IRF4

SAN MATEO, Calif. and CAMBRIDGE, Mass., March 05, 2024 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to transforming the lives of those affected by cancer, today announced that three abstracts have been selected for presentation at the American Association for Cancer Research (AACR) annual meeting, being held from April 5-10, 2024 in San Diego, California. “We are excited to present our data at AACR showing that targeting p300’s enzymatic KAT domain can selectively downregulate IRF4, a long sought after transcription factor dependency in multiple myeloma. Although p300 is an essential gene, our data show that through its relationship as a critical IRF4 cofactor, we can achieve selective antiproliferative effects against myeloma cells,” said Charles Lin, Ph.D., Senior Vice President, Research and Development of Kronos Bio. Details for the AACR 2024 abstracts are as follows: Title: p300 catalytic inhibition selectively targets IRF4 oncogenic activity in multiple myelomaPresenter: Charles Y. Lin, Ph.D., Kronos BioAbstract #: 1691Poster Session: Chromatin Organization and Regulators of Chromatin BiologyLocation: Poster Section 15 Date and Time: Monday, April 8, 2024, from 9:00 a.m. to 12:30 p.m. PT Title: A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in relapsed, refractory and transcriptionally addicted solid tumorsPresenter: Miguel Villalona-Calero, M.D., Citi of Hope National Medical CenterAbstract #: CT158Poster Session: Phase I Clinical Trials in Progress 2Location: Poster Section 50Date and Time: Monday, April 8, 2024, from 1:30 p.m. to 5:00 p.m. PT Title: KB-0742, an oral highly selective CDK9 inhibitor, demonstrates preclinical activity in transcription factor fusion driven adenoid cystic carcinoma patient-derived modelsPresenter: Luis A. Carvajal, Kronos BioAbstract #: 7550Poster Session: Molecular Biology in Clinical Oncology: Characterizing and Modulating Epigenetics and Gene ExpressionLocation: Poster Section 43 Date and Time: Wednesday, April 10, 2024, from 9:00 a.m. to 12:30 p.m. PT About Kronos Bio, Inc.Kronos Bio is a biopharmaceutical company that is advancing an investigational CDK9 inhibitor compound, KB-0742, in clinical trials as a treatment for MYC-amplified solid tumors and other transcriptionally addicted solid tumors as well as a preclinical development candidate, KB-9558, targeting the KAT domain of p300 for multiple myeloma. The Company’s scientific focus is on developing medicines that target deregulated transcription, the hallmark of cancer and other serious diseases. Kronos Bio is based in San Mateo, Calif., and has a research facility in Cambridge, Mass. For more information, visit https://www.kronosbio.com/ or follow the Company on LinkedIn. Company Contact:Margaux BennettVice President, Corporate Development and Investor Relations, Kronos Bio650-781-5026mbennett@kronosbio.com

Replacing the three jettisoned C-suite roles will be four SPV positions overseeing: R&D; clinical development; corporate strategy and portfolio management; and corporate operations and legal. Kronos Bio had already trimmed back its headcount and pipeline in the wake of a mid-stage cancer flop. Now, it’s the company’s C-suite who are heading to the exits. The biotech has “eliminated three executive officer roles”—meaning Chief Medical Officer Jorge DiMartino, M.D., Chief Scientific Officer Christopher Dinsmore, Ph.D., and Chief Operating Officer and General Counsel Barbara Kosacz will all be out of a job. The company explained the changes were needed to ensure a “streamlined leadership structure designed to focus on pipeline advancement and align with Kronos Bio’s current operating needs.” The three executives will leave the company on Feb.16, although they will remain as strategic advisors for the business, according to a Jan. 25 press release. The leadership shakeup follows a headcount reduction of 19% in November in order to fund KB-0742, a CDK9 inhibitor currently in a phase 1/2 trial for solid tumors and non-Hodgkin lymphoma. A month after the layoffs, Kronos said it was discontinuing a cancer trial for lanraplenib and seeking a partner for the SYK inhibitor in the wake of a mid-stage trial flop. “This new leadership structure is designed to streamline our operations and reflects our ongoing effort to advance our pipeline, optimize our resources, and efficiently deliver on our business objectives,” CEO Norbert Bischofberger, Ph.D., said in the release. “I would like to thank Jorge, Chris, and Barbara for their leadership and dedication, and I wish them well in their future endeavors,” Bischofberger added. “They each built and managed strong teams, laying the groundwork for this new structure and preparing our future leaders for success.” Replacing the three jettisoned C-suite roles will be four SPV positions overseeing R&D; clinical development; corporate strategy and portfolio management; and corporate operations and legal. Those positions are filled by Charles Lin, Ph.D., Elizabeth Olek, Rocio Martin Hoyos and Allison Frisbee, respectively. Kronos said it expects to make savings from the changes, even after termination costs are accounted for. Besides KB-0742, Kronos has a partnership with Roche’s Genentech for several undisclosed discovery programs. Inked a year ago, 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. Kronos also recently 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.

Lanraplenib is one of Kronos’ two clinical-stage assets. 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.”