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Kyverna Therapeutics' Cell Therapy Safe in First 30 Autoimmune Patients, Leads to Remission in Most

Doctor and patient going over medical results

NEW YORK – Patients who received an experimental CAR T-cell therapy from Kyverna Therapeutics have sustained drug-free remission from various autoimmune diseases for more than a month, including one who has been free of symptoms for more than a year, according to clinical trial results presented Friday.

One early patient to receive the treatment has experienced recurrent disease, which the company believes may be attributed to the lower treatment dose they received.

Kyverna's lead candidate KYV-101, an autologous anti-CD19 CAR T-cell therapy, has been used to treat 30 patients across 15 rheumatological and neurological autoimmune conditions, including lupus nephritis, myasthenia gravis, and multiple sclerosis, researchers reported at the European Alliance of Associations for Rheumatology Congress in Vienna last week.

KYV-101 is designed to modify a patient's own immune T cells to target CD19, a protein expressed on the surface of B cells, which are a critical component of the immune system but can become overactive in autoimmune diseases. The aim is to enable T cells to recognize and deplete B cells in a patient's body, as a way of "resetting" the immune system, said James Chung, Kyverna's chief medical officer, during a press conference Friday.

"We see a very promising profile of KYV-101," he said, which suggests that the one-time CAR T-cell therapy has potential across multiple B-cell driven autoimmune conditions.

The clinical trial results comprise data from Emeryville, California-based Kyverna's Phase I/II clinical trial in lupus nephritis and systemic sclerosis and Phase II clinical trial in myasthenia gravis and multiple sclerosis, as well as investigator-initiated clinical trials and studies on individual patients. Patients have been enrolled and received the CAR T-cell therapy at multiple sites in the US and Europe.

The earliest patient to get KYV-101, for myasthenia gravis, has more than a year of follow-up data. That patient experienced a significant improvement in mobility within 60 days of treatment, as measured by a reduction in Quantitative Myasthenia Gravis scores, walking distance, and time she could hold out her arm horizontally, as reported last year in the Lancet Neurology.

She remains free of disease symptoms without taking immunosuppressants or glucocorticoids. Her B cells repopulated by day 132 post-treatment.

Across the 30 patients, there have been 25 instances of cytokine release syndrome (CRS) and three instances of immune effector cell-associated neurotoxicity syndrome (ICANS), all of which were categorized as being a low level of severity and observed only within the first two weeks after treatment.

That compares to use of the treatment in cancer, where the same CAR T-cell therapy had led to some high-grade toxicities in a small study.

The US National Institutes of Health, which originally developed KYV-101, tested it in 20 patients with B-cell lymphoma within a Phase I trial, in which two patients experienced CRS of at least grade 3 and one patient experienced ICANS of at least grade 3.

"The typical safety issues associated with CAR T-cell therapy in oncology do not pertain one-to-one to autoimmune patients," Georg Schett, VP of research at the Friedrich-Alexander-University in Erlangen, Germany, and a member of Kyverna's scientific advisory board, said during the press conference. "That's very reassuring."

He added that investigators studying other CAR T-cell therapies in autoimmune indications have likewise seen promising results. In a clinical study in Germany, on which Schett was an investigator, 15 patients with systemic lupus erythematosus, idiopathic inflammatory myositis, or systemic sclerosis achieved drug-free remission after receiving an autologous CAR T-cell therapy, for example.

"The credibility of the whole field gets much bigger if independent groups find the same effects," Schett said.

Investigators have observed B-cell depletion in all 30 of the patients treated with KYV-101, all of whom have at least 28 days of follow-up data. All but one experienced CAR T-cell expansion.

Eleven patients have been free from immunosuppressants for at least three months. Ten of the patients have achieved drug-free remission, but with follow-up of less than three months. The remaining nine patients have not reached durable drug-free remission, which may be attributed to lack of CAR T-cell expansion or polyautoimmunity, or they may be slow responders, per the presentation Friday.

Twenty-two patients have experienced an improvement in disease symptoms. Two patients with concomitant myasthenia gravis and Lambert-Eaton myasthenic syndrome, for example, have experienced clinical recovery after treatment with the CAR T-cell therapy with improvements in mobility, which were sustained through four and six months post-treatment, respectively.

"Let's remember that these are patients who have failed many conventional therapies," Chung said. "To see responses like this is very encouraging."

Of seven patients who have received KYV-101 for lupus nephritis, six have remained free of immunosuppressive agents — other than a taper of low-dose corticosteroids in some patients — through their most recent follow-up of up to seven months post-treatment. However, one patient's disease recurred after five months, at which point she resumed immunosuppressants and corticosteroids.

The patient had experienced B-cell depletion and CAR T-cell expansion, although lower than other patients experienced. She initially had been able to discontinue immunosuppressants.

Kyverna, which went public earlier this year, experienced a 34 percent drop in its stock price Friday after reporting these results, closing at $9.53 per share Friday compared to $14.44 per share at market close Thursday. The company opened at $9.62 per share Monday.

The patient's recurrent disease might be attributed to the fact she only received 50 million cells, half of the target dose of 100 million cells, Chung hypothesized. That may not have been a high enough dose for the patient, who also had a high body mass index.

"We learn a lot from patients like this," he said.

Only the earliest treated patients received 50 million cells before Kyverna was able to progress into higher dosing. Of the 30 patients who have been treated, 27 have been treated with 100 million cells.

In an interview with Precision Medicine Online, Kyverna CEO Peter Maag said he's pleased with the data generated so far, which have demonstrated safety and efficacy into one year post-treatment. 

Kyverna hasn't decided which indication it is aiming to gain regulatory approval for first. The biggest opportunity, with the largest potential patient base, is likely multiple sclerosis, Maag said. However, company leadership is also considering whether there are smaller indications where they may be able to prove efficacy and produce data needed for regulatory applications more quickly. Kyverna will discuss options with the FDA as it's deciding which programs to advance into Phase III clinical trials.

"We'll be communicating around that indication going forward," Maag said.