Exatecan mesilate

2024年6月18日，Day One Biopharmaceuticals宣布已与MabCare Therapeutics（MabCare）就MTX-13达成独家许可协议。根据协议条款，Day One拥有全球（大中华区除外）开发、制造和商业化MTX-13的独家权利（引进后更名为DAY301）。 MabCare将获得首付款5500万美元，以及有权按照开发、注册和商业化里程碑获得其余11.52亿美元，外加基于大中华区以外净销售额的低到中个位数权益分成。 DAY301是一种靶向蛋白酪氨酸激酶7（PTK7）的新型ADC。该酶在成人食管癌、卵巢癌、肺癌和子宫内膜癌以及儿童神经母细胞瘤、横纹肌肉瘤和骨肉瘤中高度表达。 DAY301：下一代PTK7 ADC 在临床前研究中，DAY301在广泛的实体瘤中显示出抗肿瘤活性。 PTK7是已经过临床验证的靶标：辉瑞/艾伯维公司cofetuzumab pelidotin 1b期试验证明了抗ptk7 ADC的抗肿瘤活性。 DAY301使用了一种全新的自裂解分子T1000，而所用的毒素是exatecan，DAR值为8。 2023年发表的一篇文献披露了MTX-13（DAY301）由5家单位合作完成，除了两所高校之外，还有三家公司。分别为Multitude Therapeutics普众发现，HySlink Therapeutics汇连生物和MabCare Therapeutics。 MTX-13已证明具有针对PTK7的特异性细胞结合能力、有效的细胞内摄取以及在体外条件下的释放能力。它通过诱发DNA损伤和细胞凋亡机制，展现出显著的细胞毒性效应，并具备强大的旁观者效应。PTK7在小细胞肺癌中被认为是一个有效的治疗靶点，MTX-13在其中表现出了彻底且持久的治疗效果。考虑到PTK7在多种来源的鳞状细胞癌中普遍呈现过表达现象，MTX-13在这类肿瘤中的高效力表明了其作为一种普遍适用的治疗手段的潜力。此外，MTX-13在结肠癌原位异种移植模型中也显示出了抑制肿瘤生长和转移的能力。 Day One计划在今年Q4或2025年的头几个月开启临床一期试验。成人适应性包括：鳞状NSCLC，eSCC，HNSCC，内膜癌，以及SCLC。儿童适应症选择比较小众的神经母细胞瘤，骨肉瘤，横纹肌肉瘤。 附录：国内ADC出海汇总 资料来源： 1.Day One inks $1.2B biobucks pact for MabCare’s solid tumor ADC.By Gabrielle Masson .Jun 18, 2024 2.https://ir.dayonebio.com/news-releases/news-release-details/day-one-expands-pipeline-potential-first-class-clinical-stage 3.https://ir.dayonebio.com/static-files/d3ce58df-b1b1-4dcb-aee4-88b3da3adbcb 4.Kong C, Pu J, Zhao Q, Weng W, Ma L, Qian Y, Hu W, Meng X, Meng T. MTX-13, a Novel PTK7-Directed Antibody-Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors. Mol Cancer Ther. 2023 Oct 2;22(10):1128-1143. 5.超12亿美元：Day one公司从中国biotech引进一款PTK7 ADC.新药猎人笔记.2024-06-19 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

TUB-040 is a next-generation NaPi2b-targeting Exatecan ADC based on Tubulis’ proprietary P5 technology with superior biophysical properties that demonstrated effective and durable responses in a range of preclinical models The clinical trial will enroll up to 140 patients with platinum-resistant high-grade ovarian cancer or relapsed/refractory adenocarcinoma non-small cell lung cancer in the US, the UK and Europe MUNICH--(BUSINESS WIRE)-- Tubulis announced today that the first patient has been treated in its first Phase I/IIa trial (NAPISTAR 1-01, NCT06303505). The study is evaluating Tubulis’ next-generation antibody-drug conjugate (ADC) TUB-040 in patients with platinum-resistant high-grade ovarian cancer (PROC) or relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC), who have exhausted other available treatment options. TUB-040 targets NaPi2b, a highly overexpressed antigen in ovarian cancer and lung adenocarcinoma. The candidate is the first to enter the clinic from the company’s growing pipeline and represents one of Tubulis’ two lead candidates developed using its proprietary suite of platform technologies, which enable the creation of uniquely matched ADCs with superior biophysical properties. The multicenter, first-in-human, dose escalation and optimization Phase I/IIa study aims to investigate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy. The trial will be conducted in the US as well as the UK, Spain, Belgium, and Germany. Phase Ia comprises the dose escalation and will determine safety and the maximum tolerated dose or the identified dose for optimization, whereas Phase IIa will focus on dose optimization, safety, and preliminary efficacy of TUB-040. The first patient has been dosed in the US following IND approval by the FDA. “ADCs are beginning to show their potential as a core treatment modality replacing conventional chemotherapy for several solid tumor indications. Based on our preclinical data we are convinced that TUB-040 can represent a new option for the effective treatment of NSCLC and ovarian cancer patients,” said Günter Fingerle-Rowson, MD, PhD, Chief Medical Officer at Tubulis. “The novel P5 technology we use in TUB-040 improves upon current limitations due to off-target toxicity and restricted durability, the main challenges of current ADC treatments. By achieving reduced non-target toxicity together with a more specific, more powerful, and continued on-tumor delivery of the payload, we aim to improve long-term anti-tumor responses and, ultimately, clinical outcomes for patients.” “Initiating our first clinical trial represents an important milestone for the entire Tubulis team and underscores our vision to innovate on all fronts of the ADC design for patient benefit,” said Dominik Schumacher, PhD, Chief Executive Officer and Co-founder of Tubulis. “Our objective is to achieve clinical proof-of-concept for our lead candidate, TUB-040, and validate our differentiated platform approach to ADC development.” TUB-040 consists of a humanized, target-specific, Fc-silenced IgG1 antibody equipped with Tubulis’ proprietary Tubutecan linker-payload technology, which is based on P5 conjugation chemistry and the topoisomerase-1 inhibitor Exatecan. Tubulis recently presented a comprehensive preclinical data set at AACR, demonstrating the superior stability and minimal loss of linker-payload conjugation for their lead candidate. In a range of preclinical models, Tubulis was also able to show high and long-lasting anti-tumor responses, even at lower expression levels of NaPi2b, with an excellent safety and tolerability profile. About TUB-040 and the P5 Technology Tubulis’ lead antibody-drug conjugate (ADC) TUB-040 is directed against Napi2b, an antigen highly overexpressed in ovarian cancer and lung adenocarcinoma. It consists of an IgG1 antibody targeting Napi2b connected to the Topoisomerase I inhibitor Exatecan through a cleavable linker system based on the company’s proprietary P5 conjugation technology with a homogeneous DAR of 8. P5 conjugation is a novel chemistry for cysteine-selective conjugation that enables ADC generation with unprecedented linker stability and biophysical properties. It originated from the fundamental work of Prof. Christian Hackenberger at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP), which unlocked the use of phosphorus chemistry for superior bioconjugation. Preclinical pharmacokinetic analysis also demonstrated that TUB-040 efficiently delivers its payload to the tumor while reducing off-site toxicities. The candidate is currently being investigated in a multicenter Phase I/IIa study (NAPISTAR 1-01, NCT06303505) that aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy. About Tubulis Tubulis’ suite of proprietary platform technologies generates uniquely matched antibody-drug conjugates with superior biophysical properties for treating solid tumors. By demonstrating durable on-tumor delivery of the payload and long-lasting anti-tumor activity, we have reached the clinic with our first program, TUB-040, in ovarian and non-small cell lung cancer. The second candidate from our growing pipeline, TUB-030, is set to follow in the near-term. We will solidify our leadership position by continuing to innovate on all aspects of ADC design to expand their therapeutic potential for our pipeline, our partners and for patients. Visit or follow us on LinkedIn. View source version on businesswire.com: Contacts For Tubulis Dominik Schumacher, CEO & Co-Founder Phone: +49 175 800 5594 Email: contact@tubulis.com Media Requests for Tubulis Trophic Communications Stephanie May, PhD Phone: +49 (0) 171 185 56 82 Email: tubulis@trophic.eu Source: Tubulis View this news release online at: