cemdomespib (RTA 901) / Biogen - LARVOL DELTA

Targeting Hsp90 with cemdomespib reduces seizure burden and alters disease course in preclinical epilepsy models. (PubMed, Epilepsia) - "Cemdomespib confers both acute seizure protection and long-term suppression of epileptogenesis, likely through Hsp90-dependent regulation of mitochondrial integrity and redox signaling. These findings highlight Hsp90 inhibition as a promising therapeutic strategy for seizure control while also mitigating the progression of epileptogenesis and its associated neurobehavioral impairments."

Journal • Preclinical • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry • CDC37 • HSP90AA1

A Phase 2 Study of RTA 901 (BIIB143) in Participants With Diabetic Peripheral Neuropathic Pain (CYPRESS) (clinicaltrials.gov) - P2 | N=209 | Terminated | Sponsor: Reata, a wholly owned subsidiary of Biogen | N=384 ➔ 209 | Trial completion date: Aug 2026 ➔ Nov 2024 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2026 ➔ Nov 2024; Sponsor decision to close study early; not due to safety concerns.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Schwann Cell Protein Kinase RNA-like ER Kinase (PERK) Is Not Necessary for the Development of Diabetic Peripheral Neuropathy but Negates the Efficacy of Cemdomespib Therapy. (PubMed, ACS Pharmacol Transl Sci) - "Nrf2 is a PERK substrate and studies using rat SCs subjected to ER stress demonstrated that cemdomespib increased Nrf2 activity. Collectively, these data suggest that activation of SC PERK by diabetes is not necessary for the onset of DPN, but serves as a target in the action of cemdomespib, potentially by increasing Nrf2 activity."

Journal • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • PERK

CYPRESS: A Phase 2 Study of RTA 901 (BIIB143) in Participants With Diabetic Peripheral Neuropathic Pain (clinicaltrials.gov) - P2 | N=209 | Terminated | Sponsor: Reata, a wholly owned subsidiary of Biogen

New P2 trial • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Trimmed pipeline (Firstwordpharma Press Release) - "Alongside its fourth-quarter results, Biogen said that as part of ongoing pipeline prioritisation efforts, it has discontinued development of: BIIB113 in early Alzheimer's disease; BIIB094 in early Parkinson's disease; BIIB101 in multiple system atrophy; and BIIB143 (cemdomespib) in diabetic peripheral neuropathic pain."

Discontinued • Alzheimer's Disease • Diabetic Neuropathy • Multiple System Atrophy • Parkinson's Disease • Peripheral Neuropathic Pain

Cemdomespib Therapy Slows the Progression of Neuromuscular Weakness and Demyelination in the R75W-Connexin 32 Animal Model of Charcot-Marie-Tooth 1X Disease. (PubMed, ACS Pharmacol Transl Sci) - "Similarly, 20 weeks of cemdomespib therapy improved the NMJ morphology and the overlap between presynaptic (synaptophysin) and postsynaptic (α-bungarotoxin) markers. These data show that cemdomespib therapy slows the rate of neuromuscular decline and demyelination and may present a disease-modifying approach for patients with gain-of-function Cx32 mutations."

Journal • Preclinical • Genetic Disorders • Pain • SYP

A Phase 2 Study of RTA 901 in Patients With Diabetic Peripheral Neuropathic Pain (CYPRESS) (clinicaltrials.gov) - P2 | N=384 | Recruiting | Sponsor: Reata Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

REATA PHARMACEUTICALS INC Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) (Market Screener) - "...Following completion of these Phase 1 studies, we plan to initiate a randomized, double-blind placebo-controlled Phase 2 trial of RTA 901 in diabetic patients with peripheral neuropathic pain in the fourth quarter of 2022."

New P2 trial • CNS Disorders • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

REATA PHARMACEUTICALS INC Management’s Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) (Market Screener) - P1, N=78; NCT02666963; Sponsor: Reata Pharmaceuticals, Inc; "We completed a Phase 1 single and multiple ascending dose trial of oral, once-daily RTA 901 in healthy adult volunteers to evaluate the safety, tolerability, and pharmacokinetic (PK) profile. The PK was linear up to the highest doses evaluated with a half-life ranging from two to nine hours, and exposures were easily achievable in 10-fold excess of those necessary for efficacy in multiple animal models. No safety or tolerability concerns were reported. Due to additional delays in clinical drug supply, we now plan to initiate additional Phase 1 studies to evaluate the PK and drug-drug interaction potential of RTA 901 in the first half of 2022 and a randomized, placebo-controlled Phase 2 study in diabetic peripheral neuropathic pain (DPNP) in the second half of 2022."

New P1 trial • New P2 trial • P1 data • CNS Disorders • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Reata Pharmaceuticals, Inc. Announces Fourth Quarter and Full Year 2020 Financial Results and Provides an Update on Clinical Development Programs (GlobeNewswire) - "RTA 901 in Diabetic Peripheral Neuropathic Pain...completed a Phase 1 trial to evaluate the safety, tolerability, and pharmacokinetic profile of RTA 901 administered orally, once-daily in healthy adult volunteers...We plan to initiate additional Phase 1 clinical pharmacology studies in the second quarter of 2021. We also expect to launch a randomized, placebo-controlled Phase 2 study in DPNP in the fourth quarter of 2021."

New P1 trial • New P2 trial • Trial completion • CNS Disorders • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain