Novel fusion protein shows potent macrophage activation, T-cell restoration, and tumor microenvironment remodeling in preclinical solid tumor models.
[Taipei, Shanghai, and San Francisco | November 5, 2025] –HanchorBio Inc. (TPEx: 7827), a global clinical-stage biotechnology company advancing next-generation immunotherapies for oncology and autoimmune diseases, today announced that the preclinical data on HCB301, a novel tri-specific immunotherapeutic fusion protein, has been accepted for presentation at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), taking place November 5-9, 2025, in National Harbor, Maryland. Featured in a poster presentation, the data highlight HCB301’s differentiated design and multi-pronged antitumor mechanism, which engages both innate and adaptive immunity.
01
Focus on tumor treatment: block, activate, capture three arrows in flight
HCB301 is designed to simultaneously:
- Block SIRPα-CD47 interaction to re-initiate macrophage-mediated phagocytosis, and subsequent T-cell activation through antigen presentation.
- Block PD-1-PD-L1 signaling to restore exhausted T-cell function.
- Trap TGFβ to overcome stromal and immune suppression in the tumor microenvironment (TME).
This tripartite approach aims to overcome the limitations of existing checkpoint inhibitors by activating both arms of the immune system and triggering dual T-cell activation. It also further enhances T cell response by restoring its ability to target cancer cells in suppressive tumor microenvironments (TMEs), where current immune therapies often fail.
02
HanchorBio Milestone of innovative immunotherapy
Scott Liu, Ph.D., Founder, Chairman, and CEO of HanchorBio, stated, “The tri-specific fusion protein of HCB301 is a showcase of the exceptional technological capabilities of HanchorBio, masterful in tackling the extremely difficult challenges in developing a structurally intricate fusion protein that includes two engineered receptors and a part (VHH domain) of an antibody. HCB301 was built directly on the foundation of HCB101, our clinical-stage SIRPα-engineered fusion protein.
By combining PD-1 blockade and TGFβ neutralization into a single molecule, HCB301 represents what we believe to be the first-in-class tri-specific fusion protein that simultaneously targets both innate and adaptive immune checkpoints and relieves immune suppression in TMEs characterized by suppressive cytokines. This design reflects our commitment to building modular, next-generation immunotherapies that may transcend the limitations of current cancer treatments.
With IND clearance and first-patient dosing now achieved in both the U.S. and China, HCB301 demonstrates the excellence and scalability of our FBDB™ platform and the outstanding execution capabilities of our research team. As we advance HCB301 into the clinic, this milestone further positions HanchorBio as a long-term innovation partner for global co-development, particularly in cancers with high resistance to traditional immunotherapies.”
03
Preclinical Highlights of HCB301
HCB301, a tri-specific fusion protein targeting SIRPα/CD47, PD-1/PD-L1, and TGFβ, promotes anti-tumor macrophage and T cell activity in preclinical models of solid tumors
- Strong immune activation: HCB301 induced robust antibody-dependent cellular phagocytosis (ADCP), promoted macrophage-mediated phagocytosis, and activated effector T cells. It also activates T-cell response, leading to elevated secretions of IL-2 and IFN-γ.
- Synergistic antitumor efficacy: In Fadu (HNSCC)/PBMC Xenograft-bearing NPGTM mice and 4T1-hPDL1-hCD47 tumor-bearing BABL/c hPD1/hPDL1/hCD47/hSIRPα transgenic mice, HCB301 demonstrated superior tumor growth inhibition compared to single- or dual-arm comparators.
- TGFβ suppression: HCB301 potently neutralized active TGFβ (a dominant immune-suppressive cytokine), reversing TME immunosuppression and restoring T-cell function.
- Fc-effector tuning: Selective Fc engineering optimized immune activation while minimizing off-target toxicity.
“HCB301 was purpose-built to break through the resistance barriers that limit current PD-1 or CD47 monotherapies,” commented Wenwu Zhai, Ph.D., Chief Scientific Officer of HanchorBio. “Each of its three arms addresses a key axis of tumor immune evasion: CD47 for innate immune clearance, PD-1 for adaptive immune reactivation, and TGFβ for TME remodeling. Our preclinical data show that HCB301 delivers synergistic immune activation and tumor control, strongly supporting its advancement into the clinic.”
04 About HCB301
To our knowledge, HCB301 is the first clinical-stage tri-specific recombinant Fc-fusion protein that simultaneously targets SIRPα/CD47, PD-1/PD-L1, and TGFβ. It was designed using HanchorBio’s proprietary Fc-Based Designer Biologics (FBDB™) platform, which integrates modular, engineered multi-arm immunotherapies with tunable Fc regions and enhanced manufacturability.
HCB301 integrates:
- An engineered SIRPα domain that binds CD47 with much higher affinity (~100-fold higher than the wild-type SIRPα) to promote macrophage phagocytosis and subsequent T-cell activation.
- A PD-1 extracellular domain that blocks PD-L1 and restores T-cell effector function.
- A TGFβRII domain that traps active TGFβ molecules to alleviate immunosuppressive signals in the tumor microenvironment.
HCB301 shows a favorable safety profile in repeat-dose toxicology studies in cynomolgus monkeys. Its differential tumor vs. RBC binding profile may reduce the risk of anemia, thrombocytopenia, or other cytopenia while maintaining potent anti-tumor activity.
Following IND clearance and first-patient dosing in both the U.S. and China in 2025. The ongoing Phase 1 study (HCB301-101; NCT06487624) is a multi-regional, multi-center, open-label, dose-finding, first-in-human trial evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical efficacy of HCB301 in patients with advanced solid tumors or relapsed and refractory classical Hodgkin lymphoma.
About HanchorBio
Based in Taipei, Shanghai, and the San Francisco Bay Area, HanchorBio (TPEx: 7827) is a global biotechnology company specializing in immuno-oncology. It is led by an experienced team of pharmaceutical industry veterans with a proven track record in biologics discovery and international development, aiming to rewrite cancer therapies. Committed to reactivating the immune system to fight diseases, the proprietary Fc-based designer biologics (FBDB™) platform enables the development of unique biologics with diverse multi-targeting modalities, unleashing both innate and adaptive immunity to overcome the current challenges 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.
新型融合蛋白在臨床前實體瘤模型中顯示強效巨噬細胞啟動、T細胞功能恢復及腫瘤微環境重塑能力
專注抗癌創新藥物開發的漢康-KY（股票代碼：7827）今（5）日公告，第40屆癌症免疫治療學會（Society for Immunotherapy of Cancer，SITC）年會於11月7日至9日在美國馬里蘭州國家海港會場舉辦，公司將以壁報形式發表三篇最新研究成果，首先登場的將是新型三功能融合蛋白藥物 HCB301 臨床前研究成果，之後則將展示廣譜抗癌新藥HCB101於單藥及聯合用藥的臨床數據成效。其中，HCB301挾獨特的分子設計與多重抗腫瘤機制，並兼具活化先天免疫及適應性免疫的特性，料將成為一大關注焦點。
01 聚焦腫瘤治療：阻斷、啟動、捕獲三箭齊發
HCB301 被設計用於同時實現以下功能：
- 阻斷SIRPα-CD47相互作用，以重新啟動巨噬細胞介導的吞噬作用，並隨後通過抗原呈遞啟動T細胞。
• 阻斷PD-1-PD-L1信號通路，以恢復耗竭T細胞的功能。 - 捕獲TGFβ，以克服腫瘤微環境中的基質和免疫抑制。
這種三方協同的策略旨在通過同時啟動免疫系統的兩大分支並觸發雙重的T細胞啟動，以克服現有檢查點抑制劑的局限性。它還能通過恢復T細胞在免疫抑制性腫瘤微環境中靶向癌細胞的能力，進一步增強T細胞反應，而目前的免疫療法在此類微環境中往往無效。
02 漢康生技 創新免疫療法里程碑
漢康生技創始人、董事長兼執行長劉世高博士表示：「HCB301的三特異性融合蛋白設計充分展示了漢康生技卓越的技術能力，我們成功應對了開發這種結構複雜的融合蛋白（包含兩個工程化受體和一個抗體VHH結構域）所面臨的極高難度挑戰。HCB301直接建立在我們的臨床階段產品HCB101（一款SIRPα工程化融合蛋白）的基礎之上。
通過將PD-1阻斷和TGFβ中和功能整合進單一分子，我們相信HCB301是首創的、能同時靶向先天性與適應性免疫檢查點並解除以抑制性細胞因子為特徵的腫瘤微環境免疫抑制的三特異性融合蛋白。這一設計體現了我們致力於構建模組化、可超越當前癌症治療局限的下一代免疫療法的承諾。
隨著中美兩地IND均已獲批並完成首例患者給藥，HCB301證明了我們的FBDB™平臺的卓越性與可擴展性，以及我們研發團隊出色的執行能力。在我們將HCB301推進臨床之際，這一里程碑進一步奠定了漢康生技作為全球聯合長期創新合作夥伴的地位，特別是在對傳統免疫療法耐藥性高的癌症領域。」
03 HCB301臨床前亮點
HCB301，一種靶向SIRPα/CD47、PD-1/PD-L1和TGFβ的三特異性融合蛋白，在臨床前實體瘤模型中促進抗腫瘤巨噬細胞和T細胞活性
- 強大的免疫啟動：HCB301誘導了強勁的抗體依賴性細胞吞噬作用，促進了巨噬細胞介導的吞噬作用，並啟動了效應T細胞。它還啟動了T細胞反應，導致IL-2和IFN-γ分泌水準升高。
- 協同抗腫瘤功效：在Fadu（頭頸鱗癌）/PBMC異種移植NPGTM小鼠模型以及4T1-hPDL1-hCD47荷瘤BABL/c hPD1/hPDL1/hCD47/hSIRPα轉基因小鼠模型中，HCB301表現出顯著優於單功能或雙功能對照組的腫瘤生長抑制效果。
- TGFβ抑制：HCB301有效中和了活性TGFβ（一種主要的免疫抑制性細胞因數），逆轉了TME的免疫抑制，並恢復了T細胞功能。
- Fc效應子功能調控：選擇性Fc工程化在優化免疫啟動的同時，最大限度地減少了脫靶毒性風險。
「HCB301的研發初衷就是為了突破限制當前PD-1或CD47單藥療法的耐藥壁壘」，漢康生技研發長翟文武博士評論道，「它的三個功能臂分別針對腫瘤免疫逃逸的一個關鍵軸心：CD47用於先天免疫清除，PD-1用於適應性免疫再啟動，TGFβ用於TME重塑。我們的臨床前資料表明，HCB301實現了協同的免疫啟動和腫瘤控制，為其進入臨床開發提供了強有力的支援。」
04 關於HCB301
據我們所知，HCB301是首個進入臨床階段、能同時靶向SIRPα/CD47、PD-1/PD-L1和TGFβ的三特異性重組Fc融合蛋白。它採用漢康生技專有的Fc-Based Designer Biologics平臺設計，該平臺可集成模組化、工程化的多臂免疫療法，並具有可調控的Fc區和增強的可生產性。
HCB301整合了：
• 一個工程化的SIRPα結構域，其以遠高於野生型SIRPα的親和力結合CD47，以促進巨噬細胞吞噬及隨後的T細胞啟動。
• 一個PD-1胞外結構域，用於阻斷PD-L1並恢復T細胞效應功能。
• 一個TGFβRII結構域，用於捕獲活性TGFβ分子，以減輕腫瘤微環境中的免疫抑制信號。
在食蟹猴重複給藥毒理學研究中，HCB301顯示出良好的安全性。其差異化的腫瘤 vs. 紅細胞結合特性可能在保持強效抗腫瘤活性的同時，降低貧血、血小板減少或其他血細胞減少症的風險。
隨著2025年在美國和中國均獲得IND批准並完成首例患者給藥，正在進行的1期研究（HCB301-101；NCT06487624）是一項多區域、多中心、開放標籤、劑量探索的首次人體試驗，旨在評估HCB301在晚期實體瘤或復發難治性經典型霍奇金淋巴瘤患者中的安全性、耐受性、藥代動力學、藥效學及初步臨床療效。
媒體報導:
《MoneyDJ》漢康-KY將於SITC年會秀研發成果，HCB301數據首亮相
https://www.moneydj.com/kmdj/news/newsviewer.aspx?a=cc128866-433a-426b-9fc3-e369a442d257
《時報資訊》SITC年會 漢康-KY三合一融合蛋白新藥HCB301數據首亮相
https://www.chinatimes.com/realtimenews/20251106001132-260410?chdtv
《財訊快報》漢康-KY SITC年會秀研發成果，三合一融合蛋白新藥HCB301數據首亮相
https://www.investor.com.tw/onlineNews/NewsContent.asp?articleNo=14202511050169
《經濟日報即時》漢康-KY三合一融合蛋白新藥HCB301數據首亮相
https://money.udn.com/money/story/5930/9119705
《工商時報即時》漢康-KY三合一融合蛋白新藥HCB301數據首亮相