oral amphotericin B (MAT2203) / Matinas - LARVOL DELTA

New and emerging drugs for the treatment of invasive fungal infections. (PubMed, Expert Opin Pharmacother) - "Data were identified using PubMed searches for the terms 'antifungal,' 'olorofim,' 'SUBA-itraconazole,' 'ibrexafungerp,' 'rezafungin,' 'fosmanogepix,' and 'encochleated amphotericin B.' Approved agents include ibrexafungerp, an oral triterpenoid inhibitor of 1,3-β-D-glucan synthase; rezafungin, a long-acting echinocandin with weekly dosing; and SUBA-itraconazole, a reformulation of itraconazole with more consistent absorption. Despite improvements, gaps remain in treatments for severe IFI, particularly given increasing resistance. These agents represent significant advances, but further research is needed to define their use in patient management."

Journal • Review • Dermatology • Infectious Disease

Optimization and prioritization of paediatric drugs for visceral leishmaniasis. (PubMed, Front Pediatr) - "The group prioritized a 20 mg scored, dispersible tablet formulation of miltefosine and an oral solid dosage form of amphotericin B, acknowledging recent developments in allometric dosing for miltefosine and ongoing research for the development of oral amphotericin B. For miltefosine, this prompted an ongoing update of the WHO Prequalification Expression of interest to promote generic manufacturing. A compound with a new mechanism of action, LXE408, which is currently being investigated in Phase II, was included in the PADO watch list, signalling that paediatric investigations should start as soon as enough data are available from adult studies, not to delay access to latest available innovations for children with VL."

Journal • Infectious Disease • Pediatrics

Experience of research nurses with oral encochleated amphotericin B for treatment of cryptococcal meningitis in a resource-limited setting. (PubMed, BMC Infect Dis) - P1/2 | "Oral amphotericin B was generally safe and well tolerated. However, it requires some training for the nurse, patient and care takers for better administration, adherence and treatment outcomes."

Journal • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease

Antifungal pipeline: New tools for the treatment of mycoses. (PubMed, Rev Iberoam Micol) - "New antifungal agents, such as ibrexafungerp, rezafungin, oteseconazole, and miltefosine, offer novel mechanisms of action along with reduced toxicity...This review provides a comprehensive overview of these new agents and their mechanisms, and explores the challenges and roles of antifungal drugs in LMICs, where the burden of fungal infections is high. Continued research and development are essential to address the rising incidence and resistance of fungal infections globally."

Journal • Dermatology • Infectious Disease

Howell-Jolly Body-Like Neutrophil Inclusions Following Hematopoietic Stem Cell Transplantation: A Case Report. (PubMed, Am J Case Rep) - "The therapeutic regimen was escalated to include oral amphotericin B, while continuing tacrolimus and discontinuing all other immunosuppressants. CONCLUSIONS The present case highlights the presence of Howell-Jolly body-like inclusions within the cytoplasm of neutrophils observed in the peripheral blood smear of a patient after hematopoietic stem cell transplantation. Morphological analysis suggests that the emergence of these inclusions is highly likely to be induced by medications used in the treatment of GVHD."

Journal • Bone Marrow Transplantation • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Human Immunodeficiency Virus • Immunology • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Transplantation

Use of Miconazole Cream As Adjunctive Therapy to Treat Isolated Sinus Mucormycosis: A Case Report and Literature Review. (PubMed, Cureus) - "An extensive surgical debridement and liposomal amphotericin B were the mainstay of treatment. Therefore, recent studies have proposed new adjuvant modalities, such as hyperbaric oxygen therapy and local treatment with amphotericin B. In this study, we propose a new adjuvant therapy using local miconazole cream which showed a good prognosis with the combination of oral amphotericin B and surgical debridement. This highlights the necessity for extensive future clinical trials to validate its effectiveness in treating isolated sinus mucormycosis."

Journal • Review • Infectious Disease • Metabolic Disorders • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Cryptococcal invasion: a comprehensive case of adrenal and systemic infection amid immunosuppression. (PubMed, BMC Infect Dis) - "The patient, previously diagnosed with primary myelofibrosis and undergoing oral Ruxolitinib treatment, exhibited immunosuppression. Following a month of oral antifungal treatment, marked reductions in capsular antigen levels were noted, to 1:640 and 1:160 in serum and cerebrospinal fluid, respectively. The patient was discharged on a regimen of oral amphotericin B, flucytosine, and fluconazole, with regular outpatient follow-ups showing no signs of recurrence or dissemination."

Journal • CNS Disorders • Endocrine Cancer • Infectious Disease • Inflammation • Myelofibrosis • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

Development and deployment of a solid oral amphotericin B dosage form to treat visceral leishmaniasis within a pediatric population. (PubMed, PLoS Negl Trop Dis) - "Currently, the intravenous single-dose liposomal amphotericin B is the first choice for the treatment of VL. To solve this problem, the development of a solid oral amphotericin B formulation that is cost-effective, safe, tropically stable, and easy to swallow, making it more accessible to children, particularly in rural communities having limited access to medical clinics or trained healthcare professionals is imperative. This viewpoint will discuss the opportunities and challenges of developing an oral amphotericin B formulation for a pediatric population."

Journal • Review • Infectious Disease • Pediatrics

Successful Treatment of Refractory Cutaneous Protothecosis With MAT2203, an Oral Lipid Nanocrystal Formulation of Amphotericin B. (PubMed, Open Forum Infect Dis) - "Prototheca wickerhamii is a rare cause of cutaneous and systemic infection that requires long treatment courses with potentially toxic medications. We describe a patient with cutaneous protothecosis refractory to triazole monotherapy who experienced clinical and radiographic improvement with the novel oral lipid nanocrystal formulation of amphotericin B without experiencing toxicity."

Journal • Infectious Disease

Oral Lipid Nanocrystal Amphotericin B (MAT2203) for the Treatment of Invasive Fungal Infections. (PubMed, Open Forum Infect Dis) - "MAT2203 was well tolerated with only modest gastrointestinal adverse effects. This new oral formulation might provide a safer treatment option for patients requiring extended courses of AmB."

Journal • Gastrointestinal Disorder • Infectious Disease

CAMB/MAT2203 in Patients With Mucocutaneous Candidiasis (clinicaltrials.gov) - P2 | N=4 | Completed | Sponsor: Matinas BioPharma Nanotechnologies, Inc. | Phase classification: P2a ➔ P2

Phase classification • Candidiasis

Efficacy of an oral lipid nanocrystal formulation of amphotericin B (MAT2203) in the neutropenic mouse model of pulmonary mucormycosis. (PubMed, Antimicrob Agents Chemother) - "We sought to compare the efficacy of MAT2203 to liposomal amphotericin B (LAMB) treatment in a neutropenic mouse model of IM due to Rhizopus arrhizus var. Furthermore, while both MAT2203 and LAMB treatment resulted in a significant reduction of ~1.0-2.0log and ~2.0-2.5log in Rhizopus delemar or M. circinelloides lung and brain burden vs placebo mice, respectively, LAMB significantly reduced tissue fungal burden in mice infected with R. delemar vs tissues of mice treated with MAT2203. These results support continued investigation and development of MAT2203 as a novel and oral formulation of amphotericin for the treatment of mucormycosis."

Journal • Preclinical • Infectious Disease

Successful In Vivo Oral Delivery of Biologically Active and Therapeutic Anti-Inflammatory mRNA-Targeted Oligonucleotides with a Lipid Nanocrystal Delivery Platform (ASGCT 2024) - "Matinas BioPharmas' lipid nanocrystal (LNC) platform successfully delivers oral amphotericin-B in patients with cryptococcal meningitis, and other ex vivo work has shown avid LNC uptake by innate immune cells... In the imiquimod psoriasis model (Figure 1) daily oral administration of an LNC formulation of the IL-17A targeted oligo resulted in both knock-down of skin IL-17 mRNA, and significant improvement in clinical parameters of redness and scaling... The LNC delivery platform can successfully orally deliver biologically active (and potentially therapeutic) oligonucleotides targeting key cytokines in inflammatory disease models. While these initial results are promising, there is still some individual heterogeneity of response; future work will be focused on optimizing the LNC formulations to improve delivery efficiency, increase their potency, and extend the application of oral cytokine-targeting oligo therapeutics in other inflammatory diseases. models.Plain..."

Preclinical • CNS Disorders • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Psoriasis • IL17A • TNFA

Pipeline of Novel Antifungals for Invasive Fungal Disease in Transplant Recipients: A Pediatric Perspective. (PubMed, J Pediatric Infect Dis Soc) - "The overarching goal of this review is to discuss the mechanisms of action, spectrum of activity, stage of development, and pediatric-specific data for the following agents: encochleated amphotericin B deoxycholate, fosmanogepix, ibrexafungerp, isavuconazole, olorofim, opelconazole, oteseconazole, and rezafungin. Additionally, key drug attributes of these novel agents and their potential future therapeutic roles in pediatric transplant recipients are discussed."

Journal • Infectious Disease • Pediatrics • Transplantation

New treatment options for critically important WHO fungal priority pathogens. (PubMed, Clin Microbiol Infect) - "While the limited number of targets and the emergence of resistance have posed challenges to antifungal treatment, new drugs such as ibrexafungerp, rezafungin, fosmanogepix, or olorofim have shown promising clinical efficacy. These drugs not only provide alternative options for invasive fungal infections but also alleviate treatment in outpatient settings. More clinical data, implementation of stewardship programs, and surveillance, including utilization of drugs in agriculture are necessary to prevent resistance development and ensure the safety and efficacy of these new agents."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Update on therapeutic approaches for invasive fungal infections in adults. (PubMed, Ther Adv Infect Dis) - "We discuss management of complex infections with specific emerging fungi such as Scedosporium spp., Fusarium spp., Trichosporon asahii, and Candida auris. We briefly explore newer antifungal agents or formulations that are now being investigated to overcome therapeutic pitfalls, including but not limited to olorofim, rezafungin, fosmanogepix, and encochleated Amphotericin B. We discuss the role of surgical resection or debridement, duration of treatment, follow-up modalities, and need for secondary prophylaxis, all of which remain challenging, especially in patients chronically immunocompromised or awaiting more immunosuppressive therapies."

Journal • Review • Bone Marrow Transplantation • Immunology • Infectious Disease • Oncology • Transplantation

5-Flucytosine Longitudinal Antifungal Susceptibility Testing of Cryptococcus neoformans: A Substudy of the EnACT Trial Testing Oral Amphotericin. (PubMed, Open Forum Infect Dis) - "There is no evidence of baseline resistance to 5FC or incident resistance during combination therapy with oral or IV amphotericin B in Uganda. Oral amphotericin B can safely be used in combination with 5FC."

Clinical • Journal • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease

MAT2203, A Novel Oral Delivery of Amphotericin B (AMB), in Phase 3 Development for the Treatment of Invasive Fungal Infections (Matinas BioPharma) (IDWeek 2023) - No abstract available

P3 data • Infectious Disease

Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial. (PubMed, Clin Infect Dis) - P1/2 | "This new oral amphotericin B LNC formulation appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than IV amphotericin."

Clinical • Journal • CNS Disorders • Dermatology • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease

Emerging Diagnostics and Therapeutics for Invasive Fungal Infections. (PubMed, Infect Dis Clin North Am) - "Compared with traditional fungal diagnostics, molecular assays promise improved sensitivity and specificity, the ability to test a range of samples (including noninvasive samples, ie, blood), the detection of genetic mutations associated with antifungal resistance, and the potential for a faster turnaround time. Antifungals in late-stage clinical development include agents with novel mechanisms of action (olorofim and fosmanogepix) and new members of existing classes with distinct advantages over existing antifungals in toxicity, drug-drug interactions, and dosing convenience (oteseconazole, opelconazole, rezafungin, ibrexafungerp, encochleated amphotericin B)."

Journal • Review • Infectious Disease • Transplantation

"Mat2203" (@TomODon20597528)

Part 2: Mucormycosis: Focus on Therapy. (PubMed, Expert Rev Anti Infect Ther) - "A literature search of mucormycosis therapies was performed via PubMed (up to December 2022), using the key words: invasive fungal infections; mold; mucormycosis; Mucorales; amphotericin B; isavuconazole; posaconazole. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy but oral triazoles (posaconazole and isavuconazole) may be effective as step-down therapy, in MCR cases refractory to or intolerant of LFAB. We encourage early surgical debridement or excision as adjunctive measures."

Journal • Review • Diabetes • Hematological Disorders • Infectious Disease • Metabolic Disorders • Neutropenia

"Mat2203" (@TomODon20597528)

"Do you expect the FDA to approve the Phase 3 trial for MAT 2203 for various IFI?" (@BestLawyerLA)

FDA event • P3 data

"Mat2203" (@TomODon20597528)