Soquelitinib

▎药明康德内容团队编辑 本期看点 1. 多肽偶联药物（PDC）AVA6000在治疗唾液腺癌（SGC）患者的1a期临床试验中获得积极数据，疾病控制率（DCR）达90%。 2. 蛋白降解药物BHV-1400在首个人体临床试验中获得积极结果，在最低剂量下只需一次注射，就可在4小时内将致病抗体水平降低60%。 3. PI3Kα共价抑制剂TOS-358在一项1期临床试验中对PI3Kα的靶点作用率达到95%。 药明康德内容团队整理 AVA6000：公布1期临床试验数据 Avacta Therapeutics公司宣布，其在研多肽偶联药物AVA6000在治疗唾液腺癌患者的1a期临床试验中获得积极数据。唾液腺癌是一种在转移性阶段尚无标准治疗方案的疾病。AVA6000是Avacta研发管线中的首个多肽偶联药物，由阿霉素（doxorubicin）与Avacta专有的pre|CISION多肽偶联而成，该多肽可在肿瘤微环境中由成纤维细胞激活蛋白-α（FAP）特异性切割。FAP在大多数实体瘤中，与健康组织相比表达水平显著升高。Avacta的多肽偶联药物利用这一特征在肿瘤微环境中特异性释放活性药物，从而降低系统暴露和毒性，为患者提供最佳治疗效果。 此次公布的数据显示，AVA6000在唾液腺癌患者中实现了显著且具有临床意义的肿瘤缩小。在接受250 mg/m²及以上剂量治疗的10名唾液腺癌患者中，DCR达90%，5名患者肿瘤显著缩小，其中包括一例部分缓解（PR，肿瘤缩小45%）和四例轻微缓解（MR，肿瘤缩小10%-19.5%）。安全性方面，在每两周一次和每三周一次两个剂量组中，AVA6000的耐受性良好，与常规剂量阿霉素相比，其血液学和心脏毒性明显降低。目前尚未在任一剂量组中确定最大耐受剂量（MTD）。 BHV-1400：公布1期临床试验的初步数据 Biohaven公司公布了其蛋白降解药物管线中的双特异性分子BHV-1400的最新结果。BHV-1400是一款基于耶鲁大学（Yale University）的MoDE技术的双特异性分子，它的一端与半乳糖缺乏型IgA1（Gd-IgA1）抗体结合，另一端与肝细胞表面的去唾液酸糖蛋白受体（ASGPR）结合。ASGPR介导肝细胞通过内吞过程，将靶点蛋白吞入细胞内进行降解。IgA肾病是由于Gd-IgA1的过度生产造成的，BHV-1400通过降低血液循环和肾脏中的Gd-IgA1水平，有望从根源治疗IgA肾病。 此次公布的初步数据显示，BHV-1400在首个人体临床试验中获得积极结果，在最低剂量下只需一次注射，就可在4小时内将致病抗体水平降低60%。在某些患者中，观察到在8小时内将Gd-IgA1水平降低70%。此外，Gd-IgA1水平的降低在单次注射后可维持数天。安全性方面，迄今为止，BHV-1400在1期临床试验中的安全性和耐受性良好，未发现具有临床意义的先天和适应性免疫力的变化，并且未观察到剂量限制性毒性。这项研究将继续提高BHV-1400的剂量，探索降低Gd-IgA1水平的范围。基于该研究的积极结果，该公司还计划直接启动关键性临床试验，评估BHV-1400治疗IgA肾病的疗效和安全性。 ▲BHV-1400快速降低Gd-IgA1水平（图片来源：Biohaven公司官网） TOS-358：公布1期临床试验数据 Totus Medicines公司公布了其在研PI3Kα共价抑制剂TOS-358的1期临床试验数据。TOS-358是一款具高度特异性、强效的PI3Kα抑制剂，可在临床前模型中实现近100%的PI3Kα抑制，诱导带有PI3Kα突变的异种移植实体瘤的细胞死亡，包含结直肠癌、肺癌、乳腺癌、卵巢癌、食管癌、头颈癌，且几乎没有观察到非靶向抑制。 此次公布的研究结果表明，TOS-358在低至5 mg每日两次（BID）的剂量下具有泛突变临床活性，对PI3Kα的靶点作用率达到95%，且观察到未经确认的完全缓解（CR）。安全性方面，未报道3/4级毒性。值得注意的是，几名接受给药的患者现在已超过6个月未发生进展。在成功完成1期剂量递增研究后，该公司现在启动了一项扩展研究，针对乳腺癌、子宫内膜癌、尿路上皮癌和头颈癌。 ORIC-944：公布1b期联合治疗试验数据 ORIC Pharmaceuticals公司公布了其选择性PRC2别构抑制剂ORIC-944联用阿帕鲁胺治疗转移性去势抵抗性前列腺癌（mCRPC）的1b期临床试验数据。截至2024年12月10日的数据，6例患者中有3例达到确认的PSA50应答（即PSA水平降低50%），其中2例达到确认的PSA90应答。所有PSA应答均维持≥12周，其中包括一例在38周时仍然持续的、确认的PSA90应答。 Soquelitinib：公布1期临床试验的中期数据 Corvus Pharmaceuticals公司公布了其小分子白细胞介素-2诱导的T细胞激酶（ITK）抑制剂soquelitinib用于治疗中度至重度特应性皮炎的1期临床试验的新中期数据。ITK是一种主要表达于T细胞中的酶，在T细胞和自然杀伤（NK）细胞的免疫功能中起重要作用。通过抑制ITK，soquelitinib有望抑制自身免疫和炎症反应。 此次公布的结果显示，与安慰剂相比，soquelitinib治疗组在研究者总体评估（IGA）评分为0/1（皮肤症状清除或几乎清除）和湿疹面积和严重度指数较基线减少75%（EASI 75）这些临床终点方面显示出良好的疗效特征。在soquelitinib组的19例患者中，26%的患者达到IGA 0/1，37%的患者达到EASI 75。在安慰剂组的7例患者中，没有人达到IGA 0/1，也没有人达到EASI 75。安全性方面，未观察到明显的安全问题，也未发现临床上显著的实验室检测异常。 ▲治疗第28天达到终点IGA 0/1、EASI 75的患者占比（图片来源：参考资料[4]） ISM5411：公布两项1期临床试验数据 英矽智能（Insilico Medicine）公司宣布，其自主研发的候选药物ISM5411已完成在澳大利亚和中国开展的两项1期研究，并取得了积极的初步结果。ISM5411是一种潜在用于治疗炎症性肠病（IBD）的小分子抑制剂，靶向PHD1/2靶点且具有新颖的分子结构，该候选药物设计和优化得到了英矽智能生成化学平台Chemistry42的支持。 此次公布的结果显示，在所有剂量组中ISM5411均表现出良好的安全性和耐受性，并初步验证了肠道限制性药代动力学（PK）特征。基于1期临床试验的积极结果，英矽智能预计将于2025年下半年启动一项评估ISM5411在活动性溃疡性结肠炎患者中的2期临床试验。 MBX 1416：公布1期临床试验数据 MBX Biosciences公司公布了在健康成年受试者中开展的MBX 1416单剂量递增和多剂量递增临床试验的积极结果。MBX 1416是一种长效胰高血糖素样肽1（GLP-1）受体拮抗剂，用于治疗减肥后的低血糖症（PBH）。MBX 1416采用MBX公司新颖、专有的精准内分泌肽（PEP）平台设计，旨在防止PBH患者发生严重低血糖，使他们能够过上更健康、更独立的生活。 此次公布的结果显示，MBX 1416通常安全性和耐受性良好，并且具有良好的药代动力学特征，支持每周一次给药。基于这些结果，该公司计划于2025年下半年在PBH患者中启动一项2期研究，以进一步优化剂量。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料（可上下滑动查看） [1] Avacta Announces Positive New Data from the AVA6000 Phase 1 trial Demonstrating Clinically Meaningful Tumor Shrinkage in Patients with Salivary Gland Cancers. Retrieved January 16, 2025, from https://www.globenewswire.com/news-release/2025/01/16/3010665/0/en/Avacta-Announces-Positive-New-Data-from-the-AVA6000-Phase-1-trial-Demonstrating-Clinically-Meaningful-Tumor-Shrinkage-in-Patients-with-Salivary-Gland-Cancers.html [2] Biohaven Highlights Portfolio Progress, Innovation, and Anticipated Milestones at the 43rd Annual J.P. Morgan Healthcare Conference; Reports Positive Degrader Data with Rapid, Deep, and Selective Lowering of Galactose-Deficient IgA1 with Next Generation Potential Therapy for IgA Nephropathy. Retrieved January 14, 2025, from https://www.prnewswire.com/news-releases/biohaven-highlights-portfolio-progress-innovation-and-anticipated-milestones-at-the-43rd-annual-jp-morgan-healthcare-conference-reports-positive-degrader-data-with-rapid-deep-and-selective-lowering-of-galactose-deficient-ig-302349336.html [3] Totus Medicines Announces Successful Completion of a Phase 1 Dose-Escalation Study and Initiation of an Expansion Trial Evaluating TOS-358, a Covalent PI3Ka Selective Therapy for the Treatment of Select Solid Tumors and Appoints Zelanna Goldberg as Chief Medical Officer. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007658/0/en/Totus-Medicines-Announces-Successful-Completion-of-a-Phase-1-Dose-Escalation-Study-and-Initiation-of-an-Expansion-Trial-Evaluating-TOS-358-a-Covalent-PI3Ka-Selective-Therapy-for-th.html [4] Corvus Pharmaceuticals Announces Data from Cohort 2 of Placebo-Controlled Phase 1 Clinical Trial of Soquelitinib for Atopic Dermatitis. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008374/0/en/Corvus-Pharmaceuticals-Announces-Data-from-Cohort-2-of-Placebo-Controlled-Phase-1-Clinical-Trial-of-Soquelitinib-for-Atopic-Dermatitis.html [5] ORIC® Pharmaceuticals Provides Early Phase 1b Combination Data for ORIC-944, Operational Highlights for 2024, and Anticipated Upcoming Milestones. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008495/0/en/ORIC-Pharmaceuticals-Provides-Early-Phase-1b-Combination-Data-for-ORIC-944-Operational-Highlights-for-2024-and-Anticipated-Upcoming-Milestones.html [6] 英矽智能公布炎症性肠病药物ISM5411两项I期临床试验的积极结果. Retrieved January 17, 2025, from https://www.prnasia.com/story/474986-1.shtml [7] MBX Biosciences Announces Positive Phase 1 Topline Results for MBX 1416 for the Treatment of Post-bariatric Hypoglycemia. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/07/3005223/0/en/MBX-Biosciences-Announces-Positive-Phase-1-Topline-Results-for-MBX-1416-for-the-Treatment-of-Post-bariatric-Hypoglycemia.html [8] Mersana Therapeutics Announces Positive Initial Clinical Data from Phase 1 Clinical Trial of Emiltatug Ledadotin (XMT-1660); Initiation of Expansion in Triple Negative Breast Cancer. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007493/0/en/Mersana-Therapeutics-Announces-Positive-Initial-Clinical-Data-from-Phase-1-Clinical-Trial-of-Emiltatug-Ledadotin-XMT-1660-Initiation-of-Expansion-in-Triple-Negative-Breast-Cancer.html [9] Axcynsis Therapeutics Receives FDA Clearance for IND Application of AT03-65, a Differentiated CLDN6-Targeting ADC, Powered by AxcynDOT™ Technology. Retrieved January 17, 2025, from https://www.prnewswire.com/news-releases/axcynsis-therapeutics-receives-fda-clearance-for-ind-application-of-at03-65-a-differentiated-cldn6-targeting-adc-powered-by-axcyndot-technology-302350114.html [10] Ocugen, Inc. Announces Positive 2-Year Data Across Multiple Mutations from Phase 1/2 Clinical Trial of OCU400 —A Novel Modifier Gene Therapy for Retinitis Pigmentosa. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008252/0/en/Ocugen-Inc-Announces-Positive-2-Year-Data-Across-Multiple-Mutations-from-Phase-1-2-Clinical-Trial-of-OCU400-A-Novel-Modifier-Gene-Therapy-for-Retinitis-Pigmentosa.html [11] Verismo Therapeutics Announces First Patient Infused in Phase 1 CELESTIAL-301 Clinical Trial of SynKIR™-310. Retrieved January 17, 2025, from https://www.prnewswire.com/news-releases/verismo-therapeutics-announces-first-patient-infused-in-phase-1-celestial-301-clinical-trial-of-synkir-310-302347464.html [12] Caribou Biosciences Initiates the CB-010 GALLOP Phase 1 Trial in Lupus and Provides Outlook for Multiple Clinical Datasets in 2025. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008079/0/en/Caribou-Biosciences-Initiates-the-CB-010-GALLOP-Phase-1-Trial-in-Lupus-and-Provides-Outlook-for-Multiple-Clinical-Datasets-in-2025.html [13] Arcturus Therapeutics Announces Initiation of Phase 1 H5N1 Flu Vaccine Trial. Retrieved January 17, 2025, from https://ir.arcturusrx.com/news-releases/news-release-details/arcturus-therapeutics-announces-initiation-phase-1-h5n1-flu [14] Korro Bio Announces Dosing of First Participants in REWRITE Phase 1/2a Study of KRRO-110 for Alpha-1 Antitrypsin Deficiency and Provides Pipeline Update. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008445/0/en/Korro-Bio-Announces-Dosing-of-First-Participants-in-REWRITE-Phase-1-2a-Study-of-KRRO-110-for-Alpha-1-Antitrypsin-Deficiency-and-Provides-Pipeline-Update.html [15] NextCure Announces First Patient Dosed in the Phase 1 Study of LNCB74 (B7-H4 ADC) as Therapeutic for Treating Multiple Cancers. Retrieved January 17, 2025, from https://ir.nextcure.com/news-releases/news-release-details/nextcure-announces-first-patient-dosed-phase-1-study-lncb74-b7 [16] LAVA Doses First Patient in Phase 1 LAVA-1266 Study in Hematological Cancers. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007674/0/en/LAVA-Doses-First-Patient-in-Phase-1-LAVA-1266-Study-in-Hematological-Cancers.html [17] Context Therapeutics Announces First Patient Dosed in the Phase 1 Clinical Trial of CTIM-76. Retrieved January 17, 2025, from https://www.globenewswire.com/de/news-release/2025/01/14/3009673/0/en/Context-Therapeutics-Announces-First-Patient-Dosed-in-the-Phase-1-Clinical-Trial-of-CTIM-76.html [18] Ocugen, Inc. Announces First Patient Dosed in Phase 1 Clinical Trial of OCU200—a Novel Integrin-Targeting Biologic for Diabetic Macular Edema. Retrieved January 17, 2025, from https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-first-patient-dosed-phase-1-clinical-trial [19] ProMIS Neurosciences Initiates Phase 1b Clinical Trial (PRECISE-AD) in Alzheimer’s Disease. Retrieved January 17, 2025, from https://www.promisneurosciences.com/news-media/press-releases/detail/236/promis-neurosciences-initiates-phase-1b-clinical-trial [20] Aptose Announces First AML Patients Dosed with Tuspetinib Triplet Frontline Therapy in TUSCANY Trial. Retrieved January 17, 2025, from https://www.aptose.com/news-media/press-releases/detail/307/aptose-announces-first-aml-patients-dosed-with-tuspetinib [21] ORYZON announces first patient dosed in NCI-sponsored iadademstat in combination with venetoclax and azacitidine clinical trial in first line acute myeloid leukemia. Retrieved January 17, 2025, from https://www.oryzon.com/en/news-events/news/oryzon-announces-first-patient-dosed-nci-sponsored-iadademstat-combination [22] 한미약품-GC녹십자, ‘파브리병’ 국내 1/2상 IND 승인. Retrieved January 17, 2025, from https://www.biospectator.com/news/view/24043 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

Jan. 13, 2025 -- Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, today announced new interim data from the randomized, double-blind, placebo-controlled Phase 1 clinical trial evaluating soquelitinib in patients with moderate to severe atopic dermatitis. The data, which include previously reported results from cohort 1 of the trial and new data covering 10 patients with 28-day follow-up from cohort 2 of the trial, demonstrated a favorable safety profile and efficacy profile. This includes significant responses in the soquelitinib treatment groups compared to placebo for clinically significant endpoints of IGA (Investigator Global Assessment) 0 or 1 and EASI (Eczema Area and Severity Index) 75. “As we increase the number of patients, we remain excited by the outlook for our Phase 1 clinical trial of soquelitinib for the treatment of atopic dermatitis,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “These additional data from cohort 2 evaluating a 200 mg once a day dose appear better than the initial results from cohort 1 reported in December. Using rigorous efficacy endpoints of IGA 0 or 1 and EASI 75, we see clinically meaningful activity of soquelitinib in both cohorts compared to the placebo group, which had no patients achieve these endpoints after four weeks of treatment. We focus on these endpoints because they have been accepted as measurements of clinical benefit and have been used as the basis for regulatory approval for several approved treatments for atopic dermatitis.” Dr. Miller added, “Based on the results to-date, we believe soquelitinib will be attractive to physicians and patients due to its convenient oral administration, safety and novel mechanism of action. It also is well positioned as a potential new treatment option for a broad range of immune disease indications based on its ability to modulate and control parallel signaling pathways in the immune system. We look forward to completing enrollment in the atopic dermatitis trial and reporting full results in the second quarter 2025 while also continuing to advance our Phase 3 registration trial in relapsed peripheral T cell lymphoma and other clinical programs.” The Company is reporting results from 16 patients in Cohort 1 (12 patients in the soquelitinib group receiving 100 mg orally twice per day vs. four receiving placebo) and 10 patients in Cohort 2 (seven patients in the soquelitinib group receiving 200 mg orally once per day vs. three receiving placebo) for which 28 days of treatment have been completed. For those 19 patients in the soquelitinib group, 26% achieved IGA 0 or 1 and 37% achieved EASI 75; and of the seven in the placebo group, none achieved IGA 0 or 1 or EASI 75 (see Figure 1 below). IGA 0 or 1 and EASI 75 have been determined by the U.S. Food and Drug Administration (FDA) to be clinically meaningful and approvable endpoints and have been the endpoints used in clinical trials for other FDA approved treatments for atopic dermatitis. No significant safety issues were observed and no clinically significant laboratory abnormalities were seen. All 10 patients from Cohort 2 completed 28 days of dosing at the full dose of 200 mg orally once per day; the remaining patients from Cohort 2 are at various stages of treatment. Cohort 2 of the trial is fully enrolled (N=16) and the Company plans to report full results from all four study cohorts in the second quarter 2025. Figure 1: Percent Patients Achieving Endpoints IGA 0 or 1, EASI 75 at Day 28 of Treatment The placebo patients from Cohort 1 (n=4) and Cohort 2 (n=3) are combined. The randomized, double-blind, placebo-controlled Phase 1 clinical trial is planned to enroll 64 patients with moderate to severe atopic dermatitis that previously failed one prior topical or systemic therapy. Patients are enrolled into one of four dosing cohorts in a 3:1 ratio (12 active and four placebo) to receive either soquelitinib or placebo. The cohorts are sequentially enrolled and will examine 100 mg orally twice per day, 200 mg orally once per day, 200 mg orally twice per day and 400 mg orally once per day. Patients are treated for 28 days and are then followed for an additional 30 days with no therapy. These doses were selected based on the Company’s prior experience evaluating soquelitinib in T cell lymphoma patients. The doses in the atopic dermatitis trial studied in Cohorts 1 and 2 are lower than the 200 mg orally twice a day dosing regimen, which is the level that has been shown to provide complete ITK occupancy and that is being evaluated in the Company’s ongoing registrational Phase 3 clinical trial of soquelitinib in peripheral T cell lymphoma. The primary endpoints include safety and tolerability. Efficacy, measured by improvement in EASI score and IGA, are secondary endpoints. Reduction in itch and various cytokine biomarkers are exploratory endpoints. EASI scores are also evaluated by the percent of patients that achieve a specified percent reduction in EASI score – EASI 50 for patients that achieved a 50% reduction; EASI 75 for a 75% reduction; and EASI 90 for a 90% reduction. Corvus and a data monitoring committee monitor the data from the trial as the trial progresses. Dr. Miller will present a corporate overview including the new data from Cohort 2 of the soquelitinib Phase 1 clinical trial at the 43rd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15 at 2:15 pm ET / 11:15 am PT. An audio webcast of the presentation will be available live and for 30 days following the event. The webcast may be accessed via the investor relations section of the Corvus website. Atopic dermatitis, also called eczema, is a chronic disease that can cause inflammation, redness, scaly patches, blisters and irritation of the skin. It affects up to 20% of children and up to 10% of adults, and treatments include topical therapies, oral therapies and systemic injectable biologic therapies. It is frequently associated with other allergic disorders such as food allergies and asthma. Atopic dermatitis, like asthma and allergy, involves the participation of Th2 lymphocytes which secrete cytokines that result in inflammation. Soquelitinib has been shown in preclinical studies to inhibit cytokine production from Th2 lymphocytes. Soquelitinib (formerly CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit ITK (interleukin-2-inducible T cell kinase), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. Soquelitinib has been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of their secreted cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with cancers, including solid tumors, and in patients with autoimmune and allergic diseases. Recent studies have demonstrated that ITK controls a switch between the differentiation of Th17 proinflammatory cells and T regulatory suppressor cells. Inhibition of ITK leads to a shift toward T regulatory cell differentiation which has the potential to suppress autoimmune and inflammatory reactions. Based on interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas, which demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, the Company has initiated a registrational Phase 3 clinical trial (NCT06561048) of soquelitinib in patients with relapsed PTCL. Soquelitinib is also now being investigated in a randomized placebo-controlled phase 1 clinical trial in patients with atopic dermatitis. A recent publication describing the chemistry, enzymology and biology of soquelitinib appeared in npj Drug Discovery in December 2024 and is available online at the Nature website and on the Publications and Presentations page of the Corvus website. Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of cancer and immune diseases. The Company’s lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Its other clinical-stage candidates are being developed for a variety of cancer indications. For more information, visit www.corvuspharma.com. The content above comes from the network. if any infringement, please contact us to modify.