Orally Administered MOMA-313 as Monotherapy or Combination Therapy in Participants with Advanced or Metastatic Solid Homologous Recombination (HR)-Deficient Tumors: Phase 1 Study Design

INTRODUCTION METHODS Orally Administered MOMA-313 as Monotherapy or Combination Therapy in Participants With Advanced or Metastatic Solid Homologous Recombination (HR)-Defi cient Tumors: Phase 1 Study Design Poster No. CT192 Amita Patnaik 1*; Wassim Abida2; Kim A. Reiss 3; Johann De Bono4; Rana R. McKay5; Alan H. Bryce 6; Eileen M. O’Reilly7; Neal Shore8; Alex Spira9; David R. Wise10; Ramaswamy Govindan 11; Vivek Subbiah12; Alexander Philipovskiy 13; Rahul Aggarwal 14; Louise Carter 15; Pasquale Rescigno16; Joaquin Mateo17; Victor Moreno18; Marta Gil-Martin 19; Diana Manzanedo 20; David Waller20; Salah Nabhan20; Jordan Krall 20; Erica Evans 20; and Marc Ballas 20 1 Co-Director of Clinical Research, Co-Founder, The START Center for Cancer Research, San Antonio, Texas, USA 2 Genitourinary Medical Oncologist, Memorial Sloan Kettering Cancer Center, New York, NY, USA 3 Associate Professor of Medicine (Hematology-Oncology), Co-Leader Cancer Therapeutics Program, Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA, USA 4 Regius Professor of Cancer Research, Professor of Experimental Cancer Medicine & Honorary Consultant in Medical Oncology, Head of Division of Clinical Studies, Director of the Drug Development Unit & Head of Prostate Cancer Targeted Therapy Group, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK 5 Medical Oncologist, Associate Professor of Medicine, UC San Diego Health, San Diego, CA, USA 6 Professor, Department of Medical Oncology & Therapeutics Research with City of Hope, City of Hope Cancer Center Phoenix, Goodyear, AZ, USA 7 Gastrointestinal Medical Oncologist, Memorial Sloan Kettering Cancer Center, New York, NY, USA 8 Medical Director, Carolina Urologic Research Center, Myrtle Beach, SC, USA 9 CEO and Clinical Director, NEXT Oncology-Virginia; Chair, Research Executive Committee, USOncology Research; Co Chair, Thoracic Committee, USOncology Research; Co Director, Virginia Cancer Specialists Research Institute, Fairfax, VA, USA 10 Section Chief, Genitourinary Medical Oncology, Perlmutter Cancer Center at NYU Langone Health, New York, NY, USA 11 Professor of Medicine, Anheuser Busch Chair in Medical Oncology, Director, Section of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA 12 Chief, Early-Phase Drug Development, Sarah Cannon Research Institute (SCRI), Nashville, TN, USA 13 Associate Director of Drug Development, Lake Mary DDU, Florida Cancer Specialists & Research Institute, Lake Mary, FL, USA 14 Professor of Medicine, Thomas Perkins Distinguished Professor in Cancer Research, Associate Director for Clinical Research, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA 15 Senior Clinical Lecturer in Experimental Cancer Medicine, University of Manchester, Honorary Consultant in Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK 16 Clinical Senior Lecturer, Honorary Consultant, Newcastle University, Tyne, UK 17 Prostate Cancer Research Group, Vall d´Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain 18 Director Clinical Research Early Phase Trials Unit, START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain 19 Medical Oncology Department, Catalan Institute of Oncology and IDIBELL, L’Hospitalet del Llobregat, Barcelona, Spain 20 MOMA Therapeutics, Cambridge, MA, USA *Presenting author, Amita Patnaik, [email protected] Scan QR code to view poster Presented by Dr. Amita Patnaik AACR April 29, 2025 Chicago, IL USA • Genes required for homologous recombination (HR)-mediated DNA repair are commonly mutated or deleted in tumors, which can create a dependence on DNA polymerase theta (Polθ)- mediated end-joining (TMEJ) for the repair of double-stranded breaks and cell survival (Figure 1A).1-3 • MOMA-313 is a novel, potent, and selective inhibitor of Polθ helicase activity (Figure 1B). • MOMA-313 may have synergistic activity with PARP inhibitors resulting in improved responses to PARP inhibition and delayed resistance by: – Deepening PARP inhibitor responses – Prolonging PARP inhibitor responses – Preventing resistance caused by reversions in HR genes – Providing a favorable safety profi le (based on data from non-clinical studies) • The primary objective is to characterize the safety and tolerability of MOMA-313 when administered as monotherapy or in combination with olaparib. • Key secondary objectives will include the following when MOMA-313 is administered as monotherapy or in combination with olaparib: – To identify the recommended Phase 2 dose – To characterize the pharmacokinetic (PK) profi le of MOMA-313 alone and in combination with olaparib – To assess preliminary antitumor activity – To assess the eff ects of food on PK parameters of MOMA-313 • Combining a Polθ inhibitor with a PARP inhibitor may increase both the sensitivity of HR-defi cient cancers to PARP inhibitors and the depth and duration of response by preventing TMEJ-mediated secondary resistance caused by reversions in HR genes. • Characterizing the properties of MOMA-313 will support its potential utility to treat HR-defi cient cancers in combination with olaparib. • The results from this Phase 1 study will help determine the MOMA-313 optimal biologic dose for monotherapy and combination treatment with olaparib for future studies. ACKNOWLEDGMENTS Medical writing support was provided by Holly Richendrfer, PhD, CMPP, of Two Labs Pharma Services. DISCLOSURES A.P.: Honoraria from Texas Society of Clinical Oncology; Consulting/advisory role for Bayer, Novartis, Merck, Seattle Genetics, Silverback Therapeutics, Shenzhen IONOVA Life Sciences, Gilead, Daiichi Sankyo, HalioDx, Janssen, Loxo Oncology at Lilly, Pfi zer, Quanta Therapeutics, Scorpion Therapeutics; Speaker’s bureau for Merck; Institutional research funding from Merck, Pfi zer, Lilly, Plexxikon, Corvus Pharmaceuticals, Tesaro, Abbvie, Forty Seven, Five Prime Therapeutics, Infi nity Pharmaceuticals, Pieris Pharmaceuticals, Surface Oncology, Livzon, Vigeo Therapeutics, Astellas Pharma, Klus Pharma, Symphogen, Syndax, Arcus, Fochon, Upsher-Smith, Exelixis, Seattle Genetics, Bolt, Ionova, Daiichi Sankyo, Sanofi , Gilead Sciences, Seagen, Shenzhen IONOVA Life Sciences, Pionyr Immunotherapeutics, Loxo Oncology at Lilly, Nektar Therapeutics, Alpine Immune Sciences, Amgen, Institut de Recherches Internationales Servier, 1200 Pharma, Genentech, Aadi Bioscience, Prelude, KSQ Therapeutics, Carrick Therapeutics, Pyrotec Therapeutics, Quanta Therapeutics, BioTheryX, MOMA Therapeutics, IGM Biosciences, Loxo Oncology, Compugen, Scorpion Therapeutics, and Olema Oncology; W.A.: Honoraria from Roche, Medscape, Aptitude Health, Clinical Education Alliance, OncLive/MJK Life Sciences, touchIME, Pfi zer, theMedNet, Prostate Cancer Foundation; Consulting/advising for Clovis Oncology, Janssen, ORIC Pharmaceuticals, Daiichi Sankyo, AstraZeneca/MedImmune, Pfi zer, Laekna Therapeutics, MOMA Therapeutics, Endeavor BioMedicines, K36 Therapeutics; Institutional research funding from AstraZeneca, Zenith Epigenetics, Clovis Oncology, ORIC Pharmaceuticals, Epizyme, Nuvation Bio, Merus, Transthera, MOMA Therapeutics; K.A.R.: Consultation honoraria from Carisma Therapeutics, AstraZeneca, BristolMyerSquib, Guardant Health, Foundation Medicine Inc, Synovation Bio, MOMA Therapeutics, Merus. Research grants from Clovis Oncology, BristolMyerSquibb, GlaxoSmithKline; J.D.B.: Received grants or contracts from Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Crescendo, Daiichi-Sankyo, Endocyte, Genentech/Roche, GlaxoSmithKline, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Pfi zer, and Sanofi Aventis; Consulting or advisory fees from Astellas, AstraZeneca, Bayer, Daiichi-Sankyo, Genentech/Roche, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Orion, Pfi zer, Sanofi Aventis, and Taiho; Payment or honoraria from Astellas, AstraZeneca, Bayer, Cellcentric, Crecendo, Daiichi, Genentech, Genmab, GlaxoSmithKline, Janssen, Merck Serono, Mycrix, MSD, Orion, Pfi zer, Sanofi Aventis, and Taiho; Inventor on patent 8,822,438; Data safety monitoring or advisory board for Amgen, AstraZeneca, Bayer, Bioxcel Therapeutics, Crescendo, Daiichi-Sankyo, Endocyte, Genentech/Roche, GlaxoSmithKline, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Oncternal, Pfi zer, and Sanofi Aventis; and Institutional royalties or licenses related to abiraterone, PARP inhibitors, and PI3K/AKT; R.M.: Consulting or advisory role for Ambrx, Arcus Biosciences, Astellas Medivation, AstraZeneca, Aveo, Bayer, Blue Earth Diagnostics, Bristol-Myers Squibb, Calithera Biosciences, Caris Life Sciences, Dendreon, Eisai, Exelixis, Janssen, Lilly, Merck, Myovant Sciences, Novartis, Pfi zer, Sanofi , Seagen, Sorrento Therapeutics, Sumitomo Pharma Oncology, Telix Pharmaceuticals, Tempus, and Vividion Therapeutics; and Institutional research funding from Artera, AstraZeneca, Bayer, Bristol-Myers Squibb, Exelixis, Oncternal Therapeutics, and Tempus; A.H.B.: Honoraria from Johnson and Johnson, Astellas, Pfi zer, Merck, Bayer, AstraZeneca, Myovant, Novartis; Grants/research support from Johnson and Johnson, PharmaMar; Advisory board membership for MOMA Therapeutics, Lantheus; Independent contractor for Astellas; E.M.O.: Consultant for Abbvie, Agenus, Alligator BioSciences, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, FibroGen, Leap Therapeutics, Merck, Merus, Momenta Pharmaceuticals, Novartis, Rafael, Regeneron, Revolution Medicines; Data and safety monitoring board for Ability Pharma; Institutional grant funding from Arcus, BioNTech, Celgene, Elicio, Genentech; Talks for Research to Practice; Editor at American Society of Clinical Oncology; N.S.: Consultant for Abbvie, Accord, Alessa Therapeutics, Amgen, Antev, Arquer, Asieris, Astellas, Astra Zeneca, Aura Biosciences, Bayer, Bioprotect, Bristol Myers Squibb, Boston Scientifi c, CG Oncology, Clarity, Cold Genesys, Dendreon, Exact Imaging, Genentech Roche, Ferring, Fize Medical, Foundation Medicine, Genesis Care, Immunity Bio, Incyte, Invitae, Janssen, Lantheus, Lilly, MDXHEALTH, Merck, Minomic, Myovant, Myriad, Nonagen, Novartis, Nymox, Palette Life, PlatformQ, Pacifi c Edge, Pfi zer, Preview, Profound Medical, Promaxo, Protara, Photocure, Propella, Sanofi , Genzyme, Specialty Networks, Telix, Tolmar, Urogen; A.S.: Leadership at Next Oncology; Stock and other ownership interests at Lilly; Honoraria from CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, Bayer; Consulting or advisory role for Array BioPharma, Incyte, Amgen, Novartis, AstraZeneca/MedImmune, Mirati Therapeutics, Gritstone Bio, Jazz Pharmaceuticals, Merck, Bristol Myers Squibb, Takeda, Janssen Research & Development, Mersana, Blueprint Medicines, Daiichi Sankyo/Astra Zeneca, Regeneron; Institutional research funding from Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma , MedImmune , Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, LAM Therapeutics, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone Bio, Plexxikon, Amgen, Loxo, Daiichi Sankyo, ADC Therapeutics, Janssen Oncology, Mirati Therapeutics, Rubius Therapeutics, Synthekine, Mersana, Blueprint Medicines, Regeneron, Alkermes, Revolution Medicines; D.R.W.: Stock and other ownership interests from Doximity; Honoraria from OncLive; Consulting or advisory roles from Leap Therapeutics, Gerson Lehrman Group, Guidepoint Global, Pfi zer, Foundation Medicine, Silverlight, Alphasights, Janssen, LabCorp, Myovant Sciences, Lilly, Bayer, Sanofi , AstraZeneca, Accutar Biotech; Travel, accommodations, expenses from Pfi zer; R.G.: none to disclose; V.S.: Research funding from: Abbvie, Agensys, Alfasigma, Altum, Amgen, Bayer, BERG Health, Blueprint Medicine, Boston Biomedical, Boston Pharmaceuticals, D3 Bio, Dragonfl y Therapeutics, Exelixis, Fujifi lm, GlaxoSmith-Kline, Idera Pharmaceuticals, Incyte, Inhibrix, Eli Lilly/Loxo Oncology, MedImmune, NanoCarrier, Novartis, PharmaMar, Pfi zer, Relay Therapeutics, Roche/Genentech, Takeda, Turning Point Therapeutics, and Vegenics; Consulting/advisory roles for Abbvie, Astex Pharmaceuticals, AstraZeneca, Bayer, Genmab, Incyte, Lilly/Loxo Oncology, Novartis, Obsidian Therapeutics, Pfi zer, Pheon Therapeutics, Regeneron, Relay Therapeutics, Roche, Endeavor Biomedicines, RevMed; Other consulting/advisory role/CME from Helsinn Healthcare, Jazz Pharmaceuticals, Incyte, Loxo Oncology/Lilly, Novartis, Relay Therapeutics, Daiichi Sankyo, Illumina, Bayer, Medscape, OncLive, Clinical Care Communications, PERS, and Med learning group; A.P.: none to disclose; R.A.: Consultant/advisory role for Pfi zer, Merck, Amgen, Alessa Therapeutics, Exelixis, Bayer, Tersera, BioXcel Therapeutics, Janssen, Novartis, AstraZeneca, Boxer Capital, EcoR1 Capital, PCCTC, MJH Life Sciences, Flare Therapeutics, Research to Practice, Guidepoint Inc, Slingshot Insights, Harpoon therapeutics, Washington Research Foundation, Curio Science; Institutional research funding from Zenith Epigenetics, Novartis, Xynomic Pharma, Janssen, Merck, Amgen, AstraZeneca; Expert testimony for University of Utah Health; Travel, accommodations, expenses from DAVA Oncology; L.C.: Consultant for Boehringer Ingelheim, Bicycle Therapeutics, and Athenex; P.R.: none to disclose; J.M.: Advisor for AstraZeneca, Amunix/Sanofi , Daichii Sankyo, Janssen, MSD, Pfi zer, and Roche; Scientifi c board member for Nuage Therapeutics; Speaker bureaus for AstraZeneca, MSD, Pfi zer, Illumina, and Guardant; Institutional grants from AstraZeneca and Pfi zer; V.M.: Consultant for Bayer, BMS, Janssen Oncology, and Merck; Speaker bureau fees from Bayer; Research funding from Abbvie, ACEA Biosciences, Adaptimmune, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, BMS, Celgene, E-therapeutics, Eisai, GSK, Janssen, Menarini, Merck, Nanobiotix, Novartis, Pfi zer, PharmaMar, PsiOxus Therapeutics, Puma Biotechnology, Regeneron, RigonTEC, Roche, Sanofi , Sierra Oncology, Synthon, Taiho Pharmaceutical, Takeda, Tesaro, and Transgene; Travel and accommodation expenses from Regeneron/Sanofi ; M.G.-M.: Personal fees from GSK, MSD, and Clovis; D.M., D.W., S.N., J.K., E.E., M.B: employment and stock ownership in MOMA. In-vivo preclinical data • MOMA-313 demonstrated robust dose-dependent tumor growth inhibition and tumor regression in combination with olaparib in tumor xenograft experiments of the BRCA2-mutant DLD1 cell line4 (Figure 2) and in BRCA-mutated pancreatic cancer patient-derived xenograft models4 (Figures 3 and 4). • The combination of MOMA-313 and olaparib in animal models was well tolerated at all dose levels with favorable PK (data not shown). • This is a Phase 1, fi rst-in-human, multi-center, open-label, dose escalation and dose optimization study designed to assess the safety, tolerability, PK, pharmacodynamics (PDx), and preliminary clinical activity of MOMA-313 (NCT06545942).5 • MOMA-313 will be administered orally either as monotherapy or combination therapy with olaparib in patients with select HR-defi cient solid tumors. • Key study inclusion and exclusion criteria are listed in Table 1. • Participants are eligible for the study if they cannot undergo curative therapy. • Participants are eligible for monotherapy if they are previously exposed to PARP inhibitors whereas participants who are either naive or previously exposed to PARP inhibitors are eligible for combination therapy. • Enrollment of initial cohorts began in the United States in August 2024; the study is currently enrolling in the United States, United Kingdom, and Spain (Figure 5). • The study design has two treatment arms (Figure 6). AE, adverse event; PK, pharmacokinetics. OBD, optimal biologic dose; PDx, pharmacodynamics; PK, pharmacokinetics. BRCA, breast cancer associated genes; HR, homologous recombination; HRD, homologous recombinant defi ciency/defi cient; PARPi, poly (adenosine diphosphate-ribose) polymerase inhibitors; Polθ, DNA polymerase theta; TMEJ, Theta-mediated end-joining. BRCAmut, breast cancer associated gene mutations, BRCA2mut, breast cancer associated type 2 mutations; DLD1, human cell line from colorectal adenocarcinoma. **p<0.01, ***p<0.001, ****p<0.0001 when compared with olaparib as a single agent. *p<0.05, **p<0.01, ***p<0.001 when compared with olaparib as a single agent. Key Study Endpoints Figure 5. Site Locations Figure 6. Study Design Figure 7. Dose Escalation Schematic Table 1. Key Study Entry Criteria5 Limited Enhanced Duration of PARPi treatment HRD (BRCA) + PARPi HRD (BRCA) + PARPi + MOMA-313 DNA single-strand break PARPi DNA double-strand break Polθ Strand-invasion Microhomology Homologous Recombination (HR) Theta-mediated end-joining (TMEJ) Homologous Recombination (HR) Theta-mediated end-joining (TMEJ) Polθ MOMA-313 PARPi DNA double-strand break Microhomology A) B)DNA single-strand break DNA single-strand break X HR Mutation Strand-invasion X HR Mutation PARP X 0 7 14 21 28 35 42 0 500 1000 1500 2000 2500 Time (d) Tumor Volume (mm3) 0 10 20 30 0 500 1000 1500 2000 2500 Time (d) Tumor Volume (mm3) MOMA-313 (1 mg/kg twice daily) + olaparib (100 mg/kg once daily)* MOMA-313 (3 mg/kg twice daily) + olaparib (100 mg/kg once daily)*** MOMA-313 (10 mg/kg twice daily) + olaparib (100 mg/kg once daily)* MOMA-313 (30 mg/kg twice daily) + olaparib (100 mg/kg once daily)** Vehicle Olaparib (100 mg/kg once daily) MOMA-313 (30 mg/kg twice daily) 0 10 20 30 40 50 0 1000 2000 2500 1500 500 Time (d) Tumor Volume (mm3) Vehicle Olaparib (100 mg/kg once daily) MOMA-313 (30 mg/kg twice daily) MOMA-313 (30 mg/kg twice daily) + olaparib (100 mg/kg once daily)* MOMA-313 (0.3 mg/kg twice daily) + olaparib (100 mg/kg once daily)** MOMA-313 (1 mg/kg twice daily) + olaparib (100 mg/kg once daily)*** MOMA-313 (3 mg/kg twice daily) + olaparib (100 mg/kg once daily)**** MOMA-313 (10 mg/kg twice daily) + olaparib (100 mg/kg once daily)**** Vehicle Olaparib (100 mg/kg once daily) MOMA-313 (10 mg/kg twice daily) Figure 2. DLD1-BRCA2mut CDX Model Figure 3. BRCA2mut Pancreatic PDX Figure 4. BRCA1mut Pancreatic PDX Figure 1. Polθ Inhibition Can Potentiate the Response to PARP Inhibitors in HRD Cancers Primary endpoints Secondary endpoints • The number of participants with AEs • Dose-limiting toxicities • Serious AEs • AEs leading to discontinuation PK endpoints: • Plasma PK parameter endpoints for both MOMA-313 and olaparib including area under the curve • Maximum concentration and time to maximum concentration • Human half-life Clinical activity endpoints: • Objective response rate • Duration of and time to response • Progression free survival and overall survival • Disease control rate Treatment Arm 1 Single-agent MOMA-313 Treatment Arm 2 Combination of MOMA-313 and olaparib • Arm 1A: The dose escalation phase will determine the presumptive optimal biologic dose (OBD) of MOMA- 313 as a single agent and will support MOMA-313 dose optimization (Figure 7) – A subset of participants in Arm 1A will participate in a sub-study to evaluate the eff ects of food on the PK and safety of MOMA-313 • Arm 1B: The dose-optimization phase will support confi rmation of the single-agent OBD to evaluate in future studies • Arm 2A: The dose escalation phase will help determine the OBD of MOMA-313 when combined with olaparib (Figure 7) – Arm 2A will also include a drug-drug interaction sub-study to assess any potential interactions between MOMA-313 and olaparib • Arm 2B: The dose-optimization phase will support confi rmation of the combination OBD to evaluate in future studies United States United Kingdom Spain Inclusion criteria ≥18 years old Histologically confi rmed advanced or metastatic solid tumors with select HR-defi cient mutations Evaluable disease defi ned by measurable or non-measurable lesion(s) using RECIST and/or PCWG guidelines ECOG PS ≤2 Fully recovered from the eff ects of prior therapy Exclusion criteria History of condition, therapy, or laboratory abnormality that might confound the results of the study or prohibit participation Has a known active infection Has severe or uncontrolled systemic disease(s) Has current, uncontrolled, active liver disease Has uncontrolled or untreated HIV /AIDS or related illness Active prior or concurrent advanced-stage malignancy Presence of advanced cardiovascular disease CNS metastases with progressive neurological symptoms Recently or currently receiving anticancer therapy, radiotherapy, and certain medications that would interact with MOMA-313 Arm 1A: Dose escalationa All HRDb mutant solid tumors where PARP inhibitor is indicated. Participants must be PARP inhibitor experienced N = up to ~36 Arm 1B: Dose optimization All HRDb mutant solid tumors where PARP inhibitor is indicated. Participants must be PARP inhibitor experienced N = up to ~40 Single-agent presumptive OBD(s) Treatment Arm 1: MOMA-313 monotherapy Arm 2A: Dose escalationa Advanced or metastatic solid tumors with alterations in BRCA1, BRCA2, CDK12, PALB2, or RAD51 paralogs. Participants can be PARP inhibitor naive or experienced N = up to ~39 Arm 2B: Dose optimization Advanced or metastatic solid tumors with alterations in BRCA2, PALB2, or RAD51 paralogs. Participants must be PARP inhibitor naive N = up to ~40 Combination presumptive OBD(s) Treatment Arm 2: MOMA-313 in combination with olaparib ATM, ataxia-telangiectasia mutated; BARD1, BRCA1-associated RING domain protein 1; BRCA1, breast cancer gene 1; BRCA2, breast cancer gene 2; BRIP1, BRCA1 interacting protein; CDK12, cyclin-dependent kinase 12; CHEK1, cell cycle checkpoint kinase 1; CHEK2, cell cycle checkpoint kinase 2; DDI, drug- drug interaction; FANCL, Fanconi anemia of complementation group L; HRD, homologous recombination defi cient(cy); OBD(s), optimal biologic dose(s); PALB2, partner and localizer of BRCA2; PARP , poly (ADP-ribose) polymerase; RAD, radiation-sensitive protein; SRC, safety review committee; ~ , approximately. Notes: Treatment Arm 1A includes a food-eff ect evaluation sub-study. Additionally, Treatment Arm 2A includes a DDI evaluation sub-study. aIncludes dose level expansion, bhomologous recombination defi ciency mutations are defi ned as an alteration in any one of the following genes: ATM; BRCA1; BRCA2; BRIP1; BARD1; CDK12; CHEK1; CHEK2; FANCL; PALB2; RAD51B/C/D; and RAD54L. BLRM, Bayesian logistic regression model; CxDx, Cycle (number) Day (number); combo, combination; EWOC, escalation with overdose control; mono, monotherapy; n, number; SRC, Safety Review Committee. aThe expansion of a dose level may be initiated once a dose level in dose escalation has been determined safe (or “cleared”) by the SRC. At least 2 dose levels will be expanded with up to approximately 12 additional participants evaluated in each dose level. bCombination dose escalation will be initiated following safety clearance of 2 dose levels in Treatment Arm 1A (as determined by the SRC) at a MOMA-313 dose 1 level below the highest cleared dose for single-agent MOMA-313. Combination dose escalation will be conducted in parallel to monotherapy dose escalation. cParticipants enrolled in the dose-escalation phase (Treatment Arm 2A) will initially begin olaparib twice daily administration starting C0D-4 with MOMA-313 twice daily administration beginning C1D1. Participants not participating in the DDI evaluation sub-study, as well as participants enrolled in dose optimization, will begin dosing twice daily olaparib and MOMA-313 on C1D1. AIDS, acquired immunodefi ciency syndrome; CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; HIV, human immunodefi ciency virus; HR, homologous recombination; PCWG, Prostate Cancer Working Group; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors. Treatment Arm 1A Monotherapy dose escalation (BLRM with EWOC) Treatment Arm 2A Combination dose escalation (BLRM with EWOC) Dose level expansionsa Dose level expansionsa Mono dose level n (n=~3)Mono dose level 3 (n=~3)Mono dose level 2 (n=~3)Mono dose level 1 (n=~3) Combo dose level n (n=~3)Combo dose level 3 (n=~3)Combo dose level 2 (n=~3)Combo dose level 1b,c (n=~3) REFERENCES 1. Groelly FJ, et al. Nat Rev Cancer. 2023;23(2):78-94. 2. Pettitt SJ, et al. Canc Discov. 2020;10(10):1475-1488. 3. Harvey-Jones E, et al. Ann Oncol. 2024;35(4):364-380. 4. Evans E, et al. Eur J Cancer. 2024;211(suppl 1):114574. 5. Study of Orally Administered MOMA-313 in Participants With Advanced or Metastatic Solid Tumors. https://clinicaltrials.gov/study/ NCT06545942. Accessed March 4, 2025. STUDY OBJECTIVES CONCLUSIONS

The release as fetched from its publisher. momatx.com ↗