Scholar Rock (SRRK) Study Update summary

Study design and objectives

• Phase 2 EMBRAZE trial was a randomized, double-blind, placebo-controlled study evaluating apitegromab plus tirzepatide versus tirzepatide alone in adults with obesity or overweight and at least one comorbidity, enrolling 100–102 subjects aged 18–65 for 24 weeks of treatment.

• Primary endpoint was change in lean mass at week 24, assessed by DEXA; secondary and exploratory endpoints included weight loss, physical function, cardiometabolic parameters, safety, and pharmacokinetics.

• Baseline demographics were well balanced; majority were female (82%), mean age early 40s, BMI ≥30.

• All participants received tirzepatide; apitegromab or placebo was administered IV every four weeks.

• Study included a 24-week treatment period and an 8-week off-treatment follow-up.

Key efficacy results

• Apitegromab plus tirzepatide preserved 54.9% more lean mass (+4.2 lbs) than tirzepatide alone at week 24 (p=0.001).

• Fat mass loss was similar between groups: 18.8 lbs with apitegromab plus tirzepatide vs 17.7 lbs with tirzepatide alone.

• Body weight loss was 12.3% with apitegromab plus tirzepatide vs 13.4% with tirzepatide alone.

• Apitegromab reduced the proportion of lean mass loss from 30% to 15%, shifting weight loss toward fat mass (85% fat/15% lean vs 70%/30%).

• High quality of weight loss was observed, with lean mass preservation and consistent fat loss.

Safety and tolerability

• Apitegromab with tirzepatide was well tolerated, with adverse events balanced between groups and consistent with tirzepatide's known profile.

• No serious adverse events or discontinuations related to apitegromab; no deaths reported.

• Adverse events leading to discontinuation and grade ≥3 events were balanced across groups.

• Safety profile was consistent with prior data and previous clinical trials.