MAT2203: LNC Formulation of Amphotericin B

Candidate & Indication Development Stage
IND Preparation Phase 1 Development Phase 2 Development Phase 3 Development Market
MAT2203 Prevention of IFI in Acute Lymphoblastic Leukemia
IND Preparation Phase complete
Phase 1 Development Phase complete
Phase 2 Development Phase in progress
Phase 3 Development Phase not started
Market Phase not started

MAT2203 is an orally-administered, LNC formulation of amphotericin B (a broad spectrum fungicidal agent). Little to no clinical resistance has been reported to date with amphotericin B as compared to the rapidly emerging drug resistance seen in other antifungal therapies. Currently, IV-only administered amphotericin B is the only broad spectrum fungicidal. However, it has significant treatment-limiting side effects, most notably nephrotoxicity. The ability to deliver amphotericin B orally may offer a promising alternative for patients and doctors.

In a Phase 1 study conducted in 48 healthy volunteers (single-dose, double-blind, dose-escalating, pharmacokinetic design), MAT2203 demonstrated a strong safety and tolerability profile with no serious adverse events or observed nephrotoxicity. A Phase 2 trial of MAT2203 conducted by the National Institutes of Health (NIH), showed three of three enrolled patients met their primary efficacy endpoint and two of these patients have been successfully taking MAT2203 for more than a year with no evidence of kidney or other toxicity frequently associated with the use of amphotericin B.

We believe that MAT2203 has the potential to be a best-in-class therapy for both prophylaxis (preventive) and treatment of invasive fungal infections (IFIs) based on its potential to treat resistant pathogens, and its safety profile/limited drug-to-drug interactions, which enables prophelactic use. This could shorten hospital stays and lower outpatient costs.

The FDA granted MAT2203 both Fast Track and Qualified Infectious Disease Product (QIDP) designations for the treatment o invasive candidiasis and aspergillosis and for the prevention of IFIs in patients on immunosuppressive therapy. Matinas has also applied for Orphan Drug Designation.

Additional Studies of MAT2203

NIH Partnership in refractory mucocutaneous candidiasis

We are currently partnering with the National Institutes of Health (NIH) on a NIH-funded Phase 2a clinical study of orally-administered MAT2203 in patients with refractory mucocutaneous candidiasis. This study is currently enrolling patients and is an open-label, dose-titration trial in up to 16 patients to study the efficacy, safety, and pharmacokinetics of MAT2203 in the treatment of mucocutaneous candidiasis (esophageal, oropharyngeal, or vulvovaginal).

To date, 100% of the three patients who have been treated with MAT2203 have met the primary endpoint of the Phase 2a study, achieving ≥ 50% clinical response. One of the patients achieved an 85% reduction in clinical symptoms after 6 weeks of treatment. MAT2203 was well tolerated with majority of adverse events observed being mild in severity and mostly unrelated to study drug. Importantly, for all patients renal and liver function parameters remained well within normal ranges during the core study as well as during the first 6-month extension of this study.

MAT2203 for the treatment vulvovaginal candidiasis

Topline data from our Phase 2 study in vulvovaginal candidiasis (VVC) using MAT2203 demonstrated that .

In the context of our overall program for MAT2203 with the aim to develop our lead product for the prevention of invasive fungal infections in patients who are immunocompromised due to immunosuppressive therapy, our goal was, in addition to further establishing the safety and tolerability of MAT2203, to demonstrate efficacy of MAT2203 through a mechanism involving systemic absorption in a non-life threatening fungal infection. This study concept is consistent with early human efficacy studies in the development of other anti- fungal therapies. This Phase 2 study was not designed or powered to support an indication for the treatment of VVC and therefore supplant fluconazole as the standard of care. The key data generated from this study includes additional safety and tolerability data.

In this VVC study, the primary endpoint of safety was met, and it was demonstrated that oral delivery of amphotericin B is safe and well tolerated without the renal and hepatic toxicities that can be seen with administration of intravenous amphotericin B. Drug-related treatment emergent adverse events in this study were mostly of mild and gastro-intestinal nature and were seen at a rate of 20%, 18% and 2% respectively for MAT2203 200mg, MAT2203 400mg, and fluconazole. Consistent with the safety observations in the NIH study, in this VVC study no drug-related effects on liver function were observed and kidney function parameters stayed within normal ranges during the entire study for all 91 patients treated with MAT2203 for 5 days.

Development Plan

In January 2018, Matinas met with the FDA to discuss its clinical development and toxicology plans for MAT2203 in Phase 2 and Phase 3 in support of an NDA submission for approval in prevention of invasive fungal infections in patients with ALL. The Company plans to conduct a Phase 2 trial using an adaptive trial design and an optimized dose which we believe will position MAT2203 for approval with a limited indication for prevention of invasive fungal infections in ALL patients. We believe that implementing this streamlined development plan and optimizing the dose could decrease the time and cost of our overall development program for MAT2203.