Part 2: Favipiravir, A Potential Treatment

Drug Topics®: Can you talk about Appili’s work with Canadian government agencies?

Balboni: Sure. We started this program with this idea of a true public private partnership. We are partnering with Fujifilm Toyama. We're the only company in the world that they've donated drug products to as part of our relationship with them. We have a long-standing and growing relationship with Fujifilm based on another program that we have with theirs, which I'm happy to talk about some other time. It's a great program, also an unmet need, an antifungal. But it certainly set the basis for this relationship. As part of that, though, we saw the need to bring in other players. And we've done that by partnering with Mount Sinai Hospital in Toronto, and Dr. Allison Mahir, great ID specialist with deep ties to the long-term-care network in Ontario, ran the influenza, also the Tamiflu studies in that population, and of course the Public Health Canada and Health Canada reviewers have been just amazing and working with us to very quickly review the packet, give us their feedback, and help guide us towards what is going to be the most beneficial trial for these residents at risk.

And then we're in continuing discussions with both the national and provincial governments in Canada with respect to funding, and it is our desire that they also step up and help pay for some of these. And so we're confident that in the end, we'll find that balance between public and private. And hopefully this is a model that others can use going forward, where companies take on a lot of that upfront risk and also leverage relationships in the business community. And the ability to move, sometimes more nimbly just because of contracting, to be able to move products forward. I think it's a good model, and hopefully we can one that we can continue to use. We, by the way, as a company, work with lots of government agencies for across all of our programs, and so we have significant relationships with NRC, for example, and the Public Health Canada, Health Canada, and FDA, and USDOD. So we certainly use this as part of our strategy developing these relationships.

Drug Topics®: So with other potential treatments such as vaccines, some researchers have tried to expedite the process of getting vaccines to 15 months, although vaccines take much longer. What is the timeline for how long it would take for an antiviral to be authorized for COVID-19?

Balboni: Small molecule drugs like favipiravir, like remdesivir, with a very well-understood mechanism of action, can be reviewed and approved much more quickly than vaccines can because the vaccines aren't necessarily starting at zero in terms of trying to build up that capability. A lot is known about the about favipiravir. Again, it's been over 3000 individuals more now. And so that builds out what's called the safety database. The regulatory agencies are most concerned, as they should be, with safety first.

Efficacy comes afterwards, obviously, as part of the entire package, but right up front, their job is to ensure that drugs are safe and efficacious for use in the population. And so it's really hard, as you correctly pointed out, to short circuit that experience in people to demonstrate safety and efficacy and I think you need only look back to the history of vaccines, and even drugs, really, the regulatory agencies were created because there used to be many, many fewer safeguards for the population for introduction of new drugs. And I think a great example of that is certainly thalidomide, where it caused all kinds of birth defects as a small molecule. Even vaccines, the polio vaccine was a great success. But early on, they tried to go very, very quickly. And there were some manufacturing problems. And so there's really there really is a need for government oversight. I think they do it very, very well. So to that end, something like favipiravir, which in the setting we're looking at, for post-exposure prophylaxis, that trial is a little bit longer than a treatment trial. And just because of the numbers of people you need to get. I think that we're probably 6 to 9 months from top-line data, which will let us know whether or not this is working in this setting. We also plan to have our first residents in long-term-care enrolled in the next week or so. It's not unreasonable to think that we could have really good data in this setting for favipiravir by the fall, late fall. There are 16 other trials ongoing for favipiravir around the world, randomized controlled trials. Now, we’re the only long-term-care setting trial for post-exposure prophylaxis, but there are treatment trials going on. I expect a readout from those trials. And the Russian trial in particular, probably first, and then a Fuji trial in Japan, sometime in July. This could move very, very quickly. And as I said before, I really do believe we're one well-controlled trial away from people really understanding that this drug works.

Drug Topics®: And as we head into what, for many, is almost their third month at home because of COVID-19, what do you envision for Appili Therapeutics as we face potentially several more months of this pandemic?

Balboni: Wow, I mean, I think you as well as anybody, having lived through this part, this is hard. It's hard enough to run a clinical trial under the best of circumstances when you're not locked down. And then now go ahead and think about locking everybody down and trying to run a trial. The good thing for the company, of course, is that we are a virtual company. We have offices in Halifax, we have offices in Toronto, I spend a lot of my time in the US, our chief medical officer in Boston, and so we were using Zoom and other technologies to be able to meet virtually for a long time. So for the day-to-day operations of the company, it's really not any different. I do think that everybody, yourself included, will have to start to think about, selective reopening, what does that look like? And then how do we best leverage that without causing further outbreaks? I think, for the long-term-care setting that we're interested in, it’s a little bit of the opposite. They're developing new protocols, thankfully, and procedures to help lock down the facilities more quickly. That certainly presents challenges for a clinical trial. But in this case, it's the right thing to do. For all those reasons, I think this has been tough on everybody. But as a company, we certainly have been used to doing this. And we're just continuing to drive on with all of our programs.

Drug Topics®: So those are all the questions that I have. Is there anything else that you wanted to add a touch upon before we wrap up today?

Balboni: I would say that my soapbox issue is running the randomized control trials. We've got to do the hard work to demonstrate whether or not these drugs work, or we run the risk of a hydroxychloroquine-like repeat in the market, which is not good for anybody. Nobody still knows whether or not that works. And by retracting studies and stopping and starting, it's really tough for the investigators to do the to do the work of enrolling, and so best to not do publication by press release. Hopefully we're avoiding that and others that have so far as well, but hopefully good things to come. At least we're asking the right question and running the right trial.

Drug Topics®: Dr. Balboni, thank you so much for joining me today.

Balboni: Thanks for having me.

Editor’s note: This interview transcription has been lightly edited for style and clarity.

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