Study of S-4321 in Participants With an Autoimmune or Immune-mediated Disease

Phase 1b, Open-Label, Exploratory Biomarker Basket Study of S-4321 in Participants With an Autoimmune or Immune-Mediated Disease

This is a multi-center, open-label Ph 1b basket study to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, biomarker response, and preliminary efficacy of multiple doses of S-4321 in adults with autoimmune or immune-mediated disease including rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), cutaneous lupus erythematosus (CLE) with or without systemic manifestations, or atopic dermatitis (AD).

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases; Rheumatoid Arthritis (RA); Cutaneous Lupus Erythematosus (CLE); Psoriasis (PsO); Atopic Dermatitis (AD); Psoriatic Arthritis (PsA)
• Intervention / Treatment: Drug: S-4321

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Seismic Contact; Phone Number: 1800 244 475; Email: clinical@seismictx.com

Study Locations

• Australia
  • New South Wales
    • Charlestown, New South Wales, Australia, 2290
      • Recruiting
      • Novatrials
      • Contact: Toni McCallum Pardey; Phone Number: +61 (02) 4089 3746; Email: toni@novatrials.com.au
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Recruiting
      • University of the Sunshine Coast Clinical Trials, Birtinya
      • Contact: Peter de Wet, MD; Phone Number: +61 (07) 5456 3872; Email: ctcvitality@usc.edu.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

All Participants Major Inclusion Criteria:

1. Adult males and females, 18 to 75 years of age (inclusive)
2. Body mass index (BMI) ≥18.0 and <40.0 kg/m2 with a minimum body weight of 45 kg
3. Use of adequate contraception for both males and females. Female volunteers must be of nonchildbearing potential or if of childbearing potential, must have a negative pregnancy test.

All Participants Major Exclusion Criteria:

1. Have received a PD-1 agonist, immune checkpoint agonist, immune checkpoint inhibitor, anti-CD19 or anti-CD20 agents, cell therapy, B cell modulating agents, alkylating agents, or any other immune cell depleting therapy.
2. Have received azathioprine, cyclosporine, mycophenolate mofetil, or tacrolimus within 4 weeks
3. Unable or unwilling to discontinue a prohibited medication
4. Presence of clinically relevant immunosuppression
5. Current infection or history of severe infection
6. Any history of malignant disease, with some exceptions

Major inclusion/exclusion for each autoimmune or immune-mediated disease:

For RA:

1. Confirmed diagnosis of moderate to severe active RA by the American College of Rheumatology (ACR) 2010/European League Against Rheumatism (EULAR) criteria for at least 3 months prior to the Screening 1 visit, and:

   1. ≥6 swollen joint count based on 66 joint count
   2. ≥6 tender joint count based on 68 joint count
   3. Seropositive for RF and/or ACPA
   4. Elevated hsCRP ≥1.2 times greater than the ULN
   5. Does not have Class IV RA according to ACR revised criteria

2. Inadequate response to, or loss of response, or intolerance to:

   1. >1 conventional synthetic DMARD after 3 months of therapy OR
   2. >1 biologic DMARD/targeted synthetic DMARD after 3 months of therapy
   3. Has not failed 3 or more bDMARDs and/or tsDMARDs

For PsA:

1. Confirmed diagnosis of adult-onset PsA classified by the Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 3 months prior to the Screening 1 visit, with all of the following:

   1. Active PsO defined by at least 1 psoriasis lesion
   2. Active disease defined by >3 swollen joints and >3 tender joints using the 76/78 swollen and tender joint count
2. Received standard doses of NSAIDs for >4 weeks or csDMARDs for >3 months and has been on a stable dose for >8 weeks, or participant has intolerance to NSAIDs or DMARDs
3. Participants may be TNF inhibitor therapy naïve or may have received 1 prior TNF inhibitor
4. Has not had inadequate response or intolerance to 2 or more bDMARDs or csDMARDs

For PsO:

1. Confirmed diagnosis of moderate to severe plaque PsO for at least 6 months, with all of the following:

   1. Psoriasis Area and Severity Index (PASI) >12 points
   2. Static Physician's Global Assessment (sPGA) >3 points
   3. Body surface area (BSA) of PsO involvement >10%
2. Cannot have a clinically significant flare within 12 weeks
3. Does not have history of erythrodermic psoriasis, generalized or localized pustular psoriasis, predominantly guttate psoriasis, or medication-induced or medication-exacerbated psoriasis
4. Has not had inadequate response to more than 2 prior bDMARDs

For CLE (with or without systemic manifestations):

1. Histologically confirmed diagnosis of CLE with or without systemic manifestations for at least 6 months
2. Has active skin manifestations as measured by CLASI-A >10 or CLASI-A >8, if there is no alopecia or mucous membrane lesions
3. Participant must have an active CLE lesion despite an adequate trial of antimalarial treatment for at least 6 months.
4. Cannot have active lupus nephritis or moderate-to-severe or chronic kidney disease with eGFR <45 mL/min/1.73m2
5. Cannot have active neuropsychiatric SLE

For AD:

1. Confirmed diagnosis of AD as defined by the American Academy of Dermatology: Guidelines of Care for the Management of Atopic Dermatitis for at least 12 months

   1. Eczema Area and Severity Index (EASI) >16
   2. Validated Investigator Global Assessment (vIGA-AD) >3
   3. BSA of AD involvement >10%
   4. PP-NRS) >4 (average of daily scores) during the 7 days prior to dosing

2. Inadequate response to existing topical medications within 6 months or has a history of intolerance to topical therapy as defined by at least 1 of the following:

   1. Inability to achieve good disease control after use TCS for at least 4 weeks
   2. Documented history of clinically significant AEs with the use of TCS
   3. Failed systemic therapies intended to treat AD within 6 months

Additional inclusion/exclusion criteria will apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-4321; SC Dose of S-4321	Drug: S-4321; Multiple doses of S-4321 via subcutaneous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Through Week 31
Incidence of serious adverse events (SAEs)	Through Week 31

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum concentration of S-4321	Through Week 28
Change from baseline in percent Receptor Occupancy (RO)	Through Week 28
Change from baseline of soluble PD-1 (sPD-1)	Through Week 28
Incidence of anti-drug antibodies (ADAs)	Through Week 28

Collaborators and Investigators

• Sponsor: Seismic Therapeutic AU Pty Ltd
• Collaborators: Avance Clinical Pty Ltd.
• Investigators: Principal Investigator: Jennifer Martin, MD, Novatrials

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: February 13, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Atopic Dermatitis (AD); Autoimmune; Cutaneous Lupus; Cutaneous Lupus Erythematosus (CLE); Psoriatic Arthritis (PsA); Psoriasis (PsO); Immune-mediated; S-4321; Seismic Therapeutic
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Spinal Diseases; Spondylarthropathies; Skin Diseases, Papulosquamous; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Spondylarthritis; Spondylitis; Dermatitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Psoriasis; Dermatitis, Atopic; Autoimmune Diseases; Arthritis, Rheumatoid; Arthritis, Psoriatic; Lupus Erythematosus, Cutaneous
• Other Study ID Numbers: S-4321-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD sharing plan is not yet developed. Sponsor will consider data sharing at a later date.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes