All right. Awesome. Good afternoon, everybody. My name is Alexa Diemer. I'm from the Cantor Biotech Equity Research Team, and I'm very honored to be sharing the stage this afternoon with Seth from Tonix Pharmaceuticals . We only have a short time to talk about a lot of stuff, but I just wanted to start off by saying congrats on the recent approval of Tonmya. We'll talk about that a lot more. Before we get started, why don't you just share a quick overview of Tonix for those that are less familiar and highlight the focus for the company over the next six to 12 months?
Thank you very much. First, thank you for inviting us to the conference and for this interview. Tonix is a public company on NASDAQ. The ticker is TNXP. As you said, just on August 15, we got the FDA approval for Tonmya, which is cyclobenzaprine sublingual tablets for treating fibromyalgia in adults. We'll talk more about that. In addition to that, we're mostly focused on the launch right now because we already market, we currently market two small prescription migraine drugs. We have a commercial infrastructure, but this is a big lift to be launching this product. I think we're relatively rare in that we've taken a product from concept to FDA approval and now launch. We're truly a fully integrated company.
We have an exciting pipeline, and we may not get to that with the short time we have, but we're very excited about some of the things we're doing in the pipeline.
Great. Let's immediately get into fibromyalgia and the unmet needs. As you mentioned, that's the indication that Tonmya was approved for. How many patients in the U.S. are affected by fibromyalgia and what percentage receive treatment?
Thank you. Let me start by saying I've worked in fibromyalgia for more than 25 years. Since fibromyalgia is a chronic pain condition, I think you almost have to have worked in it for 25 years to make progress in this because it's not something that you can understand in a short time. The concept of fibromyalgia is evolving. The current epidemiology suggests there are 10 million American adults with fibromyalgia, and of those, about 3 million are currently diagnosed and treated. A lot of the epidemiology is from before the COVID epidemic. There are a number of ways in which people think the fibromyalgia population in the United States is growing. One of them is that a number of patients with long COVID are believed to suffer from fibromyalgia also.
Interesting.
The pre-2019 epidemiology suggested about 10 million.
Got it. What, roughly 30% of the patients are diagnosed? What goes into this diagnosis process, and how long does it take patients to receive a diagnosis from the onset of symptoms?
Thanks. Fibromyalgia is really a condition where the thinking is evolving. There were three drugs approved: 2007, 2008, 2009. They were approved on a standard called the 1990 ACR criteria. At that time, the diagnosis required the evaluation of what are called tender points. If a physician on an examination pushes down, they listen to tenderness. That was really a diagnosis that needed a doctor or health care provider visit. Our drug was approved on the newer standard of 2016 criteria, 26 years later. There is an evolution. Now you do not need to evaluate tender points to make the diagnosis. It is really a diagnosis based on history and probably amenable to telehealth now that it does not require the evaluation of tender points.
Fibromyalgia, if you speak to experts in the field, someone wrote about it beautifully. It is like hearing a symphony that you are familiar with a key part of, and you see it. Often when you are talking to a patient, you appreciate that this is starting to line up. The history and the rest of it is fibromyalgia. Generally, the core symptom, the sine qua non, is widespread pain, meaning pain in more than one area of the body.
Got it. Do symptoms present the same in all patients? Aside from sleep, what are the other most common patient complaints?
Yeah. Actually, I forgot to respond to one of your questions. There's literature out there that on average, it takes six years for fibromyalgia patients to be diagnosed, which is really appalling if you think the FDA, by granting us fast track, FDA acknowledged that fibromyalgia is a serious condition. I really don't know of many other serious conditions that go undiagnosed for six years. The other symptoms, fibromyalgia is now called the prototypic nociplastic syndrome. Nociplastic is now the third primary type of pain, but it's also associated with fatigue, sleep problems, and what's called brain fog. It's really a constellation of things. Patients complain about different of the symptoms in different ways. Pain is still the key aspect. It's a chronic pain condition regulated by the pain division at FDA. The primary endpoint of our studies is pain. Consequently, our drug, Tonmya, is called a non-opioid analgesic.
The other symptoms are very important to patients.
Do all patients present the same way?
Patients present in different ways. First of all, there are many roads to fibromyalgia. One of the roads to fibromyalgia is recovering from an infection. It's now widely regarded as an IACI, infection-associated chronic illness. That's why COVID, for example, and long COVID precipitated a lot of new cases of fibromyalgia. Other people get fibromyalgia after, for example, an accident or a burn. I believe one of the most famous fibromyalgia patients is Howard Hughes, who crashed his airplane and then wound up with chronic pain. It was so much pain that he couldn't even wear clothes because it hurt to have clothes on his body. You can also get fibromyalgia from trauma. For example, even just psychological trauma, similar to a PTSD-type trauma. An increasing reason why people are getting fibromyalgia now is chemotherapy and cancer.
For example, women with breast cancer after chemotherapy, it's increasingly common to get fibromyalgia. They present in different ways. The origin of fibromyalgia can almost be thought of as a common final pathway. It's all these different ways of feeding into it. They then get a syndrome that's pretty homogeneous. I left out probably another common way of getting fibromyalgia: it starts with a regional pain syndrome, and then the pain generalizes or spreads around the body. That's another way. All of them relate to the same problem in the brain, which is something that alters sensory processing so that normal stimuli seem painful. Going along with that are the sleep and the fatigue.
Got it. I'm just going to announce this so people listening can hear. We had a question from the audience about what the physician's role is. Once a patient comes in presenting with symptoms of pain, what is the role of the physician in treating and diagnosing?
Yeah. Fibromyalgia can be diagnosed by a primary care doctor. The key opinion leaders are rheumatologists. Fibromyalgia patients are often also cared for by pain specialists or neurologists. The key point is there's no diagnostic test. There's no X-ray. There's no objective evidence. It's really not just the physician, but health care provider listening to the history and evaluating mostly the symptoms. One of the key things that's poorly understood about fibromyalgia is it is not a diagnosis of exclusion. That's a common misunderstanding that a doctor would have to do tests and rule out other things. In fact, fibromyalgia commonly co-exists with other problems.
That's one of the most interesting areas, for example, in rheumatology, with rheumatologists treating someone with lupus who also has fibromyalgia or rheumatoid arthritis who also has fibromyalgia and trying to figure out if a flare is an exacerbation of the activity of their fibromyalgia or of their lupus. Fibromyalgia is not a diagnosis of exclusion. It can and should be diagnosed in the presence of other conditions.
What role does sleep play in fibromyalgia? Is this an aspect that is often overlooked by physicians?
Yes, sleep is very important. This is an interesting, ironic, and sad story that the role of sleep was identified in 1975 by Harvey Moldofsky, a psychiatrist in Toronto. He was very important in the development of our program and other programs. He was well aware that our PDUFA date was August 15th. He passed away on August 15. Fifty years after making an audacious claim that fibromyalgia should be regarded as a sleep disorder, he really led to work that transformed the understanding of fibromyalgia. Our drug is first in class of drugs that are designed to target the non-restorative sleep. Our drug is taken at bedtime. It's a sublingual tablet, two tablets at bedtime. We believe that the improvement of sleep leads to the improvement of pain. What's on the package insert is just the reduction in pain.
Got it. We'll get into Tonmya in a bit, in a few minutes. The last question I had about fibromyalgia in general is, you said it takes around six years for patients to receive a diagnosis. Is there any literature that supports that earlier intervention can alter disease progression?
There's a growing literature, and we hope to contribute to it. As I mentioned, I've been working in fibromyalgia for 25 years or so. I was at Columbia Medical School on the faculty. I was in the Division of Rheumatology. I've seen fibromyalgia firsthand. As a young doctor, one of the things that really attracted me to study fibromyalgia was I attended a lecture by Larry Einhorn, who revolutionized the treatment of testicular cancer. Before Larry Einhorn started, everyone with testicular cancer died. Someone asked him, "Why did you?" Because now, after his work, it has over 95% survival and essentially almost cure. He said, "Why did you pick this topic?" Because it was young men showing up with metastases all over the body. Larry Einhorn said, "Because I noticed that some patients got better." You can say the same thing about me with fibromyalgia.
It's not that common, but there are people that can have serious fibromyalgia for a year or two where fibromyalgia has taken over their lives, bona fide fibromyalgia, and then it can go away. We hope that earlier treatment might be able to increase a rate of remission. That is for future research, and it's something that we would love to contribute to. I will say that generally, there is some low level of spontaneous remission. People will say that generally, fibromyalgia peters out or something in the 70s or 80s. You know, a typical person is diagnosed at about 50. Over a course of decades and whatnot, it would tend to burn out. There is a background rate, and then there are these cases of just dramatic remission. It's not something that is general about fibromyalgia patients.
In working with a fibromyalgia patient, I think it's always important to mention that to give them some hope. When they're suffering from it, it seems, and they'll often say, "It's stolen my life from me. I can't play my traditional roles of, you know, it's often women, mother, you know, wife, you know, job, you know, all the things." It literally steals people's lives. Half of fibromyalgia patients go on disability.
All very interesting. There's still so much to learn about this space. Now moving on to Tonmya. It's a sublingual formulation of cyclobenzaprine, which is often prescribed orally as a muscle relaxant. How does its mechanism target the underlying pathophysiology of fibromyalgia?
Thank you. It's very interesting that the latest thing in fibromyalgia, Tonmya, was also probably the first drug tested in fibromyalgia. In the late 1980s, Merck was already marketing Flexeril, which is an oral swallowed form of cyclobenzaprine, and actually sponsored a large double-blind randomized study that's published. It was published in 1994, correct? It showed that oral cyclobenzaprine doesn't work. It had a transient benefit at one month, but then the benefit was lost. For a chronic pain medication, one month of benefit is not meaningful. Merck killed the program. People like me, I guess mostly me, looked at it and said, you know, the glass may be half full. We looked at this and said, what can we do to take this one-month benefit and extend it? We realized that if we could deliver cyclobenzaprine transmucosally, it's not just sublingual.
Many sublingual or oral dissolving tablets or buccal ultimately get swallowed. Ours is designed for transmucosal, the idea being that we wanted to bypass hepatic metabolism and reduce the amount of the major metabolite, norcyclobenzaprine. Those engineering goals were met. We dramatically reduced the amount of norcyclobenzaprine on chronic dosing. The fact that we now presented FDA with two statistically significant phase III studies and with a durable separation, a durable reduction in pain is testimony to the idea that we think we made that our hypothesis about norcyclobenzaprine is correct. What was the hypothesis? Norcyclobenzaprine is a much more potent NRI, norepinephrine reuptake inhibitor, than cyclobenzaprine. As a bedtime medicine, NRI is not something you want in there because an NRI generally be kind of associated with, for example, insomnia.
What we did by lowering the norcyclobenzaprine is we allowed the parent to target sleep quality, we think, more effectively, and together created something that could be durable. The easiest way to say it is swallowed oral cyclobenzaprine doesn't work. Ours has proven durable pain reduction over three months and an FDA label.
Very impressive. How is Tonmya's profile differentiated from some of the other approved therapies in fibromyalgia, such as Lyrica or Cymbalta?
Yes. There are three approved drugs representing two classes. Lyrica is a gabapentinoid. Generally, people think it slows nerve conduction. That was very important in the history of fibromyalgia. It was the first drug approved, but it's rarely prescribed today. We can get into that. The other two drugs that are approved before us are Cymbalta and Savella. They're both SNRIs, so they have the same mechanism. Cymbalta was a much more successful product than Savella, but they both work basically the same way. It's a little bit complicated, but they so-called normalize descending inhibition. It's a real mechanism. Of the approved drugs, Cymbalta is the most widely prescribed today. Finally, we came along as the first member of a new class, which we called a tertiary amine tricyclic. We target non-restorative sleep and have kind of a fundamentally different view. I would say, how do we compare?
I think if you look at the whole package of our activity, our drug is more active. I explain in the sense that you can't compare between studies. The population that we enrolled was different than the population that Lyrica, [Savella, and Cymbalta] were studied on. All in all, I think that probably in pain reduction, we have about the same level of activity. In sleep, fatigue, and other things, which I can refer you to our published literature, it's not on the label. I think that we have a more, call it, broad spectrum effect on fibromyalgia. That's consistent with Harvey Moldofsky's theory that we're probably addressing it closer to the source as opposed to being a more symptomatic treatment than the other two. The other big differentiator, and again, no head-to-head data, but I think a big differentiator for us is tolerability.
If you look at claims data and if you, we've done a number of marketing studies, primary research, et cetera, there are a lot of issues with either called persistence or how long people stay on the other drugs. Lyrica has weight gain, hip fractures, different things. Cymbalta and Savella have a lot of GI side effects, decreased sexual function, some insomnia. Again, no comparative data, but our tolerability profile is impressive. I like to say that we have three benefits: activity, tolerability, and the combination of activity and tolerability. Sometimes when you have one, you don't have the other.
What is the significance of Tonmya not being DEA scheduled? How common is off-label opioid use in fibromyalgia? You mentioned there's three approved therapies, but they don't really work well, and they have a ton of safety issues. How common is it for physicians to prescribe opioids off-label for these patients that just have really horrible chronic pain?
Yeah. It's great that we're not DEA scheduled. First, let me compare it to Lyrica, which has the lowest level of DEA scheduling. We think just because of that, Lyrica is rarely prescribed today despite being on-label. There's a large amount of prescribing of off-label gabapentin, which a lot of experts think doesn't work. One of the problems with the compendia is the compendia is like a roach motel. If you get something in the compendia, it gets prescribed. If you look behind the curtain, there's no kind of there there. A lot of people think that actually the differences in Lyrica and gabapentin are such that it shouldn't work for a number of reasons. The fact that, in the modern world, even the DEA scheduling for Lyrica very much biases against its use. You get to the opiates.
The opiates are a big story because we find a big difference in our primary research talking to doctors where they say, "I wouldn't prescribe opiates for fibromyalgia." You look at the claims data. On our website, you can see the results of the study that 18 months after a diagnosis of fibromyalgia, many more people get opiates than all three of the FDA-approved drugs combined. Opiates are widely used. In defense of doctors, fibromyalgia patients are desperate. They doctor shop. They keep going around it. It's an old expression. If you're looking for trouble, you'll find it. It may be that doctors actually are trying to hold the line, but they'll come in and complain of other things or other doctors or something. The opiates are way too widely used.
Not only should opiates not be used, but some experts believe they should be contraindicated, that long-term opiate use actually sensitizes fibromyalgia patients to, essentially makes it worse. We hope that we are in the lead, I think, of non-opioid analgesics. It's an exciting area. Vertex obviously got Journavx approved in January. That's for acute pain, a non-opioid. We are for fibromyalgia, a chronic pain disorder. I think it's a very exciting time in the area of non-opioid analgesics. Acute pain and chronic pain are very different. The only thing connecting them is the pain part. For example, with Journavx, it's an advantage to have a non-opioid. Opioids are approved and useful for acute surgical pain. In fibromyalgia, our battle is different. Opiates shouldn't be used.
It's a much stronger case to providers, managed care, other things that whatever you're doing in this system that's biasing towards this widespread use of opiates, you got to look at more carefully.
All right. Let's transition to commercial launch plans for Tonmya. You mentioned earlier that there's 10 million patients with fibromyalgia. Around 3 million are diagnosed. What percentage of this 3 million that are diagnosed, and maybe you'll even target some of those undiagnosed patients that make up that bigger group of the 10 million. What percentage of that is your initial launch target? Maybe you can also touch upon some challenges that exist when trying to get more widespread adoption, going from that 3 million to 10 million.
Great. Let me talk about the staging of it. The first is two years ago, we bought two marketed migraine products so that we would have our own commercial infrastructure to build this launch on. That was a great investment because we're really prepared to do a robust launch. One of the things that's very unique about the fibromyalgia marketplace is how concentrated it is. To just summarize some research, if you ask how many HCPs, how many providers have made the diagnosis in the past year, it's about 450,000 providers. You look at that number and 5% diagnose 70% of the fibromyalgia patients and write 70% of the prescriptions. Our low-hanging fruit is 25,000 HCPs that account for 70% of the fibromyalgia prescription. We think that that's our inroad into this 3 million diagnosed and treated, which is obviously the low-hanging fruit.
We're going to, we have 10 internal reps. We've publicly said that we're going to hire 70, 80 more first contract, but in a kind of rent-to-buy model where we can ultimately internalize them. We think that we can do some, we can cover this market pretty well. Not all 25,000 with face-to-face field force, but a combination of that and, you know, omnichannel where the call patterns are obviously dictated in part by the regions and, you know, the concentration of prescribers. Our initial focus is on the low-hanging fruit. We think that ultimately, we want to get into that 7 million that hasn't been diagnosed and, you know, traditionally. One of the things we've found even among patient advocates is that they may know they have fibromyalgia, but they haven't bothered to be diagnosed because they don't find the current treatments appealing.
There are a lot of people for whom fibromyalgia diagnosis as part of a plan to get appropriate treatment and, you know, get prescriptions and reimbursement would be not that challenging. We think particularly with our value proposition of, you know, risk-benefit with, you know, favorable activity and good tolerability, we could really kind of attract people to being diagnosed with fibromyalgia.
Which contract sales organization are you using? Who plans to bring this task completely in-house?
Yes, we haven't. We're using one of the big ones, but we haven't publicly disclosed it. To save myself the 8-K, I'll just say we're using one that you would have heard of.
OK.
I don't know. At some point, we will disclose it. The way they operate, they basically function like Tonix reps. They're not doing all the things at the same time. It is our plan to selectively start by cherry-picking. Ultimately, we do plan to internalize the sales force because we think ultimately that's the most effective kind of organization to really promote the benefits of a product.
Have you announced the price yet? If not, what are the factors that are shaping pricing strategy?
Thanks. We have not yet announced WAC. We hope to do so in the near future. There's a lot that goes into it. We're still collecting a lot of data. Some of the important things that go into it are the health economics, how expensive fibromyalgia patients are to the system in terms of hospitalizations, ER visits, unnecessary surgeries, multiple prescriptions, and also the way that fibromyalgia acts out differently in different people can be expensive to the system. For example, some people, you know, women, big generalization, but women tend to internalize fibromyalgia. They kind of present in one way. Men tend to externalize some of their frustrations with treatment, maybe leading to crime, incarceration, drug use, drug-related crimes, all this kind of stuff. The system really would benefit in many ways from having chronic pain patients treated with non-opiates.
We think it'll be a very appealing value proposition, particularly to people, to the groups that self-insure and are more interested in the overall outcome as opposed to just managing a single pharmacy benefit.
Got it. OK, we are all out of time. Seth, this was a pleasure. There's so much to look forward to for Tonix. You know, I'm personally excited to keep track of the launch and learn of any more updates. Thank you again for coming out. You know, I hope you enjoy the rest of your conference.
Thank you very much for having me.
Of course.