• LC-FAOD program to move forward into the next stage of clinical development
• Enrollment of pivotal STRIDE study in primary mitochondrial myopathies (PMM) patients with mitochondrial DNA (mtDNA) defects on track to be completed year-end 2022
• Alignment with European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA); single pivotal trial for registration of REN001 in PMM patients with mtDNA defects
• New program to be initiated in PMM patients with nuclear DNA (nDNA) defects

Reneo Pharmaceuticals, Inc. (Nasdaq: RPHM), a clinical stage pharmaceutical company focused on the development and commercialization of therapies for patients with rare, genetic mitochondrial diseases, today reported positive results from the REN001 long-chain fatty acid oxidation disorders (LC-FAOD) study and provided additional development updates.

“The Reneo team continues to make good progress across all of our REN001 development programs,” said Gregory J. Flesher, President and CEO of Reneo Pharmaceuticals. “We have completed two LC-FAOD clinical trials, including a Phase 1b study where we have further evaluated safety and tolerability of REN001, and identified a group of patients that may benefit from treatment. We have enrolled over two-thirds of the planned patients into the pivotal STRIDE study, we have gained alignment with the EMA and FDA on our registration plan for PMM, and we are now planning to expand the REN001 development program to include PMM patients with nuclear DNA defects,” concluded Mr. Flesher.

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) total score for patients who completed both baseline and week 12 are summarized in Table 1. Symptom improvement is represented by an increase in SF-36 energy/domain score or a decrease in MFIS total score.

Table 1. Mean (SE) Baseline and Week 12 Change by Subgroup¹

¹ TFP not summarized as only 1 subject completed the study

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) total score for patients who completed both baseline and week 16 are summarized in Table 2. Symptom improvement is represented by an increase in SF-12 vitality score or a decrease in MFIS total score.

Table 2. Mean (SE) Baseline and Week 16 Change by Subgroup

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.

“We are very encouraged by the results of the LC-FAOD Phase1b study,” said Dr. Alejandro Dorenbaum, Chief Medical Officer of Reneo Pharmaceuticals, Inc. “Safety and tolerability of REN001 in this study was consistent with prior REN001 studies. In addition, the increase in walk distance observed in both the LCHAD and CPT2 subgroups supports the use of the 12-minute walk test as key efficacy measurement for future LC-FAOD clinical trials. We look forward to meeting with regulatory agencies to discuss next steps,” concluded Dr. Dorenbaum.

The Company intends to present additional data from the LC-FAOD studies at a medical conference in 2022.

PMM Program

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 today also 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.

About Reneo Pharmaceuticals

Reneo is a clinical-stage pharmaceutical Company focused on the development and commercialization of therapies for patients with rare genetic mitochondrial diseases, which are often associated with the inability of mitochondria to produce adenosine triphosphate (ATP). Our lead product candidate, REN001, is a potent and selective agonist of the peroxisome proliferator-activated receptor delta (PPARδ). REN001 has been shown to increase transcription of genes involved in mitochondrial function and increase fatty acid oxidation, and may increase production of new mitochondria. For additional information, please see reneopharma.com.

About REN001

REN001 is a potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist currently in clinical development for two rare genetic mitochondrial diseases that typically present with myopathy and have high unmet medical needs: primary mitochondrial myopathies (PMM) and long-chain fatty acid oxidation disorders (LC-FAOD). For additional information, please see clinicaltrials.gov.

About PMM

PMM are a group of rare, genetic metabolic disorders caused by mutations or deletions in the mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). These genetic alterations hamper the ability of mitochondria to generate energy from nutrient sources, resulting in energy deficits that are most pronounced in tissues with high energy demand such as muscle, brain, and heart. The symptoms of PMM include muscle weakness, exercise intolerance, movement disorder, deafness, blindness, and droopy eyelids among others. The prognosis for these disorders ranges in severity from progressive weakness to death.

About LC-FAOD

LC-FAOD are a group of rare, genetic metabolic disorders caused by mutations or deletions in the nuclear DNA (nDNA). These genetic alterations prevent the body from breaking down long-chain fatty acids during metabolism. The most severe cases of LC-FAOD are diagnosed within the first few days or weeks of life. Young patients often present with a severe energy deficit that results in lethargy, liver dysfunction, hypoglycemia, encephalopathy, and high risk for sudden death. Older patients usually present with muscle weakness, exercise intolerance, muscle aches, or rhabdomyolysis which can damage the heart and kidneys and cause permanent disability or even death.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the results, conduct, progress and timing of Reneo’s clinical trials, presentation of data from clinical trials, and the regulatory approval path for REN001. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “plans,” “will,” “believes,” “anticipates,” “expects,” “intends,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Reneo’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Reneo’s business in general, and the other risks described in Reneo’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Reneo undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Contacts

Joyce Allaire
Managing Director
LifeSci Advisors, LLC
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Gregory J. Flesher
Chief Executive Officer
Reneo Pharmaceuticals, Inc.
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