Relmada Therapeutics Inc. Q1 2023 Earnings Call

Speaker 1: Thank you.

Speaker 2: Good afternoon. Thank you for attending today's Realmata Therapeutics, Inc. first quarter 2023 earnings call. My name is Forum and I will be your moderator for today's call. All lines will remain muted during the presentation portion of the call with an opportunity for questions and answers at the end.

Speaker 2: If you would like to ask a question, please press star 1 on your telephone keypad. It is now my pleasure to pass the conference over to our host, Tim McCarthy from Lifesci Advisors. Mr. McCarthy, please proceed.

Speaker 3: Thank you, operator, and thank you all for joining us this afternoon. With me on today's call are Chief Executive Officer Sergio Traversa, Chief Medical Officer Dr. Cedric O'Gorman, and Chief Financial Officer Megan Shinoda.

Speaker 3: This afternoon, Romada issued a press release providing a business update announcing financial results for the three months ended March 31, 2023.

Speaker 3: Please note that certain information discussed on the call today is covered under the Safe Harbor Provisions of the Private Securities Litigation Reform Act.

Speaker 3: We caution listeners that during this call, Ramada's management team will be making forward-looking statements.

Speaker 3: Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business.

Speaker 3: These sporting statements are qualified by the cautionary statements contained in Real Modest Press release issue today and the company's SEC findings, including in the annual report on form 10K for the year and December 31, 2022 and subsequent findings.

Speaker 3: of this live broadcast May 11, 2023. The amount of undertakes, no obligations or revisor update any forward looking statements to reflect events or circumstances after the date of this conference call. Now I would like to turn the call over to Sergio. Sergio?

Speaker 4: Thank you, team. As always, and good afternoon to everyone.

Speaker 4: I am pleased to welcome you to the RELMADA First Water 2023 conference call. During today's call, we will provide an overview of our ongoing Phase 3 program for REL1017 in major depressive disorder. CEDRIC will provide a clinical review and update and MAGET will review our financial results.

Speaker 4: We have implemented clinical-chase critical changes to the ongoing study 302, a Phase 3 2-on placebo-controlled Pivotal study, evaluating REL1017-25 milligram, and we really initiate our new trial study 304.

Speaker 4: for adjunctive MDD. Our study 302 protocol amendment was finalized and is now being implemented across all clinical sites. The new study 304 protocol has been drafted and will be ready for study initiation by mid-2023.

Speaker 4: force that the true most important drivers for study success are recruiting the appropriate patient with true MDD and controlling for placebo response.

Speaker 4: Red-1017, unlike the conventional monomin energy antidepressant X by blocking the NMD-A receptor and correcting the consequences of these regulated glutamatergic pathways believed to underlie the path of physiology of MBD. It does not affect mood by altering neuro-classmeters levels or independent...

Speaker 4: Since our last call, we have been focused on optimizing the design of our clinical trial for signal detection, via the amendment of the study 302 protocol, and via the drafting of a new stream-like study 304 protocol.

Speaker 4: Both the resulting protocols that concentrate on recruiting appropriately diagonal subject.

Speaker 4: control and placebo response and the anything signal detection. Additionally, we have been finalizing the selection of the preferred clinical sites, and they have been visiting these sites as we strengthen our relationship and collaboration with them on our clinical trials.

Speaker 4: I'm also pleased to report that the open label, one year safety study for WELCM17, study 310, is concluding with all treatment visit completed and finally, safely follow-up visit occurring in the next couple of weeks. Therefore, attain in a necessary long-term safety exposure

Speaker 4: that Rellmada is sufficiently funded to fully execute our plans to reach data readouts from both Phase 3 trials.

Speaker 4: I will turn now the call over to Sedrik, our chief medical officer, to go over the clinical progress in the quarter and provide an update on the plans moving forward.

Speaker 4: Cedric, thank you, Sergio. As Sergio indicated, we've now amended our study 302 protocol, which has been IRB approved and subjects are already being screened under this streamlined protocol. The amendment has significantly lessened the burden to both subjects and sites.

Speaker 4: By reducing required time spent by subjects at the site, this was achieved by removing duplicative assessments and evaluations that were of exploratory interest.

Speaker 4: The amended protocol capitalizes on our learnings from the completed control trials and optimizes the potential for reduction in the high placebo response seen in those completed studies.

Speaker 4: As you recall, when we analyzed the results of the 301 study which failed to meet its primary endpoint, we saw in a post-talk analysis of subjects from verifiable versus non-verifiable sources a striking difference.

Speaker 4: Verified resource patients were defined as patients who were known to the sites, such as current patients. Patients obtained from the site database and healthcare professional referrals. All of these elements increase the confidence in these subjects having a confirmed diagnosis of MDD.

Speaker 4: As contrasted with nonverifiably sourced subjects, nonverifiably sourced subjects with those recruited through radio and TV ads, social media, via the internet and through recruitment agencies. We observed that reliably sourced subjects treated with RAL1017 had a change from baseline of 15.2 points on the Madras Total Score at day 28 versus 11.8 points for placebo.

Speaker 4: This amounts to a 5.5 point placebo with just a difference with a p-value of 0.016.

Speaker 4: From this post-doc analysis of our study 301 data, it is clear to us that in clinically depressed patients from verifiable sources, Rel1017 has a strong signal of efficacy.

Speaker 4: In the ongoing 302 study and the upcoming 304 study, we will require that patients coming from verified sources have documented evidence of their MDD diagnosis. We will require medical records from prospective subjects to verify MDD diagnosis and antidepressant treatment history.

Speaker 4: Additionally, as you recall, two of our sites in rolling sites in the 301 study were particularly impacted by paradoxical data and high placebo response.

Speaker 4: When we excluded all data from these two sites, the population was reduced by only approximately 40 patients, and we saw a 4.1 point placebo adjusted difference at day 28 on the Madras total score of favoring RAL-1017. These important post-doc learnings have allowed us...

Speaker 4: to make site selection improvements and prioritize moving forward with those sites who were better able to control for placebo response.

Speaker 4: Our open label One Year Safety Study for Route 1017, Study 310, is concluding with final safety follow-up visits occurring over the next couple of weeks, fulfilling the long-term safety exposure requirements for our NDA filing. We expect data from this study to be available later this year. As we continue to advance our ongoing phase three program for Route 1017, we're also focused on further enhancing the growth of published and presented data in support of our promising late-stage product requires funding.

Speaker 4: To this end, we have had two late-breaking posters accepted for presentation at the upcoming 2023 American Society of Clinical Psychopharmacology Meeting or ASCP at the end of May. One presentation will highlight the protocol efficacy results from study 301.

Speaker 4: As a reminder, this was a pre-specified analysis. The verb protocol refers to the population of patients who were treated today 28 and did not have major protocol deviations. This pre-specified analysis resulted in the exclusion of only 29 patients compared to the full analysis set.

Speaker 4: Per protocol comprised 198 subjects compared to 227 in the full analysis set. The change in Madness Total Score from baseline at day 28 was 15.6 points for a route 1017 and 12.5 points for placebo for a placebo adjusted difference of 3.1 points.

Speaker 4: all signs and symptoms in the trial. There was no difference between rail 1017 and placebo treatment groups in terms of drug likability, abuse potential, and withdrawal effects.

Speaker 4: I will now turn the call over to maggot to review our first quarter financial results. maggot, sure, thank you, Senator. Today we issued a press release announcing our business and financial results for the three months ended March 31, 2023, which I will now review.

Speaker 5: For the first quarter ended March 31, 2023, total research and development expense was approximately $15.9 million, as compared to $25 million for the comparable period of 2022. The decrease was primarily associated with the completion of Study 301 and Study 303 in late 2022.

Speaker 5: Total General Administ and Administrative Expense for the first quarter ended March 31, 2023. It was approximately $12.3 million. This compared to $13.3 million for the comparable period of 2022. A decrease of approximately $1 million. The decrease was primarily driven by a decrease in stock-based compensation. This non-cash-charged totaled $9.4 million into most recently completed first quarter. The decrease of approximately $1 million. The increase of approximately $1 million.

Speaker 5: For the first quarter ended March 31, 2023, and that loss was $26.3 million or $87 cents per basic end to dementia.

Speaker 5: Compared with a net loss of $39.7 million, $1.40 for basic and limited chair in the comparable period of 2022.

Speaker 5: Netcash used an operating activities for the three months and in March 31, 2023, totaled $16.5 million, compared to $19.4 million for the three months and in March 31, 2022.

Speaker 5: As of March 31, 2023, we had cash, cash equivalents, and short-term investments of approximately $132.4 million, compared to cash, cash equivalents, and short-term investments of approximately $148.3 million as of December 31, 2022. Based on our clinical development plan, we have a total of $1.8 million in cash equivalents and short-term investments.

Speaker 5: Our current cash position provides us with ample runways or through the end of 2024.

Speaker 5: We have known the conclusion of study 310 with Sergio discussed earlier as well as completion of certain earlier stage studies will support this expected cash runway. I'll now ask the operator to please open the cloud for questions. Certainly. If you would like to ask a question.

Speaker 2: We will pause here briefly as questions are registered. Our first question comes from the line of Mark Goodman with SVB Securities. Mark, your line is now open. I think so to you my question. This is Judy on the line for Mark.

Speaker 6: I just want to aim based on the current data from Realize 1 and 2. Do you believe that four weeks is the right duration to more four weeks, another trial? And do you think a longer trial like maybe four, five or six weeks may have increased the separation? Thanks.

Speaker 7: Thanks for the question, Sergio. Cedric, I believe the question is for you.

Speaker 4: Thanks for the question. We have looked at that and looking at the trajectory of the improvements observed with drug and placebo in the completed studies. We believe that if we can control placebo response and still get the same results, we can get the same

Speaker 4: see the trajectory of the improvement, but essentially is the rapid acting antidepressant through it's an NDA antagonism. We think the four weeks is sufficient in order to separate and have a positive study. And also we've got agreement with the regulatory agencies to pursue a four week. So we think that the best approach now is to pursue four weeks. And also...

Speaker 4: When you look at the protocol analysis and the other postdoc analysis, the protocol being pre-specified on the postdoc, we believe that if we can control the CIFR response for weeks, it would be a sufficient duration. Got it. This is very helpful. Thank you. Thank you, Sadi. If you look at the curve on the 301 data, it may be

Speaker 7: days, four weeks would be like an appropriate primary and point timeline. Hope we answer your question.

Speaker 7: like an appropriate primary and point timeline. Hope we answer your question. What makes us appreciate the color?

Speaker 8: Thank you for your questions.

Speaker 5: Our next question comes from the line of Oi Air with Mizzou Ho. Your line is now open. Guys, thanks for taking my question. I have two questions. My first question is, so you have, I think you said you have completed selection of sites for the 304 studies. Just wondering if there's any overlap with the 302 studies, and I think you also indicated you're limiting the number of patients enrolled in each of these sites. Just wondering like, how many patients are you expecting to enroll at each of the sites? And I guess, how many sites are there with 304? You can share that.

Speaker 4: three, but now you're just saying 2023 is wondering if there's a change. Thanks. Thank you, we said Rick, I believe that also this question is for you. Sure, so hopefully I'll hit on all the questions here, but the first one was about the selection of sites for 304 and whether there's an overlap with 302. No, because we will be starting the 304 study mid-J year and middle of this year and so therefore 302 is ongoing and so that they are unique sites across the two studies. I think you said you asked him

Speaker 4: data from the open label. We did say middle of the year, and the study is completing, but you know, that's the last follow-up safety business occurring in the next two weeks. So then it's just a question of how quickly we can, you know, clean the data and get it to you. So I wouldn't say that we, I wouldn't say that we are changing our expectation there because we can still, me to just include as soon as we clean.

Speaker 7: we have a complete understanding of the data before we release them and it will provide quite a bit of quite a bit of new data so we want to do it appropriately and it will be sometime in the second half

Speaker 2: Okay, thank you. Thank you for your question. Our next question comes from the line of Andrew Tsai with Jeffries. Andrew, your line is now open.

Would you say, how are you balancing quality of patients and sites versus getting the data as fast as possible for investors? Are you kind of operating in such a way that you are not taking quote unquote, no shortcuts whatsoever? Just so it's a high level question to start. Yeah, I'll give you the top down and Cedric can expand and give his opinion as well. Just in light of the experience that we had with the other two studies, clearly quality is the driver.

And of course we have to consider time too because the study has to be concluded on a reasonable amount of time. Let's put it in this way, plus minus three months, we don't think that would make a difference for investors.

Yeah, I would just echo what you said Sergio in terms of the focus being on quality, not on speed. And I think that quality sites have been selected based on what we were able to learn from those sites that did a better job of controlling placebo response versus not. And also the sites that did a better job at being able to verify confirmed diagnosis and get the right patients into the trial versus the more unverified resource patients. Also, we're applying a really rigorous eligibility review process now. So as a result of that and requiring medical records, it obviously slows down the rate somewhat in making sure that we...

don't cut corners here and that we really get the most appropriate patients into the studies.

Right. Makes sense. And so another thing just came to my mind is, I think last time you showed maybe a subgroup analysis where patients, you know, how patients perform differently pre and post COVID. So it made me think what if there was a new COVID variant?

later this year, knock on wood. If that were to happen, what would you do for your study? Would you kind of pause enrollment? Just would be curious to gauge your thinking here. Thank you. Yes, Cedric, would you mind?

already. It wasn't just our study. So it is a valid concern, but I would also say that there are other aspects in the analysis that we did, which showed a more profound effect when you considered the verified patients with confirmed diagnosis versus unverified. Even the per protocol pre-specified analysis showed that there was good retention throughout the entire study. We had very low discontinuation rates. Route 1017 has a particularly placebo-like side effect profile and...

And this is really, in two senses, it's aided continuation through the study. And in the other sense, often trials...

So, somewhat paradoxically, benefit from this aspect of functional and blinding, it would appear that patients truly cannot distinguish between drug and placebo. That's my interpretation of the data that I've been looking at. So, if it was a pandemic, I think we'd have to look at that closely.

I'm hoping that we're path that now and that's the importance in getting this and the studies are up and running right now and the new studies set to start. So let's hope we don't have another COVID pandemic.

Thanks for the update.

Right, yes. Okay, very good. Thanks for the update. Thank you, Andrew.

Thank you for your question. Our next question comes from the line of Andrea Tan with Goldman Sachs. Andrea, your line is now open. Hi, everyone. Thanks for taking my question. Two for me, please. First, with respect to the open label safety study, I know you've spoken in the past about the potential to understand the real world.

real-world effect of treatment through that data set, but just given that these are patients who rolled over both from the failed Reliance 1 and 3 trials, just wondering if you could help frame expectations for that data read and how they should be interpreted within that context. And then secondly, just

Thank you, Andrea. And great question. I believe Cedric. It's to answer Cedric.

how patients might get the drug medication in the real world, and it can provide very important information regarding response, durability, continuation, tolerability of the drug in the real world. And you have it out to 12 months, which is really nice long-term exposure. It has quite a number of subjects in the study. And as you point out, some are very

we look forward to parsing out and being able to to share with you. So again we'll have to see what the data is and with the study completing the safety follow-ups we will have there'll be more to come on that. And then with regards to the safety the data monitoring committee we always

both internally have a rigorous safety review process for all our trials and we would continue to use the data monitoring committee and with regards to potentially increasing the size of the study that's certainly on the table for us to have a look at as well.

Got it. Maybe just one sorry, one follow up on the considerations for increasing the study size. Maybe if you could just provide a little bit more color around that comment.

Go ahead, Sadi.

Well, what I was going to say was we haven't actually given any guidance about our planning. So take 304 for example, the protocol is in its final stages of development and when that's finalized the design will be shared and it will be often clinical drives out but I would be sort of hesitant to...

to jump into detailed around plans for interim analysis or optimizing the trial only because we haven't finalized design, we haven't spoken about our plans in that regard yet, so I would want to prematurely comment on that.

Okay, thank you. Thank you for your question. Our final question comes from the line of Gethine Sumedja with Guggenheim partners. Gethine your line is now open.

Yeah, a few questions from me. Could you comment on your interactions with the FDA? Have you met with them and discussed these in amendment to the protocol for the Lions too?

And then, you know, you made the modification. There are patients that were added before the modification. So how will the mixed data be analyzed? Just curious what the interaction or the agreement has been.

have noticed how . Good go witnesses therefore we are so in regards to . Okay go Position

communication that the FDA, clearly we don't comment on specific interactions with the FDA, but we do have an ongoing dialogue with the FDA. And we certainly wouldn't do anything that didn't have the approval of the regulatory authority than any of our plans or decisions moving forward.

With regards to the question around the pictures before and after the amendment, I mean ultimately we will finalize the statistical analysis plan and submit that to the FDA. And you know I won't comment on the specifics of our plan statistical analysis plan.

we feel confident that if RAL-1017 has a signal for efficacy, that this can be a positive study based on our calculations. Okay, second one more if I may. And this is with regard to the onset of action.

So if we look at the first very first study that was done, I mean the onset was pretty rapid, nice separation within a week. What has changed, like even in a subset of analysis, then we take all the precautions and we'll be a post-doc, the onset, we look a little bit slower and the curves are not similar. So what's going on?

Thanks.

because you're absolutely right in the phase two and the week one profound improvement with drug was like 16.8 points compared to 8.8 with placebo and we saw effect sizes of the order of 0.7 to 1.0 so that was an incredibly

well-controlled inpatient study. Now what we do know is that outpatient, well going from phase two to phase three is a challenge in itself, but then also the outpatient population is a little bit more difficult to control as we have seen from the various post-hoc analysis that we have seen so far.

that I've already mentioned. But what is striking in 301, for example, is that the majority of the placebo response happened in the first week.

And so you're seeing an almost, ultimately the change from baseline with placebo in the 301 study was 12.9 points. And the vast majority of that had occurred by day seven. And in looking at the protocol, we were able to see that the screening visit was...

very very long. The baseline visit was long, we had a day four visit which was long and then by day seven when they came in they were having another extensive visit on site and getting interaction with the staff.

we are focused now on minimizing.

site patient interaction in that crucial first week. And I think that what I'm hopeful for is that with the new amended protocol and the new study planned, you'll see less of a significant placebo change in that first week. And it'll be more gradual, whereas...

the potential for route 1017 to see closer to what we saw in phase two, I'm hopeful that we'll be able to isolate that effect with this careful trial design that we've implemented.

Thank you Cedric and Jatin if I can add a little bit of color. We have seen from the data there now we have significant amount of data available and RAL1017 has a marked effect when the patient is really infected.

percent to patient that were affected by other situational depression and or not depressed at all. And so that, you know, the data have been kind of skewed in the opposite direction because of the patient selection. We do believe that if we, like the patient

enrolled is the patient affected by the pressure, we should see an early response.

is the patient affected by the pressure, we should see an early response similar to phase 2.

Got it. Very helpful. I hope we answered your question. Yeah, no, that's very helpful. One more question, if I may. Maybe Magat can comment on the expenses. Nice control on the R&D side. Curious how to think about the next three quarters and G&A is still a little bit higher. Would love to understand how that would shape up. Thank you so much.

So slightly up, slightly down, but on average around that for the remainder of the year.

spend in the third quarter, but all of this in around, I would say, the $15 to $16 million range per quarter. Very helpful. Thank you. Thanks for the questions, Yatham. Thank you for your question. This concludes our Q&A session for today's call. I will now pass back to the management team for any closing remarks. Thank you.

Well, thank you. In summary, we remain confident that we have an approval drug, and then we have the right plan and the team in place to optimize the chances for success. We also believe we have the most reliable site identified and know how to identify the most suitable MDD patient, patients affected by major depression.

We have greatly improved our study protocols, and also as a reminder, all other preclinical and clinical and CMC pieces are in place for a successful NDA filing for RAL 1017. We are sufficiently funded to fully execute on our plans for RAL 1017 development.

to support the important work that they are doing. That said, a big thank you to all the participants and everybody interested in the progress on Armada and we'll update you on the next development.