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PL-3994 for Heart Failure

PL-3994, discovered and developed by scientists at Palatin Technologies, is a natriuretic peptide receptor A (NPR-A) agonist compound under development for heart failure, acute asthma and other pulmonary indications. PL-3994 has successfully completed Phase 1 safety trials.

PL-3994 is a synthetic molecule, incorporating a novel and proprietary amino acid mimetic developed by Palatin Technologies.  PL-3994 has an extended half-life, with reduced affinity for natriuretic peptide clearance receptors and increased resistance to neutral endopeptidase, an endogenous enzyme that degrades natriuretic peptides. The result is a drug with improved pharmacokinetic and pharmacodynamic properties.

PL-3994 activates NPR-A, a receptor known to play a role in cardiovascular homeostasis. PL-3994 increases plasma cyclic guanosine monophosphate (cGMP) levels, a pharmacological response consistent with the effects of endogenous (naturally produced) natriuretic peptides on cardiovascular function and smooth muscle relaxation. PL-3994 also decreases activity of the renin-angiotensin-aldosterone system (RAAS), a hormone system that regulates blood pressure and fluid balance.

We have planned but not yet scheduled a repeat dose Phase 2 clinical trial in patients with heart failure to evaluate safety profiles as well as pharmacokinetic (period to metabolize or excrete the drug) and pharmacodynamic (period of action or effect of the drug) endpoints. Patient populations would include patients diagnosed with heart failure, including patients with reduced levels of endogenous active natriuretic peptides.

Assuming favorable results from the repeat dose trial, we have planned a repeat dose Phase 2 proof-of-principle clinical trial in patients with heart failure, which would involve treatment for a three to six month period, and would evaluate cardiac function, effects on remodeling, symptom improvement and hospitalization admission rates. This trial will be initiated following completion of the first repeat dose Phase 2 clinical trial.

  • Patients who have been admitted to the hospital with an episode of worsening heart failure have an increased risk of either death or hospital readmission in the three months following discharge. Up to 15% of patients die in this period and as many as 30% need to be readmitted to the hospital. We believe that decreasing mortality and hospital readmission in patients discharged following hospitalization for worsening heart failure is a large unmet medical need for which PL-3994 may be effective. PL-3994 could potentially be utilized as an adjunct to existing heart failure medications, and may, if successfully developed, be self-administered by patients as a subcutaneous injection following hospital discharge. We believe that PL-3994, through activation of NPR-A, may, if successful, reduce cardiac hypertrophy (increase in heart size due to disease), which is an independent risk factor for cardiovascular morbidity and mortality. For the presentation on the PL-3994 Phase 1 study at the 12th Annual Scientific Meeting of the Heart Failure Society of America, click here.
  • For the presentation on the PL-3994 Phase 2a study at the 13th Annual Scientific Meeting of the Heart Failure Society of America, click here.