Kronos discontinues mid-stage AML trial after poor patient response

After a mid-stage flop, Kronos Bio is discontinuing a cancer trial for lanraplenib and seeking a partner to continue development of the SYK inhibitor—the second acute myeloid leukemia (AML) candidate to disappoint the biotech.

The announcement, which was made last night after market close, sent the biotech’s stock spiraling 13%, from $1.47 per share yesterday to $1.27 as of 10:40 a.m. ET today.

The pipeline update follows a review of phase 1b data from Kronos’ phase 1b/2 trial assessing lanraplenib in combo with Xospata among 24 patients with FLT3-mutated relapsed/refractory AML. The patients were split up across four groups, receiving 20 mg to 90 mg of lanraplenib in combination with 120 mg of Xospata. No complete responses (CRs) or CRs with partial hematologic recovery (CRh) were observed and several patients discontinued treatment early on, according to Kronos.

The company has now chosen not to proceed with the phase 2 part of the trial but does want to continue development of lanraplenib with a partner.

“Patients in our study were older, more heavily pre-treated, and frailer than the relapsed/refractory patients in earlier studies. Many patients experienced non-drug related infectious disease complications leading to discontinuation during the first two months of treatment without achieving the count recovery needed to achieve a CR or CRh,” Jorge DiMartino, M.D., Ph.D., chief medical officer and executive vice president of clinical development at Kronos, said in a Dec. 18 release. “Given the changes in the treatment landscape for relapsed/refractory FLT3-mutated AML, it would be challenging to demonstrate the clinical benefit of adding lanraplenib to gilteritinib in this population.”

This summer, the FDA approved Daiichi Sankyo’s quizartinib (marketed as Vanflyta), the first FLT3 inhibitor approved across three phases of the common blood cancer.

Lanraplenib is one of Kronos’ two clinical-stage assets. Attention will now turn to KB-0742, the company’s first internally discovered molecule. In November, the biotech shared positive preliminary phase 1/2 trial data for the solid tumor candidate and announced efforts to streamline operations that included a 19% workforce reduction.  

Besides KB-0742, Kronos has a partnership with Roche’s Genentech for several undisclosed discovery programs. Inked in January, the Genentech partnership is crucial for Kronos, coming right after the biotech kicked a late-stage AML asset called entospletinib to the curb. The Roche unit jumped in to save the day for the struggling biotech with a $20 million upfront payment plus milestones that could top $177 million for the first program and $100 million for the first licensed product.

Now, after another AML disappointment, Kronos has revealed a new development candidate, dubbed KB-9558. The preclinical asset is designed to modulate the IRF4 transcription regulatory network—a key driver in multiple myeloma. KB-9558 is Kronos’ second internally created product and is currently in IND-enabling studies, which are expected to be completed in the fourth quarter of next year.

“Existing therapies for this disease, including CAR-T and bispecific antibody therapies, are not curative, and there is substantial need for new therapies,” said Norbert Bischofberger, Ph.D., Kronos Bio president and CEO. “Preclinical data indicate that treatment of multiple myeloma cells with KB-9558 leads to a rapid and potent down-regulation of IRF4, and we believe our product candidate has the potential to be an innovative treatment for patients with this incurable disease.”