Aclaris Therapeutics, Inc. · NASDAQ:ACRS
Aclaris Therapeutics — Q1 2023 Earnings Presentation
26 slides from Aclaris Therapeutics's earnings presentation, May 8, 2023
Slide 1: Q1 2023 Investor Conference Call
Q1 2023 Investor Conference Call May 8, 2023 ©©Copyright Copyright2023 2023Aclaris AclarisTherapeutics, Therapeutics,Inc. Inc.AllAllrights rightsreserved reserved
Slide 2: Cautionary Note Regarding Forward-Looking Statements
Cautionary Note Regarding Forward-Looking Statements Any statements contained in this presentation that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by wo
Slide 3: Agenda
Agenda Opening Remarks Douglas Manion, Chief Executive Officer Clinical Development Update and HS Trial Gail Cawkwell, Chief Medical Officer ATI-450 Pharmacodynamic Analysis Joe Monahan, Chief Scientific Officer Financial Results Kevin Balthaser, Chief Financial Officer Closing Remarks Douglas Manio
Slide 4: Drug Development Pipeline
Drug Development Pipeline Drug Route of Development Topline Data Target Indication Candidate/Program Administration Phase Expected Immuno-Inflammatory Rheumatoid arthritis Phase 2b Q4 2023 Zunsemetinib (moderate to severe) MK2 inhibitor Oral (ATI-450) Psoriatic arthritis Phase 2a H1 2024 (moderate t
Slide 5: ATI-1777 (Topical “Soft” JAK Inhibitor)
ATI-1777 (Topical “Soft” JAK Inhibitor) (Investigational Drug Candidate) ©©Copyright Copyright2023 2023Aclaris AclarisTherapeutics, Therapeutics,Inc. Inc.AllAllrights rightsreserved reserved
Slide 6: Aiming to Develop an Effective and Safe Therapy for Atopic Dermatitis
Aiming to Develop an Effective and Safe Therapy for Atopic Dermatitis Atopic dermatitis (AD) is a ATI-1777 Goal chronic, pruritic (investigational compound) inflammatory skin condition1 • Comparable efficacy to • First-in-human Phase 2a trial • The U.S. prevalence of other topical JAKs but a in subj
Slide 7: Positive Data Demonstrated in ATI-1777 Phase 2a Study in Atopic Dermatitis
Positive Data Demonstrated in ATI-1777 Phase 2 Study in Atopic Dermatitis Phase 2a Trial Highlights % Change in mEASI - LOCF (95% CI) • ATI-1777 achieved statistically significant Primary Efficacy result in the primary efficacy Endpoint: % Change in endpoint at week 4 mEASI – LOCF • Positive trends
Slide 8: Low Plasma Levels of ATI-1777 Following Topical Application
Low Plasma Levels of ATI-1777 Following Topical Application PK Plasma Concentrations of ATI-1777 in Subjects • >86% of samples tested following ATI-1777 administration exhibited ATI-1777 Concentrations (ng/mL) blood levels below the detectable level • Average concentration in subjects receiving ATI-
Slide 9: Phase 2a Study of Zunsemetinib in Hidradenitis Suppurativa
Phase 2a Study of Zunsemetinib in Hidradenitis Suppurativa ©©Copyright Copyright2023 2023Aclaris AclarisTherapeutics, Therapeutics,Inc. Inc.AllAllrights rightsreserved reserved
Slide 10: Subject Disposition and Discontinuations
Subject Disposition and Discontinuations Enrolled N=191 Randomized (FAS=ITT) N=95 Placebo Zunsemetinib Allocation N=47 N=48 Discontinued Treatment 15 (32%) 22 (46%) 4 (8.5%) Adverse Event 11 (22.9%) 0 Lack of Efficacy 1 (2.1%) 1 (2.1%) Non-Compliance with IP 0 Reason for Discontinuation 2 (4.3%) Pro
Slide 11: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics Placebo Zunsemetinib (N=47) (N=48) Age in years Mean (SD) 36.6 (9.32) 35.1 (9.87) Female (at birth) 40 ( 85.1%) 39 ( 81.3%) White – African American - Other 57.4 - 42.6 - 0% 58.3 - 37.5 - 4.2% Duration of HS in years Mean (SD) 13.5 (9.97) 11.3 (8.28) Baselin
Slide 12: TEAEs in >1 Patient on Either Treatment Arm
TEAEs in >1 Patient on Either Treatment Arm The most common TEAEs on zunsemetinib were dizziness, headache, diarrhea and acne Treatment-Emergent Adverse Event Preferred Term Placebo (N=47) Zunsemetinib (N=48) Dizziness 0 8 (16.7%) Headache 2 (4.3%) 6 (12.5%) Diarrhea 4 (8.5%) 6 (12.5%) Acne 0 5 (10.
Slide 13: Discontinuations due to AEs
Discontinuations due to AEs 11 patients on zunsemetinib and 4 patients on placebo Of the 11 patients who Discontinuations were generally discontinued study treatment discontinued on zunsemetinib individual events except: due to adverse events. Most of due to TEAEs: these: • Were due to events that h
Slide 14: CK Elevations Were Common on Zunsemetinib and Placebo
CK Elevations Were Common on Zunsemetinib and Placebo and all Were Without Muscle Symptoms Maximum CK during the study at any point ATI-450 Placebo • 26 patients had a CK elevation at some Grade 1 (>ULN - 2.5 x ULN ) 7 5 point during the study Grade 2 (>2.5 x ULN - 5 x ULN) 3 0 – 15 on zunsemetinib
Slide 15: CK Elevations Generally Transient and Generally Resolved on Treatment
CK Elevations Generally Transient and Generally Resolved on Treatment Subject noted intense exercise CK increase assessed as unrelated to study treatment by the investigator CK only elevated before randomization Discontinued treatment due to Discontinued treatment due to asymptomatic AE of CK elevat
Slide 16: Zunsemetinib in HS: Safety Profile Consistent, Efficacy Not Demonstrated
Zunsemetinib in HS: Safety Profile was Generally Consistent with Previous Zunsemetinib Studies, while Efficacy was Not Demonstrated • ATI-450-HS-201 50 mg BID did not demonstrate efficacy in the Hidradenitis Suppurativa study • PK and PD were generally consistent with prior zunsemetinib studies • No
Slide 17: Exploratory PD Efforts – Looking toward RA2b
Zunsemetinib HS-201 Exploratory PD Efforts – Looking toward RA2b ©©Copyright Copyright2023 2023Aclaris AclarisTherapeutics, Therapeutics,Inc. Inc.AllAllrights rightsreserved reserved
Slide 18: HS-201: Exploratory Pharmacodynamic Analysis
HS-201: Exploratory Pharmacodynamic Analysis Analysis of Cytokines in Ex vivo Stimulated Analysis of HS Patient Endogenous Patient Blood Plasma Cytokines • Assay - Ex vivo LPS stimulated cytokine • Assay – Measurement of endogenous production in whole blood cytokines,chemokines and markers of • Samp
Slide 19: MK2 Pathway Cytokine Dependence and Response Durability
MK2 Pathway Cytokine Dependence and Response Durability Ex vivo LPS-Stimulated Blood Analyses Across Zunsemetinib Studies Phase 1 Phase 2a Phase 1 : MAD Phase 2a : RA Phase 2a : HS1 • Zunsemetinib potently inhibited TNFa and IL1b on day 1 suggesting that proinflammatory cytokine production in health
Slide 20: Lower Endogenous Plasma Cytokines Observed in HS vs RA Phase 2a Studies
Lower Endogenous Plasma Cytokines Observed in HS vs in RA Phase 2a Studies Median Cytokine Levels Pre-Dose Ratio of RA/HS Cytokine Levels Endogenous proinflammatory cytokines and CRP were lower in the HS phase 2a study compared with the RA phase 2a study consistent with a lower level of systemic inf
Slide 21: Zunsemetinib Modulation of Endogenous Cytokines
Zunsemetinib Modulation of Endogenous Cytokines Comparison of RA and HS Phase 2a Studies RA Study HS Study 21 © Copyright 2023 Aclaris Therapeutics, Inc. All rights reserved
Slide 22: Zunsemetinib Did Not Inhibit Anti-Inflammatory IL-1RA Cytokine
Zunsemetinib Did Not Inhibit the Anti-Inflammatory IL-1 Receptor Antagonist (IL-1RA) Cytokine in either HS or RA Phase 2a Studies RA Phase 2a Study HS Phase 2a Study The anti-inflammatory cytokine IL-1RA was elevated in both HS and RA patients and was not inhibited by zunsemetinib in contrast to the
Slide 23: Zunsemetinib Treatment Resulted in Sustained Inhibition of CRP
Zunsemetinib Treatment Resulted in a Sustained Inhibition of CRP in both RA-201 and HS-201 Studies RA Phase 2a Study HS Phase 2a Study Sustained inhibition of plasma CRP in HS patients was observed with zunsemetinib treatment similar to that observed in the RA-201 Phase 2a study 23 © Copyright 2023
Slide 24: Summary and Conclusions
Summary and Conclusions • Ex vivo stimulated cytokine inhibition in whole blood ‒ Consistent results across three studies demonstrate marked and sustained inhibition of proinflammatory cytokines and no evidence of tachyphylaxis • Endogenous pharmacodynamic plasma biomarker analysis ‒ A subset of cyt
Slide 25: Q1 2023 Financial Results Highlights
Q1 2023 Financial Results Highlights Q1 2023 total revenue • Licensing revenue increased driven primarily by higher royalties from licensed IP of $2.5M, up 74% YoY • Research and development expense increased by $8.3M, driven by ‒ Zunsemetinib clinical trials in RA ‒ ATI-1777 in AD Q1 2023 net loss
Slide 26: Q&A Session
Q&A Session ©©Copyright Copyright2023 2023Aclaris AclarisTherapeutics, Therapeutics,Inc. Inc.AllAllrights rightsreserved reserved