Scholar Rock recently announced that a poster presentation highlighting preclinical and Phase 1 healthy volunteer data for SRK-015 will be presented at the World Muscle Society Congress. The 24th Annual International Annual Congress of the World Muscle Society is being held in Copenhagen, Denmark this week.
SRK-015 is a highly selective inhibitor of the activation of myostatin, a negative regulator of muscle mass. It is being evaluated in the TOPAZ Phase 2 clinical trial for the treatment of patients with Type 2 and Type 3 spinal muscular atrophy (SMA).
Consistent with previously reported results, the preclinical and Phase 1* clinical data at the World Muscle Society show:
- Improved muscle strength following administration of muSRK-015P (mouse analog of SRK-015) in mouse models of early and late SMN restoration. Treatment with muSRK-015P resulted in 20%-51% increases in maximal torque (at ≥ 40 Hz) of the plantar flexor muscle group and a greater percentage of muscle fibers compared to treatment with placebo (vehicle).
- Multi-fold increase in serum latent myostatin levels following treatment with muSRK-015P in both early and late SMN restoration mouse models confirm the presence of the latent myostatin target in a modeled diseased setting.
- Relative dose-proportional accumulation of serum latent myostatin, demonstrating target engagement, in rats and cynomolgus monkeys following administration of SRK-015 compared to no meaningful change with placebo.
- Well-behaved pharmacokinetic (PK) profile displayed across animal species (adult rats and cynomolgus monkeys).
Phase 1 healthy volunteer trial:
- SRK-015 was well-tolerated with no apparent safety signals and no dose-limiting toxicities were identified up to the highest evaluated dose of 30 mg/kg.
- Robust and sustained target engagement, along with durable saturation, following administration of SRK-015 in both the single-ascending and multiple-ascending dose portions of the Phase 1 trial.
- Well-behaved PK profile, supporting dosing once every 4-weeks, which is being evaluated in the ongoing Phase 2 trial.
The details for the SRK-015 poster at the World Muscle Society Congress are as follows:
- Title: SRK-015, a Fully Human Monoclonal Antibody Inhibiting Myostatin Activation, Offers Sustained Target Engagement Across Multiple Species, Including Humans
- Number: P126
- Presentation Date: Wednesday, October 2, 2019, 4:45 – 6:15pm (local time)
- Poster Hall: Andersen Hall, Lumbye Hall and Gemyse
*Preclinical and Phase 1 clinical data are not predictive of clinical outcomes in Phase 2 and Phase 3 clinical trials.
SRK-015 works by inhibiting myostatin. Myostatin is a protein that works with other proteins and hormones to help regulate muscle mass. In healthy individuals, myostatin limits muscle growth and differentiation, to prevent muscles from growing too large. For individuals affected by SMA, inhibiting this protein may combat the muscle weakness and atrophy that characterizes the disease. A Phase 1 clinical trial in healthy volunteers is ongoing. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for SRK-015 for the treatment of SMA.