On April 25, 2025 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that it will present new data from studies evaluating two of its internally developed, next-generation, investigational oncology therapies that it has global rights to, ZL-6201, a novel leucine-rich repeat-containing protein 15 (LRRC15) antibody-drug conjugate (ADC) targeting multiple solid tumors, and ZL-1222, an innovative anti-PD-1/ interleukin-12 (IL-12) immunocytokine for cancer immunotherapy, during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago, Illinois this week (Press release, Zai Laboratory, APR 25, 2025, View Source [SID1234652168]). The data provide strong evidence supporting continued evaluation of both investigational therapies.
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"The latest findings that will be presented at AACR (Free AACR Whitepaper) 2025 demonstrate impressive potential for the continued advancement of these next-generation oncology therapies," said Linda Liu, Ph.D., Senior Vice President, Biologics Discovery, Zai Lab. "We look forward to continuing our evaluation of these therapies that may provide the opportunity to broaden treatment options for patients who have been unresponsive or resistant to current treatments across a broad range of cancer types."
ZL-6201 is a potential first- and best-in-class ADC with high affinity and specificity for LRRC15, an appealing target for cancer therapy due to its overexpression in multiple solid tumor types such as sarcoma, glioblastoma and melanoma. The compound was designed with a novel ADC technology platform called TMALIN, which leverages the tumor microenvironment to overcome challenges associated with first-generation ADC therapies, including off-target payload toxicity.
Findings to be presented at AACR (Free AACR Whitepaper) 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.
ZL-1222 is a PD-1 targeted, next-generation IL-12 immunocytokine designed to leverage the anti-tumor potential of IL-12 while lowering the associated systemic toxicity. Previous preclinical studies have demonstrated that IL-12 can have dramatic anti-tumor activity. However, in clinical investigations, systemic administration of IL-12 has been associated with a narrow therapeutic index with severe adverse events.
Findings from preclinical studies to be presented Monday, April 28, at AACR (Free AACR Whitepaper) 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. These results indicate its potential to benefit patients who are unresponsive or resistant to the current immuno-oncology therapies.
"At Zai Lab we are building a robust portfolio of potential first- and best-in-class oncology therapies to expand treatment options for patients around the world," said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. "Findings from our preclinical studies of ZL-6201 and ZL-1222 demonstrate our commitment to identifying innovative approaches that address limitations associated with first-generation therapies. These include the ability to deliver higher concentrations of cytotoxic agents and limit off-target toxicity, in order to deliver meaningful treatment options for patients with a range of cancer types."
Details regarding the Zai Lab poster presentations at AACR (Free AACR Whitepaper) 2025 are as follows:
Title: Discovery and characterization of a novel LRRC15-targeting antibody-drug conjugate (ADC) for the treatment of solid tumors
Presenter: Bing Wan, Ph.D., Executive Director, Biology, Zai Lab
Session Title: New and Emerging Cancer Drug Targets
Date/Time: Tuesday, April 29, 2025, from 9:00 a.m. – 12:00 p.m. CT
Location: McCormick Place Convention Center, Poster Section 17
Poster Board Number: 23
Published Abstract Number: 4266
Title: Cis-delivery of a potency-reduced IL-12 via an anti-PD-1 single-chain antibody exhibits potent anti-tumor activity
Presenter: Linda Liu, Ph.D., Senior Vice President, Biologics Discovery, Zai Lab
Session Title: Late-Breaking Research: Clinical Research 1
Date/Time: Monday, April 28, 2025, from 2:00 p.m. – 5:00 p.m. CT
Location: McCormick Place Convention Center, Poster Section 53
Poster Board Number: 1
Published Abstract Number: LB204