ZL-1222 / ZAI Lab - LARVOL DELTA

Anticipated Major Milestones:…ZL-1222 (PD-1/IL-12) (Businesswire) - "Submit an IND application in the U.S. and initiate a global Phase 1 study in 2027."

IND • New P1 trial • Oncology

ZL-1222, a PD-1-targeted potency-reduced IL-12 immunocytokine, overcomes PD-1 resistance and enhances antitumor immunity with an accepted safety profile (AACR 2026) - "In a pilot toxicity study, cynomolgus monkeys tolerated single doses of ZL-1222 up to 10 mg/kg without evidence of systemic cytokine storm (IL-6 < 50 pg/mL; TNFα not detectable).In conclusion, ZL-1222, a PD-1-targeted, potency-reduced IL-12 immunocytokine, achieves potent antitumor activity in PD-1-resistant models via delivery to PD-1⁺ TILs, engaging CD8⁺ T and NK cells in the TME while minimizing systemic toxicity. It induces durable immune memory, demonstrates dose-dependent efficacy with robust PK/TGI correlation, and shows favorable tolerability in non-human primates, supporting its potential as a next-generation immunotherapy for solid tumors."

Clinical • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL12A • IL6 • TNFA

Data from two additional Zai Lab internally developed investigational oncology therapies will also be presented at AACR (Businesswire) - "Researchers will share promising findings from preclinical studies of ZL-6201, a leucine-rich repeat-containing protein 15 (LRRC15) targeting ADC for the treatment of sarcoma and epithelial tumors with LRRC15 expressing cancer-associated fibroblasts; and, ZL-1222, a potential next generation anti-PD-1 and interleukin-12 (IL-12) signaling attenuated mutein agonist immunocytokine for cancer immunotherapy."

Preclinical • Sarcoma

Cis-delivery of a potency-reduced IL-12 via an anti-PD-1 single-chain antibody exhibits potent anti-tumor activity (AACR 2025) - "In a SARS-CoV-2 Spike protein recall assay, ZL-1222 demonstrates significantly higher IFN-γ production in human PBMCs compared to the combination of potency-reduced IL-12 and the αPD-1 ScAb. Additionally, in a co-culture of human cancer cells and primary PBMCs, ZL-1222 demonstrates superior IFN-γ release and tumor killing compared to the combination treatment.In vivo, systemic administration of ZL-1222 mouse surrogates, m34 or m45, shows strong antitumor activity with reduced mouse body weight loss in the B16F10 syngeneic tumor model in human PD-1 knock-in C57Bl/6 mice and the B16F10.OVA syngeneic model in wild-type C57Bl/6 mice compared to treatment with wild type IL-12.These results position ZL-1222 as a promising next-generation IL-12 immunocytokine for cancer immunotherapy, potentially combining potent antitumor activity with improved systemic safety."

IO biomarker • Late-breaking abstract • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL12A

Zai Lab to Present New Data on Three Internally Developed Oncology Candidates at AACR 2026, Including Zocilurtatug Pelitecan, a DLL3-Targeting Antibody-Drug Conjugate (ADC) (Businesswire) - "Zoci data show intracranial response in small-cell lung cancer (SCLC) with brain metastases, as well as activity in other neuroendocrine carcinomas. ZL-6201 will be highlighted in a poster presentation showcasing its potential as an innovative ADC for the treatment of sarcoma and other LRRC15-positive solid tumors. ZL-1222, a PD-1/IL-12, will also be featured in a poster presentation highlighting its potential as a next-generation immunocytokine therapy for the treatment of solid tumors....Zoci is on track to become Zai Lab’s first global oncology launch, with plans for three registration-enabling studies across 2L+ SCLC, 1L SCLC, and extrapulmonary NECs by the end of 2026."

Clinical data • New trial • Neuroendocrine Carcinoma • Sarcoma • Small Cell Lung Cancer

2026 Strategic Priorities (Businesswire) - "ZL-1222 (PD-1/IL-12 immunocytokine): Investigational New Drug (IND)-enabling studies expected to be completed in 2026; ZL-1311 (T-cell engager (TCE) targeting MUC17): IND submission expected by year end."

IND • Oncology • Solid Tumor

Zai Lab Presents Data Highlighting Potential of Internally Developed, Next-Generation Oncology Therapies at AACR 2025 (Businesswire) - "Findings to be presented at AACR 2025 on Tuesday, April 29, demonstrate that ZL-6201 efficiently internalizes within and kills tumor cells, while also exhibiting a strong bystander killing effect in the tumor microenvironment where the target is often expressed. In multiple in vitro and in vivo pre-clinical studies, treatment with ZL-6201 effectively suppressed the growth of established tumors. Based on these findings, Zai Lab plans to initiate Investigational New Drug (IND)-enabling studies of ZL-6201 as a potential treatment for patients with sarcoma and other LRRC15-positive solid tumors, such as breast cancer and other malignancies, in 2025....Findings from preclinical studies to be presented Monday, April 28, at AACR 2025 suggest that ZL-1222, through precisely tailored IL-12 activity and PD-1 targeting, demonstrate potent anti-tumor activity in both anti-PD-1 sensitive and resistant tumor models, with improved systemic safety."

Preclinical • Breast Cancer • Hematological Malignancies • Sarcoma • Solid Tumor

Zai Lab to Present New Data from Internally Developed, Next-Generation Oncology Candidates at AACR 2025 Annual Meeting (Businesswire) - "Poster presentation will highlight the potential of ZL-6201 as an innovative antibody-drug conjugate (ADC) for the treatment of sarcoma and other leucine-rich repeat-containing protein 15 (LRRC15)-positive solid tumors. Late-breaking poster presentation will summarize data from preclinical evaluation of ZL-1222, a promising next-generation interleukin-12 (IL-12) immunocytokine therapy for the treatment of various cancers."

Late-breaking abstract • Preclinical • Sarcoma • Solid Tumor