Amplyx boosts pipeline with Novartis antiviral, unveils phase 2 data for lead antifungal

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Amplyx's lead drug, fosmanogepix, attacks fungal cells from the inside as well as the outside. It works by blocking an enzyme called Gwt1 that works in the endoplasmic reticulum, what the company's CEO calls the “manufacturing hub” of the cell. (Pixabay)

Amplyx Pharmaceuticals revealed early data for a phase 2 study of its lead program in the fungal infection candidemia and licensed a phase 2-ready program for the treatment of BK virus infection from Novartis. 

The San Diego-based biotech was founded in 2015 to create a new class of antifungals that can cause life-threatening infections, with a focus on vulnerable, immune compromised patients. It is developing its lead program, fosmanogepix (APX001) to treat fungal infections, including candidemia, when Candida gets into the bloodstream 

Amplyx had a pair of data review committees look at the data from the first 10 patients in the phase 2 study of fosmanogepix: “One is charged with evaluating efficacy and the other is charged with evaluating safety,” Amplyx CEO Ciara Kennedy, Ph.D., told FierceBiotech. 

The data review committee found that the drug showed a “high level of treatment success” at the end of the open-label study based on a trio of measures. Data from open-label studies can be hard to analyze, but Amplyx went ahead with it because its endpoints are binary. 

“If you’re studying pain, results can be challenging to interpret,” Kennedy said. “But our endpoint is objective as it is—blood culture either goes negative or it doesn’t. Patients are either alive or they’re not. They either had additional antifungal drugs given or they haven’t. The study definition of therapeutic success is they meet all three of the criteria.” 

The data safety monitoring board recommended the study continue. Amplyx will enroll a total of 20 patients in the U.S., Europe and Israel by the end of the year. 

Fosmanogepix goes after fungal pathogens using a completely new mechanism of action. It’s one of several reasons Kennedy got involved with Amplyx back in 2015. Fosmanogepix attacks fungal cells from the inside as well as the outside. It works by blocking an enzyme called Gwt1, which works in the endoplasmic reticulum, what Kennedy calls the “manufacturing hub” of the cell. 

"Its job is to process mannoproteins so they can be exported to the cell wall and cover the cell wall … If you strip a cell of mannoprotein, it becomes visible and vulnerable to the immune system and is also not as viable as a cell that has the proper mannoprotein cell wall constitution. It’s a good way to attack a fungal cell,” she said. 

What’s more, inhibiting Gwt1 means mannoproteins don't exit the endoplasmic reticulum, causing a stress response and leading the cell to die. 

Fosmanogepix is suitable for tackling fungi beyond Candida because Gwt1 is “highly conserved across a broad range of fungal pathogens,” Kennedy said. “Most importantly, it’s not in the human body, so there’s no target-driven toxicity in patients.” 

RELATED: Spying a chance to stop a ‘catastrophic threat,’ VCs funnel $67M into Amplyx to trial a broad-spectrum antifungal

As for the Novartis deal, Amplyx picked up the exclusive worldwide rights to a monoclonal antibody, MAU868, but kept financial details under wraps. The drug targets BK virus, a virus that most people catch in childhood and that can cause symptoms like that of the common cold. 

“The difference is that BK virus doesn’t get cleared by the immune system entirely. It will hide out in the epithelial cells of the kidney and never present you another challenge in your lifetime unless you become immune suppressed,” Kennedy said. 

The dormant virus can “wake up” in people who have had organ transplants, as they need immunosuppressive drugs to stop their body from rejecting their new organ. Amplyx aims to start phase 2 trials in two patient groups: patients who have undergone kidney transplant and patients who have received a stem cell transplant. The studies are slated to launch early next year, Kennedy said. 

MAU868 binds to all four serotypes of the BK virus, “mops it up” and prevents its spread to other cells, she said. 

If left unchecked in kidney transplant patients, BK virus replicates in individual cells, which can burst, spreading virus to the blood and other kidney cells. This could damage the transplanted kidney enough to shorten its life, necessitating another transplant for the patient. 

Stem cell transplant patients can face kidney damage from BK virus, but mostly suffer inflammation that’s localized to their bladders. 

“It can be extraordinarily painful, can require blood transfusion and pain relief, and impedes recovery from a bone marrow transplant. It can extend a hospital stay by weeks and weeks to keep it under control,” Kennedy said.