| Investors would think a pharmaceutical company heading into Phase 2b/3 human trials for treating the third most malignant disease after lung cancer and pancreatic cancer would draw eyes from major players. If that same company announced it was embarking on Phase2b/3 human trials for a COVID-19 treatment, investors would expect worldwide attention. Step up Algernon Pharmaceuticals (CSE.AGN, Forum) who were methodically progressing repurposed drug Ifenprodil for treating Idiopathic Pulmonary Fibrosis (IPF) and Chronic Cough. Around 30,000-40,000 people in the US every year are diagnosed with IPF. They're given another 3.5 to 5 years to live. It's serious and Algernon were conscientious to a fault to ensure their science merited human trials and raised funds in difficult market conditions to do so. When Covid-19 hit, Algernon's Chief Science Officer, Dr. Mark Williams, discovered a Chinese team had eliminated thousands of compounds from the drug bank database leaving Ifenprodil as one of two key drugs to treat H1N5 - the deadliest form of Avian flu. Suddenly the possibility of Ifenprodil as a treatment for Covid-19 became plausible. One drug for multiple treatments, how could that be possible? As Algernon's human trials for treating COVID-19 began in the US, Romania, and the Philippines, investors newer to the Algernon story became skittish, fearing every announcement around a positive treatment or vaccine and losing perspective. They ignored not only Algernon's drug repurposing business model and pipeline, but ultimately the only thing that matters, helping people recover from illness. Still, there are questions, not least of which is, how Algernon seems to be flying under the radar. A positive announcement within a few months could lead them to be an overnight sensation, but such quick success couldn't be further from the truth; there are several years of hard science behind the company. Stockhouse Editorial recently sat down with Algernon CEO, Christopher J. Moreau, who found time from a hectic schedule to answer some pressing questions. SH: Chris, thanks for taking the time to speak with us today. What has been the biggest practical challenge for Algernon around the COVID-19 trials? CJM: I think when we started to develop a clinical program for Ifenprodil and COVID-19, the biggest challenge in front of us initially was getting our U.S. FDA investigational new drug (IND) application completed in what was really record time. This process usually takes months and we did it in about 30 days. It was a monumental task for a small company and of course it turned out well for us when the FDA cleared our multinational Phase 2 b/3 COVID- 19 human trial for Ifenprodil. SH: What has been the biggest challenge with investors? CJM: I think the biggest challenge with the stock side of the business has been investors who don't really understand or appreciate what is involved in planning, starting and running a Phase 2 multi-national clinical trial. We have compressed into weeks what usually takes many, many months and still investors ask why we don't have data yet. In many ways of course I get it, COVID-19 is having a toxic impact on our way of life, globally, and so the anxiety is understandable, but it has created a serious additional burden of work to manage everyone's expectations. SH: Would you say treating COVID-19 usurped the IPF/Chronic Cough studies and confused investors, and if so, how should they make sense of these studies? CJM: There may be still some confusion in the market that we are investigating Ifenprodil for more than just COVID-19, but, it's not the first time that a company has run more than one trial for a drug for different indications. Hopefully folks get that now…. In terms of awareness, I think its accurate to say the recent “energy” in our stock and story is because of our COVID-19 clinical program. I believe that has been the reason we have had the value creation and the increase in liquidity in the stock since we announced our plans for COVID back in early March of this year. On the other hand, it has also made the stock more volatile. SH: Taking a step back, for investors who might be new to drug repurposing, what are the advantages of this process for Ifenprodil? CJM: Drug re-purposing dramatically reduces the risk of a failure during the development period due to already known safety data, since an older drug will have a well-known safety history. It is also very capital efficient because once you complete your animal trials, you can usually move the drug into an off label Phase 2 human trial very quickly, compared to trying to advance a new chemical entity forward. 90% of new drugs never make it to Phase 2 trials at a per drug- cost of well over $50M. If you sit back and think about it, that is an astonishingly high-risk gamble. SH: Can you explain the procedure and timeline for the Phase 2b/3 COVID-19 trial? CJM: The trial will begin as a Phase 2b study of an aggregate of 150 patients. With positive preliminary data, the clinical trial will move directly into a Phase 3 trial. The data from the Phase 2b study will determine the number of patients needed to reach statistical significance in the Phase 3 trial. Patients will be randomized in a one-to-one manner and will either be treated using an existing standard of care, or standard of care plus Ifenprodil 60 mg (taken as one 20 mg tablet three-times daily) for one arm or standard of care plus Ifenprodil 120 mg (taken as two 20 mg tablets three-times daily) for two weeks. Over the testing period, doctors will observe whether there is an improvement in a number of secondary endpoints, including mortality, blood oxygen levels, time spent in intensive care and time to mechanical ventilation. We enrolled our first patient on August 5th and recently announced that we enrolled our 50th patient on September 2nd. The trial is being conducted in 4 countries including the U.S. Australia, Romania and the Philippines. SH: What are the chances of there being one “magic” treatment for COVID-19? CJM: I think we should be thinking of a therapeutic cocktail approach instead of a silver bullet. It is possible that one drug will do the trick however, COVID involves highly complex transmission, replication, and pathogenesis. So, I think we will need a number of different drugs perhaps in combination in order to achieve meaningful treatment options. SH: The science is complex and in interviews there's repeated reference to NDMA receptors. Can you explain the function of the NDMA receptors, and is this where Ifenprodil is seen to be potentially effective in treating many diseases?  CJM: Ifenprodil is an N-methyl-D-aspartate (NMDA) receptor antagonist specifically targeting the NMDA-type subunit 2B (Glu2NB). Ifenprodil prevents glutamate signalling. The NMDA receptor is found on many tissues including lung cells, T-cells, and neutrophils. The Company believes Ifenprodil can reduce the infiltration of neutrophils and T-cells into the lungs where they can release glutamate and cytokines respectively. The latter can result in the highly problematic cytokine storm that contributes to the loss of lung function and ultimately death as has been reported in COVID-19 infected patients. SH: Do you know how Big Pharma and medical journalists have missed Ifenprodil? CJM: Big Pharma likes new chemical entities since the patent position is one that they are used to working with. This is despite the billion-dollar success stories of re-purposed drugs like Tecfidera and thalidomide. I believe that as we advance with Phase 2 trials, the data will drive big pharma interest in our story. In the end it's all about the data. As for earned media, it's a tough position to be in. There are a few hundred clinical trials underway now for COVID-19, each one with their own story, and only so much bandwidth available with the news networks. There is also an election going on in the US with all of the related issues being covered. We always try to get the story in front of bigger news media however we may have to wait until our Phase 2b results come out. We did recently get front page coverage with the Miami Herald which focussed on our first US clinical trial site for our COVID study. SH: You've made comparisons before to Bellus around value, can you explain how this is a fair assessment? CJM: The more important comparison I have been trying to make with this is between Ifenprodil and Bellus' lead drug. In reviewing their corporate information, it would appear that BLU - 5937 is their main asset and so I only think it's fair to look at how the market and analysts value that drug by looking at the company's market cap. Ifenprodil outperformed Merck's Phase 3 drug Gefapixant by 110% in the same animal study that Bellus used when it was trying to compare BLU-5937 to Gefapixant. Bellus outperformed Merck's drug by only 60% and so a fairly direct comparison can be drawn. Ifenprodil, like BLU-5937, also has no known taste disturbance. I acknowledge there are many other factors behind a company's market cap, including cash on hand, their NASDAQ listing, number of institutional investors in the deal, all of these things have an impact on valuation. SH: What does Big Pharma make of your efforts, and do you have contact with them? CJM: Despite successful billion dollar re-purposed drug stories like Biogen's Tecfidera and Celgene's Thalidomide, big pharma are cautious when it comes to finding new uses for old drugs. Patents get far more complicated and there are additional layers of challenges that make extracting value so highly specialized, that few engage in it. I think once a re-purposed drug achieves positive human trial data, there will be a much more robust response from possible big pharma suitors SH: As Ifenprodil is a repurposed drug, how has Algernon protected their IP? CJM: Algernon has filed new intellectual property rights globally for NP-120 (Ifenprodil) for the treatment of respiratory diseases, called method of use patents and is also working to develop a proprietary injectable and slow release formulation. In addition, one of the diseases that Algernon is investigating is called idiopathic pulmonary fibrosis (IPF) and that is an orphan indication disease which affords additional market protection from generic competition from major global regulatory agencies. SH: If successful, how much Ifenprodil would be needed, and are Algernon as a small company in a position to produce enough to meet demand? CJM: In order to calculate the number of Ifenprodil tabs that would be required on a global basis, if our clinical studies show a strong efficacy, you need to look at the current infection rate in the U.S., Europe and the rest of the world. Based on a 2-week treatment of Ifenprodil at the highest dose, and assuming that 10% of people who are infected will present at emergency seeking treatment, that would translate into approximately 40M tablets monthly or about ½ billion tablets in 1 year. This is a mind-boggling number and is something we are working to plan for if the trial is a success. SH: We've mostly ignored the IPF/Chronic study, is their any relationship to the COVID-19 study? CJM: Well, the IPF and cough animal data we generated definitely showed Ifenprodil is active in the lung. Further, when we compared it against the 2 leading human treatments for IPF in the study, Ifenprodil outperformed them in the reduction of fibrosis (scarring). There has been some indications that folks that survive COVID are developing fibrosis in their lungs at a higher than normal rate and so its possible Ifenprodil can have a double effect, not only reducing the severity and duration of a COVID infection but it may also have an impact on reducing fibrosis. SH: How is it that study progressing, and is there a timeline so investors can mark their calendars? CJM: We have enrolled 4 patents to date and have been projecting top line data from the cough part of the study in Q1, 2021 and the final data from the IPF part of the study in Q2, 2021. SH: Chris, the answers have been enlightening. Do you have anything else you would like to add? CJM: Nothing other than my wanting to thank our investors for their ongoing support of our research. |