Evoke Pharma, Inc. (EVOK) Earnings Call Transcript & Summary

Well, I think GIMOTI is probably the best clinical innovation and change of paradigm shift in treatment that's probably come out in the last 40 years. The other -- the only other medication that I can even think closely as any kind of same type of effect is rifaximin in hepatic encephalopathy and cirrhosis. So they have similar pathways of what they do, but -- so I really think that GIMOTI, because diabetes is a much more common condition, I think the most common condition in the United States and 42 million diabetics, 5 million gastroparesis. So unlike rifaximin, which has a very limited population to cirrhosis, GIMOTI is going to be far more retainer impactful because diabetes and diabetic gastroparesis is the most -- is just much more common. And the other thing, diabetic gastroparesis is the first neuropathy anyone experiences with diabetes. So people don't know that and as more -- the more GIMOTI is in widespread literature and use, this is going to become more recognized and more and more primary care providers are going to be using it left and right.

Dr. Senadhi, you were mentioning a case example earlier. I was wondering if you could just dive into either that case or another one that you're -- you could really highlight to us, the need. And what's typical out there from a patient that presents to you, what the typical path is to get to you and what that might be like. You could talk about maybe flares and time spent in hospitals, things like that.

Sure. Let's go to Slide 19 to illustrate a couple of stories of patients of mine, which I've alluded to in some of our discussions. So this is first individual, 45-year-old female. Typical with the disease, more common in female. She has severe diabetic gastroparesis in 2011. So I've mentioned her several times and I've told how life-changing things have occurred. So basically, she's got type 2 diabetes. She was hospitalized for 143 days during 1 year. So I mean, could you imagine, 143 days she was hospitalized and this was the patient that I mentioned that had such severe disability. She was almost put in hospice or end-of-life care. She was almost committed. So essentially, what -- she was socially restricted. So she's failed at everything. You can see, she was on rifaximin. She was on all of these medications off-label, liquid Reglan, different medications. So what did GIMOTI do for her? I've mentioned it several times. She started eating again. She started cooking meals again. She started to join her family. And there, her family stopped thinking that she needs psychiatric help. She started attending church. She stopped being admitted to the hospital completely, going to the ER. She went from underweight where she was literally about 75 pounds when I met her and she was about 5'4". So imagine this emaciated starving woman who just looks like she's on death's door. And now she's at a regular weight. I mean she's actually in a normal weight range. She's able to attend and live her life again. I mean, this was -- I mean this was life changing. I mean the people are still -- in her church still talk about her and how her recovery was. And this is really -- it was very strong -- before GIMOTI, this wasn't feasible. So this is one example of how amazing that someone's life can change. And these are patients that people -- she was labeled a drug seeker. She was labeled stop coming to ER. This is -- I mean this is how deeply impactful this was for her. So there's an example of one type of patient. We can go to the next slide to talk about another different type of patient. So I've referenced him as well. This is an unfortunate individual who has diabetes type 1. This is obviously an autoimmune condition, nothing he did to get this. This is genetics. Diagnosed at the age of 14 and his diagnosis of diabetic gastroparesis, as you can see, it was delayed until he was 19. So this was a gentleman who every time he came to the clinic had abdominal pain with chronicity. He needs narcotics. He would go to the ER, we can get them, nobody wanted to treat him. He was just in such acute pain. He was crying, tears in front of his eyes. His mother would be with him and just pleading just to [indiscernible]. Her's life is destroyed. He couldn't go to school. I mean, this has destroyed his life in every single way. Everything he's tried. He had surgery done, BOTOX, pylori, different surgical interventions, pacemakers. I mean these are different options in these conditions that I won't get into for the sake of time. But basically, everything that's ever been -- you can do for gastroparesis at university level. This is at university. I've referred him to get the pacemaker. I did this BOTOX. These are all what you would do with John Hopkins or Harvard University. So we have the best of health care and the highest quality of health care, but it didn't do anything. It didn't solve his issue. And then when I got him on GIMOTI, he literally stopped having pain that same week. I mean the medication worked within 48 hours, he was already feeling better. Hasn't had any ER visits, had a better quality of life, no anxiety and depression. His mother even died, and I was the only person that was ever there for him, but still, after this, he was able to make his physician's appointments which never occurred prior to this. I want to show the audience a slide that really, to me, illustrates what I mentioned about his pain. Can we go to the -- to Slide 14? So if you go here, this is -- I want to show you, this is a clinical trial for GIMOTI. There's a total symptom score for gastroparesis, but I wanted to point out week 1. At week 1, there was a 55% greater improvement in the total symptom score in patients treated with GIMOTI. And I'm bringing this up now because this is what I see in my clinical practice. I mean week 1 -- I mean this -- I'm literally given all -- these 2 patients that I mentioned to you, I gave them a GIMOTI script. In that first week, already their nausea, vomiting is better. His pain has actually got better week -- within the first week, and you see why. You see a 52% improvement in their symptoms of nausea, vomiting, abdominal pain and bloating within the first week. So -- and look at the -- as you go progressively into week 2 and week 3, there's a huge improvement that are all statistically significant even to week 4. So I think that that's -- this is where you're giving a prescription to someone who's never had anything worked for them, who is suffering. And within the first week, they're coming back in a week and say, "I'm already better. I'm eating again. I'm not having pain." I mean this is truly inspiring. Can we go to the next slide? This is also a great illustration. So this is another slide basically looking at the symptom scores treated to GIMOTI, and this is just showing an improvement in about 86% in total symptom score. And the symptoms of nausea, abdominal pain, they were completely better in these stats. So just showing you improvement, and that's why I kind of mentioned in my patient case how different it is. And now let's proceed to Slide 21. So this is one last patient that I'll mention. So this is a 63-year-old African-American female. So she has type 2 diabetes. So she's a corporate executive. She's got a lot of resources. She's well educated. So she used to have hospitalizations for diabetic gastroparesis. She was put on a medication that's not FDA approved, not available in the United States, that domperidone that basically you have to try to get from Canada and you can't get a prescription for it. So she was on this medication. And then she had some -- there's some cardiac side effects that are known from domperidone. So because of this, she was put on GIMOTI, which doesn't have this side effect profile and she did similarly improve and was able to avoid having to risk the long-term risk of domperidone and cardiology issues. Her husband had died of an MI. So I was very dear to her. I mean, he died of a heart attack or myocardial infarction. So this was another avenue where GIMOTI was used in a patient with great access to health care and subsequently was able to be put on long term.

Great. Just in the interest of time, I was hoping we can move to patient access, and I wanted to ask, what's it like for your patients accessing GIMOTI through their insurance plans? And do you -- how do you help them as a physician? Do you see any patients who are unable to be treated with GIMOTI due to coverage restrictions? And what settings do you prefer to prescribe oral versus GIMOTI or GIMOTI versus oral based on these access issues?

So let's go to Slide 23. So I don't really have any difficulty getting GIMOTI. If insurance covers, so we go through a mainstay pharmacy for GIMOTI. If insurance covers GIMOTI, there's zero-dollar copay. If it doesn't cover GIMOTI, it's only $20 for cash-paying patients. Everyone that I prescribed GIMOTI, unlike other medications, I've been able to get GIMOTI. The company has a great, generous sample process as well. So we can also supplant with samples. Samples are usually good enough for a month even. But everyone I have prescribed GIMOTI, I've been able to get GIMOTI through EvokeAssist. If you can go back a slide. So EvokeAssist is support program for patients and physicians. So it is utilized for GIMOTI access. And we can go to Slide 24. So this is similar to other very successful models in the pharmaceutical literature. So the patients, there's benefits verification, nursing support, they process the claim. And they actually deliver the medication to the patient's house. So this is great. All of our patients love this. GIMOTI comes to our house. We don't need to track them. There's an individual keeping track of and communicating with the patient. And in GIMOTI's case, we've always -- the patient will tell you, they called me this day, they told me it's coming this day. So I've had great experiences with EvokeAssist support program. And for the provider side, they go through the benefits, they get authorizations, they go to work with office. And we've had wonderful experiences, as exemplified for the fact that everyone I've prescribed GIMOTI for had been able to get the medication. Does it impact me prescribing oral GIMOTI? I go ahead and what I'll do is I'll just give them a sample of GIMOTI and go ahead and prescribe it through EvokeAssist. And by the time -- even before they've done their sample, about 95% of patients have their med already delivered to their home.

Wow, so it sounds like a pretty straightforward process for you and your practice then?

Yes, very feasible and easy in comparison to other meds which are a lot more difficult.

Great. Dr. Senadhi, I was wondering if you could talk about tardive dyskinesia and the risk of tardive dyskinesia with GIMOTI versus oral metoclopramide. Is it different? And how easy is this to manage? That would be great.

Well, so let's go back to the label slide. So tardive dyskinesia is a warning that occurs with metoclopramide. It's a warning -- it's basically tardive dyskinesia is a movement disorder that can occur while on any formulation of metoclopramide. So I think there's a lot of recent data that shows that tardive dyskinesia really is more in the realm of patients that are suffering from psychiatric conditions that are being treated with antipsychotics. So it did get this label for gastroparesis, although the studies in gastroparesis were very limited. It just -- it requires to discontinue treatment after 12 weeks of being on metoclopramide. But this is available to do with a -- he was able to be in a drug holiday. So to answer your question, I've never had a case of tardive dyskinesia with any of my patients on metoclopramide in my entire career. As I said, metoclopramide has been safe. For 40 years, it's been in the pharmaco availability in pharmacies and has a safe profile over the last 40 years. So in my patients, I've never had anyone who's experienced tardive dyskinesia on oral or liquid metoclopramide. And all my GIMOTI patients, I've not had anybody experience any signs of even -- some minor side effects related to any kind of movement disorder. So we can go to Slide 16, but -- so I would just state that when they're properly managed and monitored that tardive dyskinesia is not prohibiting me from prescribing medication in any form or manner. There's more data coming up in the next couple of months that shows that the actual risk of tardive dyskinesia in metoclopramide and GIMOTI is actually a very, very low percentage and the chances are very, very small even when -- and that can even be tracked further with monitoring. So in my opinion, it's not -- it doesn't -- it's not anything that would change by prescribing habit. And I think when more data comes out in the next couple of months, that it's going to -- really GIMOTI is going to explode onto the scene of the paradigm shift and being the #1 option for gastroparesis in a guideline [indiscernible].

Understood. So just to reiterate, the 12 weeks is not a limitation that's on the label. It's something that is there, but patients tolerate GIMOTI very well and are able to...

Sure. Sure. And that's also -- if you extrapolate it into the 80-milligram dose, I mean it's the high dose of metoclopramide in older patients and that there's concerns. As I mentioned, most of my patients, about 95% of them are going down to the twice-a-day dose, which is not even -- that's basically 20 milligrams of metoclopramide. So I'm successfully treating their condition with basically, what, 25% of the dose, with only 25% of the dose. So I that's -- I've never seen an issue with GIMOTI in my clinical practice in the sample size of over 100 patients in terms of any kind of movement disorder.

Okay. And then just broadly, patients that discontinue treatment or if you could give kind of like the -- kind of the scale of how that is in your practice, if any, and how that might differ from oral metoclopramide or is that just a class effect?

So one of the things -- to answer further on your question, if you want to, after the 12 weeks, you can just stop GIMOTI for a week. Let's consider a drug holiday. There's -- you can do that. It's really -- most of our patients have tolerated it pretty well. I mean I had -- the patient 1 I showed you the case of that was hospitalized 143 days, she was off. She accidentally didn't have her GIMOTI for a week and she was actually -- did well. So there's -- so that can occur even in the toughest of patients and they still do very relatively fine. So we've not had anyone who was off their GIMOTI for some period of time that suddenly recurred. So it's easy to just give them a drug holiday of a week, if you would like to, after 12 weeks.

Okay. Great. So I wanted to touch on EVERSANA and the sales reps that visit. Could you just describe the interactions you've had? How often they visit? And what are some of those messages that resonate with you and you think might resonate with your peers?

And also, one of the other things that I think we're particularly interested in is how you've seen the interactions with the EVERSANA reps evolve over the course of the COVID-19 pandemic. And if you're seeing more interactions with them now, more efforts by them to reach out to you given the current status of the pandemic, that would be very helpful.

Sure. Can we go to Slide 24? Yes. So to comment on the EVERSANA interactions, I'm always available from EvokeAssist to get the support I need. For the reps, we do see them pretty often. We're always able to get samples. In fact, we have probably 30, 40 boxes of GIMOTI. We have 7 providers that -- the Medical Director here. So we're -- we have access to samples. And then in the support program, we always have the exact -- we get updated on any kind of verifications. As I mentioned before, that our patients are being called by EvokeAssist and EVERSANA teams to get their medications. They are always on track with delivery from the time for prescription. There's a statistic people who track as far as prescription to actually patient, and I feel that all my prescriptions have gotten and then reached my patients, which is probably unheralded in this day and age of insurance and pre-authorization. So I think that they're doing from -- I'm able to get my medication to all my patients, my reps are supportive. I think having been at the EVERSANA meeting and their global mission meeting, I think that EVERSANA is going to be the premier physician support and medicine support organization that's able to get medications to the end of the patients, to develop disease algorithms that better cure patients with rare conditions as well as patients with common conditions. So I believe being diabetic gastroparesis being very common condition, I feel that with EVERSANA's support, that GIMOTI is just sky is the limit. When you're someone like EVERSANA and you're able to treat a condition like Castleman syndrome, which is such a rare condition I've seen at Hopkins once or twice and provide patient databases and connect providers across the world and change the algorithm of treatment in something like Castleman syndrome, which is such a rare condition, I can only imagine what they could do in the realm of diabetic gastroparesis, a common condition with many, many patients, 5 million patients in the United States. So I feel that the best is yet to come. And with their support and the dedication of Evoke and their close relationship, I think that this is going to be a revolutionary change in the field of diabetic gastroparesis and weigh the suffering of patients that have really had no options for years.

Great. That's a very helpful overview. And just the last thing from us. We know the options are limited in diabetic gastroparesis, but we're just wondering if we could pick your brain about any additional developmental therapies that you would be interested in or that you're aware of that you'd like to talk about?

So to be honest with you, everything has been tried in this -- remember, this is the only FDA-approved medication in 40 years, the new -- a new medication per se. So for 40 years, no one has come up with anything. Gastric pacemakers, I actually interrogate gastric pacemaker, I turned on someone's gastric pacemaker the other day. So when I modified settings. I'm one of the few, probably 1% of gastroenterologists who would do this. So I do -- I am aware, I was at Indiana University as well, it's one of the #1 gastroenterology programs in the country and gastroparesis center. So we have a gastroparesis center there, and it's one of the best motility centers. And to be honest with you, we've -- there's literally been everything tried for gastroparesis. We have off-label treatment, this and that. So there's nothing in the horizon in this arena. There really isn't anything that is being developed. Because this was looked at as almost a hopeless population until GIMOTI came. So everything else has been tried, the surgeries, they're not going to get better. There's something called G-POEMs which I didn't mention, which is like -- which is also used, but there's only very few providers in the United States that do G-POEM. But this is an endoscopic surgical intervention. So I mean, these are not -- this is not like taking a nasal spray. This is cutting out the end of your stomach through an upper endoscope scope. So even that, which has been -- being used in gastroparesis, is limited by the number of providers available that are able to do this. And as well as the data, data -- surgical data takes a long time to collect, obviously, with the fewer numbers getting these type of advanced procedures. So there's nothing, medication or off-label or anything that I can think of from a surgical, endoscopic or pharmaceutical standpoint that's coming in the horizon that would displace GIMOTI or that would be an advent in gastroparesis. And that's evidenced by the 40 years.

And just as a follow-up to that, Dr. Senadhi, I think that we have seen in recent times, since the approval of GIMOTI, at least one pivotal example of a drug that was experimental in nature that failed pretty resoundingly, which probably only illustrates the challenges associated with doing de novo clinical development in this indication. Would you say that's a fair assessment?

Yes. I would say that's a fair assessment. In fact, what's actually even more interesting is because of the clinical trials done by Evoke on gastroparesis, they're now being used as a standard for gastroparesis. The questionnaire is validated. The clinical trial is now what -- there was an IBS trial in the beginning that was done, I want to say it's by Allergan. That became a standard for all IBS trials. That's the first model. This was about 5, 7 years ago. But now Evoke is now becoming the clinical standard for gastroparesis trial. So because of the study design and the data and how the effect on -- impact on patient care. So to answer your question, it really -- that truly is the case, Evoke and EVERSANA now being a leader in field and basically the pharmacologic FDA role model for clinical trial per se.

We have a few questions that were written in from the audience. I'd like to go to those at this point if, Mitchell, you don't have anything else?

No, that's all for me.

Okay. So one point of clarification, I guess, is how long a typical acute flare will last? And is this very variable from patient to patient? I'm assuming that the frequency is very high, especially in situations where you're seeing patients spending upwards of 100 days per year in the hospital. But maybe you can clarify for us what the typical duration of an acute flare is.

So basically, once someone goes into an acute flare, which is defined as usually acute nausea, vomiting and diabetic gastroparesis, they're vomiting all their medications, it's almost -- I would just compare it to your first food poisoning episode or maybe in those types of situations with just uncontrolled nausea and vomiting. So it's similar to that. That's the feeling. It's a horrible feeling. You're sick for days. So it's -- that's what I would relate that question to. So once you're there, you get dehydrated and usually you're ending up in the ER. You're getting fluids, you're getting admitted, if you're depending on electrolytes. So these last about 3 to 5 days. If you're able to curb them and suffer for 2 days outpatient and they're not going to the ER but most, depending on how severe it is, then these are still going to be like 2, 3 days. But 3 to 5 days and sometimes getting admitted for that period -- that period of time, as shown by the data of the hospitalizations. And then they recur. When the patients are severe, they keep recurring, maybe 10 times, 15 times a year because there's nothing being done differently to treat them, right? There's nothing that we're adding because there's nothing available. So you can say this is a flare, but what are we going to do the next flare? The answer is nothing, unfortunately, until GIMOTI and the nasal formulation of metoclopramide came back. The other options like surgery and all these other things, these have already been tried on other patients. You saw my second patient. I gave you an example. He had surgery. He had his end of his stomach cut out. He had a pacemaker. He's maximized. He still had flares. He had abdominal pain still. So this was the only medication that impacted him.

Very informative. Another question pertains specifically to the underdiagnosis of diabetic gastroparesis. And specifically, what kinds of diabetic gastroparesis questions are likely to be underdiagnosed. So the assumption is that patients with highly refractory, very problematic diabetic gastroparesis are probably not the ones who are being missed, so to speak. But can you comment a little bit on that? And if there is indeed a silent population of underdiagnosed or misdiagnosed patients who actually have severe diabetic gastroparesis but who are not actually actively being treated.

So there's -- gastroparesis -- obviously, paralysis of the stomach is delayed gastric emptying. Most diabetics who are not under control will have delayed gastric emptying. That doesn't always correlate with gastro -- having diagnosed with gastroparesis having symptoms. You have to have the symptoms to correlate. But the question is, what are those symptoms? So what is a mild gastroparetic patient have symptoms of? They're probably symptoms not going to be caught by their primary care physician because it's not often recognized as the first neuropathy. So let's say your hemoglobin A1c is 9.5%. It's a little -- it's elevated. Not horrible, but it's not great. These patients may have mild gastroparesis. They may have some occasional bloating. They may have some occasional nausea. They may get sick once in a while here and there. And then maybe they can attribute it to, oh, didn't sit well with me, I have gastritis. So these will be treated with other conditions such as gastritis, you have H. Pylori or something else. And they're really just having gastroparesis, but no one knows it yet. And it gets -- as time goes on, it gets worse. And then they start not have -- their diabetes gets out of control because they can't absorb their oral meds. They have high blood pressure. They usually are very hypertensive because their medications aren't reaching to the small intestine and controlling their blood pressure, they're sitting in their stomach. So this is how these things get missed because diabetics, complicated population. Primary care physicians are spending most of the time treating the diabetes, which is obviously what they're aimed to do. And gastroparesis often gets missed in these mild patients. So that's why you probably have another 2.5 million patients that are undiagnosed. They just don't know it or they're thinking that they have gastritis or inflammation of the stomach or reflux. It often presents as reflux. So people who have gastroparesis, their food is not coming up, so it's coming out. The food is not going -- I mean being digested, so it's coming up and they think they have reflux. But if they don't have reflux, they actually have gastroparesis. So there's where -- a condition where you can have mild gastroparesis and not even know. In the ACG guidelines, they say it because of refractory reflux and esophagitis or inflammation of the esophagus which is -- can be caused by gastroparesis and you should screen for gastroparesis. So that's the guideline in the GI field. So that's kind of one example of mild and going to moderate. And so to answer your second question, too, which was what about severe gastroparetics that do not -- are not recognized? So this happens in patients that have abdominal pain from gastroparesis. They're considered pain seekers. They're considered -- their CTs are negative. So they are thought to be pain seekers and they're kind of shunned by the medical community. They're kind of isolated. So they may have gastroparesis as the cause of pain. In fact, the first person to describe that was one of my mentors at John Hopkins, Dr. [indiscernible] who described first the evidence of gastroparesis causing epigastric pain or pain in the center of your stomach. So these are patients that could have gastroparesis. They can miss because they're not presenting with the nausea, vomiting like most gastroparetics do. They were having the pain first then the nausea, vomiting. So when you come into pain management in America, people coming with abdominal pain, it is always a difficult dilemma for any practitioner. So these are -- some of these patients do have -- if they have diabetes, are actually having diabetic gastroparesis. They may be monitored [indiscernible] that is not being diagnosed.

Last question here. I think it's a particularly apropos one. You talked earlier about the possibility of within as little as a year GIMOTI effectively gaining primacy over all other formulations of metoclopramide and being formally accepted as the standard of care for treatment of diabetic gastroparesis. What do you think is likely to constitute the key tipping point here? You mentioned guidelines. Is it going to be formal ACG guidelines indicating that GIMOTI should be used as the preferential metoclopramide formulation? Or do you think that in the absence of a specific guideline change, the drug is still going to inevitably gain acceptance?

I think GIMOTI is going to inevitably be, by provider, by the medical community, as the most prescribed medication for diabetic gastroparesis because of just the nasal formulation and mechanism of action and the pharmacokinetics. I mean that -- the 7 -- we saw the concentration at 9.5, almost 10x the oral equivalent at that same interval of 15 minutes. That is the tale of the tape there. And that's why I think it's going to be by all providers that are in the field or most providers in the field are going to be the #1 medication used for diabetic gastroparesis. Frankly, off-label, there's going to be a lot of providers that use it for gastroparesis. There are a lot of them that do that now as well because, again, there are no options in the syndrome. But that's -- and so I think that will naturally occur, and it's already occurring, to be honest. But as more and more -- as GIMOTI more and more hits the desks and pharmacies and mainstream of the United States, that this is going to inevitably happen. And then eventually, this will become a guideline change. And this is similar, no difference than other medications in arena with the same effects. But the nasal formulation is distinctive. So that actually gives us an exponential chance to go in this direction at a faster pace.

Thank you so much. I think we have to leave it there, but really very much appreciate your unique insights, your detailed answers to these key questions and your ability to elegantly and eloquently highlight for us such an interesting and impactful treatment innovation. Thank you so much, Dr. Senadhi, for joining us. And thank you to our audience for your attention.

Thank you, Ram. It's an honor and a pleasure. Thank you, everyone.

Thank you, Dr. Senadhi.

Thank you, Mitchell.