Core Viewpoint - Molecular Partners AG has appointed Martin Steegmaier, Ph.D., as Chief Scientific Officer (CSO), effective October 1, 2025, to enhance its oncology drug development efforts, particularly in DARPin therapeutics [1][2]. Company Overview - Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, which are custom-built protein drugs aimed at addressing medical challenges that other drug modalities cannot effectively tackle [6]. - The company has a pipeline that includes various programs in pre-clinical and clinical development, with a primary focus on oncology [6]. Leadership Appointment - Martin Steegmaier brings extensive experience in oncology drug development from previous roles at Roche, MorphoSys, Boehringer Ingelheim, and SOTIO Biotech, where he led the development of a broad pipeline of oncology programs [1][3][2]. - The CEO of Molecular Partners, Patrick Amstutz, expressed confidence that Steegmaier's expertise will significantly contribute to the company's research organization and the advancement of its targeted DARPin therapeutics [2]. Educational Background - Martin Steegmaier holds a Ph.D. in biochemistry from the University of Basel and an MBA from the Edinburgh Business School, which complements his extensive experience in the biotech and pharmaceutical sectors [4]. Future Directions - The company aims to innovate and advance its pipeline of targeted DARPin therapeutics, including Radio-DARPins and Switch-DARPins, which are designed for logic-gated immune cell activation [2][5].

Radio-DARPin Therapy & MP0712 - Molecular Partners is focused on oncology with differentiated assets like MP0533 and MP0712, addressing unmet medical needs[8] - The company has CHF ~149 million, ensuring funding into 2027[8, 110] - MP0712, a 212Pb-DLL3 targeted radiotherapeutic, addresses the critical unmet need in SCLC, where >85% of patients express DLL3[36, 39] - Preclinical data shows MP0712 induces complete tumor regression in ~70% of mice at 4x 10µCi and ~20% of mice at 8x 5µCi in the NCI-H82 tumor model at day 63[45] - MP0712 clinical development strategy includes Phase 0 imaging studies and Phase 1 dose escalation studies starting in H2 2025, with initial clinical data expected by YE[54] Next-Gen Immune Cell Engagers & MP0533 - MP0533 is a tetra-specific T-cell engager designed to kill AML cells by targeting CD33, CD123, and CD70[69, 77] - Preliminary data from the MP0533 Phase 1/2a study shows 4 responders reported in DR 1-7 with manageable safety[80] - An improved MP0533 exposure was achieved at DR 8 with a steeper and denser step-up dosing regimen[82, 86] Switch-DARPin Platform - The Switch-DARPin platform aims to overcome limitations of current T cell engagers by enabling targeted and conditional activation of immune cells[94, 101] - Preclinical data shows the EpCAM-MSLN-CD2/CD3 Switch induces tumor regression more efficiently than a MSLN-CD3 engager (Tritac)[107]

Company Overview - Molecular Partners is a clinical-stage biotech company pioneering DARPin therapeutics for patients, with operations in Switzerland and the US[8] - The company is well financed into 2027 with approximately CHF 149 million[8] (Note: The outlook section mentions CHF ~131 million[95], so there might be a slight discrepancy) - Molecular Partners has proprietary DARPin platforms, including Radio-DARPins and Switch / T cell engagers[8] Pipeline Highlights - MP0712 (Radio-DARPin Therapy targeting DLL3) is in co-development for SCLC & NECs[9] - The co-development agreement with Orano Med includes up to 10 RDT programs, including MP0712[9] - MP0533 (Next-Gen Immune Cell Engager) is being developed for r/r AML and AML/MDS[9] MP0712 (Radio-DARPin Therapy) - MP0712 is the first 212Pb-DLL3 targeted radiotherapeutic for SCLC, where >85% of SCLC patients express DLL3[25] - Preclinical studies show MP0712 induces complete and durable tumor regression in the NCI-H82 tumor model at 10µCi injected every week[28] - Phase 1 study is expected to start in H2 2025, with initial safety and efficacy data in 2026[33] MP0533 (Tetra-specific T-cell Engager for AML) - MP0533 is designed to induce T cell-mediated killing preferentially when 2 or 3 AML-associated antigens are co-expressed[66] - Preliminary data from the Phase 1/2a study shows encouraging blast reduction, particularly in patients with lower disease burden at baseline[75] - Improved MP0533 exposure was observed at DR 8 with a steeper and denser step-up dosing regimen[78]

Core Insights - Molecular Partners AG and Orano Med have announced the launch of MP0726, a Radio-DARPin candidate targeting mesothelin (MSLN), with preclinical data to be presented at the 2025 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging [1][2] Group 1: Product Development - MP0726 demonstrates high affinity and selectivity for the membrane-proximal domain of MSLN, showing a tumor accumulation of up to 34% and a tumor to kidney ratio of up to 4.5 in vivo [2][3] - The candidate is designed to target ovarian cancer, leveraging the unique properties of DARPins to selectively bind to MSLN, which is highly expressed in tumors but lower in healthy tissues [3][8] - MP0726 is the second Radio-DARPin program to enter preclinical development, following MP0712, which targets DLL3 and is set to begin dosing in a Phase 1 study in the US in the second half of 2025 [6] Group 2: Strategic Collaboration - The collaboration between Molecular Partners and Orano Med has shown significant progress, highlighting the effectiveness of their joint R&D efforts in developing differentiated clinical candidates [4][5] - Orano Med's capabilities in R&D and manufacturing, along with a virtually unlimited supply of the starting isotope, position it uniquely to support the development of these new therapies [4] Group 3: Company Background - Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, with oncology as its main area of focus [9] - Orano Med specializes in targeted alpha-particle therapies using lead-212 (Pb), with its most advanced asset, AlphaMedix, having received Breakthrough Designation from the FDA in 2024 [10]

Core Viewpoint - Molecular Partners AG announced positive updated data from a Phase 1/2a trial of its tetraspecific T-cell engager MP0533 for relapsed/refractory acute myeloid leukemia (AML) at the EHA Congress in Milan [1][2] Group 1: Trial Results - In cohort 8, 3 out of 8 evaluable patients (over 30%) achieved a clinical response after the first cycle, including 1 complete response and 2 complete responses with partial hematologic recovery [3] - Patients in cohort 8 maintained exposure to MP0533 for over 4 days within the predicted therapeutic range, with 5 out of 8 patients showing more than 50% blast reduction [4] - The safety profile of MP0533 was deemed acceptable after the adjustment of the target dose in cohort 8 [9] Group 2: Dosing Regimen - Cohort 8 implemented a higher starting dose and an additional day of dosing, reaching the target dose by day 12 instead of day 15, which contributed to improved clinical responses [3][6] - The amended protocol for cohort 9 includes further acceleration of the step-up dosing, increased frequency of dosing, and the introduction of anti-CD20 premedication to enhance therapeutic exposure and response duration [7][9] - Initial data from cohort 9, which is currently dosing patients, is expected in the second half of 2025 [8] Group 3: Company Overview - Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, with oncology as its main area of focus [10] - The company was founded in 2004 and operates in both Zurich, Switzerland, and Concord, Massachusetts, USA [10]

Core Insights - Molecular Partners AG is undergoing a strategic review to enhance operational efficiency and focus on advancing its clinical assets, resulting in a workforce reduction of up to 40 positions, approximately 24% of total staff [1][2][4] Group 1: Strategic Review and Workforce Reduction - The company has initiated a strategic review aimed at increasing efficiency and sharpening focus on clinical assets, leading to a potential reduction of up to 40 positions [1][4] - The decision to reduce workforce is part of a plan to extend the company's cash runway into 2028, beyond the previous guidance of 2027 [4][7] - A consultation process with employees has begun in accordance with Swiss employment law, and support will be provided to affected employees, including severance packages and job-seeking assistance [3][4] Group 2: Clinical Development Focus - The company is prioritizing the development of clinical assets MP0533 and MP0712, which are expected to provide significant value for patients and shareholders [2][4] - Clinical data from both MP0533 and MP0712 is anticipated in the second half of 2025, maintaining previously announced timelines [4][7] - The strategic review identified redundancies primarily in research and associated functions, allowing for a more focused approach to clinical development [4] Group 3: Financial Outlook - The workforce reduction is expected to lead to cost savings that will become fully effective by early 2026 [3][4] - The company plans to report its half-year financials on August 25, 2025, which will provide further insights into its financial health and operational adjustments [4]

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 is focused on oncology and has licensed programs to other companies, including a $150 million deal with Novartis for an anti-spike trispecific program [3] - The collaboration with Aranomed involves the development of up to six programs on a 50/50 basis, with the company retaining commercial rights to the first two programs [17] Business Line Data and Key Metrics Changes - The company is working on two distinct areas: radiopharmaceuticals and multispecific DARPins, with a focus on DLL3 and AML programs [3][10] - DLL3 is expected to enter clinical trials in the second half of the year, with promising data from compassionate use programs [38] Market Data and Key Metrics Changes - The radiopharmaceutical market is experiencing broader adoption, with increasing interest from doctors and patients [28] - The company is strategically positioned to leverage the growing demand for targeted radiopharmaceuticals, particularly with its unique DARPin platform [8][10] Company Strategy and Development Direction - The company aims to expand its pipeline through collaborations and innovative approaches in radiopharmaceuticals and immune cell engagers [16][60] - The focus is on developing differentiated therapies that avoid competition with existing treatments, such as targeting the proximal membrane portion of mesothelin [39] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of radiopharmaceuticals, comparing the current landscape to the early days of antibody-drug conjugates (ADCs) [27] - The company is optimistic about the durability of its treatments and the ability to drive patients to complete responses quickly [59] Other Important Information - The collaboration with Aranomed is significant due to their established capabilities in manufacturing and logistics for radiopharmaceuticals [15][22] - The company is exploring pretargeting systems and half-life modulation to enhance the efficacy and safety of its therapies [32][34] Q&A Session Summary Question: How does the company view the competitive landscape for DLL3-targeted therapies? - Management noted that while there are other DLL3-targeted therapies, they have not seen a significant decrease in DLL3 expression, indicating potential for their radiopharmaceuticals [46][47] Question: What are the expectations for the upcoming data from the CD3 switch DARPin? - The company anticipates presenting data showing improved response rates and the ability to maintain patients in complete response [58] Question: How does the company plan to balance its focus between radiopharmaceuticals and other platforms? - Management indicated that if both platforms prove successful, they will have the opportunity to choose the best path forward, inviting interest from potential partners [60]

Core Insights - Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, which are custom-built protein drugs designed to address medical challenges that other drug modalities cannot effectively tackle [4] Group 1: Upcoming Events - The management team of Molecular Partners will participate in two investor conferences: the H.C. Wainwright 3rd Annual BioConnect Investor Conference on May 20, 2025, and the TD Cowen's 6th Annual Oncology Innovation Summit on May 28, 2025 [2][3] - Both events will be webcast and accessible on the Molecular Partners website under the investors tab [3] Group 2: Company Overview - Molecular Partners was founded in 2004 and has its offices in Zurich, Switzerland, and Concord, Massachusetts, USA [4] - The company is primarily focused on oncology and has various programs in different stages of pre-clinical and clinical development [4] - Molecular Partners collaborates with leading pharmaceutical companies to leverage the advantages of DARPins for unique patient solutions [4]

Core Insights - Molecular Partners AG is advancing its clinical programs and expects to achieve key milestones in 2025, including the IND filing and initial clinical data for its lead program MP0712 [2][5][8] - The company has a strong financial position with cash reserves of CHF 131 million as of March 31, 2025, which is projected to fund operations well into 2027 [19] Research & Development Highlights - The strategic partnership with Orano Med has been expanded to co-develop up to ten Pb-labeled radiotherapy programs, including MP0712 targeting DLL3 for small cell lung cancer [3][8] - Preclinical data for MP0712 presented at the AACR 2025 showed high tumor uptake and a favorable toxicity profile, supporting its efficacy in mouse models [4][9] - The IND application for MP0712 is planned for mid-2025, with a Phase 1 dose-escalation study set to begin in the second half of 2025 [5][8] - The second RDT program targeting MSLN is also in development, with promising preclinical data indicating effective binding despite high shedding of MSLN [7][9] Clinical Programs - MP0533, a multispecific T cell engager, is in a Phase 1/2a trial for acute myeloid leukemia, with recent data showing increased response rates in cohort 8 [10][11] - The study protocol for MP0533 has been amended to enhance exposure and response rates, with additional data expected in 2025 [12] - The Switch-DARPin platform aims to improve T cell engagers' safety and potency, with preclinical proof-of-concept data presented at AACR 2025 [13] Financial and Business Outlook - The company anticipates total operating expenses of CHF 55-65 million for 2025, with a portion allocated to non-cash effective costs [18] - The current cash position is expected to support operational needs and capital expenditures through 2027 [19] Corporate Governance Highlights - All motions proposed by the Board of Directors at the Annual General Meeting in April 2025 were approved by shareholders [17]