TG Therapeutics Reports Initial Clinical Results for Azer-Cel CAR T-Cell Therapy in Progressive Multiple Sclerosis
TG Therapeutics, Inc. has announced initial clinical results from its ongoing Phase 1 study evaluating azercabtagene zapreleucel (azer-cel), an investigational allogeneic CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with progressive multiple sclerosis (MS). The findings represent the first reported clinical evaluation of an allogeneic CD19-directed CAR T-cell therapy in this patient population and provide early evidence of biological activity, an encouraging safety profile and potential improvements in disability measures.
The results were presented in a late-breaking oral session at MSToronto 2026, the 10th Joint Meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS), held October 21–23, 2026, in Toronto, Canada. The presentation, titled “First Clinical Evaluation of an Allogeneic CD19-Directed CAR T-Cell Therapy in Progressive Multiple Sclerosis: Initial Results from the Phase 1 TG-Azercel-101 Study,” describes findings from 26 participants treated across six dose levels.
The early data are notable because all participants had experienced progression independent of relapse activity (PIRA) within the 12 months before enrollment despite receiving high-efficacy disease-modifying therapies. Every participant had also previously received anti-CD20 treatment, indicating that the study population had substantial ongoing disease burden despite prior therapeutic intervention.
According to TG Therapeutics, most evaluable participants experienced stable or improved disability scores during follow-up. Investigators also observed depletion of B cells in peripheral blood and reductions in CD19-positive B-cell events in cerebrospinal fluid (CSF). These findings support further investigation of azer-cel as a potential treatment approach for progressive MS, a disease setting in which options capable of preventing or reversing disability remain limited.
The company emphasized that the results are preliminary. The study remains ongoing, participant numbers are small, and follow-up varies considerably. Further dose escalation and longer-term monitoring will be required to establish the durability of the observed effects and better characterize the treatment’s safety and clinical benefit.
Phase 1 study evaluates an off-the-shelf CAR T-cell approach
The TG-Azercel-101 study is an open-label Phase 1 clinical trial designed to evaluate azer-cel in patients with progressive multiple sclerosis. The therapy is an investigational allogeneic CAR T-cell product directed against CD19, a protein expressed on B cells that play important roles in immune system activity.
Unlike autologous CAR T-cell therapies, which are manufactured using cells collected from the individual patient receiving treatment, allogeneic CAR T-cell therapies are developed using donor-derived cells. This approach may allow a product to be manufactured in advance and made available for treatment without the need to produce a customized cellular therapy for every patient. Such an approach is often described as an off-the-shelf treatment strategy.
Azer-cel is being investigated for its ability to target CD19-positive B cells and potentially modify immune mechanisms involved in multiple sclerosis. B cells can contribute to MS through antibody production, antigen presentation and interactions with other immune cells. Therapies that target B cells are already part of the treatment landscape for certain forms of MS, but some patients continue to experience disability progression despite high-efficacy treatment.
CAR T-cell therapy offers a different strategy by engineering T cells to recognize and eliminate cells expressing a specific target. In autoimmune diseases, researchers are investigating whether this approach could produce a deeper or more sustained alteration of disease-associated immune cell populations than conventional treatments.
In the TG-Azercel-101 study, participants received azer-cel at one of six dose levels ranging from 30 million to 500 million CAR T cells. Treatment was preceded by bendamustine lymphodepletion, a preparatory regimen intended to reduce existing immune cells and support the activity and expansion of the administered CAR T cells.
The study enrolled 26 participants with progressive MS. All had experienced PIRA during the preceding 12 months despite treatment with high-efficacy disease-modifying therapies, and all had previously received anti-CD20 therapy.
The median baseline Expanded Disability Status Scale (EDSS) score was 6.0, reflecting substantial disability. At this level, patients commonly require assistance to walk relatively short distances, although individual functional abilities vary.
As of the September 3, 2026, data cutoff, median follow-up was 4.9 months, with a range of 0.1 to 15.0 months. The variation in follow-up is important when interpreting the findings because not every participant had reached the same assessment milestones.
Initial safety findings show no dose-limiting toxicities
Safety was a central focus of the early-stage study. TG Therapeutics reported an encouraging initial safety profile across the six evaluated dose levels, with no dose-limiting toxicities observed.
The company also reported no Grade 3 or higher cytokine release syndrome (CRS), no Grade 2 or higher immune effector cell-associated neurotoxicity syndrome (ICANS), no graft-versus-host disease, no immune effector cell-associated hemophagocytic syndrome (IEC-HS), and no Grade 3 or higher infections.
These findings are relevant because CAR T-cell therapies can produce inflammatory and immune-mediated complications. CRS can occur when activated immune cells release inflammatory signaling molecules, while ICANS refers to neurological toxicities associated with immune effector cell treatments. The severity of these events can vary, making close monitoring and prompt clinical management important elements of CAR T-cell therapy.
The absence of the specified high-grade events in this initial cohort provides an early safety signal that may support continued investigation of azer-cel. However, the findings do not establish that the therapy is free of serious risks. A study involving 26 participants may not detect uncommon adverse events, and longer follow-up is needed to assess both acute and delayed complications.
The treatment also involves lymphodepletion with bendamustine before CAR T-cell infusion. Consequently, the overall safety assessment must consider the complete treatment process, including the preparatory regimen and the subsequent effects of the cellular therapy.
As dose escalation continues, researchers will need to evaluate whether safety outcomes remain consistent at higher dose levels and whether any differences emerge according to dose, patient characteristics or duration of follow-up.
Disability scores remained stable or improved in most evaluable participants
The study’s initial efficacy findings focused on disability measures, walking performance, upper extremity function, cognitive processing speed and MRI assessments.
Despite documented disease progression before enrollment, 16 of 18 evaluable participants, or 89%, had stable or improved EDSS scores at Day 90. At Day 180, seven of eight evaluable participants, or 88%, maintained stable or improved scores.
The EDSS is a widely used clinical scale for measuring disability in multiple sclerosis. It incorporates neurological examination findings and places considerable emphasis on walking ability at higher levels of disability. Stability or improvement on the scale may be meaningful in progressive MS, where patients can experience gradual functional decline even when conventional measures of inflammatory disease activity show limited change.
Three participants achieved EDSS improvements of at least 2.0 points at Day 90. One participant experienced a 4.0-point improvement, according to the company.
Changes of this magnitude may represent substantial differences in measured disability. Nevertheless, the results should be interpreted cautiously because they come from a small, uncontrolled study. Additional research is necessary to determine whether the improvements are sustained, how they relate to everyday function and whether they can be attributed to azer-cel rather than other factors.
The findings are particularly relevant because all participants had experienced progression despite previous high-efficacy treatment, including anti-CD20 therapy. The observed stability or improvement raises the possibility that azer-cel could have clinical activity in patients whose disease continues to worsen despite existing treatment approaches.
However, the study was not designed to establish comparative effectiveness against approved therapies. The absence of a control group also limits the ability to distinguish treatment effects from variability in disability measurements or the natural course of disease.
Walking, upper extremity function and cognition show encouraging signals
Additional assessments at Day 90 indicated that most evaluable participants maintained or improved performance across several functional domains.
Walking performance was stable or improved in 16 of 17 evaluable participants, representing 94%. Upper extremity function was stable or improved in 17 of 18 participants, also representing 94%. Cognitive processing speed was stable or improved in 14 of 18 evaluable participants, or 78%.
These findings provide a broader view of participants’ clinical status beyond EDSS scores alone. Walking ability is particularly important for people with progressive MS because worsening mobility can affect independence, daily activities and quality of life. Upper extremity function can influence the ability to perform tasks such as dressing, eating and handling objects, while cognitive processing speed can affect information processing and everyday functioning.
The high proportions of participants with stable or improved walking and upper extremity function are therefore encouraging early observations. The cognitive findings also suggest that many participants maintained or improved their performance on the reported measure during the assessment period.
Nonetheless, the results do not establish that azer-cel reverses disability across the broader progressive MS population. The denominators are small, and the study’s open-label design means that the findings need confirmation in larger studies with longer follow-up and appropriately defined outcome measures.
MRI findings show no new or enlarging lesions in evaluable participants
MRI assessments provided another measure of disease activity. Among the 22 participants evaluable by MRI, investigators observed no gadolinium-enhancing T1 lesions and no new or enlarging T2 lesions.
Gadolinium-enhancing T1 lesions can indicate areas of active inflammation and disruption of the blood-brain barrier. New or enlarging T2 lesions can reflect the development or expansion of areas of tissue abnormality associated with MS.
The absence of these findings among the evaluable participants suggests that there was no detected new MRI lesion activity during the reported assessment period. This may complement the disability stability observed in many participants.
However, MRI findings require careful interpretation in progressive MS. Disability progression can occur independently of overt relapses and without new inflammatory lesions visible on routine MRI. Therefore, the absence of new lesions does not by itself demonstrate that progression has stopped or that neurological damage has been reversed.
Longer-term imaging and clinical assessments will be needed to determine whether the early MRI observations persist and how they correspond with disability, walking ability and other measures of neurological function.
B-cell depletion observed in blood and cerebrospinal fluid
The study also evaluated the biological effects of azer-cel by measuring B-cell populations in peripheral blood and cerebrospinal fluid.
Peripheral blood B-cell counts fell to below 10 cells per microliter in 25 of the 26 participants, or 96%. This indicates that substantial B-cell depletion was achieved in nearly the entire study population.
Investigators also examined CSF samples from 21 participants. At Day 10, the median reduction in CD19-positive B-cell events was 52.3%.
The CSF findings are of particular interest because multiple sclerosis affects the central nervous system, and immune activity within the central nervous system may differ from activity measured in peripheral blood. A reduction in CD19-positive B-cell events in CSF suggests that the treatment’s biological effects were not limited to circulating blood cells.
However, the reported reduction in CSF B-cell events should not be interpreted as complete depletion of B cells throughout the central nervous system. The result represents a median change in the measured events among the sampled participants, and additional work is needed to characterize the depth, duration and clinical significance of the effect.
B-cell reconstitution was observed as early as Day 42, with returning B-cell populations favoring transitional and naïve cells. This pattern may be relevant to understanding how the immune system recovers after treatment.
The timing and composition of B-cell reconstitution could help researchers assess whether the treatment produces a sustained change in immune cell populations and whether those changes correlate with clinical outcomes. Further analyses will be required to determine whether the observed reconstitution pattern is associated with longer-term disease stability or changes in disability.
TG Therapeutics highlights potential in a population with substantial unmet need
Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics, said the initial findings were encouraging because all participants entered the study with progressive disability despite previous treatment with high-efficacy therapies, including anti-CD20 treatment.
He highlighted the safety findings, evidence of B-cell depletion in both blood and CSF, and stable or improved disability scores in most evaluable participants as early signs of biological and potential clinical activity.
Weiss also emphasized the disability improvements observed in five of the 18 evaluable patients, including three participants who achieved improvements of two or more points on the EDSS scale. One participant experienced a 4.0-point improvement.
He noted that even slowing progression can represent an important therapeutic advance in a disease where disability may accumulate over time.
Weiss added that an off-the-shelf CAR T-cell therapy could potentially provide a new treatment option for patients with progressive MS, while acknowledging that the findings remain preliminary. The company plans to continue dose escalation and evaluate longer-term outcomes.
His comments reflect TG Therapeutics’ interest in exploring CAR T-cell technology for autoimmune diseases, where deeper immune modulation could potentially address mechanisms that are not adequately controlled by current therapies.
Further studies will determine the significance of the findings
The initial TG-Azercel-101 results provide early evidence that azer-cel can produce substantial peripheral B-cell depletion, reduce CD19-positive B-cell events in CSF and achieve stable or improved disability measures in many evaluable participants with progressive MS.
The absence of the specified high-grade CAR T-associated toxicities in the initial 26-participant cohort is also an encouraging preliminary safety observation. At the same time, the limited sample size and variable follow-up mean that uncommon adverse events and longer-term risks cannot yet be ruled out.
The clinical findings also need to be confirmed in additional participants. The EDSS improvements, functional stability and MRI observations are based on small evaluable groups, and the study does not include a control arm that would allow investigators to establish comparative efficacy.
Future research will need to determine the most appropriate dose, the durability of B-cell depletion, the pattern of immune reconstitution and the relationship between these biological effects and longer-term disability outcomes. Researchers will also need to assess whether the observed changes translate into meaningful and sustained benefits for patients’ mobility, independence and quality of life.
For progressive MS, where patients may continue to accumulate disability despite high-efficacy treatment, new approaches that can alter disease-associated immune activity remain an important research priority. The potential convenience of an allogeneic, off-the-shelf cellular therapy may also be relevant if future trials establish a favorable benefit-risk profile.
TG Therapeutics said dose escalation and longer-term follow-up are ongoing. The full presentation is available through the Publications page of the company’s website at TG Therapeutics Publications.
Overall, the first reported clinical evaluation of an allogeneic CD19-directed CAR T-cell therapy in progressive MS represents an early step in investigating cellular immunotherapy for this challenging disease. Azer-cel has demonstrated biological activity and preliminary signals of disability stability or improvement, but larger studies and longer observation will be necessary to determine whether these findings translate into a safe, durable and clinically meaningful treatment option.
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