HuaYuan Securities: Focus on the opportunity of new substrates in the molecular degradation glue track, the increase lies in new target proteins and differentiated disease areas.

HuaYuan Securities released a research report stating that in the CRBN-IKZF1/3 hematological tumor molecular glue pathway, the market is currently mainly dominated by multinational pharmaceutical companies (BMS/Celgene); the competition in the domestic market depends on whether individual products can make breakthroughs and be clinically validated as the best in their class (BIC); true incremental value may lie in new target proteins (such as GSPT1, VAV1) and differentiated disease areas (autoimmune, solid tumors, etc). In the short term, it is recommended to focus on the share replacement of upgraded varieties of CRBN-IKZF1/3 and the potential realization of cash flows, while in the medium to long term, it is recommended to focus on the platform capabilities for discovering new target points and the differentiation of autoimmune/solid tumor indications; domestic focus should be on the clinical data readouts of HP-001 and the first-in-class opportunities in the VAV1 direction. Key points from HuaYuan Securities: Why molecular glue is needed TPD breakthrough "16% undruggable proteins" have great commercial potential, and molecular degradation glue is one of the pathways for this. Molecular degradation glue is one of the technical pathways in the TPD platform, using events that drive pharmacology by "making proteins disappear", to leverage a large pool of targets that were previously considered "undruggable", opening up space beyond traditional small molecules/antibodies. About 16% of human proteins are determined to be "undruggable", and currently only about 4% of proteins are truly utilized by traditional drugs, while molecular degradation glue, with "small molecules, no linker, orally friendly" features, may have higher drug-like and commercial efficiency within TPD. What is molecular glue + industry development Molecular degradation glue reduces the number of target proteins by degrading them to achieve disease suppression effects. The industry has shifted from "CRBN-IKZF1/3-hematological tumor IMiDs upgrade" to "new E3-new substrates-new indications (GSPT1, VAV1, HuR, NEK7, etc)", with Chinese companies currently mainly in the "fast-follow and me-better" stage in the CRBN-IKZF1/3 pathway, with true incremental value lying in platform capabilities and differentiated target pipelines. The industry believes that the CRBN-IKZF1/3 pathway has been largely dominated by multinational pharmaceutical companies in most areas, with China focusing more on the beta game; new potentials come from new E3, new substrates + differentiation in areas such as autoimmune/solid tumors, with rapid progress globally in GSPT1 (NSCLC, etc), VAV1 (autoimmune), NEK7/HuR (inflammation/solid tumors), and around 2026 Monte Rosa's three major pipelines and domestic HP-001 readouts may become key points for price reactions. Why focus on the molecular glue pathway now 2025-2027 will see key data readouts for new E3 platforms such as Monte Rosa and phase I/II data for domestic projects such as HP-001, ICP-490, VAV1 degradation glue. Currently, the main companies in the domestic CRBN-IKZF1/3 pathway are BeiXin Biotechnology/InnoCare Pharma/ChaoYang Pharmaceuticals/KangPeng Biology/GluBio Therapeutics, with preclinical data showing that the core product HP-001 of ChaoYang Pharmaceuticals as an oral CRBN molecular glue, in terms of CRBN binding affinity, IKZF1 degradation efficiency, substrate selectivity, and preclinical model efficacy, is significantly better than existing IMiDs and representative CELMoDs, with potential BIC features. Related target companies: US stocks: Monte Rosa; BMS; A-share targets: Chengdu Easton Biopharmaceuticals; InnoCare Pharma Risk factors: Risks of R&D progress falling short of expectations; risks of patent barriers; risks of intensified industry competition.