Core Viewpoint - The ATTC platform developed by Hutchison China MediTech Limited (HCM) aims to overcome the toxicity and resistance issues associated with traditional antibody-drug conjugates (ADCs), with potential for combination therapy with chemotherapy as a first-line standard treatment [1][6]. Summary by Sections ATTC Platform - The ATTC platform is designed to link targeted therapeutic agents with antibodies, producing candidate drugs that can target specific driver mutations, potentially reducing chemotherapy toxicity and enabling combination therapy with standard treatments [1][6]. HMPL-A251 - HMPL-A251 is the first candidate drug from the ATTC platform to enter clinical stages, composed of a PI3K/PIKK inhibitor and a HER2 antibody. It is expected to enter Phase 1 clinical trials in Q4 2025 [1][2][6]. - Preclinical data shows that HMPL-A251 exhibits effective endocytosis in HER2-positive cells and demonstrates HER2 expression-dependent cell growth inhibition, overcoming HER2 heterogeneity through a bystander killing effect [2]. PAM Pathway - The PAM (PI3K-AKT-mTOR) pathway plays a crucial role in cell growth, proliferation, differentiation, and apoptosis, with alterations in this pathway closely linked to various human tumors. Overactivation of PI3K is frequently reported in multiple cancer types [3]. - Existing PAM-targeted therapies have limited clinical benefits due to toxicity associated with PI3K/mTOR inhibition, which restricts the safety window for targeted treatments [3]. Future Pipeline - HCM anticipates two additional ATTC candidates (HMPL-A580 and HMPL-A830) to enter global clinical stages in 2026 [3]. - Clinical data for the first-line treatment of PDAC with surufatinib will be presented at the ESMO Asia conference, and the SAFFRON study of savolitinib combined with osimertinib has completed patient enrollment [1][6]. Investment Recommendation - The new generation ATTC platform from HCM is worth attention, with a smoothly advancing pipeline, maintaining an "outperform" rating [1][6].

Summary of Celcuity (CELC) Investor Call - July 28, 2025 Company Overview - **Company**: Celcuity (CELC) - **Focus**: Development of geditalisib for HR positive, HER2 negative advanced breast cancer Key Industry Insights - **Clinical Trial**: Phase III VICTORIA-one trial results presented - **Target Population**: Patients with HR positive, HER2 negative advanced breast cancer, specifically those with PIK3CA wild type tumors Core Findings and Results - **Progression-Free Survival (PFS)**: - **Triplet Regimen (geditalisib + fulvestrant + palbociclib)**: Median PFS of 9.3 months vs. 2 months for fulvestrant alone, with a hazard ratio of 0.24, indicating a 4.2 times higher likelihood of survival without disease progression [10][25] - **Doublet Regimen (geditalisib + fulvestrant)**: Median PFS of 7.4 months vs. 2 months for fulvestrant alone, with a hazard ratio of 0.33, indicating a 3 times higher likelihood of survival without disease progression [11][26] - **Significance**: These results are unprecedented in the treatment of this patient population, establishing new milestones in drug development [11][12] Mechanism of Action - **PAM Pathway**: Geditalisib targets the PAM pathway, which is crucial in cancer progression. The drug provides comprehensive blockade of the pathway, reducing the potential for adaptive resistance [8][19] - **Efficacy Across Mutation Status**: Preliminary data shows objective response rates over 50% in patients with or without PIK3CA mutations [20] Safety and Tolerability - **Adverse Events**: Both triplet and doublet regimens were well tolerated, with lower discontinuation rates due to treatment-related adverse events compared to previous studies [28][44] - **Overall Survival Trends**: Positive trends observed, although data is still immature due to crossover from the control arm [29][60] Market Opportunity - **Patient Population**: Estimated 34,000 patients transitioning to second-line treatment after CDK4/6 inhibitors, with approximately 60% being PIK3CA wild type [46] - **Market Size**: Projected market opportunity of $5 billion for geditalisib [46] - **Reimbursement Dynamics**: IV administered drugs like geditalisib typically face smoother reimbursement processes compared to oral drugs [46] Future Plans - **NDA Submission**: Anticipated submission for geditalisib in Q4 2025 [52] - **Upcoming Data Presentations**: Full results from the VICTORIA-one trial to be presented at major medical conferences [30][52] - **Continued Research**: Ongoing studies to explore the efficacy of geditalisib in combination with other therapies, including oral SERDs [74] Conclusion - **Strategic Positioning**: Celcuity is well-positioned to address significant unmet needs in the treatment of HR positive, HER2 negative advanced breast cancer, with geditalisib showing promising clinical results and a strong market opportunity ahead [48][49]