Kronos Bio Presents Positive Preliminary Data from Phase 1 Dose Escalation Portion of Phase 1/2 KB-0742 Study at AACR-NCI-EORTC

Rhea-AI Summary

Kronos Bio announces positive preliminary data from Phase 1 trial of KB-0742 for treating transcriptionally addicted solid tumors.

Positive

• KB-0742 demonstrates on-mechanism anti-tumor activity in heavily pre-treated patients with transcriptionally addicted tumors. No grade 3/4 neutropenia observed. Dose escalation and enrollment in dose expansion phase ongoing.

Negative

• None.

Demonstrated on-mechanism, single agent anti-tumor activity in heavily pre-treated patients with transcriptionally addicted solid tumors

Showed manageable safety profile, with no grade 3/4 neutropenia, dose proportional exposure, dose-dependent target engagement, and 24-hour plasma half-life

Dose escalation continues; dosing of patients at the 80 mg dose level is ongoing

Enrollment ongoing in dose expansion phase in MYC-dependent and other transcriptionally addicted solid tumors, including lung, ovarian, and triple negative breast cancers

Company to host conference call and webcast today at 4:30 PM ET with key opinion leader and
KB-0742 trial investigator, Miguel Villalona-Calero, M.D., of City of Hope National Medical Center

SAN MATEO, Calif. and CAMBRIDGE, Mass., Oct. 13, 2023 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to transforming the lives of those affected by cancer, today announced positive preliminary data from the Phase 1 dose escalation portion of the ongoing Phase 1/2 clinical trial of KB-0742 at the AACR-NCI-EORTC International Conference in Boston, Mass. KB-0742 is the company’s internally discovered, highly selective, orally bioavailable cyclin dependent kinase 9 (CDK9) inhibitor being developed to treat transcriptionally addicted solid tumors. These tumors include transcription factor fusion driven cancers such as sarcomas, as well as MYC-dependent tumors, such as triple negative breast, ovarian, and lung cancer.

The preliminary analysis included 28 patients enrolled in a dose escalation study who received doses from 10 mg up to 60 mg (data cut-off September 1^st, 2023). KB-0742 demonstrated on-mechanism single agent anti-tumor activity in heavily pre-treated patients with transcriptionally addicted tumor types and exhibited a manageable safety profile, with no grade 3/4 neutropenia observed. KB-0742 also demonstrated dose proportional exposure and target engagement and a 24-hour plasma half-life, enabling intermittent dosing. The long plasma half-life enabled KB-0742 to achieve sustained pharmacologically active concentrations while avoiding potentially toxic peak (C_max) concentrations. The most common tumor types of these patients were colorectal (5), chordoma (4), sarcoma (4), lung (3) and breast (3). Because the maximum tolerated dose has not yet been identified, enrollment in the dose escalation portion continues and dosing of patients at the 80 mg dose level is underway. In parallel, the ongoing dose expansion portion of the study, which commenced in January 2023, is enrolling patients with MYC-dependent and other transcriptionally addicted tumors across two cohorts at the 60 mg dose level. Data from this dose expansion portion of the study are expected in mid-2024.

“These positive preliminary efficacy and safety data underscore the promise of KB-0742 to treat patients with transcriptionally addicted tumors. The observed anti-tumor activity and absence of grade 3/4 neutropenia are particularly encouraging as we continue to enroll patients and explore a maximum tolerated dose,” said Jorge DiMartino, M.D., Ph.D., Chief Medical Officer and Executive Vice President, Clinical Development. “We look forward to advancing the study and reporting additional results, including data from the dose expansion portion of the study, mid next year.”

“CDK9 has been an attractive yet elusive target in oncology research. The results from today’s presentation, however, demonstrate that KB-0742 has demonstrated on-mechanism clinical activity and a manageable safety profile, which is a significant achievement,” said Miguel Villalona-Calero, M.D., Medical Oncologist and Director of Early Therapeutics at City of Hope National Medical Center. “Based upon the unique pharmacologic properties of KB-0742 and data to date, I consider KB-0742 to be a promising agent to treat a wide variety of cancers with high unmet need.”

Single Agent Anti-Tumor Activity in Heavily Pre-Treated Patients with Transcriptionally Addicted Tumor Types

As of the September 1^st, 2023 data cut-off date, 28 patients were enrolled in the dose escalation portion of the trial with doses ranging from 10 mg to 60 mg. Patients had received a median of 3.5 prior lines of therapy and the median treatment duration was 57 (range 2 to 398) days and median follow up was 86 (range 57 to 114) days.

At the 60 mg dose level (n=14), evidence of target engagement was observed by pSER2 reduction and proportional changes to CDK9 responsive genes. Tumor reduction (1 PR, 1 SD) was observed in two patients with myxoid liposarcoma, a transcriptionally addicted tumor type characterized by a chimeric fusion TF, consistent with on-mechanism activity. Of these two patients with myxoid liposarcoma, one (7^th line) had a partial response (per RECIST v1.1) lasting 113 days and the second achieved a 26% reduction in tumor diameters with stable disease. Nine (44%) patients across numerous cancer types had stable disease as the best response, and the overall disease control rate was 48% (defined as a complete response, partial response, or stable disease). Myxoid liposarcomas are driven by a transcription factor fusion supporting the therapeutic hypothesis that CDK9 inhibition with KB-0742 can selectively target these and other transcriptionally addicted tumors.

Manageable Safety Profile with No Grade 3 or 4 Neutropenia

Treatment-emergent adverse events (TEAEs) that occurred in >20% of patients included nausea (64%), vomiting (68%) and fatigue (29%), all of which were grade 1/2. No grade 3/4 neutropenia was observed, and no treatment-related deaths were observed. The most common reasons for treatment discontinuation were progressive disease, TEAEs, and withdrawal of consent.

Webcast and Conference Call

Kronos Bio will host a virtual conference call and webcast today, October 13, 2023, at 4:30 p.m. ET., followed by a Q&A session. The event will feature key opinion leader and trial investigator, Miguel Villalona-Calero, M.D, Medical Oncologist and Director of Early Therapeutics, City of Hope National Medical Center, along with Kronos Bio management, who will provide an overview of the KB-0742 program and discuss the data presented today.

A live webcast of the conference call can be accessed under “Events & Presentations” on the investors section of the Company’s website at ir.kronosbio.com/events-presentations. To participate in the live call, please register using this link. It is recommended that participants register at least 15 minutes in advance of the call. Once registered, participants will be informed of the dial-in numbers and PIN. An archived webcast will be available following the event.

The poster presentation from the AACR-NCI-EORTC International Conference is available on publications section of Kronos Bio’s website at kronosbio.com/publications.

About KB-0742

KB-0742 is a highly selective, orally bioavailable inhibitor of cyclin dependent kinase 9 (CDK9) in development for the treatment of transcriptionally addicted solid tumors. CDK9 is a global regulator of transcription and plays an essential role in both the expression and function of oncogenic transcription factors such as MYC, a well-characterized oncogene that is amplified in approximately 30% of all solid tumors, and amplified or highly overexpressed in lung, ovarian, and triple negative breast cancers. KB-0742 was generated and optimized from a compound that was identified using the company’s proprietary small molecule microarray (SMM) screening platform.

About Kronos Bio, Inc.

Kronos Bio is a biopharmaceutical company that is advancing two investigational compounds in clinical trials for patients with cancer. The company is developing the CDK9 inhibitor KB-0742 as a treatment for MYC-dependent solid tumors and other transcriptionally addicted solid tumors and lanraplenib, a next-generation SYK inhibitor, for patients with FLT3-mutated acute myeloid leukemia. The company’s scientific focus is on developing medicines that target the deregulated transcription that is 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 www.kronosbio.com or follow the company on LinkedIn.

Forward-Looking Statements

Statements in this press release that are not statements of historical fact are forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release, in some cases, uses terms such as “on track to,” “plan,” “potential,” “will,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding Kronos Bio’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, Kronos Bio’s the expected timing for data from the dose expansion portion of the study, the promise of KB-0742 to treat patients with transcriptionally addicted tumors, KB-0742 being a promising agent to treat a wide variety of cancers with high unmet need, future results that may be implied from preliminary data, and other statements that are not historical fact. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: whether Kronos Bio will be able to progress its clinical trials on the timelines anticipated, including due to risks inherent in the clinical development of novel therapeutics; risks related to Kronos Bio’s lack of experience as a company in conducting clinical trials; and the risk that results of preclinical studies and early clinical trials (including preliminary results) are not necessarily predictive of future results. These and other risks are described in greater detail in Kronos Bio’s filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in its Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, filed with the SEC on August 8, 2023. Any forward-looking statements that are made in this press release speak only as of the date of this press release and are based on management’s assumptions and estimates as of such date. Except as required by law, Kronos Bio assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Company Contact:
Sarah Connors, Vice President of Investor Relations and Corporate Communications
Kronos Bio
857-290-7305
sconnors@kronosbio.com

Agency Contact:
Brendan Strong, Managing Director
Argot Partners
212-600-1902
kronosbio@argotpartners.com

FAQ

What is KB-0742?

KB-0742 is an orally bioavailable cyclin dependent kinase 9 (CDK9) inhibitor being developed to treat transcriptionally addicted solid tumors.

What are transcriptionally addicted tumors?

Transcriptionally addicted tumors include sarcomas, MYC-dependent tumors (triple negative breast, ovarian, and lung cancer), and other tumors driven by transcription factor fusions.

What were the results of the Phase 1 trial?

KB-0742 demonstrated anti-tumor activity and a manageable safety profile. No grade 3/4 neutropenia observed. Dose escalation and enrollment in dose expansion phase ongoing.

What is the next step for KB-0742?

The ongoing trial will continue dose escalation and enrollment in the dose expansion phase. Data from the dose expansion portion of the study are expected in mid-2024.