The active ingredient in our product Bulanta  ^TM   and the existing product on the market is busulfan, a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates. Its chemical designation is 1,4- butanediol dimethanesulfonate. IV busulfan is used in pediatrics and adults as a conditioning agent prior to bone marrow transplantation in leukemias, lymphomas, and myeloproliferative disorders. It was approved in 1999 for the treatment of chronic myeloid leukemia (CML) and today there are various generic forms on the market.

For solubility, IV busulfan uses excipients comprised of N,N- Dimethylacetamide (“DMA”) and PEG400. DMA is classified as a Type 2 solvent, which the FDA defines as “Solvents to be limited…because these are Nongenotoxic animal carcinogens or possible causative agents of other irreversible toxicity such as neurotoxicity or teratogenicity [or] Solvents suspected of other significant but reversible toxicities.” The Daily Permissible Exposure to DMA is listed as 10.9 mg/day.

Our new IV busulfan formulation, Bulanta ^TM, does not contain DMA. It is common practice to dose patients with current IV busulfan formulations containing DMA that exceed the permitted daily exposure (PDE) of 10.9 mg/day (ICH; International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Step 4, April 2021). For example, a young adult male with a height of 5’10” and a weight of 75 kg (165 lbs.) would, when conditioned with IV busulfan in combination with either cyclophosphamide or fludarabine in a myeloablative regimen, receive a total DMA dose that would be approximately 13.2 grams daily for four days, exceeding by more than 1,000 times the exposure permitted by the ICH. Further, a significant fraction of the population is heavier than 75 kg, and their busulfan dose/DMA exposure would increase accordingly.

We are optimistic that the removal of the Class 2 solvent DMA from the excipients will improve therapies and expand use of our new drug Bulanta ^TM .