface of B cells, CD19 CAR-Ts have demonstrated the ability to induce deep and complete depletion of cancerous cells. The therapy’s known capacity to achieve this ‘tissue clearance’ of autoreactive B cells has made it an attractive prospect for autoimmune conditions, especially those that are considered B-cell mediated, such as lupus, rheumatoid arthritis, myasthenia gravis and multiple sclerosis. Early data points to the possibility that the therapy’s elimination of autoreactive B cells can restore the patient’s immune system, thus enabling an ‘immune reset.’

“This emerging realization was built over a period of almost a decade of physicians becoming more comfortable — whether that’s controlling any sort of adverse events for these CAR-T cell therapy drugs or just gaining a better understanding of how they work,” says Fate’s Goulding.

But against the backdrop of scientific breakthroughs, the shortcomings of the broad CGT field — chief among them, access — have stolen the spotlight. The manual and patient-specific nature of the manufacturing processes, particularly for autologous CAR-T cell therapies, extends timelines and drives up costs. Currently, the estimated acquisition cost of CAR-T cell products ranges from $373,000 to $475,000 and once associated treatment expenses are factored in, the total price tag can exceed $1 million per patient. These high costs and logistical complexities have meant that, for many patients, treatments are out of reach.

While sky-high costs have challenged the health care system in oncology, CGTs could meet with even greater payer resistance in autoimmune disease treatment. An analysis conducted by data analytics firm MMIT revealed that Medicare and private insurance coverage policies already create significant barriers to access existing autoimmune disease medicines — treatments priced much lower than the theoretical price point for CGTs.

Although no company has yet advanced a CAR-T cell therapy for autoimmune diseases into late-stage clinical trials, demonstrating commercial viability has become as critical as achieving scientific milestones — particularly in a challenging financial climate where smaller biotechs must capture the attention of investors or potential pharma partners.

“Commercial viability is essential, not just for patients but for investor confidence. It’s not just about good science, it’s about good business,” says Miguel Forte, MD, Ph.D., CEO of Kiji Therapeutics and current International Society of Cell and Gene Therapy president. “This will be a litmus test for the field. Investors are watching.”

A manufacturing revamp

The first wave of CAR-T cell therapies was marked by costly scale-up and manufacturing issues — hurdles that drugmakers are now actively working to overcome, particularly as they steer these therapies into the promising but complex terrain of autoimmune disease.

BMS’ first CD19-directed autologous CAR-T cell therapy, Breyanzi, was not exempt from early commercialization growing pains. First approved in the U.S. in 2021 for patients with relapsed or refractory large B-cell lymphoma, the therapy’s approval was extended into second-line treatment the following year, broadening its eligible patient base. While the therapy (since expanded into four types of relapsed/refractory blood cancers) is now a substantial revenue-generator for the company with global sales of $$747 million last year, BMS initially struggled with scale-up and capacity constraints that hindered Breyanzi’s commercial rollout.

To address these challenges, the company began developing its NEX-T manufacturing platform, that, according to Ricafort, “balances speed and robustness with the goal of enhancing  turnaround time, but also maintaining the composition of the cell therapy product so that it matches patients’ needs.”

BMS is now exploring the use of a CD19 NEX-T cell therapy, which incorporates the same CAR construct as Breyanzi and leverages the NEX-T manufacturing platform, in autoimmune diseases, including systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, systemic sclerosis, relapsing and progressive forms of multiple sclerosis and myasthenic gravis. The first clinical trial patient with SLE was treated with CD19 NEX-T in September 2023. Positive safety results and some preliminary efficacy results were shared in 2024.

The new platform reduces the need for ex vivo expansion of CAR-T cells, instead facilitating cell expansion within the patient’s body. It currently takes a median time of 19 days to manufacture Breyanzi in the U.S. BMS is exploring efficiencies in the manufacturing time for CD19 NEX-T, and, according to Ricafort, the NEX-T process allows BMS to use a much lower dose in autoimmune disease trials — about one tenth of the oncology dose — and still see the same cellular kinetics (the way the CAR-T cells behave inside the patient) as Breyanzi.

“The in vivo expansion and the enhanced turnaround time allows for an increased yield and a better drug product composition to optimize outcomes,” says Ricafort.

BMS is not the only multinational pharma company that has added a manufacturing upgrade to a commercialized oncology asset and moved it into autoimmune diseases.

Novartis unveiled its T-Charge platform in late 2021, initially utilizing it for a CD19 CAR-T cell therapy for B-cell lymphoma.The asset, which uses the same CAR construct as Kymriah, was later extended into development for SLE, lupus nephritis, systemic scleroderma, myositis, myasthenia gravis and multiple sclerosis. Like other first-gen CAR-T cell therapies, Kymriah’s commercial rollout had also been slowed by manufacturing issues.

Similar to BMS’ platform, with the T-Charge platform, CAR-T cell expansion occurs primarily in vivo, eliminating the need for an extended culture time outside of the body, which saves time and limits T cell exhaustion. Novartis says the products on the platform will have a higher likelihood of better and more durable responses, improved long-term outcomes and a reduced risk of severe adverse events.

The promise of more streamlined manufacturing offers a more efficient and agile era of CAR-T cell therapy — one better suited for a broader therapeutic future in autoimmune disease.

Taking aim at durability

Despite CAR-T cell therapies’ groundbreaking ability to induce prolonged remission in some patients, there are still subsets of patients who fail to achieve remission or who relapse. Failures are still observed in 15-50% of patients, depending on the type of cancer.

In hematological cancers, tumors can alter or lose the antigens that CAR-T therapies are designed to recognize. In solid tumors, the problem is more pronounced, where tumor cells utilize various mechanisms to obstruct the targeting of tumor cells. This concept, known as antigen escape, is a common cause of tumor relapse during CAR-T cell treatment.

Developing CAR-T cells that target multiple antigens simultaneously can help prevent antigen escape, as cancer cells have a higher probability of retaining at least one target antigen. As several companies explore new CAR constructs aimed at improving cell therapy’s effectiveness in cancer, these efforts have also benefited autoimmune disease treatments.

For example, Gracell Bio is repurposing its clinical-stage CD19/BCMA dual-targeting CAR-T oncology asset in SLE. iCell Gene Therapeutics is developing its CD19/BCMA compound CAR, clinically validated in leukemia, in SLE and multiple sclerosis.

Minneapolis-based Luminary Therapeutics is taking it a step further to overcome the deficiencies of the single-antigen CAR. Using technology licensed from Case Western Reserve University, Luminary is developing a unique ligand-based CAR to tackle non-Hodgkin lymphoma and multiple myeloma by targeting three antigen receptors (BAFF, BCMA and TACI) found on many cancers.

In the autoimmune space, Luminary is betting on this same novel CAR construct, which the company refers to as a BAFF CAR, to remove autoreactive B cells by directly targeting the B-cell activating factor receptors, which would in turn eliminate the cause of inflammation. It is hoped that the clearance of B cells through the use of the engineered BAFF CAR therapy can bring complete remission of autoimmune disease inflammation.

“It’s possible that the CD19 therapies that are out there today will struggle to catch the entire population of the B cells that are causing the problem in many autoimmune diseases,” says Jeff Liter, CEO and founder of Luminary Therapeutics.

“The question remains for autoimmune diseases, will the CD19 perform really well for the first two or three years and then relapse at rates similar to what you get in the oncology space? We’re hypothesizing at Luminary that the BAFF CAR’s complete reset of the entire B-cell compartment could provide a more durable response — and that’s what we’re hoping to see in our clinical evidence as we start to treat patients.”

Scaling to new heights

While the patient-specific nature has been a selling point of CAR-T cell therapy — a personalized therapy where the body’s own T cells are genetically modified to fight cancer — it also has limitations. All seven FDA-approved CAR-T cell therapies are autologous products, which adds considerable logistics to the manufacturing process. The development of allogeneic therapies has been positioned as one path to meeting the impending supply demands of larger markets. These ‘off-the-shelf’ cell therapies could offer a less expensive, more scalable approach, which would expand patient access to treatments.

Since its founding in 2019, Luminary has been driven by the need to make CAR-T cell therapies affordable and accessible. Central to that mission is its work to validate allogeneic platforms as a safe, cost-effective alternative to autologous products.

“Autologous CAR-T therapies to date only reach 20% to those patients who could benefit from them. If you consider autoimmune’s larger market size, that one-to-one manufacturing won’t scale. Allogeneic is for sure required to approach the autoimmune space,” says Liter.

Although inconsistent data makes the autoimmune disease market difficult to quantify, William Blair analysts estimate that approximately 200,000 patients in the U.S. could be initially eligible for CAR-T therapies targeting B cell–mediated autoimmune diseases (seven indications with established clinical precedent), assuming use is limited at first to those with severe or highly refractory disease.

Luminary’s allogeneic approach is based on a type of white blood cell known as gamma delta T cells. While the more commonly used CAR-T construct relies on alpha beta cells, gamma delta cells have the advantage of naturally migrating to tissues, which is important in autoimmune diseases where patients experience organ damage, potentially providing better clearance of B cells in organ tissues.

Leveraging its proprietary platform, Gamma 2.0+, Luminary has developed two therapeutic programs, one in solid tumors and one in autoimmune disease, specifically, lupus. The company is also utilizing a non-viral gene editing system to manufacture its CAR-T cells, which speeds manufacturing time and cuts costs.

“We’re able to produce about 450 patient doses from a healthy donor. We can make a product for under $10,000 that can be frozen and available in any hospital in the world,” says Liter.

San Diego-based Fate Therapeutics is also developing off-the-shelf treatments. The company’s CAR-T cell product candidates are created from clonal master engineered induced pluripotent stem cell (iPSC) lines, rather than the repeatedly-sourced donor cells used in more traditional allogeneic treatments. Similar to how master cell lines are used to mass produce monoclonal antibody drugs, clonal master iPSC lines are used as a starting cell source to manufacture engineered cell products.

“One massive advantage of our platform is that because we can direct master iPSC cells to create immune system cells, it’s hugely scalable and cost effective,” says Fate’s Goulding. “Because iPSCs can be genetically engineered and indefinitely expanded in culture, we can generate a potentially unlimited supply of cells.”

Fate forayed into the autoimmune space in 2023, pivoting its iPSC-derived CD19 CAR-T product candidate (FT819) from lymphoma into moderate to severe SLE, with plans to expand clinical development into ANCA associated vasculitis, idiopathic inflammatory myositis and systemic sclerosis.

Safety remains a key concern in the development of allogeneic treatments — particularly the risk that donor-derived stem cells could view the recipient’s cells as a threat and attack them, resulting in graft-versus-host disease (GvHD). However, emerging clinical data from the oncology field is beginning to ease those fears.

Fate believes that its iPSC platform — which allows the company to completely delete the T-cell receptor expression to eliminate the potential of GvHD — could give the platform an additional leg up in safety. Interim clinical data from a phase 1 study of Fate’s allogeneic asset in relapsed/refractory B-cell malignancies indicated a favorable safety profile, with no events of any grade of immune effector cell-associated neurotoxicity or GvHD and low incidence of low-grade cytokine release syndrome.

Allogeneic therapies also could ease the burden of bringing CAR-T cell therapies to the busy rheumatology setting, allowing for therapy that is readily available for immediate use and administered without the need for leukapheresis to collect patient cells or bridging therapies to manage disease during a lengthy manufacturing process.

“This is where the different risk profile comes in, which is you have to not only produce a highly safe and effective product, but you have to provide a patient experience or therapeutic workflow that is minimally disruptive and maximizes patient access,” says Goulding. “At Fate, we’re walking towards that with regards to minimizing hospitalization stays, providing a cost-effective medicine, reducing the amount of conditioning patients require, and having the medicine available on-demand for immediate treatment. Our vision is to have this in a community hospital setting where you don’t have to go to a distant specialty hospital to receive the treatment.”

Navigating the noise

CGT developers are not the only companies getting in on the I&I action. 

Across the broad biopharma space, momentum from 2023 carried into 2024 with a series of high-value deals. In April 2024, Vertex bought immunotherapy company Alpine Immune Sciences for $4.9 billion in a cash deal that centered around Alpine’s lead asset, a dual BAFF/APRIL antagonist that has shown potential best-in-class efficacy in IgA nephropathy. A month later, Biogen agreed to pay up to $1.2 billion to acquire HI-Bio, bolstering its pipeline with the company’s investigational anti-CD38 mAb with best-in-class potential across a range of immune-mediated diseases. In July 2024, Eli Lilly announced a $3.2 billion all-cash deal to buy Morphic Holding, building up its autoimmune disease portfolio with Morphic’s investigational oral integrin therapies. Most recently, Sanofi inked a potential $1.8 billion deal with Earendil Labs for the rights to a pair of bispecific antibodies targeting ulcerative colitis, Crohn’s disease and skin inflammation.

For the CGT sector, the surge of companies pursuing autoimmune disease treatments and renewed clinical momentum have been a bright spot amid an uncertain investment climate — but many market analysts caution that a real-world reckoning still lies ahead.

“I&I could be another ticking time bomb of just too much over investment, too much crowding into one space,” says Carl Schoellhammer, associate partner at market intelligence and strategy firm DeciBio Consulting, where he leads the advanced therapies practice.

According to Schoellhammer, for CGT developers, navigating this crowded space means “companies will have to be smart and focused from an indication standpoint.” He compares the current trajectory of cell therapies to the past flux of adeno-associated virus (AAV) gene therapies.

“The AAV space experienced gold rush pandemic years and lots of over investment. It then went through tremendous pullback and culling of pipelines. And then it came out the other end with a more logical, more streamlined portfolio of products,” says Schoellhammer.

Pashazadeh, who spent over a decade in health care investment banking prior to founding TreeHill in 2014, backs this idea of highly focused drug development. “A significant amount of effort needs to be spent deciding what indication, and within that indication, what subpopulation of patients you’re going for. And unless companies do that, they may be developing a great therapy, but that great therapy is going to then be competing against incumbents.”

Already, certain indications have seen immense crowding in the clinic. A William Blair industry report tracked just over 30 CGT companies pursuing development in autoimmune diseases, with 15 of them developing treatments for SLE and its more severe manifestation, lupus nephritis.

The initial rush into SLE isn’t surprising. As a prototypical autoimmune disease, SLE can affect any organ or tissue, which means research on the condition can often translate into better understanding of other autoimmune diseases. The Lupus Foundation of America estimates that up to 1.5 million Americans have some form of lupus; about 40-65% of that population has lupus nephritis, which has a higher mortality risk and can result in end-stage renal disease.

“If you can get on top of lupus, once you’ve generated data, you can then cross read to other indications as well,” says Pashazadeh.

Ultimately, the competition is challenging the industry to rethink its more traditional drug development model and put early consideration into the end market. “Instead of the historic sequential way of, ‘let me generate some data, then figure out the right indication, then figure out the manufacturing and how to commercialize it,’ you need the drug development team, commercialization team, and manufacturing team to all be there right at the beginning and all the way along,” says Pashazadeh.

A big piece of the commercialization puzzle is outlining how the therapies will be administered. According to BMS, one of the anticipated challenges in the autoimmune space is that cell therapies are brand new modalities for the rheumatologists, immunologists and neurologists who will have to educate and select patients.

“At BMS, we are not a stranger in pioneering new technologies, and we hope to introduce CAR-T cell therapies for patients with autoimmune and neuroinflammatory diseases,” says Ricafort. “But we know that we can’t do that alone.”

To that end, BMS began building a cross-disciplinary collaboration, officially unveiling the Autoimmunity Cell Therapy Network (ACTioN) to the external community in 2024. ACTioN’s ‘clinical excellence’ pillar focuses on facilitating knowledge exchange across the various multidisciplinary medical care teams who collaborate to treat patients with autoimmune and neuroinflammatory diseases. The consortium aims to bring these clinicians together with global scientific experts and patient advocates to accelerate the development and delivery of cell therapies.

“It’s been wonderful to see all these leaders coming together and I think it really makes us poised to propel the field forward. And hopefully it won’t be too long before we can deliver on that promise,” says Ricafort.

The industry may start seeing answers soon. Companies will likely be positioned to share meaningful trial readouts in the next one to two years. “Once it plays out with the clinical data, then it comes down to cost, availability and patient experience,” says Goulding.

“When those first commercial products finally get out there and you see three to four years’ worth of data as to what the durability and remission rates are, that’s going to be a major inflection point,” says Luminary’s Liter.

That long-awaited moment could redefine not only the treatment landscape for autoimmune diseases, but the trajectory of the entire CGT field — transforming scientific vigor into life-changing therapies for a much broader patient population.

“There’s always this element of hype and everyone, including myself, that has spent time and emotion developing these products, want it to work. But at the end of the day, this is about the patients,” says Goulding. “Knowing that I helped tens of thousands of people either be cured of a disease or have their quality of life massively improved, that would be an amazing outcome for anybody in their career.” 

References

Immunology Market Size, Share & Industry Analysis, By Drug Class. (2025, April). Fortune Business Insights.

Autoimmune Association. What is autoimmunity? [accessed April 23, 2025]

Mackensen, A., et. al. (2022). Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 28, 2124–2132.

ASGCT clinical trials finder. American Society of Gene & Cell Therapy. [accessed April 11, 2025]

The Hammer Finds a Bigger Nail: Cell Therapy for Autoimmune Disorders. (2023, Nov. 29) CELLect Horizons. William Blair. [industry report]

No evidence that CAR T cell therapy causes secondary cancers, Penn study finds. (2025, Feb). Penn Medicine News.

Cappell, K., et. al. (2023). Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol 20, 359–371.

Barnas, J., et. al. (2019). B cell targeted therapies in autoimmune disease. Current opinion in immunology, 61, 92–99.

Rampotas, A., et. al. (2025). CAR-T cell therapy embarks on autoimmune disease. Bone Marrow Transplant 60, 6–9.

The Economics of CAR T-Cell Therapy. (2024). Association of Cancer Care Centers.

Health Insurance Access Barriers: A National Scorecard. (2023, Jan). Let My Doctors Decide.

Bristol Myers Squibb Reports Fourth Quarter and Full-Year Financial Results for 2024. (2025, February). BMS. [Press release]

Stanton, D. (2022, Sept). BMS confident Breyanzi capacity issues will be resolved in 2023. Bioprocess International.

Vinluan, F. (2022, May). BMS shows what’s NEX-T for CAR T, plus its strategy for next-gen cancer cell therapy. Med City News.

Novartis announces T-Charge, next-generation CAR-T platform with first-in-human data at ASH 2021. (2021, Dec). Novartis. [Press release]

Pagliarulo, N. (2018, Dec). In CAR-T, manufacturing a hurdle Novartis has yet to clear. Biopharma Dive.

Baguet, C., et. al. (2024). Early predictive factors of failure in autologous CAR T-cell manufacturing and/or efficacy in hematologic malignancies. Blood Adv 8, 337–342.

Lin, H., et. al. Antigen escape in CAR-T cell therapy: Mechanisms and overcoming strategies. (2024). Biomed Pharmacother 178,117252.

Fate Therapeutics Announces Clinical Safety and Activity Data of First-ever iPSC-derived CAR T-cell Therapy at 2022 ASH Annual Meeting. (2022, Dec). Fate Therapeutics. [press release]