Dianthus Therapeutics, Inc. · NASDAQ:DNTH
Dianthus Therapeutics — Magenta Therapeutics — ASH Annual Meeting 2022
31 slides from Dianthus Therapeutics's conference presentation, Dec 13, 2022
Slide 1: MGTA-117 Clinical Data Update, ASH Annual Meeting
Exhibit 99.2 MGTA-117 Clinical Data Update ASH Annual Meeting December 13, 2022 (NASDAQ: MGTA)
Slide 2: Agenda & Introductions
Agenda & Introductions Introduction Review of MGTA-117 Phase 1/2 Clinical Results – Cohorts 1-3 Next Steps Q&A Session Jason Gardner, D.Phil. CEO, President and Co-founder Lisa Olson, Ph.D. Chief Scientific Officer Shawn Rose, M.D., Ph.D. Senior Vice President, Clinical Development Steve Mahoney, J.
Slide 3: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, as amended. These statements include, without limitation, implied and express statements relating to: Magenta’s future business expectations, p
Slide 4: Improve Outcomes and Expand Use of Stem Cell Transplant & Gene Therapy
Improve Outcomes and Expand Use of Stem Cell Transplant & Gene Therapy Transplant could be a path to a cure Barriers to transplant Opening the door to a cure 90,000 stem cell transplants/year globally1 Blood Cancers (AML, MDS) Gene Therapy (Sickle Cell Disease) Autoimmune (Multiple Sclerosis) ~60% o
Slide 5: Differentiated Pipeline with Potentially First-in-Class ADC Targeted Conditioning
Differentiated Pipeline with Potentially First-in-Class ADC Targeted Conditioning Disease Area Preclinical IND-Enabling Phase 1 Phase 2 Clinical Trial Partners Product Rights MGTA-117 Targeted Conditioning: MGTA-145 Stem Cell Mobilization and Collection: CD45-ADC Targeted Conditioning: Research Plat
Slide 6: Targeted Conditioning MGTA-117
TARGETED CONDITIONING MGTA-117
Slide 7: MGTA-117: Antibody-Drug Conjugate Designed to Selectively Deplete Target Cells
MGTA-117: Antibody-Drug Conjugate Designed to Selectively Deplete Target Cells TARGETED BLOCKING Selective binding to CD117+ target cells Blocks Stem Cell Factor (SCF) binding Short half-life to rapidly clear the ADC from the body Short half-life to rapidly clear the ADC from the body Amanitin Paylo
Slide 8: Multiple CD117+ Target Cells in Bone Marrow and Blood Across Diseases
Multiple CD117+ Target Cells in Bone Marrow and Blood Across Diseases Relapsed / Refractory AML & MDS Patients High numbers of cancer blast cells in blood and bone marrow Transplant-Eligible AML & MDS Patients Limited cancer blast cells in bone marrow Gene Therapy Patients No cancer blast cells in b
Slide 9: Current Data Set & Dosing Regimen Expected to Support Move to Transplant and Gene Therapy Studies
Current Data Set & Dosing Regimen Expected to Support Move to Transplant and Gene Therapy Studies Dec 2022 AML / MDS Cohorts 1-3 Data at ASH Data submitted to regulatory agencies Enables Additional AML Cohort Data at a scientific conference in Q1 ’23 Regulatory alignment on AML / MDS transplant stud
Slide 10: MGTA-117 Anti-CD117 ADC in R/R AML and MDS-EB: Initial Findings
American Society of Hematology Helping hematologists conquer blood diseases worldwide MGTA-117, an Anti-CD117 Antibody-Drug Conjugated With Amanitin, in Participants With Relapsed/Refractory Adult Acute Myeloid Leukemia (AML) and Myelodysplasia With Excess Blasts (MDS-EB): Safety, Pharmacokinetics a
Slide 11: MGTA-117: Phase 1/2 Clinical Trial Design
MGTA-117: Phase 1/2 Clinical Trial Design Phase 1/2 Study in CD117+ Relapsed / Refractory AML and MDS-EB Key Inclusion / Exclusion Criteria CD117+ R/R AML or MDS-EB Age 18-75 with identified HSCT donor ECOG performance status ≤2 No significant organ dysfunction No systemic infections No APL, active
Slide 12: MGTA-117 Phase 1/2 Schedule of Assessments
MGTA-117 Phase 1/2 Schedule of Assessments Baseline Blood Baseline Bone Marrow Screening Peripheral Blood for RO, PK Peripheral Blood (Flow analysis) Peripheral Blood (Flow analysis) Peripheral Blood (Flow analysis) MGTA-117 Dose (IV) Bone Marrow Collection Bone Marrow Collection (Optional) End of D
Slide 13: Participant Disposition Through the DLT Observation Period
Participant Disposition Through the DLT Observation Period *Interim data through Cohort 3 is subject to further verification and analysis Cohort 3 MGTA-117 0.076 mg/kg N=5 Cohort 2 MGTA-117 0.04 mg/kg N=6 Cohort 1 MGTA-117 0.02 mg/kg N=4 Participant discontinuations from the study were all considere
Slide 14: Baseline Participant Demographics and Disease Characteristics
Baseline Participant Demographics and Disease Characteristics R/R AML study population has a poor prognosis with a high burden of disease and multiple previous lines of therapy Characteristics Age, Years, Median (range) Sex, Male/Female Total (N=15) 65 (26-74) Diagnosis, n, AML/MDS ELN Risk Classifi
Slide 15: MGTA-117 Rapidly Bound to CD117+ Cancer Blast Cells in Blood
MGTA-117 Rapidly Bound to CD117+ Cancer Blast Cells in Blood %Receptor Occupancy Receptor Occupancy (N=15) 125- 100- 75- 50- 25- A Cohort 3 (n=5) Cohort 2 (n=6) → Cohort 1 (n=4) 0 0 8 16 24 32 40 48 mean + standard deviation Time (hours) Key Results Binding of CD117+ cells observed in all particip
Slide 16: MGTA-117 Depleted CD117+ Cancer Blast Cells in Peripheral Blood
MGTA-117 Depleted CD117+ Cancer Blast Cells in Peripheral Blood Depletion in Blood (N=14) %Change in CD117+ Blasts Relative to Baseline 100 -80 -60 -40 -20 0 3000 Cohort 3 (n=5) Cohort 2 (n=5) Cohort 1 (n=4) Key Results Depletion of CD117+ cancer blast cells was observed in the blood in Cohorts 2 an
Slide 17: MGTA-117 Depleted Cancer Blast Cells in the Bone Marrow
MGTA-117 Depleted Cancer Blast Cells in the Bone Marrow Cohort 1 Cohort 2 Cohort 3 Absolute % change from baseline Key Results Greater depletion was observed in the bone marrow in Cohort 3 participants compared to previous cohorts MGTA-117 depleted cancer blast cells in blood AND bone marrow in 3 pa
Slide 18: A Single Dose of MGTA-117 Resulted in Two Participants Becoming Transplant Eligible
A Single Dose of MGTA-117 in Participants with Relapsed/Refractory AML/MDS Resulted in Two Participants Becoming Transplant Eligible Case Study: 58-year-old male with FLT3 mutation and treatment refractory AML (Cohort 1) Diagnosis Disease and Treatment Course Transplant 37% BM cancer blast cells 18%
Slide 19: MGTA-117 Was Well-Tolerated in Cohorts 1-3
MGTA-117 Was Well-Tolerated in Cohorts 1-3 Cohort 1 Cohort 2 Cohort 3 Category (N=4) (N=6) (N=5) n (%) n (%) n (%) Participants with Treatment-Emergent Adverse Events (TEAEs) TEAEs classified as dose-limiting toxicities Serious AEs (all unrelated) Grade 3 or higher TEAEs TEAEs resulting in death (al
Slide 20: Summary of Phase 1/2 Trial Results – Cohorts 1-3
Summary of Phase 1/2 Trial Results – Cohorts 1-3 Goals Clinical Observations Target Engagement: Measurable MGTA-117 binding to CD117+ target cells in Engage the blood of all participants Deplete Cell Depletion: MGTA-117 depletes target cells in the blood and bone marrow Clear Pharmacokinetics: MGTA-
Slide 21: MGTA-117 Depletion in R/R Population Provides Readthrough for Next Phase
MGTA-117 Depletion in the R/R Patient Population Provides an Important Readthrough for the Next Phase of Development Relapsed MDS / Refractory Patients AML & blast High numbers cells of cancer in blood and bone marrow BLOOD BONE MARROW DEPLETION in blood and bone marrow BLOOD BONE MARROW CD117+ Canc
Slide 22: Potential for Robust Bone Marrow Depletion in Transplant-Eligible and Gene Therapy Patients
Potential for Robust Bone Marrow Depletion in Transplant-Eligible AML/MDS and Gene Therapy Patients MGTA-117 expected to more efficiently target CD117+ blast and/or stem cells in bone marrow due to lower number or absence of blasts MGTA-117 targets CD117+ cells for DEPLETION in bone marrow Transplan
Slide 23: Anticipated Further Development in Transplant-Eligible and Gene Therapy Patients
Anticipated Further Development in Transplant-Eligible and Gene Therapy Patients Current Study Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) or (MDS-EB) Enrolling Complete Complete Complete Cohort 5* Cohort Expected Alignment with regulators on path to transplant Anticipated Next Steps: Studi
Slide 24: Potential to Address Sub-Optimal Outcomes in AML/MDS and Gene Therapy
Potential to Address Sub-Optimal Outcomes in AML/MDS and Gene Therapy Potential Outcomes Potential Impact of MGTA-117 MG stered as a single agent, single dose AML & MDS Gene Therapy Reduce disease burden prior to Reduced Intensity Conditioning (RIC) by depletion of target cancer blast cells and stem
Slide 25: MGTA-117 Next Steps
MGTA-117 NEXT STEPS Confidential
Slide 26: MGTA-117 Summary of Cohorts 1-3 and Next Steps
MGTA-117 Summary of Cohorts 1-3 and Next Steps Single Agent Depletion Activity Transition to Transplant-Eligible AML & MDS Advance into Gene Therapy MGTA-117 has shown target cell depletion in the blood and bone marrow, providing evidence of an active dose MGTA-117 is the first targeted ADC in the c
Slide 27: Acknowledgements
Acknowledgements Thank you to our trial participants and their loved ones Thank you to the 117-HEM-101 trial investigators and their site staff MGT CD117 Receptor Stem Cell Factor (SCF) STEM CELL 27
Slide 28: Q&A
Q&A
Slide 29: Appendix
APPENDIX () magenta THERAPEUTICS
Slide 30: MGTA-117 Rapidly Cleared From the Blood Without ADC Degradation
MGTA-117 Rapidly Cleared From the Blood Without ADC Degradation Pharmacokinetics (n=15) 0 500 1000 1500 MGTA-117 Concentration (ng/ml) Cohort 1 (n=4) Cohort 2 (n=6) Cohort 3 (n=5) T1/2 ≤10 hours 0 8 16 24 32 40 48 Time (hours) mean + standard deviation Key Results • Maximum concentrations of MGTA-11
Slide 31: Availability of Data Across Phase 1/2 Cohorts 1-3
Availability of Data Across Phase 1/2 Cohorts 1-3 Participant discontinuations from the study were all deemed unrelated to MGTA-117 PARTICIPANTS DOSED (N=15 for RO, Tolerability; N=12 for PK) Participants completing DLT observation period (n=11 of 15) Cohort 3 MGTA-117 0.08 mg/kg N=5 Cohort 2 MGTA-1