Intranasal Delivery for Post-Viral Smell Loss with Cyrano Therapeutics' Rick Geoffrion

COVID-19 and other viruses have drawn increased attention to the debilitating effects and potentially consequential underlying causes of hyposmia or anosmia (reduced or complete inability to smell). In this episode of Sit and Deliver, Rick Geoffrion, founder and CEO of regenerative medicine company Cyrano Therapeutics, talks with Sit and Deliver host Tom von Gunden about why an effective therapeutic response may well involve – you guessed it – a payload through the nose.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Sit and Deliver, the series that provides timely updates from leading thinkers in drug delivery. My name is Tom von Gunden, Chief Editor and Community Director at online information exchange Drug Delivery Leader. Today, I am joined by Rick Geoffrion, founder and CEO of Cyrano Therapeutics, a regenerative medicine company focusing on treatments for taste and smell loss.

Welcome, Rick.

Rick Geoffrion, CEO, Cyrano Therapeutics:

Thank you, Tom. Appreciate it.

If we could start by surveying the patient need and the therapeutic landscape, why these treatments and why now?

There are over 50 million people now, in the U.S. and Europe alone, with post-viral smell loss, also known as hyposmia or anosmia. If you lose your sense of smell, you also lose 80% of what you perceive as taste. What we're really talking about is the loss of two out of the main five senses that we have as humans.

Traditionally or historically, how have these issues or conditions been treated, if they've been treated at all?

Great question. To date, there have been no scientifically validated treatments for post-viral smell loss. There is some literature out there, some anecdotal reports of platelet rich plasma working in some cases, but there's no formal or randomized trial that has evaluated it. That would require direct needle injection up the nose to the top of the nasal cavity. Corticosteroids have been tried through the nose because they're also tried for things like congestion, but they don't address post-viral smell loss specifically.

From a delivery standpoint, your treatment is done intranasally via spray. Perhaps that seems obvious for something that's targeting smell loss, but can you tell us a little bit more about how that mechanism of action works for this particular condition?

At the very top of our nasal cavity, we have about 5 or 6 million olfactory receptors that bond to your odorants and send a signal to the brain. What happens is that the virus attacks that region. It doesn't attack the 5 or 6 million receptors, but it attacks a cell that's right next to them. That cell is responsible for transmitting energy to the receptor neurons so that it can fire a signal. When that area is permanently damaged by the virus, as is the case in these 50 million people, the environment around the receptor neuron is no longer providing the same amount of energy that it did prior to the viral assault. As a result, the receptor neurons are not able to fire a signal. We're targeting that area with our drug. Our drug allows that receptor to then fire a signal even though it's getting less energy, but we have to get the drug to that region in order for it to have an effect. Delivering intranasally is the most obvious way to go.

Previously, the drug had been tried orally, and there was a modicum of success. The challenge was that patients couldn't take enough drug to get up and stay in the therapeutic window. The side effects were significant. By delivering intranasally, we're able to deliver 500 to 1000 times less drug, because instead of taking it down into the gut to get to the top of the nasal cavity, why not just deliver it directly to the top of the nasal cavity? That’s what we did.

Feel free to show us on the mechanism if there's anything to illustrate there.

I have a couple of pumps right here that I can show you. When we started thinking about the approach, we knew the drug had promise. But, again, how are you going to reliably deliver the drug to the top of the nasal cavity? Although the word is cavity, it's not a wide-open cavity; there's tissue in there. How are you going to get the droplets that are initiated here at the bottom of the nose all the way to the top?

We did some nasal cast work. First, we looked at standard pumps. Here's a standard pump, just like the kind of pump you'd purchase at a pharmacy. We took a look there and found that maybe we're getting 10% coverage up in that olfactory region with a standard pump. That doesn't inspire a lot of confidence. We’ve now developed a pump that's specifically designed to get the drug up there. This is a pump that mechanically is the same inside, but it has a tiny silicon chip at the end. There are tiny holes that are etched into it. Those holes bring the droplet down to a size that is much lighter and able to waft up to the top of the nasal cavity.

I'll demonstrate here. If you can see that fog, if you look closely, you can see how the air just moves it, even though I'm not blowing at it. That really allows even a small amount of air movement inside the nasal cavity to just waft and bring those droplets up. We get beautiful, even coverage, which inspires a lot more confidence that the drug will get where it needs to go to have an effect.

That all sounds very promising for those who suffer from smell loss. Are there any other therapeutic areas or conditions that what you're working on could have promising results for if targeted successfully?

Yes, absolutely. Neurodegenerative diseases are also associated with smell loss and, specifically, there are close to 1 million Parkinson's patients in the US and about 10 million worldwide. 95% of Parkinson's patients experience chronic smell loss. It's often the first symptom of the disease, and it can occur five years prior to tremors. Parkinson's patients suffer from a loss of dopaminergic cells in a specific area of the brain called the substantia nigra. They also have an overpopulation of these dopaminergic cells in the olfactory bulb, and the dopamine produced by these cells is thought to suppress olfactory transduction or signal transmission.

The mechanism of action for our formulation is the stimulation of olfactory signaling or transduction. On top of that, the biopsy of the olfactory region found that if you have Parkinson's versus no Parkinson's, the olfactory region is unremarkable, meaning that the end of the epithelium associated with the receptors may be working. Patients during the earlier stages of the disease do not exhibit reduced olfactory bulb size, which suggests that the olfactory bulb may be working. It's just that the overexpression of dopamine is inhibiting the normal signaling or transduction. We have a pilot study to look into this and see if we can find a signal as well. It requires the same type of delivery. We need to get the drug to the olfactory epithelium so that some of it may pass through and move into the olfactory bulb.

I want to thank you for joining me on this episode of Sit and Deliver for our Drug Delivery Leader audience.

Thank you, Tom. Appreciate the time today.