Could you provide a brief overview of Amplyx and the evolution of the company over the last few years?
Amplyx has been in existence for approximately 10 years. For the first seven years, we were a research-focused, NIH grant-funded company, formed on a medicinal chemistry platform licensed from Stanford that focused on re-engineering effective drugs to reduce their toxicities. This work led Amplyx to the fungal space, as many drugs that are effective at killing pathogenic fungi also damage human cells, and we are now developing leading molecules for the treatment of life-threatening infections in vulnerable, immune-compromised patients. Our patients undergoing chemotherapy and other immunosuppressive treatment regimens, which makes them particularly susceptible to fungal infections. Existing therapies for invasive fungal infections are extremely limited, can be difficult to administer, often have toxic side effects and are ineffective against fungi that have developed resistance. We have made it our focus to advance a novel class of therapies within the fungal space, creating products which can have transformational value for patients.
Could you introduce us to your lead molecule – APX001?
Amplyx is currently advancing a novel small-molecule therapy - APX001 - in clinical development. This molecule is an inhibitor of an enzyme, Gwt1, responsible for the modification and cell surface localization of mannoproteins: proteins that anchor the fungal cell wall and provide cell wall integrity. Mannoproteins are synthesized in the endoplasmic reticulum (ER) and exported to the fungal cell wall. When a cell wall is coated with mannoproteins, the cell is pathogenic and can evade the host immune system, thereby propagating the infection. However, when the mannoprotein is eliminated from the fungal cell wall, the cell wall is defective and causes the cell to lose its pathogenicity and ability to evade the host immune system. Amplyx’s target has a dual effect: it impacts the cell wall, which impacts how the cell can function; the compound also creates a backlog within the trafficking machinery of the cell, which causes ER stress, resulting in cell death.
It’s important to note that Gwt1 is highly conserved across pathogenic yeasts and molds, including multi-drug resistant strains and the rare, hard-to-treat molds. In addition, the closest human analogs for Gwt1 is a protein called PigW, we know that APX001 has no activity against PigW, so we believe that targeting Gwt1 could provide a much safer way to combat fungal infections. Our molecule, which is now in Phase 2 of clinical trials, aims to counteract resistance, as we have seen activity against resistant pathogens in preclinical studies. Based on a growing set of Phase I data, Amplyx now has the potential to bring forward a novel safe antifungal drug, with a broad spectrum of activity, covering yeast infections, molds, rare molds and dimorphic fungi. This product can also be used in combination with other drugs, and it can uniquely be delivered in both IV and oral formulations. The Centers for Disease Control and Prevention (CDC) has tested our product against its full panel of Candida auris, an emerging multi-drug resistant pathogen, and has found our target to be the most active agent. Our current prediction is that the APX001 will be effective for at least 15 years post-launch.
Could you elaborate on the current investment climate for infectious diseases?
In 2015, the infectious disease space was making a comeback (with respect to investment), and there were a significant number of companies with healthy market cap valuations. The investment climate looks quite differently now, and there are companies that have followed all the right steps for their programs but have comparatively low market caps. Antibacterial companies are particularly suffering and are being hurt by commercial dynamics, as well as the way in which anti-bacterial products are used in hospitals, and how they are being reimbursed in particular. Conversely, anti-viral companies are doing fine. Previously, positive results in Phase I for anti-infective companies were viewed as a significant de-risk of developmental programs, therefore attracting high-quality private investors. In the current capital markets climate, it is significantly challenging for infectious disease companies to raise funds.
As an antifungal company, we see some of the same challenges that many antibacterial companies face, but antibacterial development is bolstered by public-private partnership models and discussions happening within the anti-bacterial space. Conversely, other than support from NIH, we do not see this sort of support and partnerships in the antifungal sector. It must be said that the commercial landscape for antifungal products is very different to that for antibacterial products, we don’t see the failed/slow uptake launches, and crowed product landscape. These factors coupled with the high mortality associated with fungal infections have enabled Amplyx to raise sufficient capital to continue to develop APX001.
In terms of commercialization and partnerships, what is Amplyx’s strategy moving forward?
We have completed our Phase I study and understand the safety, tolerability and pharmacokinetics of APX001 administered by intravenous infusion. In our Phase 2 study, we will investigate the ability of the product to cure patients. Following that, the next step is registration studies for Candida and rare molds. Once we have validated our targets, we will initiate our registration studies. We will then have our data package to support registration and approval of our IV and oral APX001.
By having the quality of investors that we have on board, we have the option of staying a private company for a while longer, but we are building in as much optionality as possible in terms of how we finance the company. The same holds true for commercialization, and we will look at all options moving forward. We expect 2019 to be a big year for Amplyx in terms of our proof of concept (POC) data.