A Phase 1b/2 Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of the Selective SYK Inhibitor Lanraplenib (LANRA) in Combination With the FLT3 Inhibitor Gilteritinib, in Patients With FLT3-mutated Relapsed or Refractory AML

The primary objective of this study is to evaluate the safety of lanraplenib (LANRA) in combination with the FMS-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib, in participants with relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML).

开始日期2022-08-05

申办/合作机构

Kronos Bio, Inc.

NCT03285711

/ Completed临床2期

A Phase 2, Randomized, Double-Blind, Multicenter Study Evaluating the Safety and Efficacy of Filgotinib and GS-9876 in Subjects With Lupus Membranous Nephropathy (LMN)

The primary objective of this study is to evaluate the efficacy of filgotinib and lanraplenib (previously GS-9876) in adults with lupus membranous nephropathy (LMN).

开始日期2017-10-06

申办/合作机构

Gilead Sciences, Inc.

NCT03134222

/ Completed临床2期

A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Filgotinib and GS-9876 in Female Subjects With Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE)

The primary objective of this study is to evaluate the efficacy of filgotinib and lanraplenib (formerly GS-9876) in females with moderately-to-severely active cutaneous lupus erythematosus (CLE).

开始日期2017-05-24

申办/合作机构

Gilead Sciences, Inc.

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100 项与 Lanraplenib 相关的临床结果

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100 项与 Lanraplenib 相关的转化医学

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100 项与 Lanraplenib 相关的专利（医药）

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项与 Lanraplenib 相关的文献（医药）

2024-04-01·Toxicology and applied pharmacology

The ABCB1 and ABCG2 efflux transporters limit brain disposition of the SYK inhibitors entospletinib and lanraplenib

Article

作者: Sparidans, Rolf W ; Beijnen, Jos H ; Bui, Viët ; Schinkel, Alfred H ; Heydari, Paniz ; Loos, Nancy H C ; Lebre, Maria C

The highly selective Spleen Tyrosine Kinase (SYK) inhibitors entospletinib and lanraplenib disrupt kinase activity and inhibit immune cell functions. They are developed for treatment of B-cell malignancies and autoimmunity diseases. The impact of P-gp/ABCB1 and BCRP/ABCG2 efflux transporters, OATP1a/1b uptake transporters and CYP3A drug-metabolizing enzymes on the oral pharmacokinetics of these drugs was assessed using mouse models. Entospletinib and lanraplenib were orally administered simultaneously at moderate dosages (10 mg/kg each) to female mice to assess the possibility of examining two structurally and mechanistically similar drugs at the same time, while reducing the number of experimental animals and sample-processing workload. The plasma pharmacokinetics of both drugs were not substantially restricted by Abcb1 or Abcg2. The brain-to-plasma ratios of entospletinib in Abcb1a/b^-/-, Abcg2^-/- and Abcb1a/b;Abcg2^-/- mice were 1.7-, 1.8- and 2.9-fold higher, respectively, compared to those in wild-type mice. For lanraplenib these brain-to-plasma ratios were 3.0-, 1.3- and 10.4-fold higher, respectively. This transporter-mediated restriction of brain penetration for both drugs could be almost fully inhibited by coadministration of the dual ABCB1/ABCG2 inhibitor elacridar, without signs of acute toxicity. Oatp1a/b and human CYP3A4 did not seem to affect the pharmacokinetics of entospletinib and lanraplenib, but mouse Cyp3a may limit lanraplenib plasma exposure. Unexpectedly, entospletinib and lanraplenib increased each other's plasma exposure by 2.6- to 2.9-fold, indicating a significant drug-drug interaction. This interaction was, however, unlikely to be mediated through any of the studied transporters or CYP3A. The obtained insights may perhaps help to further improve the safety and efficacy of entospletinib and lanraplenib.

2024-01-01·Molecular biology of the cell

Signaling pathways regulating the extracellular digestion of lipoprotein aggregates by macrophages

Article

作者: Maxfield, Frederick R ; Steinfeld, Noah ; Ma, Cheng-I J

The interaction between aggregated low-density lipoprotein (agLDL) and macrophages in arteries plays a major role in atherosclerosis. Macrophages digest agLDL and generate free cholesterol in an extracellular, acidic, hydrolytic compartment known as the lysosomal synapse. Macrophages form a tight seal around agLDL through actin polymerization and deliver lysosomal contents into this space in a process termed digestive exophagy. Our laboratory has identified TLR4 activation of MyD88/Syk as critical for digestive exophagy. Here we use pharmacological agents and siRNA knockdown to characterize signaling pathways downstream of Syk that are involved in digestive exophagy. Syk activates Bruton’s tyrosine kinase (BTK) and phospholipase Cγ2 (PLCγ2). We show that PLCγ2 and to a lesser extent BTK regulate digestive exophagy. PLCγ2 cleaves PI(4,5)P2 into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Soluble IP3 activates release of Ca2+ from the endoplasmic reticulum (ER). We demonstrate that Ca2+ release from the ER is upregulated by agLDL and plays a key role in digestive exophagy. Both DAG and Ca2+ activate protein kinase Cα (PKCα). We find that PKCα is an important regulator of digestive exophagy. These results expand our understanding of the mechanisms of digestive exophagy, which could be useful in developing therapeutic interventions to slow development of atherosclerosis.

2023-07-01·The Journal of investigative dermatology

Neutrophil-Specific Syk Expression Is Crucial for Skin Disease in Experimental Epidermolysis Bullosa Acquisita

Article

作者: Szilveszter, Kata P ; Balogh, Lili ; Németh, Tamás ; Káposztás, Eszter ; Mócsai, Attila

Autoantibodies against the dermal-epidermal junction component type VII collagen (C7) trigger skin disease in the inflammatory form of epidermolysis bullosa acquisita. We have previously identified the Syk tyrosine kinase as a crucial participant in anti-C7 antibody-induced experimental epidermolysis bullosa acquisita. However, it is still unclear which cellular lineage needs to express Syk during the disease process. In this study, we show that the loss of Syk, specifically from neutrophils, results in complete protection from the anti-C7 antibody-initiated skin disease both macroscopically and microscopically. Mice with a neutrophil-specific Syk deletion had decreased neutrophil accumulation and abrogated CXCL2 and IL-1β levels in the skin upon anti-C7 treatment, whereas isolated Syk-deficient neutrophils had decreased superoxide release, cell spreading, and cytokine release on C7-anti-C7 immune complex surfaces. Entospletinib and lanraplenib, two second-generation Syk-specific inhibitors, effectively abrogated immune complex-induced responses of human neutrophils and decreased the anti-C7 antibody-initiated, neutrophil-mediated ex vivo dermal-epidermal separation in human skin samples. Taken together, these results point to a crucial role for Syk in neutrophils in the development and progression of epidermolysis bullosa acquisita and suggest Syk inhibition as a potential therapeutic strategy.

项与 Lanraplenib 相关的新闻（医药）

2025-05-01

·GlobeNewswire-Health Care

Kronos Bio Enters into Agreement to Be Acquired by Concentra Biosciences for $0.57 in Cash per Share Plus a Contingent Value Right

CAMBRIDGE, Mass., May 01, 2025 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. ("Kronos Bio") (Nasdaq: KRON), a biotechnology company that has been developing small molecule therapeutics to address cancers and other diseases driven by deregulated transcription, today 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; (iii) 100% of cost savings realized prior to closing; (iv) 80% of cost savings realized between the merger closing date and the second (2nd) anniversary of the merger closing date; and (v) 50% of cost savings realized between the second (2nd) anniversary of the merger closing date and the third (3rd) anniversary of the merger closing date, each pursuant to the contingent value rights agreement (the “CVR Agreement”). Following a review process conducted with the assistance of its legal and financial advisors, the Kronos Bio Board of Directors has determined that the acquisition by Concentra is in the best interests of all Kronos Bio shareholders and has approved the Merger Agreement and related transactions. Pursuant and subject to the terms of the Merger Agreement, a wholly owned subsidiary of Concentra will commence a tender offer (the “Offer”) by May 15, 2025 to acquire all outstanding shares of Kronos Bio Common Stock. Closing of the Offer is subject to certain conditions, including the tender of Kronos Bio Common Stock representing at least a majority of the total number of outstanding shares (including any shares held by Concentra), the availability of at least $40.0 million of cash (net of transaction costs and other liabilities) at closing, and other customary closing conditions. Kronos Bio officers, directors and their respective affiliates holding approximately 27% of Kronos Bio Common Stock have signed tender and support agreements under which such parties have agreed to tender their shares in the Offer and support the merger transaction. The merger transaction is expected to close mid-2025. About Kronos BioKronos Bio is a biopharmaceutical company that has historically focused on the discovery and development of small molecule therapeutics to address deregulated transcription, a hallmark of cancer and autoimmune diseases. Kronos Bio has a research facility in Cambridge, Mass. For more information, visit https://www.kronosbio.com. AdvisorsGoodwin Procter LLP is acting as legal counsel to Kronos Bio and Leerink Partners is acting as sole financial advisor to Kronos Bio. Gibson, Dunn & Crutcher LLP is acting as legal counsel to Concentra. Forward-Looking Statements This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Kronos Bio’s beliefs and expectations and statements about the Offer, merger, related transactions contemplated by the Merger Agreement and the CVR Agreement (the “Transactions”), including the timing of and closing conditions to the Transactions, and the potential effects of the proposed Transactions on Kronos Bio and the potential payment of proceeds to the Kronos Bio stockholders, if any, pursuant to the CVR Agreement. These statements may be identified by their use of forward-looking terminology including, but not limited to, “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” and “would,” and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance and involve risks and uncertainties that could cause actual results to differ materially from those projected, expressed or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the possibility that various closing conditions set forth in the Merger Agreement may not be satisfied or waived, including uncertainties as to the percentage of Kronos Bio’s stockholders tendering their shares in the Offer; the possibility that competing offers will be made; the risk that the Transactions may not be completed in a timely manner, or at all, which may adversely affect Kronos Bio’s business and the price of its common stock; costs associated with the proposed Transactions; the risk that any stockholder litigation in connection with the Transactions may result in significant costs of defense, indemnification and liability; the risk that activities related to the CVR Agreement may not result in any value to the Kronos Bio stockholders; and other risks and uncertainties discussed in Kronos Bio’s most recent annual report filed with the Securities and Exchange Commission (the “SEC”) as well as in Kronos Bio’s subsequent filings with the SEC. As a result of such risks and uncertainties, Kronos Bio’s actual results may differ materially from any future results, performance or achievements discussed in or implied by the forward-looking statements contained herein. There can be no assurance that the proposed Transactions will in fact be consummated. Kronos Bio cautions investors not to unduly rely on any forward-looking statements. The forward-looking statements contained in this release are made as of the date hereof, and Kronos Bio undertakes no obligation to update any forward-looking statements, whether as a result of future events, new information or otherwise, except as expressly required by law. All forward-looking statements in this document are qualified in their entirety by this cautionary statement. Additional Information and Where to Find It The Offer described in this release has not yet commenced, and this release is neither a recommendation, nor an offer to purchase nor a solicitation of an offer to sell any shares of the common stock of Kronos Bio or any other securities. On the commencement date of the Offer, a tender offer statement on Schedule TO, including an offer to purchase, a letter of transmittal and related documents, will be filed with the SEC by Concentra and its acquisition subsidiary, and a Solicitation/Recommendation Statement on Schedule 14D-9 will be filed with the SEC by Kronos Bio. The Offer to purchase the outstanding shares of the common stock of Kronos Bio will only be made pursuant to the offer to purchase, the letter of transmittal and related documents filed as a part of the Schedule TO. INVESTORS AND SECURITY HOLDERS ARE URGED TO READ THE TENDER OFFER MATERIALS (INCLUDING THE OFFER TO PURCHASE, A LETTER OF TRANSMITTAL AND RELATED DOCUMENTS) AND THE SOLICITATION/RECOMMENDATION STATEMENT ON SCHEDULE 14D-9 REGARDING THE OFFER, AS THEY MAY BE AMENDED OR SUPPLEMENTED FROM TIME TO TIME, WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION THAT INVESTORS AND SECURITY HOLDERS SHOULD CONSIDER BEFORE MAKING ANY DECISION REGARDING TENDERING THEIR SHARES, INCLUDING THE TERMS AND CONDITIONS OF THE OFFER. Investors and security holders may obtain a free copy of these statements (when available) and other documents filed with the SEC at the website maintained by the SEC at www.sec.gov or by directing such requests to the information agent for the Offer, which will be named in the tender offer statement. Investors and security holders may also obtain, at no charge, the documents filed or furnished to the SEC by Kronos Bio under the “Investors & Media” section of Kronos Bio’s website at https://ir.kronosbio.com/financials-filings/sec-filings. Contact Information: Investors: Denise Powell denise@redhousecomms.com Media: Kelli Perkins kelli@redhousecomms.com

并购

2025-03-01

·精准药物

综述｜氧杂环丁烷：专利布局与活性分子设计回顾

「氧杂环丁烷（Oxetane）」作为一种四元含氧杂环化合物，近年来因其独特的理化性质成为药物化学领域的研究热点。本文系统综述近期氧杂环丁烷在临床候选药物、专利布局及分子设计中的关键进展，并探讨其工业化面临的合成与稳定性挑战。 01 氧杂环丁烷的分子特性与药物化学优势 1.1 氧杂环丁烷（C₃H₆O）核心优势：“四大武器”‌： ‌低分子量（58.08 g/mol）‌：符合现代药物“分子精简”设计趋势（如Ro5优化）； ‌高极性（偶极矩4.3 D）‌：显著改善化合物水溶性（LogP降低0.5-1.5单位）；三维立体构型‌：三个sp³杂化碳原子赋予分子刚性，提升靶点结合特异性（Ki值优化达10倍）；代谢调控功能‌：通过mEH酶通路代谢，规避CYP450介导的药物相互作用（DDI风险降低60%）。 ‌代表性案例‌：辉瑞PF-06821497（非霍奇金淋巴瘤候选药）通过氧杂环丁烷修饰，将血浆半衰期从2.3小时延长至8.7小时。 1.2 作为偕二甲基基团和羰基衍生物的潜在电子等排体： 02 临床开发管线分析‌ 截至2025年2月，全球共有9款含氧杂环丁烷结构的候选药物进入临床阶段： a. Pfizer公司：Crenolanib (CAS: 670220-88-9)是有效和选择性的野生型和突变型III类受体酪氨酸激酶抑制剂，抑制FLT3 和PDGFRα/β 的Kd分别为0.74nM，2.1nM，3.2nM。 b. Genentech公司：Fenebrutinib (GDC-0853, CAS : 1434048-34-6) 是一种有效的，具有口服活性的，选择性和非共价的布鲁顿酪氨酸激酶 (Btk) 抑制剂，对野生型 Btk，及突变型C481S，C481R，T474I，T474M 的Ki分别为0.91nM，1.6，1.3，12.6 和 3.4nM。有潜力用于类风湿关节炎和系统性红斑狼疮的研究。 c. Roche公司：Ziresovir (AK0529; RO-0529，CAS : 1422500-60-4) 是一种口服有效的，选择性呼吸道合胞病毒 (RSV) 融合 (F) 蛋白 (RSV F) 抑制剂，显示抗RSV活性 (EC50=3 nM)，并具有药代动力学表现。 d. Gilead公司：Lanraplenib (GS-9876, CAS: 1800046-95-0) 是一种高度选择性的口服SYK抑制剂 (IC50=9.5 nM) ，用于研究炎症性疾病。通过糖蛋白 VI (GPVI) 受体抑制血小板中的 SYK 活性，而不会延长猴子或人类的出血时间 (BT)。 e. Pfizer公司：Danuglipron (PF-06882961, CAS: 2230198-02-2) 是一种具有口服活性的胰高血糖素样肽-1 受体 (GLP-1R) 激动剂，具有用于 2 型糖尿病研究的潜力。 f. Genentech公司：GDC-0349 （CAS: 1207360-89-1）是一种有效的，ATP竞争性的选择性 mTOR 抑制剂，Ki 值为 3.8 nM，抑制 mTORC1 和 mTORC2 复合体。 e. Principia Biopharma公司：Rilzabrutinib （CAS: 1575591-66-0) 凭借氧杂环丁烷结构的创新设计，在BTK抑制剂中展现出显著的代谢稳定性和安全性优势，2024-2025年期间在天疱疮等适应症中取得关键临床进展，成为氧杂环丁烷在激酶抑制剂领域的标杆案例。 03 专利与合成技术进展‌ 3.1 专利布局‌2017-2025年间，全球共公开327项氧杂环丁烷相关药物专利。 ‌取代模式：3-氨基氧杂环丁烷（42%）、3-酮基氧杂环丁烷（28%）、螺环氧杂环丁烷（15%）； ‌头部企业‌：罗氏（23项）、辉瑞（18项）、诺华（15项）。 3.2 合成挑战‌ ‌环张力控制‌：氧杂环丁烷环张力（106.8 kJ/mol）导致开环副反应（酸性条件下产率<40%）； ‌立体选择性合成‌：3-取代氧杂环丁烷的非对映体比例调控仍依赖手性催化剂（ee值>95%成本增加3倍）； ‌工业化瓶颈‌：目前公斤级合成依赖[2+2]环加成反应，收率波动范围达±15%。 3.3. 合成工艺突破‌ 专利号‌：WO2025-123456A1（Pfizer） ‌技术‌：光催化[2+2]环加成构建氧杂环丁烷，反应收率提升至85%（传统方法≤50%）； ‌应用‌：支持公斤级生产，成本降低60%。3.4. 稳定性增强设计‌ 专利号‌：US2025/789012B2（Moderna） ‌技术‌：氧杂环丁烷-磷酰胺酯前药设计（pH敏感型开环）； ‌效果‌：口服生物利用度F=55%（原药12%）。 04 未来研究方向‌ ‌4.1 计算化学驱动设计‌ AI预测模型‌：利用AlphaFold 3.0预测氧杂环丁烷-靶点复合物构象（RMSD<1.0 Å）；代谢通路模拟‌：Quantum Mechanics/Molecular Mechanics (QM/MM)优化mEH代谢路径。 ‌4.2 新型构建模块开发‌ ‌氧杂环丁烷酮衍生物‌：通过引入羰基增强稳定性（T½延长至72小时）； ‌光响应型氧杂环丁烷‌：实现时空选择性药物释放（如肿瘤微环境pH触发开环）。 4‌.3 放射性药物‌：氧杂环丁烷作为¹⁸F标记位点（如⁸F-Oxetan-3-ol，标记效率>95%）； 4.4 ADC连接子‌：利用其酶促水解可控性（如Val-Cit-Oxetane连接子，血浆稳定性T½=120小时）。 05 结论氧杂环丁烷凭借其多维度的分子优化能力，正在重塑小分子药物的设计范式。尽管合成工艺与稳定性问题仍需突破，但随着自动化合成平台（如ChemSpeed SLT-100）与AI辅助技术的深度融合，预计2030年前将有5-8款氧杂环丁烷药物获批上市，尤其在肿瘤靶向治疗和慢性病管理领域潜力显著。声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

2024-03-21

·BioSpace

Kronos Bio Reports Recent Business Progress and Fourth-Quarter and Full-Year 2023 Financial Results

Phase 1/2 study of KB-0742 is on track to clear 80mg four-days-on, three-days-off schedule in the third quarter of 2024; topline data from expansion cohort at this schedule expected in the first half of 2025 IND-enabling studies for KB-9558 expected to complete in 2024 with first-in-human study anticipated to commence in the first half of 2025 $175.0 million in cash, cash equivalents and investments as of December 31, 2023, providing expected cash runway into the second half of 2026 SAN MATEO, Calif. and CAMBRIDGE, Mass., March 21, 2024 (GLOBE NEWSWIRE) -- Kronos Bio Inc (Nasdaq: KRON), a company dedicated to transforming the lives of those affected by cancer, today reported recent business progress and fourth-quarter and full-year 2023 financial results. “In 2023, we made great progress across our portfolio and business. We demonstrated that KB-0742 has a safety pro is clearly differentiated from all other CDK9 inhibitors, and we believe our extended dosing schedule will show increased efficacy signals while maintaining a favorable safety profile,” said Nobert Bischofberger, Ph.D., president and chief executive officer of Kronos Bio. “We also announced our second development candidate, KB-9558, which is designed to target the KAT domain of p300 and downregulate IRF4 transcription in multiple myeloma. We are looking forward to completing the IND-enabling studies in 2024 and expect to dose our first patients in the first half of 2025.” Clinical Program and Recent Company Updates KB-0742 At the 2023 AACR-NCI-EORTC International Conference, the Company reported target engagement, tumor regressions, and an acceptable safety pro KB-0742 dosed at 60mg three-days-on, four-days-off in heavily pre-treated patients with transcriptionally addicted solid tumors. Out of fourteen “all-comer” patients, two patients with myxoid liposarcoma exhibited tumor regressions: one (7th 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. KB-0742 also cleared the 80mg three-days-on, four-days-off schedule in dose escalation and is currently enrolling patients in the KB-0742 60mg four-days-on, three-days-off dose escalation cohort of the Phase 1/2 trial. 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. KB-9558 In December 2023, the Company announced the nomination of KB-9558, a p300 KAT inhibitor, as a development candidate. KB-9558 is the second development candidate to emerge from Kronos Bio’s product engine, where the Company identified that inhibition of the lysine acetyltransferase (KAT) domain on p300 inhibits expression of interferon regulatory factor 4 (IRF4) and thus collapses the transcription regulatory network that is required for the survival of multiple myeloma cells. The Company plans to present data on KB-9558 at the American Association for Cancer Research (AACR) annual meeting, being held from April 5-10, 2024 in San Diego, California, including how targeting p300’s enzymatic KAT domain can selectively downregulate IRF4. Pending completion of IND-enabling studies in 2024, the Company intends to initiate a first-in-human trial in relapsed or refractory multiple myeloma in the first half of 2025. Lanraplenib In December 2023, after a review of data from the Phase 1b portion of its Phase 1b/2 trial of lanraplenib in combination with gilteritinib in FLT3-mutated relapsed/refractory acute myeloid leukemia (AML), the Company decided not to proceed to Phase 2. Company Update Kronos Bio extended its expected cash runway by a year, into the second half of 2026, through restructurings and resource optimization. Fourth-Quarter and Full-Year 2023 Financial Highlights Cash, Cash Equivalents and Investments: With its ongoing and currently planned clinical programs and $175.0 million in cash, cash equivalents and investments as of December 31, 2023, the Company anticipates sufficient resources to fund its planned operations into the second half of 2026. R&D Expenses: Research and development expenses were $18.7 million for the fourth quarter of 2023, which includes non-cash stock-based compensation expense of $2.5 million. For the full year of 2023, research and development expenses were $86.4 million, which includes non-cash stock-based compensation expense of $12.0 million. G&A Expenses: General and administrative expenses were $10.9 million for the fourth quarter of 2023, which includes non-cash stock-based compensation expense of $2.7 million. For the full year of 2023, general and administrative expenses were $41.7 million, which includes non-cash stock-based compensation expense of $13.0 million. Net Loss: Net loss for the fourth quarter of 2023 was $25.3 million, or $0.43 per share, including non-cash stock-based compensation expense of $5.2 million. Net loss for the full-year 2023 was $112.7 million, or $1.95 per share, including non-cash stock-based compensation expense of $25.0 million. About Kronos Bio, Inc. Kronos Bio is a biopharmaceutical company that is advancing an investigational CDK9 inhibitor compound, KB-0742, in a Phase 1/2 clinical trial 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 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 “anticipate,” “believe,” “could,” “expect,” “on track,” “plan,” “potential,” “promising,” “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, the Phase 1/2 study of KB-0742 being on track to clear 80mg four-days-on, three-days-off schedule in Q3 2024; expected clinical results from the KB-0742 study; the expected timing for additional clinical data from the Phase 1/2 KB-0742 study; the potential completion of IND-enabling studies and the initial of a clinical trial for KB-9558 and the timing thereof; future pipeline development activities or outcomes; the potential of Kronos Bio’s product candidates; Kronos Bio’s expected cash runway; 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: risks associated with changes to the assumptions underlying estimated expenses and savings; changes in the macroeconomic environment or competitive landscape that impact Kronos Bio’s business; 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 limited experience as a company in conducting clinical trials; the risk that results of preclinical studies and early clinical trials (including preliminary results) are not necessarily predictive of future results; and risks associated with the sufficiency of Kronos Bio’s cash resources and need for additional capital. 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 September 30, 2023, filed with the SEC on November 13, 2023, and in its Annual Report on Form 10-K for the year ended December 31, 2023, being filed with the SEC today. 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. Kronos Bio, Inc. Statements of Operations and Comprehensive Loss (in thousands, except per share data) (Unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Revenue $ 2,286 $ — $ 6,288 $ — Operating expenses: Research and development 18,704 23,168 86,379 93,715 General and administrative 10,926 10,514 41,739 43,400 Total operating expenses 29,630 33,682 128,118 137,115 Loss from operations (27,344 ) (33,682 ) (121,830 ) (137,115 ) Other income (expense), net: Interest and other income, net 2,024 1,900 9,157 3,911 Total other income (expense), net 2,024 1,900 9,157 3,911 Net loss (25,320 ) (31,782 ) (112,673 ) (133,204 ) Other comprehensive income (loss): Net unrealized gain (loss) on available-for-sale securities 274 258 811 (753 ) Net comprehensive loss $ (25,046 ) $ (31,524 ) $ (111,862 ) $ (133,957 ) Net loss per share, basic and diluted $ (0.43 ) $ (0.56 ) $ (1.95 ) $ (2.37 ) Weighted-average number of shares used to compute net loss per share, basic and diluted 58,268 56,523 57,744 56,201 Kronos Bio, Inc. Selected Balance Sheet Data (in thousands) (Unaudited) December 31, 2023 December 31, 2022 Cash, cash equivalents and investments $ 174,986 $ 247,947 Total assets $ 213,279 $ 294,938 Total liabilities $ 54,201 $ 50,439 Total stockholders’ equity $ 159,078 $ 244,499 Investor & Media Contact: Margaux Bennett Vice President, Corporate Development and Investor Relations, Kronos Bio 650-781-5026 mbennett@kronosbio.com

临床1期财报AACR会议高管变更临床结果

100 项与 Lanraplenib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11596	-	-	DB14770

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
难治性急性髓细胞白血病	临床2期	美国	Kronos Bio, Inc.	2022-08-05
难治性急性髓细胞白血病	临床2期	西班牙	Kronos Bio, Inc.	2022-08-05
复发性急性髓细胞白血病	临床2期	美国	Kronos Bio, Inc.	2022-08-05
复发性急性髓细胞白血病	临床2期	西班牙	Kronos Bio, Inc.	2022-08-05
膜性肾小球肾炎	临床2期	美国	Gilead Sciences, Inc.	2017-10-06
皮肤红斑狼疮	临床2期	美国	Gilead Sciences, Inc.	2017-05-24
皮肤红斑狼疮	临床2期	加拿大	Gilead Sciences, Inc.	2017-05-24
干燥综合征	临床2期	美国	Gilead Sciences, Inc.	2017-05-01
干燥综合征	临床2期	波兰	Gilead Sciences, Inc.	2017-05-01
干燥综合征	临床2期	西班牙	Gilead Sciences, Inc.	2017-05-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03285711 (CTgov)	临床2期	膜性肾小球肾炎	9	Filgotinib placebo+Lanraplenib (Lanraplenib 30 mg)	繭餘窪構鬱壓艱繭願願(簾製鹽襯蓋窪壓選餘艱) = 憲網網構壓鹹簾築獵廠壓壓鹽觸淵觸鑰構遞顧更多	-	2020-05-18
				Lanraplenib placebo+Filgotinib (Filgotinib 200 mg)	繭餘窪構鬱壓艱繭願願(簾製鹽襯蓋窪壓選餘艱) = 醖製遞餘鬱憲積鹽艱齋壓壓鹽觸淵觸鑰構遞顧 (選遞窪壓蓋艱構顧顧窪, 25.67) 更多
NCT03134222 (CTgov)	临床2期	皮肤红斑狼疮	47	Filgotinib placebo+Lanraplenib (Lanraplenib 30 mg)	獵築獵蓋壓選醖餘膚繭(觸獵齋糧窪築餘繭蓋艱) = 壓繭餘範憲範餘廠衊網膚淵夢餘廠繭獵衊繭淵 (膚廠糧獵艱鏇網艱餘鏇, 1.91) 更多	-	2020-04-08
				Lanraplenib placebo+Filgotinib (Filgotinib 200 mg)	獵築獵蓋壓選醖餘膚繭(觸獵齋糧窪築餘繭蓋艱) = 獵顧網網襯顧衊網網膚膚淵夢餘廠繭獵衊繭淵 (膚廠糧獵艱鏇網艱餘鏇, 1.85) 更多
NCT03100942 (CTgov)	临床2期	干燥综合征	152	Filgotinib placebo+Lanraplenib (Lanraplenib)	選醖構鹽網淵築願齋鑰 = 蓋鹽網積壓壓網醖淵積齋衊顧廠窪夢廠淵積範 (膚糧鹹醖餘艱願鹹積鹽, 顧簾簾蓋網膚醖蓋艱醖 ~ 蓋鏇醖膚蓋簾鏇餘鬱艱) 更多	-	2020-01-22
				Tirabrutinib placebo+Filgotinib (Filgotinib)	選醖構鹽網淵築願齋鑰 = 範襯構鹽襯網構顧觸獵齋衊顧廠窪夢廠淵積範 (膚糧鹹醖餘艱願鹹積鹽, 顧淵築鹹夢壓糧糧蓋壓 ~ 顧膚鏇衊廠餘憲淵廠鬱) 更多
NCT02959138 (CTgov)	临床1期	白内障 \| 炎症	36	lanraplenib (Cohort 1: Moderate Renal Impairment)	觸範夢遞壓積襯鑰憲築(構糧繭築築餘襯願製願) = 簾鬱繭繭鹽觸憲襯鹹襯鑰蓋餘鏇觸鬱繭夢顧餘 (膚窪齋衊齋壓簾選繭製, 813.83) 更多	-	2019-10-25
				lanraplenib (Cohort 1: Healthy Control)	觸範夢遞壓積襯鑰憲築(構糧繭築築餘襯願製願) = 範齋鑰簾選糧夢夢觸願鑰蓋餘鏇觸鬱繭夢顧餘 (膚窪齋衊齋壓簾選繭製, 424.52) 更多
EULAR2019	临床2期	类风湿关节炎 DAS28(CRP) \| ACR20/50/70 \| HAQ-DI	83	GS-9876 10 mg	積膚壓網廠簾選夢齋網(鏇觸獵憲觸糧餘壓鏇膚) = 窪糧膚艱積製襯鑰築製網憲遞膚廠窪憲壓觸願 (淵鹹鹹糧遞鹹鑰淵網鑰 )	-	2019-06-12
				GS-9876 30 mg	積膚壓網廠簾選夢齋網(鏇觸獵憲觸糧餘壓鏇膚) = 築壓壓憲廠獵鏇襯構繭網憲遞膚廠窪憲壓觸願 (淵鹹鹹糧遞鹹鑰淵網鑰 )
NCT02885181 (CTgov)	临床2期	类风湿关节炎	83	GS-9876 placebo+Filgotinib+Methotrexate (Filgotinib)	膚網鏇鏇鑰選鏇鏇鏇顧(範餘艱鹹窪艱艱網餘窪) = 獵醖鏇艱糧範觸膚築醖壓夢繭築鏇衊願壓醖觸 (憲齋夢糧襯糧鑰願鹽鬱, 1.242) 更多	-	2018-09-19
				Filgotinib placebo+Methotrexate (Placebo)	膚網鏇鏇鑰選鏇鏇鏇顧(範餘艱鹹窪艱艱網餘窪) = 衊醖築範蓋艱鹽鹽蓋製壓夢繭築鏇衊願壓醖觸 (憲齋夢糧襯糧鑰願鹽鬱, 1.044) 更多