Thoughts on Zilurgisertib's Results at ENDO; Maintain OP

Research evidence excerpt

Thoughts on Zilurgisertib's Results at ENDO; Maintain OP

June 15, 2026

favored the active treatment arm across all secondary endpoints, although we caution

against directly comparing placebo-adjusted outcomes given these differences in

study design and duration. We are encouraged by zilu's reduction in new HO lesion

volume relative to placebo (nominal p < 0.0001). Garetosmab also demonstrated a

meaningful treatment effect, though the result did not reach statistical significance

(p = 0.13). For safety, treatment related TEAEs were numerically higher with

garetosmab under cross trials comparison. Skin/soft tissue infections was also seen

commonly with garetosmab (65% at 10 mg/kg dose). Overall, we view both drugs

as supportive of clinical benefit in FOP; however, assuming FDA approval, zilu's oral

formulation could provide a meaningful real-world adoption advantage relative to

garetosmab's IV administration.

We note that the unmet need in FOH remains high (~300 pts in the U.S. and ~900

global), with only one FDA-approved therapy, Sohonos. Despite being approved

for ~three years, Sohonos generates only ~€20M in annual sales, likely reflecting

its unfavorable risk-benefit profile, including black box warnings for premature

epiphyseal closure and embryo-fetal toxicity, an age-restricted label, and rejection by

the EMA. Mirum has also noted that many physicians prefer enrolling pts in clinical

trials rather than prescribing Sohonos. Accordingly, we believe the availability of

zilu would likely drive pt switches from Sohonos. Overall, while zilu is not a major

value driver for MIRM, we remain optimistic about its approval prospects and the

company's upcoming catalysts, including brelovitug's AZURE-1/-4 Phase III topline