Reneo Pharmaceuticals, Inc. reported positive results from the REN001 long-chain fatty acid oxidation disorders (LC-FAOD) study and provided additional development updates. LC-FAOD Program: The Company completed a 12-week, open-label Phase 1b study in LC-FAOD patients with different nDNA defects to assess the safety and tolerability of REN001, and explore potential efficacy measurements for use in future clinical trials. A total of 24 patients were enrolled, including patients with defective long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD, n=5), carnitine palmitoyltransferase 2 (CPT2, n=8), very long-chain acyl-CoA dehydrogenase (VLCAD, n=9), or trifunctional protein (TFP, n=2).

In the LC-FAOD Phase 1b study, REN001 was safe and well tolerated. The most common adverse events experienced by patients were rhabdomyolysis (4 patients) and myalgia (4 patients), the majority reported to be mild or moderate in severity. Results of the 12-minute walk test (12MWT), 36-Item Short Form Health Survey (SF-36) energy/fatigue domain score, and Modified Fatigue Impact Scale (MFIS) Symptom improvement is represented by an increase in SF-36 energy/domain score or a decrease in MFIS total score.

The Company also completed a 16-week, observational, non-interventional study in LC-FAOD patients with different nDNA defects to better understand the natural history of LC-FAOD and changes in patient function and symptoms over time. A total of 58 patients participated in the study, including patients with defective long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD, n=16), carnitine palmitoyltransferase 2 (CPT2, n=30), or very long-chain acyl-CoA dehydrogenase (VLCAD, n=12). In the LC-FAOD natural history study, the most common adverse events experienced by patients were rhabdomyolysis (7 patients) and COVID-19 infection (5 patients), the majority reported to be mild or moderate in severity.

Results of the 12-minute walk test (12MWT), 12-Item Short Form Health Survey (SF-12) vitality domain score, and Modified Fatigue Impact Scale (MFIS). Symptom improvement is represented by an increase in SF-12 vitality score or a decrease in MFIS total score. Based on the results of the LC-FAOD Phase 1b study, in conjunction with the results of the LC-FAOD natural history study, the Company intends to continue development of REN001 for patients with LC-FAOD.

The Company plans to request meetings with U.S. and European regulatory agencies to discuss the results of the studies and obtain alignment on the study design, patient population, and endpoints for the next clinical trial. The Company intends to present additional data from the LC-FAOD studies at a medical conference in 2022. The Company is currently enrolling the pivotal STRIDE study, a global, randomized, double-blind, placebo-controlled Phase 2b clinical trial designed to assess the efficacy and safety of 100 mg REN001 administered orally once daily to approximately 200 adult PMM patients with mtDNA defects and a history of myopathy.

Over two-thirds of the patients have been enrolled into the 24-week study, with enrollment on track to be completed by year-end 2022. Based on the current enrollment timeline, topline data is anticipated in the second half of 2023. The Company is also enrolling the STRIDE AHEAD study, an open-label, long-term safety trial of 100 mg REN001 administered orally once daily to adult PMM patients with mtDNA defects and a history of myopathy.

The majority of patients who complete STRIDE, or who participated in the prior PMM Phase 1b study, are eligible for participation in the 2-year safety study. The Company recently held a meeting with EMA to discuss the ongoing PMM development program. The EMA confirmed that positive results from the ongoing STRIDE and STRIDE AHEAD studies could support registration of REN001 for adult PMM patients with mtDNA defects.

The EMA feedback is aligned with feedback previously received from the FDA. Finally, the Company announced plans to initiate development of REN001 for adult PMM patients with nDNA defects. The next steps for this third REN001 development program include requesting meetings with U.S. and European regulatory agencies to discuss the planned program .