HCB101 / HanchorBio, Fosun Pharma - LARVOL DELTA

First-in-human phase I study of HCB101, a 3.5th-generation CD47-SIRPα fc fusion protein: Cytopenia-sparing safety, broad pharmacologic window, and low-dose clinical activity in relapsed/refractory non-Hodgkin lymphoma (ASH 2025) - P1 | "HCB101, a 3.5th-generation CD47-SIPRα Fc fusion protein, demonstrates a favorable, cytopenia-sparingsafety profile (no DLTs, no Grade ≥3 TRAEs), a low-dose PD saturation (≥90% RO at 1.28 mg/kg and ≥99%RO at 5 mg/kg; MTD not reached at >24 mg/kg), and durable monotherapy activity at 8.00 mg/kg inheavily pretreated R/R NHL. Compared with earlier CD47-targeting modalities, including first-generationantibodies (e.g., Gilead, I-MAB) and second-generation wild-type SIRPα-Fc fusions (e.g., Pfizer,ImmuneOnco), HCB101 achieves superior receptor occupancy, safety beyond 24.0 mg/kg, and earlyclinical efficacy at 8.00 mg/kg – well below the upper dose levels – supporting a broad pharmacologicwindow. The selective CD47-SIRPα fusion design distinguishes HCB101 from first-generation antibodies,which are limited by anemia and dosing complexity."

Clinical • First-in-human • IO biomarker • P1 data • B Cell Lymphoma • Hematological Malignancies • Leukopenia • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Solid Tumor • Thrombocytopenia • CD47 • SIRPA

Dose-dependent antitumor activity of HCB101 plus ramucirumab and paclitaxel in previously treated gastric cancer. (ASCO-GI 2026) - P1/2 | "Clinical Trial Registration Number: NCT06771622 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Key Findings Highlighted in the Mini-Oral: Monotherapy (HCB101-101; NCT05892718) (PRNewswire) - "HanchorBio Announces oral presentation of HCB101 at the ESMO Immuno-Oncology Congress 2025....Clean, cytopenia-sparing safety across 12 cohorts up to 36 mg/kg QW....Durable antitumor activity, including confirmed PRs in: HNSCC -Head and neck squamous cell carcinoma (~42% tumor regression, ≥32 weeks); MZL - Marginal zone lymphoma (~89% tumor regression, ≥16 weeks); Stable disease ≥4-9 months across colorectal cancer (CRC), ovarian cancer, non-small cell lung cancer (NSCLC), and sarcoma."

P1 data • Colorectal Cancer • Marginal Zone Lymphoma • Non Small Cell Lung Cancer • Ovarian Cancer • Sarcoma • Squamous Cell Carcinoma of Head and Neck

Key Findings Highlighted in the Mini-Oral:…Combination Therapy (HCB101-201; NCT06771622) (PRNewswire) - "HanchorBio Announces oral presentation of HCB101 at the ESMO Immuno-Oncology Congress 2025....Well-tolerated across gastric cancer (GC), triple-negative breast cancer (TNBC), CRC, and HNSCC. No new safety signals across all evaluated combinations....2L GC: 58.3% ORR (7/12) for all cohorts evaluated, 77.8% ORR (7/9) for mid-dose cohorts, and 100% DCR; Tumor shrinkage up to -78.2%; 1L HER2+ GC: 33% ORR (1/3); 1L TNBC: 50% ORR (3/6) and 100% DCR."

P1/2 data • Colorectal Cancer • Gastric Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

HanchorBio Presents First-in-Human Data of HCB101 Monotherapy in Relapsed/Refractory Non-Hodgkin Lymphoma at ASH 2025 (PRNewswire) - "Key Results (data cutoff: October 14, 2025): Thirteen patients with R/R NHL received HCB101 (5.12 – 24.0 mg/kg QW). No dose-limiting toxicities (DLTs) were observed, and the maximum tolerated dose (MTD) was not reached. All treatment-related adverse events were Grade 1-2, confirming a cytopenia-sparing safety profile. CD47 receptor occupancy (RO) reached ≥ 75-85% at 1.2 mg/kg and ≥ 90% at 8 mg/kg, demonstrating a broad pharmacologic window."

First-in-human • P1 data • Non-Hodgkin’s Lymphoma

HCB101, a differentiated SIRpα-fc fusion protein, demonstrates favorable safety and early antitumor activity across solid tumors and lymphomas (ESMO-IO 2025) - P1, P1/2 | "In HCB101-201, combinations showed striking efficacy: in 2L GC, HCB101 with ramucirumab and paclitaxel achieved 100% ORR (6/6) at 5.12–8.0 mg/kg, with regressions up to –78.2%, far exceeding historical benchmarks (∼28%). Safety across combination cohorts was consistent with known SOC toxicities and manageable with standard interventions, with no new immune-related or off-target safety signals attributable to HCB101.Conclusions HCB101 demonstrates a favorable safety profile, durable monotherapy activity in HNSCC and NHL, and striking combination efficacy in GC and TNBC. These data establish HCB101 as a differentiated SIRPα-CD47 therapy with the potential to overcome class limitations and support registrational development across multiple tumor types.Clinical trial identification HCB101-101 (NCT05892718) HCB101-201 (NCT06771622).Legal entity responsible for the study HanchorBio Inc."

Clinical • Breast Cancer • Gastric Cancer • Head and Neck Cancer • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • SIRPA

HanchorBio Presents First-in-Human Phase 1 Data of HCB101 at the 67th American Society of Hematology (ASH) Annual Meeting (HanchorBio Press Release) - "The accepted abstract (#3299) includes a focused sub-analysis from HanchorBio’s ongoing multinational, open-label Phase 1 study evaluating HCB101 monotherapy across solid and hematologic malignancies, highlighting results from the R/R NHL cohort. HCB101 demonstrated a cytopenia-sparing safety profile along with early signals of clinical activity, representing a meaningful advancement in CD47–SIRPα therapeutic design."

P1 data • Non-Hodgkin’s Lymphoma

Title: Phase 1b/2a Study of HCB101 Combined with Standard Therapies Demonstrates Manageable Safety and Dose-Dependent Antitumor Activity in Immunologically Cold Advanced Solid Tumors (PRNewswire) - "HanchorBio Presents...Late-Breaking Abstracts at the Society for Immunotherapy of Cancer 2025....In second-line gastric cancer (GC): 100% confirmed partial response rate (6/6 evaluable patients) at active doses when combined with ramucirumab and paclitaxel. Tumor shrinkage up to 78%, surpassing the ~26.5% ORR benchmark from RAINBOW. In first-line triple-negative breast cancer (TNBC): Confirmed partial response with 73% tumor reduction at the effective dose."

Late-breaking abstract • P1/2 data • Gastric Cancer • Triple Negative Breast Cancer

Title: HCB101, a Next-Generation Fc-Engineered SIRPα-CD47 Fusion Protein, Demonstrates Favorable Safety and Early Antitumor Activity in Advanced Cancers (PRNewswire) - "HanchorBio Presents...Late-Breaking Abstracts at the Society for Immunotherapy of Cancer 2025....In the ongoing Phase 1a dose-escalation, no dose-limiting toxicities (DLTs) have been observed at doses up to 24 mg/kg. CD47 receptor occupancy ≥99% achieved at doses ≥5 mg/kg, with dose-proportional pharmacokinetics. Confirmed partial responses seen in head and neck squamous cell carcinoma (HNSCC) and marginal zone lymphoma (MZL). Several patients achieved stable disease, with progression-free survival up to 32 weeks."

Late-breaking abstract • P1 data • Marginal Zone Lymphoma • Squamous Cell Carcinoma of Head and Neck

HanchorBio will also present two late-breaking abstracts on November 7 to showcase clinical data on its SIRPα-Fc fusion protein HCB101…at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC)… (PRNewswire)

Clinical data • Late-breaking abstract • Oncology

Phase Ib/IIa Study of HCB101 Combined with Standard Therapies Demonstrates Manageable Safety and Dose-Dependent Antitumor Activity in Immunologically Cold Advanced Solid Tumors (SITC 2025) - P1, P1/2 | "Cohorts included: a) second-line (2L) GC (HCB101 plus ramucirumab and paclitaxel); and b) first-line (1L) TNBC (HCB101 plus toripalimab and nab-paclitaxel). NCT06771622Ethics Approval The study was approved by following ethics committees: 1.Cancer Hospital of Shandong First Medical University Ethics Committee; Number of theapproval: SDZLEC2024-412-04; 2.The Fifth Affiliated Hospital, Sun Yat-sen University Ethics Committee; Number of the approval:2025-Y241-3; 3.Dongguan People's Hospital Ethics Committee; Number of the approval: DRYA2025-015-B3; 4.Qilu Hospital of Shandong University Dezhou Hospital Ethics Committee; Number of the approval: 2025-003-002; 5.Binzhou Medical University Affiliated Hospital Ethics Committee; Number of the approval: 2025-011-03; Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this..."

Clinical • Late-breaking abstract • Metastases • P1/2 data • Breast Cancer • Gastric Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • CD47 • SIRPA

HCB101, a Next-Generation Fc-Engineered anti-CD47 SIRPα Fusion Protein, Demonstrates Favorable Safety and Early Antitumor Activity in Advanced Cancers (SITC 2025) - "Dezhou Hospital of Qilu Hospital of Shandong University Ethics Committee; Number of the approval: 2025-008-003.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal."

Clinical • IO biomarker • Late-breaking abstract • Metastases • Head and Neck Cancer • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD47 • SIRPA

HCB101: a novel potent ligand-trap Fc-fusion protein targeting the CD47-SIRPα pathway with high safety and preclinical efficacy for hematological and solid tumors. (PubMed, J Hematol Oncol) - "HCB101 demonstrates high-affinity binding to CD47, robustly promotes macrophage-mediated phagocytosis of tumor cells without affecting red blood cells and exhibits unique advantages over current CD47-targeting agents, including Hu5F9-G4, TTI-622, and ALX148. Additionally, HCB101 treatment increased the M1/M2 macrophage ratio in the tumor microenvironment, suggesting repolarization of tumor-associated macrophages (TAMs) toward a pro-inflammatory phenotype. No dose-limiting toxicities or hematologic adverse effects were observed in murine or non-human primate studies."

IO biomarker • Journal • Preclinical • Hematological Disorders • Oncology • Solid Tumor • CD47 • SIRPA

HanchorBio Presents Phase 1 HCB101 Clinical Results at FACO 2025 Demonstrating Safety and Early Antitumor Activity (PRNewswire) - "Key highlights from the study as of July 10, 2025, include: Favorable safety profile: Among 49 patients enrolled across 10 dose levels (0.08-18.00 mg/kg, QW), only one dose-limiting toxicity (DLT) was observed, a transient Grade 3 thrombocytopenia at the 2.56 mg/kg dose level....; Encouraging antitumor activity: Two confirmed partial responses (PRs) in head and neck squamous cell carcinoma (HNSCC) and non-Hodgkin lymphoma, alongside durable disease control in multiple patients."

P1 data • Non-Hodgkin’s Lymphoma • Squamous Cell Carcinoma of Head and Neck

HanchorBio today announced that its proprietary HCB101…has been officially granted a US patent (Patent No. 12,447,195) by the United States Patent and Trademark Office (USPTO) (PRNewswire) - "...The patent represents major international recognition for the company's innovative technology for immuno-oncology....The USPTO recognized HCB101's original mutation design and unprecedented potency as clear evidence of novelty and inventive step....Following this US patent grant, HanchorBio will advance patent filings across Europe, Taiwan, and other Asian countries as part of its broader global IP roadmap."

Patent • Oncology

HanchorBio Showcases Pipeline Momentum with HCB101…Data Across...Major Oncology Meetings in Q4 2025 (PRNewswire) - "HanchorBio...announced that new clinical data from HCB101, its differentiated, engineered SIRPα-Fc fusion protein...will be presented at...major international oncology congresses in the fourth quarter of 2025. The upcoming presentations will showcase progress from HCB101, including both the HCB101-101 monotherapy (NCT05892718) and the HCB101-201 combination (NCT06771622) studies..."

Clinical data • Lymphoma • Solid Tumor

The Phase 1b/IIa, Open-label, Dose Escalation and Dose Expansion to Evaluate Safety, Tolerability, and Preliminary Efficacy of the Combination of HCB101, Cetuximab/Bevacizumab, and FOLFOX/FOLFIRI in Advanced or Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: Chang Gung Memorial Hospital

New P1/2 trial • Colorectal Cancer • Oncology • Solid Tumor

A Phase I/II Trial of HCB101 in Combination With Pembrolizumab for Patients With Platinum-Refractory, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (SirH&N Trial) (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Taipei Veterans General Hospital, Taiwan

New P1/2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

HanchorBio Receives Third Taiwan TFDA Approval for HCB101 Combination Therapy in Advanced Gastric Cancer (HanchorBio Press Release) - "HanchorBio...announced that the Taiwan Food and Drug Administration (TFDA) has approved a third investigator-initiated trial (IIT) evaluating HCB101 in combination with zolbetuximab and chemotherapy for the first-line treatment of patients with HER2-negative, CLDN18.2-positive advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The study will be conducted at Kaohsiung Medical University Chung-Ho Memorial Hospital....The open-label, dose-escalation, and dose-expansion trial (HCB101-IIT-GC-202501) is designed to evaluate the safety, tolerability, and preliminary efficacy of HCB101 in combination with zolbetuximab and chemotherapy in patients with HER2-negative, CLDN18.2-positive advanced or metastatic gastric or GEJ adenocarcinoma who have progressed following prior standard therapy."

New trial • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

A Safety and Efficacy Study of HCB101, Fc-fusion Protein Targeting SIRPα-CD47 Pathway, in Solid or Hematological Tumors (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: FBD Biologics Limited | Trial completion date: Nov 2025 ➔ Nov 2029 | Trial primary completion date: May 2025 ➔ May 2027

Trial completion date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

HanchorBio and Henlius Sign Major Licensing Deal for HCB101 to Expand Global Immuno-Oncology Reach (PRNewswire) - "HanchorBio...announces the signing of a major out-licensing agreement with Shanghai Henlius Biotech, Inc. (hereafter 'Henlius'). The deal grants Henlius exclusive development and commercialization rights to HCB101 across Greater China (including Mainland China, Hong Kong, and Macau), key Southeast Asian countries, as well as all countries in the Middle East and North Africa (MENA). Under the terms of the agreement, HanchorBio will receive an upfront payment of USD 10 million, with additional payments tied to development and regulatory milestones of up to USD 192 million. Henlius will also pay tiered royalties and assume full responsibility for development, manufacturing, and commercialization in the licensed territories. HanchorBio retains all rights outside the licensed regions."

Licensing / partnership • Hematological Malignancies • Solid Tumor

HanchorBio Presents Promising Data on HCB101 Checkpoint Inhibitor Immunotherapy at ASCO (PRNewswire) - P1 | N=60 | NCT05892718 | "While previous generations of CPI treatments tended to be either safe or effective, HCB101 stands out for its potential to achieve both. Utilizing the engineered signal-regulatory protein α (SIRPα) that targets CD-47, it has demonstrated efficacy against both solid and hematologic tumors, while earlier clinical trial data from the completed Phase 1a confirmed 100% safety across all dose levels. It can also be used as both a standalone treatment and in combination with other therapies. In terms of efficacy, HCB101 demonstrated a 26.7% disease control rate in the Phase 1a data, with 16.7% of subjects maintaining disease control for over four months."

P1 data • Head and Neck Cancer • Non-Hodgkin’s Lymphoma

HanchorBio Presents Promising Phase 1 HCB101 Data at ASCO 2025 - Confirmed Partial Response Observed in Solid Tumor and Lymphoma Patients (HanchorBio Press Release) - P1 | N=60 | NCT05892718 | Sponsor: FBD Biologics Limited | "The ongoing Phase 1 dose-escalation trial (NCT05892718) is evaluating HCB101...in patients with advanced solid tumors or relapsed/refractory (R/R) non-Hodgkin lymphomas (NHLs). As of April 23, 2025, the study had enrolled 36 patients....Key findings include: (i) Favorable safety and tolerability across escalating doses; (ii) High-level CD47 receptor occupancy in peripheral immune cells; (iii) Partial responses were observed in patients with head and neck cancer (HNSCC) and NHL. Importantly, early signs of anti-tumor activity were observed. Six patients reported Stable Disease (SD) as the best response, one of which with ovarian cancer (1.28 mg/kg) exceeded 24 weeks of disease control. Two patients reported Partial Response (PR), one of which with HNSCC (5.12 mg/kg) initially exhibited a 27% reduction in the sum of diameters (SOD) for target lesions at week 8, which subsequently deepened to a confirmed PR..."

P1 data • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Ovarian Cancer • Squamous Cell Carcinoma of Head and Neck

Phase 1 trial of HCB101, a novel Fc-based anti-SIRPα-CD47 fusion protein, in subjects with advanced cancers. (ASCO 2025) - P1 | "HCB101 demonstrated an acceptable safety profile and preliminary antitumor activity in heavily pretreated advanced cancer patients. These findings support its further clinical development, including expansion cohorts to evaluate efficacy in specific tumor types or in combination with other agents."

Clinical • Metastases • P1 data • Anemia • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • SIRPA

HanchorBio to Present Interim Clinical Data at ASCO 2025 Annual Meeting (HanchorBio Press Release) - "The accepted abstract (#2584: Phase 1 trial of HCB101, a novel Fc-based anti-SIRPα-CD47 fusion protein, in subjects with advanced cancers) highlights emerging data from the ongoing Phase 1 dose-escalation trial (NCT05892718) of HCB101, a differentiated SIRPα-Fc fusion protein rationally engineered to enhance phagocytosis and innate immune activation, without the hematologic toxicity that has hindered earlier CD47-targeting therapies....The poster presentation is scheduled for June 2, 2025, during the ASCO Immunotherapy session."

P1 data • Non-Hodgkin’s Lymphoma • Solid Tumor