Investment Rating - The report maintains a positive outlook on the development of dual and triple antibodies in multiple myeloma (MM) and recommends monitoring the progress of TCE monotherapy and combination therapies in MM, including the EMD population [1][15]. Core Insights - The 67th ASH Annual Meeting highlighted significant advancements in hematology, particularly in the treatment of multiple myeloma, diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) [31]. - In multiple myeloma, the Tec-Dara combination therapy demonstrated a 36-month overall survival (OS) rate of 83.3%, significantly higher than the 65.0% in the control group, with a hazard ratio (HR) of 0.46 [32]. - The MSD ROR1 ADC showed promising first-line potential in DLBCL, with 24-month OS and progression-free survival (PFS) rates of 94% and 84%, respectively, outperforming existing treatments [33]. - Eli Lilly's Pirto showed improved PFS and OS trends compared to BR, but the executive admitted it may not become the first-line choice for CLL/SLL due to limited follow-up data and current treatment practices favoring covalent BTK inhibitors [34]. Summary by Sections 1. R/R MM: Focus on Dual/Triple Antibodies and TCE Therapies - Johnson & Johnson's BCMA/CD3+daratumumab therapy received FDA's "National Priority Voucher," reducing review time to 1-2 months, showing excellent efficacy in high-risk patients [7][15]. - IBI3003 from Innovent demonstrated an overall response rate (ORR) of 83.3% in high-risk patients, with a 100% minimal residual disease (MRD) negative rate in those achieving complete response (CR) [16]. - AstraZeneca's AZD0120 (BCMA/CD19 CAR-T) is projected to exceed $5 billion in sales, with a 100% ORR in treated patients [20][21]. 2. DLBCL: MSD ROR1 ADC Shows First-Line Potential - The MSD ROR1 ADC demonstrated a 24-month OS rate of 94% and a PFS rate of 84%, outperforming R-CHOP and Pola-CHP treatments [22][23]. - In high-risk populations, the ORR was 75% for patients with extramedullary disease (EMD), with a 100% ORR in the 1200 µg/kg dose group [23]. 3. CLL/SLL: Pirto May Not Become First-Line Choice - Pirto vs BR showed a 24-month PFS of 93.4% vs 70.7%, but the data is still immature, with a median follow-up of 28 months [25][27]. - The safety profile of Pirto indicated a 40% incidence of grade 3 or higher treatment-emergent adverse events (TEAEs), compared to 67.4% for BR [25][27].

Core Insights - The report highlights the promising potential of GPRC5D/BCMA/CD3 tri-antibody therapy for relapsed/refractory multiple myeloma (RRMM), showcasing an overall response rate (ORR) of 100% and a 12-month progression-free survival (PFS) rate of 96.3% [4]. Market Trends - The report notes that multiple myeloma (MM) is the second most common hematological malignancy, with over 300,000 new cases globally each year. Most MM cases progress to RRMM, indicating a significant unmet medical need after standard treatments fail [4]. Industry Commentary - GPRC5D and BCMA are highly expressed on the surface of malignant plasma cells, making them attractive targets for immunotherapy in MM. The JNJ-79635322 tri-antibody is the first to enter Phase III clinical trials for RRMM, targeting BCMA, GPRC5D, and CD3 to precisely modulate immune signaling [4]. - In early clinical trials, JNJ-79635322 demonstrated superior survival benefits, with a 12-month PFS rate of 96.3% in patients who had not previously received BCMA/GPRC5D therapy. The overall response rate (ORR) for the entire population was 73% [4]. - IBI3003, another candidate, showed an ORR of 83.3% in patients who had undergone at least four prior lines of treatment, indicating its efficacy in heavily pre-treated RRMM patients [4]. Clinical Data - JNJ-79635322 exhibited an ORR of 100% in a subgroup of patients who had not received prior BCMA/GPRC5D therapy, with a median follow-up of 15 months. Adverse events included infections (80.6%) and cytokine release syndrome (CRS) [4]. - IBI3003 demonstrated an ORR of 77.8% in patients previously treated with BCMA and/or GPRC5D therapies, with a good safety profile [4].

Core Insights - Innovent Biologics announced initial data from the first-in-human trial of IBI3003, a novel trispecific antibody targeting GPRC5D, BCMA, and CD3 for relapsed or refractory multiple myeloma, showing favorable tolerability and encouraging efficacy signals, especially in high-risk patients [1][10][11] Group 1: Study Design and Patient Demographics - IBI3003 is designed to target both GPRC5D and BCMA to overcome single antigen escape in multiple myeloma [2] - The Phase 1 study enrolled 39 patients with a median age of 62 years, where 64.1% were classified as high-risk and 46.2% had extramedullary disease [5] - Patients had a median of 4 prior lines of therapy, with 76.9% being refractory to their last treatment [5] Group 2: Treatment Administration and Safety Profile - IBI3003 was administered subcutaneously once weekly, with a switch to every two weeks for patients achieving a partial response after 6 months [4] - The safety profile was manageable, with 97.4% of patients experiencing treatment-emergent adverse events, primarily hematological disorders [8][10] - The incidence of cytokine release syndrome (CRS) was 64.1%, with all cases being Grade 1-2 and resolved with treatment [8] Group 3: Efficacy Results - Among patients treated with 120 g/kg, the overall response rate (ORR) was 83.3%, including stringent complete response in 4 cases and very good partial response in 7 cases [7][9] - The minimal residual disease negativity rate was 100% among patients achieving complete response or better [14] - Encouraging efficacy was particularly noted in high-risk patients, including those with extramedullary disease or prior anti-BCMA and/or anti-GPRC5D therapies [10][11] Group 4: Future Outlook - The company is conducting ongoing dose optimization for IBI3003 in the Phase 1 study, with expectations for deeper anti-tumor responses with continued treatment [10][12] - There is an urgent clinical need for effective treatments in patients with relapsed or refractory multiple myeloma, particularly those with high-risk features [11]

Investment Rating - The industry investment rating is "Outperform" [1] Core Viewpoints - The report emphasizes the potential of second-generation 4-1BB agonists, particularly dual-target antibodies, which have shown promising efficacy while addressing safety concerns associated with liver toxicity [4][24] - The report highlights significant recent industry events, including Merck's acquisition of Cidara for approximately $9.2 billion and Pfizer's acquisition of Metsera, indicating a trend of consolidation in the biopharmaceutical sector [6] - The report suggests a long-term positive outlook for China's innovative drug sector, driven by increasing data catalysts and new product sales, recommending specific companies for investment [6] Summary by Sections 4-1BB Overview - 4-1BB (CD137) is a key member of the tumor necrosis factor receptor superfamily, crucial for T cell activation and immune response enhancement [4][10] - The second-generation CAR-T cell technology utilizing 4-1BB has been validated for inducing prolonged activation and survival of CAR-T cells in vivo [4][12] First-Generation 4-1BB Agonists - First-generation 4-1BB agonists like urelumab and utomilumab faced limitations due to liver toxicity and insufficient efficacy [16][22] - Urelumab demonstrated significant hepatotoxicity at doses ≥1.0 mg/kg, leading to its discontinuation [21][22] Second-Generation 4-1BB Agonists - Second-generation 4-1BB agonists are primarily dual-specific antibodies targeting various pathways, with a focus on balancing efficacy and safety [24][26] - LBL-024, a promising candidate, has shown unprecedented efficacy and is expected to submit a BLA by Q3 2026 [4][6] Recent Industry Events - Merck's acquisition of Cidara for $9.2 billion and Pfizer's acquisition of Metsera highlight ongoing consolidation in the biopharmaceutical industry [6] - The report notes that the innovative drug sector is under pressure but is expected to rebound with a focus on companies with strong revenue capabilities [6] Investment Strategy - The report recommends focusing on companies with differentiated innovation pipelines and strong revenue capabilities, including specific biopharma and pharma leaders [6] - Suggested companies for investment include Innovent Biologics, BeiGene, and I-MAB, among others [6]

Group 1: IBI363 Development and Clinical Trials - IBI363 is positioned as a promising next-generation immuno-oncology (IO) therapy with Phase 3 trials underway, showing strong survival benefits and broad potential, especially for IO-resistant and cold tumors [1] - In squamous non-small cell lung cancer (sq-NSCLC), IBI363 (3mg/kg) achieved a median progression-free survival (mPFS) of 9.3 months, significantly outperforming docetaxel, which had mPFS of 3.9 months for sq- and 3.6 months for non-squamous NSCLC [1] - The 12-month overall survival (OS) rate for IBI363 reached 70.9% in sq-NSCLC and 71.6% in non-squamous NSCLC, surpassing the 65% OS rate reported for AK112 + docetaxel in IO-resistant NSCLC patients [1] Group 2: Future Trials and Market Potential - The pivotal Phase 2 trial in first-line melanoma is expected to complete enrollment by year-end, with Phase 3 trials set to begin in the second half of 2025, targeting IO-resistant sq-NSCLC and third-line MSS colorectal cancer [1] - Innovent anticipates releasing Phase 1b/2 proof-of-concept data for IBI363 in first-line NSCLC and MSS colorectal cancer in 2026, indicating broader market opportunities [1] - IBI363 also has potential for combination therapies with antibody-drug conjugates (ADCs) and out-licensing opportunities, enhancing its market positioning [1] Group 3: Innovent's Broader Pipeline - Innovent is developing a robust pipeline of next-generation IO agents and ADCs, including PD-1/IL-12, PD-L1/CD40, and multiple T-cell engagers (TCEs) targeting various cancer markers [1] - IBI3003, a TCE targeting GPRC5D/BCMA/CD3, has shown superior efficacy compared to existing therapies in preclinical models, indicating its potential to compete with CAR-T therapies [1] - Innovent is also advancing a diverse ADC pipeline, including monoclonal ADCs and bispecific ADCs, with promising signals observed in multiple tumor models [1] Group 4: Non-Oncology Innovations - Innovent launched mazdutide, China's first domestic dual-target GLP-1 drug for obesity, marking a significant milestone in its non-oncology portfolio [1] - Other non-oncology assets like IBI311 (for thyroid eye disease), IBI306 (for hypercholesterolemia), and IBI112 (for psoriasis) are expected to become important revenue drivers [1] - The company is advancing a strong early-stage cardiovascular medicine (CVM) pipeline and has several assets in clinical development for autoimmune diseases [1] Group 5: Financial Outlook - The company maintains a positive outlook on the global potential of its innovative pipelines and is on track to achieve EBITDA breakeven this year [2] - The successful development of IBI363 has led to an improved probability of success for the asset, prompting an increase in the discounted cash flow (DCF)-based target price to HK$102.95 from HK$94.74 [2]

Investment Rating - The report rates Innovent shares as "Buy" with a target price raised to HK$90 from HK$60, indicating an expected share price return of 16.4% [5][18]. Core Insights - Innovent is leading the development of next-generation immuno-oncology (IO) and antibody-drug conjugate (ADC) combinations, which are expected to provide broader-spectrum, highly-potent, and less-toxic cancer treatments [9][18]. - The key product IBI363 has shown promising data in various cancers, including non-small cell lung cancer (NSCLC) and mucosal/acral melanoma, positioning it as a cornerstone for next-generation IO therapy [2][10]. - Innovent aims to achieve Rmb20 billion in product revenue by 2027 and advance five pipeline assets into global multi-regional clinical trials by 2030 [1][3]. Financial Projections - Revenue forecasts for 2025, 2026, and 2027 have been fine-tuned by 1%, 2%, and 2% respectively, with expected earnings per share (EPS) of Rmb0.05, Rmb0.53, and Rmb1.22 [3]. - Innovent's revenue is projected to grow from Rmb9.4 billion in 2024 to Rmb16.6 billion by 2027, reflecting a compound annual growth rate (CAGR) of approximately 23.1% [4][8]. Clinical Development - IBI363 is currently undergoing registrational trials for various indications, including head-to-head trials against pembrolizumab for melanoma and NSCLC, with enrollment expected to complete by the end of 2025 [2][12]. - Innovent is also developing multiple ADC platforms, including SyntecanE, SoloTx, and DuetTx, which are designed to enhance efficacy and reduce toxicity in cancer treatments [11][12]. Market Position - Innovent has transformed from a biotech start-up to a leading biopharma company with 15 launched commercial products, showcasing strong R&D and commercialization capabilities [17][18]. - The company is positioned to leverage its dedicated R&D platform, Innovent Academy, which employs over 500 scientists focused on developing innovative cancer therapies [9][18].

Core Insights - Innovent is positioned as a leader in China's biopharmaceutical sector, particularly in oncology, with over 3 million cancer patients treated using its therapies [1] - The company is focusing on global innovation through a robust pipeline, aiming to advance at least five pipeline assets into MRCT Phase 3 trials by 2030 [1][5] - Innovent's strategy emphasizes dual innovation in next-generation immunotherapy (IO) and antibody-drug conjugates (ADC), targeting significant challenges in cancer treatment [2][3] R&D Strategy - Innovent's oncology pipeline includes nearly 10 next-generation molecules in global development, with multi-regional trials in the U.S., EU, and Asia [4] - The company is investing in R&D infrastructure, with hubs in Shanghai and San Francisco, and manufacturing capacity exceeding 140,000L [4] - Innovent Academy serves as the discovery engine, aiming to generate 6–8 novel molecules per year, focusing on next-gen IO and ADC [9] Pipeline Highlights - Key candidates include IBI363, a first-in-class PD-1/IL-2α-bias fusion protein, and IBI343, an innovative CLDN18.2 ADC, both showing significant survival benefits in clinical trials [5][6] - IBI363 has received two Breakthrough Therapy Designations from the NMPA CDE and two Fast Track Designations from the FDA, indicating its rapid advancement toward registrational development [7] - The pipeline also features IBI3001, IBI3003, and IBI3020, targeting various solid tumors with innovative mechanisms [6][13] Global Innovation and Market Position - Innovent is expanding its global footprint, with a vision to influence global oncology standards through its innovative therapies [10][11] - The company is recognized for its potential to lead in the next global oncology paradigm, driven by advancements in translational capabilities and patient-centric trial execution [11] - Innovent's commitment to high-quality, accessible cancer treatments positions it as a premier biopharmaceutical leader [15]