Glenmark Specialty S.A. / Jiangsu Hengrui Pharmaceuticals Co. Ltd.

HER2-positive/mutated solid tumors (NSCLC, breast cancer)

55K US cases/yr · $15.0B Global HER2-targeted therapy market 2024 · 5-8K US HER2-mutated NSCLC annual incidence

Disease Overview

HER2 (ERBB2) alterations drive tumorigenesis across multiple solid malignancies. HER2 overexpression occurs in approximately 15-20% of breast cancers and 15-20% of gastric/GEJ adenocarcinomas, while HER2 activating mutations (most commonly exon 20 insertions like Y772_A775dup) occur in 2-4% of non-small cell lung cancers (NSCLC), a previously underserved molecular subset. Additional HER2-altered tumors include colorectal (3-5% amplified), bladder, biliary tract, and endometrial cancers. In the US, HER2-positive breast cancer accounts for roughly 40,000 new cases annually, HER2-mutated NSCLC for approximately 5,000-8,000 cases, and HER2-positive gastric cancer for 5,000-7,000. The therapeutic landscape transformed with trastuzumab (Herceptin), pertuzumab (Perjeta), and T-DM1 (Kadcyla), and has been further redefined by trastuzumab deruxtecan (Enhertu), which demonstrated efficacy in HER2-low breast cancer and HER2-mutated NSCLC. Despite this, resistance mechanisms, CNS progression, and ADC-related ILD toxicity drive continued unmet need. Trastuzumab rezetecan (SHR-A1811), a HER2-directed ADC with a novel topoisomerase-I inhibitor payload, received NMPA approval in China in May 2025 for HER2-mutated NSCLC — the first China-developed ADC to achieve this indication.

Competitive Landscape

Competitive intensity in HER2 solid tumors is extreme. Foundational agents include trastuzumab (Herceptin, Roche/Genentech — biosimilars from Amgen, Pfizer, Mylan, Celltrion, and Samsung Bioepis), pertuzumab (Perjeta, Roche), lapatinib (Tykerb, Novartis), neratinib (Nerlynx, Puma Biotechnology), and tucatinib (Tukysa, Pfizer/Seagen). ADCs dominate the next-generation landscape: Kadcyla (T-DM1, trastuzumab emtansine, Roche), Enhertu (trastuzumab deruxtecan, Daiichi Sankyo/AstraZeneca) — the category-defining ADC with blockbuster status in HER2-low breast cancer and HER2-mutated NSCLC — and disitamab vedotin (Aidixi, RemeGen; licensed to Pfizer/Seagen in 2021 for ex-Asia rights). In HER2-mutated NSCLC specifically, Enhertu received FDA accelerated approval in 2022 and remains the reference standard. Trastuzumab rezetecan (SHR-A1811) enters a market anchored by Enhertu but differentiates on a potentially improved therapeutic index and lower ILD (interstitial lung disease) rates per Hengrui's pivotal Chinese registrational data. Glenmark's deal secures ex-China rights in emerging markets spanning India, Latin America, Southeast Asia, CIS, MENA, Africa, Australia, and New Zealand. Other HER2 ADCs in development include ARX788 (Ambrx/NovoCodex — acquired by J&J in 2024), MRG002 (Miracogen), and SYD985 trastuzumab duocarmazine (Byondis), plus HER2 bispecifics such as zanidatamab (Jazz/BeiGene) and KN026 (Alphamab Oncology), creating a layered competitive field.