Other early trials

Mechanism-first map of active IIM trials (plus the most relevant public readouts)

1)

JAK–STAT pathway inhibition

(interferon + other cytokines downstream)

Deucravacitinib (selective TYK2 inhibitor, oral) — refractory DM/JDM (open-label Phase 2)

• Trial: NCT07012057 (Phase 2)
• MOA: selective TYK2 inhibition (JAK–STAT modulation with a different selectivity profile than classic JAK1/2/3 inhibitors).
• Public results: none from this study yet (registered; outcomes pending).
• Sponsor listed as NIAMS.

2)

Type I interferon targeting (ligand or receptor blockade)

Dazukibart / PF-06823859 (anti–IFN-β monoclonal antibody) — Dermatomyositis

• Evidence base (public): randomized trial publication reporting clinical activity and target engagement.
• MOA: neutralizes IFN-β (a type I IFN ligand), aiming to reduce the interferon-driven program in DM.
• “Going on” now: Pfizer has additional ongoing/registry-listed IIM work around this program (check current recruiting status per site/region on the registry).

Anifrolumab (anti-IFNAR1 monoclonal antibody; SC) — PM/DM

• Trial: NCT06455449 (randomized, placebo-controlled).
• MOA: blocks IFNAR1 → shuts down signaling from multiple type I IFN ligands.
• Public results in IIM: none yet (trial ongoing/registry-listed).
• Sponsor: AstraZeneca (trial listing).

3)

IgG lowering via FcRn blockade

Efgartigimod PH20 SC (FcRn inhibitor) — IIM (DM, ASyS, IMNM; subtype per protocol strata)

• Trial: ALKIVIA NCT05523167 (seamless Phase 2/3)
• MOA: FcRn blockade accelerates IgG catabolism → lowers total IgG and (by extension) pathogenic autoantibodies in antibody-associated phenotypes.
• Public results: Phase 2 proof-of-concept results presented (EULAR 2025 / abstracts/posters).
• Developer: argenx.

4)

Complement terminal pathway inhibition

Ravulizumab (C5 inhibitor) — Dermatomyositis

• Trial: NCT04999020 (Phase 2/3)
• MOA: blocks C5 → prevents terminal complement activation (MAC formation).
• Public results: no definitive efficacy readout I could confirm as published for DM yet; trial remains the key public source for status/endpoints.
• Sponsor/developer: Alexion Pharmaceuticals (within _{AstraZeneca}_).

5)

Innate immune sensor blockade (TLR7/8)

Enpatoran / M5049 (TLR7/8 inhibitor, oral) — DM/PM (IIM)

• Trial: NEPTUNIA NCT05650567
• MOA: inhibits TLR7/8 signaling (innate activation that can amplify interferon programs and autoantibody-pathogenic loops).
• Public results in IIM: I didn’t find a peer-reviewed efficacy dataset for IIM yet; trial registry is the best “live” source.
• Developer: Merck KGaA / EMD Serono (platform developer; trial sponsor specifics can vary).

6)

Plasmacytoid dendritic cell axis (upstream interferon production)

Daxdilimab (anti-ILT7; pDC modulation/depletion) — DM / anti-synthetase inflammatory myositis

• Trial: NCT05669014 (Phase 2 proof-of-concept)
• MOA: targets ILT7 on pDCs → reduces type I IFN production upstream (conceptually “before JAK/IFNAR”).
• Public results: trial listed; I did not confirm a definitive peer-reviewed efficacy readout yet.
• Developer: Amgen.

7)

B-cell depletion with monoclonal antibodies (CD20)

Ublituximab (anti-CD20 monoclonal antibody) — autoantibody+ IMNM

• Trial: NCT07103746 (Phase 2)
• MOA: CD20 B-cell depletion (autoantibody production support, antigen presentation, cytokine networks).
• Public results: none yet (trial listed).

8)

“Immune reset” cell therapy (CD19 CAR-T)

Rese-cel / CABA-201 (fully human CD19 CAR-T) — DM, antisynthetase syndrome, IMNM cohorts

• Trial: RESET-Myositis NCT06154252 (Phase 1/2)
• MOA: deep (intended transient) CD19+ cell depletion after a single infusion, with the goal of durable remission without chronic therapy.
• Public results: early initial clinical data updates have been publicly released; peer-reviewed mechanistic/clinical case-level data also exist in IMNM context.
• Developer: Cabaletta Bio.

KYV-101 (CD19 CAR-T) — adult dermatomyositis

• Trial: NCT06298019
• MOA: CD19 CAR-T depletion of B-cell lineage cells; similar “one-time reset” logic.
• Public results in DM: none yet (trial listed).
• Linked developer: Kyverna Therapeutics (program context).

Mechanism-adjacent, but clinically important in IIM because they target

key complications

9)

Fibrosis/ILD progression pathway modulation

Nintedanib (antifibrotic multi-kinase inhibitor) — myositis-associated ILD

• Trial: NCT05799755 (MINT)
• MOA: antifibrotic signaling inhibition (used in progressive fibrosing ILD paradigms; here tested specifically in MA-ILD).
• Public results: trial-design publication + registry; efficacy results pending.

10)

T-cell costimulation blockade

Abatacept (CTLA-4–Ig) — antisynthetase syndrome ILD

• Trial: NCT03215927
• MOA: blocks CD80/86 → reduces T-cell activation.
• Public results: pilot RCT results exist in the literature (helpful for “what signal is plausible” even as additional studies evolve).

11)

IL-6 receptor blockade in a very specific phenotype

Tocilizumab (anti-IL-6R) — anti-MDA5+ DM

• Trial: PROMIS-MDA5 NCT07377058 (posted Jan 29, 2026)
• MOA: IL-6R blockade (targets inflammatory amplification; mechanistic fit is phenotype-dependent).
• Public results: trial newly listed; outcomes pending.
• Sponsor: Peking Union Medical College Hospital.

A “keep your priors honest” bucket: mechanism worked biologically, but trial outcome matters

Immunoproteasome inhibition (zetomipzomib / KZR-616) — DM/PM

• Trial: PRESIDIO NCT04033926 (Phase 2; completed)
• MOA: immunoproteasome inhibition → broad immunomodulation (T-cell subsets, cytokines, plasma cell biology).
• Public results: topline outcomes have been publicly reported; interpret as “mechanism of interest, but not a straightforward win in this program.”