Amplyx: Amplyx touts upbeat readout from a small PhII study for lead antifungal

Amplyx, a biotech focused on treating patients with compromised immune systems, is touting its lead program following a Phase II study.The San Diego-based company announced its results Monday morning for fosmanogepix, an antifungal that treats life-threatening Candida infections. Execs at the company say that topline data from the study indicated a treatment success rate of 80 percent, meeting the primary endpoint and paving the way to a pivotal trial ahead."Treatment success here means that they cleared their infections, and they didn't need any other antifungal drugs, and they didn't die," Amplyx CEO Ciara Kennedy told Endpoints News. "So 80 percent of patients had the perfect response to this drug, and they tolerated the drug well."Amplyx enrolled 21 patients in a small, open-label study, and 20 were included in the modified "intent-to-treat" population. Individuals were treated for 14 days, with at least the first three days requiring IV treatment once or twice daily. Following that period, patients could choose to continue IV treatments once a day or switch to pills for the remainder of that period.At the end of 14 days, 16 of the 20 individuals saw clearance of Candida from blood cultures without needing additional antifungal treatment. After 30 days, 18 of the 21 patients survived, meeting a secondary endpoint. Though it's difficult to draw any sweeping conclusions, Amplyx is focused on advancing to the next step."The dose that we selected to go into this trial is a very active, well-tolerated dose, and a dose that would pair well in Phase III, because in Phase III these are not placebo control trials; that would be unethical," Kennedy said. "These are active comparator Phase III trials where you're going up against the standard of care. So we know that, based on this data, we'll go into our Phase III with confidence."Kennedy added that a Phase III trial will likely start sometime next year and take about two years to complete, with Amplyx planning to apply for an NDA sometime in 2023 or 2024 should fosmanogepix continue to prove effective.The compounds that Amplyx researches and develops are not meant to treat what people typically think of as fungal infections, like skin or toenail infections, Kennedy emphasized. Rather, the biotech focuses on diseases in which sick or immunosuppressed people are already vulnerable. These are caused by two categories of fungal pathogens: yeast, like Candida strains, and mold, like aspergillus.These pathogens are generally everywhere, Kennedy said. Everyone breathes in mold spores all the time, but immune systems can fight them off when functioning normally. Candida, on the other hand, lives in humans' GI tracts. At-risk individuals can contract Candida infections if the fungus gets into the bloodstream during surgery or after a traumatic injury."Any time you're accessing a patient's blood and deliver drugs or nutrition or fluids, or anything like that, or a catheter to remove fluids, that's a source of Candida infections," Kennedy said. "It's a hospital-acquired infection, just like a bacterial infection, and obviously hospitals do their best to control the source of these infections. It's almost impossible to completely eliminate that risk."Treatments for these types of Candida infections have only developed relatively recently, and many of them came with severe side effects. Older medicines induced kidney or liver toxicity and some are still in use today simply because hospitals don't have better options. Today, the most common treatment is the administration of an echinocandin through an IV, but the molecules themselves are large - sometimes infections can recur after symptoms diminish because the treatment misses a "reservoir" of Candida in tighter spaces, Kennedy said.Fosmanogepix differs from previous treatments because it specifically inhibits GWT1, a fungal enzyme not present in humans that helps process proteins inside fungal cells. This not only makes the cell more vulnerable by attacking its "armor," but also causes a buildup of proteins within the cell causing it to implode."One underlying theme in this whole space is diagnostic tools are slow, you have to wait for the bug to grow, but you have to start treating patients right away," Kennedy said. "We really wanted to show that this new mechanism has the safety profile, has the efficacy profile, can deal with the resistance issue, and the data all lines up beautifully."There isn't much competition on the market in this area except against the echinocandins, Kennedy said. However, Amplyx also saw signs indicating fosmanogepix can treat a wide-range of fungal infections due to GWT1 targeting, including strains that are typically drug-resistant.If the human testing continues to perform as well as Amplyx's animal testing, Kennedy sees far broader potential for fosmanogepix."In oncology, for example, you can give a mouse a tumor and cancer, and cure it, but that drug will go on to fail in the clinic," Kennedy said. "The translation is much, much higher in the whole infectious disease setting ... the translation from animal to clinical is exactly as you would expect."