Kyverna therapeutics is trying to use data to prove that there are still companies on this road when the self free car-t track repeatedly presses the brakes due to safety problems.

On September 24, kyverna therapeutics released long-term clinical data of its self immune car-t cell drug mivocabtagene autoleucel (MIV cel, R & D Code: kyv-101), showing the sustained efficacy and positive safety of MIV cel, further supporting the potential regulatory approval of MIV cel.

MIV cel is the world's first self exempt car-t to submit a listing application. If it is successfully listed, it will not only open a new growth space for kyverna, but also expand the commercial landscape of car-t therapy from tumor to autoimmunity, which is a milestone for the whole cell therapy industry.

01. Consolidate the registration evidence of long-term efficacy

MIV cel is an autologous CD19 car-t cell therapy, and is one of the first self immune car-t products to enter the clinic. In November 2022, MIV cel received the first FDA approval of ind for lupus nephritis.
In May 2026, kyverna has officially started to submit the biologics license application of MIV cel to FDA in a rolling manner for the treatment of stiff person syndrome (SPS) - this is the first free car-t to submit a marketing application.
SPS is a rare, progressive and extremely disabling neuroautoimmune disease. Patients will eventually lose their mobility due to progressive stiffness and painful spasms of the whole body muscles, with a probability of up to 80%. There are only about 1-2 cases of this rare disease per million people. Currently, there is no FDA approved therapy. Patients can only rely on off label treatment with limited efficacy and heavy side effects.

Although the total market volume is small, the competition in the field of SPS treatment is far less than that of other indications, and because of its rapid progress, it can obtain clinical research results faster.

Previously, kyverna has reached an agreement with the FDA that the phase II trial kysa-8 will be a kyv-101 registration study for SPS, and its primary endpoint is the 25 foot walk (t25fw) test.

According to the data released by kyverna in December last year, among the 26 patients, the MIV cel reached the primary endpoint of the trial, that is, the timed 25 foot walk test (t25fw) at week 16 improved by 46% compared with the baseline. Of these, 81% achieved "clinically meaningful" improvement, defined as a reduction of at least 20% from baseline.

In April this year, a detailed analysis released at the AAN annual meeting showed that among the 12 patients who needed walking aids at baseline, 8 (67%) no longer needed AIDS at week 16. At the last follow-up, all 26 patients in the kysa-8 trial had discontinued all immunomodulatory or immunosuppressant treatments for SPS.

In terms of secondary endpoints, MIV cel achieved significant improvements in a number of indicators measuring disability, mobility, muscle stiffness, spasticity sensitivity, etc.

Despite the breakthrough evidence, it is still an open question how long the efficacy of MIV cel can last - this is particularly important because car-t therapy usually only needs to be administered once.

With the release of the top line data of kysa-8 trial in September, the long-term efficacy of MIV cel has been strengthened.

As of July 2026, when the database was locked, the median t25fw test time of patients improved by 49% from baseline, while it was 46% at week 16

(the change from baseline in the 12th month was statistically significant [p<0.0001]). Among patients who achieved clinically meaningful improvement (more than 20% reduction from baseline in test time) at the time of the primary analysis, 95% of patients still maintained this improvement at month 12.

In addition, among the 12 patients who needed walking aids before treatment, 67% could still walk without walking aids during follow-up; 92% of patients did not need to receive long-term immunotherapy for SPS in the 12th month.

Kyverna plans to incorporate the 1-year data of kysa-8 study into the rolling biologics licensing application (BLA) for the treatment of SPS with MIV cel, which is expected to be submitted in the fourth quarter of 2026. The company is seeking priority review.

William Blair said in his report to investors that the one-year results of MIV cel in SPs were "strong", and added that these results further reduced the risk submitted by BLA and enhanced the commercial value of the therapy.

Warner Biddle, CEO of kyverna, said, "these one-year SPS data further strengthen our ongoing rolling BLA submission, which is expected to be completed in the fourth quarter. The differentiated construction design and mature production process of MIV cel support these longer-term results and highlight the opportunity to provide a one-time transformative therapy for people with severe neuroimmune diseases. ”The

Kyverna's updated long-term follow-up data will further support the regulatory approval of MIV cel. Perhaps the first self exempt car-t product with regulatory approval will appear in the near future.

02. Wider application boundaries

In the announcement on the same day, kyverna also released the positive long-term data of the phase 2 part of the registered phase ii/iii kysa-6 trial in generalized myasthenia gravis (GMG).

In phase II of kysa-6 study, a total of 7 moderate to severe patients who failed previous immunosuppressive therapy were included. The results showed that at week 24, all 7 patients achieved clinically significant improvements in the MG-ADL and QMG scores, which were 8.3 and 11.7 points lower than the baseline.

In the 5 patients who had been followed up for 1 year or more, the above clinical improvements were maintained. Up to the last follow-up, 57% of patients maintained the minimum symptom performance status (MSE), that is, the MG-ADL score was 0 or 1; Six of the 7 patients still did not need immunosuppressive therapy.

In terms of safety, in the long-term follow-up of SPS and GMG, MIV cel was generally well tolerated, and no high-grade cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (icans) or immune effector cell associated hemophagocytic lymphohistiocytosis like syndrome (iec-hs) were reported.

This safety result is particularly important in the context of the safety setbacks of the current self free car-t track.

Previously, Novartis reported that three patients who received car-t therapy rap cel died after the occurrence of "severe immune effector cell associated hemophagocytic syndrome (iec-hs)" event. Novartis subsequently suspended multiple immunological and neurological studies of this candidate drug.

BMS also followed suit, voluntarily freezing its car-t asset zolacabtagene autoleucel's autoimmune test after observing a "transient and reversible inflammatory event".

Peers have stepped on the brakes due to safety problems, making the immunotoxicity risk of self immunized car-t become the focus of regulatory and clinical attention. The

In contrast to the above safety signals, MIV cel did not show iec-hs, high-level CRS or icans in the long-term follow-up of SPS and GMG, suggesting that its safety characteristics may become a differential advantage, and also provide important support for its rolling BLA submission and broader indications.

Warner Biddle, CEO of kyverna, said in an interview with Biospace: "I think both sets of data strengthen kyverna's leading position in bringing these transformative cell therapies to patients with autoimmune diseases. ”The
He said: "in both cases, we showed the continuation of the clinical benefits read out earlier this year... At that time, we showed significant clinical improvement in patients. Now through these longer-term follow-up, for one year or more, we show that this can produce lasting effects in patients and give patients the opportunity to achieve disease-free remission, which is exactly what they want in the end."

At present, kyv-101 is being evaluated in a variety of autoimmune diseases mediated by B cells.

In addition to SPS and GMG, MIV cel also obtained preliminary positive data in the investigator initiated phase I trial of progressive multiple sclerosis (PMS).

In two studies conducted by Stanford University and UCSF, patients treated with MIV cel showed stable or improved EDSS scores, significant relief of fatigue symptoms, and did not report high-grade CRS or icans. Mechanistic studies revealed that car-t cells can effectively penetrate the central nervous system and clear oligoclonal bands in CSF, suggesting the possibility of "immune reset".

Based on the above phase I data, in August 2026, FDA granted MIV cel advanced regenerative medicine therapy (rmat) for the treatment of inactive progressive multiple sclerosis (naspms). Rmat determined that it would provide kyverna with closer interaction with FDA and qualifications for priority review and rolling review. The company plans to share the PMS development strategy in early 2027.

03. Auto free car-t for beach scramble in different paths

At the same time when MIV cel announced its long-term efficacy and safety data, adicet bio, another biotechnology company, was exploring a different self immune car-t path -- spot type (allogeneic universal) γδ car-t therapy prula cel, and achieved early positive signals in lupus treatment.

On September 28, adicet bio reported that its spot cell therapy, prula cel, had alleviated lupus in more than half of patients in a small phase I trial without dangerous side effects. One year after treatment, 12 of the 22 evaluable patients achieved remission of lupus symptoms; Eight of the 16 lupus nephritis patients had relief of renal symptoms.

In terms of safety, adicet reported no cases of immune effector cell associated hemophagocytic lymphohistiocytosis like syndrome (iec-hs), no cases of immune effector cell associated neurotoxicity syndrome (icans), and almost all cases of cytokine release syndrome (CRS) were grade 1.

The differential design of prula cel lies in its cell source and subtype. Unlike autologous car-t such as MIV cel, prula cel is derived from donor cells and is an "allogeneic" off the shelf therapy with faster production and lower cost; The "γδ" T cells on which it is built are also different from the "αβ" T cells used by Novartis, Bristol Myers Squibb and many other companies.

Chen Schor, CEO of adicet, explained to fierce that γδ T cells naturally exist in human tissues, rather than circulating in the blood, "which makes them likely to be very beneficial for autoimmune diseases, because in the final analysis, the disease occurs in organs."

In addition, prula cel targets CD20 expressed on B cells, which are immune cells that produce abnormal antibodies in autoimmune diseases such as lupus. Adicet is seeing early signs that the therapy successfully resets the patient's immune system. The newly generated B cells are initial B cells and show no signs of pathogenicity.

Although the results came from a small early trial, the data also showed the efficacy of "competitive compared with cell therapy and antibody comparable products". Dennis Ding, an analyst at Jeffery, believes that these data are "impressive" and may encourage pharmaceutical companies to "start turning to more elegant solutions, such as γδ T cells, to treat immune diseases".

Adicet plans to further develop prula cel as a one-time treatment for lupus. Schor said that the FDA has approved a single arm pivotal trial for lupus nephritis, which should start next year and may be expanded to include lupus patients without kidney disease. The company also plans to discuss with regulators the possibility of expanding key research on patients without lupus nephritis.

In addition to autologous and spot car-t, in vivo car-t also shows therapeutic potential in autoimmune indications.

At the beginning of September, the New England Journal of Medicine (NEJM) communication column published the research carried out by the team of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology in cooperation with Shenzhen Jiyin Biotechnology Co., Ltd. that the lentiviral vector based in vivo CD19 car-t cell therapy (jy231) was used for refractory nervous system autoimmune diseases - this is also the first time to verify the feasibility of the in vivo car-t pathway in neuroimmune diseases.

Sixteen adult patients with refractory neurological autoimmune diseases were included in the study. All patients had car T cell expansion in vivo and achieved rapid and complete B cell clearance; At a median follow-up of 6 months, clinical and biological improvement signals were observed in all disease cohorts.

It can be predicted that the next few years will be a critical window period for the free car-t to move from "proof of concept" to "clinical landing".

Whether kyverna's autologous car-t, adicet's spot γδ car-t, or in vivo car-t, the ultimate competition is not only the advantages and disadvantages of the technical route, but also who can take the lead to produce enough long-term, safe, and large-scale data, so that "one-time treatment, no drug relief" from the vision into a reality accessible to patients.

For patients with autoimmune diseases who need immunosuppression and hormone therapy for a long time, the significance of this race is far more than the approval of a new drug - it is expected to promote the fundamental rewriting of the treatment paradigm.

References:
1.Kyverna Therapeutics Reports Positive One-Year Data Demonstrating Durable Clinical Responses and Favorable Safety Profile for Miv-cel in Stiff Person Syndrome and Generalized Myasthenia Gravis
2.Biospace，Kyverna steps closer to FDA-first CAR T for an autoimmune condition with durability data
3.BiopharmaDive，An ‘off-the-shelf’ CAR-T therapy from Adicet shows promise against lupus
4.FierceBiotech，Adicet Bio CAR-T sparks lupus remissions in early trial as ‘new era’ of autoimmune treatment approaches
5. same freehand brushwork, free car-t, go to the night before cash
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7. talk with freehand brushwork and tanaishi: car-t in lentivirus has broken into neuroimmune disease for the first time