NanoPhoria’s lead asset is NP-MP1, an investigational therapy for the treatment of Heart Failure with reduced Ejection Fraction (HFrEF).
On a molecular level, NP-MP1 aims to address dysregulation of the L-type calcium channels (LTCCs) found in cardiomyocytes,
the cells most responsible for cardiovascular function.
NP-MP1 is currently being investigated in CTA-enabling studies. In a study of Göttingen minipigs with induced HFrEF, NP-MP1 improved left ventricular ejection fraction by 17% +/- 6%. These findings were also mirrored ex vivo in cardiac myofibrils.
There is a substantial pharmacotherapeutic gap in HFrEF. Currently available treatments, such as neuro-hormonal counter regulation drugs, do not address the underlying molecular cause of HFrEF. This ‘traps’ patients in a state of constant discomfort with little improvement of symptoms.
NanoPhoria’s lead candidate, NP-MP1 is a three-level dry powder formulation specifically designed for inhaled delivery. At its core is MP1, a first-in-class molecule that regulates dysfunctional LTCC trafficking in cardiomyocytes, which is a mechanism strongly linked to heart failure progression.
The therapeutic Peptide is adhered to calcium phosphate (CaP) nanoparticles, a biomimetic carrier that is safe, non viral, and highly versatile.
These nanoparticles are complexed with lung friendly polyalcohols to form a inhalable micro-scale dry powder.
The dry powder formulation is further engineered for deposition deep into the lungs via a user-friendly inhaler, enabling self administration at home without the need for injection.
This innovative three-layer approach enables precise, tissue-directed delivery while minimizing systemic exposure and improving the patient experience, thus also improving adherence.
NP-MP1 is designed to leverage the lung as a gateway to the heart, bypassing the filtering effects of the liver.
Inhalation: Patients inhale the dry powder formulation using a simple puff-based inhaler.
Targeting of the Heart: Due to their negative charge and biomimetic properties, CaP nanoparticles are readily taken up by cardiomyocytes.
Alveolar Deposition: Nano-in-micro NP MP1 dry powder formulation reaches the deep lung and dissolves in the alveolar space, releasing MP-loaded CaP nanoparticles.
Intracellular Release: Once inside cardiomyocytes, the peptide is released to exert its therapeutic effect.
Translocation: These CaP nanoparticles cross the blood-air barrier and enter systemic circulation.
Heart failure with reduced ejection fraction (HFrEF) is heavily associated with dysregulation of L-type calcium channels (LTCCs) subcellular positioning in cardiomyocytes. When LTCC trafficking is impaired, calcium handling becomes dysfunctional, contributing to contractile failure and disease progression – to simplify, LTCC dysregulation stops the heart beating properly.
NanoPhoria’s Mimetic Peptide (MP) addresses this root cause by binding to these altered LTCCs in cardiomyocytes and correcting their position. This restores the natural physiological channel density and function, thereby improving cardiac contractility. Preclinical studies in small and large animal models have demonstrated that MP effectively regulates LTCC trafficking, positioning NP-MP1 as a potential disease-modifying therapy rather than a symptomatic treatment.
