复宏汉霖获得lasofoxifene在中国的开发、生产和商业化独占许可；Sermonix则保留其他全球区域的权利；

复宏汉霖将加入lasofoxifene的国际多中心III期临床研究并负责合作区域的临床开发；

Sermonix将获得首付款、可达5800万美元的里程碑付款及合作区域销售分成。

上海和俄亥俄州哥伦布市，2024年1月11日，复宏汉霖（2696.HK）与Sermonix Pharmaceuticals, Inc. （“Sermonix”）宣布达成战略合作和独占许可协议，以在中国开发、生产和商业化后者的核心在研产品lasofoxifene。

根据协议条款，复宏汉霖将获得lasofoxifene在合作区域内用于至少两项ER+/HER2-乳腺癌适应症的独占权利和分许可权，Sermonix将保留其它的全球区域的权利。Sermonix将从本次合作中获得首付款及可达5800万美元的里程碑付款，并享有在复宏汉霖区域的销售分成。

复宏汉霖高级副总裁兼首席商务发展官 曹平女士

lasofoxifene在两项II期临床研究中已展现出对ESR1突变的ER+/HER2-乳腺癌治疗的潜力，可以与复宏汉霖现有的乳腺癌产品管线优势互补、实现叠加效应。我们期待与Sermonix通力合作，加速为更多中国患者提供更加有效、个性化的精准治疗方案。

Sermonix创始人兼首席执行官 David Portman博士

复宏汉霖在研发资源和商业化能力上构筑了强大的护城河，是推动lasofoxifene进入中国的理想合作伙伴。过往的研究结果证明了lasofoxifene具备'同类最优'的治疗潜力，我们将携手复宏汉霖共同推动国际多中心III期临床研究ELAINE-3在中国的开发进程，助力产品尽早惠及中国患者。

乳腺癌是全球发病率最高的癌症，据GLOBOCAN数据显示，2020年全球乳腺癌新发病例达226万，中国乳腺癌新发病例逾41万[1]。雌激素受体（Estrogen receptor，ER）阳性乳腺癌占乳腺癌总数的60%-70%[2]。内分泌治疗是雌激素受体阳性（ER+）乳腺癌的主要治疗手段，其中最常使用的芳香化酶抑制剂（aromatase inhibitor，AI）已被美国国立综合癌症网络（NCCN）和中国临床肿瘤学会（CSCO）等指南推荐成为ER+/HER2-乳腺癌患者的辅助及一线标准治疗方法[3-4]，然而几乎所有经AI治疗的患者会产生原发性或获得性耐药[5]，其中雌激素受体α基因（ESR1）获得性突变最为常见，高达40%，被认为是内分泌治疗重要耐药机制[6]，目前针对ESR1突变的ER+/HER2-乳腺癌治疗方案有限，存在较大治疗需求。

ELAINE-3研究（NCT05696626）是Sermonix在ESR1突变患者群体中评估lasofoxifene的第三项研究。在已完成的两项II期研究（ELAINE-1和ELAINE-2研究）中，针对日益普遍的ESR1突变肿瘤，lasofoxifene均展现出显著的临床疗效[7-8]。Sermonix已于2023年12月在美国启动了ELAINE-3的患者招募。ELAINE-3将探索lasofoxifene联合礼来公司的CDK4/6抑制剂阿贝西利（Verzenio®）与氟维司群和阿贝西利相比，在400例绝经前和绝经后患有ESR1突变的局部晚期或转移性ER+/HER2-乳腺癌受试者中的疗效。复宏汉霖将负责Elaine-3研究在中国的临床开发与患者招募并承担相关资金，以及该区域的注册申报、上市后生产和商业化。

【参考文献】

[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and MortalityWorldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249.

[2] Ignatiadis M, Sotiriou C. Luminal breast cancer: from biology to treatment[J]. Nat Rev Clin Oncol, 2013, 10(9): 494-506. doi: 10.1038/nrclinonc.2013.124.

[3] 《中国临床肿瘤学会（CSCO）乳腺癌诊疗指南2023》

[4] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.5.2023

[5] Rozeboom B, Dey N, De P. ER+ metastatic breast cancer: past, present, and a prescription for an apoptosis-targeted future. Am J Cancer Res. 2019;9(12):2821-2831. Published 2019 Dec 1.

[6] Spoerke JM, Gendreau S, Walter K, et al. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat Commun. 2016;7:11579. Published 2016 May 13. doi:10.1038/ncomms11579

[7] Goetz MP, Bagegni NA, Batist G, et al. Lasofoxifene versus fulvestrant for ER+/HER2- metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial. Ann Oncol. 2023;34(12):1141-1151. doi:10.1016/j.annonc.2023.09.3104

[8] S. Damodaran, C.C. O’Sullivan, A. Elkhanany, I.C. Anderson, M. Barve, S. Blau, M.A. Cherian, J.A. Peguero, M.P. Goetz, P.V. Plourde, D.J. Portman, H.C.F. Moore, Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2− breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2. Ann Oncol. 2023;34(12):1131-1140. doi:10.1016/j.annonc.2023.09.3103.

关于Lasofoxifene

Lasofoxifene是一款正处于临床开发阶段的新型内分泌疗法。作为一款ESR1拮抗剂，其在乳腺癌的治疗，尤其是ESR1基因突变型乳腺癌的治疗中具有强大的靶向治疗作用。在II期临床研究中，lasofoxifene作为单药或联合CDK4/6抑制剂使用均展现出抗肿瘤活性，其独特的组织选择性有别于其他现有和在研内分泌疗法。此外，既往临床研究结果证明其对阴道和骨骼也能产生有益的影响。lasofoxifene曾由Ligand Pharmaceuticals Inc.（纳斯达克：LGND）向Sermonix授权全球许可，并在针对非肿瘤适应症开展的I至III期临床试验中于全球范围内入组逾15000多位绝经后女性。从lasofoxifene对雌激素受体突变的生物利用度和药物活性来看，该产品有望为内分泌治疗后产生获得性耐药ESR1突变的患者群体带来希望。而ESR1突变在转移性激素受体阳性乳腺癌中较为常见，存在较大未尽之需。lasofoxifene针对ESR1基因突变的机制最初由杜克大学发现，Sermonix 拥有该领域产品的独家开发权和商业化权。作为一类新型靶向和组织选择性口服内分泌疗法，lasofoxifene有望于获批后在晚期ER+乳腺癌的精准医学治疗中发挥关键作用。

关于Sermonix

Sermonix Pharmaceuticals Inc. 是一家私营生物制药公司，专注于女性特异性肿瘤产品的开发，目前正在围绕其主要研究药物lasofoxifene开展一项III期临床研究。由创始人David Portman博士带领的公司管理团队在乳腺癌领域的药物开发、监管和商业化过程的全生命周期均拥有丰富经验。欲了解更多信息，请访问SermonixPharma.com。

关于复宏汉霖

复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已在中国上市5款产品，在国际上市2款产品，19项适应症获批，3个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，上海徐汇基地和松江基地（一）均已获得中国和欧盟GMP认证。

复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖20多种创新单克隆抗体，并全面推进基于自有抗PD-1单抗H药汉斯状®的肿瘤免疫联合疗法。继国内首个生物类似药汉利康®（利妥昔单抗）、中国首个自主研发的中欧双批单抗药物汉曲优®（曲妥珠单抗，欧洲商品名：Zercepac®，澳大利亚商品名：Tuzucip®和Trastucip®）、汉达远®（阿达木单抗）和汉贝泰®（贝伐珠单抗）相继获批上市，创新产品汉斯状®（斯鲁利单抗）已获批用于治疗微卫星高度不稳定（MSI-H）实体瘤、鳞状非小细胞肺癌、广泛期小细胞肺癌和食管鳞状细胞癌，并成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。公司亦同步就16个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。

Henlius and Sermonix Announce Strategic Collaboration and Exclusive License Agreements for Novel Endocrine Therapy Lasofoxifene

Partnership expands Henlius’ portfolio with license of exclusive China rights to develop, manufacture and commercialize lasofoxifene; Sermonix retains all other global rights

Henlius to facilitate clinical development for the initiated Phase 3 MRCT (ELAINE-3) of lasofoxifene in the territory

Sermonix receives upfront payment, milestone payments of up to $58M and royalties upon commercialization in the territory

COLUMBUS, Ohio, & SHANGHAI, Jan. 11, 2024 - Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers harboring ESR1 mutations, and Shanghai Henlius Biotech, Inc. (2696.HK), today announced a strategic collaboration agreement in which Henlius will receive exclusive rights to develop, manufacture and commercialize Sermonix’s lead investigational drug, lasofoxifene, in China.

Under the terms of the agreement, Henlius will receive exclusive rights and sublicenses to lasofoxifene for at least two estrogen receptor-positive (ER+)/HER2- breast cancer indications in the territory, with Sermonix retaining all other global rights. Sermonix received an upfront payment and is further eligible to receive up to $58 million in certain predetermined milestones, in addition to royalties upon Henlius commercialization in China.

“In Phase 2 clinical trials, investigational lasofoxifene demonstrated its potential for the treatment of ER+/HER2- breast cancer harboring ESR1 mutation,” said Ping Cao, senior vice president and chief business development officer of Henlius. “Lasofoxifene will play a critical role in complementing Henlius' pipeline of its HER2+ breast cancer product. In collaboration with Sermonix, we look forward to accelerating the access of more effective, personalized, precise and well-tolerated treatment solutions for Chinese patients.”

“With a strong platform of R&D resources and commercialization capabilities, Henlius is an ideal partner to bring lasofoxifene into the therapeutic landscape in China,” said Dr. David Portman, Sermonix founder and chief executive officer. “Previous studies demonstrated lasofoxifene’s best-in-class potential and we will work with Henlius to accelerate the clinical development of the Phase 3 ELAINE-3 multi-regional clinical trial in China, making lasofoxifene available to Chinese patients as soon as possible.”

Breast cancer is the cancer with the highest incidence rate in the world, according to GLOBOCAN 2020. There were 2.26 million new cases of breast cancer in 2020 globally, including more than 410,000 in China [1]. ER+ breast cancer comprises 60-70% of all breast cancers [2]. Endocrine therapy remains the mainstay treatment for ER+ breast cancer and the most widely used class of aromatase inhibitor (AI) has been recommended by the National Comprehensive Cancer Network (NCCN) and Chinese Society of Clinical Oncology (CSCO) guidelines to be the adjuvant and first-line standard of care for patients with ER+/HER2- breast cancer [3-4]. However, almost all patients treated with AIs develop primary or acquired resistance [5], with acquired mutations in the estrogen receptor α gene (ESR1) being the most prevalent (up to 40%). This is a significant mechanism of resistance to endocrine therapy[6]. Currently, there are limited treatment options for ER+/HER2- breast cancer with ESR1 mutations, and thus a large clinical need exists.

The Phase 3 ELAINE-3 multi-regional clinical trial (NCT05696626) is the third of Sermonix’s Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) studies. With the Phase 2 ELAINE-1 and ELAINE-2 studies both completed and having shown compelling anti-tumor activity against tumors with increasingly prevalent ESR1 mutations [7-8], Sermonix in December 2023 activated and began enrollment for ELAINE-3 in the U.S.

ELAINE-3 will assess the efficacy of lasofoxifene and Eli Lilly and Company’s (NYSE:lly) CDK4/6 inhibitor abemaciclib (Verzenio®) compared to fulvestrant and abemaciclib in 400 pre- and post-menopausal subjects with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation.

Henlius will fund the clinical development and patient enrollment of the ELAINE-3 study in China, and be responsible for regulatory approval and post-marketing manufacturing and commercialization in the region.

About Lasofoxifene

Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

About Sermonix

Sermonix Pharmaceuticals Inc. is a privately held biopharmaceutical company focused on the development of female-specific oncology products and is currently undertaking a Phase 3 clinical studies of lasofoxifene, its lead investigational drug. The Sermonix management team, led by founder Dr. David Portman, has significant experience in all stages of the drug development, regulatory and commercialization processes in the breast cancer drug development arena.Learn more at SermonixPharma.com.

About Henlius

Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable, and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases, and ophthalmic diseases. Up to date, 5 products have been launched in China, 2 has been approved for marketing in overseas markets, 19 indications are approved worldwide, and 3 marketing applications have been accepted for review in China, the U.S., and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Facility and Songjiang First Plant, both certificated by China and the EU GMP.

Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAbs) and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab for injection, trade name in Europe: Zercepac®; trade names in Australia: Tuzucip® and Trastucip®), the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC), making it the world's first anti-PD-1 mAb for the first-line treatment of SCLC. What's more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets.