On April 17, 2026, Shanghai Henlius Biotech, Inc. (2696.HK) announced that it will present the latest prelinical data from seven innovative pipeline programs at the American Association for Cancer Research (AACR) Annual Meeting 2026, to be held from April 17 to 22 in San Diego, USA.

The innovations to be presented are enabled by the company’s advanced proprietary technology platforms, including the Hanjugator™ antibody–drug conjugate (ADC) platform and the multispecific T-cell engager (TCE) platform, covering a broad range of high-potential cutting-edge targets with strong development potential, including PD-L1, B7-H3, STEAP1, EGFR, c-MET, HER2, ADAM9, ALPP, and ALPPL2. Preclinical data indicate that several of these molecules have demonstrated first-in-class or best-in-class potential in head-to-head comparisons.

(I) TCE Platform: Incorporation of CD28 Co-stimulation to Remodel Immunologically “Cold” Solid Tumors

In the treatment of solid tumors, insufficient T-cell infiltration and an immunosuppressive tumor microenvironment (TME) represent key bottlenecks limiting the efficacy of TCE therapies. To address this challenge and optimize the therapeutic window of TCEs in solid tumors, Henlius has developed a multispecific TCE platform incorporating CD28 co-stimulatory signaling. By simultaneously delivering CD3 activation (signal 1) and CD28 co-stimulation (signal 2), the platform significantly enhances sustained T-cell–mediated cytotoxic activity. In addition, through multiple synergistic mechanisms—including target-dependent activation, affinity tuning, and cis-binding of CD3/CD28—the platform improves antitumor efficacy while effectively controlling systemic toxicity risk. More than five early-stage innovative molecules have been generated from this platform. Among them, HLX3901 (DLL3×DLL3×CD3×CD28 tetraspecific antibody) and HLX3902 (STEAP1×CD3×CD28 trispecific antibody) represent key assets in this field, focusing on the treatment of solid tumors such as small cell lung cancer and prostate cancer, and have been advanced to the IND or IND-accepted stage.

HLX3902 (STEAP1×CD3×CD28 trispecific TCE)

HLX3902 is a trispecific antibody that precisely targets STEAP1, which is highly expressed in prostate cancer, as well as CD3 and CD28, and represents one of the company’s core assets in this field. Preclinical studies show that HLX3902 induces target-dependent T-cell activation and cytotoxicity, with particularly pronounced activity under low effector-to-target (E:T) ratios (1:5–1:10). Compared with bispecific TCEs and their combination approaches, this molecule significantly enhances T-cell function, proliferation, and memory T-cell expansion, and demonstrates more durable in vitro cytotoxicity. In addition, in in vivo models, HLX3902 demonstrated superior and more durable antitumor activity compared with Amgen’s AMG509(STEAP1×CD3 bispecific TCE) at a single dose of 0.01 mg/kg. This activity is accompanied by increased T-cell infiltration and activation, as well as sustained intratumoral CD8⁺ T-cell effector function mediated by CD28 co-stimulation. In cynomolgus monkeys, HLX3902 showed good tolerability at weekly intravenous dosing of 45 μg/kg. The IND application for this molecule has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China

·Title: A novel anti-CD3×CD28×STEAP1 tri-specific T-cell engager with enhanced and durable antitumor responses in prostate cancer

·Session Title: Redefining Targeted Therapy: Bispecific T-Cell Engagers and Antibody-Drug Conjugates 2

·Format: Poster Session

·Abstract Number: 5397

·Date and Time: April 21, 2026, 9:00 AM-12:00 PM 

·Location: Poster Section 48, Board #10

In addition, HLX3901, another promising TCE molecule derived from this platform, is a tetraspecific antibody targeting DLL3 dual epitopes, CD3, and CD28, and its IND application was approved by the National Medical Products Administration (NMPA) in March 2026. HLX3901 integrates AI-driven drug design with the TCE platform. Through its optimized molecular design, the molecule enables sustained and specific T-cell activation, enables activity in tumors with low T-cell infiltration, and significantly reduces the risk of cytokine release syndrome (CRS), aiming to address key limitations of first-generation TCEs in solid tumors. Preclinical studies show that HLX3901 demonstrates superior cytotoxicity under low E:T ratio conditions. In human pan-T cell reconstitution models, HLX3901 exhibits stronger and more durable antitumor activity compared with benchmark molecules such as tarlatamab. In addition, preliminary toxicology studies in cynomolgus monkeys indicate that HLX3901 is well tolerated and shows a wider therapeutic window. Preclinical data for this molecule were first presented at the 2025 Antibody Engineering & Therapeutics conference.

(II) Hanjugator™ ADC Platform: Tunable Payload Design to Expand the Therapeutic Window

In the design of antibody–drug conjugates (ADCs), highly potent payloads can effectively eliminate tumor cells but may also significantly limit clinically achievable dosing, making it difficult to reach optimal antibody exposure and resulting in a narrow therapeutic window. To address this challenge, Henlius has developed a next-generation ADC technology platform, Hanjugator™, a customizable and modular camptothecin-based linker–payload platform. A key advantage of this platform lies in its highly hydrophilic camptothecin linker–payload design, which enables selection of optimal payload potency based on target characteristics, with cytotoxic activity ranging from approximately one-third that of DXd to levels comparable to exatecan. This approach broadens the therapeutic window while preserving antibody functionality, achieving an optimal balance between antibody-mediated signaling blockade/internalization and potent small-molecule cytotoxicity, thereby delivering synergistic therapeutic effects. 

In addition, ADCs generated from this platform exhibit a bystander killing effect more than ten-fold greater than that of deruxtecan-based ADCs, which may help overcome tumor heterogeneity. The differentiated payload design may also help circumvent common resistance mechanisms associated with conventional toxins, providing a differentiated approach for next-generation ADC development. To date, the Hanjugator™ platform has generated more than 12 early-stage innovative assets, including HLX48 (EGFR/c-MET bispecific ADC), HLX49 (HER2 biparatopic ADC), HLX403 (CDH17 ADC), HLX402 (ADAM9 ADC), HLX85 (ALPP/ALPPL2 ADC), and HLX41 (LIV-1 ADC).

HLX48 (EGFR/c-MET bispecific ADC)

HLX48 is a novel ADC candidate independently developed by Henlius based on the Hanjugator™ platform, comprising an EGFR/c-MET bispecific antibody conjugated to a camptothecin-derived topoisomerase I inhibitor payload. Given that dual-targeting EGFR/c-MET ADCs often require relatively high clinical doses to achieve optimal receptor occupancy, HLX48 adopts a highly hydrophilic linker strategy combined with a moderate-potency payload design, with a drug-to-antibody ratio (DAR) of approximately 4, aiming to achieve an optimal balance between potent antitumor activity and manageable toxicity. Preclinical pharmacology studies demonstrate that HLX48 exhibits significant antitumor activity across multiple tumor models, with a single dose of 3 mg/kg inducing marked tumor regression. In the HT29 colorectal cancer model, its efficacy surpassed that of AstraZeneca’s AZD9592. In addition, HLX48 showed good tolerability in cynomolgus monkeys at 60 mg/kg (every three weeks), supporting the feasibility of its moderate-potency payload design.

·Title: Hanjugator camptothecin platform: effective, low-toxicity design maximizing antibody functionality and enabling a potential best-in-class EGFR/cMet bispecific ADC

·Session Title: Tumor Microenvironment, Multispecifics, and Immunomodulation

·Format: Poster Session

·Abstract Number:  5856

·Date and Time: April 21, 2026, 2:00 PM-5:00 PM 

·Location: Poster Section 17, Board #25

HLX49 (HER2 biparatopic ADC)

HLX49 is a HER2 biparatopic ADC candidate engineered to target two distinct epitopes within domain IV, derived from Henlius’s proprietary rastuzumab (Hanquyou^®) and dulpatatug*(a novel anti-HER2 antibody), thereby enabling biparatopic engagement. This molecule adopts an efficient, low-toxicity payload design, enabling higher dosing and improved receptor coverage, thereby enhancing tumor cell killing. In BT-474 and NCI-N87 cell lines, HLX49 demonstrated superior internalization efficiency compared with KN026 (a HER2-targeting bispecific antibody from Alphamab Oncology) and trastuzumab deruxtecan (a HER2 ADC). Across multiple cell lines, this biparatopic ADC showed improved antitumor activity relative to trastuzumab deruxtecan. In various xenograft models, a single dose of 6 mg/kg induced significant tumor regression. In head-to-head comparisons with trastuzumab deruxtecan, HLX49 demonstrated superior efficacy across a range of models, including HER2-positive (IHC 3+, IHC 2+/FISH+), HER2-low (IHC 2+/FISH− or IHC 1+), and HER2 ultra-low (IHC <1+) tumors. Preliminary toxicology studies showed that HLX49 was well tolerated in cynomolgus monkeys following three doses at 60 mg/kg.

·Title: A best-in-class HER2xHER2 biparatopic antibody-drug conjugate with an efficacious, low-toxicity design that maximizes antibody functionality

·Session Title: Antibody Technologies and Platforms 2

·Format: Poster Session

·Abstract Number: 4395

·Date and Time: April 21, 2026, 9:00 AM-12:00 PM 

·Location: Poster Section 11, Board #3

HLX402 (ADAM9 ADC)

ADAM9 (a disintegrin and metalloproteinase domain-containing protein 9) is overexpressed in multiple solid tumors, including pancreatic, lung, and gastric cancers; however, prior clinical development efforts on the target have been discontinued due to drug-related ocular toxicity. HLX402 incorporates a novel camptothecin-based linker–payload design, aiming to mitigate such ocular toxicity while providing a wider therapeutic window. Preclinical studies demonstrate that the antibody component of HLX402 exhibits nanomolar affinity to ADAM9 in both humans and cynomolgus monkeys. The antibody shows efficient, time-dependent internalization (>50% at 4 hours) across multiple tumor cell lines (MKN-45, MiaPaCa-2, and Calu-3), along with potent cytotoxicity and a strong bystander killing effect. In the Calu-3 (non-squamous NSCLC) CDX model, a single dose of 3 mg/kg achieved a tumor growth inhibition (TGI) of 109.3%, significantly outperforming a benchmark ADC (91.1%). In the DLD-1 (colorectal cancer) CDX model, HLX402 achieved a TGI of 90.2% at the same dose, compared with 39.2% for the benchmark ADC. In rats, HLX402 demonstrated excellent plasma stability and favorable pharmacokinetics, with minimal release of free payload and an antibody-like half-life.

•Title: Preclinical characterization of a potential best-in-class camptothecin-based antibody-drug conjugate targeting ADAM metallopeptidase domain 9

•Session Title: Antibody Technologies and Platforms 2

•Format: Poster Session

•Abstract Number: 4418

•Date and Time: April 21, 2026, 9:00 AM-12:00 PM ET

•Location: Poster Section 11, Board#26

HLX85 (ALPP/ALPPL2 ADC)

ALPP (placental alkaline phosphatase) and ALPPL2 (placental-like alkaline phosphatase 2) are promising targets due to their expression in multiple solid tumors and minimal expression in normal tissues, including ovarian cancer (60%), endometrial cancer (50%), pancreatic cancer (30%), and gastric cancer (15%). HLX85 is a potential first-in-class ADC targeting ALPP/ALPPL2, consisting of a high-affinity monoclonal antibody conjugated via a protease-cleavable linker to a proprietary camptothecin-based payload. Preclinical studies demonstrate that HLX85 exhibits target-mediated cytotoxicity in vitro in HEP2 (high ALPP/ALPPL2 expression) and NCI-H1651 (moderate expression) cell lines. Its bystander killing effect is more than ten-fold greater than that of deruxtecan-based ADCs. In vivo, a single dose of 1 mg/kg induced significant tumor regression in the Capan-1 CDX model. In a gastric adenocarcinoma PDX model resistant to MMAE-based ADCs, a single dose of 8 mg/kg achieved deep tumor remission. In non-human primates, HLX85 demonstrated linear pharmacokinetics and excellent tolerability, with a highest non-severely toxic dose (HNSTD) ≥40 mg/kg.

•Title: Development of a first-in-class camptothecin-based antibody-drug conjugate targeting ALPP/ALPPL2 with potent antitumor activity and excellent tolerability

•Session Title: Antibody Technologies and Platforms 2

•Format: Poster Session

•Abstract Number: 4419

•Date and Time: April 21, 2026, 9:00 AM-12:00 PM 

•Location: Poster Section 11, Board#27

(III) Additional Innovative Pipeline Candidates

HLX43 (PD-L1 ADC)

In parallel with advancing its technology platforms, Henlius continues to discover innovative molecules featuring breakthrough mechanisms of action. HLX43 is a potential best-in-class pan-tumor PD-L1–targeted antibody-drug conjugate (ADC), combining immune checkpoint blockade with payload-mediated cytotoxicity. The molecule comprises an engineered humanized anti-PD-L1 IgG1 antibody (HLX20) conjugated via a protease-cleavable tripeptide linker to a potent camptothecin-derived topoisomerase I inhibitor (C24), with a drug-to-antibody ratio (DAR) of approximately 8. Preclinical studies show that HLX43 retains the binding affinity and internalization properties of HLX20, while demonstrating favorable stability and potent antitumor activity.

Its mechanism of action integrates immune checkpoint inhibition, targeted cytotoxicity, and tumor microenvironment (TME) modulation. As an anti-PD-L1 agent, HLX43 effectively blocks the PD-1/PD-L1 axis, restoring T-cell activity, as evidenced by increased IL-2 and IFN-γ secretion in mixed lymphocyte reaction (MLR) assays. Its direct cytotoxicity is driven by DNA damage induced by the topoisomerase I inhibitor payload, leading to inhibition of DNA repair and induction of tumor cell apoptosis. In addition, HLX43 induces immunogenic cell death (ICD), further enhancing antitumor immune responses. Within the TME, the linker can be cleaved by proteases such as matrix metalloproteinases (MMPs) and cysteine proteases, enabling payload release that is not strictly dependent on PD-L1 binding. The released payload diffuses within tumor tissue and exerts a bystander effect, killing adjacent PD-L1-negative tumor cells. Therefore, HLX43 demonstrates robust antitumor activity even in PDX models with highly heterogeneous PD-L1 expression. Beyond direct tumor cell killing, HLX43 also remodels the TME, significantly increasing infiltration of cytotoxic CD8⁺ T cells, reducing regulatory T cells (Tregs), and enhancing CD8⁺ T-cell effector function.

•Title: Preclinical studies reveal that protease-mediated payload release and immuno-oncology/immunomodulatory effects contribute to the antitumor activity of HLX43

•Session Title: Mechanisms of Anticancer Drug Action

•Format: Poster Session

•Abstract Number: 5704

•Date and Time: April 21, 2026, 2:00 PM-5:00 PM 

•Location: Poster Section 12, Board #20

HLX316 (B7-H3 × Sialidase Fusion Protein)

B7-H3 is an immune checkpoint-related protein highly expressed across multiple solid tumors—including lung, breast, colorectal, pancreatic, prostate, and ovarian cancers—and is associated with tumor progression and poor prognosis, while exhibiting low expression in normal tissues. HLX316 is a potential first-in-class B7-H3-targeted human sialidase fusion protein, co-developed by Henlius and Palleon Pharmaceuticals. It addresses a key immune evasion mechanism in cancer, whereby hypersialylation on tumor cell surfaces engages Siglec receptors on immune cells, suppressing both innate and adaptive immune responses.

HLX316 selectively accumulates in tumor tissue via B7-H3 targeting and exerts potent desialylation activity, thereby reversing glyco-immune checkpoint suppression mediated by the sialic acid–Siglec axis, restoring immune cell function in the TME, and enhancing both innate and adaptive antitumor immunity.

Preclinical studies show that in B7-H3-positive, highly sialylated tumor cell lines, HLX316 demonstrates over 1,000-fold higher desialylation activity compared with non-targeted sialidases. In vivo, HLX316 exhibits more durable desialylation activity in tumors and significantly prolongs pharmacodynamic effects. Additionally, HLX316 enhances antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thereby strengthening antibody-mediated immune clearance of tumor cells. Across multiple mouse tumor models, HLX316 demonstrated significant monotherapy antitumor activity. In the A375 humanized mouse model, its efficacy exceeded that of B7-H3 antibodies, non-targeted sialidase, and anti-PD-1 antibodies. GLP repeat-dose toxicology studies in non-human primates showed that HLX316 was well tolerated, with no significant toxicity observed, and a no observed adverse effect level (NOAEL) of 150 mg/kg.

·Title: E-688/HLX316: A first-in-class B7-H3 targeted sialidase for boosting innate and adaptive anti-tumor immunity / Human sialidase-armed anti-B7-H3 antibody that enhances innate and adaptive antitumor immune responses 

·Session 1: New Drugs on the Horizon: Part 2 

·Format: Oral Session

·Abstract Number: ND05 

·Date and Time: April 19, 3:05 PM–3:20 PM 

·Location: Ballroom 20 CD - Upper Level - Convention Center 

·Session 2: Overcoming Microenvironmental and Delivery Barriers in Cancer Therapy 

·Format:  Poster Session

·Abstract Number: 7158 

·Date and Time: April 22, 9:00 AM–12:00 PM 

·Location: Section 15, Poster #15

About Henlius

Shanghai Henlius Biotech, Inc. (2696.HK) is a global, innovation-driven biopharmaceutical company committed to delivering high-quality, affordable biologic therapies to patients worldwide. The Company focuses on major disease areas including oncology, autoimmune diseases, and ophthalmic diseases. Founded in 2010, Henlius has established an integrated, end-to-end biopharmaceutical platform encompassing global R&D, clinical operations, regulatory affairs, manufacturing, and commercialisation. The Company employs nearly 4,000 people globally and operates across multiple regions, including China, the United States, and Japan. Leveraging the stable cash flow generated from its biosimilar portfolio to support innovation, Henlius is steadily advancing into its “Globalisation 2.0” phase, building a scalable and sustainable global growth model. As of early 2026, Henlius has achieved regulatory approvals for 10 products across over 60 countries and regions worldwide, including seven approvals in China. The Company has also reached multiple milestones in major biopharmaceutical markets, with four products approved by the U.S. Food and Drug Administration (FDA) and four products approved by the European Commission (EC), reflecting its globally aligned R&D capabilities, quality systems, and manufacturing standards.

Driven by innovation, Henlius has built a diversified, platform-based technology ecosystem through coordinated R&D efforts across Shanghai, the United States, and other regions. Its innovation platforms span immune checkpoint inhibitors, immune cell engager technologies (including multispecific T cell engagers), antibody-drug conjugates (ADCs), and AI-enabled early discovery platforms. The Company currently has more than 50 early-stage innovative assets, approximately 70% of which are expected to be best-in-class, with over 30 clinical trials ongoing globally. Henlius’ core product, serplulimab (trade name: Hetronifly^® in Europe), is the world’s first anti–PD-1 mAb approved for first-line treatment of small cell lung cancer and has been approved in more than 40 markets worldwide with an accelerated globalisation process. In parallel, multiple high-potential innovative assets—including the PD-L1 ADC HLX43 and the novel epitope anti-HER2 mAb HLX22—are advancing through global pivotal clinical development. Supported by a biologics manufacturing network with a total capacity of 84,000L and GMP certifications from regulatory authorities in China, Europe, and the United States, Henlius has established a stable global supply system serving six continents. Guided by a patient-centred mission, Henlius remains focused on addressing unmet medical needs and translating scientific innovation into meaningful clinical value and patient access, contributing sustainably to the global biopharmaceutical ecosystem.

To learn more about Henlius, visit https://www.henlius.com/en/ and connect with us on LinkedIn at https://www.linkedin.com/company/henlius/.

*注：药品通用名处于pINN状态

*Note: This INN is currently under review (pINN status)