Gemcitabine Hydrochloride

Promising preliminary Phase 2b (ASCEND) pancreatic cancer data (Cohort A) reported with Cohort B data anticipated in the coming months Enrollment completed in Qilu’s Phase 2 trial evaluating certepetide for the treatment of first-line mPDAC Advancing development portfolio with multiple milestones projected over the next 12+ months Cash runway extending into the second quarter of 2026 with no debt Conference call scheduled for today at 4:30 p.m. Eastern Time BASKING RIDGE, N.J., Feb. 27, 2025 (GLOBE NEWSWIRE) -- Lisata Therapeutics, Inc. (Nasdaq: LSTA) (“Lisata” or the “Company”), a clinical-stage pharmaceutical company developing innovative therapies for the treatment of advanced solid tumors and other serious diseases, provides a business update and reports financial results for the twelve months ended December 31, 2024. “Throughout 2024 and now into early 2025, we continue to advance our development portfolio centered around our novel product candidate, certepetide,” stated David J. Mazzo, Ph.D., President and Chief Executive Officer of Lisata. “Following the encouraging preliminary results from the ASCEND and iLSTA trials reported at this year’s ASCO-GI Symposium, we remain committed to exploring the broad application of certepetide’s unique mechanism of action. Our development portfolio encompasses multiple clinical and preclinical trials evaluating certepetide for the treatment of various solid tumors, including pancreatic cancer, cholangiocarcinoma, glioblastoma, colon cancer, appendiceal cancer, and melanoma. In addition, we are exploring certepetide’s versatility in non-cancerous settings such as endometriosis. For Lisata, we expect 2025 to be a data-rich year and we look forward to sharing key developments as they become available.” Development Portfolio Highlights Certepetide as a treatment for solid tumors in combination with other anti-cancer agents Certepetide (formerly LSTA1) is an internalizing RGD, or iRGD, (arginylglycylaspartic acid) cyclic peptide designed to selectively activate the C-end rule active transport mechanism in a tumor specific manner, resulting in systemically co-administered anti-cancer agents more efficiently penetrating and accumulating in the tumor. Additionally, certepetide has been shown to modify the tumor microenvironment, diminishing its immunosuppressive nature, enhancing cytotoxic T cell concentration and inhibiting the metastatic cascade. Lisata and its collaborators have amassed significant non-clinical data demonstrating enhanced delivery of various existing and emerging anti-cancer therapies, including chemotherapies, immunotherapies, and RNA-based therapeutics. To date, certepetide has also demonstrated favorable safety, tolerability, and clinical activity in completed and ongoing clinical trials designed to demonstrate its ability to enhance the effectiveness of standard-of-care (SoC) chemotherapy for pancreatic cancer as well as the combination of chemotherapy and immunotherapy in a variety of solid tumors. Certepetide has been awarded Fast Track designation (U.S.) and Orphan Drug Designation for pancreatic cancer (U.S. and E.U.) as well as Orphan Drug Designation for glioma, osteosarcoma, and cholangiocarcinoma (U.S.). Additionally, certepetide has received Rare Pediatric Disease Designation for osteosarcoma (U.S.). Currently, certepetide is the subject of multiple ongoing or planned clinical studies being conducted globally across several solid tumor types in combination with a variety of anti-cancer regimens, including: ASCEND: Phase 2b double-blind, randomized (2:1 ratio), placebo-controlled trial evaluating two dosing regimens of certepetide in combination with SoC chemotherapy (gemcitabine/nab-paclitaxel) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). The trial is being conducted across 25 sites in Australia and New Zealand led by the Australasian Gastro-Intestinal Trials Group (AGITG) and coordinated by the National Health and Medical Research Council Clinical Trial Centre at the University of Sydney. Cohort A, with 95 patients receiving a single intravenous (IV) dose of certepetide 3.2 mg/kg or placebo in combination with SoC, completed enrollment in the third quarter of 2023. Preliminary Cohort A data presented at the 2025 ASCO-GI Symposium showed a positive trend in overall survival, including four complete responses in the certepetide-treated group compared to none in the placebo treated group. Data from Cohort B, with 63 patients receiving two IV doses of certepetide 3.2 mg/kg or placebo administered 4 hours apart in combination with SoC, is expected in the coming months with a final analysis of both cohorts available thereafter. The exact timing is dependent on accumulating the requisite number of endpoint events in Cohort B and is not something that can be accurately predicted. BOLSTER: Phase 2a double-blind, placebo-controlled, multi-center, randomized trial in the U.S. evaluating certepetide in combination with SoC chemotherapy in first- and second-line cholangiocarcinoma (CCA). The Company achieved complete enrollment in first-line CCA nearly six months ahead of plan, accelerating anticipated topline data readout to mid-2025. Based on this rapid enrollment rate and the pressing need to improve treatment outcomes in patients that have progressed after first-line CCA treatment, a second cohort has been added to the BOLSTER trial evaluating certepetide in combination with SoC in subjects with second-line CCA. In September 2024, Lisata announced first patient treated in the second-line CCA cohort, with enrollment completion targeted for later this year. CENDIFOX: Phase 1b/2a open-label trial in the U.S. evaluating certepetide in combination with neoadjuvant FOLFIRINOX based therapies in pancreatic, colon and appendiceal cancers. In December 2024, the Company announced enrollment completion in all three cohorts. The single-center study, conducted solely at the University of Kansas Cancer Center, was designed with a 3-cycle run-in period to ensure patients met specific criteria before receiving treatment. Of the 66 patients enrolled, 50 patients met the criteria and were treated with certepetide across three cohorts, including 24 with resectable or borderline resectable pancreatic cancer, 15 with high-grade colon or appendiceal cancer and peritoneal metastasis, and 11 with oligometastatic colon cancer. The trial will provide Lisata with valuable pre- and post-treatment tumor tissue data for immune profiling, along with long-term patient outcome information. CENDIFOX data are expected in the coming months; however, given this is an investigator-initiated study, the exact timing is not in Lisata’s control. The trial is funded by the University of Kansas Cancer Center and Lisata is supplying certepetide. Qilu Pharmaceutical, the licensee of certepetide in the Greater China territory, is currently evaluating certepetide in combination with gemcitabine and nab-paclitaxel as a treatment for first-line mPDAC. During the 2023 ASCO Annual Meeting, Qilu Pharmaceutical presented an abstract sharing preliminary data from the study which corroborated previously reported findings from the Phase 1b/2a trial of certepetide plus gemcitabine and nab-paclitaxel conducted in Australia in patients with first-line mPDAC. Qilu has completed enrollment in its Phase 2 trial and data are expected in the coming months. iLSTA: Phase 1b/2a randomized, single-blind, single-center, safety and pharmacodynamic trial in Australia, funded by WARPNINE Inc., is evaluating certepetide in combination with SoC chemotherapy (nab-paclitaxel and gemcitabine) plus SoC immunotherapy (durvalumab) versus SoC alone in patients with locally advanced non-resectable PDAC. An interim analysis of the iLSTA trial, presented at the 2025 ASCO GI Symposium, showed preliminary results from the first 17 of the 30 targeted patients, corroborating preclinical data that certepetide enhances the effectiveness of immunotherapy. With 27 of the 30 patients enrolled, enrollment remains on track to be completed by the first half of 2025. A Lisata-funded Phase 2a, double-blind, placebo-controlled, randomized, proof-of-concept study evaluating certepetide in combination with SoC temozolomide versus temozolomide alone in patients with newly diagnosed glioblastoma multiforme (GBM) is being conducted across multiple sites in Estonia and Latvia and is planned to also include a site in Lithuania. The study is targeted to enroll 30 patients with a randomization of 2:1 in favor of the certepetide treatment group. Enrollment completion is targeted for the second half of 2025. FORTIFIDE: Phase 1b/2a, double-blind, placebo-controlled, three-arm, randomized study in the U.S. evaluating the safety, tolerability, and efficacy of a 4-hour continuous infusion of certepetide in combination with SoC in subjects with first-line mPDAC. As part of this study, Lisata has engaged Haystack Oncology to use its MRD™ technology to measure circulating tumor DNA levels at multiple timepoints in patients throughout the study as an exploratory endpoint for analyzing the early therapeutic effect of certepetide. The Company expects to enroll the first patient in the study in the first half of 2025. However, in parallel, management is investigating a potentially faster and more cost-effective approach to achieving the study objective, which may become the preferred strategy. Lisata has entered into multiple research collaborations, including a sponsored research agreement with the University of Cincinnati to assess certepetide in combination with bevacizumab (a VEGF inhibitor) in a preclinical murine model for the treatment of endometriosis. Lisata is also partnering with Valo Therapeutics (ValoTx) to investigate the benefits of combining certepetide with ValoTx's platform technology, PeptiCRAd, an oncolytic virus, and a checkpoint inhibitor in a preclinical murine model for the treatment of melanoma. In November 2024, Lisata entered into an Exclusive License and Collaboration Agreement with Kuva Labs, Inc. (“Kuva”), in which Lisata granted Kuva an exclusive license to explore the synergistic potential of certepetide as a targeting and delivery agent for Kuva’s NanoMark™ imaging technology in solid tumors. Under the agreement, Kuva will assume full responsibility for research, development, and commercialization costs, while Lisata will be responsible for supplying certepetide pursuant to a Clinical Supply Agreement. As consideration for the license, the Company is to receive a $1.0 million upfront license fee and is eligible for certain development and commercial milestone payments of up to $19.0 million, as well as a single-digit percentage royalty on net sales. Full Year 2024 Financial Highlights For the year ended December 31, 2024, revenue totaled $1.0 million in connection with an upfront license fee related to the Exclusive License and Collaboration Agreement with Kuva Labs, Inc. The Company did not have any revenue for the year ended December 31, 2023. For the year ended December 31, 2024, operating expenses totaled $23.4 million compared to $25.7 million for the year ended December 31, 2023, representing a decrease of $2.3 million or 8.9%. Research and development expenses were approximately $11.3 million for the year ended December 31, 2024, compared to $12.7 million for the year ended December 31, 2023, representing a decrease of approximately $1.4 million, or 11.0%. This was primarily due to a reduction in expenses associated with the Phase 2b ASCEND trial which completed enrollment in the prior year, lower spend on chemistry, manufacturing and controls, and lower equity expense. General and administrative expenses were approximately $12.1 million for the year ended December 31, 2024, compared to $13.0 for the year ended December 31, 2023, representing a decrease of approximately $0.9 million or 6.9%. This was primarily due to one-off related severance costs in the prior year associated with the elimination of the Chief Business Officer position on May 1, 2023, a reduction in equity expenses, a decrease in directors’ and officers’ insurance premiums, and a reduction in spend on legal fees partially offset by one-off settlement related costs and an increase in consulting expenses. Overall, net losses were $20.0 million and $20.8 million for the years ended December 31, 2024 and 2023, respectively. Balance Sheet Highlights As of December 31, 2024, Lisata had cash, cash equivalents, and marketable securities of approximately $31.2 million. Based on its existing and planned activities, the Company believes available funds will support current operations into the second quarter of 2026. Net Operating Loss Sale Earlier this year Lisata received $0.9 million in non-dilutive funding as an approved participant of the Technology Business Tax Certificate Transfer Program (the “Program”) sponsored by the New Jersey Economic Development Authority (NJEDA). The Program enables qualifying New Jersey-based biotechnology or technology companies to sell a percentage of their New Jersey net operating losses and research and development tax credits to unrelated qualifying corporations with a lifetime cap on the tax benefit sales of $20.0 million. To date, under the Program, the Company has sold $19.6 million in tax benefits for net proceeds of $18.4 million. Conference Call Information Lisata will hold a live conference call today, February 27, 2025, at 4:30 p.m. Eastern Time to discuss financial results, provide a business update, and answer questions. Those wishing to participate must register for the conference call by way of the following link: CLICK HERE TO REGISTER. Registered participants will receive an email containing conference call details with dial-in options. To avoid delays, the Company encourages participants to dial into the conference call 15 minutes ahead of the scheduled start time. A live webcast of the call will also be accessible under the Investors & News section of Lisata’s website and will be available for replay beginning two hours after the conclusion of the call for 12 months. About Lisata Therapeutics Lisata Therapeutics is a clinical-stage pharmaceutical company dedicated to the discovery, development and commercialization of innovative therapies for the treatment of advanced solid tumors and other major diseases. Lisata’s cyclic peptide product candidate, certepetide, is an investigational drug designed to activate a novel uptake pathway that allows co-administered or tethered anti-cancer drugs to selectively target and penetrate solid tumors more effectively. Lisata has already established noteworthy commercial and R&D partnerships based on its CendR Platform® technology. The Company expects to announce numerous milestones over the next 1.5 years and believes that its projected capital will fund operations into the second quarter of 2026, encompassing anticipated data milestones from its ongoing and planned clinical trials. Learn more about certepetide’s mechanism of action in our short film. For more information on the Company, please visit www.lisata.com. Forward-Looking Statements This communication contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this communication regarding the Company’s clinical development programs are forward-looking statements. In addition, when or if used in this communication, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Lisata or its management, may identify forward-looking statements. Examples of forward-looking statements include, but are not limited to, the potential efficacy of certepetide as a treatment for patients with metastatic pancreatic ductal adenocarcinoma and other solid tumors; our beliefs about the potential uses and benefits of certepetide; statements relating to Lisata’s continued listing on the Nasdaq Capital Market; expectations regarding the capitalization, resources and ownership structure of Lisata; the approach Lisata is taking to discover and develop novel therapeutics; the adequacy of Lisata’s capital to support its future operations and its ability to successfully initiate and complete clinical trials; and the difficulty in predicting the time and cost of development of Lisata’s product candidates. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: results observed from a single patient case study are not necessarily indicative of final results and one or more of the clinical outcomes may materially change following more comprehensive reviews of the data and as more patient data becomes available, including the risk that unconfirmed responses may not ultimately result in confirmed responses to treatment after follow-up evaluations; the risk that product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials; the safety and efficacy of Lisata’s product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in Lisata’s clinical programs, Lisata’s ability to finance its operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of Lisata’s scientific studies, Lisata’s ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in Lisata’s markets, the ability of Lisata to protect its intellectual property rights; and legislative, regulatory, political and economic developments. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in Lisata’s Annual Report on Form 10-K filed with the SEC on February 27, 2025, and in other documents filed by Lisata with the Securities and Exchange Commission. Except as required by applicable law, Lisata undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events, or otherwise. Lisata Therapeutics Contact: Investors: Lisata Therapeutics John Menditto Vice President, Investor Relations and Corporate Communications Phone: 908-842-0084 Email: jmenditto@lisata.com Media: ICR Healthcare Elizabeth Coleman Account Supervisor Phone: 203-682-4783 Email: elizabeth.coleman@icrhealthcare.com – Tables to follow – This press release was published by a CLEAR® Verified individual.

同源康医药近日宣布，其自主研发的新一代口服、高效、高选择性的小分子CDK7抑制剂TY-2699a联合不同给药方案治疗晚期实体瘤获得国家药品监督管理局药品审评中心（CDE）同意开展临床试验的正式函件。此前，TY-2699a单药已获得CDE和美国食品药品监督管理局(FDA)同意开展临床试验的正式函件（Study May Proceed Letter, IND 169813）。全球目前没有获批上市的CDK7抑制剂，针对此靶点开发的药物具有广泛的临床应用前景。 关于TY-2699a TY-2699a 是浙江同源康医药股份有限公司自主研发的一款口服的高效、高选择性的小分子CDK7抑制剂，联合给药拟用于治疗多种晚期实体瘤，包括乳腺癌、胰腺癌、头颈鳞状细胞癌。I期临床试验结果表明TY-2699a单药的整体不良反应级别低，可逆且可控，其绝大多数不良事件均为1-2级，这也和临床前体外及体内药效试验结果相互印证，即在正常细胞不敏感的剂量下，仅选择性地抑制癌细胞的生长，因此具有良好的耐受性和安全性。TY-2699a单药亦对部分受试者表现出疾病稳定的初步治疗效果。以上临床数据为联合用药临床研究的开展提供了坚实的基础。 关于CDK7联合用药 联合氟维司群或口服SERD（特异性雌激素受体降解剂）治疗乳腺癌的机制 体内研究发现，单纯CDK7抑制剂处理导致阻止雌激素受体（ER）的丝氨酸118位点磷酸化，从而上调ER表达，激活ER信号通路。当CDK抑制剂与氟维司群联用时，ER阳性乳腺癌肿瘤生长明显受到抑制。此外，RB缺失，ER突变的T47D Palbciclib耐药细胞对CDK7抑制剂非常敏感。同样的结果也被CDK7抑制剂同类药和近期发表的其它高质量研究报告证明，此外，CDK7抑制剂联合口服SERD代表ER阳性乳腺癌治疗的重要方向。 Clin Cancer Res 2024;30:1889–905 联合吉西他滨和白蛋白紫杉醇化疗药物的机制 白蛋白紫杉醇可以通过抑制吉西他滨主要代谢酶-胞苷脱氨酶的活性来增强吉西他滨的稳定性；其次，在胰腺癌中，CDK7高表达阻碍了白蛋白紫杉醇联合吉西他滨引起的肿瘤细胞凋亡，CDK7 抑制通过STAT3-MCL1-CHK1 信号通路轴来诱导细胞周期停滞，细胞凋亡，及DNA 损伤等功能。因此，靶向抑制CDK7可以显著增强白蛋白紫杉醇联合吉西他滨的疗效 J Exp Clin Cancer Res. 2022;41(1):241. 联合PD-1抗体的作用机制 我司临床前研究显示CDK7抑制剂TY-2699a处理FaDu以及Cal-27两株细胞之后，激活免疫系统，引起免疫应激反应。同类药选择性CDK7抑制剂YKL-5-124联合抗PD-1在多种高侵袭性SCLC小鼠模型中提供了显著的生存获益，为由CDK7抑制剂和免疫疗法组成的新联合方案提供了理论依据。对于NSCLC患者，CDK7抑制剂THZ1增加了PD-1抗体的免疫治疗疗效,其机制和p38α/MYC/PD-L1通路有关。一款处于临床前阶段的同类药THZ1和和鼻咽癌细胞共培养，会导致肿瘤细胞内下游基因也就是和疗效相关的基因发生显著变化。 Cancer Cell 37, 37–54 参考文献 Guarducci, C., et al., Selective CDK7 Inhibition Suppresses Cell Cycle Progression and MYC Signaling While Enhancing Apoptosis in Therapy-resistant Estrogen Receptor-positive Breast Cancer. Clin Cancer Res, 2024. 30(9): p. 1889-1905. Pancholi, S., et al., Tumour kinome re-wiring governs resistance to palbociclib in oestrogen receptor positive breast cancers, highlighting new therapeutic modalities. Oncogene, 2020. 39(25): p. 4781-4797. Frese, K.K., et al., nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov, 2012. 2(3): p. 260-269. Zeng, S., et al., CDK7 inhibition augments response to multidrug chemotherapy in pancreatic cancer. J Exp Clin Cancer Res, 2022. 41(1): p. 241. Bashir, B., et al., Phase 1/1b study of SY-5609, a selective and potent CDK7 inhibitor, in advanced solid tumors and in 2L/3L pancreatic ductal adenocarcinoma (PDAC) in combination with gemcitabine +/- nab-paclitaxel. 2023. 41(16_suppl): p. 3080-3080. Zhang, H., et al., CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer. Cancer Cell, 2020. 37(1): p. 37-54.e9. Jian W., et al., CDK7 inhibitor THZ1 enhances antiPD-1 therapy efficacy via the p38α/MYC/PD-L1 signaling in non-small cell lung cancer. J Hematol Oncol. 2020 Jul 20;13(1):99. Gao, L., et al., Gene expression profile of THZ1-treated nasopharyngeal carcinoma cell lines indicates its involvement in the inhibition of the cell cycle. Transl Cancer Res, 2021. 10(1): p. 445-460.