A Study of SPY072 in Rheumatic Disease

This is a multi-center, double-blind, placebo-controlled, Phase 2, proof-of-concept basket study with the goal of assessing the efficacy and safety of SPY072 compared to placebo in adults (aged ≥18 years) with rheumatic disease (RD).

The basket study comprises of substudies in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatric arthritis (PsA) as follows: * RA substudy: Moderately to severely active RA despite treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), biologic disease modifying anti-rheumatic drugs (bDMARDs), or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) * axSpA substudy: Moderately to severely active axSpA despite treatment with non-steroidal anti-inflammatory drugs (NSAIDS), bDMARDs, or tsDMARDs * PsA substudy: Moderately to severely active PsA despite treatment with NSAIDs, csDMARDs, bDMARDs, or tsDMARDs

Inclusion Criteria: For rheumatoid arthritis: * Moderate-to-severely active RA as defined by the presence of ≥4 swollen joints (based on 28 joint count) and ≥4 tender joints (based on 28 joint count) at Screening and Day 1. * Documentation of ≥1 of the following: 1. Positive test results for rheumatoid factor or anti-citrullinated peptide antibodies at Screening, OR 2. Radiology report documenting bony erosions in hands or feet consistent with RA on previous radiographs * Inadequate response (defined as signs and symptoms of persistently active disease, loss of response, or intolerance) to: 1. ≥1 csDMARD treatment; AND/OR 2. ≤2 classes of bDMARD/tsDMARD treatment (\>2 classes of bDMARDs and/or tsDMARDs is exclusionary) For axial spondyloarthritis: * Moderate-to-severely active axSpA defined by BOTH of the following at Screening AND Day 1: 1. BASDAI ≥4, AND 2. Back pain ≥4 (from BASDAI Item 2) * hsCRP greater than the ULN per the central laboratory at Screening * Inadequate response (defined as signs and symptoms of persistently active disease, loss of response, or intolerance) to: 1. 2 different NSAIDs given at the maximum tolerated dose for ≥4 weeks or intolerant to or has a contraindication to NSAID therapy; AND/OR 2. ≤2 classes of bDMARD (anti-TNF or anti-IL-17)/tsDMARD at an approved dose for ≥12 weeks (\>2 classes of bDMARDs/tsDMARDs is exclusionary) For psoriatic arthritis: * Screening and Day 1 TJC ≥3 out of 68 and SJC ≥3 out of 66 (dactylitis counts as 1 joint each) * ≥1 active plaque psoriasis lesion and/or a documented history of psoriasis * Inadequate response (defined as signs and symptoms of persistently active disease, loss of response, or intolerance) to: 1. ≥1 NSAID treatment; AND 2. ≥1 csDMARD treatment; AND/OR ≤2 classes of bDMARD/tsDMARD treatment (\>2 classes of bDMARDs and/or tsDMARDs is exclusionary) Exclusion Criteria: * Inadequate response to \>2 classes of bDMARDs/tsDMARDs * Other autoimmune, rheumatologic, inflammatory diseases or pain-amplification syndromes that might confound the evaluations of efficacy of SPY072