Amphotericin B You Can Swallow A Two-Phase Oral Regimen for Cryptococcal Infection

This application covers a method of treating or preventing a fungal infection caused by Cryptococcus, in which the old standby drug amphotericin B is given by mouth rather than by drip. The patient first gets an “induction” phase of encochleated amphotericin B (a lipid-wrapped form, abbreviated cAMB) together with 5-flucytosine or an azole antifungal, then a “consolidation” phase. It was filed by Matinas BioPharma Nanotechnologies, Inc. and names Ruying Lu, Theresa Matkovits and Raphael J. Mannino as inventors. It is an Australian divisional of application 2020329230.

The Problem

Cryptococcosis is an opportunistic fungal infection. The specification puts it at an estimated 1 million cases and 625,000 deaths a year, driven largely by infection of the central nervous system. Early mortality from HIV-associated cryptococcal meningitis is particularly high, and the document blames this in large part on the cost and toxicity of effective antifungals.

The drug that clears the fungus from cerebrospinal fluid fastest and most reliably is amphotericin B. The trouble is how it has to be given. It goes in intravenously, which means a hospital bed, intravenous fluids and supplemental electrolytes, and because it can be toxic it also needs rapid and reliable laboratory monitoring. The specification says that is exactly why treatment centres in low and middle income countries, where cryptococcal meningitis is most common, often find it hard to use amphotericin B at all.

What This Invention Does

Claim 1 is a method of treating or preventing a fungal infection in a subject comprising a Cryptococcus species. The method has an induction treatment phase and a consolidation treatment phase. In the induction phase the subject receives encochleated amphotericin B and 5-flucytosine or an azole, and both drugs are given mucosally. The spec says “mucosally” means orally or intranasally, and dependent claim 3 narrows it to oral.

The title and abstract describe the same method. One small point worth knowing: the abstract and some body passages say just “amphotericin B (cAMB)”, while claim 1 is explicit that the amphotericin B is encochleated. The article follows the claim.

The dependent claims fill in the regimen with numbers. The cumulative daily dose of cAMB in induction is at least 1 gram (claim 5), 1.5 grams (claim 6) or 2 grams (claim 7), given as a divided dose rather than in one hit (claim 4). Flucytosine is dosed at 100 mg/kg/day, the induction phase is 14 days in the claimed embodiment, and the consolidation phase can use oral fluconazole at about 800 mg/day, with an optional maintenance phase of fluconazole at about 200 mg/day. Further dependent claims cover cryptococcal meningitis, Cryptococcus neoformans, Cryptococcus gattii, HIV-infected subjects, and infections showing reduced sensitivity or resistance to fluconazole. A final dependent claim recites the cAMB formulation itself: amphotericin B with a phospholipid, EDTA, water, vitamin E, calcium chloride, methylcellulose and a list of preservatives and flavouring agents.

The worked example is a Phase I safety trial run in Kampala, Uganda between October 2019 and January 2020 in HIV-positive people who had survived earlier cryptococcal meningitis. Phase 1A enrolled 27 participants in three cohorts of nine, dosed at 1.0, 1.5 and 2.0 grams a day in 4 to 6 divided doses. Phase 1B enrolled 9 more on 1.5 grams a day for 7 days, taken as outpatients. No serious adverse events occurred in any cohort, and the 1.5 gram dose was picked for Phase 1B as the dose that was 100 per cent tolerated. Nausea was scored “none” for 8 of 9 participants in each of the 1 gram and 1.5 gram cohorts and 7 of 9 in the 2 gram cohort. After the study, 96 per cent (26 of 27) of Phase 1A participants said they would prefer cAMB to intravenous amphotericin B for treating cryptococcal meningitis.

On pharmacokinetics, the plasma exposure did not differ significantly across the three doses, averaging 2350 ng*h/mL. The half-life was 53 hours and the mean peak concentration was 63.0 ng/mL at 24 hours. In the 1.5 gram Phase 1B group, the 24 hour level was 77 per cent of the day 7 level.

Phase II is described in the future tense. It is a proposed four-stage randomised study with oral cAMB plus oral flucytosine in the induction phase, ending in Stage 4, which tests oral cAMB with no intravenous amphotericin B at all (40 experimental participants against 20 on the standard regimen). The specification contains no efficacy results from that study.

Key Features

• Both induction drugs go in by mucosal route. Claim 1 requires the cAMB and the flucytosine or azole to be given mucosally, which the spec says includes oral and intranasal routes. The aim is to take intravenous infusion out of the induction phase.
• Encochleated amphotericin B. The drug is carried in a cochleate, a rolled-up lipid structure that the specification describes as protecting the cargo and being engulfed by macrophages, where the drug is released.
• Divided daily dosing. Instead of one large dose, the cAMB is spread across several doses a day, with individual doses typically below 400 mg. The spec argues this allows up to 2 grams a day in total with fewer gastrointestinal adverse events and greater bioavailability than a single daily dose.
• Induction then consolidation. A 14-day induction is followed by a consolidation phase, in which oral fluconazole at about 800 mg/day can be combined with oral cAMB, and then fluconazole at about 200 mg/day as maintenance.
• Works without fluconazole. Because the induction can use flucytosine alone as the partner, the spec says the regimen can serve patients whose infection is less sensitive to or resistant to fluconazole.
• Stated target for fungal clearance. The spec ties the regimen to an early fungicidal activity of at least -0.20 log10 CFU/mL/day of cerebrospinal fluid, which it links to better 10-week survival.

Who Is Behind It

The applicant is Matinas BioPharma Nanotechnologies, Inc., which appears to be the operating subsidiary of Matinas BioPharma Holdings, Inc. That company’s website at matinasbiopharma.com describes a Lipid Nano-Crystal platform for oral delivery of small molecules, and describes its MAT2203 product as an amphotericin B product built on that platform. The specification itself never names MAT2203, so the link between that product and this claim is an inference from the company’s own description, not something the document says. The same site lists a July 2026 announcement of a business combination with GH Power and a definitive agreement to sell the platform and MAT2203 to Azurity Pharmaceuticals, so ownership of this family may change.

The specification says the work was made with US government support under National Institutes of Health grant R01 NS110519.

On priority, the application is a divisional of Australian application 2020329230, the Australian national phase of PCT/US2020/046114 filed 13 August 2020. It claims four US provisional applications: 62/886,118 (13 August 2019), 62/916,482 (17 October 2019), 62/962,427 (17 January 2020) and 63/011,091 (16 April 2020). That makes the priority country the United States.

Why It Matters

The treatment standard that the specification measures itself against is the World Health Organization’s guidance. The 2018 guideline quoted in the document recommends two weeks of flucytosine plus fluconazole, or two weeks of amphotericin B deoxycholate plus fluconazole, for induction. WHO’s later 2022 guideline moved to a single high dose of liposomal amphotericin B together with flucytosine and fluconazole, which it says is as effective with lower toxicity and fewer monitoring demands. The motivation for the cAMB approach is the same one WHO is addressing: amphotericin B works best, and the hurdle is the delivery route and the monitoring around it.

Where this application differs is that it tries to remove the infusion altogether. If an oral formulation can do the job in outpatients, a clinic without hospital beds and a laboratory could in principle use the most effective antifungal. The Phase I data show it can be taken at 1 to 2 grams a day with mostly mild adverse events in a small group of 36 people, but those people had already recovered from the disease. Whether oral dosing clears the fungus from the cerebrospinal fluid of people with active infection is the question Phase II is designed to answer, and this document does not report that answer.

Related Concepts

• Cryptococcosis – the fungal disease the regimen treats, including its meningitis form.
• Amphotericin B – the polyene antifungal whose intravenous toxicity the oral formulation tries to avoid.
• Flucytosine – the induction partner drug, dosed at 100 mg/kg/day in the claimed regimen.
• Fluconazole – the azole used in the consolidation and maintenance phases.
• Cochleate – the lipid carrier structure that wraps the amphotericin B for oral delivery.
• Cryptococcus neoformans – the main yeast species named in the dependent claims.

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AU 2026202236 was published in the Australian Official Journal of Patents on 9 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.