The Clock Is TYKing Down On SLE Data

Research evidence excerpt

The Clock Is TYKing Down On SLE Data

July 8, 2026

support for ALMS shares, while positive SLE data could be seen as de-risking

for not just SLE but also CLE, Sjörgen's and other large opportunities.

What is the biologic rationale for TYK2 inhibition in SLE?

This is straightforward. In addition to the mechanistic rationale provided by

Saphnelo, there is strong genetic rationale for TYK2 inhibition in SLE.

●~5% of Caucasians carry a loss of function genetic mutation in the TYK2

gene that is phenotypically silent but protective against SLE.

●Heterozygous carriers show indication-specific protection of ~40–60%

for lupus (and psoriasis).

●Homozygous individuals have ~80–90% protection from autoimmune

diseases including lupus.

In addition, BMY's Sotyktu, a first-generation TYK2 inhibitor that has inferior

pharmacology relative to envu' and TAK's zasocitinib, succeeded in a Phase

2 trial in SLE (HERE) and is currently undergoing Phase 3 investigation with

data expected later this year.

What is the study design and factors that favor success?

LUMIS trial is a ~480-patient, 48-week, randomized, placebo-controlled

Phase 2b that was designed to serve as one of two potential pivotal studies.

Management obtained FDA feedback on the design prior to initiation and

incorporated all agency suggestions. The trial tests three active doses:

20mg QD, 20mg BID, and 40mg BID.

The last patient was enrolled in mid-2025. Data readout is expected in Q3,

most likely in August or September.

LUMIS is enrolling patients with skin manifestations of disease.100% of

patients have skin involvement at the time of enrollment as adjudicated

by a panel of experts. This is important as (1) interferon activity appears

to originate in skin before becoming systemic, (2) skin responders drove