MAT2203: Encochleated Formulation of Amphotericin B

MAT2203 is Matinas BioPharma’s most advanced anti-infective product candidate. MAT2203 is a lipid-crystal nano-particle formulation of Amphotericin B. Amphotericin B is a broad spectrum anti-fungal agent and is the only approved anti-fungal with fungicidal properties (fungicidal agents KILL the fungus or yeast at the minimum effective concentration). The other approve agents for the treatment of fungal infections are in the azole and echinocandin classes. The compounds in these latter two classes are fungi-static agents (they stop the growth but do not KILL the fungus or yeast) and still require the intervention of the immune-system to kill an invasive fungus or yeast infection.

Because of its fungicidal properties, Amphotericin B is well suited for the treatment of fungal or yeast infection in immunocompromised patients. Unfortunately, in the currently available formulations Amphotericin B is intravenously (IV) administered and has significant side-effects. Besides tremors, fevers, chills, nausea, and vomiting, the potential damage to the kidneys (nephrotoxicity) is of most concern. Despite these significant side effects and the substantial cost of therapy (the liposomal Amphotericin B list price is over $1,000 per day), Amphotericin B has remained the therapy of choice for fungal infections associated with complex medical conditions and serious invasive fungal infections. In addition, the emergence of azole resistant fungal and yeast infections has elevated Amphotericin B to the treatment of last resort status.

The side effects are dose dependent and the nephrotoxicity is the consequence of sensitive kidney tissue being exposed directly to Amphotericin B. The data from animal studies for our cochleate lipid-crystal nano-particle formulation of Amphotericin B [see Our Science Page] indicate toward a significant side-effect advantage over previously approved Amphotericin B formulations, most likely based on two phenomena:

• The lipid-crystal nano-particle is a solid particle, and unlike liposomes, does not significantly “leak” its nephrotoxic content while circulating. The particle releases its medication pay-load when inside the target cells, and thus protects the kidney and other sensitive tissues from many of the Amphotericin B side effects.
• Because of the targeted approach, the required dose level is typically lower than other formulations. So besides the protective effects of the technology itself, the lower dose further contributes to a more beneficial side-effect profile.

MAT2203 was extensively studied in animal model studies of candidiasis, cryptococcal meningitis, aspergillosis, and visceral leichmaniasis.

In addition, in the vast majority of these animal studies the MAT2203 product was administered orally. If confirmed in human efficacy studies, the oral administration is a second major differentiator of our technology which offers significant health-economic benefit since patients do not need to stay in the hospital to receive the therapy. Because of these strong differentiators brought by the cochleate lipid-crystal nano-particle technology, we believe that MAT2203 will be able to obtain a significant market share of the invasive fungal infection market.

MAT2203 has completed a Phase I study and preparations for initiation of a Phase 2a study in patients are ongoing.

ABOUT SERIOUS FUNGAL INFECTIONS

Serious opportunistic fungal infections are most often diagnosed or suspected in individuals with compromised immune systems. These immunocompromised patients typically include patients with haematological malignancies (such as lymphomas or various forms of leukemia), stem cell transplants (also known as bone-marrow transplants), and solid organ transplants. In the US, the number of annual cases in these categories amount to more than 140,000 cases. In addition, patients with severely weakened immune systems due to viral infections (such as HIV), are at high risk for cryptococcal meningitis, aspergillosis and other invasive fungal infections. These type of invasive infections in severely immunocompromised patients may require many weeks of treatment to resolve. In the US, approximately 3,000 hospitalizations for cryptococcal mengingitis are being recorded annually and the CDC estimates approximately 6,000 cases of invasive aspergillosis each year.