Slide 1: 2023 ASH Management Call Clinical Data Updates: Bitopertin and DISC-0974
Exhibit 99.2 2023 ASH Management Call Clinical Data Updates: Bitopertin and DISC-0974 December 11, 2023
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: Bitopertin and DISC-0974 are investigational agents
Bitopertin and DISC-0974 are investigational agents and are not approved for use as therapies in any jurisdiction worldwide CONFIDENTIAL 3
Slide 4: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated BEACON Data Bruce Wang, MD, Professor of Gastroenterology, University of California San Francisco Will Savage, MD, PhD, Chief Medical Officer • EPP Commercial Opportunity Jonathan Yu,
Slide 5: Bitopertin: Summary of Phase 2 BEACON Data Update
Bitopertin: Summary of Phase 2 BEACON Data Update Data presented at ASH established proof of concept and demonstrated functional benefit for EPP patients. Key findings: Significant, dose- Significant Improved patients’ Generally well dependent increases in reported quality tolerated with stable redu
Slide 6: DISC-0974: Summary of Initial Data from Phase 1b Studies in MF and CKD
DISC-0974: Summary of Initial Data from Phase 1b Studies in MF and CKD Initial data from both Phase 1b studies in MF and CKD demonstrated proof of concept and improvement in anemia. Key findings: Substantial Corresponding Positive impact on Generally well reductions in increases in iron tolerated at
Slide 7: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated BEACON Data Bruce Wang, MD, Professor of Gastroenterology, University of California San Francisco Will Savage, MD, PhD, Chief Medical Officer • EPP Commercial Opportunity Jonathan Yu,
Slide 8: Bruce Wang, MD Disclosures
Bruce Wang, MD Disclosures • Alnylam (consultant, investigator in clinical trial, grant funding) Principal • Disc Medicine (consultant, Investigator in investigator in clinical trial) Professor at UCSF • US Porphyrias Mitsubishi-Tanabe (consultant, investigator in clinical trial, grant Consortium fu
Slide 9: In EPP, a genetic mutation leads to the buildup of protoporphyrin IX (PPIX)
In EPP, a genetic mutation leads to the buildup of protoporphyrin IX (PPIX) Gly Heme In most patients, EPP is caused by deficient ferrochelatase activity due to mutations of the EPP and XLP Patients FECH gene High PPIX Levels ALAS FECH Protoporphyrin The deficiency causes a failure to convert IX pro
Slide 10: PPIX is a highly toxic and photoreactive metabolite
PPIX is a highly toxic and photoreactive metabolite PPIX molecule absorbs light radiation Absorption increases energy content and enables excess energy to be transferred to oxygen, resulting in reactive oxygen species (ROS) These oxygen species can injure tissue by membrane lipid peroxidation, compl
Slide 11: Accumulation of this toxic metabolite can cause a variety of symptoms
Accumulation of this toxic metabolite can cause a variety of symptoms Skin Hepatobiliary • • Porphyrin ring absorbs light and emits PPIX accumulation in bile canaliculae, energy and heat causing oxidative damage • • Oxidative damage to endothelial capillaries Cholelithiasis requiring surgery or impa
Slide 12: Primary manifestation is photosensitivity that can result in debilitating pain
Of these symptoms, the primary manifestation is photosensitivity that can result in debilitating pain Upon exposure to the sun, EPP patients experience disabling pain attacks that can last for days These attacks cause burning sensations, swelling, itching, and erythema, and can lead to chronic skin
Slide 13: Bitopertin: Investigational Oral, Selective GlyT1 Inhibitor
Bitopertin: Investigational Oral, Selective GlyT1 Inhibitor Bitopertin modulates heme biosynthesis by blocking uptake of glycine in erythrocytes +Succinyl ALAS CoA ALAD HMBS FECH Glycine ferrochelatase UROS Iron Critical and initiating precursor for heme UROD biosynthesis and is supplied by GlyT1 tr
Slide 14: EPP Phase 2 Development Program
EPP Phase 2 Development Program Ongoing BEACON and AURORA Trials—Enrollment Complete Today’s Focus Data Early 2024 EPP and XLP; N = >22 (fully enrolled for adults, EPP; N = 75 (fully enrolled) now enrolling adolescents) US (study opened October ’22) Australia (study opened July ’22) Open-Label, rand
Slide 15: BEACON Trial Overview
BEACON Trial Overview Enrollment data as of 20 Oct 2023 Screening Randomized, Treatment Period (6 months) OLE (28 Days) 1:1 Bitopertin 20 mg (N=11) and Bitopertin 60 mg (N=11) (Up to 6 Months) Screen D1 D2 D15 D29 D43 D71 D113 D155 D169/EOS Q8 Weeks Bitopertin 20 mg Bitopertin 60 mg Total (n=11) (n=
Slide 16: Updated BEACON Data: % Change in Whole-Blood PPIX
Updated BEACON Data: % Change in Whole-Blood PPIX Bitopertin significantly reduced whole-blood (WB) metal-free PPIX levels by >40% Dose-dependent reductions were observed across broad range of baseline whole-blood PPIX levels (144-3,410 µg/dL) PPIX Changes Over Time 0 Overall 20 mg 60 mg >40% -20 (p
Slide 17: Updated BEACON Data: PPIX and Light Tolerance
Mean Max Change in WB PPIX (%) Updated BEACON Data: PPIX and Light Tolerance Improvements in light tolerance were observed in every patients Greatest improvements in light tolerance seen in participants with any PPIX reduction ≥30% Any PPIX Reduction No PPIX Reduction ≥30% >30% 1000 800 600 400 N=11
Slide 18: Updated BEACON Data: Time to Prodrome
Updated BEACON Data: Time to Prodrome Improvements in light tolerance during sunlight-exposure challenges were significant (>3x) and increased with time Time to Prodrome 150 100 >3x 50 (p<0.001 vs baseline) 0 0 4 8 12 16 20 24 Week a 22 19 21 20 19 18 21 15 15 17 14 16 14 No. of Participants No. of
Slide 19: Updated BEACON Data: Light Tolerance Days without Symptoms or Prodromes
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%
Slide 20: 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 Impression of Change Much better No change A little better “Ov
Slide 21: 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 22: Updated BEACON Data: Safety and Tolerability
Updated BEACON Data: Safety and Tolerability Overall 20 mg 60 mg • No serious adverse events 16 • Stable mean Hgb levels; no anemia AEs reported 14 • Favorable safety profile consistent with prior studies enrolling 12 >4,000 participants 10 0 15 43 71 113 169 • Safety profile supports enrollment of
Slide 23: Key Takeaways from Updated BEACON Data
Key Takeaways from Updated BEACON Data Proof of Functional Quality of Life Safety Concept Outcomes Impact Significant Significant Patients reported Generally well reduction in PPIX improvement in an improved tolerated and no at low and high sunlight tolerance, quality of life meaningful doses includ
Slide 24: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated BEACON Data Bruce Wang, MD, Professor of Gastroenterology, University of California San Francisco Will Savage, MD, PhD, Chief Medical Officer • EPP Commercial Opportunity Jonathan Yu,
Slide 25: Historical EPP estimates likely underrepresent prevalence
Historical EPP estimates likely underrepresent prevalence Based on methodology reported in literature and patient journey Historically accepted 1:100,000 Implied # Addressable Patients ~ 3 K US ~1.6-1.8K ~2.3 K ~4.2 K ~4.3 K ~5.7 K ~ 20 K ~ 7.7 K ~4.2-4.7K ~ 5.9 K ~ 11 K ~ 11.2 K ~ 14.8 K ~ 40-50 K
Slide 26: EPP Prevalence: Est. 3-6K addressable patients in the US
EPP Prevalence: Est. 3-6K addressable patients in the US Based on analysis of ICD-10 codes in claims data US EPP Prevalence Comparable to Major Rare Diseases Prevalence of EPP Patients in the U.S. Duchenne Phenylketonuria SMA Expansion ~ 20K Misdiagnosed or have not Predicted Genetic 2 sought treatm
Slide 27: EPP patients are identifiable and can be addressed through a highly efficient operating model
EPP patients are identifiable and can be addressed through a highly efficient operating model Distribution of EPP Patients >350 Concentration of patients in key accounts enables a targeted and efficient field force = EPP Center of Excellence Source: Trinity Life Sciences; Komodo Claims Data (2016-20
Slide 28: Real world data confirm EPP has a significant impact on patients' lives
Real world data confirm EPP has a significant impact on patients’ lives across multiple domains Psychosocial Concomitant Medication 56% have anxiety Skin and/or depression 57% 30% 19% receive steroid treated get prescription <30 min. treatment with narcotics Vitamin D sun exposure before symptoms He
Slide 29: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated BEACON Data Bruce Wang, MD, Professor of Gastroenterology, University of California San Francisco Will Savage, MD, PhD, Chief Medical Officer • EPP Commercial Opportunity Jonathan Yu,
Slide 30: 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 31: Targeting HJV to Suppress Hepcidin
Targeting HJV to Suppress Hepcidin Critical and specific target for hepcidin expression Inhibiting Hemojuvelin (HJV) Prevents Hepcidin Expression and Increases Iron • Genetic validation in patients with Juvenile Hemochromatosis (lower hepcidin and elevated iron levels) • Loss-of-function mutations i
Slide 32: DISC-0974 Phase 1 SAD Healthy Volunteer Data
DISC-0974 Phase 1 SAD Healthy Volunteer Data Dosing of DISC-0974 demonstrated a reduction of hepcidin and iron mobilization DISC-0974 Reduced Hepcidin Production DISC-0974 Increased TSAT IV = intravenous; PBO = placebo; SAD = single ascending dose; SC = subcutaneous; TSAT = transferrin saturation 32
Slide 33: DISC-0974 Phase 1 Healthy Volunteer SAD Data (cont.)
DISC-0974 Phase 1 Healthy Volunteer SAD Data (cont.) Top dose (56 mg) pharmacodynamic activity improved key clinical parameters (> 1 g/dL Hgb) § 56 mg SC o Placebo Time Post Dose (Days) Conc = concentration; Hgb = hemoglobin; PK = pharmacokinetic; SAD = single ascending dose; SC = subcutaneous; TSAT
Slide 34: Hepcidin is a Key Driver of Myelofibrosis (MF) 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 • 16,000 to 18,500 patients (
Slide 35: DISC-0974 MF Anemia Trial Overview
DISC-0974 MF Anemia Trial Overview Data as of October 20, 2023 Phase 1b Dose Escalation Phase 2 Planned for Transfusion Dependent (TD) and Non-Transfusion Dependent (NTD) Design Study Population Design † • N = 1-9 per cohort , initial dose: 14mg SC • N = 40-50 • Open-label • • Open-label, adaptive d
Slide 36: Initial DISC-0974 Anemia of MF Data: Hepcidin
Initial DISC-0974 Anemia of MF Data: Hepcidin DISC-0974 decreased hepcidin in a dose-dependent manner Hepcidin decreases were consistent across all treated patients Median and Range of Serum Hepcidin after 28 mg Dose Median Serum Hepcidin 250 100 14 mg 200 80 28 mg 150 60 100 40 50 20 0 0 0 0.25 2 8
Slide 37: Initial DISC-0974 Anemia of MF Data: Serum Iron
DISC-0974 Conc (ng/mL) Initial DISC-0974 Anemia of MF Data: Serum Iron Serum iron increased in a dose-dependent manner Dosing at 28 mg led to a >75% decrease in serum hepcidin and a >75% increase in serum iron Hepcidin and Iron Change Relative to Baseline Median Serum Iron and DISC-0974 Concentratio
Slide 38: Initial DISC-0974 Anemia of MF Data: Hematologic Response
Initial DISC-0974 Anemia of MF Data: Hematologic Response Four of seven evaluable NTD subjects (57%) had >1.5 g/dL hemoglobin increase from baseline; effect was seen regardless of concomitant JAK inhibitor use 1 One of the two transfusion-dependent subjects receiving 28 mg achieved transfusion indep
Slide 39: Initial DISC-0974 Anemia of MF Data: Safety
Initial DISC-0974 Anemia of MF Data: Safety Generally well tolerated at all evaluated dose levels Majority of AEs deemed not related to DISC-0974 AEs Occurring in 14 mg DISC-0974 28 mg DISC-0974 50 mg DISC-0974 >2 Subjects (N=1) (N=7) (N=3) Any Grade Grade 3 Any Grade Grade 3 Any Grade Grade 3 Subje
Slide 40: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated BEACON Data Bruce Wang, MD, Professor of Gastroenterology, University of California San Francisco Will Savage, MD, PhD, Chief Medical Officer • EPP Commercial Opportunity Jonathan Yu,
Slide 41: Hepcidin is a Key Driver of CKD Anemia
Hepcidin is a Key Driver of CKD Anemia Anemia is a significant issue in CKD, with most patients currently untreated Anemia of CKD Hepcidin Levels Elevated in CKD Patients ~20× higher than healthy subjects and increases (NDD and DD) with disease severity 5-6M CKD Patients with Anemia (US Only) 1000 *
Slide 42: DISC-0974 NDD-CKD Anemia Trial Overview
DISC-0974 NDD-CKD Anemia Trial Overview Data as of October 20, 2023 Trial Population Phase 1b | Single-Ascending Dose 90 mg • Stage II-V CKD; Adult • Not receiving dialysis 60 mg • Hgb (g/dL) <10.5 (F), 11 (M) 40 mg • Exclude iron-deficient N = 8 per Cohort (6 Active, 2 Placebo) anemia by ferritin a
Slide 43: Initial DISC-0974 Anemia of CKD Data: Hepcidin and Iron
Initial DISC-0974 Anemia of CKD Data: Hepcidin and Iron First Cohort: 28 mg SC Meaningful reduction in serum hepcidin with corresponding increase in serum iron Similar PK/PD relationship as seen in healthy volunteers Hepcidin Changes Over Time Iron Changes Over Time Iron Changes Over Time vs. HV Saf
Slide 44: Key Takeaways from Initial DISC-0974 Data
Key Takeaways from Initial DISC-0974 Data Signal of Initial Proof Hematologic Safety of Concept Response Dose-dependent, Improvements in Generally well meaningful hemoglobin and tolerated at all reductions in transfusion burden evaluated dose hepcidin and across broad range levels increases in iron
Slide 45: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated BEACON Data Bruce Wang, MD, Professor of Gastroenterology, University of California San Francisco Will Savage, MD, PhD, Chief Medical Officer • EPP Commercial Opportunity Jonathan Yu,
Slide 46: Summary of Data
Summary of Data Bitopertin DISC-0974 Heme Synthesis Modulator Hepcidin Suppression Phase 1b/2 in Myelofibrosis and Anemia • Consistent, significant reductions in PPIX; • Initial data demonstrated: >40% on average • Consistent decrease in serum hepcidin (>75%) • Significant improvement in sunlight to
Slide 47: Disc Continues Strong Growth Trajectory Towards Becoming a Leading Hematology Company
Disc Continues Strong Growth Trajectory Towards Becoming a Leading Hematology Company Significant Accomplishments in 2023 Strong Series of Catalysts in 2024 • AURORA readout early 2024 Positive initial Phase 2 data • Regulatory interactions & Phase 3 prep Bitopertin • POC in DBA • Additional POC dat
Slide 48: Agenda
Agenda Introduction and Data Summary 01 John Quisel, JD, PhD, Chief Executive Officer Bitopertin in EPP 02 • Updated BEACON Data Bruce Wang, MD, Professor of Gastroenterology, University of California San Francisco Will Savage, MD, PhD, Chief Medical Officer • EPP Commercial Opportunity Jonathan Yu,
Slide 49: Q&A
Q&A