Siamab Therapeutics, Inc.

AUSTIN, Texas--(BUSINESS WIRE)-- PanTher Therapeutics (“PanTher” or the “Company”), a clinical-stage oncology company developing high-dose, long lasting, localized treatments for cancer, announced that John Edwards has been appointed as the Executive Chair of the Board of Directors. “John has been an outstanding addition to our Board and management team since joining the company in September. We look forward to further benefiting from his experience as we continue to advance our lead program, PTM-101, into later stage clinical trials,” said Laura Indolfi, PhD, Chief Executive Officer and co-founder of PanTher. “John has successfully guided many biotech companies through key stages in their evolution and he is a tremendous resource for our organization.” John brings over 35 years of experience in discovery, development, and global commercialization of biopharmaceuticals to PanTher. His experience includes involvement with ten FDA approved biologics and eight biotech companies with successful exits, including Tilos Therapeutics, Siamab, Adnexus, F-star and Genetics Institute. Most recently, John held the role of Executive Chair and CEO at Abcuro, where he transformed the small preclinical-stage company into a well-funded organization with a highly experienced C-suite, and advanced its lead program into a phase III clinical trial. During his time as Executive Chair at Tilos, he helped the company from founding to acquisition by Merck in just two years. While at F-star, John helped grow the company from discovery-stage into to a leading clinical-stage developer of bispecific antibodies, raising over $230M in non-dilutive capital, including several asset-based M&A transactions. Under his guidance as COO, Adnexus evolved from a start-up to a $450M acquisition by BMS within 4 years; he then continued as President of the company for three years. Early in his career, John was Vice President of Sales, Marketing, and Medical Affairs at Transkaryotic Therapies and had a 15-year tenure with Genetics Institute/Wyeth, during which time he built what has become a >$1B global pharmaceutical business in hematology. He received his MBA from Boston University and his BS in chemical engineering from the University of Massachusetts at Amherst. “I am very impressed with PanTher’s lead program and therapeutic platform, which I feel has the potential to be transformative for the treatment of locally advanced, solid tumors,” said John. “PanTher’s approach combines established cancer treatments, whose dosing is limited by toxicity, with their technology that enables continuous, high-dose, delivery to the tumor. In doing so, drug levels at the site of a tumor are >100 fold higher than what is currently possible, leading to more effective treatments without unwanted dose-limiting systemic side effects. This unlocks the full potential of potent therapeutic agents to more effectively treat cancer. I am excited to work with Laura, the management team, and Board to help guide the company’s future direction as it prepares to enter phase 1b clinical trials with its lead program.” About PanTher Therapeutics PanTher Therapeutics is a clinical-stage oncology company offering transformational localized treatment of cancer. This is accomplished through its proprietary Sagittari™ platform which enables continuous, high-dose treatment of potent oncology agents exclusively at the site of a tumor. The Sagittari™ treatment platform is a revolutionary solution for local administration of therapeutic agents. This foundational technology was invented at the Massachusetts Institute of Technology by PanTher’s founder and CEO. Sagittari is a polymer-based system that allows therapeutic agents to be formulated in a wide range of dosage forms that can be administered to the surface of a cancerous organ or implanted directly into a tumor. The drug product is designed to continuously deliver drug for weeks or months at a desired dose level, without unwanted dose-limiting side effects. PanTher’s lead clinical candidate, PTM-101, has successfully been evaluated in a Phase 1 clinical trial in treatment naïve localized non-metastatic pancreatic cancer patients. PanTher is exploring opportunities to utilize its platform technology in additional solid tumor indications. For more information, visit . About PTM-101 PanTher’s lead clinical candidate, PTM-101, is a proprietary flexible absorbable film that enables sustained, high-dose administration of paclitaxel directly to the peritumoral area, maximizing anti-tumor potency and avoiding the severe side effects typically seen with systemic administration of paclitaxel. PTM-101 was designed to easily integrate with well-established laparoscopic procedures that can be used for peritumoral placement. PTM-101 is being evaluated for the treatment of localized non-metastatic pancreatic cancer, where the company recently completed a successful phase 1 study. PanTher is now preparing to initiate a Phase 1b trial of PTM-101, to further assess safety, tolerability, and anti-tumor activity across two different dose levels. View source version on businesswire.com: Contacts Media: Christine Quern 617-650-8497 cq@christinequern.com Source: PanTher Therapeutics View this news release online at:

肿瘤领域潜力靶点的寻找，是新药研发者持续进行的狩猎行为。早期靶点虽然风险系数高，但往往更具研究价值和探索的乐趣。对此，sTn在一定程度上符合该特征，且仅有极少品种在研及早期技术布局，可关注跟进。01sTn-靶点清楚&通路清晰sTn抗原，即唾液酸Tn（Sialyl Tn）抗原，是Tn抗原（GalNAc-α-Ser/Thr）的唾液酸化形式。sTn抗原具有明确的生理机制并关联多种疾病，其中一个非常重要的概念是“O-糖基化”。O-糖基化，常见于肿瘤的发生与发展。正常细胞内成熟的O-聚糖，先是形成Tn抗原，而sTn抗原是由Tn抗原过早发生2,6-唾液酸化，是不完全糖基化过程的产物。该过程详细如下：1）N-乙酰基半乳糖转移酶将UDP-GalNAc上的N-乙酰半乳糖氨（GalNAc）以链接的方式链接到丝氨酸/苏氨酸（Ser/Thr）上，形成Tn抗原（Tn antigen），即GalNAc-α-Ser/Thr；2）Tn抗原在T抗原合成酶（T-synthase）的辅助下获得一个来自UDP-Gal的Gal并合成核心1型结构（T抗原），但是当体内缺乏T抗原合成酶或少数情况下，Tn抗原在ST6GalNAc-I的作用下获得一个来自CMP-Neu5Ac的Neu5Ac并形成唾液酸Tn抗原（sTn抗原），也就是被截断的O-聚糖。研究还证实，sTn抗原的生物合成还与唾液酸转移酶ST6GalNAc1的表达以及伴侣蛋白Cosmic基因的突变和杂合性（如甲基化）的缺失相关。  图1-1O-糖基化及Tn-T-sTn-sT相关抗原合成途径（Biomolecules 2015, 5, 1783-1809. DOI:10.3390/biom5031783）02sTn-肿瘤&高表达现阶段，对于sTn的研究倾向于肿瘤适应症领域。有文献报道，超过80%的癌细胞中有sTn抗原的表达，并且sTn抗原与癌症患者的不良预后相关。相对而言，在许多上皮类型的肿瘤中有sTn抗原的过度表达，如胃癌、结肠癌、乳腺癌、肺癌、食管癌、胰腺癌、前列腺癌、膀胱癌和子宫内膜癌等。以膀胱癌为例，sTn抗原在膀胱癌中呈现阳性表达，且主要是在肿瘤侵袭区，也可见于临近侵袭区的癌旁组织中。与未发生转移的肿瘤比较，sTn抗原过表达在伴有淋巴结转移的原发肿瘤患者中更常见。另，sTn抗原还与膀胱癌的分期、分级相关，有望成为膀胱癌患者非侵入性检查的一种选择，在膀胱癌患者的诊疗及预后发挥重要作用。  图2-1肿瘤细胞与免疫细胞的sTn特异性相互作用（Oncology. 2023. DOI 10.3389/fonc.2022.1093496）03sTn-相关药物开发进展以sTn作为药物靶标来进行新药开发，整体还处于早期阶段。有文献报道：1）1981年，第一个针对Tn抗原开发的单抗，源自小鼠模型，过程中相继发现一些抗体对Tn和sTn抗原均产生作用。如CC49单抗，该品种曾开发为CC49 I-131和90Y-CC49等，临床前/临床用于肿瘤（如卵巢癌）的诊断与治疗，但目前总体进展缓慢，部分研究已暂停。2）另，Theratope sTn-KLH为sTn方向疫苗，可产生sTn免疫应答，曾开发进入到临床，适应症为转移性乳腺癌，一定程度上提高了患者的生存率，早年曾吸引多家公司共同开发（如默克），但现今处于无进展。在上述研究历史背景基础上，结合智慧芽新药情报库（英文名：Synapse）sTn靶点下的研发机构热点分析，当前在研品种总体上受关注度较大的为Seagen公司开发的SGN-STNV，以及Siamab Therapeutics布局的技术及品种。➣ SGN-STNV（Seagen Inc，临床I期）SGN-STNV，是sTn领域值得关注的品种之一。开发公司为Seagen，通过使用vedotin(ADC)技术开发，用于晚期实体瘤的潜在静脉治疗，目前处于临床I期。2020年11月递交IND；2021年该品种的临床前数据于AACR年会公开，显示SGN-STNV在多个异种移植模型中（如胃癌、卵巢癌、食管癌、非小细胞肺癌）存在较好的活性。注：Seagen Inc是全球ADC药物开发的龙头企业，有多款ADC药物上市，且在研临床阶段ADC品种十余款。图3-1 SGN-STNV临床信息https://clinicaltrials.gov/study/NCT04665921?tab=table➣ Siamab Therapeutics（2款临床前品种）另，综合使用智慧芽新药情报库（英文名：Synapse）和智慧芽专利数据库查询发现，Siamab Therapeutics同样深耕sTn药物开发。进入Synapse，靶点选项输入“sTn”，共搜索出3个品种，除上述Seagen Inc的SGN-STNV，另两个品种均来自Siamab Therapeutics，为抗体类药物，在研适应症暂锚定卵巢癌等实体瘤，且当前均处于临床前阶段。其中，ST1为ADC药物，部分临床前试验数据已在AACR年会进行公开，初步证实了早期较好的安全性、耐受性、药代动力学特性；而药效方面，在卵巢癌异种瘤模型中显示了较好的肿瘤抑制作用。  图3-2智慧芽-新药情报库（Synapse）-sTn搜索结果再，进入智慧芽-patsnap数据库，输入“Siamab”，共计发现118条专利，受理局排序依次为美国、欧洲、WIPO、日本、中国、澳大利亚等，进入中国的专利共计6件。有趣的是，授权专利CN 108463248 B原始申请（专利权）人为Siamab Therapeutics, Inc.，当前申请（专利权）人为Seagen Inc，产生了权利转移。专利CN 108463248 B，当前已于中国授权，申请日为2016.11.10，发明名称为“聚糖相互作用化合物及使用方法”。技术方面，权利要求共计60项，其中：权1“一种抗体，其结合唾液酸(a2,6)N-乙酰半乳糖胺(STn),其中所述抗体包含序列如选自SEQ ID NO:237-241的氨基酸序列所示的重链可变结构域(VH)和序列如SEQ ID NO:235或236的氨基酸序列所示的轻链可变结构域”；权8“一种抗体-药物缀合物，其包含缀合至治疗剂的权利要求1-7任一项所述的抗体”；权22“权利要求1-7任一项所述的抗体或权利要求8-13任一项所述的抗体-药物缀合物在制备用于治疗受试者中癌症的药物中的用途”。  图3-3专利CN 108463248 B附图内容小结从肿瘤细胞及其微环境特点来看，sTn呈现出不同于正常细胞的特征，具备成药靶点的潜力。ADC龙头企业Seagen Inc对sTn领域品种的布局开发，进一步证实该靶点的成药价值。同时，Seagen Inc还对Siamab Therapeutics的专利进行介入，也足见sTn靶点的潜在价值以及Seagen Inc对该方向的早期垄断。而此时，国内药企尚未对sTn形成具竞争力的布局，赛道开发环境良好，值得尝试跟进。参考资料1.医学研究杂志2022年11月第51卷第11期. DOI10.11969/j.issn.1673-548X.2022.11.0052.Chinese Journal of Clinical Research，May 2017，Vol．30，No．5. DOI:10.13429/j.cnki.cjcr.2017.05.0383.生命的化学，2016，36（6）:945-949.doi:10.13488/j.smhx.201606314.Int. J. Mol. Sci. 2016, 17, 275; doi:10.3390/ijms170302755.Biomolecules 2015, 5, 1783-1809; doi:10.3390/biom50317836.DOI 10.3389/fonc.2022.10934967.https://synapse.zhihuiya.com/drug/9d2c4bfbda804092820c6f269848f0268.https://www.cn-healthcare.com/articlewm/20220529/content-1366145.html9.https://synapse.zhihuiya.com/patent-list?query_id=5e0c67e6-a2be-41e3-9d82-61758a14e714&tab=analysis10.https://synapse.zhihuiya.com/target/5bbe07bab825404dad84b924d806386c点击图片，免费GET海量新药信息 👇👇👇

John Edwards, newly-appointed CEO of Verseau Therapeutics, is continually searching for something special. He calls it “the third dimension,” and it’s the element that separates the ordinary from the extraordinary, both in his personal, as well as his professional, life. His photography – a passion since childhood – is one example. “I was on a remote island in Indonesia when I saw a herd of horses running on the beach in the distance. I immediately grabbed my camera and ran down to the beach,” Edwards said. “To my surprise one of the horses headed into the surf and I followed close behind. As this bizarre scene unfolded, all of sudden a wave crashed over the horse, and I captured the moment.” Other work, like the reflection of the Buddha, is more contemplative but equally striking. Edwards could be called a biotech whisperer who has helped bring ten products to market. “This has included my involvement with products at all stages of development, from programs in early discovery or in clinical development, as well as products preparing for commercialization,” he said. He recently served as executive chair at Tilos Therapeutics (acquired by Merck after two years) and at F-star. As chief operating officer at Adnexus, he helped take the company from start-up through a $450 million acquisition by Bristol Myers Squibb, and then served as Adnexus’ president. He has served as VP of sales, marketing, and medical affairs at Transkaryotic Therapies, and worked at Genetics Institute/Wyeth for 15 years, leading the effort to take the company’s first product from research to FDA and EMA approvals. He also had key roles in building Siamab and Exonics, and was among the first employees of Genzyme. What he learned is that “like sports, you have to surround yourself with the A team in every area of the company. If a company doesn’t have the A team, I either do not get involved or I make sure there is a willingness to change the situation.” By an ‘A’ team, Edwards means people who not only have the skills and knowledge, but who also have the willingness to challenge each other. “No matter how experienced people are, they must think critically. What’s important to the clinical staff can be different than what’s important to the manufacturing or financial staff,” he pointed out. Therefore, team members need to consider how changes in one area affect the others. “I had one chief scientific officer (CSO) who told me, ‘You’re my favorite person to argue with,” Edwards recalled. “It wasn’t about ego, but about finding the best way to develop a drug and build a successful company.” By challenging each other, they sometimes found even better options. Given we are an industry with a high failure rate, to build successful companies, he said, “one needs to do everything possible to stack the deck to increases your odds of being successful.” That means: “Sweat the details .” Biopharma companies have many visionaries, but they also need well-grounded, critical thinkers. .” Biopharma companies have many visionaries, but they also need well-grounded, critical thinkers. “Don’t let your competition drive your decisions .” Be aware of competitors, but don’t let them paralyze you. Often, their programs could be synergistic to yours. .” Be aware of competitors, but don’t let them paralyze you. Often, their programs could be synergistic to yours. “Believe in your product ,” but whenever possible make decisions based on data . ,” but whenever possible make decisions based on data “Conduct your project-killing experiments as soon as possible .” Know which experiments will provide the data to either move forward or close-up shop. “There’s success in not spending investors’ money running endless experiments.” .” Know which experiments will provide the data to either move forward or close-up shop. “There’s success in not spending investors’ money running endless experiments.” “If you fail, fail for the right reason …” That ties back to having the A team to limit human errors and try to constrain failures to biology that simply did not pan out. …” That ties back to having the A team to limit human errors and try to constrain failures to biology that simply did not pan out. “Have a compelling, credible, story.” Making others as excited about your product or company begins and ends with the science. But this must not come at the expense of jeopardizing credibility or of having compelling data to support your statements. It’s not about having a good story, but about having a special one. You need a clear mechanism of action that translates to clear, meaningful biology…that ties to the potential for a meaningful drug for patients.” L. Patrick Gage, Ph.D., then EVP of R&D for Genetics Institute, Inc., and later president, Wyeth Research, was one of Edwards’ early mentors. “He got the whole picture. He understood the science, drug development, and the importance of people and culture. Pat taught me early on the importance of EQ (emotional quotient) in an IQ (intelligence quotient) dominated industry,” Edwards recalled. Gage took a chance on Edwards, hiring him as executive director for a drug discovery program early in his career. Edwards was atypical for this and other roles throughout his career. For example, he graduated with a BS in chemical engineering from the University of Massachusetts Amhurst and an MBA from Boston University. And, he added, “When recruiting me to lead one of Genetics Institute’s key programs I was only 32, when other (colleagues) were in their 40s with Ph.D.s., and post-docs from Ivy league schools. There was understandably some nervousness about how I would handle the job.” He ended up leading this drug from discovery to marketing, going from the start of Phase I to FDA approval in a record 24 months. A few years later he jumped from more established biotech companies to helping build early-stage companies. Adnexus Therapeutics was the first company he helped to raise a Series A financing. “I became chief operating officer pretty quickly, and then president,” Edwards said. He generated an 8-fold return on investment for shareholders in three years when Adnexus was acquired by BMS. “What’s cool is that unlike many typical acquisitions by pharma, BMS brought us into their company and truly wanted to leverage the best of what a start-up biotech company can offer. Under BMS, Adnexus grew from 50 to 100 people and became one of the top 100 companies to work for in Massachusetts.” Edwards envisions similar success for Verseau, which is repolarizing macrophages to enhance cancer therapy. “Macrophages are present in about 75% of tumors, so they have the potential for broader applications across more tumor types and patients, and a more potent effect than T cells,” he said. “Essentially, Verseau is shifting M2 (immune suppressive) macrophages into M1 (tumor-killing) macrophages. Ex vivo experiments using patient tumors have demonstrated an equal or better anti-tumor response to treatment with one of our lead programs compared to treatment with PD-1 antibodies alone.” Verseau plans to file an Investigational New Drug application (IND) later this year, and a second program in late 2022. Some of the immuno-oncology segment’s leading players are looking into the potential of macrophages, too. “Although there is growing competition in this important new space, we have reason to believe that some macrophage repolarizers will be better suited to some indications than others, so their significant investment encourages me,” he said. Rather than being concerned about the competition, Edwards’ approach is to “understand where we are most competitive and focus on that.”