Immunic, Inc. · NASDAQ:IMUX
Immunic — Technical Presentation (December 2021)
99 slides from Immunic's technical presentation, Dec 14, 2021
Slide 1: IMU-935: Phase 1 SAD/MAD Data and Preclinical Update
Immunic Therapeutics IMU-935: Phase 1 SAD/MAD Data in Healthy Human Subjects and Preclinical Update NASDAQ: IMUX | December 14, 2021
Slide 2: Cautionary Note Regarding Forward-Looking Statements
Cautionary Note Regarding Forward-Looking Statements This presentation contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities
Slide 3: Development Pipeline
Development Pipeline Program Target Preclinical Phase 1 Phase 2 Phase 3 Key 2021/22 Milestones Relapsing Multiple Sclerosis (RMS) Progressive Multiple Sclerosis (PMS) vidofludimus calcium DHODH Ulcerative Colitis (UC) § Phase 2 UC: top-line data expected in Q2/2022 (IMU-838) Crohn’s Disease (CD) Pri
Slide 4: IMU-935: Phase 1 SAD/MAD Data and Preclinical Update
IMU-935: Phase 1 SAD/MAD Data in Healthy Human Subjects and Preclinical Update Phase 1 Clinical Trial of IMU-935 01 § Trial Design and Status § Results Part A: Single Ascending Doses § Results Part B: Multiple Ascending Doses § Ongoing Part C in Psoriasis Patients 02 Newly Obtained In Vivo Data 03 S
Slide 5: Autoimmune Diseases and IMU-935
Autoimmune Diseases and IMU-935 Unmet Need in Psoriasis Care IL-17 in Autoimmune Diseases High IL-17 UNMET MEDICAL antibodies NEED § Autoimmune diseases affect millions of patients worldwide[1] Addressable area IL-12/IL-23 for next- § Th17/IL-17/RORγt axis plays an important role in auto immunity-re
Slide 6: Phase 1 Clinical Trial of IMU-935
01 Phase 1 Clinical Trial of IMU-935 Results Part A: Results Part B: Trial Design Single Multiple and Status Ascending Doses Ascending Doses Ongoing Part C in Psoriasis Patients
Slide 7: Phase 1 Clinical Trial of IMU-935
01 Phase 1 Clinical Trial of IMU-935 Results Part A: Results Part B: Trial Design Single Multiple and Status Ascending Doses Ascending Doses Ongoing Part C in Psoriasis Patients
Slide 8: Clinical Trial Design and Current Status
Clinical Trial Design Phase 1 IMU-935 and Current Status PART A PART B PART C Evaluation of Evaluation of Evaluation of single ascending doses (SAD) multiple ascending doses (MAD) moderate-to-severe psoriasis patients receiving 28-day Healthy volunteers Healthy volunteers randomized treatment of eit
Slide 9: Results Part A: Single Ascending Doses
01 Phase 1 Clinical Trial of IMU-935 Results Part A: Results Part B: Trial Design Single Multiple and Status Ascending Doses Ascending Doses Ongoing Part C in Psoriasis Patients
Slide 10: Dose Escalation Scheme
Dose Escalation Scheme Part A: Single Ascending Doses Part A: Initial Lipid-Based Pilot Formulation Part A-N: Powder-in-Capsule Formulation Cohort 4 Bridging cohort Cohort 6N 200 mg IMU-935 100 mg IMU-935 BID 400 mg IMU-935 or placebo (ratio 6:2) or placebo (ratio 6:2) or placebo (ratio 6:2) Cohort
Slide 11: Summary of Safety and Tolerability Findings
Summary of Safety and Tolerability Findings Part A-N Single Doses of IMU-935 in Healthy Human Subjects Were Found to Have a Favorable Safety and Tolerability Profile No serious adverse events No dose-dependency in adverse events No maximum tolerated dose reached No trends for post-dose changes in an
Slide 12: Most Common Treatment-Emergent Adverse Events
Most Common Treatment-Emergent Adverse Events Part A-N Number (%) of subjects with TEAEs occurring in more than 2 subjects [Number of TEAEs reported] Single doses of MedDRA 300 mg 300 mg IMU-935 using the 100 mg 200 mg 300 mg 400 mg Active Placebo Preferred Term (N=5) (N=6) (N=6) fasted fed (N=6) (N
Slide 13: Summary of Safety and Tolerability Profile
Summary of Safety and Tolerability Profile Part A-N § Serious AEs (SAE) § Summary of laboratory variables - None (N=0) - No trend for changes over time for any parameter § Treatment discontinuations due to AEs - Shift tables showed no trend of individual changes - None (N=0) beyond the normal range
Slide 14: No Change in Neutrophils Compared to Placebo
Laboratory Parameters: No Change in Neutrophils Compared to Placebo Part A-N Laboratory Values Over Time Individual Laboratory Values Hematology - Neutrophils Hematology - Neutrophils Hematology Blood Neutrophils (10^9/L) Day 1 vs Baseline Hematology Blood Neutrophils (10^9/L) Day 2 vs Baseline Neut
Slide 15: No Increase of ALT Compared to Placebo
Laboratory Parameters: No Increase of ALT Compared to Placebo Part A-N Laboratory Values Over Time Individual Laboratory Values Biochemistry - ALT Biochemistry - ALT Biochemistry Serum Alanine Aminotransferase (U/L) Day 1 vs Baseline Biochemistry Serum Alanine Aminotransferase (U/L) Day 2 vs Baselin
Slide 16: No Hy's Law Range Cases Observed
Laboratory Parameters: No Hy’s Law Range Cases Observed Part A and Part A-N Combined Bilirubin vs. ALT Showed Bilirubin vs. AST Showed No Evidence of DILI Potential No Evidence of DILI Potential Hy's Law Plot: BIL vs ALT across all post-dose visits Hy's Law Plot: BIL vs AST across all post-dose visi
Slide 17: Conclusions
Conclusions Part A-N: Single Ascending Doses § The powder-in-capsule formulation provided favorable pharmaceutical properties in Part A-N of this clinical trial. § Its favorable safety and tolerability allowed smooth transition from Part A (SAD) to Part B (MAD) in healthy human subjects.
Slide 18: Results Part B: Multiple Ascending Doses
01 Phase 1 Clinical Trial of IMU-935 Results Part A: Results Part B: Trial Design Single Multiple and Status Ascending Doses Ascending Doses Ongoing Part C in Psoriasis Patients
Slide 19: Design of Part B: Multiple Ascending Doses
Design of Part B: Multiple Ascending Doses of IMU-935 Dose Escalation Scheme Study Period Screening Treatment Post treatment End of study Cohort 8 D -28 D -2 D1 D 14 D 15 D 18 D 28 150 mg IMU-935 or placebo BID over 14 days (ratio 5:2) Visits D -1 to 4 D7 D 13 to 16 D 17 D 18 D 28 Cohort 7 150 mg IM
Slide 20: Pharmacokinetic Results Part B
Pharmacokinetic Results Part B: Summary of QD and BID Dosing Regimen for IMU-935 IMU-935 concentration time profiles (log-linear scale) Favorable PK Properties for IMU-935 at Time [days] Steady-State Observed 0 7 14 Pharmacokinetic parameters 150 mg QD 150 mg BID Mean plasma concentration [ng/mL] in
Slide 21: Summary of Safety and Tolerability Findings
Summary of Safety and Tolerability Findings Part B Daily Dosing of IMU-935 in Healthy Human Subjects Over 14 Days Was Found to Have a Favorable Safety and Tolerability Profile No serious adverse events No dose-dependency in adverse events No maximum tolerated dose reached No trends for post-dose cha
Slide 22: Overall Summary of TEAE, SAE and AE Severity
Overall Summary of TEAE, SAE and AE Severity Part B Treatment Daily 14-day dosing of Category 150 mg QD 150 mg BID Active Placebo IMU-935 using the (N=6) (N=5) (N=11) (N=4) powder-in-capsule Subjects with TEAEs, n (%) 6 (100%) 4 (80%) 10 (91%) 4 (100%) formulation was found to be safe and well- Subj
Slide 23: Most Common Treatment-Emergent Adverse Events
Most Common Treatment-Emergent Adverse Events Part B Number (%) of subjects with TEAEs occurring in more than 1 subject [Number of TEAEs reported] Daily 14-day dosing of MedDRA 150 mg QD 150 mg BID Active Placebo IMU-935 using the Preferred Term (N=6) (N=5) (N=11) (N=4) powder-in-capsule formulation
Slide 24: Summary of Safety and Tolerability Profile
Summary of Safety and Tolerability Profile Part B § Serious AEs (SAE) § Summary of laboratory variables - None (N=0) - No trend for changes over time for any parameter § Treatment discontinuations due to AEs - Shift tables showed no trend of individual changes - None (N=0) beyond the normal range fo
Slide 25: No Change in Neutrophils Compared to Placebo
Laboratory Parameters: No Change in Neutrophils Compared to Placebo Part B Laboratory Values Over Time Individual Laboratory Values Hematology - Neutrophils Hematology - Neutrophils Hematology Neutrophils (10^9/L) Day 1 vs Baseline Hematology Neutrophils (10^9/L) Day 7 vs Baseline Reference Lines: N
Slide 26: No Increase in ALT Compared to Placebo
Laboratory Parameters: No Increase in ALT Compared to Placebo Part B Laboratory Values Over Time Individual Laboratory Values Biochemistry - ALT Biochemistry - ALT Biochemistry Alanine Aminotransferase (U/L) Day 1 vs Baseline Biochemistry Alanine Aminotransferase (U/L) Day 7 vs Baseline Reference Li
Slide 27: No Hy's Law Range Cases Observed
Laboratory Parameters: No Hy’s Law Range Cases Observed Part B Bilirubin vs. ALT Showed Bilirubin vs. AST Showed No Evidence of DILI Potential No Evidence of DILI Potential Hy's Law Plot: BIL vs ALT across all post-dose visits Hy's Law Plot: BIL vs AST across all post-dose visits 3xULN 3xULN 10 Hy's
Slide 28: Conclusions
Conclusions Part B: 14-Days Multiple Ascending Doses § Multiple ascending doses of IMU-935 demonstrated a favorable safety, tolerability and pharmacokinetic profile. § This allowed smooth transition from Part B (MAD) to Part C (28-day dosing in psoriasis patients) which is currently ongoing.
Slide 29: Ongoing Part C in Psoriasis Patients
01 Phase 1 Clinical Trial of IMU-935 Results Part A: Results Part B: Trial Design Single Multiple and Status Ascending Doses Ascending Doses Ongoing Part C in Psoriasis Patients
Slide 30: Ongoing First-in-Human Study: Study Design
Ongoing First-in-Human Study Part C: IMU-935 in Psoriasis Patients Study Design § Double-blind, placebo-controlled dose escalation study to evaluate safety, tolerability, pharmacodynamics and exploratory efficacy of IMU-935 in patients with moderate-to-severe psoriasis § Psoriasis patients will rece
Slide 31: Ongoing First-in-Human Study: Dose Escalation Scheme
Ongoing First-in-Human Study Part C: IMU-935 in Psoriasis Patients Dose Escalation Scheme Study Period Screening Treatment Post treatment EoS Cohort 11 (N=36) D -28 D -2 D1 D 28 D 29 D 55 D 56 Part B high dose 150 mg IMU-935 or placebo completed BID over 28 days (ratio 3:1) Visits D1 D8 D 15 D 22 D
Slide 32: Newly Obtained In Vivo Data
02 IMU-935: An Oral IL-17 Inhibitor Newly Obtained In Vivo Data
Slide 33: IMU-935 Selectively Inhibits Th17 Differentiation and IL-17 Secretion
IMU-935 Selectively Inhibits Th17 Differentiation and IL-17 Secretion The differentiation towards Th17 cells is inhibited by IMU-935 The production of IL-17A and IL-17F is inhibited by IMU-935 The physiological maturation of T cells within the thymus is not affected by IMU-935 Th: T helper; IL: inte
Slide 34: IMU-935 in vitro Selectivity Confirmed, Differentiated from Other RORγt Inhibitors
IMU-935’s in vitro Selectivity on Th17 Suppression Confirmed, Well Differentiated to Other RORγt Inhibitors IL-17A 50 EV DMSO 40 IMU-935 140 (% of CD4+ T cells) MRL-871 Cintirorgon (agonist) (relative to % viable cells in vehicle) IL-17A+ cells 30 Cinitirorgon (agonist) 120 Cpd1 20 100 Vehicle IM105
Slide 35: IMU-935 Allows Normal Thymocyte Maturation in vivo (Acute)
IMU-935 Allows Normal Thymocyte Maturation in vivo Acute Model, 3 Days of Treatment In contrast to MRL-871, IMU-935 does not impact thymus size, thymocyte cell numbers or thymocyte maturation in an acute mouse § IMU-935 (100 mg/kg BID), MRL-871 (100 mg/kg BID) and Cintirorgon (30 mg/kg BID) were tes
Slide 36: IMU-935 Allows Normal Thymocyte Maturation in vivo (Chronic)
IMU-935 Allows Normal Thymocyte Maturation in vivo Chronic Model, 28 Days of Treatment In contrast to Cpd1, IMU-935 does not impact thymus size, thymocyte cell numbers or thymocyte maturation in a chronic mouse § C57BL/6j mice (male, 9wks, n=8-9 per group) were administrated with IMU-935 (100 mg/kg)
Slide 37: Favorable Safety Profile in Preclinical Studies
IMU-935 Has Shown a Favorable Safety Profile in Preclinical Studies 6-months (rats) and 28-day safety studies in rats 3-months safety studies 9-months (dog) long- and dogs completed in rats and dogs term safety studies before start of phase 1 completed in 2021 scheduled for 2022 § 3-months tox studi
Slide 38: Summary
03 IMU-935: An Oral IL-17 Inhibitor Summary
Slide 39: IMU-935: A Potentially Best-in-Class Oral IL-17 Inhibitor
IMU-935: A Potentially Best-in-Class Oral IL-17 Inhibitor § IMU-935 showed a very favorable safety, tolerability and PK profile in this phase 1 clinical trial with no serious adverse events seen in the SAD and MAD parts. § In particular, IMU-935 was safe and well-tolerated in 14-day repeated oral do
Slide 40: Outlook: Multiple Value Inflection Points Expected in 2022
Outlook: Multiple Value Inflection Points Expected in 2022 vidofludimus calcium (IMU-838) § Phase 2 top-line data in ulcerative colitis expected to be available in Q2/2022 IMU-935 § Initial phase 1b psoriasis data expected to be available in Q2/2022 § Initial phase 1 CRPC data expected to be availab
Slide 41: Thank You!
Thank You! Immunic, Inc. 1200 Avenue of the Americas Immunic AG New York City, NY 10036 Gräfelfing (Munich) USA Germany Immunic Research GmbH Weinberg Campus Halle (Saale) Jessica Breu Germany Head of IR & Communications Phone: +49-89-2080477-09 Email: ir@imux.com Immunic Australia Pty. Ltd. Web: ww
Slide 42: Extended Information Section
Phase 1 Clinical Trial of IMU-935 Extended Information Section
Slide 43: Part A: Evaluation of Single Ascending Doses
Initial Lipid-Based Pilot Formulation Part A: Evaluation of Single Ascending Doses
Slide 44: Demographics
Demographics Part A: Lipid-Based Formulation Treatment 50 mg 100 mg 25 mg 100 mg 200 mg Active Placebo food effect BID (N=6) (N=6) (N=6) (N=6) (N=6) (N=30) (N=10) In total, 40 healthy Age (years), mean 27.0 37.8 32.3 23.8 30.5 30.3 31.4 male and female Gender subjects entered Male, n (%) 2 (33%) 6 (
Slide 45: Pharmacokinetic Results: Lipid-Based Formulation
Pharmacokinetic Results Part A: Pharmacokinetic Properties of Lipid-Based Formulation IMU-935 concentration time profiles (log-linear scale) Dose-Proportional Pharmacokinetics of Lipid- Based Formulation of IMU-935 200 mg Mean plasma concentration [ng/mL] Pharmacokinetic 100 mg 25 mg 50 mg 100 mg 20
Slide 46: Overall Summary of TEAEs
Overall Summary of TEAEs Part A: Lipid-Based Formulation Treatment 50 mg 50 mg 25 mg 100 mg 200 mg 100 mg BID Active Placebo Category fasted fed (N=6) (N=6) (N=6) (N=6) (N=30) (N=10) (N=6) (N=6) Subjects with TEAEs, n (%) 6 (100%) 4 (67%) 5 (83%) 5 (83%) 5 (83%) 6 (100%) 28 (93%) 9 (90%) Subjects wi
Slide 47: Dose-Dependent Increase of Some Local Gastrointestinal Events
Dose-Dependent Increase of Some Local Gastrointestinal Events Part A: Lipid-Based Formulation Number (%) of subjects with related TEAEs [Number of related TEAEs reported] Active Treatment IMU-935 Placebo Treatment MedDRA 50 mg 50 mg 100 mg Total 50 mg 50 mg 100 mg Total Preferred Term 25 mg 100 mg 2
Slide 48: Analysis of TEAEs
Analysis of TEAEs Part A: Lipid-Based Formulation § SAEs - None § Severe TEAEs - Headache After a single dose of placebo, subject R0101-001 reported 40 minutes post-dose an episode of severe headache. The TEAE lasted 3.5 hours, was unrelated to study treatment and recovered without sequelae. § Moder
Slide 49: Analysis of Laboratory Parameters
Analysis of Laboratory Parameters Part A: Lipid-Based Formulation § Laboratory values over time - Descriptive statistics showed no trend of values over time for any parameter § Individual changes - Shift tables showed no trend of individual changes beyond the normal range for any parameter § Individ
Slide 50: Laboratory Parameters
Laboratory Parameters Part A: Lipid-Based Formulation § Narratives of TEAEs associated with laboratory parameters - Blood creatine kinase increased After a single dose of placebo, subject R0101-008 had elevated CK (mild, unrelated) at the end-of-study visit (day 14). All other post-dose values of cr
Slide 51: Pharmacokinetic Results: Formulation Comparison
Pharmacokinetic Results Part A: Comparison of Lipid-Based and Powder-in-Capsule Formulation IMU-935 concentration time profiles (log-linear scale) Comparable PK for the Two Different Oral Formulations of IMU-935 100 mg New Formulation Pharmacokinetic 100 mg lipid-based 100 mg new Mean plasma concent
Slide 52: Conclusions
Conclusions Part A: Lipid-Based Formulation § The semi-solid lipid-based formulation was adequate to enable initial non-clinical and clinical evaluations of IMU-935. § However, an ongoing effort to improve the formulation led to its replacement with a new and improved powder-in-capsule formulation d
Slide 53: Part A-N: Evaluation of Single Ascending Doses
Powder-in-Capsule Formulation Part A-N: Evaluation of Single Ascending Doses
Slide 54: Demographics
Demographics Part A-N Treatment 300 mg 100 mg 200 mg 300 mg 400 mg Active Placebo food effect (N=5) (N=6) (N=6) (N=6) (N=29) (N=10) (N=6) In total, 39 healthy Age (years), mean 26.8 35.3 23.3 21.3 33.5 28.1 33.4 male and female Gender subjects entered Male, n (%) 4 (80%) 4 (67%) 5 (83%) 2 (33%) 1 (1
Slide 55: Pharmacokinetic Results Part A-N
Pharmacokinetic Results Part A-N IMU-935 concentration time profiles (log-linear scale) Dose-Proportional PK of New Powder-in- Capsule Formulation of IMU-935 400 mg Pharmacokinetic Mean plasma concentration [ng/mL] 300 mg 100 mg 200 mg 300 mg 400 mg parameters (mean) 100 200 mg Cmax (ng/mL) 119 195
Slide 56: Pharmacokinetic Results: Minimal Food Effect
Pharmacokinetic Results Part A-N IMU-935 concentration time profiles (log-linear scale) Minimal Food Effect of New Powder-in- Capsule Formulation of IMU-935 300 mg, fasted Pharmacokinetic Mean plasma concentration [ng/mL] 300 mg, fed 300 mg fasted 300 mg fed parameters (mean) 100 Cmax (ng/mL) 304 12
Slide 57: Overall Summary of TEAEs
Overall Summary of TEAEs Part A-N Treatment 300 mg 300 mg 100 mg 200 mg 300 mg 400 mg Active Placebo Category fasted fed (N=5) (N=6) (N=6) (N=6) (N=29) (N=10) (N=6) (N=6) Subjects with TEAEs, n (%) 4 (80%) 4 (67%) 3 (50%) 5 (83%) 3 (50%) 4 (67%) 21 (72%) 8 (80%) Subjects with mild TEAEs, n (%) 4 (80
Slide 58: Analysis of Laboratory Parameters
Analysis of Laboratory Parameters Part A-N § Laboratory values over time - Descriptive statistics showed no trend of values over time for any parameter § Individual changes - Shift tables showed no trend of individual changes beyond the normal range for any parameter § Individual clinically signific
Slide 59: Laboratory Parameters
Laboratory Parameters Part A-N § Narratives of TEAEs associated with laboratory parameters After a single dose of 300 mg IMU-935 in the fed state, the subject had elevated CK (severe, unrelated) and elevated AST Blood creatine kinase (moderate, unrelated) at the end-of-study visit (day 28) only. All
Slide 60: Laboratory Parameters
Laboratory Parameters Part A-N § Narratives of TEAEs associated with laboratory parameters – Blood creatine kinase increased After a single dose of 300 mg IMU-935 in the fed state, subject R015NF-707 had elevated CK (severe, unrelated) at the end-of-study visit. The subject reported increased alcoho
Slide 61: Laboratory Parameters
Laboratory Parameters Part A-N § Narratives of TEAEs associated with laboratory parameters - Aspartate aminotransferase increased After a single dose of 300 mg IMU-935 in the fed state, subject R015NF-707 had elevated AST (moderate, unrelated) at the end-of- study visit. The subject reported increas
Slide 62: Laboratory Parameters
Laboratory Parameters Part A-N § Narratives of TEAEs associated with laboratory parameters - Neutropenia After a single dose of 100 mg IMU-935, subject R013N-204 had a neutropenia (mild, unrelated) on day 1. The subject was seen to have neutropenia already at screening (but not at baseline), hence t
Slide 63: Laboratory Parameters
Laboratory Parameters Part A-N § Narratives of TEAEs associated with laboratory parameters - Lipase increased After a single dose of placebo, subject R016N-202 had elevated lipase (mild, related) on day 2. All other post-dose values of lipase were in the normal range. The lipase increase was asympto
Slide 64: Laboratory Parameters
Laboratory Parameters Part A-N § Narratives of TEAEs associated with laboratory parameters - Transaminases increased After a single dose of 300 mg IMU-935, subject R015N-208 had elevated AST and ALT (mild, unrelated) at the end-of-study visit. The subject had an infected pilonidal cyst and was treat
Slide 65: Laboratory Parameters
Laboratory Parameters Part A-N § Narratives of TEAEs associated with laboratory parameters - Transaminases increased (cont.) After a single dose of 300 mg IMU-935, subject R015N-208 had elevated AST and ALT (mild, unrelated) at the end-of-study visit. The subject had an infected pilonidal cyst and w
Slide 66: Laboratory Parameters: Leukocytes
Laboratory Parameters: Leukocytes Part A-N Laboratory Values Over Time Individual Laboratory Values Hematology - Leukocytes Hematology - Leukocytes Hematology Blood Leukocytes (10^9/L) Day 1 vs Baseline Hematology Blood Leukocytes (10^9/L) Day 2 vs Baseline Leukocytes (10^9/L) Reference Lines: Norma
Slide 67: Laboratory Parameters: Erythrocytes
Laboratory Parameters: Erythrocytes Part A-N Laboratory Values Over Time Individual Laboratory Values Hematology - Erythrocytes Hematology - Erythrocytes Hematology Blood Erythrocytes (10^12/L) Day 1 vs Baseline Hematology Blood Erythrocytes (10^12/L) Day 2 vs Baseline Erythrocytes (10^12/L) Referen
Slide 68: Laboratory Parameters: Platelets
Laboratory Parameters: Platelets Part A-N Laboratory Values Over Time Individual Laboratory Values Hematology - Platelets Hematology - Platelets Hematology Blood Platelets (10^9/L) Day 1 vs Baseline Hematology Blood Platelets (10^9/L) Day 2 vs Baseline Platelets (10^9/L) lo Reference Lines: Normal R
Slide 69: Laboratory Parameters: AST
Laboratory Parameters: AST Part A-N Laboratory Values Over Time Individual Laboratory Values Biochemistry - AST Biochemistry - AST Biochemistry Serum Aspartate Aminotransferase (U/L) Day 1 vs Baseline Biochemistry Serum Aspartate Aminotransferase (U/L) Day 2 vs Baseline Reference Lines: Normal Range
Slide 70: Laboratory Parameters: Bilirubin
Laboratory Parameters: Bilirubin Part A-N Laboratory Values Over Time Individual Laboratory Values Biochemistry - Bilirubin Biochemistry - Bilirubin Biochemistry Serum Bilirubin (umol/L) Day 1 vs Baseline Biochemistry Serum Bilirubin (umol/L) Day 2 vs Baseline Bilirubin (umol/L) lo Reference Lines:
Slide 71: Analysis of Vital Signs
Analysis of Vital Signs Part A-N § Vital signs over time - Descriptive statistics showed no trend of values over time for any parameter § Individual changes - Shift tables showed no trend of individual changes beyond the normal range for any parameter § Individual clinically significant abnormalitie
Slide 72: Vital Signs: Pulse Rate
Vital Signs: Pulse Rate Part A-N Vital Signs Over Time Individual Vital Signs Pulse Rate Pulse Rate Pulse Rate (beats/min) Day 1 3h post vs Baseline/Day 1 pre Pulse Rate (beats/min) Day 1 6h post vs Baseline/Day 1 pre Pulse Rate (beats/min) Reference Lines: Normal Range (lo, hi) lo hi Reference Line
Slide 73: Vital Signs: Diastolic Blood Pressure
Vital Signs: Diastolic Blood Pressure Part A-N Vital Signs Over Time Individual Vital Signs Diastolic Blood Pressure Diastolic Blood Pressure Diastolic Blood Pressure (mmHg) Day 1 3h post vs Baseline/Day 1 pre Diastolic Blood Pressure (mmHg) Day 1 6h post vs Baseline/Day 1 pre Diastolic Blood Pressu
Slide 74: Vital Signs: Systolic Blood Pressure
Vital Signs: Systolic Blood Pressure Part A-N Vital Signs Over Time Individual Vital Signs Systolic Blood Pressure Systolic Blood Pressure Systolic Blood Pressure (mmHg) Day 1 3h post vs Baseline/Day 1 pre Systolic Blood Pressure (mmHg) Day 1 6h post vs Baseline/Day 1 pre Systolic Blood Pressure (mm
Slide 75: Analysis of 12-Lead Electrocardiograms
Analysis of 12-Lead Electrocardiograms Part A-N § 12-lead ECG parameters over time - Descriptive statistics showed no trend of values over time for any parameter § Individual changes - Shift tables showed no trend of individual changes beyond the normal range for any parameter - In subjects with nor
Slide 76: 12-Lead Electrocardiograms: PR Interval
12-Lead Electrocardiograms: PR Interval Part A-N 12-Lead ECGs Over Time Individual 12-Lead ECGs PR Interval PR Interval PR [msec] Day 1 3h post vs Baseline/Day 1 pre PR [msec] Day 1 6h post vs Baseline/Day 1 pre PR [msec] Reference Lines: Normal Range (lo, hi) lo hi Reference Lines: Normal Range (lo
Slide 77: 12-Lead Electrocardiograms: QRS Duration
12-Lead Electrocardiograms: QRS Duration Part A-N 12-Lead ECGs Over Time Individual 12-Lead ECGs QRS Duration QRS Duration QRS [msec] Day 1 3h post vs Baseline/Day 1 pre QRS [msec] Day 1 6h post vs Baseline/Day 1 pre QRS [msec] Reference Lines: Normal Range (N/A, hi) hi Reference Lines: Normal Range
Slide 78: 12-Lead Electrocardiograms: QTcF Interval
12-Lead Electrocardiograms: QTcF Interval Part A-N 12-Lead ECGs Over Time Individual 12-Lead ECGs QTcF Interval QTcF Interval QTcF [msec] Day 1 3h post vs Baseline/Day 1 pre QTcF [msec] Day 1 6h post vs Baseline/Day 1 pre QTcF [msec] Reference Lines: Normal Range (N/A, hi males, hi females) hi m hi_
Slide 79: Part B: Evaluation of Multiple Ascending Doses
Powder-in-Capsule Formulation Part B: Evaluation of Multiple Ascending Doses
Slide 80: Demographics
Demographics Part B Treatment 150 mg QD 150 mg BID Active Placebo In total, 15 (N=6) (N=5) (N=11) (N=4) healthy male and Age (years), mean 34.8 36.4 35.5 31.0 female subjects Gender entered part B Male, n (%) 4 (67%) 2 (40%) 6 (55%) 1 (25%) multiple dose Female, n (%) 2 (33%) 3 (60%) 5 (45%) 3 (75%)
Slide 81: Related TEAEs by Incidence and Treatment
Related TEAEs by Incidence and Treatment Part B Number (%) of subjects with related TEAEs MedDRA [Number of related TEAEs reported] Preferred Term 150 mg QD 150 mg BID Active Placebo (N=6) (N=5) (N=11) (N=4) 1 (17%) 3 (60%) 4 (36%) 1 (25%) Headache [1] [3] [4] [4] 1 (17%) 1 (9%) Electrocardiogram PR
Slide 82: Analysis of TEAEs
Analysis of TEAEs Part B § SAEs - None § Severe TEAEs - None § Moderate related TEAEs - Constipation After multiple doses of placebo BID, subject R0108-002 reported constipation (moderate, related). The TEAE occurred on day 16 (i.e., 2 days after completion of dosing), required no treatment and reso
Slide 83: Analysis of Laboratory Parameters
Analysis of Laboratory Parameters Part B § Laboratory values over time - Descriptive statistics showed no trend of values over time for any parameter § Individual changes - Shift tables showed no trend of individual changes beyond the normal range for any parameter § Individual clinically significan
Slide 84: Laboratory Parameters: Leukocytes
Laboratory Parameters: Leukocytes Part B Laboratory Values Over Time Individual Laboratory Values Hematology - Leukocytes Hematology - Leukocytes Hematology Leukocytes (10^9/L) Day 1 vs Baseline Hematology Leukocytes (10^9/L) Day 7 vs Baseline Reference Lines: Normal Range (lo, hi) Reference Lines:
Slide 85: Laboratory Parameters: Erythrocytes
Laboratory Parameters: Erythrocytes Part B Laboratory Values Over Time Individual Laboratory Values Hematology - Erythrocytes Hematology - Erythrocytes Hematology Erythrocytes (10^12/L) Day 1 vs Baseline Hematology Erythrocytes (10^12/L) Day 7 vs Baseline Reference Lines: Normal Range (lo, hi) Refer
Slide 86: Laboratory Parameters: Platelets
Laboratory Parameters: Platelets Part B Laboratory Values Over Time Individual Laboratory Values Hematology - Platelets Hematology - Platelets Hematology Platelets (10^9/L) Day 1 vs Baseline Hematology Platelets (10^9/L) Day 7 vs Baseline Reference Lines: Normal Range (lo, hi) Reference Lines: Norma
Slide 87: Laboratory Parameters: AST
Laboratory Parameters: AST Part B Laboratory Values Over Time Individual Laboratory Values Biochemistry - AST Biochemistry - AST Biochemistry Aspartate Aminotransferase (U/L) Day 1 vs Baseline Biochemistry Aspartate Aminotransferase (U/L) Day 7 vs Baseline Reference Lines: Normal Range (lo, hi) Refe
Slide 88: Laboratory Parameters: Bilirubin
Laboratory Parameters: Bilirubin Part B Laboratory Values Over Time Individual Laboratory Values Biochemistry - Bilirubin Biochemistry - Bilirubin Biochemistry Bilirubin (umol/L) Day 1 vs Baseline Biochemistry Bilirubin (umol/L) Day 7 vs Baseline Reference Lines: Normal Range (lo, hi) Reference Line
Slide 89: Analysis of Vital Signs
Analysis of Vital Signs Part B § Vital signs over time - Descriptive statistics showed no trend of values over time for any parameter § Individual changes - Shift tables showed no trend of individual changes beyond the normal range for any parameter § Individual clinically significant abnormalities
Slide 90: Vital Signs: Pulse Rate
Vital Signs: Pulse Rate Part B Vital Signs Over Time Individual Vital Signs Pulse Rate Pulse Rate Pulse Rate (beats/min) Day 1 3h post vs Baseline/Day 1 pre Pulse Rate (beats/min) Day 7 vs Baseline/Day 1 pre Pulse Rate (beats/min) Reference Lines: Normal Range (lo, hi) lo hi Reference Lines: Normal
Slide 91: Vital Signs: Diastolic Blood Pressure
Vital Signs: Diastolic Blood Pressure Part B Vital Signs Over Time Individual Vital Signs Diastolic Blood Pressure Diastolic Blood Pressure Diastolic Blood Pressure (mmHg) Day 1 6h post vs Baseline/Day 1 pre Diastolic Blood Pressure (mmHg) Day 7 vs Baseline/Day 1 pre Diastolic Blood Pressure (mmHg)
Slide 92: Vital Signs: Systolic Blood Pressure
Vital Signs: Systolic Blood Pressure Part B Vital Signs Over Time Individual Vital Signs Systolic Blood Pressure Systolic Blood Pressure Systolic Blood Pressure (mmHg) Day 1 6h post vs Baseline/Day 1 pre Systolic Blood Pressure (mmHg) Day 7 vs Baseline/Day 1 pre Systolic Blood Pressure (mmHg) Refere
Slide 93: Analysis of 12-Lead Electrocardiograms
Analysis of 12-Lead Electrocardiograms Part B: Powder-in-Capsule Formulation § 12-lead ECG parameters over time - Descriptive statistics showed no trend of values over time for any parameter § Individual changes - Shift tables showed no trend of individual changes beyond the normal range for any par
Slide 94: 12-Lead Electrocardiograms
12-Lead Electrocardiograms Part B § Narrative of TEAE associated with 12-lead ECG parameters - PR prolongation After a multiple dose of 150 mg IMU-935 QD, subject R0107-001 had a prolonged PR interval (mild, related) on day 13. The PR interval returned to normal values in the few days thereafter and
Slide 95: 12-Lead Electrocardiograms: PR Interval
12-Lead Electrocardiograms: PR Interval Part B 12-Lead ECGs Over Time Individual 12-Lead ECGs PR Interval PR Interval PR [msec] Day 1 3h post vs Baseline/Day 1 pre PR [msec] Day 7 vs Baseline/Day 1 pre PR Interval, Single Beat (msec) Reference Lines: Normal Range (lo, hi) lo hi Reference Lines: Norm
Slide 96: 12-Lead Electrocardiograms: QRS Duration
12-Lead Electrocardiograms: QRS Duration Part B 12-Lead ECGs Over Time Individual 12-Lead ECGs QRS Duration QRS Duration QRS [msec] Day 1 3h post vs Baseline/Day 1 pre QRS [msec] Day 7 vs Baseline/Day 1 pre QRS Duration, Single Beat (msec) Reference Lines: Normal Range (N/A, hi) hi Reference Lines:
Slide 97: 12-Lead Electrocardiograms: QTcF Interval
12-Lead Electrocardiograms: QTcF Interval Part B 12-Lead ECGs Over Time Individual 12-Lead ECGs QTcF Interval QTcF Interval QTcF [msec] Day 1 3h post vs Baseline/Day 1 pre QTcF [msec] Day 7 vs Baseline/Day 1 pre QTcF Interval, Single Beat (msec) Reference Lines: Normal Range (N/A, hi males, hi femal
Slide 98: Part C: Evaluation of 28-Day Multiple Ascending Doses in Psoriasis Patients
Phase 1 Clinical Trial of IMU-935 Part C: Evaluation of 28-Day Multiple Ascending Doses in Psoriasis Patients
Slide 99: Ongoing First-in-Human Study: Eligibility and Endpoints
Ongoing First-in-Human Study Part C: IMU-935 in Psoriasis Patients Eligibility Criteria Key Objectives/Endpoints § Age 18 to 65 years (inclusive) Primary: § Diagnosis of chronic plaque-type psoriasis for § Safety and tolerability at least 6 months: Secondary: - PASI score ≥ 10, or PASI score < 10 an