MAT2203: Encochleated Formulation of Amphotericin B
|Candidate & Indication||Development Stage|
|MAT2203 Fungal Infections||
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, encochleated 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 available but its IV-delivery results in significant treatment-limiting side effects, including nephrotoxicity. The ability to provide amphotericin B orally using our proprietary and novel oral formulation may offer a new and promising alternative for patients and doctors. MAT2203 is also being explored for treatment of additional anti-fungal indications and may have the potential for Orphan Drug Designation in certain of these indications.
We believe that MAT2203 has the potential to be a best-in-class therapy for both prophylaxis (preventive) and treatment of invasive fungal infections by offering the following key benefits.
- Potential to treat resistant pathogens. We believe that MAT2203 can be used to prevent and treat fungal infections caused by drug resistant fungi, including those resistant to existing azoles and echinocandins, due to amphotericin B's fungicidal (i.e. killing the fungi) nature and potency against resistant strains and the ability of our cochleate drug delivery platform to provide higher and safer drug exposure early in the course of therapy.
- Enabling prophylaxis regimens. Many patients cannot receive azole prophylactic therapy due to drug to drug interactions or poor tolerability, while the long term preventative use (6-14 weeks) of IV echinocandins is impractical and expensive. Amphotericin B is known to have limited drug to drug interactions. We therefore expect that our orally available MAT2203 could provide for better prophylactic therapy on an inpatient and outpatient basis, particularly for those patients with a hematologic malignancy, such as leukemia.
- Single agent treatment. Rather than treating patients with an IV echinocandin followed by an oral azole solely to enable earlier hospital discharge, MAT2203 is expected to allow physicians to either begin treatment with a safe and effective broad spectrum antifungal or use MAT2203 as a preventative treatment in those patients who are most susceptible to contracting a serious or deadly IFI due to immunosuppressive therapy.
- Shorter and less costly hospital stays and lower outpatient costs. By providing physicians and patients with access to an orally available, broad spectrum fungicidal agent in MAT2203, there is the potential to significantly reduce hospital costs, which account for over 70% of the overall treatment cost of invasive candidiasis.
The FDA has designated MAT2203 as a Qualified Infectious Disease Product (QIDP) for the treatment of invasive candidiasis and the treatment of aspergillosis, as well as for the prevention of invasive fungal infections due to immunosuppressive therapy. The QIDP designation offers certain incentives for the development of new antibacterial or antifungal drugs, priority review and, if approved by the FDA, eligibility for an additional five years of marketing exclusivity. Fast Track designation enables more frequent interactions with FDA to expedite drug development and review.
We are currently partnering with the National Institutes of Health (NIH) on a NIH -funded Phase 2a clinical study with MAT2203 (CAMB) in patients with refractory mucocutaneous candidiasis. This study is ongoing and enrolling patients and is an open-label, dose-titration trial in up to 16 patients to study the efficacy, safety, and pharmacokinetics of oral CAMB in the treatment of mucocutaneous candidiasis (esophageal, oropharyngeal, or vulvovaginal). In early June 2017, the Company reported interim data from the NIH-Conducted Phase 2a Clinical Study of Orally-Administered MAT2203 for the Treatment of Chronic Refractory Mucocutaneous Candidiasis. At that time, two out of the two patients with long-standing azole resistant mucocutaneous candidiasis met the primary endpoint of the Phase 2a study, achieving ≥ 50% clinical response with treatment of MAT2203. Patient #01 achieved a 57% reduction in clinical symptoms after 8 weeks on therapy while patient #02 achieved an 85% reduction in such 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 both 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. In July 2017, the NIH/NIAID institutional review board approved continuation of treatment of patients in the study-extension for an additional 6 months, for total extension of up to one year.
In late June 2017, we announced the topline data from our Phase 2 study evaluating MAT2203 for the treatment of Vulvovaginal Candidiasis (VVC). The Company met its primary endpoint and was able to demonstrate that oral delivery of encochleated amphotericin B is safe and well tolerated without the severe kidney and liver toxicities typically 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.
The goal of the VVC study was to further establish the safety and tolerability profile of MAT2203 while demonstrating efficacy through a mechanism involving systemic absorption. Given the limited study options because of ethical constraints, we chose VVC as it provided a model to demonstrate oral and safe systemic delivery while allowing for efficient and expedient recruitment of patients. In other words, this study indication would increase patient exposure and put us on a faster path toward a pivotal registration trial however, our intention was never to pursue an indication for the treatment of VVC. Because placebo controlled trials are not conducted in this area for obvious reasons, we were left to utilize the standard of care in VVC, fluconazole, as an active control. According to the key clinicians and opinion leaders in this space, comparison to fluconazole is really of limited or no relevance given the ultimate development goals for MAT2203 in indications where fluconazole is contraindicated or inferior.
Based on the overall data set we have generated to date, we plan to seek an FDA meeting in the near term to discuss the data and the development path forward toward commencing a registration trial for an indication for the prevention of invasive fungal infections in patients with ALL (Acute Lymphoblastic Leukemia) as the next step in our overall development program for MAT2203 following the conclusion of our planned and announced Phase 2 PK/Tolerability study of MAT2203 in leukemia patients.
We are pursuing a first indication for the prevention of invasive fungal infections in patients with ALL because the risk for invasive fungal infections (IFIs) in patients being treated for ALL is high, with an associated high risk of lethality. Currently, there is no standard of care for preventing these high risk IFIs in ALL patients. The established treatment regimens for ALL are highly sensitive to liver-metabolized drug-drug interactions, causing serious concerns for drug-drug interaction induced side-effects. amphotericin B is not liver metabolized and when incorporated in the lipid-crystal nano-particle structure of MAT2203, this otherwise toxic IV only compound can now be safely orally administered (providing patient convenience over ~12 weeks prophylactic treatment duration), without the typical kidney and liver toxicity associated with other amphotericin B formulations.