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

Good morning. My name is I-Eh Jen, Senior Biotech Analyst of Laidlaw & Company. We appreciate your attending our fireside chat this morning to discuss the Real-World GIMOTI benefits over Oral Metoclopramide from the recent DDW, Digest Disease Week meeting presentations. We will also have additional discussions of other relevant issues in treating gastroparesis with author, Dr. David Kunkel. Overall, we believe this is the first major academic analysis, providing a tangible and quantifiable benefits of GIMOTI. Let me begin first that we are very honored to have Dr. David C. Kunkel from UC San Diego to provide his analysis and discussion with us. He is an associate clinical professor of Medicine and the Board certified and practicing gastroenterologist specializing in the diagnosis and the treatment of gastrointestinal motility disorders, such as GERD, gastroparesis, bloating and other disorders. He is a member of the American Neurogastroenterology and Motility Society and was a recipient of the Training Award through award in motility in 2013. He also is a member of the American Gastroenterological Association and the American College of Gastroenterology. Dr. Kunkel also has conducted researchers in various gastroenterological disorders such as gastroparesis, short bowel syndrome, and he has been published for more than -- with more than 30 articles in peer review journals. Welcome, and thank you, Dr Kunkel. First, could you provide more information about yourself, if I have missed anything during the introduction. And also, could you give us some information about your MetroPractice, such as average number of gastroparesis patients you have treated per week or maybe per month and how frequent if you need to prescribe GIMOTI. Thank you.

Thank you, Yale, and good morning. I am based at the University of California, San Diego, as you mentioned. I'm a gastroenterologists who subspecialize in motility disorders, and we have a tertiary referral motility practice. Every single patient I see has a motility or movement disorder in the gut. Gastroparesis, of course, features prominently in that group. Gastroparesis refers to patients where the movement of food from the stomach is slow or impaired giving rise to a number of symptoms. We have a huge catchment area here in Southern California, extending well beyond San Diego County to Imperial County Riverside, Northern Mexico as well. And our practice has a significant proportion of medical tourism. So I'm seeing folks from all throughout the country. With COVID, we've seen a telehealth boom. So anyone in California, anyone in Arizona now can request an appointment with me and can have that without needing to present in person. So I see a lot of gastroparetic patients every week. I'm seeing at least 10 new patients per week, and I've written multiple prescriptions for GIMOTI.

Okay. Great. As I thought, I would like you first to provide us a brief summary of your oral presentation at the DDW meeting and of the reduction of the Real-World Healthcare Resource Utilization or HCRU for the diabetic gastroparesis patient treated with oral versus the intranasal metoclopramide. And afterwards, I will have some questions, and they can be categorized into 2 groups. The first is related to the presentation and the second will be much more broadly in terms of gastroparesis in the use of GIMOTI, and please go ahead for the DDW presentations.

Absolutely. So I'm really pleased to share this presentation with you and our audience today. And to give some background, I'm a reviewer for DDW myself. And so, this presentation made it not only through our section of gastroparesis, but it was elevated multiple runs above our section, meaning people gastroenterologists who don't treat gastroparesis, reviewed this data and said, this is so important that it was selected for plenary presentation, meaning it was designated one of the most important abstracts in the prior year. And in the area of clinical practice, so gastroenterologists to treat patients, not necessarily basic science translational science, but on the front lines. So this research was presented in the abstract in the oral plenary session dedicated to the most impactful clinical practice abstracts. So it was right there with the latest on colon cancer and inflammatory bowel disease. So that really reflects the importance that was recognized by multiple layers of reviewers extending beyond the motility in gastroparesis space. So I'm excited to talk about it. And really, this is about the significance of metoclopramide administration...

I think the signal is...

Typically comparing the nasal delivery route, which is what GIMOTI offers versus Oral Metoclopramide. My disclosures are listed here. I receive support from Evoke Pharma, the developer of GIMOTI. So diabetic gastroparesis is a chronic stomach disorder characterized by delayed gastric emptying and it leads to cardinal symptoms, including nausea, vomiting, feeling full quickly, what we call early satiation bloating and abdominal pain, which can be severe. In 2022, the prevalence of gastroparesis was $267 per 100,000 U.S. adults with diabetes constituting the most common cause. The symptoms of diabetic gastroparesis not only impact the quality of life for affected individuals, but also lead to poorly controlled diabetes which increases the risk of mortality. To manage these symptoms, patients typically follow dietary restrictions, use antiemetics, which are medicines that reduce nausea and vomiting and undergo treatment with the only FDA-approved medication metoclopramide or resort to surgery and implantation of stimulator devices, for example. However, most patients with gastroparesis have expressed dissatisfaction with the available treatment options. And I would say this is mirrored by physicians and health care providers as well. The economic impact of diabetic gastroparesis is substantial with patients experiencing 3x greater emergency department costs, 3x greater inpatient admission cost to the hospital and twice the outpatient cost compared to non-gastroparesis patients. In the middle of COVID, the summer of 2020, GIMOTI was FDA-approved, and it was the first non-oral outpatient treatment for patients with diabetic gastroparesis. It had to go through bioequivalence testing to oral metoclopramide Phase III, double-blind, placebo-controlled trial and GIMOTI patients experienced significant reduction in their symptoms compared to a placebo group. What's so powerful with GIMOTI, which is going to be abbreviated as MCP on these slides for nasal metoclopramide is what I refer to as the GIMOTI jump, it becomes active, present in the bloodstream within minutes. So keep the GIMOTI jump in mind as we go through this data. That's its advantage over oral nasal metoclopramide provide. So after it became FDA approved, then immediately, it becomes possible to assess the so-called real-world impact that it's had. And so our research objective is to compare the frequency of physician office, outpatient facility, emergency department and inpatient admissions for patients with diabetic gastroparesis who were treated with nasal metoclopramide versus those with oral metoclopramide. By understanding the differences in Healthcare Resource Utilization between these 2 treatment options, we aim to provide insights into their effectiveness and potential impact on patient outcomes and healthcare costs. So that is what we set out to do. Now how can you go about answering that question? Well, we retrospectively identify GIMOTI patients by linking specialty pharmacy data to the Symphony Integrated Dataverse via data app. We included oral Metoclopramide patients who had diabetic gastroparesis and who initiated treatment between June 2020, which is when nasal metoclopramide GIMOTI was approved in December 31, 2021, and were adults. Importantly, patients needed to have a minimum of 6 months data before and after what we call continuous capture. So we needed to have a full data set. We used this validated technique called propensity score matching to match oral metoclopramide patients to demote patients based on age, sex, region, Charleston Comorbidity Score, how sick someone is and any 6-month hospitalization or emergency department visit pre-index. Then we compared mean all-cause visits and also separately diabetic gastroparesis and symptom-related visits for physician office, hospital outpatient, inpatient hospitalization and emergency department between these 2 cohorts for the 6 months following treatment initiation of oral metoclopramide or nasal metoclopramide. And then we carried out a statistical analysis, which I will spare you from going into unless we've got any statisticians on the line. So this is what it looks like. You can see millions of people, millions of oral metoclopramide, and we winnowed that down to 257 that matched the nasal metoclopramide patients. That's what this slide is detailing, matched in what sense, how sick they were, age, insurance, how often they were visiting the emergency department, hospital and their doctor in the 6 months leading up to their -- the comparison point. And so, we propensity score matched the patients on 1 to 1. We wanted to ensure that we captured complete follow-up on these patients. So red dots, our pre propensity score matching and blue-green dots is our post propensity score matching. So I'm going to make this really easy. Red dots are bad, and we want everything to be blue-green, then that means you're matched. So from those $2.9 million, winnowing them down to the 257 that looked just like the nasal metoclopramide patients. That's what this slide is demonstrating. So, after we go through propensity score matching, then we can take a look and see, all right, how did the GIMOTI patients compared to the oral metoclopramide patients. And these 2 groups should be quite similar if the propensity score matching has worked out. And you can see they absolutely are. So here are the clinical characteristics of these 2 cohorts. After matching the average age of patients was 53 years. 77% were women and over 60% were commercially insured. Exactly what we would think about in terms of the demographics that we see for patients who have diabetic gastroparesis in the U.S. This is predominantly a female population. And these are folks who are in their fifth decade of life on average. So once we've done that, now we can then see, well, how did things turn out over the 6 months afterwards, specifically with an eye towards patient outcomes and health care resource utilization for this very expensive condition of diabetic gastroparesis. So this is a really important slide and the green here is the GIMOTI or nasal -- excuse me, I have that backward. So the green is our oral metoclopramide patients and then the light blue is the GIMOTI, or nasal metoclopramide patients. This slide is showing that we found that patients treated with GIMOTI experienced a significant reduction in visits and hospitalizations across 3 key health care settings, office visits, trips to the emergency department and the most expensive thing on the planet inpatient hospitalizations. So just in the 6 months following this separation between nasal metoclopramide and oral metoclopramide, patients had an average of 0.68 outpatient visits compared to 1.1 visits for the oral metoclopramide cohort. And so if we do some math, this translates into a reduction in physician office visits of 99 fewer visits for these 257 patients in 6 months. Furthermore, this translates into 84 fewer emergency department visits, 34 fewer inpatient hospital admissions over the same 6-month period. No doubt, this is the data that led to this presentation being elevated to oral plenary at DDW. Now this slide shows all-cause health care resource utilization. So if we look beyond just diabetic gastroparesis, any type of health care visit, was there a reduction? And so this encompasses the full range of situations from COVID-19 infections, which were ranging at that time, broken bones. And sure enough, we found a significant reduction in physician office and emergency department visits, among them GIMOTI cohort. And so this would have led to 124 fewer physician office visits, 55 fewer outpatient facility visits, 37 fewer hospitalizations and 167 fewer emergency department visits for any cause comparing the GIMOTI cohort versus the oral metoclopramide cohort. In terms of diabetic gastroparesis related healthcare resource utilization, the difference in absolute rates of resource utilization led to a 36% reduction in the likelihood of visiting a physician's office, a 68% reduction in the likelihood of being admitted to the hospital and a 60% reduction in the likelihood of receiving care in the emergency room for patients treated with GIMOTI. These reductions were observed over a 6-month period. These are what we call incidence rate ratios. So to put this all together, to wrap this up, our large retrospective cohort study demonstrates that patients who receive nasal metoclopramide experience significantly reduced health care resource utilization in the 6 months following treatment initiation. This finding translates into a substantial decrease in the burden of illness for both patients and providers by avoiding a significant number of visits across outpatient emergency room and inpatient settings. We hypothesized that this improvement is likely due to better control of diabetic gastroparesis vis-a-vis the GIMOTI jump. However, further research is, of course, needed to validate this hypothesis. As with any retrospective study, selection bias is possible when you're applying inclusion, exclusion criteria in a retrospective manner, you can always be vulnerable to confounding the propensity scoring though this validated methodologic approach mitigates potential bias and the impact of confounding factors in our analysis. And so I'm going to pause here and Yale, I'll be happy to go through some questions with you. Thank you for your attention.

Great. Thanks. And that's a very impressive outcome. And again, as I mentioned earlier, these are very tangible and quantifiable attributes or differences, which is very important, I guess, in physicians' mind when they make the decisions of prescription. So let me start with probably 2 questions regarding your presentation. The first one is, as your DDW presentation illustrate the benefits of intranasal versus the oral metoclopramide is based on aggregate of patients, so, could you give us some yours or maybe your colleagues experience, when you prescribe these 2 type of therapy at the individual patient level and what have you observed a subsequent sort of impact reaction and maybe I have another follow-up after this.

Absolutely. One of the most disputing things a patient can tell you who as gastroparesis is, they were feeling nauseous. They were feeling bloated. They were on the verge of vomiting. So they took their metoclopramide. And then they vomited and they saw the pill in their emesis or material they vomited. That's extremely sole crushing because that pill is of no use once it's been vomited out. It's never had a chance to make it past that morass that is the stomach and get into the intestine where it gets absorbed and then becomes active. So in this space, we've all had our patients report that experience if they have volume. So what I like hearing from patients where I asked them how things are going on GIMOTI, the feedback, of course, that I think resonates most is that it was more convenient and more effective than oral metoclopramide, because they knew they weren't going to vomit it back up, and they started feeling better within minutes because that's how quickly the drug gets absorbed. So that's the kind of feedback I'm listening for. And that is -- makes all the difference for a patient not to worry about vomiting back the medicine that's supposed to help them feel better.

Okay. Great. That is very helpful. Maybe I'm going to drill down a little bit more specifically as one of your -- actually, our first data slides suggest that the 2 symptoms, which is nausea and vomiting, which you highlighted. So I just want to get a little bit more color in terms of these 2, why these 2 was something you've been choosing for your presentation? And are those symptoms have the greatest impact on gastroparesis patients, then maybe I have another one in terms of the abdominal pain. And if you want to also elaborate more on that.

So nausea is the most common symptom in gastroparesis. In fact, if someone does not have nausea, I almost question the diagnosis. We know from Henry Parkman and the Gastroparesis Consortium, that of every symptom is the keystone symptom really at the heart of gastroparesis. So when we're talking about symptoms that we want to improve, then obviously, we want to be addressing public enemy #1. It goes without saying, if you improve nausea and vomiting, you're going to have a significant impact on quality of life for these patients. Abdominal pain is a difficult symptom to manage because it's complex, multifactorial, the nature of pain perception, and I would say the pain piece often requires a multimodal approach. But yes, absolutely, I'm happy to dive deeper into that yield.

Okay. And maybe just one follow-up on this one is, once the vomiting and the nausea as well as abdominal pain was alleviated, would patients feel most appreciative of this level of relief? Was that the general experience you've seen from gastroparesis patients?

Short answer is yes. If there's one symptom that I can improve, it is the nausea and vomiting piece, that's the most important piece. Guess what? Everyone here on this call, every human experience is nausea and vomiting. So this is not an abstract concept. This is something we've all experienced. And we all know how unpleasant that is. Fortunately, for most of us, the frequency of those symptoms is reduced. If you're gastroparetic this is either a daily or weekly symptom. And so it is the most important to address Metoclopramide is unique among treatments for gastroparesis because it works both centrally and peripherally. What I mean by that is it helps the stomach empty more quickly. It addresses the gastroparesis piece, but it also acts centrally in the brain to reduce the burden of nausea and vomiting.

Okay. Great. That is very insightful and helpful. Maybe I will move to the second part of the question, which is that much broader in general, broader issues related to gastroparesis treatments. My first question here is that among the various symptoms of gastroparesis, which one or a combination that will trigger you to admit this person to a hospital.

So generally, any severe or uncontrolled symptoms of gastroparesis could potentially necessitate hospital admission, but especially intractable vomiting that can lead to dehydration, electrolyte imbalances, malnutrition and in diabetic patients, dangerous metabolic disarray. Folks who have really bad vomiting can't eat, they can't maintain their fluids. And so certainly, that would be a reason to admit them to the hospital where primarily what's done is to just bypass the stomach and put an IV in and start giving fluids and medicines through the IV. That's basically what is done in addition to monitoring for downstream complications, such as diabetic ketoacidosis.

Okay. Great. Also, based on the different levels of severities, what might be the treatment selection for you when you're treating gastroparesis patients.

So treatment selection generally depends on severity of an individual patient's symptoms. Patients with mild symptoms, dietary modification and 1 or 2 medications will suffice. Patients who have more severe symptoms and who have had multiple emergency department visits, multiple hospitalizations. That's where we're going to start thinking about advanced treatments, more invasive treatments and those folks will be put in the severe refractory ban.

Okay. That's very useful. And also, one patient failed there generally probably the first oral metoclopramide therapies. What may be the determined factors in selecting different other treatment options? Then I have another one follow this.

Yes. So the next line of treatment could depend on the specific symptoms that we're not adequately controlled patient preference, risk-benefit profile, side effects. Certainly, though, adequate absorption of the medication would be assessed based on symptom control. So if somebody is vomiting out their oral metoclopramide, they're not having side effects, the pill is not getting absorbed naturally that would be a situation where we would want to offer GIMOTI.

Okay, and I know most of the patients in gastroparesis have a number of motility at the same time in terms of different diseases. Would you be able to assess patients that because of the throughout the pills that other sort of disease worsened or that kind of situation? And was there something else do you need to managing or treat maybe given in collaboration with other specialists?

So I'm on the hook if patients are throwing up their pills because guess what, they're not only throwing up their gastroparesis pills, but they're also throwing up their diabetes management pills, they've hypoglycemic agents, Metformin, Libre. And so the endocrinologists who are the diabetologists managing the patient's diabetes if they've had a solid organ transplant and are antirejection meds, which absolutely can't be vomited up, all of a sudden, all the guns of these other specialists get pointed at me. And so the pressure is on absolutely. We cannot have this patient vomiting. They're going to reject their heart, their lungs. Their diabetes is going to be impossible to control if the oral hypoglycemic agents aren't being taken and processed in a predictable manner. So these are situations where immediately we want to get on that. We want to leverage all the tools available, our full armamentarium. And in some cases, that means just bypassing the stomach completely with use of an enteral tube. That's how important it can be to ensure optimal absorption of medications. Sometimes we just have to skip that waiting room that is these gastroparetic patients stomachs.

Okay. That certainly is important given the severity of the sort of collateral damage, I guess, to the patient other than simply the core problem you are treating. And my next question is that what portion of our patients generally fail the original treatment and may need to go to the second-line therapies.

So estimates vary, but a considerable patients require second-line therapies due to insufficient symptom control or side effects. I'm a tertiary referral center. So I'm seeing generally the more complicated and complex patients that might gastroenterology colleagues are struggling to manage on their own. Occasionally, the endocrinologist will send a patient over to me who hasn't been under the care of a gastroenterologist separately. But I'm biased in the sense that patients I'm seeing tend to be on the more complicated spectrum. But if we're speaking more generally, as a general rule, second-line therapies are going to be coming into play for a considerable proportion of these patients.

So would that be the case that when given you the academic settings and the treasury referring centers, you mentioned that you're getting more severe patients more often. And so you've been seeing the -- presumably seeing the benefits of being able to bypass the GI tract for treatments that will be -- will have a significant impact compared to other situation community settings.

Absolutely. It's my job to be aware of the latest treatments, the latest data. It's my job to be at the spear tip, and I think that's been one of the hard things with GIMOTI, in that it was -- it came out in the middle of COVID where there was a lot of distractions in health care. And so for me, though, that's my job, I need to know everything. I need to know the latest. And so absolutely, it's a tool that we've been leveraging from the outset for our patients in my motility practice.