mavodelpar (REN001) / vTv Therapeutics, OnKure - LARVOL DELTA

SELECTIVE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR Δ AGONIST AS A TREATMENT FOR MITOCHONDRIAL BIOENERGETICS DISRUPTION IN CELLS FROM PATIENTS WITH INHERITED METABOLIC DISEASES (SSIEM 2024) - "Previous studies had shown that bezafibrate, the most studied pan-PPAR agonist, has potential to improve mitochondrial function in different inherited metabolic diseases...Case Study/ Fibroblasts from healthy adults and patients with CPT2, MCAD, LCHAD and CI deficiencies were treated with a Mavodelpar for 48 hours in absence of glucose, to assess their ability to accommodate an energy source shift from glucose to fatty acids... These findings provide mechanistic evidence that the PPARδ agonist can improve mitochondrial function, confirming the effectiveness of the compound tested as a potential adjuvant therapy for FAODs and complex I (CI) deficiency."

Clinical • Metabolic Disorders

TREATMENT OF MOLYBDENUM COFACTOR DEFICIENCY PATIENT'S FIBROBLAST WITH A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR Δ AGONIST ALLEVIATES MITOCHONDRIAL DYSFUNCTION (SSIEM 2024) - "Our data demonstrate that mitochondrial bioenergetics and control quality are impaired in MOCS1 deficient fibroblasts. Treatment with Mavodelpar reversed bioenergetic alterations in the deficient cells, identifying this molecule as a potential therapeutic agent for all forms of MoCD."

Clinical • Genetic Disorders • Metabolic Disorders • Ocular Inflammation • DNM1L • MOCS1 • MOCS2 • OPA1

Mavodelpar, a selective peroxisome proliferator-activated receptor delta (PPARδ) agonist, improves cellular bioenergetics in fibroblasts from patients with primary mitochondrial myopathy and complex I defiency (SIMD 2024) - "These findings provide mechanistic evidence that the bioenergetic deficiencies and mitochondrial dysfunction observed in CI-deficient patient fibroblasts with either nDNA or mtDNA defects can potentially be alleviated by treatment with mavodelpar."

Clinical • Genetic Disorders • Metabolic Disorders • Myositis

An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead) (clinicaltrials.gov) - P2/3 | N=155 | Terminated | Sponsor: Reneo Pharma Ltd | Trial completion date: Jul 2025 ➔ Jan 2024 | Enrolling by invitation ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Dec 2023; Parent study failed to show therapeutic effect

Trial completion date • Trial primary completion date • Trial termination • Myositis

STRIDE: An Efficacy and Safety Study of 24 Week Treatment With Mavodelpar (REN001) in Primary Mitochondrial Myopathy Patients (clinicaltrials.gov) - P2 | N=213 | Completed | Sponsor: Reneo Pharma Ltd | Active, not recruiting ➔ Completed

Trial completion • Myositis

Mavodelpar clinical development program in adult patients with primary mitochondrial myopathy: results from a Phase 1b study and design of ongoing pivotal study (STRIDE) (SSIEM 2023) - P2 | "These Phase 1b results support further development. The pivotal STRIDE Study REN001-201 (NCT04535609) is a fully enrolled 24 week, multicenter, randomized, double-blind, placebo-controlled trial of mavodelpar 100 mg oral, once-daily in adults with PMM and confirmed mitochondrial DNA defects (N=213). Results are expected Q4 2023."

Clinical • P1 data • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Metabolic Disorders • Myositis • Novel Coronavirus Disease • Pain

An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead) (clinicaltrials.gov) - P2/3 | N=200 | Enrolling by invitation | Sponsor: Reneo Pharma Ltd | Recruiting ➔ Enrolling by invitation | N=80 ➔ 200

Enrollment change • Enrollment status • Myositis

STRIDE: An Efficacy and Safety Study of 24 Week Treatment With Mavodelpar (REN001) in Primary Mitochondrial Myopathy Patients (clinicaltrials.gov) - P2 | N=213 | Active, not recruiting | Sponsor: Reneo Pharma Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Myositis

"$RPHM Reneo Pharmaceuticals Achieves Target Enrollment in the Pivotal STRIDE Study of Mavodelpar (REN001) in Primary Mitochondrial Myopathies https://t.co/Fh8cDHJoBS" (@stock_titan)

Myositis

PPARδ agonism ameliorates renal fibrosis in an Alport syndrome mouse model. (PubMed, Kidney360) - "These results indicate that REN001 slows kidney disease progression in Alport mice. REN001 has a different mechanism of action from ACEi, so we therefore hypothesize that combining the two treatments may show additive effects to attenuate renal injury and slow progression to renal failure."

Journal • Preclinical • Acute Kidney Injury • Chronic Kidney Disease • Fibrosis • Genetic Disorders • Immunology • Inflammation • Nephrology • Renal Disease • COL4A5 • Collagen Type IV

A Phase 1b Study of the Safety of REN001 in Patients With Fatty Acid Oxidation Disorders (clinicaltrials.gov) - P1b | N=24 | Completed | Sponsor: Reneo Pharma Ltd | Active, not recruiting ➔ Completed | Phase classification: P1 ➔ P1b

Phase classification • Trial completion • Metabolic Disorders

STRIDE: A Study of the Efficacy and Safety of 24 Week Treatment With REN001 in Patients With Primary Mitochondrial Myopathy (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Reneo Pharma Ltd | Trial completion date: Dec 2022 ➔ Oct 2023 | Trial primary completion date: Dec 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Myositis

REN-001 (HFSA 2022) - "Company Name: Renovacor Inc. Description: Renovacor’s mission is to deliver innovative precision therapies to improve the lives of patients and families battling genetically-driven cardiovascular and mechanistically-related diseases."

Cardiovascular

Treatment of VLCAD-Deficient Patient Fibroblasts with Peroxisome Proliferator-Activated Receptor δ Agonist Improves Cellular Bioenergetics. (PubMed, Cells) - " Treating VLCAD-deficient fibroblasts with the REN001 PPARδ agonist results in an increase in VLCAD protein and enzyme activity, and a decrease in cellular stress. These results establish REN001 as a potential therapy for VLCADD as enhanced expression may provide a therapeutic increase in total VLCAD activity, but suggest the need for mutation-specific treatment augmented by other treatment measures."

Journal • Cardiomyopathy • Cardiovascular • Hepatology • Hypoglycemia • Myositis

REN001, PPARδ Agonist, Preserves Muscle Strength and Promotes Recovery of Muscle Atrophy After Leg Immobilization (ICNMD 2022) - No abstract available

Muscular Atrophy

Renovacor Announces Data from Pilot Pig Study Showing Successful Cardiac Transduction with REN-001 Delivered Via Low-Dose Retrograde Coronary Sinus Infusion Published in Journal of the American College of Cardiology: Basic to Translational Research (Businesswire) - "REN-001 is an AAV-based gene therapy designed to directly address the underlying cause of BAG3‑associated dilated cardiomyopathy (BAG3-DCM) by using a validated AAV9 capsid to deliver a functional copy of the BAG3 gene to cardiac tissue. In the pilot Yucatan pig study featured in JACC: BTS, low doses (<1e13 vector genome (vg) per kilogram (kg)) of REN-001 delivered locally to the heart using RCSI resulted in each evaluated cardiomyocyte containing, on average, at least one copy of the delivered BAG3 gene (i.e., vector copy number threshold ≥1)."

Preclinical • Cardiovascular • Dyslipidemia • Metabolic Disorders

REN001, a novel peroxisome proliferator-activated receptor delta (PPARδ) agonist, improves gait in patients with primary mitochondrial myopathy after 12 weeks (NMTR 2022) - No abstract available

Clinical • Myositis

An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead) (clinicaltrials.gov) - P2/3 | N=80 | Recruiting | Sponsor: Reneo Pharma Ltd

New P2/3 trial • Myositis

An unblinded , multi-centre study to determine the long term safety and tolerability of the study drug REN001 in Primary Mitochondrial Myopathy (PMM) subjects. Un estudio multicéntrico no ciego para determinar la seguridad y tolerabilidad a largo plazo del fármaco del estudio REN001 en sujetos con miopatía mitocondrial primaria (PMM). (clinicaltrialsregister.eu) - P2 | N=80 | Ongoing | Sponsor: Reneo Pharma Ltd.

New P2 trial • Myositis • Tourette Syndrome

A Study of the Safety of REN001 in Patients With McArdle Disease (clinicaltrials.gov) - P1b; N=19; Completed; Sponsor: Reneo Pharma Ltd; Recruiting ➔ Completed

Clinical • Trial completion • Metabolic Disorders

A Study of the Safety of REN001 in Patients With Fatty Acid Oxidation Disorders (clinicaltrials.gov) - P1; N=24; Active, not recruiting; Sponsor: Reneo Pharma Ltd; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Metabolic Disorders

STRIDE: A Study of the Efficacy and Safety of 24 Week Treatment With REN001 in Patients With Primary Mitochondrial Myopathy (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: Reneo Pharma Ltd; Phase classification: P2/3 ➔ P2

Clinical • Phase classification • Myositis

STRIDE: A Study of the Efficacy and Safety of 24 Week Treatment With REN001 in Patients With Primary Mitochondrial Myopathy (clinicaltrials.gov) - P2/3; N=200; Recruiting; Sponsor: Reneo Pharma Ltd; Not yet recruiting ➔ Recruiting

Enrollment open • Myositis

A Study of the Safety of REN001 in Patients With McArdle Disease (clinicaltrials.gov) - P1b; N=16; Recruiting; Sponsor: Reneo Pharma Ltd; Trial completion date: Mar 2021 ➔ Dec 2021; Trial primary completion date: Mar 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Metabolic Disorders

A Study of the Safety of REN001 in Patients With Fatty Acid Oxidation Disorders (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Reneo Pharma Ltd; N=12 ➔ 24

Clinical • Enrollment change • Metabolic Disorders