HANCHORBIO ANNOUNCES US FDA CLEARANCE OF IND APPLICATION FOR HCB301 TRI-SPECIFIC FUSION PROTEIN TO TREAT SOLID AND HEMATOLOGICAL MALIGNANCIES

HANCHORBIO ANNOUNCES US FDA CLEARANCE OF IND APPLICATION FOR HCB301 TRI-SPECIFIC FUSION PROTEIN TO TREAT SOLID AND HEMATOLOGICAL MALIGNANCIES
TAIPEI, SHANGHAI, and SAN FRANCISCO, June 28th, 2024 – HanchorBio Inc., a global clinical-stage biotechnology company focusing on the discovery and development of innovative immuno-biomedicines to treat a wide variety of patients suffering from hard-to-treat solid tumors or hematological malignancies, today announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s investigational new drug (IND) application to initiate a multi-regional clinical trial of its independently-developed novel drug candidate, HCB301, for the treatment of patients with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.  HCB301 is an engineered tri-specific fusion protein comprised of an anti-PD-L1 (Ig) V domain, a parallel-engineered human SIRPα (Ig) V domain fused to an IgG4 Fc protein, and an engineered human transforming growth factor- (TGF) trap at the Fc tail that creates synergies between innate immunity checkpoint, an adapted immunity checkpoint, and an immune suppressive cytokine to triggers the modulation of tumor microenvironment, potentially addressing a novel multi-specific immune-therapy approach to tackling cancer.

“The IND clearance marks another significant milestone as we advance our pipeline of multi-targeting Fc-based designer biologics (FBDB™) immunotherapy in cancers,” said Scott Liu, Ph.D., Founder, Chairman, and Chief Executive Officer of HanchorBio. “This is our second IND clearance within 3.5 years since the inception of the company and underscores our focused dedication towards developing safe and effective treatments derived from our FBDB™ platform to re-engage innate and adaptive immunity through multifunctional designs to overcome the inadequacies of anti-PD1/L1 therapies. HCB301 IND is the first tri-specific fusion protein targeting SIRPα/CD47, PD-1/PD-L1, and TGFβ/TGFβ trap pathways simultaneously.”

“Based on our in-vitro and in-vivo pre-clinical studies, HCB301 has demonstrated remarkable inhibition of multiple tumor cell lines and murine xenograft tumor models of solid and hematological malignancies, compared with TGF trap, anti-PD-L1 agents, anti-CD47 agents, in either multi-specific antibody or in their disparate soluble combinations,” said Jonathan Wang, Ph.D., Senior Director of Research Department of HanchorBio. “Unlike other CD47-blocking agents, HCB301 exhibits lower binding activity in preclinical settings to human red blood cells (RBCs), but similar binding activity to platelets, with no obvious abnormality of RBC or platelet levels being observed in the repeat-dose cynomolgus monkey toxicology studies.”

“ Given the encouraging outcomes thus far regarding HCB101 (an engineered extracellular domain of SIRPα fused to the Fc region of IgG4 as a safer and more potent biologic than the anti-CD47 monoclonal antibodies) in our ongoing Phase 1 trial (NCT05892718), we are optimistic about the potential benefits that may emerge of HCB301 based on the foundation of HCB101,” stated by David Sun, M.D., Ph.D., Senior Vice President of Global Clinical and Medical Affairs of HanchorBio. “Our medical and clinical teams look forward to advancing the clinical development of HCB301 to bring clinically meaningful benefits to patients as early as possible.”

About HCB301
Using structure-guided protein design and engineering supplemented with relevant screening technologies, HCB301 is a tri-specific fusion protein: an engineered IgV domain of human SIRPα fused to an anti-PD-L1 (Ig) V domain and an engineered human TGFRII. This results in blocking the checkpoint CD47 simultaneously with T-lymphocyte checkpoint PD-L1 blocking while inhibiting the activities of TGF-mediated immune-suppression functions. HCB301 exhibits good safety profiles in the repeat-dose cynomolgus monkey toxicology studies, as no obvious abnormality of RBC or platelet levels was observed, and a unique differential binding to tumor cells vs. RBC binding and subsequent significant decreases in phagocytosis may potentially reduce patient’s risk of anemia, thrombocytopenia, or any other cytopenia while maintaining potent anti-tumor activities.

About Multi-regional Clinical Trial of HCB301 (NCTXXXX)
HCB301-101 is a multiregional, multicenter, open-label, dose-finding, first-in-human (FIH) study of adults with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas in the United States, Australia, and Taiwan. The study evaluates the safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of weekly HCB301 intravenous injections. The HCB301 IND is on track to be reviewed by the Australia Therapeutic Goods Administration (TGA) and the Taiwan FDA.

About HanchorBio 
Based in Taipei, Shanghai, and the San Francisco Bay Area, HanchorBio is led by an experienced team of pharmaceutical industry veterans with a proven track record of success in biologics discovery and global development to transcend current cancer therapies. Committed to reactivating the immune system to fight against diseases, the proprietary Fc-based designer biologics (FBDB™) platform enables unique biologics with diverse multi-targeting modalities to unleash both innate and adaptive immunity to overcome the current inadequacies of anti-PD1/L1 therapies. The FBDB™ platform has successfully delivered proof-of-concept data in several in vivo tumor animal models. By making breakthroughs in multi-functional innovative molecular configurations in R&D and improving the manufacturing process in CMC, HanchorBio develops transformative medicines to address unmet medical needs. For more information, please visit HanchorBio or follow us on LinkedIn.

臺北、上海、舊金山,2024年6月28日
漢康生技(HanchorBio Inc.),一家處於臨床開發階段、專注於免疫治療新藥研發以解決各種難治性實體瘤、血液瘤免疫治療領域中尚未滿足的臨床需求的全球性生物技術公司,今天宣佈其自主研發的創新型候選藥物HCB301獲得美國食品藥品監督管理局(FDA)授予的新藥臨床試驗(IND)許可,即將開展多地區多中心的臨床試驗,此藥將用於治療晚期實體瘤患者、復發或頑固型典型霍奇金淋巴瘤患者。HCB301是一種工程化三特異專一性的融合蛋白,其中包含將抗PD-L1 (Ig) V區域結構與人類的SIRPα (Ig) V區域結構共同平行地接上抗體 IgG4 Fc 區域,而IgG4 Fc 區域的尾端則接上工程化人類的轉化生長因子-β (TGFβ)為一配體陷阱的呈現,借此可同時在腫瘤微環境中觸發三種免疫調控與協同機制,包含先天免疫檢查點、適應性免疫檢查點和免疫抑制細胞因數作用,並可能在癌症免疫治療領域帶來一種新穎的多特異性免疫療法。

漢康生技的創始人、董事長兼執行長劉世高博士評論道:“HCB301於美國FDA獲批臨床試驗許可是我們在“Fc為基礎的多功能創新型生物製劑(FBDB™)”平臺及其相關管線產品研發的有一重要里程碑。這是公司成立3.5年來的第二個新藥臨床試驗許可,也突顯了專注於從“Fc為基礎的多功能創新型生物製劑(FBDB™)”平臺開發安全有效的治療方案、通過多功能設計重新計畫先天性免疫系統和適應性免疫系統的潛力、以克服現有抗PD-1/L1免疫療法中所遇到療效不足的決心。並且,HCB301所取得的也是首個同時針對SIRPα/CD47、PD-1/PD-L1和TGFβ/TGFβ trap三個信號通路的三特異性融合蛋白的臨床試驗許可。”

漢康生技研發部資深總監王錦堂博士說道:“我們的體外和體內臨床前研究資料顯示,與TGFβ trap、抗PD-L1藥物、抗CD47藥物相比(無論是多特異性抗體還是它們各種不同的療法組合),HCB301均表現出對多種腫瘤細胞系和實體瘤及血液惡性腫瘤的小鼠異種移植腫瘤模型的顯著抑制作用。並且,與其他CD47阻斷劑不同,HCB301在臨床前研究中對人類紅血球(RBCs)表現出較低的結合活性,但對血小板的結合活性相似,在重複劑量的食蟹猴毒性研究中,也未觀察到紅血球或血小板水準的明顯異常。”

漢康生技全球臨床醫學事務部資深副總孫巍博士也說道:“有鑒於我們當前正在進行的HCB101(一個與IgG4-Fc連結,經過工程化改構的SIRPα融合蛋白,比抗CD47單克隆抗體更安全、更有效的一種生物製劑)的臨床I期試驗(NCT05892718)中取得的積極成果,我們對以HCB101為基礎而進一步研發的HCB301持樂觀態度。我們的臨床醫學事務團隊非常期待推進HCB301的臨床開發,以期能儘早為患者帶來具有臨床意義的益處。”

關於HCB301
利用結構引導的蛋白設計和工程改造,並輔以相對應的篩選技術,HCB301為一種三特異性融合蛋白:由人SIRPα經過工程改造的IgV結構域、抗PD-L1(Ig)V結構域和經過工程改造的人TGFRII融合而成。這不僅能同時阻斷檢查點CD47和T淋巴細胞檢查點PD-L1,還能抑制TGFβ介導的免疫抑制功能。在重複劑量的食蟹猴毒理學研究中,HCB301表現出良好的安全性,未觀察到紅血球或血小板水準的明顯異常,且其對腫瘤細胞與紅血球之間具有獨特的差異化結合,並且其吞噬作用顯著降低,使得其可能在保持強大抗腫瘤活性的同時降低患者在發生貧血、血小板減少或其他細胞減少症的風險。

關於HCB301的多地區多中心臨床試驗(NCTXXXX)
HCB301-101是一項在美國、澳大利亞和臺灣開展的多地區、多中心、非盲、劑量探索的首次人體(FIH)臨床試驗,用於治療晚期實體瘤或復發頑固型經典型霍奇金淋巴瘤的成年患者。該研究的目的是評估每週進行HCB301靜脈注射的安全性、耐受性、藥代動力學和初步臨床療效。HCB301的新藥臨床試驗申請(IND)正在接受澳大利亞藥品管理局(TGA)和臺灣衛生福利部食品藥物管理署(TFDA)的審查。

關於漢康生技
漢康生技是一家位於臺北、上海以及美國舊金山灣區的,由在生物製藥研發方面擁有多年跨國製藥公司的豐富經驗的團隊所領導的致力於超越現今的抗癌治療模式而有更創新突破的全球性生物科技公司。通過其專有的“Fc為基礎的多功能創新型生物製劑(FBDB™)”平臺可開發出具有多種靶向模式的獨特生物產品,能夠充分協同先天性免疫系統和適應性免疫系統的潛力,以克服現有抗PD-1/L1療法中所遇到療效不足的挑戰。通過FBDB™平臺開發的生物產品已經成功地在多種小鼠腫瘤模型中得到了概念性的驗證資料。通過在研發階段對創新分子構型功能上的突破、以及在工藝開發階段對生產工藝的優化與改進,漢康生技致力於以創新生物產品來解決腫瘤免疫治療領域中尚未滿足的臨床需求。