Core Viewpoint - Roche's Lunsumio VELO™ (mosunetuzumab) has received FDA approval as a subcutaneous treatment for adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy, based on the phase I/II GO29781 study results [1][3][4] Group 1: FDA Approval and Treatment Benefits - The FDA approval is based on the results from the GO29781 study, which demonstrated an objective response rate of 75% and a complete response rate of 59% in patients treated with Lunsumio VELO [3][7] - Lunsumio VELO significantly reduces treatment administration time to approximately one minute, compared to the previous 2-4 hour intravenous infusion, thus aligning treatment with patient needs [2][7] - The treatment can be administered in outpatient settings and is designed for a fixed duration, potentially as short as six months, contrasting with indefinite treatment options [2][3] Group 2: Clinical Study Insights - The GO29781 study evaluated the safety, efficacy, and pharmacokinetics of mosunetuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, establishing efficacy based on objective response rate and duration of response [6] - The median duration of response for Lunsumio VELO was reported as 22.4 months [3] - The most common adverse reactions (≥20%) included injection site reactions, fatigue, rash, and cytokine release syndrome (CRS), with a CRS rate of 30% primarily occurring during Cycle 1 [3][4] Group 3: Ongoing Research and Development - Roche is advancing its bispecific antibody program in lymphoma, with ongoing phase III studies evaluating Lunsumio and Lunsumio VELO in earlier lines of treatment [5] - The SUNMO study is investigating Lunsumio VELO in combination with Polivy® for second-line or later large B-cell lymphoma, while the MorningLyte study is exploring its use with lenalidomide in previously untreated follicular lymphoma [5] Group 4: Follicular Lymphoma Overview - Follicular lymphoma (FL) is the most common slow-growing form of non-Hodgkin lymphoma, accounting for about 20% of cases, and is characterized by periods of remission and relapse [8] - More than 110,000 people are diagnosed with FL each year worldwide, and the disease typically becomes harder to treat with each relapse [8]

Core Insights - NovaBridge Biosciences announced new data from the expanded Phase 1 dosing study for ragistomig, a bispecific antibody targeting 4-1BB and PD-L1, to be presented at ESMO-IO 2025 [1][2] - The study successfully extended the therapeutic window for ragistomig, demonstrating strong anti-tumor efficacy and improved tolerability, including enhanced hepatic safety [2][3] - Ragistomig aims to provide new treatment options for patients resistant to checkpoint inhibitors, a significant drug class in cancer therapy [3][5] Company Overview - NovaBridge is a global biotechnology platform focused on accelerating access to innovative medicines, combining business development expertise with clinical development [8] - The company is developing a differentiated pipeline, including ragistomig and givastomig, targeting various cancers and conditions [8][9] - Ragistomig is being developed in collaboration with ABL Bio, utilizing advanced bispecific antibody technology to minimize off-tumor toxicity [5][6] Clinical Study Details - The Phase 1 study of ragistomig is ongoing in the U.S. and South Korea, with a primary focus on defining dose-limiting toxicity and adverse event profiles [5][6] - The new dosing schedule, Q6W, has shown promising results in PD-L1 non-responders, balancing safety and sustained efficacy [6][7] - Interim results, including immunological data, are expected to be presented at the upcoming ESMO-IO meeting [6][7]

Core Viewpoint - Roche has received conditional marketing authorization from the European Commission for Lunsumio® (mosunetuzumab) subcutaneous (SC) for treating adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy, based on the phase I/II GO29781 study results [1][3]. Group 1: Product Details - Lunsumio SC can be administered via a one-minute subcutaneous injection, significantly reducing treatment administration time compared to the 2-4 hour intravenous (IV) infusion [2]. - The treatment is designed to provide flexibility and improve the patient experience, aligning with individual clinical requirements and lifestyle preferences [2][8]. - The drug has shown a favorable benefit-risk profile with high rates of deep and durable remissions in patients with third-line or later FL [3][8]. Group 2: Clinical Study Insights - The GO29781 study demonstrated pharmacokinetic non-inferiority of Lunsumio SC compared to IV administration, with an overall response rate (ORR) of 74.5% and a complete response (CR) rate of 58.5% in patients treated with the SC formulation [7]. - The median duration of CR for patients receiving Lunsumio SC was 20.8 months [7]. - Common adverse events included injection-site reactions (60.6%), fatigue (35.1%), and cytokine release syndrome (CRS) [9]. Group 3: Ongoing Research and Development - Phase III studies involving Lunsumio SC are ongoing, including the MorningLyte trial, which investigates its use in combination with lenalidomide in previously untreated FL [5]. - Roche continues to explore new formulations and combinations of Lunsumio and other bispecific antibodies to enhance treatment options for patients [5]. Group 4: Market Context - Follicular lymphoma is the most common slow-growing form of non-Hodgkin lymphoma, with over 110,000 new cases diagnosed annually worldwide [10]. - The disease typically becomes harder to treat with each relapse, highlighting the need for effective treatment options like Lunsumio [10].

Summary of Compass Therapeutics FY Conference Call Company Overview - **Company**: Compass Therapeutics (NasdaqCM:CMPX) - **Location**: Boston - **Focus**: Monoclonal antibody discovery and development in oncology - **Pipeline**: Three drugs currently in clinical trials, including a DLL4 VEGFA bispecific antibody for advanced biliary tract cancer [2][3] Key Points on Clinical Programs Tuvesimig and Biliary Tract Cancer (BTC) - **Market Opportunity**: Approximately 25,000 new BTC cases diagnosed annually in the U.S. Only 15%-20% of patients have actionable mutations for targeted therapy. The remaining 80%-85% lack approved second-line therapies, presenting a significant commercial opportunity exceeding $1 billion annually in the U.S. [4][5] - **COMPANION-002 Study**: - Focuses on Tuvesimig (DLL4 VEGFA bispecific) combined with paclitaxel versus paclitaxel alone in second-line BTC patients. - Achieved a statistically significant increase in overall response rate (p-value of 0.031) and a notable reduction in progressive disease rates at week eight (42.1% in control vs. 16.2% in combination arm) [6][7]. - Safety data monitored by a data safety monitoring committee showed no new safety signals [8]. - Future readouts for progression-free survival (PFS) and overall survival (OS) expected in late Q1 2026 [9][10]. Regulatory Considerations - The FDA required paclitaxel as the control arm for the study, despite FOLFOX being in NCCN guidelines [14]. - Historical precedent from the Tibsovo study suggests that positive PFS results could support regulatory filings even without significant OS improvements [10][11]. Other Pipeline Developments PD-1, PD-L1 Bispecific Antibody (8371) - **Mechanism**: Acts as a next-generation checkpoint inhibitor, converting PD-1 positive T cells to PD-1 negative T cells, enhancing T cell engagement [17][18]. - **Phase One Data**: No dose-limiting toxicities observed across 15 patients, with three responses noted in post-checkpoint inhibitor patients [19][20]. - **Cohort Expansion**: Plans to expand cohorts in triple negative breast cancer and non-small cell lung cancer [21]. CD137 Agonist (471) - **Phase One Study**: Enrolled 60 patients across 17 tumor types, with five responses observed. A complete response was noted in a small cell lung cancer patient [25][26]. - **Future Plans**: An NCAM-positive basket study is set to begin in Q1 2026, with multiple clinical readouts anticipated in 2026 [26]. Financial and Operational Outlook - Compass Therapeutics is funded through 2028 to support ongoing clinical programs and development efforts [26]. Conclusion - Compass Therapeutics is positioned to capitalize on significant market opportunities in oncology, particularly in biliary tract cancer, with promising clinical data supporting its lead programs. The company is actively preparing for future regulatory submissions and expanding its clinical pipeline.

XmAb819 Clinical Trial - Key Findings - The Phase 1 dose-escalation study of XmAb819 in ccRCC showed a manageable safety profile, with most CRS events being Grade 1/2 and occurring during priming [47, 51, 136] - Correct dose preparation resulted in 4% Grade 3 CRS (2/51), while dose preparation errors led to 28% Grade 3 CRS (5/18) [40, 136] - In the target dose range, correct dose preparation resulted in 6% Grade 3 CRS (1/18), while dose preparation errors led to 50% Grade 3 CRS (3/6) [40, 136] - XmAb819 demonstrated an objective response rate (ORR) of 25% (95% CI: 9-49) and a disease control rate (DCR) of 70% (95% CI: 46-88) in the efficacy-evaluable target dose range (N=20) [55, 89, 125] - The median number of prior regimens for patients in the XmAb819 study was 4 (range: 1-8), with 70% having received ≥3 prior regimens [35, 89, 119] XmAb819 Development & Market Opportunity - Xencor is planning to start a pivotal study of XmAb819 as monotherapy in advanced ccRCC in 2027 [79, 104] - The global RCC market is expected to reach approximately $12 billion by 2030 [80] - In the U S, there are approximately 60,000 new cases of ccRCC per year [84] XmAb541 Early Results - Early data from the Phase 1 dose escalation study of XmAb541 showed promising anti-tumor activity in advanced ovarian cancer, endometrial cancer, and germ cell tumors [4, 93, 97] - The total sales in 1H25 for ovarian cancer drugs were $338 million, and for endometrial cancer drugs were $196 million [100]

Core Insights - The Phase III HARMONi trial data for ivonescimab plus chemotherapy shows an improving overall survival (OS) trend with a nominal p-value of 0.0332 compared to chemotherapy alone, particularly in North American patients with an OS hazard ratio (HR) of 0.70 [1][4][6] Group 1: Trial Overview - HARMONi trial evaluated ivonescimab plus platinum-doublet chemotherapy against placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who progressed after third-generation EGFR TKI treatment [2][18] - The trial's primary endpoints were progression-free survival (PFS) and overall survival (OS), with previous PD-1 monoclonal antibodies failing to show benefits in similar settings [2] Group 2: Efficacy Results - In the primary analysis, ivonescimab plus chemotherapy showed a median OS of 16.8 months versus 14.0 months for placebo plus chemotherapy, with a hazard ratio of 0.79 (95% CI: 0.62 – 1.01; p=0.057) [4][6] - Longer-term follow-up analysis indicated a median OS of 17.0 months for ivonescimab compared to 14.0 months for placebo in Western patients, with an improved hazard ratio of 0.84 [6][7] - The overall response rate was higher in the ivonescimab arm at 45% compared to 34% in the placebo arm, with a median duration of response of 7.6 months versus 4.2 months [10] Group 3: Safety Profile - Ivonescimab plus chemotherapy demonstrated a manageable safety profile, with 7.3% of patients discontinuing due to treatment-related adverse events (TRAEs) compared to 5.0% in the placebo group [12][13] - The most common TRAEs included anemia and decreases in white blood cell counts, with less than 1% experiencing Grade 3 or higher hemorrhage events [12][13] Group 4: Future Developments - Summit Therapeutics plans to host a conference call on September 8, 2025, to discuss the ivonescimab data presented at the WCLC 2025 [14][30] - The company is engaged in multiple Phase III clinical trials for ivonescimab, including HARMONi-2 and HARMONi-6, which are expected to further evaluate its efficacy [19][20]

Core Insights - RemeGen Co., Ltd. has received clearance from the FDA for its IND application for phase II clinical trials of its bispecific antibody RC148 in the US [1][2] - RC148 targets PD-1 and VEGF and is developed using RemeGen's bispecific antibody technology platform [2] - The FDA clearance is a significant milestone that is expected to expedite the global development process of RC148 [2] Company Developments - RemeGen is currently conducting clinical trials of RC148 as both a monotherapy and in combination therapy for advanced solid tumors in China [2] - The successful IND application clearance marks an important step in RemeGen's strategy to expand its presence in the global oncology market [1][2]

Core Viewpoint - The FDA has granted accelerated approval for Lynozyfic™ (linvoseltamab-gcpt) to treat adult patients with relapsed or refractory multiple myeloma who have undergone at least four prior lines of therapy, marking a significant advancement in treatment options for this patient population [1][5][6]. Group 1: FDA Approval and Clinical Trial Results - Lynozyfic is the first FDA-approved BCMAxCD3 bispecific antibody, allowing for a flexible dosing schedule that can adapt based on patient response [2][3]. - The approval is based on the LINKER-MM1 trial, where 70% of patients achieved an overall response rate, with 45% achieving a complete response or better [6][5]. - The median time to first response was 0.95 months, and the median duration of response was not reached, with an estimated 89% of responders maintaining their response at 9 months [6][12]. Group 2: Safety and Administration - Lynozyfic has a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity, with common adverse reactions including musculoskeletal pain, cough, and fatigue [4][18]. - The treatment involves a step-up dosing regimen, requiring hospitalization for safety during the initial doses [10][20]. - Lynozyfic is available only through a restricted program called the Lynozyfic Risk Evaluation and Mitigation Strategy (REMS) due to the associated risks [4][22]. Group 3: Company Commitment and Future Development - Regeneron is committed to advancing the treatment landscape for multiple myeloma and has launched Lynozyfic Surround™, providing financial and educational resources for patients [5][6]. - The company is rapidly advancing its clinical development program for Lynozyfic, exploring its use in earlier lines of therapy and in combination with other treatments [5][13]. - Regeneron utilizes its proprietary VelocImmune technology to develop Lynozyfic, showcasing its expertise in creating fully human antibodies [9][17].

Core Insights - Roche announced positive phase I/II data for NXT007, a next-generation bispecific antibody for haemophilia A, supporting its progression to phase III clinical development [1][2] - NXT007 demonstrated a tolerable safety profile with no thromboembolic events reported, indicating its potential for haemostatic normalization in patients without factor VIII inhibitors [1][4] Company Overview - Roche has over 25 years of experience in developing medicines for blood diseases and is committed to advancing care for patients with haemophilia A [9] - The company aims to provide innovative treatment options, including NXT007, to enhance therapeutic choices and reduce treatment burdens for patients [2][6] Clinical Development - NXT007 is currently undergoing a robust clinical development program, with ongoing phase I/II trials and additional phase II data expected later this year [3] - Three phase III studies are planned for 2026, including a head-to-head study with Hemlibra, Roche's existing prophylactic treatment for haemophilia A [3][4] Product Details - NXT007 is engineered to optimize factor VIII-mimetic activity and enhance potency, efficacy, and administration convenience, aiming for sustained elevated bleed protection [6][5] - The clinical trials for NXT007 involve participants aged 12 to 65, with no treated bleeds observed in the highest dose cohorts [4][7] Market Context - Haemophilia A affects approximately 900,000 people globally, leading to significant health concerns due to uncontrolled bleeding [8][7] - The development of inhibitors to factor VIII replacement therapies presents a serious complication, highlighting the need for innovative treatments like NXT007 [8]

Investment Rating - The report assigns an "Overweight" (OW) rating to Akeso with a price target of HK$99.00 by December 2025 [2][5]. Core Insights - Akeso's AK104, a PD-1/CTLA-4 bispecific antibody, has received approval in China for first-line treatment of persistent, recurrent, or metastatic cervical cancer, which is expected to significantly boost sales in China [1][4]. - The report anticipates a global development plan for AK104 to be announced in the second half of 2025, which could attract investor interest [1][4]. - Upcoming catalysts include sales figures for AK104 and AK112, the potential global development plan announcement, and detailed data from the HARMONi studies [4][5]. Summary by Sections Approval and Efficacy - AK104's approval is based on strong results from the Phase 3 COMPASSION-16 study, showing a median overall survival (mOS) not reached in the AK104+chemo cohort compared to 22.8 months in the control group, and a median progression-free survival (mPFS) of 12.7 months versus 8.1 months [4]. Market Potential - The report estimates that AK104 could generate approximately RMB 6 billion in peak sales in China, while AK112 is expected to achieve over RMB 5 billion in peak sales in non-small cell lung cancer (NSCLC) [5]. Valuation - The price target of HK$99.00 is based on a discounted cash flow (DCF) valuation, assuming a terminal growth rate of 3.0% and a weighted average cost of capital (WACC) of 9.4% [6].