IMM-27M

▎药明康德内容团队编辑 8月接近尾声，本月中国创新药授权合作领域持续活跃。即刻药数数据库显示，截至8月26日，中国公司8月份就创新药至少达成了12项授权合作案例，披露总金额有望高达58亿美元*。其中普众发现、同润生物、嘉和生物、宜明昂科等公司就创新药达成了”license-out“国际授权合作，信立泰、翰森制药、华东医药、默沙东（MSD）等则引进了多款创新产品。（*本文为不完全统计，仅展示部分创新药授权合作事件） 通过梳理，我们发现了以下特点和趋势： 从产品类型来看，授权合作的产品涵盖了小分子、单抗/双抗、抗体偶联药物（ADC）、CAR-T细胞治疗药物、碱基编辑药物等多种类型； 从产品研发阶段来看，约一半的产品处于早期（2期以前）研发阶段，其中还有至少3款授权产品处于临床前研发阶段； 从授权合作金额来看，至少8项合作的总金额超过了10亿元，其中还有至少3项合作金额超过了10亿美元； 从疾病领域来看，至少5项授权合作的产品针对癌症，其他产品针对的疾病领域则涵盖了自身免疫性疾病、心血管、眼科等领域。 图片来源：123RF 授权方：尧唐生物 引进方：信立泰 产品：YOLT-101 作用机制：PCSK9靶点碱基编辑药物 8月26日晚间，信立泰发布公告称，拟与尧唐生物（YolTech Therapeutics）签订协议，获得后者拥有的在研PCSK9靶点的碱基编辑药物YOLT-101于中国大陆区域的独家许可权益，包括但不限于研发、注册、生产、商业化销售等。YOLT-101目前尚处于临床前研究阶段，拟开发的适应症包括家族性高胆固醇血症等。 信立泰将根据交易进度和研发进展情况，以自筹资金付款，其中首付款及研发里程碑款总金额最高不超过2.05亿元。如该产品获批上市销售，信立泰还将支付销售里程碑款，销售里程碑累计最高不超过8.3亿元。 授权方：普众发现 引进方：Adcendo公司 产品：AMT-754 作用机制：靶向TF的抗体偶联药物（ADC） 8月20日，普众发现（Multitude Therapeutics）和Adcendo公司共同宣布，双方就新型、高度差异化的靶向组织因子（Anti-TF）的ADC产品ADCE-T02（普众发现研发代号AMT-754）达成许可协议，Adcendo将获得该产品在大中华区以外的全球独家开发和商业化权利，而普众发现将保留在大中华地区的开发和商业化权利。ADCE-T02已在澳洲申报进入临床试验，预计将于近期申报美国IND。 普众发现和Adcendo公司均是处于临床阶段的生物医药公司，专注于ADC产品的开发。根据协议的财务条款，普众发现将获得数千万美元的首付款，并在达成后续开发、监管及商业里程碑时，将收取总计超过10亿美元的总里程碑付款。 授权方：科伦博泰 引进方：默沙东 产品：SKB571项目 作用机制：双抗ADC 8月20日消息，基于此前达成的合作的延续，科伦博泰收到默沙东书面告知，默沙东将就创新双抗ADC项目SKB571项目行使独家选择权，并向科伦博泰支付3750万美元，且待达致特定开发及销售里程碑后向科伦博泰支付进一步里程碑付款。科伦博泰将保留在中国内地、香港及澳门跨地区开发、使用、制造及商业化SKB571的权利。 SKB571是一款创新双抗ADC，主要针对肺癌、消化道肿瘤等多种实体瘤。该产品将于近期递交IND申请。据悉，科伦博泰还计划于近期递交与默沙东已达成授权许可合作的其他临床前ADC资产的IND申请，同时将持续与默沙东探讨新的合作机会。 授权方：IMBiologics 引进方：华东医药 产品：IMB-101和IMB-102 作用机制：靶向OX40L的双抗和单抗 8月14日消息，华东医药全资子公司中美华东与IMBiologics（一家专注于为自身免疫性疾病和癌症开发创新产品的韩国生物技术公司）宣布，就IMB-101和IMB-102在包含中国在内的37个亚洲国家（不含日本、韩国和朝鲜）的开发、注册、生产和商业化达成独家战略合作协议。华东医药将负责许可产品在许可区域的开发、注册、生产和商业化；IMBiologics公司将获得600万美元的首付款，200万美元技术转移里程碑付款，最高不超过3.075亿美元的开发、注册及销售里程碑付款。 IMB-101是靶向OX40L和TNFα的双特异性抗体，目前正在美国进行1期临床试验，拟用于治疗类风湿关节炎。IMB-102是一种靶向OX40L的单克隆抗体，目前处于临床前研究阶段，潜在适应症包括中重度特应性皮炎及其他自身免疫性疾病。 授权方：爱尔康 引进方：欧康维视 产品：干眼治疗和手术用滴眼液产品组合 8月12日消息，欧康维视宣布与爱尔康（Alcon）达成协议，欧康维视将从爱尔康获得8款干眼治疗和手术用滴眼液产品组合的在华相关权益，包括7款已经上市的成熟产品和一款处于临床开发阶段的产品。此外，欧康维视将向爱尔康发行股份，爱尔康将成为欧康维视的最大股东之一。根据该安排的条款，每家公司都授予对方未来产品的优先谈判权。 根据协议内容，欧康维视将在中国完全获得新泪然®、倍然、爱尔凯因®、历设得和赛飞杰的产品权益，以及思然®和AR-15512（一种针对干眼的新型局部药物候选物）在中国的商业化权利。欧康维视将可以在过渡期后在中国生产这些取得完整权益的产品，以及在中国开发、制造和商业化AR-15512。 授权方：同润生物医药 引进方：默沙东 产品：CN201 作用机制：CD3/CD19双抗 8月9日，默沙东宣布与同润生物医药（Curon）达成最终协议，默沙东将通过子公司收购新型在研临床阶段双特异性抗体CN201。默沙东将通过子公司支付7亿美元的现金首付款，获得CN201的全部全球权利。基于CN201的开发和获批相关进展，同润生物也将获得最高6亿美元的里程碑付款。 CN201是一种新型靶向CD3/CD19的双特异性抗体，旨在介导T细胞活化清除B肿瘤细胞，拟用于治疗B细胞相关疾病。CN201目前处于1期和1b/2期临床试验阶段，分别针对复发或难治性非霍奇金淋巴瘤（NHL）和复发或难治性B细胞急性淋巴细胞白血病（ALL）。根据新闻稿，默沙东计划评估CN201作为B细胞恶性肿瘤疗法的表现，并研究其作为自身免疫性疾病新型可扩展疗法的潜力。 授权方：麓鹏制药 引进方：翰森制药 产品：LP-168 作用机制：新一代BTK抑制剂 8月8日，翰森制药与麓鹏制药共同宣布，双方就后者自主研发的新一代BTK抑制剂LP-168签署合作协议。翰森制药获得LP-168所有非肿瘤适应症在中国（包括中国香港、澳门和台湾地区）的研发、注册、生产及商业化的权益。同时，翰森制药将支付首付款和研发、注册及基于销售的商业化里程碑潜在付款合计不超过7.29亿元人民币。 截至目前，麓鹏制药正就LP-168开展多项临床研究，其在中国的最高研发阶段为肿瘤2期关键注册临床研究。根据新闻稿，本次合作将使翰森制药进一步扩展治疗自身免疫疾病的管线组合。 授权方：拨康视云 引进方：参天制药 产品：CBT-001 作用机制：多激酶抑制剂 8月6日消息，拨康视云（Cloudbreak Pharma）宣布与参天制药株式会社（简称“参天制药”）签署了一项授权协议，拨康视云将其在研的多激酶抑制剂CBT-001的开发、生产和商业化权利授于参天制药，该授权涉及日本、韩国、越南、泰国、马来西亚、菲律宾、新加坡和印度尼西亚在内的东南亚地区。拨康视云将获得总额高达9100万美元的首付款及里程碑付款。 CBT-001是拨康视云研发的一种乳化型尼达尼布滴眼液，主要用于治疗翼状胬肉。尼达尼布是一种多激酶抑制剂，主要用于VEGF（血管内皮生长因子）受体、PDGF（血小板衍生生长因子）受体和FGF（成纤维细胞生长因子）受体，从而抑制血管新生和纤维化。CBT-001能通过滴眼液的方式为医生和患者提供一种新的翼状胬肉治疗选择，抑制病情发展。该产品已经在美国完成了2期临床试验，目前正在美国、中国、澳洲、新西兰和印度开展大规模的全球多中心3期临床试验。 授权方：嘉和生物 引进方：TRC 2004 产品：GB261 作用机制：CD20/CD3双抗 8月5日，嘉和生物宣布与TRC 2004（一家由Two River及Third Rock Ventures共同创立的公司）订立许可协议以及股权协议。根据协议，嘉和生物已同意授予TRC 2004全球独家许可，以开发、使用、制造、商业化及以其他方式利用GB261（不包括中国大陆、香港、澳门及台湾地区）。嘉和生物将获得被许可人数量可观的股权、数千万美元的首付款、高达4.43亿美元的里程碑付款，以及占净销售额个位数到双位数百分比的分层特许权使用费。 GB261是一种新型差异化CD20/CD3双特异性T细胞接合剂（TCE），具有超低CD3结合亲和力和完整的Fc功能（ADCC和CDC）。嘉和生物先前已在中国和澳洲完成针对B细胞非霍奇金淋巴瘤进行的1/2期多中心研究。本次与TRC 2004的合作将主要集中在探索GB261在自体免疫疾病方面的潜力。 授权方：艺妙神州 引进方：华东医药 产品：IM19注射液 作用机制：靶向CD19的CAR-T产品 8月4日，华东医药与艺妙神州宣布，双方就后者靶向CD19的自体CAR-T候选产品IM19注射液达成在中国大陆地区的商业化合作。根据协议条款，艺妙神州将获得1.25亿元人民币首付款，并有权获得最高不超过9.5亿人民币的注册及销售里程碑付款。艺妙神州将继续负责IM19注射液在中国大陆地区的开发、注册和生产。 IM19注射液是艺妙神州自主研发的第一款CAR-T细胞治疗产品，针对复发难治弥漫大B细胞淋巴瘤、急性B淋巴细胞白血病和套细胞淋巴瘤三个适应症已进入注册临床研究阶段。艺妙神州预计于2024年四季度提交该产品的上市许可申请。 授权方：润佳医药 引进方：迈威生物 产品：RP901项目及伴随诊断 作用机制：小分子药物 8月2日，迈威生物宣布全资子公司泰康生物与润佳医药签订许可协议。润佳医药许可泰康生物在大中华区域内研究、开发、注册、商业化以及销售RP901项目及伴随诊断（仅为使用许可产品之目的开发）的权益。根据协议，润佳医药将收到首付款5000万元人民币，最高可达10.7亿元人民币的研发及注册里程碑、商业里程碑款，以及至高净销售额10%的提成费。 RP901是一款骨关节炎治疗领域小分子药物。它经口服进入人体之后，可富集于关节腔内，通过提高关节软骨合成代谢及降低关节软骨分解代谢改善骨关节炎患者的软骨破坏，从而发挥对骨关节炎的治疗作用。该产品已经于今年3月启动治疗膝骨关节炎的2期临床研究。 授权方：宜明昂科 引进方：Instil Bio 产品：IMM2510、IMM27M 作用机制：PD-L1xVEGF双特异性抗体；下一代CTLA-4抗体 8月1日，宜明昂科宣布和与Instil Bio达成协议。根据该协议，Instil Bio公司将获得宜明昂科专有的PD-L1xVEGF双特异性抗体IMM2510以及下一代CTLA-4抗体IMM27M在大中华区以外的开发和商业化权利。宜明昂科将保留在大中华地区的开发和商业化权利，同时将获得高达5,000万美元的首付款及潜在近期付款，并将在达成若干开发、监管及商业里程碑时，有望收取总计超过20亿美元的里程碑付款。 IMM2510是一种新型的、潜在“best-in-class”的PD-L1xVEGF双特异性抗体，已经完成了一项用于晚期实体瘤的剂量递增临床试验；IMM27M是具有增强型ADCC活性的新一代CTLA-4抗体，已经完成了一项剂量递增的临床试验，并于2024年7月在中国进入与IMM2510的联合研究。 参考资料： [1]各公司官方新闻稿及官方公开资料 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。转载授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 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。

In-licensed SYN-2510/IMM2510, a potentially best-in-class PD-L1xVEGF bispecific antibody, and SYN-27M/IMM27M, a next-generation ADCC-enhanced anti-CTLA-4 antibodyEntered into a 15-year lease for our cell therapy manufacturing facility to AstraZeneca Pharmaceuticals LP DALLAS, Aug. 13, 2024 (GLOBE NEWSWIRE) -- Instil Bio, Inc. (“Instil”) (Nasdaq: TIL), a clinical-stage biopharmaceutical company focused on developing a pipeline of novel therapies, today reported its second quarter 2024 financial results and provided a corporate update. “We have expanded our pipeline with a pair of clinical-stage, potentially best-in-class therapeutics by in-licensing SYN-2510 and SYN-27M,” said Bronson Crouch, CEO of Instil. “By executing a 15-year lease of our Tarzana cell therapy manufacturing facility, we have strengthened our financial foundation to support Instil’s near-term clinical development of these assets.” Recent Highlights: In-licensed SYN-2510 and SYN-27M: In August 2024, SynBioTx, Inc., a wholly owned subsidiary of Instil, entered into a license and collaboration agreement with ImmuneOnco (HKEX:1541) for the exclusive global development and commercialization rights outside of Greater China of SYN-2510, a potentially best-in-class PD-L1xVEGF bispecific antibody, and SYN-27M, a next-generation ADCC-enhanced CTLA-4 antibody. SYN-2510 and SYN-27M have completed Phase 1a dose escalation studies in multiple solid tumor types in China, and ImmuneOnco is continuing patient enrollment in both programs to support dose optimization and dose expansion. Executed lease of our cell therapy manufacturing facility to AstraZeneca Pharmaceuticals LP: In July 2024, Instil reported the execution of a lease of its U.S. cell therapy manufacturing facility to AstraZeneca Pharmaceuticals LP. Under the terms of the agreement, initial base rent is greater than $7.5 million annually, and escalates at 3% per annum, with the tenant also required to pay certain operating expenses and tax expenses, subject to certain rent abatement in the first year of the 15-year lease term. Exploring further opportunities to in-license or acquire novel therapeutic candidates: Instil continues to explore further opportunities to in-license or otherwise acquire novel therapeutic candidates with first-in-class or best-in-class potential.Cash runway expected beyond 2026. Second Quarter 2024 Financial and Operating Results: As of June 30, 2024, Instil had cash, cash equivalents, marketable securities and long-term investments of $152.6 million, which consisted of $6.8 million in cash and cash equivalents, $141.8 million in marketable securities, and $4.0 million in long-term investments, compared to $175.0 million in cash, cash equivalents, marketable securities and long-term investments as of December 31, 2023, consisting of $9.2 million in cash and cash equivalents, $1.5 million in restricted cash, $141.2 million in marketable securities, and $23.2 million in long-term investments. Instil expects that its cash, cash equivalents, marketable securities and long-term investments as of June 30, 2024 will enable it to fund its operating plan beyond 2026. Research and development expenses were $2.9 million and $10.2 million for the three and six months ended June 30, 2024, respectively, compared to $8.5 million and $29.1 million for the three and six months ended June 30, 2023, respectively. General and administrative expenses were $10.7 million and $23.1 million for the three and six months ended June 30, 2024, respectively, compared to $11.5 million and $24.7 million for the three and six months ended June 30, 2023, respectively. Restructuring and impairment charges were $0.5 million and $4.8 million for the three and six months ended June 30, 2024, respectively, compared to $1.0 million and $25.6 million for three and six months ended June 30, 2023, respectively. Net loss per share, basic and diluted were $2.29 and $6.03 for the three and six months ended June 30, 2024, respectively, compared to $2.87 and $11.64 for the three and six months ended June 30, 2023, respectively. Non-GAAP net loss per share, basic and diluted, were $1.57 and $3.95 for the three and six months ended June 30, 2024, respectively, compared to $2.03 and $6.33 for the three and six months ended June 30, 2023, respectively. Note Regarding Use of Non-GAAP Financial Measures In this press release, Instil has presented certain financial information that has not been prepared in accordance with U.S. generally accepted accounting principles (“GAAP”). These non-GAAP financial measures include non-GAAP net loss and non-GAAP net loss per share, which are defined as net loss and net loss per share, respectively, excluding non-cash stock-based compensation expense and restructuring and impairment charges. Instil believes that these non-GAAP financial measures, when considered together with the GAAP figures, can enhance an overall understanding of Instil’s financial performance. The non-GAAP financial measures are included with the intent of providing investors with a more complete understanding of Instil’s operating results. In addition, these non-GAAP financial measures are among the indicators Instil’s management uses for planning purposes and to measure Instil’s performance. These non-GAAP financial measures should be considered in addition to, and not as a substitute for, or superior to, financial measures calculated in accordance with GAAP. The non-GAAP financial measures used by Instil may be calculated differently from, and therefore may not be comparable to, non-GAAP financial measures used by other companies. Please refer to the below reconciliation of these non-GAAP financial measures to the comparable GAAP financial measures. About Instil Bio Instil Bio is a clinical-stage biopharmaceutical company focused on developing a pipeline of novel therapies. Instil’s lead asset, SYN-2510, is a novel and differentiated PD-L1xVEGF bispecific antibody in development for the treatment of multiple solid tumor cancers. For more information visit www.instilbio.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “expects,” “expected,” “exploring,” “future,” “intends,” “may,” “plans,” “potential,” “projects,” and “will” or similar expressions are intended to identify forward-looking statements. Forward-looking statements include express or implied statements regarding our expectations with respect to the license and collaboration agreement with ImmuneOnco, the therapeutic potential of SYN-2510 and SYN-27M, clinical development of SYN-2510 and SYN-27M and the generation of clinical data for SYN-2510 and SYN-27M; concerning or implying our ability to acquire and develop additional product candidates; our research, development and regulatory plans for our product candidates; our expectations regarding our capital position, resources, and balance sheet and the expected impact of the lease of our U.S. manufacturing facility with respect thereto, and the potential impact thereof on the development of any product candidates; and other statements that are not historical fact. Forward-looking statements are based on management's current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements, including risks and uncertainties associated with acquiring additional product candidates, the costly and time-consuming drug product development process and the uncertainty of clinical success; the risks inherent in relying on collaborators and other third parties, including for manufacturing and generating clinical data, and the ability to rely on any such data from clinical trials in China in regulatory filings submitted to regulatory authorities outside of China; the risks and uncertainties related to successfully initiating, enrolling, completing and reporting data from clinical studies, particularly collaborator-led clinical trials, as well as the risks that results obtained in any clinical trials to date may not be indicative of results obtained in ongoing or future trials and that our product candidates may otherwise not be effective treatments in their planned indications; risks related to macroeconomic conditions, including as a result of international conflicts and U.S.-China trade and political tensions, as well as interest rates, inflation, and other factors, which could materially and adversely affect our business and operations; the risks and uncertainties associated with the time-consuming and uncertain regulatory approval process and the sufficiency of our cash resources; and other risks and uncertainties affecting us and our plans and development programs, including those discussed in the section titled “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 to be filed with the SEC, as well as our other filings with the SEC. Additional information will be made available in other filings that we make from time to time with the SEC. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. These forward-looking statements speak only as the date hereof, and we disclaim any obligation to update these statements except as may be required by law. Contacts: Investor Relations:1-972-499-3350 investorrelations@instilbio.comwww.instilbio.com INSTIL BIO, INC.SELECTED FINANCIAL DATA (Unaudited; in thousands, except share and per share amounts)Selected Condensed Consolidated Balance Sheet Data June 30, 2024 December 31, 2023Cash, cash equivalents, restricted cash, marketable securities and long-term investments$152,578 $175,018Total assets$294,316 $325,630Total liabilities$99,297 $99,801Total stockholders’ equity$195,019 $225,829 Condensed Consolidated Statements of Operations Three Months Ended Six Months Ended June 30, June 30, 2024 2023 2024 2023 Operating expenses: Research and development$2,921 $8,459 $10,177 $29,129 General and administrative 10,706 11,518 23,130 24,740 Restructuring and impairment charges 508 1,010 4,783 25,564 Total operating expenses 14,135 20,987 38,090 79,433 Loss from operations (14,135) (20,987) (38,090) (79,433)Interest income 1,919 2,287 3,981 4,358 Interest expense (1,999) (590) (3,980) (1,226)Other (expense) income, net (702) 628 (1,130) 571 Net loss$(14,917) $(18,662) $(39,219) $(75,730)Net loss per share, basic and diluted$(2.29) $(2.87) $(6.03) $(11.64)Weighted-average shares used in computing net loss per share, basic and diluted 6,503,913 6,503,913 6,503,913 6,503,913 INSTIL BIO, INC.Reconciliation of GAAP to Non-GAAP Net Loss and Net Loss per Share (Unaudited; in thousands, except share and per share amounts) Three Months Ended Six Months Ended June 30, June 30, 2024 2023 2024 2023 Net loss$(14,917) $(18,662) $(39,219) $(75,730)Adjustments: Non-cash stock-based compensation expense 4,173 4,413 8,688 8,943 Restructuring and impairment charges 508 1,010 4,783 25,564 Non-GAAP net loss$(10,236) $(13,239) $(25,748) $(41,223)Net loss per share, basic and diluted$(2.29) $(2.87) $(6.03) $(11.64)Adjustments: Non-cash stock-based compensation expense per share 0.64 0.68 1.34 1.38 Restructuring and impairment charges per share 0.08 0.16 0.74 3.93 Non-GAAP net loss per share, basic and diluted*$(1.57) $(2.03) $(3.95) $(6.33)Weighted-average shares outstanding, basic and diluted 6,503,913 6,503,913 6,503,913 6,503,913 * Non-GAAP net loss per share, basic and diluted may not total due to rounding.