– Breadth of Alto’s pipeline and Precision Psychiatry Platform™ will be highlighted across twelve posters and presentations at the Society of Biological Psychiatry and American Society of Clinical Psychopharmacology Annual Meetings – – Presented comprehensive identification and prospective replication of neurobiological markers linked to cognitive impairment associated with schizophrenia; Results inform design of planned ALTO-101 proof-of-concept study in CIAS – – Importance of developing ALTO-100 in depression characterized by poor cognition highlighted through new analyses demonstrating baseline cognition does not moderate response for vortioxetine and poor cognition in turn drives functional impairment in depression – LOS ALTOS, Calif.--(BUSINESS WIRE)-- Alto Neuroscience, Inc. (“Alto”) (NYSE: ANRO) today announced upcoming data presentations that highlight the company’s precision psychiatry pipeline and biomarker-based analyses at the Society of Biological Psychiatry (SOBP) and American Society of Clinical Psychopharmacology (ASCP) Annual Meetings, to take place May 9-11 in Austin, TX, and May 28-31 in Miami Beach, FL, respectively. “The vast amount of clinical and biomarker data we’ve generated to date enables our team to make important contributions to the scientific community and develop novel compounds for patients in need, in both depression and schizophrenia,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “Alto’s precision psychiatry platform continues to get stronger with each new dataset we analyze. Importantly, we have systematically identified and prospectively replicated neurobiological markers linked to cognitive impairment associated with schizophrenia in a comprehensive analysis inclusive of all major candidate biomarkers. Our rigorous data science approach derives its impact from prospectively validating important discoveries. In this case, doing so enables us to identify the most pertinent and consistent signals to use as primary outcome measures for proof-of-concept studies – with theta response as a notable example of this in the planned ALTO-101 study.” Summary of Data Presentations Across Clinical Programs ALTO-100: Data from the completed Phase 2a study highlight the identification, and prospective replication, of a memory-based cognitive marker predicting greater antidepressant response to ALTO-100. New analysis of vortioxetine Phase 3 data demonstrates that baseline cognitive performance is not a moderator of response to vortioxetine. Vortioxetine does not show greater benefit in patients with poor baseline cognitive performance despite its reported benefits for aspects of cognition. New analysis of a large depression trial demonstrates that poor memory predicts worse functional outcomes in depression – further highlighting the need for better treatment options for this underserved population. ALTO-101: Data from a completed randomized, double-blind, placebo-controlled Phase 1 study in healthy adult volunteers demonstrate significant effects of ALTO-101 on electrophysiological measures relevant to cognitive processing, including theta response, as well as information processing speed, an important area of cognitive impairment associated with schizophrenia. A new analysis of the Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP) studies identified, and prospectively replicated, theta response as the EEG marker best linked to schizophrenia diagnosis and cognitive impairment in patients. A notable relationship between theta response and processing speed, which is thought to underpin cognitive impairment in schizophrenia, was observed. ALTO-300: Data from the completed Phase 2a study highlight the identification, and prospective replication, of an EEG-based cognitive marker predicting greater response to ALTO-300. The details of each presentation follow: Society of Biological Psychiatry Annual Meeting Thursday, May 9, 2024 Poster Session I: 5:30-7:30 p.m. CT, Griffin Hall Presentation Title: Identification and Prospective Replication of a Cognitive Biomarker for Predicting the Antidepressant Effect of ALTO-100, a Novel Pro-plasticity Drug Candidate, in Patients with Major Depression: Results from a Large Phase 2a Study Poster Authors: Joshua T. Jordan, Ph.D., Nicholas J. Cooper, Ph.D., Faizan Badami, M.S., Jessica Powell, Wei Wu, Ph.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D. Presentation Title: Identification and Prospective Replication of Electrophysiological Markers Linked to Cognitive Impairment in Schizophrenia Poster Authors: Chao Wang, Ph.D., Sam Goncalves, M.S., Joshua T. Jordan, Ph.D., Maimon Rose, Ph.D., Akshay Sujatha Ravindran, Ph.D., Mike Avissar, M.D., Ph.D., Greg Hajcak, Ph.D., Faizan Badami, M.S., Yueqi Guo, Ph.D., Wei Wu, Ph.D., Jessica Powell, Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D. Presentation Title: Verbal Memory and Inhibitory Control Predict Functional Capacity in Major Depressive Disorder: A Secondary Analysis of the ReMIND SWITCH Trial Poster Authors: Joshua T. Jordan, Ph.D, Li Shen, Ph.D, Wei Wu, Ph.D., Adam J. Savitz, M.D., Ph.D., Amit Etkin, M.D., Ph.D. Friday, May 10, 2024 Concurrent Symposia: 4:00-6:00 p.m. CT, JW Grand Ballroom 2 Session Title: Bringing Precision Psychiatry out of the Lab and Into the Clinic: Developing Biomarkers for Diagnosis, Drug Development, Treatment Selection and Tracking Clinical Status Speakers: Amit Etkin, M.D., Ph.D., founder and CEO of Alto will serve as Chair, and Adam Savitz, M.D., Ph.D., CMO of Alto, will serve as Co-chair of the session. Additional presenters include Daniel Mathalon, M.D., Ph.D., University of California, San Francisco; Magali Haas, M.D., Ph.D., Cohen Veterans Bioscience; Katharine Dunlop, Ph.D., University of Toronto Dr. Etkin will present from 5:25-5:50 p.m. CT: Development and Prospective Replication of Biomarkers for Predicting Treatment Outcome With ALTO-100 and ALTO-300 in Major Depression: Data from Multiple Phase 2 Programs. Dr. Savitz will serve as a discussant for the panel. Poster Session II: 6:00-8:00 p.m. CT, Griffin Hall Presentation Title: Identification and Prospective Replication of an EEG Biomarker for Predicting the Antidepressant Effect of ALTO-300 in Patients with Major Depression: Results from a Large Phase 2a Study Poster Authors: Maimon Rose, Ph.D., Joshua T. Jordan, Ph.D., Chao Wang, Ph.D., Faizan Badami, M.S., Jessica Powell, Fadi Abdel, M.D., Wei Wu, Ph.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D. Presentation Title: Baseline Cognition is Not Associated with Depression Outcomes with Vortioxetine for Major Depressive Disorder: Findings from Placebo-Controlled Trials Poster Authors: Joshua T. Jordan, Ph.D., Li Shen, Ph.D., Nicholas J. Cooper, Ph.D., Samantha V. Goncalves, M.S., Madhukar H. Trivedi, M.D., Alan F. Schatzberg, M.D., Wei Wu, Ph.D., Adam J. Savitz, M.D., Ph.D., & Amit Etkin, M.D., Ph.D. Saturday, May 11, 2024 Poster Session III: 5:00-7:00 p.m. CT, Griffin Hall Presentation Title: Identification of Brain/Behavior-based Pro-cognitive Pharmacodynamic Effects for ALTO-101 in Healthy Volunteers: Results from a Randomized, Double-blind Phase 1 Study Poster Authors: Akshay Ravindran, Ph.D., Guhan Sundar, Samantha Goncalves, M.S., Chao Wang, Ph.D., Li Shen, Maimon Rose, Ph.D., Joshua T. Jordan, Ph.D., Nicholas J. Cooper, Ph.D., Sebastian Marquez, Ph.D., Faizan Badami, M.S., Wei Wu, Ph.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D. American Society of Clinical Psychopharmacology Annual Meeting Tuesday, May 28, 2024 Pharmaceutical Pipeline Session: 2:00-4:00 p.m. ET, Salon 3 Presentation Title: Pro-cognitive Pharmacodynamic Effects of ALTO-101: Results from Brain and Behavioral Outcomes in a Randomized, Double-blind Phase 1 Study Poster Authors: Akshay Ravindran, Ph.D., Guhan Sundar, Samantha Goncalves, M.S., Chao Wang, Ph.D., Li Shen, Ph.D., Maimon Rose, Ph.D., Joshua T. Jordan, Ph.D., Nicholas J. Cooper, Ph.D., Sebastian Marquez, Ph.D., Tabitha Carreira, MPH, Jessica Powell, Faizan Badami, M.S., Wei Wu, Ph.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D. Workshop: 4:15-6:15 p.m. ET, Poinciana 3-4 Presentation Title: Good News/Bad News: Precision Neuroscience and the Clinical Trials Ecosystem Speakers: Mark Opler, Ph.D., M.P.H. (Chair); Adam Savitz, M.D., Ph.D., Alto Neuroscience; Seth C. Hopkins, Ph.D., Sumitomo Pharma America; John Carlos Diaz, GeoSera; John Sonnenberg, Ph.D., Uptown Research Institute; Barbara Echevarria, Ph.D., WCG; George Garibaldi, M.D., Garibaldi Consulting GMBH Wednesday, May 29, 2024 Individual Research Reports: 3:00-4:30 p.m. ET, Salon 2 Presentation Title: Baseline Cognition is not Associated with Depression Outcomes with Vortioxetine for Major Depressive Disorder: Findings from Placebo-controlled Trials Poster Authors: Joshua T. Jordan, Ph.D., Li Shen, Ph.D., Nicholas J. Cooper, Ph.D., Samantha V. Goncalves, M.S., Madhukar H. Trivedi, M.D., Alan F. Schatzberg, M.D., Wei Wu, Ph.D., Adam J. Savitz, M.D., Ph.D., & Amit Etkin, M.D., Ph.D. Thursday, May 30, 2024 Poster Session II: 12:30-2:15 p.m. ET, Salon 4 Presentation Title: A Biomarker-Based Enrichment Strategy for Neuropsychiatric Drug Development: Examples from Two Ongoing Phase 2b Studies Poster Authors: Michael Avissar, M.D., Ph.D., Joshua T. Jordan, Ph.D., Nicholas Cooper, Ph.D., Maimon Rose, Ph.D., Chao Wang, Ph.D., Faizan Badami, M.S., Peter Emmel, Kaitlly Zhu, Jessica Powell, Fadi Abdel, M.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D. Presentation Title: Prevalence and Correlates of Cognitive Impairment in Depression: Findings from the Texas Resilience Against Depression Study Poster Authors: Joshua T. Jordan, Ph.D., Li Shen, Ph.D., Cherise Chin-Fatt, Ph.D., Adam J. Savitz, M.D., Ph.D., Amit Etkin, M.D., Ph.D., & Madhukar H. Trivedi, M.D. About Alto Neuroscience Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto’s Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto’s clinical-stage pipeline includes novel drug candidates in depression, PTSD, schizophrenia, and other mental health conditions. For more information, visit or follow Alto on X. Forward Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto’s expectations for the timing, progress, and results of its studies. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including uncertainties inherent in the initiation, progress and completion of Alto’s studies and other important factors, any of which could cause Alto’s actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled “Risk Factors” in Alto’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 filed with the Securities and Exchange Commission (“SEC”) as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law.

临床2期临床1期ASCO会议临床结果

2024-05-01

·药明康德

基因疗法关键指标临床结果积极；治疗多种癌症，靶向5种KRAS突变的疫苗进入临床…… | 一周盘点

▎药明康德内容团队编辑本期看点1. 治疗杜氏肌营养不良的候选基因疗法GNT0004在1/2/3期临床试验中展现治疗潜力，治疗后第8周时最高有85%的肌纤维表达微肌营养不良蛋白，治疗后第12周时关键生物标志物肌酸磷酸激酶的水平下降了50%-87%。2. 治疗1型脊髓性肌萎缩症的基因疗法EXG001-307在给药后三个月就使患者的头部控制有所改善，11个月时患者无需外部辅助就能保持坐姿。3. 用于治疗抗精神病药引起的体重增加（AIWG）的候选疗法RDX-002能够使服用抗精神病药的患者的餐后甘油三酯降低约82%，并显著抑制其体重的增加。4. 靶向5种KRAS常见突变的治疗性癌症疫苗HB-700的IND申请获得了FDA的许可。药明康德内容团队整理GNT0004：公布1/2/3期临床试验的初步数据由Genethon与伦敦大学皇家霍洛威学院团队和巴黎肌肉研究所合作开发的候选基因疗法GNT0004的1/2/3期临床试验的初步数据积极。GNT0004是一种基于腺相关病毒8（AAV8）载体的基因疗法，含有一个缩短但功能正常的DMD基因（hMD1），编码杜氏肌营养不良患者缺乏的蛋白质——肌营养不良蛋白。hMD1转基因由Spc5.11启动子驱动，可在骨骼肌和心肌等关键组织中表达。截至目前，已有5名年龄在6至10岁之间的患者接受了GNT0004治疗，其中2名患者接受了第一剂量水平的治疗，3名患者接受了第二剂量水平的治疗。初步的安全性和药效学结果表明，GNT0004与免疫预防治疗相结合具有良好的耐受性，在微肌营养不良蛋白表达和功能改善方面也有疗效。接受第二剂量水平的患者在注射GNT0004后的第8周时，免疫组化检测结果显示，最高有85%的肌纤维表达微肌营养不良蛋白（平均54%；范围15%-85%），并重建了肌营养不良蛋白相关蛋白质复合体。这种表达与每个肌纤维核中的转基因拷贝数量显著相关，最高可达2.4（平均1.2；范围0.4-2.4）。治疗后第12周时，患者肌肉损伤的生物标志物肌酸磷酸激酶的水平下降了50%-87%（平均74%）。此外，队列2中首位患者的一年疗效结果积极，NorthStar门诊评估量表（NSAA）得分明显改善，其他功能评估（10米步行测试和起立能力）也呈现出积极的趋势。EXG001-037：公布1/2期临床试验的初步数据Exegenesis Bio公司公布了其用于治疗1型脊髓性肌萎缩症的重组AAV基因疗法EXG001-307的1/2期临床试验的疗效和安全性数据。EXG001-307具有独特的AAV设计，包括一个新颖的pro-NS启动子，与目前可用的基因疗法相比，可在目标脊髓组织中实现高表达，并减少在肝脏和心脏这类非目标组织中的表达。此次公布的结果显示，EXG001-307低剂量组患者在用药3至6个月后实现了头部控制，在用药11个月后无需外部辅助即可保持坐姿。中剂量组中的首位患者在用药3个月后就能在辅助下保持坐姿。安全性方面，EXG001-307具有高耐受性，无剂量限制性毒性，无>2级试验品相关严重不良事件，无>1级转氨酶或心肌酶升高。RDX-002：公布1b期临床试验数据Response Pharmaceuticals公司公布了其用于治疗抗精神病药引起的体重增加的潜在“first-in-class”候选疗法RDX-002的1b期临床试验的初步结果。RDX-002是一种强效、选择性和肠道特异性的小分子甘油三酯微粒体转移蛋白（MTP）抑制剂，旨在降低餐后体内甘油三酯和胆固醇的含量。RDX-002正在开发中，可作为服用非典型抗精神病药物患者的辅助治疗药物，也可作为临床上体重增加和/或不良代谢变化普遍存在的其他情况下的潜在治疗药物。此次公布的结果显示，在为期两周的开放标签试验中，RDX-002队列中的受试者达到了主要疗效终点，即餐后甘油三酯有所降低。接受奥氮平（一种与AIWG相关的高效抗精神病药物）治疗的受试者在第8天时与第1天相比，餐后甘油三酯的平均AUC增加了54%（p=0.009），并在第15天保持升高。而奥氮平+RDX-002治疗组在第15天时与第8天相比，餐后甘油三酯的平均AUC下降了81.6%（p<0.001）。此外，接受奥氮平单药治疗的受试者在治疗的第一周和第二周体重明显增加，而接受奥氮平+RDX-002治疗的患者在第二周时体重没有明显变化。安全性方面，RDX-002的耐受性良好，不良反应主要限于轻度至中度消化道反应，研究期间没有发生严重不良反应或与治疗相关的停药。HB-700：IND申请获得FDA许可HOOKIPA Pharma公司宣布，其用于治疗KRAS突变癌症的新型治疗性疫苗HB-700的IND申请已获得美国FDA的许可。HB-700旨在通过靶向这些疾病中最常见的五种KRAS突变（G12D、G12V、G12R、G12C和G13D），治疗KRAS突变的肺癌、结直肠癌、胰腺癌和其他癌症。与单一突变抑制剂相比，该候选疫苗有望使更多患者受益。RB-ADSC：1期临床试验完成首例患者输注Regeneration Biomedical公司宣布，其用于治疗轻度至中度阿尔茨海默病患者的自体Wnt激活脂肪来源干细胞（RB-ADSC）的1期临床试验已完成首例患者输注。RB-ADSC是Wnt激活的脂肪源性干细胞，取自患者自身的脂肪组织。采集后，干细胞在体外进行培养和扩增，筛选出Wnt表达的干细胞，然后通过植入位于头皮下，可直接进入大脑的一个侧脑室的Ommaya储存器重新输回患者体内。在两种动物模型中的研究结果表明，注入脑室系统的干细胞会自行分布到大脑实质中。此外，没有观察到炎症、脑脊液循环受阻或其他安全信号。VCN-01：公布1期临床试验数据Theriva Biologics公司公布了其在研溶瘤腺病毒疗法VCN-01在眼内视网膜母细胞瘤患者（9人）中进行两次玻璃体内注射的安全性和耐受性。VCN-01是一种溶瘤腺病毒，旨在选择性地在肿瘤细胞内积极复制，并降解肿瘤基质（一种在癌症治疗中重要的物理和免疫抑制屏障）。此次公布的结果显示，玻璃体内注射VCN-01显示出良好的抗肿瘤活性，似乎不会改变视网膜功能。4名患者的症状有明显改善。截至目前，3名患者避免了眼球摘除术，其中一名患者的眼球在随访4年后仍得以保留。安全性方面，VCN-01玻璃体内给药的耐受性良好，最常报告的治疗相关不良反应为1级或2级。在评估期间，没有出现剂量限制性毒性反应，也没有出现≥3级的眼部或全身毒性反应。注射VCN-01后观察到一定程度的眼部炎症和相关浑浊。通过局部和全身使用抗炎药物，炎症能够得到控制，玻璃体混浊在某些情况下也能够得到改善。ONC-841：IND申请获得FDA许可OncoC4公司宣布，美国FDA已经批准了其用于治疗实体瘤的SIGLEC 10阻断抗体ONC-841的IND申请。SIGLEC 10是一种免疫检查点，可抑制先天性和适应性免疫细胞的激活。ONC-841通过抑制SIGLEC 10，阻止癌细胞的免疫逃逸。支持IND申请的临床前研究表明，ONC-841能改善肿瘤浸润T细胞的功能，增强对癌细胞的吞噬能力。其他体内和异种移植肿瘤模型显示，使用ONC-841治疗后，对癌细胞的免疫排斥反应增强了。ONC-841单药治疗的安全性、药代动力学和临床活性的1期临床试验的初步数据预计将于2025年下半年公布。ALTO-101：公布1期临床试验数据Alto Neuroscience公司公布了其用于治疗精神分裂症相关认知障碍（CIAS）的新型PDE4抑制剂ALTO-101的1期研究的积极结果。ALTO-101采用专有的透皮给药（transdermal formulation）系统，旨在提供稳定的浓度，以提高药物的安全性、耐受性和药代动力学。在1期临床试验中，ALTO-101表现出了脑渗透性、强大的中枢神经系统相关的药效学效应，并且在治疗相关剂量范围内耐受性良好。此次公布的研究结果表明，与口服给药相比，ALTO-101通过透皮给药系统给药时具有良好的耐受性和更好的药代动力学。透皮制剂的药物暴露水平明显高于口服给药的全身暴露水平，并且透皮制剂的血浆浓度在服药后的第2天（24-48小时）内依然保持稳定。此外，透皮制剂大大降低了通常与PDE4抑制剂相关的不良反应。接受口服给药的患者有40%出现了头晕，并有20%的患者出现了恶心，而接受透皮给药的患者只有7.1%出现了头晕，没有患者出现恶心。该公司计划在2024年上半年启动一项概念验证研究，评估ALTO-101在CIAS患者中的疗效，预计在2025年下半年获得初步数据。 ▲ALTO-101口服制剂和透皮制剂的药代动力学曲线（图片来源：参考资料[11]）KNS366：公布1期临床试验数据Kynos Therapeutics公司公布了其用于治疗急性和慢性炎症性疾病的小分子犬尿氨-3-单加氧酶（KMO）抑制剂KNS366的积极1期临床试验数据。KMO是一种在色氨酸代谢的犬尿氨酸途径中起关键作用的酶，能将犬尿氨酸转化为3-HK。通过抑制KMO的活性，KNS366可降低升高的3-HK，从而防止炎症期间出现的过度的组织损伤和免疫系统失调。此次公布的结果显示，所有剂量的KNS366都是安全的，而且该分子显示出极佳的耐受性。药效学指标清楚地表明，KNS366是一种强效的KMO酶抑制剂，代谢产物3-HK的大幅减少证明了它具有很强的抑制作用。▲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] Ocugen Announces Dosing Completion of Subjects with Geographic Atrophy in Cohort 2 of Phase 1/2 ArMaDa Clinical Trial of OCU410—A Modifier Gene Therapy. Retrieved April 22, 2024, from https://www.globenewswire.com/news-release/2024/04/19/2866086/0/en/Ocugen-Announces-Dosing-Completion-of-Subjects-with-Geographic-Atrophy-in-Cohort-2-of-Phase-1-2-ArMaDa-Clinical-Trial-of-OCU410-A-Modifier-Gene-Therapy.html[2] GC녹십자, ‘산필리포증후군’ 약물 “美 IND 신청” . Retrieved April 24, 2024, from http://www.biospectator.com/view/news_view.php?varAtcId=21741[3] Kynos Therapeutics announces positive top-line results from the first-in-human Phase I study of its KMO inhibitor, KNS366, demonstrating safety, tolerability and target engagement. 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Retrieved April 24, 2024, from https://investors.centessa.com/news-releases/news-release-details/centessa-pharmaceuticals-announces-open-ind-orx750-proof-concept[6] Enlivex Announces Dosing of First Two Patients in its Randomized, Controlled Phase I/II Trial Evaluating Allocetra™ in Patients with Knee Osteoarthritis. Retrieved April 24, 2024, from https://www.globenewswire.com/en/news-release/2024/04/22/2866825/0/en/Enlivex-Announces-Dosing-of-First-Two-Patients-in-its-Randomized-Controlled-Phase-I-II-Trial-Evaluating-Allocetra-in-Patients-with-Knee-Osteoarthritis.html[7] Neurogene Announces Upcoming Presentation of Safety Data from Phase 1/2 Trial of NGN-401 Gene Therapy for Rett Syndrome at ASGCT Meeting. Retrieved April 24, 2024, from https://www.businesswire.com/news/home/20240422214954/en[8] Response Pharmaceuticals’ Drug Candidate for the Treatment of Antipsychotic-Induced Weight Gain (AIWG) Achieves Primary Endpoint in Phase 1b Clinical Trial. Retrieved April 24, 2024, from https://www.businesswire.com/news/home/20240423868454/en[9] Theriva™ Biologics Announces Positive Topline Data from Investigator Sponsored Phase 1 Trial of Intravitreal VCN-01 in Pediatric Patients with Refractory Retinoblastoma. Retrieved April 24, 2024, from https://www.globenewswire.com/news-release/2024/04/23/2867520/0/en/Theriva-Biologics-Announces-Positive-Topline-Data-from-Investigator-Sponsored-Phase-1-Trial-of-Intravitreal-VCN-01-in-Pediatric-Patients-with-Refractory-Retinoblastoma.html[10] OncoC4 Announces FDA Clearance of IND Application for Novel SIGLEC 10 Immune Checkpoint Inhibitor ONC-841 for Solid Tumors. 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Retrieved April 24, 2024, from https://pipelinereview.com/regeneration-biomedical-doses-first-patient-in-a-first-in-human-phase-i-clinical-trial-of-stem-cell-therapy-delivered-directly-into-the-brain-of-patients-with-alzheimers-disease/[13] ITM, Helmholtz Munich and University Hospital Münster Announce First Patient Dosed in Phase I Investigator-Initiated Glioblastoma Trial. Retrieved April 24, 2024, from https://www.globenewswire.com/news-release/2024/04/23/2867438/0/en/ITM-Helmholtz-Munich-and-University-Hospital-M%C3%BCnster-Announce-First-Patient-Dosed-in-Phase-I-Investigator-Initiated-Glioblastoma-Trial.html[14] First Clinical Trial Results of Gene Therapy (GNT0004) for Duchenne Muscular Dystrophy Presented at International Myology 2024 Congress. Retrieved April 24, 2024, from https://www.businesswire.com/news/home/20240423774806/en[15] HOOKIPA Pharma Announces FDA Clearance of its Investigational New Drug Application for HB-700 for the Treatment of KRAS-Mutated Cancers. 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Retrieved April 24, 2024, from extension://emelgiiiemoiljnmikcgbmjkapalgcme/assets/pdf-viewer/web/viewer.html?file=https%3A%2F%2Fpep-therapy.com%2Fwp-content%2Fuploads%2F2024%2F04%2F20240417-PR-First-patients-Phase-Ib-vf.pdf[21] Exegenesis Bio to Present 9-Patient Data from a Phase 1/2 Clinical Trial of EXG001-307, a Novel rAAV Gene Therapy for Spinal Muscular Atrophy (SMA) Type 1: Improved Head Control and Sitting Without External Assistance. Retrieved April 24, 2024, from https://www.businesswire.com/news/home/20240425546173/en/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

基因疗法临床申请临床结果临床研究疫苗

2024-04-23

·BioSpace

Alto Neuroscience Announces Positive Phase 1 Results for ALTO-101, a Novel PDE4 Inhibitor in Development for Schizophrenia

– ALTO-101 demonstrated a favorable pharmacokinetic and tolerability profile; novel transdermal formulation delivered significantly greater drug exposure and fewer adverse events typically associated with PDE4 inhibitors – – First-in-human achievement of target exposure with proprietary transdermal patch formulation developed in partnership with MEDRx – – Proof-of-concept study in cognitive impairment associated with schizophrenia (CIAS) to be initiated in the first half of 2024 – LOS ALTOS, Calif.--(BUSINESS WIRE)-- Alto Neuroscience, Inc (“Alto”) (NYSE: ANRO) today announced positive results from its healthy volunteer Phase 1 study of ALTO-101, a novel PDE4 inhibitor in development for cognitive impairment associated with schizophrenia (CIAS). Results from the study demonstrated favorable tolerability and improved pharmacokinetics of ALTO-101 when administered via a transdermal delivery system (TDS) compared to oral administration. The TDS formulation is being developed in partnership with MEDRx. The drug exposure levels achieved with the transdermal formulation were significantly greater than systemic exposure with oral administration while also reducing typical class-wide adverse events. The Company plans to initiate a proof-of-concept study evaluating ALTO-101 in patients with CIAS in the first half of 2024, with topline data expected in the second half of 2025. This press release features multimedia. View the full release here: The pharmacokinetic curve illustrates stable drug exposure and achievement of the desired plasma concentration with the transdermal formulation as compared to orally administered ALTO-101. (Graphic: Alto Neuroscience, Inc.) “These positive results provide a strong indication that ALTO-101 could become an important therapeutic option for a broad range of indications,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “Oral PDE4 inhibitors have shown promise as pro-cognitive therapeutics but are associated with burdensome and dose-limiting side effects. Despite these dosing and tolerability challenges, PDE4 inhibitors are used widely in other non-CNS indications, often with sub-optimal dosing regimens. We have now demonstrated transdermal administration of ALTO-101 results in significantly greater, stable drug concentration with a once-daily formulation that is well-tolerated. We believe the reduction in typical class-wide adverse events observed with ALTO-101 provides a significant point of differentiation compared to other PDE4 inhibitors currently available, or in development. We look forward to advancing this product candidate for patients with CIAS who currently have few treatment options.” Phase 1 Study Design and Results The study was designed to evaluate the safety, tolerability, pharmacokinetics, and adhesion properties of a proprietary transdermal formulation of ALTO-101 compared to oral administration of ALTO-101 in healthy human volunteers. It included a 2-way crossover design consisting of two dosing periods. Fifteen adults between 40-64 years old were enrolled in the study. In period 1, participants received a single oral dose of 1 mg ALTO-101, following a 7-day washout period; in period 2, participants received continual transdermal dosing of 18 mg ALTO-101 for two days – patches were administered once-daily and worn for 24 hours. In both periods pharmacokinetics and tolerability were evaluated during and following treatment to measure absorption and elimination. Topline Results from the ALTO-101 Phase 1 study include: ALTO-101 delivered transdermally resulted in significantly higher, and consistent, drug concentrations compared to oral administration: Area under the curve (AUC) was 62% and 170% higher on day 1 and day 2 respectively for the transdermal formulation relative to oral administration (day 1 p=0.01; day 2 p<0.001). The maximum concentration (Cmax.) on day 2 of the transdermal dosing was similar to the Cmax of 1mg of orally administered ALTO-101 (27.9 ng/mL for TDS vs. 30.1 ng/mL oral). Plasma concentrations for the transdermal formulation remained stable throughout the 24 hours of dosing on day 2. ALTO-101 delivered transdermally resulted in substantially lower class-related adverse events typically associated with PDE4 inhibitors. Dizziness - 40% oral vs. 7.1% TDS Nausea - 20% oral vs. 0% TDS All adverse events reported in the study were mild in severity, and there were no reported serious adverse events. No participants discontinued the study due to adverse events. The transdermal formulation demonstrated favorable adhesion properties and there were no application site reactions that led to patch removal or intolerance. Overall, the results from this Phase 1 study indicate a favorable pro ALTO-101 with higher levels of drug exposure, expected to be within the necessary therapeutic range, and lower rates of adverse events. The pharmacodynamic effects observed with orally administered ALTO-101, which were previously reported by the Company, inform the relevant therapeutic range believed to be required to achieve the desired pro-cognitive and clinical effects. Under the terms of the development agreement between Alto and MEDRx, upon this achievement of the desired pharmacokinetic pro ALTO-101, MEDRx is eligible to receive a milestone payment of $1.5 million from Alto that is payable in a combination of cash and common stock of Alto Neuroscience. About ALTO-101 ALTO-101 is a novel small molecule PDE4 inhibitor being developed for cognitive impairment associated with schizophrenia, a disease state defined by negative and cognitive symptoms with no currently available targeted treatments. Through a proprietary transdermal delivery system, ALTO-101 is designed to provide steady state concentrations to improve drug safety, tolerability, and pharmacokinetics. The proprietary transdermal delivery system for ALTO-101 has been developed in partnership with MEDRx. In Phase 1 clinical trials, ALTO-101 demonstrated human brain penetration, robust CNS-relevant pharmacodynamic effects, and was well tolerated across therapeutically relevant dose ranges. About Alto Neuroscience Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto’s Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto’s clinical-stage pipeline includes novel drug candidates in depression, PTSD, schizophrenia, and other mental health conditions. For more information, visit or follow Alto on X. Forward Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto’s expectations for ALTO-101, the timing for the initiation of the ALTO-101 proof-of-concept trial, and the timing of the readout from the trial. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including the risk that Alto’s expectations concerning ALTO-101 which could cause Alto’s actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled “Risk Factors” in Alto’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 filed with the Securities and Exchange Commission (“SEC”) as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law.

临床结果临床1期引进/卖出

100 项与 ALTO-101 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
神经系统疾病	临床2期	-	Alto Neuroscience, Inc.初创企业	-
认知功能障碍	临床1期	-	Alto Neuroscience, Inc.初创企业	-
精神分裂症	临床1期	-	Alto Neuroscience, Inc.初创企业	-
神经系统变性病	临床前	美国	Alto Neuroscience, Inc.初创企业	2023-11-23
神经精神综合征	临床前	美国	Alto Neuroscience, Inc.初创企业	2023-11-23

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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


Biospace 人工标引	临床1期	精神分裂症	15	ALTO-101 (In period 1 oral)	(鏇糧膚鏇範齋遞築範獵) = 餘製醖鑰膚構範廠糧壓遞鏇餘選鏇憲窪構壓醖 (廠膚獵窪積廠鬱夢襯齋 ) 更多	积极	2024-04-23
				ALTO-101 (in period 2 TDS)	(鏇糧膚鏇範齋遞築範獵) = 襯鹹齋廠襯遞艱網觸築遞鏇餘選鏇憲窪構壓醖 (廠膚獵窪積廠鬱夢襯齋 ) 更多