As noticed by many other colleagues, ICAAC 2015 was a shadow of its former self. Few participants overall, fewer posters, and even fewer exhibitors. Reviewing the posters, there were relatively few from industry, most came from university or small research labs. In a way, ICAAC 2015 was a true reflection of the State of Affairs in anti-infective drug development: it felt like Atlantic City without casinos, or Detroit without car industry: a bit depressing.
Two new antifungals deserve attention. A new start-up, F2G Ltd., presented data on their novel compound (F-901318) which is active against molds, i.e., Aspergillus, Scedosporium and Fusarium. We are told that MICs against aspergillus sp. are all in the 0.01 mg/L range which is excellent but given the technical issues with susceptibility testing in molds it needs confirmation and correlation with in vivo data. It has a novel MoA by inhibiting the dihydroorotate dehydrogenase (DHODH) enzyme. Fungal selectivity is good and fungicidal activity was seen in 2 animal infection models. It is absorbed well enough (>45%) to make oral delivery feasible. In addition, it also has a long plasma t½ (20-30 hrs) and good lung penetration which is important for the obvious reasons.
F-901318 is in Phase 1 and some 80 patients / probands were studied so far. I am not so convinced that the drug is totally free of safety issues; the presentation was just a bit too uncritical in that respect. For instance, we were told neither about the NoAEL from preclinical studies nor about any target organ toxicity at maximum tolerated doses (MTD). Hence, the jury is still out on the safety of this drug. Nonetheless, there is much to like about F-901318.
Another poster caught my eye. A new formulation of amphotericin B (MAT-2203) developed by Matinas BioPharma makes oral delivery possible. This new liposomal formulation of amphotericin (the company calls it “encochleated” AmB) has seemingly made possible a trifecta: oral absorption, macrophage targeting, and specific organ delivery. Of interest, even pulmonary delivery was achieved, something that other liposomal preparations had trouble with (most were only distributed by the RES system to liver and spleen). The drug is ready to go into Phase 2 later this year; it has recently been granted QIDP status by FDA.
Did I mention that MAT-2203 is also claimed to be less toxic than amphotericin B deoxycholate? Well, let’s cross our fingers on this one and wait for Phase 2 data from comparative studies. It’s early days and the bubble of optimism may still pop any time as data accumulate.
Obviously, there is still much good research going on out there. We will continue to follow these promising drug candidates at the next ICAAC. Well, there won’t be any more ICAAC the way it used to be; instead, there will be a new conference called “ASM Microbe”. Good bye, ICAAC, we will miss you. You were a great venue for education and personal meetings. And a lot of fun, too.
