Dose-ranging safety and efficacy studies to advance novel mechanism-of-action drug candidates to reverse age-related muscle degeneration

In the USthe number of individuals agedand older will increase byover the next decadeConcurrentlyMedicare costs are expected to double to treat chronic diseases that will plague this increasing
number of older adultsOne of the most wide spread chronic diseases that affects older adults is sarcopeniawhich is observed inof adults overyears of age andof adults overyears of ageThis
disease is characterized by progressive age associated skeletal muscle atrophythe degenerative loss of
muscle mass and tissue quality cause significant reductions in muscle strengthfunctionand regenerative
capacity of the tissuegreatly deteriorating overall health and quality of lifeMoreoversarcopenia is a core
component of the debilitating frailty syndromewhich severely impacts an individualandapos s independence and
longevityCurrent recommendations to prevent and treat sarcopenia include resistance exercise and proteinrich dietsWhile these recommendations appear logicalthere is no substantial evidence to suggest these
treatments consistently increase muscle mass and improve physical function and performance in aged
individualsGiven the current scope and projected impact of sarcopeniathere is a clear unmet need for
effective therapies to slow and reverse sarcopenia to support healthier lives for older AmericansThe objective of this Phase I project is to demonstrate proof of principal and safety for novel mechanismof action therapeutic candidates using translationally relevant muscle growth function models in aged animals
and appropriate in vivo safety modelsrespectivelyRidgeline Therepeutics is developing first in class oral
drugs that selectively target and inhibit nicotinamide N methyltransferaseNNMTan enzyme upregulated in
aged skeletal muscle and newly discovered to regulate cellular metabolic pathwaysparticualrly NADbiosynthesis that is highly compromised in aged muscleThe lead series of small molecule NNMT inhibitors
have excellent physicochemical propertiesi ehighly solublestablepermeableand good oral bioavailabilitywith no early signs of toxicityPreliminary results using our candidate lead NNMT inhibitor in an aged mouse
model for muscle regeneration and functional improvementrevealed significantly improved muscle
mitochondrial oxidative capacityenhanced muscle fiber growthand increased muscle stem cell
proliferation activityThese promising results suggest that our lead series has the potential to improve defects
in aged muscle pathophysiology and reverse sarcopeniaTo further derisk our lead candidates as potential therapeutics to greatly improve muscle growthmassand function in aged individualsthis Phaseproject will completedose ranging efficacy studies in aged
animals to demonstrate proof of principal for our drug candidates to improve muscle growth and functionandin vivo long term safety toxicity studiesPreclinical GLP safetyformulation developmentand IND enabling
studies for FDA submission will follow this Phase I project PROJECT NARRATIVEThis project will complete critical dose ranging studies to significantly derisk our novel small
molecule therapeutic leads that selectively target nicotinamide N methyltransferases to increase muscle
growth and function in aged animals