Aclaris Therapeutics : ATI-052 full SAD/MAD results + ATI-2138 update (44ce59)

Published: 2026-04-28 07:26:15 ET ACRS

Published on 04/28/2026 at 07:26 am EDT

April 28, 2026

Th2 Driven Indications

Total Addressable Market (TAM)

Global, 2028-2034

($ billion)

Purigo nodularis

Significant opportunity for new innovative biologics targeting indications with heterogeneous subtypes

Chronis spontaneous urticaria

Eosinophilic esophagitis

COPD Asthma Atopic

dermatitis

ATI-052: Harnesses the power of TSLP and IL-4Rα inhibition to create a potential best-in-class bispecific

Tezepelumab and Dupilumab drive multibillion dollar annual revenues across numerous indications

Combining mechanisms has the potential to better address the unmet needs across approved indications

Potential opportunities for ATI-052

Potential first line therapy

Raise efficacy ceiling

Inhibition upstream and downstream of Th2 cascade

Faster onset, better symptom control, durable, deeper, and more consistent effect

Better address breadth of inflammatory mediators involved in Th2 diseases

Improved convenience and practical dosing schedule

Potential Q3 month dosing

Effective Dual Binding of TSLP and IL-4Rα

Anti-IL4Rα scFV

Designed to inhibit immune cells downstream of the Th2 cascade

YTE Mutation

Fc engineered to bind more tightly to FcRn, potentially extending half-life

AQQ Mutation

Fc mutation limits effector functionality, potentially reducing off-target binding and potential toxicity

CH2

ATI-052

Anti-TSLP Fab

Same anti-TSLP antibody binding regions of Bosakitug, designed to inhibit TSLP upstream of the Th2 cascade

CH3

Retains dissociation kinetics, residence time, and potency advantages of bosakitug over comparator antibodies

Lower Dissociation Rate Drives Longer Residence Time

Fractional Response (yi/yo)

1.0

0.5

0.0

Dissociation of TSLP from mAbs (TR-FRET)

ATI-045

ATI-052

bosakitug

GSK-5784283 V1 (hu3-13)* GSK-5784283 V2 (hu179-33)*

Solrikitug/MK-8226** Tezepelumab**

0 1000 2000 3000 4000

Time (min)

Residence Time

416

402

TSLP

(n=3)

TSLPR1

(n=2)

14.3

8.11

22.1

3.59

20.7

ATI-052

bosakitug

Tezepelumab**

Solrikitug/MK-8226**

GSK-5784283 V2 (hu179-33)*

GSK-5784283 V1 (hu3-13)*

UPB-101

(hours)

ATI-045

ATI-052

ATI-052 demonstrates very slow dissociation kinetics from TSLP

Residence time for ATI-052 is ~30-116x longer than comparator antibodies

SPR: Residence Time based on apparent kd (dissociation constant) using standard TSLPR immobilization density and bivalent fit; *Analog mAb; **Biosimilar mAb

ATI-052 Has the Same Anti-TSLP Antibody Binding Regions of Bosakitug

Tezepelumab Bosakitug (ATI-045)

Only Bosakitug binds all six Light Chain and Heavy Chain CDRs

Bosakitug interface uniquely spans from TSLP N-terminal Y29 to C-terminal P154

Bosakitug: Extensive Binding Interface Drives Higher Retention Time and Neutralization Duration of TSLP

Simultaneous Binding of TSLP and IL-4Rα

Binding Sequence

TSLP:ATI-052

Stoichiometry*

sIL-4Ra:ATI-052

Stoichiometry*

ATI-052 capture / sIL-4Ra dose-response

n/a

2.25

ATI-052 capture / TSLP load / sIL-4Ra dose-response

1.82

2.10

ATI-052 capture / TSLP dose-response

2.04

n/a

ATI-052 capture / sIL-4Ra load / TSLP dose-response

1.83

1.97

ATI-052

Demonstrates High Affinity to Both Targets Simultaneously:

ATI-052 binds

~two molecules of TSLP and

sIL-4Rα with the potential to saturate all 4 binding sites at the same time

* determined using molecular weights based on amino acid sequence, does not account for glycosylated species

~2 molecules of sIL-4Rα bound to ATI-052 in the absence (2.25:1) and presence (2.10:1) of TSLP

~2 molecules of TSLP bound to ATI-052 in the absence (2.04:1) and presence (1.82:1) of sIL-4Rα

High Affinity to Both TSLP and IL-4Rα

ATI-052 Binds Both Targets Effectively

High affinity to either target is not altered by the binding to the other

Comparison of Affinity for sIL-4Rα Binding to ATI-052 or ATI-052:TSLP Complex

Parameter

ATI-052

ATI-052:TSLP

KD (pM)

348

215

Comparison of Affinity for TSLP Binding to ATI-052 or ATI-052:sIL-4Rα Complex

Parameter

ATI-052

ATI-052:sIL-4Rα

KD (pM)

41.2

33.9

ATI-052 is Substantially More Potent than the Combination of Dupilumab and Tezepelumab

ATI-052 Demonstrates Greater Potency than the mAb Combination

mAb Concentration

Antibody

IC50 (nM)

ATI-052

0.016

Dupilumab + Tezepelumab

0.069

Fold change

4.3

Screening

Randomization

3:1

Cohort 2 (120mg): SC, N=8 D1-113

Part A Single Ascending Dose (SAD) in Healthy Volunteers (HV)

Treatment and Follow-up Period

Cohort 1 (30mg): SC, N=8 D1-113

Cohort 3 (360mg): SC, N=8 D1-113

Cohort 4 (720mg): SC, N=8 D1-113

Part B Multiple Ascending Dose (MAD) in Healthy Volunteers

Treatment and Follow-up Period

D1 D8 D15 D22 D29 D141

Cohort 1 (240mg): SC, N=8 Q7D x 5 Doses

Screening

Randomization

3:1

Cohort 2 (480mg): SC, N=8 Q7D x 5 Doses

D15

D22

D29

D141

Supports Potential for Up to Every 3-Month Dosing

SAD Cohort 1 (30 mg)

SAD Cohort 2 (120 mg)

SAD Cohort 3 (360 mg) SAD Cohort 4 (720mg)

MAD Cohort 1 (240 mg)

MAD Cohort 2 (480 mg)

Dose proportional PK observed across pharmacologic dose range

PK results provided an estimated half-life of 45 days1

High Hurdle for Complete Inhibition

hWB Assays

Robust PD activity ex vivo hWB closely

reflects the real biological environment in patients with disease by maintaining the

0.5 ng/mL TSLP stimulation-48 hours 2 ng/mL IL-4 stimulation-48 hours

CCL17 release (% pos ctrl - unstim)

140

100

CCL17 release (% pos ctrl)

120

complex composition of fluids and cells present in circulation

Assay in human whole blood (hWB) designed to assess the following:

o TSLP stimulated CCL17 in whole blood

0.01

0.1

0.0001

0.001

[ATI-052] nM

100

0.0001

0.01

0.1

0.001

[ATI-052] nM

o IL-4 stimulated CCL17 in whole blood

hWB assay sets high biological bar: Assesses inhibition of up to 500-fold more TSLP and IL-4 than endogenous levels

5 ng/ml*

IC50 (nM)

0.025

± SEM

±0.0042

S/N

IC50 (nM)

0.203

± SEM

±0.039

S/N

41 ng/ml

*IC50 for the inhibition of TSLP-stimulated CCL17 in whole blood was lower than the Lower Limit Of Quantitation (LLOQ) for the PK

ATI-052 binds both targets effectively

with complete inhibition at pharmacologically relevant doses beyond the PK profile

Evidence of sustained inhibition of TSLP corroborate long residence time

The combination of PK duration and the strong and sustained PD effect support the potential for up to every three-month dosing

CCL17 Production (% Predose, Mean ±SEM)

TSLP Stimulated CCL17 (TARC):

Sustained, complete / near complete inhibition observed for

at least five months at 240 and 480 mg MAD dose

Potential best-in-class residence time and potency

MAD Cohort 1 (240 mg)

MAD Cohort 2 (480 mg)

CCL17 Production (% Predose, Mean ±SEM)

IL-4 Stimulated CCL17 (TARC):

Sustained complete inhibition observed for at least three months at 480 mg MAD dose

Note: No samples taken at weeks 8, 10, 14 and 18

Weeks

Placebo

SAD Cohort 1 (30 mg)

SAD Cohort 2 (120 mg)

SAD Cohort 3 (360 mg) SAD Cohort 4 (720mg)

Weeks

Robust Target Engagement + Sustained Complete Inhibition in MAD Cohorts

ATI-052 exhibited a potential best-in-class PD profile:

Dose and concentration dependent inhibition of IL-4 and TSLP-stimulated CCL17 (TARC) release observed across all SAD and MAD cohorts

Near complete inhibition of TSLP stimulated CCL17 observed for at least 5 months in 240 mg MAD Cohort

Complete inhibition of TSLP stimulated CCL17 observed for at least 5 months

in 480 mg MAD Cohort

480 mg MAD Cohort results demonstrated complete and sustained inhibition of IL-4 stimulated CCL17 for at least three months

PK/PD package support the potential to raise the efficacy ceiling and an

extended dosing schedule of up to every three months

Observed inhibitory results further validate the potency of ATI-052

Update Provides Confidence in Continued Development

Low rate of drug related treatment emergent adverse events; predominantly Grade 1

No SAEs; no adverse events led to study discontinuation

No Grade 3 drug-related TEAEs

No conjunctivitis

Full results confirm strong safety profile observed at interim analysis

Favorable tolerability and safety profile demonstrated across all ATI-052 SAD and MAD cohorts

Enrollment and Dosing Ongoing

Screening/ Washout

12 AD Patients

EASI >21

Randomization

3:1 Active to Placebo

Day 57