By John Otrompke
Immunology
company Kyverna Therapeutics, Inc., will be exploring a new role for CAR
T-cells in treating lupus nephritis, after the company received approval on
Nov. 11 from the FDA for its investigational new drug application to begin
trying its agent, KYV-101, in humans.
“CAR Ts are very effective
depleters of B-cells, which in lupus nephritis are abnormally located in
nephrotic tissues,” explained chief medical officer James Chung, MD PhD. The
Emeryville, California, company plans to begin a phase 1 / 2 trial next year, and
should have clinical data within 6 months, he added.
“This is sort of a ‘Goldilocks’ moment,
because the agent has efficacy on B-cells, and on the other hand, it also has a
great safety profile. These lupus nephritis patients can live 20 or 30 years,
so we can’t give them the level of side effects you see in oncology patients,”
noted CEO Peter Maag, PhD, who was hired by the company in October. (Maag had
previously served as the CEO of Brisbane, California-based CareDx, Inc., a
personalized medicine company in the transplant medicine space).
The announcement comes on the heels
of an article published
in October in Nature Medicine, which described the success of the therapy in treating
five patients. (“Anti-CD19 CAR T cell therapy for refractory systemic lupus
erythematosus,” Mackensen A, Müller F, Mougiakakos D, et al. Nat Med. 2022
Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.
Erratum in: Nat Med. 2022 Nov 3;: PMID: 36109639).
“Seventeen months out, they still
have no need for additional immune suppression. If that’s true in five
patients, the discovery might amount to a paradigm shift, achieved by pushing
the immune system’s reset button through the deep depletion of B-cells,” added
Maag.
Lupus occurs mostly in young women
with about 65% of cases occurring in those between the ages of 16 and 55.
Approximately 40% of adults will develop lupus nephritis, 60% of whom will fail
standard of care and approved treatments, said Chung, and up to 40% of those
with diffuse disease will ultimately develop kidney failure, requiring dialysis
or a kidney transplant to stay alive.
The treatment, an anti-CD19
chimeric antigen receptor T-cell (CAR T) construct for which Kyverna has obtained
exclusive, global licensing from the NIH to use in both autologous and
allogeneic CAR T-cell therapies, will be tested first in open label clinical
trials, Maag said.
“The FDA and other health agencies
have accepted objective endpoints for lupus nephritis, such as serum
creatinine, which is a measure of renal function,” Chung noted.
While multiple gene signatures have
been identified in lupus patients, KYV-101 does not target them; instead, the
company hopes to target a broader population of lupus patients through
depletion of B cells.
“There are a number of diseases in
which B-cell depletion might be relevant; there is some evidence in multiple
sclerosis, for example,” said Maag, adding that the company is in talks with
the FDA regarding such an application.
