PresentationOkay. Welcome, ladies and gentlemen, to the last day of the JPMorgan Healthcare Conference. My name is [indiscernible], and I'm very happy to introduce the team of Molecular Partners, who will be taking you through their presentation, mostly Patrick, but then we have Martin, Michael and Michael here as well. After the presentation, there's time for some Q&A. So feel free to save your questions for the end, and I'll leave it to the team. Patrick?Patrick AmstutzCo-Founder, CEO, Member of Managemen ...

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]

Company Overview - Molecular Partners is a clinical-stage biotech company founded in 2004, with operations and listings in Switzerland (SIX, 2014) and the US (Nasdaq, 2021)[12] - The company is financed with approximately USD 116 million / CHF 93 million to reach upcoming value inflection points[12] - Molecular Partners focuses on oncology with differentiated assets like MP0712 (targeted radiotherapy) and MP0533 (next-gen immune cell engagers)[12] Radio-DARPin Therapeutics (RDT) - The company is developing Radio-DARPin therapeutics, which are designed for precise delivery of potent radio-isotopes to tumors[26, 27] - Molecular Partners has a global partnership with Orano Med to develop 212Pb Radio-DARPin therapeutics, with a 50:50 cost and share split for 4 programs[33, 36] - MP0712, a 212Pb x DLL3 Radio-DARPin, is in Phase 1/2a clinical trials in the US for small cell lung cancer (SCLC) and other neuroendocrine cancers (NECs), with early data expected in 2026[43, 77] - Preclinical data for MP0712 shows high tumor accumulation (Tumor > Kidney) and reduction of established tumors in mice[51] - MP0726, a 212Pb x MSLN Radio-DARPin, is being developed for ovarian cancer and is progressing towards first-in-human (FIH) imaging[86, 94] Other Pipeline Programs - MP0317, a FAP-localized CD40 agonist, is in a Phase 2 combo study in advanced biliary tract cancer, with interim analysis expected by YE 2027[104, 117, 123] - MP0533, a tetra-specific T-cell engager for AML, is in Phase 1/2a, with decisional data expected in H1 2026[124] - The company is developing Switch-DARPin platform for next-generation T cell engagers, with a lead candidate selection expected in H1 2026 and an update at AACR 2026[99, 140] Financial Outlook - The company's cash of approximately USD 116 million (CHF 93 million) ensures funding until 2028[99]

Core Insights - Molecular Partners AG is advancing its clinical-stage pipeline of DARPin therapeutics, focusing on targeted radiotherapy and immune cell engagers, with significant milestones expected in 2026 [1][20]. Financial Overview - As of December 31, 2025, the company reported cash and cash equivalents of CHF 93.1 million, sufficient to fund operations until 2028 [3]. Clinical Development Updates - The Phase 1/2a trial for MP0712, a Radio-DARPin targeting DLL3 for small cell lung cancer (SCLC), has commenced, with initial patient dosing expected in Q1 2026 and initial clinical data anticipated in the same year [2][4][7]. - MP0726, another Radio-DARPin targeting mesothelin (MSLN) for ovarian cancer, is also in development, with preclinical data presented at the 2025 SNMMI meeting [6]. - An investigator-initiated Phase 2 trial for MP0317 in cholangiocarcinoma is ongoing, with the first patient treated in early 2026 [10][11]. - MP0533, a tetra-specific T cell engager for acute myeloid leukemia (AML), is in a Phase 1/2a trial, with updates on its clinical development expected in H1 2026 [12][14]. Scientific Advisory Board - The formation of a scientific advisory board, chaired by Prof. Ken Herrmann, aims to accelerate the development of targeted radiotherapeutics [8]. DARPin Technology - Molecular Partners' DARPin therapeutics are designed for high specificity and stability, enabling effective delivery of radioactive payloads to tumors while minimizing damage to healthy tissues [19].

Core Insights - 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 [3] Group 1: Company Overview - Molecular Partners AG is listed on both SIX and NASDAQ under the ticker MOLN and was founded in 2004 [3] - The company has its headquarters in Zurich, Switzerland, and an office in Concord, Massachusetts, USA [3] - The primary focus of the company is oncology, with various programs in different stages of pre-clinical and clinical development [3] Group 2: Upcoming Events - The CEO, Patrick Amstutz, will present the latest developments and outlook for 2025 at the 44th Annual J.P. Morgan Healthcare Conference on January 15, 2025, from 10:30 AM to 11:10 AM PT [2] - A webcast of the presentation will be available on the Molecular Partners website under the Events tab [2] Group 3: Strategic Partnerships - Molecular Partners collaborates with leading pharmaceutical companies to leverage the advantages of DARPins and provide unique solutions to patients [3]

Core Insights - 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 [3] Group 1: Company Overview - Molecular Partners AG is pioneering the design and development of DARPin therapeutics, with a primary focus on oncology [3] - The company has various programs in different stages of pre-clinical and clinical development [3] - Founded in 2004, Molecular Partners has offices in Zurich, Switzerland, and Concord, Massachusetts, USA [3] Group 2: Upcoming Presentation - The CEO, Patrick Amstutz, will present the company's latest developments and outlook for 2025 at the 44th Annual J.P. Morgan Healthcare Conference on January 15, 2025 [2] - The presentation will take place from 10:30 AM to 11:10 AM PT at the Westin St. Francis in San Francisco, CA [2] - A webcast of the presentation will be available on the Molecular Partners website [2]

Core Insights - Molecular Partners AG has established a Scientific Advisory Board (SAB) for its radiopharmaceuticals, chaired by Prof. Ken Herrmann, a leading expert in nuclear medicine [1][4]. Group 1: Scientific Advisory Board Formation - The SAB will guide the development of Molecular Partners' Radio-DARPin platform, focusing on transitioning from early clinical validation to strategic clinical development [3][5]. - Prof. Ken Herrmann expressed enthusiasm for the potential of Radio-DARPins to deliver targeted radiopharmaceuticals effectively [2][8]. Group 2: Radio-DARPin Technology - Molecular Partners' Radio-DARPin candidates, including MP0712 and MP0726, are designed to target specific tumor markers, with MP0712 aimed at DLL3 for small cell lung cancer and MP0726 targeting mesothelin in various cancers [8]. - The technology aims to balance the delivery of potent radioactive payloads to tumors while minimizing damage to healthy tissues [8]. Group 3: Expertise of SAB Members - The SAB includes experts such as James Cook, Jason Lewis, and Michael Morris, who bring extensive clinical and industry experience to support the company's strategic development [5][6]. - Ken Herrmann's leadership is expected to be crucial in shaping the company's direction as it moves towards pivotal development decisions [5].

Core Insights - Molecular Partners AG is presenting updated data from a Phase 1/2a trial of its T-cell engager MP0533 for treating acute myeloid leukemia (AML) at the 67th ASH Annual Meeting [1][2] Group 1: Trial Results - The multicenter, open-label study shows that densified dosing of MP0533 is tolerable and leads to improved serum exposure with preliminary antitumor activity [2][4] - As of September 1, 2025, 54 patients have been treated with MP0533, with 8 out of 48 evaluable patients achieving a response, including 5 reaching composite complete responses [4] - The trial indicates that patients with lower disease burden are more likely to benefit from MP0533, with 6 of 8 responders presenting with less than 20% bone marrow blasts at baseline [4][7] Group 2: Expert Commentary - Prof. Courtney DiNardo expressed optimism about the clinical benefits of MP0533 in a mutation-agnostic manner for R/R AML patients, particularly those with lower disease burden [3] - Philippe Legenne highlighted the progress of the trial, noting the feasibility of the densified dosing regimen and the interest from consortia for further studies [5] Group 3: Mechanism of Action - MP0533 is a novel tetra-specific T cell-engaging DARPin that targets three tumor-associated antigens (CD33, CD123, CD70) on AML cells and the immune activator CD3 on T cells, designed to preferentially kill AML cells while minimizing damage to healthy cells [6] Group 4: Presentation Details - The poster presentation titled "Phase 1/2 study of MP0533" outlines clinical benefits with an acceptable safety profile across 9 dosing regimens, emphasizing the feasibility of accelerated step-up dosing [7][8]

Core Insights - Molecular Partners AG is presenting updated data from a Phase 1/2a trial of its T-cell engager MP0533 for treating acute myeloid leukemia (AML) at the 67th ASH Annual Meeting [1][2] Group 1: Trial Results - The multicenter, open-label study shows that densified dosing of MP0533 is tolerable and leads to improved serum exposure with preliminary antitumor activity [2][4] - As of September 1, 2025, 54 patients have been treated with MP0533, with 8 out of 48 evaluable patients achieving a response, including 5 reaching composite complete responses [4] - Six of the eight responders had less than 20% bone marrow blasts at baseline, indicating that patients with low disease burden are likely to benefit the most from MP0533 [4][7] Group 2: Expert Commentary - Prof. Courtney DiNardo expressed optimism about the clinical benefits of MP0533 in mutation-agnostic R/R AML patients, particularly those with lower disease burden, supporting further investigation in a Phase 2 setting [3][5] Group 3: Drug Mechanism and Design - MP0533 is a novel tetra-specific T cell-engaging DARPin that targets three tumor-associated antigens (CD33, CD123, CD70) on AML cells and the immune activator CD3 on T cells, designed to preferentially kill AML cells while minimizing damage to healthy cells [6][9] Group 4: Future Development - The trial is progressing well, with the densified dosing regimen showing feasibility and an acceptable safety profile, prompting interest from several consortia for further studies in both R/R and front-line AML settings [5][9]

Core Insights - The company is initiating the clinical phase of its collaboration with Orano Med, focusing on pioneering radiotherapy with the introduction of the first Radio-DARPin human image [2][3] Group 1: Company Overview - Patrick Amstutz, the CEO, emphasized the significance of the collaboration agreement signed approximately two years ago with Orano Med [2] - The webcast aims to discuss the lead program and upcoming studies related to the Radio-DARPin technology [2] Group 2: Key Personnel - The presentation includes contributions from Dani Steiner, Head of Radio Strategy, Philippe Legenne, Chief Medic, and Michael Stumpp, the program lead, who will handle the Q&A session [3]