Summary of Cullinan Therapeutics 2026 Conference Call Company Overview - **Company**: Cullinan Therapeutics (NasdaqGS: CGEM) - **Focus**: Development of T cell engager programs for autoimmune diseases and oncology Key Priorities and Portfolio - **2026 Significance**: First year with catalysts across the entire portfolio, particularly for two high-priority T cell engager programs: - **CLN-978**: CD19 x CD3 bispecific T cell engager for autoimmune diseases - **CLN-049**: FLT3 x CD3 T cell engager for acute myeloid leukemia (AML) [5][6] CLN-978 Program - **Potential**: Considered a best-in-class molecule for autoimmune diseases with a global development program targeting lupus, rheumatoid arthritis (RA), and Sjögren's disease [6] - **Differentiation**: High binding affinity for CD19, small molecular size for better tissue penetration, and subcutaneous administration convenience [6] - **Data Readouts**: Planned throughout 2026 for all three indications [6] - **Market Interest**: B cell depletion remains a hot area, with strategic acquisitions in the sector, indicating strong market interest [7] CLN-049 Program - **Potential**: First-in-class potential for a broad group of AML patients, with compelling monotherapy efficacy data presented at ASH [8] - **Regulatory Designation**: Received Fast Track designation from the FDA, facilitating a pivotal single-arm study for potential approval [8] - **Commercial Opportunity**: Aiming for significant commercial potential in the AML market, with plans for a combination study later in the year [8][34] Financial Position - **Cash Reserves**: Over $430 million reported at the end of 2025, providing a runway into 2029 to advance programs without immediate capital raising needs [9] Clinical Development Updates - **Enrollment Progress**: Completed first two dose cohorts for CLN-978 and currently accruing into the 30 microgram dose level for lupus and RA studies [11] - **Efficacy Expectations**: Anticipating a dose-response effect for B cell depletion in upcoming data releases [14][15] Competitive Landscape - **Market Position**: The company aims to be the first to present company-sponsored data for a CD19 T-cell engager, enhancing competitive positioning [19] - **Strategic Acquisitions**: Acquired a BCMA TCE to expand the reach in autoimmune diseases, allowing for a broader patient base [27][28] Future Plans - **Pivotal Studies**: Plans to initiate a phase 2 single-arm study for CLN-049 in 2027, targeting relapsed refractory AML patients [40] - **Combination Studies**: Intent to begin a phase 1b/2 combination study with AZA in previously untreated AML patients [37] Zipalertinib Program - **NDA Submission**: Completion of the relapsed study marks a significant milestone, with Taiho leading further development [41] - **Financial Impact**: Potential for $130 million in regulatory milestones and a 50/50 profit share in the U.S. [42] Conclusion - **Outlook for 2026**: A defining year for Cullinan Therapeutics with multiple catalysts and significant potential in both autoimmune diseases and oncology, supported by a strong financial position and strategic development plans [9][43]

Core Insights - IN8bio has promoted Kate Rochlin, Ph.D., to President and Chief Operating Officer, effective immediately, to enhance leadership during a critical growth phase [1][2] Company Overview - IN8bio is a clinical-stage biopharmaceutical company focused on developing innovative gamma-delta (γδ) T cell therapies and T cell engagers for cancer and autoimmune diseases [1][6] - The company's lead program, INB-100, targets acute myeloid leukemia, while other programs include INB-200 and INB-400 for glioblastoma, and INB-600 for oncology and autoimmune indications [6] Leadership and Experience - Dr. Rochlin has over 17 years of experience in biotechnology, including roles in scientific research, intellectual property, business development, and clinical manufacturing [3] - Prior to her role at IN8bio, she served as Chief Business Officer at Curadigm, contributing to the company's spin-out from Nanobiotix [3] Clinical Advancements - Under Dr. Rochlin's leadership, IN8bio has advanced its clinical programs, including the development of INB-619, which has shown promising preclinical results in achieving complete B cell depletion with minimal adverse effects [4] - The company has made significant progress in its clinical manufacturing program, supporting multiple Phase 1 and 2 clinical trials in glioblastoma and hematological cancers [4] Future Outlook - Dr. Rochlin expressed confidence in the company's position to build on momentum from encouraging clinical data and aims to execute corporate priorities for long-term success [5]

Summary of Molecular Partners FY Conference Call Company Overview - **Company Name**: Molecular Partners (NasdaqGS:MOLN) - **Focus**: Development of DARPin candidates, particularly in the field of radiotherapy - **Financial Position**: Over $100 million in cash (approximately CHF 93 million) available for investment in R&D [4][30] Key Industry Insights - **Biotech Sector Outlook**: Increased confidence in a turnaround for the biotech sector in 2026, following a challenging period [3] - **Radiotherapy Market**: Positive feedback and renewed interest in radiotherapy, highlighted by the successful IPO of Aktis Oncology [3] Core Product Focus - **Primary Candidate**: MP0712, a DLL3-targeted DARPin, is expected to drive value creation in the upcoming year [4][6] - **Pipeline Overview**: Emphasis on MP0712, with additional focus on MPO 317 and MPO 533, which are also in development [6][11] Product Development and Clinical Trials - **MPO 317**: Initially considered a dead program, it has been revived due to promising phase one data showing immune activation in colorectal carcinoma. A new trial will involve 75 patients across 11 centers in France, with results expected in 2027 [10][11] - **MPO 533**: A multispecific DARPin targeting acute myeloid leukemia (AML), designed to eradicate residual disease clones. The focus will be on low disease burden patients [11][12] Radiotherapy Mechanism - **Mechanism of Action**: MP0712 utilizes a DARPin vector linked to a radioisotope (Lead-212) to target DLL3 in small cell lung cancer. The approach aims to combine the efficacy of T cell engagers with the durability of antibody-drug conjugates (ADCs) [14][16][18] - **Clinical Strategy**: The company plans to initiate a phase one dose escalation trial, starting with a 75-megabecquerel dose, with a fast-to-market strategy for small cell lung cancer [27][30] Safety and Efficacy Considerations - **Safety Profile**: The rapid decay of Lead-212 is expected to result in minimal hematological toxicity, with recovery of blood values anticipated [34][37] - **Patient Experience**: Radiotherapy is expected to offer a better quality of life for patients compared to T cell engagers, which often cause acute side effects [37] Partnerships and Collaborations - **Orano Med Partnership**: A 50/50 partnership focused on the supply of Lead-212, with Orano Med providing a robust supply chain and infrastructure for the isotope [40][43] - **Future Collaborations**: The company is open to exploring partnerships for other isotopes, such as actinium, to enhance treatment options [45][46] Future Directions - **Expansion of Indications**: Beyond small cell lung cancer, there are plans to explore other neuroendocrine tumors with DLL3 expression [47][48] - **Innovative Imaging Techniques**: The use of imaging agents to select patients with DLL3 expression is seen as pivotal for maximizing treatment efficacy [48] Conclusion - **Focus for 2026**: The primary focus will be on MP0712, with expectations for first-in-human results and safety data in the first half of the year, followed by activity data in the second half [30]

Core Insights - CLN-049 monotherapy shows promising efficacy in patients with relapsed/refractory acute myeloid leukemia (R/R AML), achieving a 31% complete response (CR) rate at the highest tested dose of 12 µg/kg [1][5][12] - The drug has received Fast Track designation from the U.S. FDA, indicating its potential to address unmet medical needs in AML treatment [1][12] - An in-person event will be held by the company to discuss the clinical data presented at the 67th American Society of Hematology Annual Meeting [1][8] Efficacy Results - As of August 2025, 45 patients were enrolled in the Phase 1 study, with 41 patients being evaluable for efficacy [3] - The CR/CRh rate at the highest dose of 12 µg/kg was 31%, with anti-leukemic activity observed at doses ≥6 µg/kg [5][6] - Among patients achieving a CR/CRh response at doses ≥6 µg/kg, 63% had a duration of response exceeding 16 weeks [4][6] Safety Profile - The safety profile of CLN-049 is favorable, with the most common treatment-emergent adverse events being cytokine release syndrome (35.6%) and infusion-related reactions (33.3%) [13] - Most adverse events were Grade 1 or 2, with no Grade 3 cytokine release syndrome observed [13] Target Population - CLN-049 targets FLT3-expressing leukemia cells, applicable to both mutated and non-mutated forms, making it relevant for a broad population of AML patients [10][13] - The drug shows particular promise for patients with TP53-mutated AML, with a 50% CR/CRh response rate observed in this subgroup at the highest dose [13] Future Development - The development of CLN-049 will continue under FDA Fast Track designation, with ongoing dose escalation and planned expansion cohorts in early 2026 [7][12]

Core Insights - CLN-049 has shown promising anti-leukemic activity in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), achieving a composite complete response (CRc) rate of approximately 30% at clinically active doses [1][11] - The drug demonstrated a manageable safety profile across all assessed doses, with the most common treatment-emergent adverse events being cytokine release syndrome (40%) and infusion-related reactions (35%) [12][7] - Cullinan Therapeutics plans to present updated clinical data at the 67th American Society of Hematology (ASH) Annual Meeting on December 8, 2025 [1][3] Company Overview - Cullinan Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing first- or best-in-class therapies for autoimmune diseases and cancer [15] - The company is advancing its pipeline with a focus on T cell engagers, which are established in oncology and are now being explored for autoimmune diseases [15] Clinical Study Details - The Phase 1 study of CLN-049 enrolled 40 patients (34 with AML and 6 with MDS) and assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy [10][4] - The study included patients who had received a median of 2 prior therapies, indicating a heavily pretreated population [4] Efficacy Results - At the highest target dose of 12 μg/kg, the CRc rate was 31% and the overall response rate (ORR) was 69% [11] - Responses were observed in patients with AML regardless of baseline genetic risk, including those with TP53 mutations, where 4 out of 5 patients showed responses [11][2] Safety Profile - The safety profile of CLN-049 was deemed manageable, with no treatment discontinuations due to adverse events [12][7] - Grade ≥3 treatment-emergent adverse events included febrile neutropenia and white blood cell count decrease, each occurring in 17.5% of patients [12]

Core Insights - Taiping Medical Health Fund has completed an investment in Hainan Xiansheng Zaiming Pharmaceutical Co., Ltd., a subsidiary of Xiansheng Pharmaceutical Group, which is a leading domestic pharmaceutical company focused on innovative anti-tumor drugs [1] - The investment aims to enhance Xiansheng Zaiming's innovative capabilities and support its participation in international competition and collaboration in tumor immunotherapy [1] - Xiansheng Zaiming has developed several advanced research and development platforms, including protein engineering, T cell engagers, NK cell engagers, ADCs, PROTACs, and AI-assisted molecular design [1] Company Developments - Xiansheng Zaiming has achieved compliance with GMP standards in both China and the United States for its independent production capabilities [1] - The company has four core innovative drugs, namely Kexaila®, Envida®, Endu®, and Enlitai®, which are already commercialized and cover various solid tumor treatments [1] - Kexaila® and Enlitai® are expected to enter the national medical insurance catalog in 2024, following Endu® [1] Strategic Partnerships - Following the investment, Xiansheng Zaiming announced a strategic partnership with Next Cure, Inc. to co-develop a new ADC drug, SIM0505, targeting the CDH6 antigen for solid tumor treatment [3] - The potential development phase of SIM0505 could yield up to $745 million in related payments, including upfront, development, and sales milestone payments, along with tiered royalties based on net sales outside Greater China [3] - Previously, Xiansheng Zaiming entered a licensing option agreement with AbbVie for SIM0500, a tri-specific antibody, with a total value of up to $1.055 billion [6]

Acquisition of Velinotamig - Cullinan Therapeutics is licensing velinotamig (BCMAxCD3) from Genrix Bio for global (ex-Greater China) rights across all indications[8] - Cullinan will pay Genrix Bio an upfront license fee of $20 million[40] - Genrix Bio is eligible to receive up to $292 million in development and regulatory milestones and $400 million in sales-based milestones[41] - Genrix Bio will also be eligible for tiered royalties from mid-single digits up to the mid-teens on potential ex-Greater China commercial sales[40] Velinotamig Clinical Development - Genrix Bio plans to initiate a Phase 1 study in China in autoimmune diseases later this year, with Cullinan planning to use the data to accelerate global clinical development[8, 27] - Velinotamig has Breakthrough Therapy Designation in China for relapsed/refractory multiple myeloma[27] - Phase 1 results of velinotamig in relapsed/refractory multiple myeloma showed an Overall Response Rate (ORR) of 85.4% at the RP2D target dose[30] - In the Phase 1 trial, 89.6% of patients experienced Cytokine Release Syndrome (CRS) of any grade, with 6.3% experiencing ≥Grade 3 CRS[34] Strategic Rationale - The acquisition complements Cullinan's CLN-978 (B cell depleter) and expands the opportunity to impact more patients across a broader range of autoimmune diseases[8] - Cullinan reiterates guidance to have cash resources into 2028 based on the current operating plan[8, 41]

Summary of Molecular Partners Conference Call Company Overview - **Company**: Molecular Partners - **Focus**: Development of DARPins, small binding proteins for targeted therapies in oncology [4][5] Key Platforms and Pipeline - **DARPins Platforms**: - **Radiotherapy DARPin Platform**: Utilizes small size to deliver radioisotopes effectively [6] - **T Cell Engager Platform**: Capable of creating bispecific to tetraspecific DARPins targeting multiple tumor antigens [6] - **Clinical Candidates**: - **MPO-712 (DLL3)**: Expected to enter Phase 1 trials in the second half of the year, targeting small cell lung cancer [12][15] - **MPO-533**: Involved in an ongoing Phase 1 trial for acute myeloid leukemia (AML) [44] DLL3 and Small Cell Lung Cancer - **Target**: DLL3, a marker for neuroendocrine tumors, particularly expressed in small cell lung cancer [15] - **Clinical Need**: High unmet medical need in small cell lung cancer, which is often chemo-resistant [15][13] - **Phase 1 Trial**: Aiming to start in the second half of the year, with a focus on relapsed refractory patients [16][19] Radioligand Therapy Insights - **Advantages of DARPins**: Selected for targets that are not easily ligandable, providing a solution for over 70% of targets [9][10] - **Imaging and Dosimetry**: Early imaging data expected to inform dosing and therapeutic windows, with results anticipated in H2 [19][20] - **Lead-212**: Chosen for its short half-life and effective energy delivery, partnered with OranoMed for supply [31][34] MPO-533 and AML Trial Adjustments - **Targeting Strategy**: Trispecific and tetraspecific DARPins designed to target multiple antigens on AML cells [46] - **Trial Adjustments**: Shifted to more frequent dosing to improve patient exposure and response rates, achieving a 30% complete response rate in recent evaluations [51][52] Future Developments - **Switched DARPin Platform**: Aiming to develop smart drugs that utilize logic gating to enhance T cell engagement [58][61] - **Investor Interest**: The new platform is generating interest from potential investors and pharmaceutical partners [62] Additional Considerations - **Supply Chain Management**: OranoMed's ability to provide a consistent supply of Lead-212 is crucial for the success of the radioligand therapy [39][41] - **Regulatory Engagement**: Ongoing constructive discussions with regulators to ensure effective clinical trial designs [29][42] This summary encapsulates the key points discussed during the conference call, highlighting Molecular Partners' innovative approaches in oncology and their strategic focus on DARPins and radioligand therapies.

Financial Data and Key Metrics Changes - The company reported a net loss of $22.6 million for Q1 2025, a decrease from a net loss of $31.7 million in Q1 2024, primarily due to increased revenue [11] - Revenue for Q1 2025 was $27.1 million, significantly up from $10 million in Q1 2024, driven by milestone revenues and development support [11][12] - Operating expenses increased to $52.7 million in Q1 2025 from $47.3 million in Q1 2024, reflecting a 10% rise [12][13] Business Line Data and Key Metrics Changes - Milestone revenue included $14 million from GSK and $3.1 million from Daiichi Sankyo, contributing to the overall revenue growth [11] - Research and development expenses rose to $35.7 million in Q1 2025 from $32 million in Q1 2024, mainly due to increased costs associated with ZW251 and other preclinical research [12] Market Data and Key Metrics Changes - The company anticipates increased royalty revenue from the potential approval of zanadatumab for advanced HER2 positive biliary tract cancer, with a final decision expected soon [10] - The company is also looking forward to presenting data at several upcoming medical conferences, which may enhance its market presence [9] Company Strategy and Development Direction - The company emphasizes a disciplined approach to cash burn and pipeline management, focusing on evidence-based decisions tied to clinical validation [8] - The R&D strategy includes advancing a diverse pipeline of ADCs and T cell engagers, with a focus on unmet needs in oncology and immunology [36][40] - The company plans to submit an IND for ZW251 by mid-2025, marking a significant milestone in its development strategy [36] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to navigate the dynamic biotech environment while delivering shareholder value [7][8] - The company remains well-capitalized with $321.6 million in cash and equivalents, projected to fund operations into the second half of 2027 [14][38] - Management highlighted the importance of clinical progress and disciplined capital allocation in creating long-term shareholder value [40] Other Important Information - The company presented six posters at the AACR annual meeting, showcasing advancements in its R&D pipeline [16][35] - The recent appointment of Dr. Sabine McCann as Senior VP of Clinical Development is expected to enhance the company's clinical strategy [37] Q&A Session Summary Question: What are the base case assumptions regarding milestone royalty revenues? - Management emphasized the importance of capital allocation and expressed excitement about the progress made by partners Jazz and Beijing, which could impact future revenues [44][46] Question: Can you provide details on the cytokine induction data for ZW209? - The design of ZW209 allows for localized T cell activation, which may limit cytokine release syndrome, presenting a favorable safety profile compared to other approaches [50][52] Question: How do you view the impact of ex-US patients in the Horizon GEA trial? - Management noted that there is generally no significant difference in efficacy across ethnicities, but they are monitoring the data closely [58][60] Question: What is the expectation for the KLK2 bispecific update at ASCO? - Management indicated that they are looking forward to the data presentation and highlighted the financial interest in the partnership with J&J [63][64] Question: How many internal programs can the company support? - The company can handle approximately five internal programs through phase one and about ten preclinical programs at any one time [87]

Financial Data and Key Metrics Changes - R&D expenses for Q1 2025 were $118.6 million, up from $100.1 million in Q1 2024, primarily due to a $30 million payment to Alnylam and expenses related to the ECLIPSE program initiation [36] - SG&A expenses for Q1 2025 were CAD 23.9 million, down from CAD 36.3 million in Q1 2024, largely due to cost savings from headcount reductions [37] - Net loss for Q1 2025 was $121 million compared to a net loss of $65.3 million in Q1 2024, driven by a significant drop in revenue from $52 million to approximately $3 million [38] Business Line Data and Key Metrics Changes - The hepatitis delta program has initiated the ECLIPSE Phase III program, with the first patient enrolled, marking a significant milestone [22] - The oncology portfolio continues to progress, with promising data from the Pro X10 dual masked T cell engager programs, particularly in HER2 positive colorectal cancer [15][28] Market Data and Key Metrics Changes - The estimated addressable market for hepatitis delta includes approximately 61,000 RNA positive patients in the U.S. and 113,000 in EU member countries plus the UK, highlighting the potential for significant commercial opportunity [10] - The company emphasizes that hepatitis delta has characteristics of a rare disease market with severe outcomes, supporting a value-based pricing model [11] Company Strategy and Development Direction - The strategic focus remains on advancing both infectious disease and oncology programs, with a commitment to developing a new standard of care for hepatitis delta virus infection [8] - The company is exploring collaborations to maximize value from the Pro X10 platform and has advanced a broadly neutralizing antibody in its HIV cure program [19] Management's Comments on Operating Environment and Future Outlook - Management acknowledges the challenging market environment for the biotechnology sector but emphasizes a disciplined approach to capital allocation and operational excellence [20] - The company maintains a strong cash position of approximately $1 billion, providing a runway extending into mid-2027 to advance key programs [39] Other Important Information - The agreement with Alnylam regarding the profit-sharing arrangement has been clarified, with the company recognizing CAD 30 million as R&D expense in Q1 2025 [39] - The company is preparing for the upcoming EASL Congress to present data from its hepatitis B program and the Solstice trial [26] Q&A Session Summary Question: Alnylam decision and future oncology updates - Alnylam opted out of the profit-sharing arrangement based on their strategic portfolio prioritization, prior to the latest HCV functional cure data being available [47] - Future oncology data updates will include mature data at higher dose levels and comparative data between dosing regimens, expected to be shared at medical congresses or focused investor events [46] Question: ECLIPSE study enrollment and timelines - The ECLIPSE one study aims to complete enrollment by the end of 2025, with ECLIPSE two having a 24-week endpoint [55] Question: Competitive positioning of T cell engagers - The company believes its dual mask technology offers a favorable safety profile and differentiates it from competitors, with a focus on convenience and quality of life for patients [60][62] Question: Functional cure rates and HBV program development - The company anticipates presenting data showing a 20% functional cure rate in the doublet and a 30% in the triplet at the upcoming EASL [77] - Further development of the HBV program is contingent on securing a global development and commercialization partner [78] Question: Changes in U.S. guidelines for HBV diagnosis - No changes have been made to U.S. guidelines for delta diagnosis, but there is hope for increased awareness and reflex testing in the future [101]