Algernon Pharmaceuticals Inc (CSE:AGN) (OTCQB:AGNPF) has been nimble — and unusual — in its hunt for a coronavirus (COVID-19) drug.
The Vancouver-based drug company has taken a generic neurological drug that Sanofi developed in the 1970’s called Ifenprodil, which is approved for use in South Korea and Japan, and is attempting to repurpose it as a potential coronavirus treatment.
Not surprisingly, this puts Algernon in the spotlight as it also steadily advances Ifenprodil as a possible treatment for idiopathic pulmonary fibrosis, acute lung injury, and chronic cough.
Significantly, the company has received the green light from South Korea to start enrolling patients next month in a Phase 2 clinical trial of Ifenprodil as a coronavirus therapy.
Proactive sat down with Algeron Phrmaceuticals CEO Christopher J Moreau to find out more about the company’s Ifenprodil program.
Was Breathtec Biomedical inspired to change its name to Algernon Pharmaceuticals in February last year by Daniel Keyes’ science-fiction masterpiece?
Yes, the idea came from our CSO Dr Mark Williams who loved the novel and the title. As you know it’s about a research program that was developed to make you smarter and the lab mouse (Algernon) did well in the experiment. He did so well in fact, that the janitor decided he wanted to try it and so he did and became smarter as well. He ends up losing all his friends though and wanting to go back to the way he was. At one point he brings flowers to the grave of Algernon. It’s interesting that our lead drug NP-120 is a neurological drug that we are trying to repurpose for lung diseases. Interestingly, when we began this journey, we didn't know which of the 11 drugs we started investigating for new diseases would end up where we are today. Here we are with Ifenprodil as the lead.
On the business side, the company was originally pursuing a point-of-care breath test to help diagnose or screen for lung diseases and since we began to reduce investment in that technology and push full forward on our drug development program, a name change was appropriate.
How does Ifenprodil work as a therapy for patients who experience respiratory complications?
Keep in mind that all of our data has been developed from animal models that mimic or match the human disease for which we are working to develop a treatment. In our initial research stages, we were investigating Ifenprodil for a disease of the lung called idiopathic pulmonary fibrosis (IPF). We used a murine animal model that created fibrosis tissue/scarring conditions in the lungs of the mice that we were studying. Ifenprodil showed a dramatic reduction in fibrosis in the treated arm of the study. We also put Ifenprodil up against two leading human treatments and it outperformed these two drugs. This told us that the drug is active in the lung and is reducing the amount of fibrosis that can build making breathing more difficult and reducing the oxygenation capacity of the lung tissue.
An independent study of Ifenprodil in H5N1 infected mice showed that the drug reduced mortality by 40%, reduced the acute lung injury and inflammation that occurs in the lungs after being infected. H5N1 is far more lethal a form of flu than COVID-19 and so the data suggests that we may see a similar if not a stronger response in humans infected with a far less aggressive or lethal form of the flu, being COVID-19.
We believe that the mechanistic activity of the drug is lessening the inflammatory response called the cytokine storm and as a result can possibly reduce the duration and severity of a COVID-19 infection.
How are you are planning to go forward with a trial in South Korea to examine the effect of ifenprodil on COVID-19 patients with severe pneumonia?
We just received approval for our first Phase 2 Ifenprodil COCVID-19 human trial in South Korea. The trial will be physician-led and will be testing the drug on patients with severe pneumonia to see if we can slow the progression of the disease and perhaps stop them from needing invasive mechanical ventilation meaning with intubation. The study is 40 patients in size with a 4-week treatment schedule and expected to start on May 8.
What’s the latest regarding your Clinical Trial Application to Health Canada for a Phase 2b/3 multinational clinical trial using Ifenprodil as a coronavirus therapy?
We are going through a typical process with Health Canada after filing our phase 2/3 application, which is basically a back and forth question and answer process. We’ve been very pleased with the way that the process has been handled by Health Canada in terms of the level professionalism, genuine interest in our approach and the speed in which they are responding to us. They have been working to expedite things at all levels with us. Being a Canadian company, it would be extremely gratifying to get approval and start a study here to see if we can help fellow Canadians, in addition to the work we are doing in other countries.
Please enligthen us on how Algernon is advancing Ifenprodil along the FDA regulatory pathway?
The US FDA has a process for companies like Algernon, whereby you provide them with your initial plans to start human trials and you get their feedback. This process is called a pre-investigational new drug (IND) application. The response from them can range from gentle recommendations for changes or more aggressive advice advising that wholesale changes to your plans need to be made or to go back to the drawing board and conduct additional research. The company then takes that advice and responds accordingly.
We’ve gone through this pre-IND process with them and have received positive feedback. We are preparing for the next step which is filing a formal IND application which is the same study we filed with Health Canada, a multinational Phase 2/3 Ifenprodil COVID-19 study.
How do you plan to scale up manufacturing of Ifenprodil to prepare for coronavirus and Acute Lung Injury clinical trials?
We have retained US-based manufacturer Cascade Chemical to produce the active pharmaceutical ingredient of Ifenoprdil for us so that we can begin toxicology testing on a new planned IV formulation. This is a key development because people who are suffering from extreme symptoms of the flu may not be able to swallow the drug or keep it down when it’s in a pill form. The IV formulation is ideal for a hospital setting and will allow the drug to be administered quickly to eligible patients.
Please tell us about some of the other lead compounds that you are advancing as part of your late-stage pipeline?
We have been investigating a number of generic compounds for kidney, bowel and liver disease and have advanced them through multiple animal studies. For a small company like Algernon, we can sometimes be limited by the availability of capital to advance additional programs. As that changes, we plan to advance some of the best and brightest of our other repurposed drug candidates into human studies as well.
What is the driving force behind Algernon’s business model?
The Algernon repurposed drug business model was the brainchild of our CSO, Dr Mark Williams. He worked for years to identify possible targets and to develop a drug development program that could repurpose a generic drug while at the same time producing an exceptional model for a meaningful return on investment. The key is finding a drug that has had a limited regional approval and exposure so that generic competition is minimized, and new intellectual property can be more easily enforced. For that reason, we only investigated compounds that have never been introduced to the US or Europe.
Contact the author Uttara Choudhury at [email protected]
Follow her on Twitter: @UttaraProactive