Development of a Novel Oral Amphotericin B Formulation (iCo-019) to Treat Systemic Fungal and Parasitic Infections
Bibliographic record
Abstract
The Wasan laboratory at the University of British in conjunction with iCo Therapeutics Inc. has made significant strides toward the development of a lipid-based amphotericin B formulation for oral administration. Pre-clinical and clinical studies completed to date indicate that our oral formulations is highly efficacious and exhibits low toxicity within the dosage range required in treating diseases such as systemic fungal infections and leishmaniasis.Each year in the Indian subcontinent alone, over 500,000 individuals play host to Leishmania donovani, an insidious parasite that invades macrophages, rapidly infiltrates the vital organs and ultimately leads to severe infection of the visceral reticuloendothelial system. Visceral leishmaniasis, also known as Kala-azar, is most prevalent in the weak and the young within a population. Left untreated, almost all infected individuals will die. The therapeutic arsenal against Leishmania is limited to a small number of parenterally administered agents, with daily injections of pentavalent antimony compound for 28 days being the usual course of action. Due to increasing resistance, antimonial drugs can no longer be used in many areas, including northeastern India where the incidence of Kala-azar is highest.Amphotericin B is the current secondary treatment of choice against leishmaniasis and has a 97% cure rate with no reported resistance. However, therapy with the first-generation formulation (FungizoneR) involves IV administration over a period of 30 to 40 days and is associated with infusion and drug-related side-effects (infection of the indwelling catheter, patient chills and shaking due to RBC haemolysis, dose-dependent renal toxicity, fever, bone pain, thrombophlebitis).Although lipid-based second-generation formulations exist (AbelcetR and AmBisomeR), which require a shorter course of therapy (3-5 days), are highly effective and exhibit lower toxicity when compared to FungizoneR, the cost of these formulations is a barrier to widespread use. Due to the difficult route of drug administration, toxicity issues and cost, amphotericin B is failing to reach the infected population and mortality rates continue to rise.The development of an inexpensive, safe and effective oral treatment is paramount in order to address both early and late stages of this deadly disease and drug-resistant forms of VL. This talk will highlight our current findings and future goals.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".