Aclaris Therapeutics, Inc. · NASDAQ:ACRS
Aclaris Therapeutics — Investor Presentation (January 2025)
33 slides from Aclaris Therapeutics's investor presentation, Jan 13, 2025
Slide 1: Investor Presentation: Corporate Overview January 2025
I N V E S T O R P R E S E N T A T I O N Corporate Overview January 2025
Slide 2: Disclaimer and Cautionary Note Regarding Forward-Looking Statements
2 Disclaimer and 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
Slide 3: Biotechnology Company Focused on Immuno-inflammatory Diseases
3 Biotechnology Company Focused on Immuno-inflammatory Diseases with Large and Small Molecule Therapeutics ATI-045 – monoclonal antibody targeting thymic stromal lymphopoietin (TSLP) ATI-052 – bispecific antibody targeting both TSLP and interleukin-4 receptor (IL4R) ATI-2138 – oral inhibitor of ITK/
Slide 4: Experienced Leadership Team
4 Experienced Leadership Team 25+ years life sciences experience Successful serial entrepreneur; founder and leader of several life science companies Board certified Dermatologist DR. NEAL WALKER Interim CEO & Chairman JOE MONAHAN, PHD Chief Scientific Officer 35+ years pharmaceutical research exper
Slide 5: Broad Immunology Development Pipeline
5 PRECLINICAL PHASE 1 PHASE 2 PHASE 3 PARTNER ATI-045 TSLP mAb Subcutaneous Severe Asthma CTTQ (China) Chronic Rhinosinusitis with Nasal Polyps CTTQ (China) Atopic Dermatitis (moderate-to-severe) COPD CTTQ (China) ATI-2138 ITK/JAK3 Inhibitor Oral Atopic Dermatitis (moderate-to-severe) ATI-052 TSLP x
Slide 6: ATI-045: Anti-TSLP Monoclonal Antibody Program
6 ATI-045: Anti-TSLP Monoclonal Antibody Program Investigational Drug Candidate
Slide 7: TSLP Overview
7 TSLP Overview • ATI-045 (Bosakitug) is a humanized monoclonal antibody targeting thymic stromal lymphopoietin (TSLP) • TSLP - Pleiotropic and broad activity – Master regulator of type 2 (Th2) immune responses at the barrier surfaces of skin and the respiratory/ gastrointestinal tract – Drives eosi
Slide 8: ATI-045 Unique Differentiation Best-in-Class Potential
8 ATI-045 Unique Differentiation Best-in-Class Potential
Slide 9: ATI-045 Key Properties
9 ATI-045 Key Properties • Very high affinity to TSLP • Extremely low dissociation rate from TSLP*, leading to long residence time and enhanced neutralization activity • Very high potency • Unique binding characteristics to TSLP • ~23-day half-life that can potentially support an extended dosing int
Slide 10: Dissociation Kinetics and Residence Time
10 Dissociation Kinetics and Residence Time Residence Time (hours) Dissociation of TSLP from mAbs (TR-FRET) 416 402 14.3 8.11 22.1 3.59 20.7 ATI-052 ATI-045 Tezepelumab** Solrikitug/MK-8226** GSK-5784283 V2 (hu179-33)* GSK-5784283 V1 (hu3-13)* UPB-101 ATI-045 and ATI-052 demonstrate very slow dissoc
Slide 11: ATI-045 Has Greater Potency Than Other TSLP/TSLPR Antibodies
11 ATI-045 Has Greater Potency Than Other TSLP/TSLPR Antibodies TSLP Stimulated CCL17 Production from hPBMC ATI-045 is the most potent of the TSLP/TSLPR antibodies evaluated in blocking CCL17 production The bifunctional antibody, ATI-052, retains much of the potency for TSLP functional blockade comp
Slide 12: ATI-045 Competitively Positioned as Potential Best-in-Class TSLP mAb
12 ATI-045 Competitively Positioned as Potential Best-in-Class TSLP mAb • Strong differentiation vs. tezepelumab and other clinical stage anti-TSLP mAbs – Slower dissociation rate – Very high residence time – Greater potency • Unique binding characteristics • Clinical translation: – Phase 2a atopic
Slide 13: ATI-045 Respiratory Program Partnered in China
13 ATI-045 Respiratory Program Partnered in China
Slide 14: Most Clinically Advanced Development-Stage TSLP mAb in Respiratory
14 Most Clinically Advanced Development-Stage TSLP mAb in Respiratory Ongoing phase 2 clinical trials of ATI-045 (TQC2731) in multiple indications by CTTQ in China: Parallel programs in China can potentially be leveraged to accelerate development timeline via data sharing with CTTQ Severe Asthma1 •
Slide 15: ATI-045 Atopic Dermatitis Program
15 ATI-045 Atopic Dermatitis Program Potential First-in-Class TSLP mAb for AD
Slide 16: Clinical Translation: ATI-045 Phase 2a POC Monotherapy
16 Clinical Translation: ATI-045 Phase 2a (US-Based) POC Monotherapy PRIMARY OBJECTIVES • To evaluate the efficacy, safety and tolerability of ATI-045 as monotherapy in subjects with moderate to severe AD SECONDARY OBJECTIVES • To evaluate the pharmacokinetics, immunogenicity and pharmacodynamic bio
Slide 17: ATI-045 Exposure and Efficacy Time Profile
17 ATI-045 Exposure and Efficacy Time Profile Demonstrated Sustained Clinical Response After the Last Dose • A time lag in efficacy response relative to exposure was observed both while the drug was onboard and after the last dose • EASI-75 sustained response after the last dose supports the possibi
Slide 18: ATI-045 Demonstrated Improvement in Efficacy Measures (Week 26)
18 ATI-045 Demonstrated Improvement in Efficacy Measures (Week 26, N=17) EASI 75 % @ Week 26 EASI 90 % @ Week 26 EASI 100 % @ Week 26 IGA 0/1 @ Week 26 94% 65% 24% 88% Data on file % of Patients Achieving EAS175 or EAS190 % of Patients Achieving IGA 0/1 Time (Week) 0% 10% 20% 30% 40% 50% 60% 70% 80%
Slide 19: Comparison to Dupilumab Mono, Combo, and Tezepelumab Combo Studies
19 Comparison to Dupilumab Mono, Combo, and Tezepelumab Combo Studies** 1. N Engl J Med. 2016 Dec 15;375(24):2335-2348. [SOLO1:NCT02277743; SOLO2:NCT02277769]; 2. 16-week study; 3. J Am Acad Dermatol. 2019 Apr;80(4):1013-1021. [NCT02525094]; 4. Lancet. 2017 Jun 10;389(10086):2287-2303. [NCT02260986]
Slide 20: ATI-052: Anti-TSLP x IL4R Bispecific Antibody Program
20 ATI-052: Anti-TSLP x IL4R Bispecific Antibody Program Investigational Drug Candidate
Slide 21: ATI-052: Key Asset Highlights
21 ATI -052: Key Asset Highlights • Bispecific utilizing same antibody binding regions of ATI -045 combined with IL4R, inhibiting TSLP upstream and immune cells downstream of the Th2 cascade • Anti -TSLP mAb component has Fc engineered to bind more tightly to FcRn, potentially extending half -life •
Slide 22: ATI-052 Exhibits Greater Cellular Bioactivity than Tezepelumab plus Dupilumab
22 ATI-052 Exhibits Greater Cellular Bioactivity than the Combination of Tezepelumab and Dupilumab on CCL17 Release Data on file Effect on CCL17 Release Induced by 10 ng/mL IL4 plus 10 ng/mL TSLP (Ex vivo PBMC assay) 10 -3 10 -2 10 -1 10 0 10 1 10 2 10 3 0.0 0.5 1.0 1.5 2.0 Ab Concentration (nM) CCL
Slide 23: ATI-2138: Novel ITK/JAK3 Inhibitor for T Cell-Mediated Diseases
23 ATI-2138: A First-Generation Novel ITK/JAK3 Inhibitor for T Cell-Mediated Diseases Investigational Drug Candidate
Slide 24: ATI-2138: Oral Covalent ITK & JAK3 Inhibitor for Autoimmune Disease
24 ATI-2138: Oral Small Molecule Covalent IL-2-Inducible Tyrosine Kinase (ITK) & JAK3 Inhibitor for Autoimmune Disease • ATI-2138 is an investigational oral compound which interrupts T cell receptor (TCR) signaling by inhibiting ITK and JAK3 signaling of common γ chain cytokines in lymphocytes (incl
Slide 25: ATI-2138: Fast Follower and Best-in-Class Potential vs Ritlecitinib
25 ATI-2138: Fast follower and Best-in-Class Potential vs Ritlecitinib • Ritlecitinib approved in Alopecia Areata • ATI-2138 is 44.4x more potent than ritlecitinib for inhibiting αCD3 induced IFNγ production (ITK) and 5.4x more potent for inhibiting JAK3 dependent IL-2 induced IFNγ production in hum
Slide 26: ATI-2138 and CPI-818 (Soquelitinib) Potency Comparison
26 ATI-2138 and CPI-818 (Soquelitinib) Potency Comparison • ATI-2138 is 15-38x more potent than CPI-818 in inhibiting the ITK enzyme activity • ATI-2138 is significantly more potent than CPI-818 in blocking the Th2 derived cytokines, IL4, IL-5 and IL-13 (~100x) 0 0.01 0.1 1 3 10 0 50 100 150 200 250
Slide 27: Rationale for Dual Inhibition of ITK and JAK3
27 Rationale for Dual Inhibition of ITK and JAK3 ITK Inhibition • Atopic dermatitis (AD) is a Th2 cell driven disease and ITK inhibition blocks Th2 cell differentiation/activation and production of IL-4 and IL-13 – Dupilumab (anti-IL4Ra) and tralokinumab (anti-IL-13) are efficacious in AD • Topical
Slide 28: Phase 2a Trial Design of ATI-2138 in Atopic Dermatitis
28 Phase 2a Trial Design of ATI-2138 in Atopic Dermatitis • Open-label design • Total 12 weeks treatment • 10mg BID dosing • Safety, PK • PD: RNA analysis, proteomics, IHC to analyze specific pathway inhibition • EASI-50, -75, -90, % change in EASI • Change in vIGA, % achieving IGA-TS • % change BSA
Slide 29: Wide Array of Disease Targets for ATI-2138
29 Wide Array of Disease Targets for ATI-2138 Alopecia Areata IBD Vitiligo Atopic Dermatitis cGvHD Genital Psoriasis Acute Inflammatory Psoriasis Asthma RA Crohn’s Disease Ulcerative Colitis Psoriatic Arthritis Atopic Palmoplantar Dermatitis Pustulosis Alopecia Areata Peripheral T cell Lymphoma Celi
Slide 30: Next-Generation Selective ITK Inhibitor
30 Next-Generation Selective ITK Inhibitor
Slide 31: Selective ITK Inhibition Impacts Th2 Mediated Disease
31 Selective ITK Inhibition Impacts Th2 Mediated Disease • ITK has a nonredundant role in the differentiation and activation of TH2 and TH 17 cells • Blockade of TH2 function inhibits production of IL-4 and IL-13, two cytokines with demonstrated importance in atopic and allergic diseases • Goal of n
Slide 32: Rich Clinical Catalyst Calendar
32 Rich Clinical Catalyst Calendar 2025 ATI-045 Severe Asthma Ph. 2 Data (CTTQ) First Half 20251 ATI-045 CRSwNP Ph. 2 Data (CTTQ) First Half 20251 ATI-2138 Atopic Dermatitis Ph. 2 Top Line Data First Half 2025 ATI-052 IND Submission and Start of Ph. 1 Program First Quarter 2025 2026 ATI-045 Atopic D
Slide 33: Company Summary
33 Company Summary 1. After the upfront payment obligations under the Biosion license agreement and expected private placement net proceeds of $77M. 2. Without giving effect to additional business development transactions or financing activities. Proven track record of R&D, business development and
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