istisociclib (KB-0742) / Ignota Labs - LARVOL DELTA

HDAC and CDK inhibitor combinations suppress neutrophil activation in myeloma (ASH 2025) - "To overcome translational barriers associated with dinaciclib and entinostat, we evaluated next-generation agents: KB0742, a selective and orally bioavailable CDK9 inhibitor, in combination with quisinostat or zabadinostat , two potent HDAC inhibitors with more favorable pharmacokinetic and safety profiles. These transcriptional changes, accompanied by increased re-expression of tumor suppressors (e.g.,p16) and TGFβ/SMAD signaling components, would predict reprogramming of an anti-inflammatory microenvironment by these combination treatments in myeloma. These findings point to a promising but underdeveloped therapeutic avenue whereby suppressing neutrophil-driven inflammation enhances anti-myeloma immunity."

Hematological Malignancies • Multiple Myeloma • Smoldering Multiple Myeloma • BCL2L1 • CXCL1 • CXCL8 • IL1A • IL23A • ITGAM • NRAS • SDC1

Ignota Labs...has announced its acquisition of Kronos’s clinical assets, istisociclib, a CDK9 inhibitor, and entospletinib and lanraplenib, SYK inhibitors. (Businesswire) - "Kronos’ valuation peaked at $3.5 billion after its IPO; however, it failed to progress its assets past Phase 2 trials and subsequently ceased operations. Given the challenges relating to safety and clinical positioning, Ignota Labs saw promise in the clinical portfolio and has acquired Kronos’s clinical IP in full."

Commercial • Hematological Malignancies • Immunology • Solid Tumor

HDAC and CDK Inhibitor Combinations Synergize in Limiting Myeloma (IMS 2025) - "Further investigation into a combined genetic signature will aid in discovering mechanisms of drug synergy and provide biomarkers for a combined response that may translate to the clinic."

Late-breaking abstract • Hematological Malignancies • Multiple Myeloma • ANXA5 • BCL2L1 • CDK1 • HDAC1 • MYC • SDC1

Kronos Bio Enters into Agreement to Be Acquired by Concentra Biosciences for $0.57 in Cash per Share Plus a Contingent Value Right (The Manila Times) - "Kronos Bio, Inc...announced that it has entered into a definitive merger agreement (the 'Merger Agreement') with Concentra Biosciences, LLC ('Concentra'), whereby Concentra will acquire Kronos Bio for $0.57 in cash per share of Kronos Bio common stock ('Kronos Bio Common Stock'), plus one non-tradeable contingent value right ('CVR'), which represents the right to receive: (i) 50% of the net proceeds in the case of a disposition of the Company's product candidates known as KB-9558 and KB-7898 that occurs within 2 years following closing; (ii) 100% of the net proceeds in the case of a disposition of the Company's product candidates known as KB-0742, lanraplenib and entospletinib that occurs prior to closing..."

M&A • Breast Cancer • Graft versus Host Disease • Lupus • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Ovarian Cancer • Prostate Cancer • Rheumatoid Arthritis

Safety and efficacy of a selective inhibitor of cyclin-dependent kinase 9 (KB-0742) in patients with recurrent or metastatic adenoid cystic carcinoma. (PubMed, Cancer Res Commun) - P1/2 | "This dose expansion cohort exploring the novel CDK9 inhibitor KB-0742 in patients with advanced ACC established favorable tolerability at the RP2D. Disease stabilization was observed in some patients despite a limited efficacy signal."

Journal • Adenoid Cystic Carcinoma • Fatigue • Gastrointestinal Disorder • Head and Neck Cancer • Oncology • Salivary Gland Cancer • Solid Tumor • CDK9 • MYB

Organoid-based drug screening identifies CDK9 as a target for stratified treatment of high-grade serous ovarian cancer (AACR 2025) - "To explore the CDK9i responses in HGSC, we profiled 18 organoid cultures against selective CDK9i (AZD4573, VIP-152, NVP-2 and KB-0742). For instance, expression of phosphodiesterase 3B (PDE3B) was correlated with CDK9i resistance (Pearson r = -0.744, p<0.001), while expression of ERBB3 was correlated with increased CDK9i sensitivity (Pearson r = 0.841, p<0.0001).Taken together, we demonstrate the application of an HGSC organoid biobank for identifying patient-specific targets, exceptional responder groups and potential CDK9i sensitivity biomarkers in HGSC. Results of this project could serve as a basis for designing a molecularly stratified CDK9 inhibitor-focused clinical trial in refractory HGSC patients."

High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CDK9 • ERBB3 • MYC

KB-0742-1001: A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC) (clinicaltrials.gov) - P1/2 | N=135 | Terminated | Sponsor: Kronos Bio | Trial completion date: Dec 2025 ➔ Feb 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Jan 2025 | N=280 ➔ 135; Due to lack of safety and futility

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • B Cell Lymphoma • Breast Cancer • Hematological Malignancies • High Grade Serous Ovarian Cancer • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • NUT Midline Carcinoma • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • MYC

Kronos Bio Reports Third Quarter 2024 Financial Results and Corporate Update Including Plan to Evaluate Strategic Alternatives (GlobeNewswire) - P1/2 | N=280 | NCT04718675 | Sponsor: Kronos Bio | "The decision to discontinue the development of istisociclib resulted from a recent safety assessment from the ongoing Phase 1/2 clinical trial patients with platinum-resistant high-grade serous ovarian cancer. Out of seven enrolled patients, five exhibited neurological events as characterized by involuntary movements, confusion and hallucinations ranging from Grade 1 to Grade 3. Of those five patients, three discontinued due to adverse events, and two reduced the dose of istisociclib."

Discontinued • P1/2 data • Ovarian Cancer

KB-0742-1001: A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC) (clinicaltrials.gov) - P1/2 | N=280 | Active, not recruiting | Sponsor: Kronos Bio | Recruiting ➔ Active, not recruiting

Enrollment closed • B Cell Lymphoma • Breast Cancer • Hematological Malignancies • High Grade Serous Ovarian Cancer • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • NUT Midline Carcinoma • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • MYC

Kronos Bio Highlights Data at AACR Ovarian Cancer Research Symposium that Supports Clinical Evaluation of Istisociclib in Advanced Ovarian Cancer (GlobeNewswire) - P1/2 | N=280 | NCT04718675 | Sponsor: Kronos Bio | "Kronos Bio...today highlighted new preclinical data from a study of istisociclib (KB-0742). The poster presentation took place over the weekend at the American Association for Cancer Research (AACR) 15th Biennial Ovarian Cancer Research Symposium...In vitro data demonstrate that istisociclib induced apoptosis/cell death; Istisociclib resulted in the accumulation of γH2AX, a sensitive molecular marker of DNA damage; Istisociclib disrupted homologous recombination (HR) DNA damage repair by downregulating BRCA1 and RAD51 creating a 'BRCAness' phenotype in platinum and PARP resistant HR-proficient ovarian cancer cells...From the dose escalation portion of the Company's ongoing Phase 1/2 trial of istisociclib....Concurrent with increased and prolonged istisociclib exposure, deeper and more sustained downregulation of CDK9-dependent genes was observed in peripheral blood mononuclear cells (PBMCs)."

P1/2 data • PK/PD data • Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Kronos Bio Announces Participation in Medical and Investor Conferences in September (GlobeNewswire) - "Kronos Bio...today announced the following upcoming conferences...Kronos Bio Director of Translational Development, Luis Carvajal, Ph.D., will present a poster...on Saturday, September 21, 2024 (Author discussion from 11:30 a.m.–1:30 p.m. PT)...Kronos Bio collaborator and Lead Scientist at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, Mariateresa Fulciniti, Ph.D., will give an oral presentation...on Saturday, September 28, 2024 (Abstract Session 10 from 10:00 a.m.–11:00 a.m. BRT)...A live audio webcast of the H.C. Wainwright presentation will be available under the Investors & Media section of the Kronos Bio website....A replay of the webcast will be available for 30 days following the event."

P1/2 data • Preclinical • Gynecologic Cancers • Hematological Malignancies • Multiple Myeloma • Oncology • Ovarian Cancer • Solid Tumor

Kronos Bio Announces First Patient Dosed with KB-0742 in an Expansion Cohort Focused on Platinum-Resistant High-Grade Serous Ovarian Cancer (GlobeNewswire) - "Kronos Bio...announced the first patient dosed in an expansion cohort with KB-0742 at a dose of 80mg given on a four-days-on, three-days-off schedule. This expansion cohort is enrolling platinum-resistant patients with high-grade serous ovarian cancer (HGSOC), a tumor type which is particularly sensitive to CDK9 inhibition due to MYC amplification or overexpression and deficiencies in homologous recombination (HRD+)....'We look forward to providing an update on the efficacy of KB-0742 in the first half of 2025'."

P1/2 data • Trial status • Ovarian Cancer

Study update of the oral CDK9 inhibitor KB-0742 in relapsed or refractory transcriptionally addicted advanced solid tumors. (ASCO 2024) - P1/2 | "KB-0742 treatment at 60 and 80 mg was well tolerated, with manageable toxicity. Achievement of long-term SD and some preliminary anti-tumor efficacy in highly pretreated patients motivates continued enrollment of patients with transcriptionally addicted tumors. Dose escalation and expansion in transcriptionally addicted (MYC amplification/overexpression) or TFF driven tumors continues."

Metastases • Adenoid Cystic Carcinoma • Anemia • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Liposarcoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CDK9 • MYC • MYCL

Kronos Bio to Present Clinical Update on Phase 1/2 Trial of KB-0742 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - P1/2 | N=280 | NCT04718675 | Sponsor: Kronos Bio | "Kronos Bio...announced the presentation of new data from its ongoing Phase 1/2 study...of KB-0742 in patients with relapsed or refractory solid tumors or non-Hodgkin lymphoma, in a poster session at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting....The poster features: Data from 103 patients with transcription factor (TF) fusion or MYC driven tumors treated with KB-0742 at 60mg (n=82) and 80 mg (n=21) three-days-on/four-days-off in escalation and expansion cohorts. Patients enrolled in the study had received a median of three prior treatments (range: 0-9). The most frequently reported treatment-emergent adverse events (AE) were manageable mild to moderate nausea (69.9%) and vomiting (52.4%). Notably, no grade 3/4 neutropenia was observed."

P1/2 data • Non-Hodgkin’s Lymphoma • Solid Tumor

KB-0742, an oral highly selective CDK9 inhibitor, demonstrates preclinical activity in transcription factor fusion driven adenoid cystic carcinoma patient-derived models (AACR 2024) - P1/2 | "In XPDXs, CDK9 inhibition with KB-0742 resulted in antiproliferative activity and stronger tumor growth inhibition in MYB-fusion positive and NOTCH co-mutated tumor models compared to MYB-fusion positive only models.These data demonstrate KB-0742 is effective in preclinical models of ACC suggesting KB-0742 may be a promising therapeutic option for ACC patients. KB-0742 is currently being evaluated in a phase 1/2 dose-escalation and cohort expansion trial in patients with ACC and other transcriptionally addicted tumors (NCT04718675)."

IO biomarker • Preclinical • Adenoid Cystic Carcinoma • Oncology • Solid Tumor • MYB • MYBL1 • NFIB

A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in relapsed, refractory and transcriptionally addicted solid tumors (AACR 2024) - P1/2 | "Exploratory objectives include assessment of KB-0742 PD in tumor tissue and profiling of treatment-related genomic, transcriptomic, and proteomic changes. The study is continuing as planned; the next data analysis will occur in 2024."

Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • CDK9 • MYC

Kronos Bio Reports Recent Business Progress and Fourth-Quarter and Full-Year 2023 Financial Results (GlobeNewswire) - "Kronos Bio, Inc...today reported recent business progress and fourth-quarter and full-year 2023 financial results...KB-0742...At a medical conference in mid-2024, the Company intends to share an update on the clinical data to date from patients with transcriptionally addicted tumors who were dosed with 60mg three-days-on, four-days-off, and from 'all-comer' patients in the dose-escalation cohort who received 80mg three-days-on, four-days-off; In the third quarter of 2024, the Company expects to clear the 80mg four-days-on, three-days-off dose escalation cohort, and begin enrolling patients in an expansion cohort including one or more of the following: non-small cell lung cancer, small cell lung cancer, ovarian cancer, and triple negative breast cancer; The Company expects to announce topline data from the expansion cohort at the 80mg four-days-on, three-days-off dose in the first half of 2025."

P1/2 data • Trial status • Gynecologic Cancers • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

Kronos Bio To Present Three Posters at AACR 2024 Annual Meeting (GlobeNewswire) - "Kronos Bio, Inc...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."

P1 data • Preclinical • Oncology • Solid Tumor

A Dose Escalation and Cohort Expansion Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=280 | Recruiting | Sponsor: Kronos Bio | N=170 ➔ 280

Enrollment change • Breast Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • NUT Midline Carcinoma • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • MYC

Kronos Bio Announces Pipeline Update and p300 KAT Inhibitor Development Candidate (GlobeNewswire) - "Kronos Bio’s first internally discovered molecule, KB-0742, an inhibitor of CDK9, has demonstrated on-mechanism, single agent anti-tumor activity and a manageable safety profile in pre-treated patients with transcriptionally addicted solid tumors. KB-0742 recently cleared the 80 mg dose in the dose escalation portion of the ongoing phase 1/2 trial. Patients currently in the two expansion cohorts will now be able to receive the 80 mg dose. The Company expects to provide data from the expansion phase of the trial in mid-2024."

P1/2 data • Trial status • Non-Hodgkin’s Lymphoma • Solid Tumor

A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in triple negative breast cancer and transcriptionally addicted relapsed or refractory solid tumors (SABCS 2023) - P1/2 | "Target accrual: Targeted total enrollment is 170 patients. For additional information, contact clinicaltrials@kronosbio.com"

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • MYC

Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent Cancers. (PubMed, J Med Chem) - "Compound 28 exhibits in vivo antitumor activity in mouse xenograft models and a projected human PK profile anticipated to enable efficacious oral dosing. Notably, 28 is currently being investigated in a phase 1/2 dose escalation and expansion clinical trial in patients with relapsed or refractory solid tumors."

Journal • Oncology • Solid Tumor • CDK9

Kronos Bio Presents Positive Preliminary Data from the Phase 1 Dose Escalation Portion of the Ongoing Phase 1/2 KB-0742 Study at the Connective Tissue Oncology Society Annual Meeting (BioSpace) - P1/2 | N=28 | "'Sarcomas are very complex to diagnose and treat so there is a significant need for innovation in this field,' said Brian Van Tine...'I am very encouraged by the positive preliminary KB-0742 data, not only for what it could mean for sarcoma patients, but also for other cancer types given evidence of on-mechanism clinical activity and a manageable safety profile. Today, I shared a case study on one of my sarcoma patients who exhausted all standard therapies as well as multiple experimental treatments. This patient received KB-0742 for more than a year and experienced objective clinical benefit, including the shrinkage of their tumor. I look forward to learning more about the utility of KB-0742 from the ongoing dose escalation and expansion studies.'"

P1 data

A FIRST-IN-HUMAN STUDY OF CDK9 INHIBITOR KB-0742 DEMONSTRATES PRELIMINARY EVIDENCE OF CLINICAL ACTIVITY IN TRANSCRIPTIONALLY ADDICTED SARCOMAS (CTOS 2023) - No abstract available

Clinical • P1 data • Oncology • Sarcoma • Solid Tumor

Kronos Bio Announces Plan to Optimize Resource Allocation, Restructure and Contain Costs Following Positive Preliminary Clinical Data from its KB-0742 Phase 1/2 Study (GlobeNewswire) - "Kronos Bio...announced a plan to optimize its resource allocation, restructure, and contain costs in light of the positive preliminary safety and efficacy clinical data from its Phase 1/2 study of KB-0742. This plan positions the company to maximize the potential of KB-0742 while continuing to advance the development of lanraplenib, currently in the dose escalation portion of a Phase 1b/2 study. The company will also focus its discovery efforts on maturing projects and its Genentech collaboration activities. Kronos Bio expects that these restructuring efforts, which include a 19% reduction in force, will extend its cash runway into 2026."

Commercial • Acute Myelogenous Leukemia • Oncology • Solid Tumor