Targeting Myasthenia Gravis at the Source: Promising Progress of CAR-T Agent KYV-101

The emergence of cell-based therapies in neuroimmunology continues to reshape the treatment landscape for generalized myasthenia gravis, particularly as researchers explore strategies that target the disease at its immunologic source. At the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, held October 29 to November 1, in San Francisco, California, Kyverna Therapeutics presented early but compelling Phase 2 data from the registrational KYSA-6 trial (NCT06193889) evaluating KYV-101, an investigational autologous CAR T-cell therapy designed to achieve deep, tissue-level B-cell depletion.

All told, the interim results showed rapid and clinically meaningful improvements across Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG), and MGC scores in all treated patients, with several reaching minimal symptom expression within months of a single infusion. These findings build on previous compassionate-use observations and signal the potential for a new therapeutic class capable of delivering durable clinical benefit without chronic immunosuppression.

In this conversation with NeurologyLive^®, Naji Gehchan, MD, MSc, chief medical and development officer at Kyverna Therapeutics, discussed the significance of these Phase 2 findings, the mechanistic rationale behind KYV-101, and the path toward the upcoming Phase 3 portion of the KYSA-6 trial. Gehchan also provides high-level insights on study design considerations, clinical expectations for CAR T use in gMG, and how a therapy capable of inducing an immune reset may ultimately redefine treatment goals for this disease.

NeurologyLive: For our clinical audience, can you provide an overview of the most notable takeaways from the phase 2 KYSA-6 trial? What stood out from a clinical perspective?

Naji Gehchan, MD, MSc: The interim Phase 2 KYSA-6 data are highly encouraging for us as we saw rapid, robust and sustained improvements in patients’ MG outcome scores, well beyond what is considered clinically meaningful. The most notable takeaway for us is that 100% of patients achieved clinically meaningful improvements in MG-ADL and QMG scores, the co-primary endpoints for our registrational Phase 3 trial, with deep and durable responses observed after just a single dose of KYV-101.

These improvements were rapid, seen as early as two weeks, and sustained through 24 weeks, with some patients reaching minimal symptom expression. Importantly, KYV-101 also significantly reduced treatment burden during this period after a single dose, with 100% of patients free of nonsteroidal immunosuppressants, high-dose steroids (>10mg/day), and FcRn and complement inhibitors, and the majority remained drug-free as of their last follow-up.

From a clinical perspective, the safety profile was consistent and manageable: no high-grade cytokine release syndrome (CRS) and no ICANS events were observed, reinforcing KYV-101’s tolerability.

These unprecedented results validate our Phase 3 trial design and underscore KYV-101’s potential to deliver durable, drug-free, disease-free remission by targeting the disease at its source through deep B-cell depletion. We’re eager to continue this progress to help address unmet needs for patients living with generalized myasthenia gravis.

Could you describe the mechanism and rationale behind KYV-101 for treating gMG, and why it may hold promise for success?

While there are many approved therapies and new therapies under development for gMG, none have been able to address the underlying disease on a mechanistic level. With KYV-101, we are taking a novel, upstream approach to directly target the disease source by tapping into the patient’s own immune cells to fight disease.

As an investigational CAR T-cell therapy, KYV-101 directly targets the disease source by deeply depleting the autoreactive B-cells in tissues. In addition, KYV-101 has been shown to have a positive impact on a broader set of immune cell types, and in particular, regulatory T-cells, which are essential for keeping the immune system in check.

These unique actions of KYV-101 could enable a holistic immune reset in patients, possibly leading to more durable treatment effects and even remission.

How challenging is it to design a trial involving a novel mechanism that has not been extensively studied in this patient population?

We believe KYV-101's clinical profile provides us with an advantage.We anticipate a large effect size based on the first patients in the compassionate use pathway that has now been confirmed in this interim Phase 2 readout. This enables us to have a more efficient study design with only ~60 patients to be randomized between standard of care and KYV-101. We are also including important PK and PD endpoints like B cell depletion and looking at effects on immune cell populations to help support our mechanistic approach that complement the other outcome assessments.

To date, KYV-101 has demonstrated deep and broad B-cell depletion with no high-grade CRS or ICANS observed across multiple autoimmune indications in more than 100 patients. Bolstered by a favorable safety profile and strong efficacy results, we feel confident going into future clinical trials with our investigational therapy, KYV-101.

When can the clinical community expect to hear the final results from the trial?

We plan to initiate enrollment for the Phase 3 trial by the end of this year and will share updated Phase 2 data next year, building on the results we recently presented with longer follow-up data on durability.

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