Karos is developing a


small-molecule for the treatment of pulmonary arterial hypertension (PAH)

Karos Science


Karos’ ability to modulate selectively peripheral serotonin (5-HT) is at the core of its R&D strategy.  The pathophysiological impact of a dysfunctional peripheral 5-HT system in various diseases is an emerging science and an opportunity for the company to target therapeutic areas with high medical need.  Karos’ focus remains on orphan indications and its lead molecule KAR5585 is a first-in-class agent for the treatment of pulmonary arterial hypertension (PAH), an orphan disease with poor prognosis.

Novel MOA Sets Karos Compound Apart

Current therapeutic modalities for the treatment of PAH target one of three pathways: prostacyclin, endothelin, or nitric oxide.  Karos’ approach leverages a distinct, fourth pathway that has been validated in both animal and human clinical settings.

  • The new pathway offers the potential to be first in class while addressing both vascular  remodeling and vasoconstriction
  • Karos’ compound has shown the ability to reduce and reverse arterial wall thickness and occlusions, indicating true disease modifying capabilities
  • The distinct MOA of the Karos’ development compound allows additivity/synergy when used in combination with standard of care therapeutics based on preclinical data.
Rigorous In Vivo Models Point to Potential for Superior Efficacy
  • Experimental results in both the Monocrotaline (MCT) and Sutent-Hypoxia models of PAH have demonstrated levels of efficacy with monotherapy using the Karos development compound that met or exceeded the efficacy of the “gold standard” current therapeutics, including ambrisentan and tadalafil.
  • Importantly, in combination with standard of  care  therapeutics, Karos’ development compound appears to offer superior performance.  Indeed, when administered with ambrisentan, Karos’ lead candidate has produced efficacy in preclinical models of PAH that surpassed even the combination of ambrisentan and tadalafil, a therapeutic modality widely viewed as  the  most efficacious available to date.
Preclinical Toxicology Testing to Date Indicates Good Safety and Tolerability

Karos preclinical safety studies have supported the IND approval of its clinical candidate.

  • Pharmacodynamic / pharmacokinetic modeling reveals drug properties supportive of oral 1-2 X daily dosing
  • GLP Safety pharmacology and chronic 28-day toxicity studies in rats and dogs indicate that the product is well tolerated, with no apparent significant safety or tolerability concerns identified to date
  • A good therapeutic index is anticipated from these studies

  • Ongoing SAD and MAD Phase 1 Clinical Trial
  • No Adverse Events to note