Slides
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Update on MP0712 program Patrick Amstutz, CEO Webcast call following TRP 2025 presentation November 12, 2025 ➢ New mechanism of action data ➢ Initial human images ➢ Outlook on Phase 1/2a study
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Disclaimer This presentation contains forward looking statements. Any statements contained in this presentation that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, as amended, including without limitation: implied and express statements regarding the clinical development of Molecular Partners’ current or future product candidates; expectations regarding timing for reporting data from ongoing clinical trials or the initiation of future clinical trials; the potential therapeutic and clinical benefits of Molecular Partners’ product candidates and its RDT and Switch-DARPin platforms; the selection and development of future programs; Molecular Partners’ collaboration with Orano Med including the benefits and results that may be achieved through the collaboration; and Molecular Partners’ expected business and financial outlook, including anticipated expenses and cash utilization for 2025. These statements may be identified by words such as “aim”, "anticipate",“expect”, “guidance”, “intend”, “outlook”, “plan”, “potential”, “will” and similar expressions, and are based on Molecular Partners’ current beliefs and expectations. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Some of the key factors that could cause actual results to differ from Molecular Partners’ expectations include its plans to develop and potentially commercialize its product candidates; Molecular Partners’ reliance on third party partners and collaborators over which it may not always have full control; Molecular Partners’ ongoing and planned clinical trials and preclinical studies for its product candidates, including the timing of such trials and studies; the risk that the results of preclinical studies and clinical trials may not be predictive of future results in connection with future clinical trials; the timing of and Molecular Partners’ ability to obtain and maintain regulatory approvals for its product candidates; the extent of clinical trials potentially required for Molecular Partners’ product candidates; the clinical utility and ability to achieve market acceptance of Molecular Partners’ product candidates; the potential that Molecular Partners’ product candidates may exhibit serious adverse, undesirable or unacceptable side effects; the impact of any health pandemic, macroeconomic factors and other global events on Molecular Partners’ preclinical studies, clinical trials or operations, or the operations of third parties on which it relies; Molecular Partners’ plans and development of any new indications for its product candidates; Molecular Partners’ commercialization, marketing and manufacturing capabilities and strategy; Molecular Partners’ intellectual property position; Molecular Partners’ ability to identify and in-license additional product candidates; unanticipated factors in addition to the foregoing that may cause Molecular Partners’ actual results to differ from its financial and business projections and guidance; and other risks and uncertainties set forth in Molecular Partners’ Annual Report on Form 20-F for the year ended December 31, 2024 and other filings Molecular Partners makes with the SEC from time to time. These documents are available on the Investors page of Molecular Partners’ website at www.molecularpartners.com. In addition, this presentation contains information relating to interim data as of the relevant data cutoff date, results of which may differ from topline results that may be obtained in the future. Any forward-looking statements speak only as of the date of this presentation and are based on information available to Molecular Partners as of the date of this release, and Molecular Partners assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. 2
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Making Alpha Therapies a Reality with DARPins and 212Pb MOLECULAR PARTNERS PIONEERS of DARPIN THERAPEUTICS ORANO MED PIONEERS of TARGETED ALPHA THERAPY FULL VALUE CHAIN PARTNERSHIP: ✓ World class technologies & capabilities combined ✓ DARPins as ideal vectors for radiopharmaceuticals ✓ 212Pb as potent therapeutic payload, proven clinical efficacy 3 Radio-DARPin HLE
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MP0712: Potent Efficacy at Clinically-Relevant Dose in Mice 0 10 20 30 40 50 60 70 80 0 500 1000 1500 2000 Days since cell injection Tumor Volume (mm3) average ± SEM MP0712 (4x10µCi) MP0712 (8x5µCi) Negative control (4x10µCi) Buffer Steiner et al, TRP 2024 (oral presentation) Croset et al, EANM 2024 (oral presentation) Lizak et al, SNMMI 2024 (oral presentation) 4 High Tumor Accumulation (Tumor > Kidney) Reduction of Established Tumors Mice xenografted s.c. with hDLL3-MC38 (Biocytogen). Dose: 10 µCi of 212Pb at 0.01 mg/kg of DLL3 DARPin. Efficacy study in NCI-H82 s.c. model / MP0712 and negative control injected 4 x 10 μCi at 0.01 mg/kg or 8 x 5 μCi at 0.01mg/kg every 1; 10 μCi = 370 kBq Blood Bladder Small intestine Colon Spleen Kidneys Liver Lung Heart Tail hDLL3-MC38 0 20 40 60 80 %ID/g 4 h 24 h 14 23 21 58
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DLL3 targeting “Why do we see High Tumor Uptake, Despite the low Copy Number” Croset et al, EANM 2024 (oral presentation) Lizak et al, SNMMI 2024 (oral presentation) NCI-H82 i.v. model: 212Pb-DOTAM-DARPin - single injection - dose: 10 µCi (0.01 mg/kg) NCI-H82 tumors 0 200 400 600 800 ABC value Low DLL3 density on tumor cells (of <1000 receptors/cell) High Tumor Accumulation (MP0712: Tumor > Kidney) ? 5
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0 10 20 30 0 2000 40000 80000 Hours Fluorescence (MFI) DARPin-AF488 Non-binding control MP0712-DLL3 DARPin is Rapidly Internalized and Accumulates Intracellularly in DLL3-expressing Cells in vitro 6 Spike DARPin + wash DAPI DARPin EEA1 Surface-bound DLL3-DARPin is rapidly internalized into SHP-77 human SCLC cells* Internalized DLL3-DARPin shows significant co-localization to the endosomal compartment in HEK-hDLL3 cells** DLL3-DARPin accumulates in HEK- hDLL3 cells over time (beyond the bound fraction at saturation)* * Internalization of DARPins labelled with anti-DARPin Fab-Alexa 488 conjugate ** Immunofluorescence co-staining of anti-DARPin antibody, an early endosomal marker (EEA1) and cell nucleus marker (DAPI) after (3 h incubation) MFI, Mean Fluorescence Intensity. Continuous DARPin presence (reloading) maximum surface binding (spike & wash)
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Hypothesis: Free Surface DLL3 is Continually Replenished for Binding and Internalization of MP0712 MP0712 – format selection: Optimized half-life and DARPin binder to exploit internalization & replenishment of DLL3 for radio- payload accumulation in SCLC cells Created with BioRender 7
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MP0712 Development Pathway 1. Imaging 2. Treatment MP0712 Pb-203 Pb-212 MP0712 SCLC patient SCLC patient MP0712 binding to tumor cells MP0712-induced tumor cell death tumor tumor Solid tumor cells Dying tumor cells 8 SPECT Re-imaging Phase 1/2a Study: Named Patient Access Program: ➢ Imaging and dosimetry with 203Pb ➢ Option for treatment with 212Pb Request from NuMeRI, Pretoria, South Africa* ➢ Safety of 212Pb ➢ Efficacy signals ➢ Includes an imaging and dosimetry step with 203Pb
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SPECT/CT Imaging of 203Pb-MP0712 in SCLC: A Case Example from a Named Patient Access Program in SA (Patient #3) 9 Patient characteristics • 69-year-old male (smoker) • Small cell neuroendocrine carcinoma of the lung • Stage III at referral, primary tumor located at superior mediastinum Treatment history • Radiotherapy and chemotherapy Dosing & Result • 5.1 mCi of 203Pb-MP0712 • Stage IV by MP0712 - SPECT with 4 liver mets Patient imaged as part of a Named Patient Access Program at NuMeRI, Pretoria, South Africa. Example of patient case series presented with courtesy of Prof. Dr. M. Sathekge. Full data are planned to be presented by the NuMeRI team at the Theranostics World Congress (TWC) 2026. 116 h post injection4 h post injection 24 h post injection Primary lesion Liver mets ➢ Initial high blood pool, followed by specific uptake in primary and metastatic lesions over time, and limited accumulation in healthy organs in line with MP0712 MoA
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Phase 2 studies MP0712 Phase 1/2a Study for SCLC and other NECs • First-in-Human, US multicenter, Phase 1/2a study of MP0712 monotherapy • Patients with small cell lung cancer (SCLC) and other neuro-endocrine cancers (NECs) • Every patient will be imaged (203Pb) before treatment (212Pb) • Patient pre-selection on DLL3 expression: not planned for SCLC and LC NEC of lung, foreseen for epNEC Registration study 2L+ SCLC patients IO, immuno-oncology; LC NEC, large cell neuroendocrine cancer; PoC, proof-of-concept; RP2D, recommended phase 2 dose. 10 Phase 1: Dose Escalation Main objectives: safety, RP2D; N=15–39 patients SCLC and lung LC NEC; N=9-39 patients epNEC 203Pb- MP0712 Imaging / dosimetry (SPECT) 75 MBq n=3* 105 MBq n=3-12* 150 MBq n=3-12* RP2D 200 MBq n=6-12* Phase 2a: Dose Expansion and PoC Main objectives: efficacy signals, confirm safety and RP2D; N=30 patients SCLC and NEC 212Pb-MP0712 (treatment): * Evaluable patients (Bayesian Logistic Regression Model guided dose escalation) **epNEC to start at a dose level previously tested in SCLC or LC NEC of lung at which a first signal of pharmacological activity is detected. RP2D for epNEC is anticipated to be same as RP2D for SCLC/LC NEC of lung. Dose Y** n=6-12* Dose X** n=3-12* … Registration in patients with other NECs 1–2L combination with IO SCLC
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MP0712 - Why DLL3 Targeted Radio Therapy for SCLC T-Cell engagers - Tarlatamab approved - 40% RR - DoR: 9.7 months - Substantial side effects Antibody-Drug Conjugates - Phase I/II - 70% RR - Risk of chemo-resistance - Manageable side effects Radio Therapy (MP0712) - Phase 0/I - SCLC highly radio sensitive - Manageable side effects - Combinable with other MoAs 11MoA, mode of action; RR, response rate. DLL3
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2 Conclusions & Outlook MP0712: 212Pb x DLL3 Radio-DARPin therapeutic candidate for SCLC • Strong pre-clinical data with attractive BioD, efficacy & safety profile • High tumor uptake leveraging rapid internalization & replenishment of DLL3 • Initial human images* show specific uptake in primary & metastatic tumor lesions supporting intended MoA Outlook • Full 203Pb-MP0712 compassionate care imaging & dosimetry data at TWC 2026 • MP0712 Phase 1 IND application filed, trial initiation expected before year end 2025 • Initial data from Phase 1 in 2026 TWC, Theranostics World Congress *Patient case from Named Patient Access / Compassionate care in South Africa, imaged with 203Pb-MP0712. 12
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Acknowledgments 13 Team at Molecular Partners AG Julien Torgue Amal Saidi Aaron Schatzmann Tania Stallons Amy Wong Federico Rojas Amanda Reyes Jessica Johnson Rob Chastain Haley Sprague Volker Wagner & clinical team Orano Med Team Patients and their Families NuMeRI Team Mike Sathekge Joseph Kabunda Honest Ndlovu