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Cyrano Pursues the First Major Smell & Flavor Loss Therapy

In Delray Beach, Florida, an emerging biopharma company, Cyrano Therapeutics, is planning a clinical trial using approved theophylline via a new intranasal pathway of administration to explore the treatment of patients who have lost or diminished senses of smell and flavor.

Cyrano Loss of Taste and Smell

Cyrano Pursues the First Major Smell & Flavor Loss Therapy

Until recently, long-term smell and flavor loss was a subject that was mostly ignored.  Without a gold-standard therapy, physicians’ have had little to discuss with prospective patients.  Patients have simply had to learn how to manage a new normal; a life without the enjoyment of food or drink, the smell of fresh air, the smell of your partner-in-life, or the acuity to determine safe food from that which is tainted.

In the US alone, over 15 million patients1 have long-term smell loss. This does not include the multitude of neurodegenerative conditions where it is a factor. For example, 95% of Parkinson’s patients share this affliction, often the first indicator of the disease. Nor does it include the more than two-thirds of cancer patients undergoing chemotherapy who report sensory perception changes, some of which can be permanent. While patients lose their sense of smell due to many different circumstances, around 30% of the population is due to allergic rhinitis, 25% due to upper respiratory viral infections such as the flu (post-viral), and 12% due to traumatic brain injury2 – according to pre-2020 surveys. When the tallies are in, it is now expected that COVID-19 will make post-viral smell loss the number one cause of long-term smell and flavor loss.

“A number of years ago, I contracted the flu.” – Rick Geoffrion

“A number of years ago, in the pre-COVID days, I contracted the flu,” begins Rick Geoffrion, Co-Founder, President & CEO of Cyrano Therapeutics. “I experienced a 102 fever, shake, and shivers. It was pretty intense, but it only lasted a couple of days. A reasonably common flu experience.”  After feeling better, Geoffrion resumed his routine, went to work, and on his first day back went to lunch. There, he ordered a chicken sandwich. Geoffrion continues, “I realized when I bit into it that I couldn’t taste it, all I could do was feel it. I knew something was wrong.”

“I realized that I couldn’t taste it. I knew something was wrong.” – Rick Geoffrion

After an appointment with Geoffrion’s primary care physician and then with a key opinion-leading otolaryngologist, he was told there was no treatment available for smell and flavor loss. “I just remember walking out of the doctor’s office and thinking to myself, wow, could it be that I will never fully experience food and drink for the rest of my life?  When you lose your sense of smell, you lose 80-90% of what you perceive as taste. Technically, you haven’t lost taste, you have lost the ability to detect flavor in food. Without smell, wine will taste just like water and proteins like beef, chicken, or fish are reduced to texture.” says Geoffrion.

“I remember walking out of the doctor’s office thinking, wow, could it be that I will never fully experience food and drink for the rest of my life?” – Rick Geoffrion

Inspired by this personal experience to find a solution, Geoffrion traveled to Washington DC, intent on meeting Robert I. Henkin, MD, PhD, a former NIH scientist and Director of The Taste and Smell Clinic. Henkin diagnosed Geoffrion and confirmed his fear; he had lost approximately 99% of his ability to sense smell and flavor. “If you put gasoline under my nose, I could tell you something was present, but not what it was,” clarifies Geoffrion, “however I had still retained a trace amount of smell function. So, Dr. Henkin thought that there could be an opportunity for treatment and recovery.” This modicum of hope was the catalyst for a partnership that would lead to the formation of Cyrano Therapeutics.

“If you put gasoline under my nose, I could tell you something was present, but not what it was.” – Rick Geoffrion

Henkin followed his diagnosis by prescribing an oral drug, theophylline. Originally prescribed for conditions such as asthma and COPD, oral theophylline has been largely abandoned with the development of more targeted drugs that carry fewer side effects. Typical side effects associated with oral theophylline therapy include insomnia, jitteriness, heart palpitations, and an elevated heart rate. Henkin had prescribed oral theophylline to more than 4,000 patients over the years with moderate success – around 50% of patients recovered a portion of their smell/flavor function. However, significant outcomes were clearly limited by the side effects.  Many patients could not tolerate the amount of systemic drug required to get to the therapeutic window. Geoffrion was prescribed the oral drug and used it habitually for nearly 3 years. “My smell and flavor were improving significantly and that was exciting, but side effects that included an elevated heart rate led me to doubt whether I should continue to take the drug over the long-term,” admits Geoffrion.

“My smell and flavor were improving significantly and that was exciting, but side effects led me to doubt whether I should continue to take the drug.” – Rick Geoffrion

After approaching Henkin with this dilemma, Henkin disclosed that many patients have had the same experience and that he was on his way to a potential solution. Henkin had been working on a theophylline nasal spray that would deliver the drug directly to the olfactory region, bypassing the systemic circulation and allowing the dose to be reduced by 1000x. Recognizing the magnitude of the unmet need and the opportunity to deliver a more practical solution, Geoffrion leveraged his more than three decades in healthcare technology to partner with Henkin. The duo went on to found Cyrano Therapeutics, a company that could shepherd the novel nasal spray through a formal regulatory path to approval.

Cyrano’s patented formulation is administered daily, at-home, via a simple intranasal spray, directly to the patient’s nasal mucosa and olfactory receptors. Geoffrion explains that “the likely mechanism of action is the stimulation of olfactory transduction. So, you may need to take the drug for the rest of your life to keep that effect going.” The expectation is that receptor/sensory neurons will repopulate, be stimulated and then synapse, allowing the brain to process odorants again.

“The likely mechanism of action is the stimulation of olfactory transduction.” – Rick Geoffrion

In November 2020, Cyrano closed on a $12.8M round led by Remiges Ventures and Lumira Ventures, with the participation of additional investors. The proceeds are currently being used to complete the prerequisite non-clinical research before initiating a formal randomized trial early next year.

In that trial, Geoffrion intends to utilize a digital strategy to maximize patient enrollment. “What we’ll do is create attention and awareness in the geographies where our clinical sites are located to drive interest from patients who potentially may qualify for the trial,” explains Geoffrion. “This unmet clinical need is tailor-made for social media. The inability to smell odors and detect flavor in food can be easily communicated and understood through social media and, therefore, attention and awareness of the clinical condition and our clinical trial can be created quite efficiently.”

“Having experienced smell and flavor loss first-hand, I know how devastating it can be to lose it and how joyful it can be to recover it.” – Rick Geoffrion

Reflecting on his own experience with loss of smell and flavor, Geoffrion stated that, “For this company, I am a missionary not a mercenary. Having experienced smell and flavor loss first-hand, effectively losing 2 out of the 5 senses we have as human beings, I know how devastating it can be to lose it and how joyful it can be to recover it. I am on a mission to spread that joy to others.”

 

Sources
  • 1National Health And Nutrition Examination Survey (2011-12)
  • 2Keller and Malaspina. BMC Ear, Nose and Throat Disorders 2013, 13:8

 

About the Author

Kayleen is the original MedTech Millennial, a #medtech business strategist, and #HealthTech journalist with 15 years in medical device intelligence and research.

Kayleen Brown Newsweek TMG360 Media Executive Editor Vice President MedTech Medical Devices

Currently, she is serving as Executive Editor & Vice President of TMG360 Media, a digital platform created to drive brand awareness, patient recruitment, strategic partnerships, and funding access in the healthtech industry. In tandem, she is proud to have been chosen by Newsweek to represent the medical device community as its HealthTech Expert; and sits on the steering committee for ScaleHealth’s ScaleOC, a global innovation ecosystem for the health and wellness industry. Kayleen is known for interviewing the top medtech executives and innovators, moderating panels at medical technology conferences, and leading commercial strategy roundtables and programs.

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