Slide 1: 2024 EHA Management Call Clinical Data Updates
Exhibit 99.2 2024 EHA Management Call Clinical Data Updates: Bitopertin, DISC-0974, and DISC-3405 June 14, 2024
Slide 2: Disclaimer and FLS
Disclaimer and FLS This presentation includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These forward-looking statements include express or implied statements relating to Disc's management team's expectations, hopes, beliefs,
Slide 3: Investigational agents not approved for use
Bitopertin, DISC-0974, and DISC-3405 are investigational agents and are not approved for use as therapies in any jurisdiction worldwide 3
Slide 4: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated AURORA Data Will Savage, MD, PhD, Chief Medical Officer DISC-0974 03 • Updated Data in Anemia of Myelofibrosis Will Savage, MD, PhD, Chief Medical Officer DISC-3405 04 • Healthy Volun
Slide 5: Bitopertin: Summary of AURORA and BEACON Data Updates
Bitopertin: Summary of Phase 2 AURORA and BEACON Data Updates Additional analysis of AURORA data confirmed bitopertin drug activity and meaningful impact on multiple aspects of EPP. Key findings: Confirmed drug Time course of Greater PPIX Generally well activity with phototoxic reactions and reducti
Slide 6: DISC-0974: Summary of Updated Data from Phase 1b Study in MF
DISC-0974: Summary of Updated Data from Phase 1b Study in MF Updated data from Phase 1b study in MF continued to demonstrate positive impacts on anemia with high response rates. Key findings: Positive impact on Substantial Generally well hemoglobin and reduction in Durable response tolerated at all
Slide 7: DISC-3405: Summary of Healthy Volunteer SAD Data
DISC-3405: Summary of Healthy Volunteer SAD Data Single-ascending dose portion of the healthy volunteer study of DISC-3405 demonstrated proof of mechanism. Key findings: Sustained reductions in iron Positive impact on Generally well Substantial levels; >50% at the hematologic tolerated at all increa
Slide 8: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated AURORA Data Will Savage, MD, PhD, Chief Medical Officer DISC-0974 03 • Updated Data in Anemia of Myelofibrosis Will Savage, MD, PhD, Chief Medical Officer DISC-3405 04 • Healthy Volun
Slide 9: Bitopertin: Investigational Oral, Selective GlyT1 Inhibitor
Bitopertin: Investigational Oral, Selective GlyT1 Inhibitor In multiple clinical studies by Roche, bitopertin was observed to modulate heme biosynthesis by blocking uptake of glycine in erythrocytes +Succinyl ALAS CoA ALAD HMBS FECH Glycine ferrochelatase UROS Iron Critical and initiating precursor
Slide 10: Erythropoietic Protoporphyria (EPP)
Erythropoietic Protoporphyria (EPP) Rare, debilitating, and lifelong condition characterized by extreme pain and damage to skin caused by light Genetic condition caused by defective heme biosynthesis – deficient enzyme ferrochelatase • Lifelong and presents in early childhood • Caused by accumulatio
Slide 11: Bitopertin: Potential Disease-Modifying Treatment
Bitopertin: Potential Disease-Modifying Treatment Designed to reduce disease-causing PPIX by limiting uptake of glycine into developing erythrocytes EPP and XLP Patients Bitopertin Treatment High PPIX Levels Designed to Reduce PPIX Levels ↓ Glycine Glycine Heme Heme ALAS2 ALAS2 FECH FECH X X (+++) (
Slide 12: PPIX in EPP: Phototoxicity in Mice
PPIX in EPP: Phototoxicity in Mice GlyT1 inhibition significantly ameliorated skin lesions after UV exposure and degree of skin lesion correlated with PPIX levels Skin Lesions at Day 18 D14 PPIX 1500 Vehicle 1000 40% 500 0 Disc Note: Initial study data; EPP mice were dosed with either vehicle (N=4)
Slide 13: EPP Development Program: BEACON and AURORA Studies
EPP Phase 2 Development Program BEACON and AURORA Studies EPP; N = 75 (fully enrolled) EPP and XLP; N = >22 US (study opened October ’22) Australia (study opened July ’22) Open-Label, randomized, 24-week study Double-blind, placebo-controlled, 17-week study 13
Slide 14: AURORA Study: Disposition and Baseline Characteristics
AURORA Study: Disposition and Baseline Characteristics Placebo Bitopertin 20 mg Bitopertin 60 mg (n=24) (n=26) (n=25) Randomized 24 26 25 Completed Study 24 26 22 Discontinued Prior to Day 121 0 0 3 Characteristic Mean Age, years 42.3 45.0 47.8 Female, n (%) 12 (50%) 14 (54%) 12 (48%) White, n (%) 2
Slide 15: AURORA Met Primary Endpoint
AURORA Met Primary Endpoint Statistically significant reductions in whole-blood (WB) metal-free PPIX Bitopertin reduced PPIX levels consistent with BEACON, taking ~6-8 weeks to reach max reduction Significant reductions observed in both 20 mg and 60 mg doses PPIX Over Time 20 +8.0% 0 -20 -21.6% (p=0
Slide 16: Key Secondary Endpoint: Cumulative time in light without pain
Updated AURORA Data: Key Secondary Endpoint Cumulative time in light without pain Bitopertin treatment effect similar to BEACON results Did not meet statistical significance due to strong performance of placebo arm Mean Cumulative 4-month Total Time in Light Without Pain (hr) 133.9 175.1 153.1 0 50
Slide 17: Time in Light Without Pain: Post-hoc longitudinal analysis
Updated AURORA Data: Time in Light Without Pain Post-hoc longitudinal analysis adjusted for baseline Statistically significant improvements in daily time in light compared to placebo Meaningful changes in daily time in light relative to baseline Sunlight Exposure Over 2-Week Intervals 28 Change from
Slide 18: Updated AURORA Data: Light Tolerance
Difference vs. Placebo in Daily Sunlight Exposure Mean (hr) Updated AURORA Data: Light Tolerance Timing of PPIX reduction aligns with the time course of increases in sunlight tolerance Change in PPIX and Placebo-Corrected Sunlight Exposure for 60 mg Group 18
Slide 19: Phototoxic Reactions with Pain
Updated AURORA Data: Phototoxic Reactions with Pain Dose-dependent reduction in rate of phototoxic reactions with pain, reaching statistical significance in the 60 mg dose group Max pain score reduced with bitopertin Incidence Rate Ratio of New Phototoxic Reactions with Pain vs. Placebo 0% -25% -60.
Slide 20: Phototoxic Reactions with Pain: time course
Updated AURORA Data: Phototoxic Reactions with Pain Consistent with profile for PPIX reductions reaching a nadir, time course of phototoxic reactions showed greater bitopertin treatment effect during the last 60 days of study First 30 days Last 60 days Participants reporting new phototoxic reactions
Slide 21: Patient-Reported Outcomes
Updated AURORA Data: Patient-Reported Outcomes Dose-dependent improvements in Patient Global Impression of Change (PGIC), reaching statistical significance in the 60 mg dose group at end of study Improved PGIC responses are associated with greater reductions in PPIX PGIC: “Since the start of the stu
Slide 22: PPIX Change and Light Tolerance
Updated AURORA Data: PPIX Change and Light Tolerance Greater PPIX reductions in bitopertin participants reporting no phototoxic reactions (-36.5%) vs phototoxic reactions (-4.0%) PPIX reductions associated with improvements in multiple measures of light tolerance Tertiles of PPIX Change PPIX Decreas
Slide 23: Safety and Tolerability
Safety and Tolerability • No serious adverse events reported with bitopertin • Stable hemoglobin levels • Favorable safety profile consistent with prior studies enrolling >4000 participants Bitopertin 20 mg Bitopertin 60 mg Placebo (n=26) (n=25) (n=24) Participants with any TEAE, n (%) 18 (75%) 20 (
Slide 24: Summary of EPP Bitopertin Data
Summary of EPP Bitopertin Data BEACON and AURORA Studies Targets underlying Significant reductions in PPIX Significant reductions in PPIX pathophysiology of EPP 40% vs placebo >40% vs baseline Significant improvement Time-dependent, 2x improvements Significant 3x increase in sunlight in sunlight tol
Slide 25: Summary of Updated Bitopertin Data
Summary of Updated Bitopertin Data Bitopertin demonstrated meaningful impact on key aspects of EPP Increases Decreases Reduces Improves Light phototoxic PPIX QoL Tolerance reactions ➢ Next Steps • End of Phase 2 meeting in second half of 2024; initiation of a pivotal study in 1H 2025 • Range of avai
Slide 26: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated AURORA Data Will Savage, MD, PhD, Chief Medical Officer DISC-0974 03 • Updated Data in Anemia of Myelofibrosis Will Savage, MD, PhD, Chief Medical Officer DISC-3405 04 • Healthy Volun
Slide 27: DISC-0974: Novel Anti-HJV mAb to Suppress Hepcidin
DISC-0974: Novel Anti-HJV mAb to Suppress Hepcidin Designed to enhance iron availability to address a wide range of hematologic disorders Enables Reduces Increases RBC Hepcidin Iron Production Inhibits endogenous Releases iron stores Potential to treat production of hepcidin Enables GI absorption wi
Slide 28: Hepcidin is a Key Driver of Myelofibrosis Anemia
Hepcidin is a Key Driver of Myelofibrosis (MF) Anemia Anemia is severe and prevalent in MF and can limit treatment Hepcidin Levels are Elevated in MF Anemia of MF ~ 12× higher than control and associated with severity of anemia and transfusion burden 6.5 Est. # Patients • 25,000 patients (US) 6 • ~8
Slide 29: Updated DISC-0974 MF Data: Baseline and Demographics
Updated DISC-0974 MF Data: Baseline and Demographics Data as of April 29, 2024 DISC-0974 14 mg DISC-0974 28 mg DISC-0974 50 mg DISC-0974 75 mg DISC-0974 100 mg (N=1) (N=7) (N=12) (N=8) (N=6) Age, median (range), years 70 71 (57, 89) 70.5 (31, 83) 74 (58, 84) 67.5 (53, 79) Time since MF diagnosis, me
Slide 30: Hepcidin and Iron
Updated DISC-0974 Anemia of MF Data: Hepcidin and Iron DISC-0974 demonstrated decreases in hepcidin and increases in serum iron Impact was consistent across all treated participants Median Serum Hepcidin Median Serum Iron 80 400 14 mg (n=1) 14 mg (n=1) 70 28 mg (n=7) 28 mg (n=7) 60 300 50 mg (n=12)
Slide 31: Hematologic Response
Updated DISC-0974 Anemia of MF Data: Hematologic Response DISC-0974 demonstrated sustained increases in hemoglobin across dose groups All evaluable participants with baseline transfusion requirement had at least a 50% reduction in transfusions over a rolling 8-week window on study compared to baseli
Slide 32: Hemoglobin Response in NTD Participants
Updated DISC-0974 Anemia of MF Data: Hemoglobin Response in NTD Participants Hemoglobin responses of ≥1.5 g/dL increase were achieved in 68.9% of NTD participants For participants who have completed at least 16 weeks of the study, 60% of NTD had a mean hemoglobin response of 1.5 g/dL above baseline
Slide 33: Safety
Updated DISC-0974 Anemia of MF Data: Safety Generally well tolerated at all evaluated dose levels Adverse events at least possibly 14 mg 28 mg 50 mg 75 mg 100 mg related to DISC-0974 (N=1) (N=7) (N=12) (N=8) (N=6) Participants with event (n) 0 3 5 1 1 Diarrhea 0 1 2 1 0 Injection site bruising 0 1*
Slide 34: Summary of Updated DISC-0974 MF Data
Summary of Updated DISC-0974 MF Data 60% Decreased 68.9% of NTD pts had hepcidin & of NTD pts had Hgb response increased Hgb response sustained for >1.5g/dL iron >12 weeks* 100% of pts with Generally 1 of 2 baseline well TD pts transfusions had reached TI tolerated >50% reduction *for participants w
Slide 35: Summary of DISC-0974 in MF Anemia
Summary of DISC-0974 in MF Anemia DISC-0974 demonstrated improved hemoglobin response and transfusion burden in MF Durably Reduces Reduces Increases increases transfusion hepcidin iron hemoglobin burden ➢ Next Steps • End of Phase 1b meeting with regulators in H2 2024 • Initiation of Phase 2 study b
Slide 36: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated AURORA Data Will Savage, MD, PhD, Chief Medical Officer DISC-0974 03 • Updated Data in Anemia of Myelofibrosis Will Savage, MD, PhD, Chief Medical Officer DISC-3405 04 • Healthy Volun
Slide 37: Anti-TMPRSS6 mAb Induces Hepcidin
Anti-TMPRSS6 mAb Induces Hepcidin Designed to limit iron levels with potential to address a wide range of hematologic disorders Limits Modulates Increases Iron RBC Hepcidin Availability Production Enables Endogenous Promotes Iron Restriction Erythrocytosis (PV) Production of Hepcidin Decreases GI Ab
Slide 38: DISC-3405 Development Plans
DISC-3405 Development Plans Phase 1 in healthy volunteers ongoing; aim to advance program into POC studies with focus on polycythemia vera Phase 2 Proof-of-Concept Study in Polycythemia Vera • Strong proof of therapeutic hypothesis; clarity on regulatory development path Phase 1 SAD/MAD in HV Initia
Slide 39: DISC-3405 Phase 1 Healthy Volunteers Study Overview
DISC-3405 Phase 1 Healthy Volunteers Study Overview Today’s Focus Single Ascending Dose Multiple Ascending Dose 300 mg SC Dose Level 2 SC (Q4W) 150 mg SC Dose Level 1 SC (Q4W) 75 mg SC 37.5 mg SC 75 mg IV N=8 per Cohort (6 Active, 2 Placebo) Assessment of safety, PK, hepcidin, and iron after each do
Slide 40: Healthy Volunteer SAD: Baseline and Demographics
DISC-3405 Phase 1 Healthy Volunteer SAD: Baseline and Demographics Placebo 37.5 mg SC 75 mg IV 75 mg SC 150 mg SC 300 mg SC Characteristic n = 10 n = 6 n = 6 n = 6 n = 6 n = 6 Age, years 48.6 (39-62) 52.7 (42-64) 36.8 (23, 49) 57.3 (49, 61) 44.0 (25, 57) 34.0 (22, 38) Gender, Female, n (%) 2 (20) 5
Slide 41: Initial DISC-3405 HV Data: PK and Hepcidin
Initial DISC-3405 HV Data: PK and Hepcidin Dose-dependent PK profiles DISC-3405 demonstrated dose-related hepcidin increases Pharmacokinetics Mean Change from Baseline in Serum Hepcidin Serum Hepcidin Pharmacokinetics 500 100000 Placebo SC (n=8) 37.5 mg SC (n=6) 37.5 mg SC (n=6) 400 75 mg SC (n=6) 1
Slide 42: Initial DISC-3405 HV Data: Iron Parameters
Initial DISC-3405 HV Data: Iron Parameters Mean serum iron reduction of more than 50% from baseline was achieved for both 150- and 300-mg doses Serum iron reductions were sustained for at least 4 weeks, supportive of monthly SC dosing Mean Change from Baseline in Serum Iron Mean Change from Baseline
Slide 43: Initial DISC-3405 HV Data: Hematologic Response
Initial DISC-3405 HV Data: Hematologic Response A single 300-mg dose of DISC-3405 demonstrated meaningful reductions in hematologic parameters (reticulocyte hemoglobin, hemoglobin, and hematocrit) Reticulocyte Hemoglobin (300 mg) Hemoglobin (300 mg) Hematocrit (300 mg) Reticulocyte Hemoglobin (CHr)
Slide 44: Initial DISC-3405 HV Data: Safety
Initial DISC-3405 HV Data: Safety Generally well tolerated at all evaluated dose levels; no serious AEs, > Grade 2 AEs, or AEs leading to study withdrawal were reported Placebo 37.5 mg SC 75 mg IV 75 mg SC 150 mg SC 300 mg SC Adverse Event n = 10 n = 6 n = 6 n = 6 n = 6 n = 6 Sore Throat 0 0 1 0 0 0
Slide 45: Summary of Healthy Volunteer SAD Data
Summary of Phase 1 Healthy Volunteer SAD Data Single-dose SC administration of DISC-3405 demonstrated dose-dependent increases in hepcidin and corresponding reductions in serum iron levels across all dose levels >50% reductions in mean serum iron were observed in patients that received 150 mg and 30
Slide 46: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated AURORA Data Will Savage, MD, PhD, Chief Medical Officer DISC-0974 03 • Updated Data in Anemia of Myelofibrosis Will Savage, MD, PhD, Chief Medical Officer DISC-3405 04 • Healthy Volun
Slide 47: Summary of EHA Data
Summary of EHA Data DISC-0974 DISC-3405 Bitopertin Heme Synthesis Modulator Hepcidin Suppression Hepcidin Induction • Meaningful improvements on • Decreased hepcidin and • Increased hepcidin and key aspects of EPP consistent increased iron sustained for reduced serum iron across all across studies s
Slide 48: Projected Upcoming Milestones and Events
Projected Upcoming Milestones and Events Multiple additional data catalysts anticipated through the rest of the year Program Indication H1 2024 H2 2024 2025 Erythropoietic Porphyrias • Phase 2 AURORA Data • End of Ph 2 Meeting / Other • Phase 3 Initiation Pending (EPP and XLP) (March-April) Regulato
Slide 49: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated AURORA Data Will Savage, MD, PhD, Chief Medical Officer DISC-0974 03 • Updated Data in Anemia of Myelofibrosis Will Savage, MD, PhD, Chief Medical Officer DISC-3405 04 • Healthy Volun
Slide 50: Q&A
Q&A
Slide 51: Updated BEACON Data: % Change in Whole-Blood PPIX
Updated BEACON Data: % Change in Whole-Blood PPIX Bitopertin significantly reduced WB metal-free PPIX levels by >40% Dose-dependent reductions were observed across broad range of baseline whole-blood PPIX levels (140-3075 µg/dL) Overall (n=22) 20 mg (n=11) 60 mg (n=11) PPIX Changes Over Time 0 >40%
Slide 52: Updated BEACON Data: Time to Prodrome
Updated BEACON Data: Time to Prodrome Significant, time-dependent improvements in light tolerance during weekly sun exposure challenges Time to Prodrome 150 100 >3x (p<0.001 vs baseline) 50 0 0 4 8 12 16 20 24 Week Time to prodrome data from weekly sunlight-exposure challenges were averaged over a 2
Slide 53: Updated BEACON Data: Light Tolerance
Updated BEACON Data: Light Tolerance Days without Symptoms or Prodromes a 92% reduction in patient-reported full phototoxic reactions An increase in the proportion of total symptom-free days (no prodrome/early warning symptoms or full phototoxic reactions) with sunlight exposure was observed 100% 10
Slide 54: Updated BEACON Data: Measures of Quality of Life
Updated BEACON Data: Measures of Quality of Life Nearly all participants reported improvements in multiple quality-of-life measures at end of study “Since the start of the study, how would you rate the change in your EPP?” Patient Global Patient Global Impression of Change Impression of Change Much
Slide 55: Updated BEACON Data: Precedented Pivotal Endpoint
Updated BEACON Data: Precedented Pivotal Endpoint Cumulative Time in Light on Days without Pain Cumulative total time in light observed over 6-month treatment period with bitopertin represents >3x increase relative to historical control Improvements in average daily light tolerance with bitopertin i
Slide 56: Updated BEACON Data: Safety and Tolerability
Updated BEACON Data: Safety and Tolerability • No serious adverse events • Stable mean Hgb levels; no anemia AEs reported • Favorable safety profile consistent with prior studies enrolling >4000 participants Bitopertin 20 mg Bitopertin 60 mg Total (n=11) (n=11) (n=22) Participants with any TEAE 9 (8