Q2 2022 Relmada Therapeutics Inc Earnings Call
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Operator: Good day, ladies and gentlemen, and welcome to the Relmada Therapeutics Inc. second quarter 2022 earnings conference call.
Good day, ladies and gentlemen, and welcome to date around Micro Therapeutics, Inc. Second quarter 2022 earnings Conference call.
Operator: Today's conference is being recorded.
Today's conference is being recorded.
This time I would like to turn the conference over to Brian Ritchie of lifestyle embodies. Our please go ahead Sir.
Operator: At this time, I would like to turn the conference over to Brian Richie of Lifesight Advisor.
Thank you operator, and thank you all for joining US. This afternoon with me on today's call are Chief Executive Officer, Sergio Traverse yet John Nixon head of commercial and Chief Financial Officer baggage.
This afternoon robotic issued a news release, providing a business update and announcing financial results for the three and six months ended June 30th 2022 and filed its quarterly report on Form 10-Q with the SEC. Please note that certain information discussed on the call today is covered under the safe Harbor provisions of the private.
Securities Litigation Reform Act, we caution listeners that during this call well modest management team will be making forward looking statements 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. These forward looking statements.
Qualified by the cautionary statements contained in real modest press release issued today and the company's SEC filings, including in the annual report on Form 10-K for the year ended December 31 2021.
And subsequent filings. This conference call also contains time sensitive information that is accurate only as of the date of this live broadcast August 11 2022.
<unk> undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances. After the date of this conference call now I'd like to turn the call over to Sergio. Please go ahead, Sir jail.
Brian Richie: Please go ahead, sir.
Brian Richie: Thank you, Operator, and thank you all for joining us this afternoon.
Thank you, Brian as always and good afternoon to everyone I'm pleased to welcome you to the role model second quarter 2022 conference call.
Brian Richie: With me on today's call are Chief Executive Officer Sergio Traversa, Don Hickson, Head of Commercial, and Chief Financial Officer Maged Shenouda.
Brian Richie: This afternoon, Relmada issued a news release providing a business update, announcing financial results for the three and six months ended June 30, 2022, and filed its quarterly report on Form 10-Q with the SEC.
During today's call I will review, our recently achieved milestones and provide an update on the anticipated timeline associated with the multiple expected clinical trial Readouts for <unk> 17.
Our lead product candidate that we are currently starting as a paradigm shifting novel treatment for patients with major depressive disorder or <unk>.
Brian Richie: Please note that certain information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act.
Following my comments <unk> <unk>, our chief financial.
<unk> will review, our financial results and balance sheet and.
Then take.
Yeah.
Brian Richie: We caution listeners that during this call, Relmada's management team will be making forward-looking statements. 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. These forward-looking statements are qualified by the cautionary statements contained in Relmada's press release issued today and the company's SEC filings, including in the annual report on Form 10-K for the year ended December 31, 2021, and subsequent filings.
We are approaching multiple key catalysts from our ongoing late stage rely on clinical development program.
Brian Richie: This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, August 11, 2022.
We anticipate completing the enrollment, though Rhode Island, three the ongoing monotherapy, a registrational phase III trial sure Mark.
Brian Richie: Relmada undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call.
Brian Richie: Now, I'd like to turn the call over to Sergio.
Specifically, we expect to enroll the last patient in this trial before the end of August probably earlier than that.
Sergio Traversa: Please go ahead, Sergio.
This will be followed by soon thereafter by a top line readout of the study in the second half of <unk>.
Sergio Traversa: Thank you, Brian, as always, and good afternoon to everyone.
We also continue to expect top line results from reliance one and rollout of <unk> in the second half of 2022.
Sergio Traversa: I'm pleased to welcome you to the Relmada second quarter 2022 conference call.
As a reminder, last one <unk> through our two ongoing phase III system, two arm placebo controlled pivotal studies evaluating well 10, 17, 25 milligram as a potential adjunctive treatment for Mds.
Sergio Traversa: During today's call, I will review our recently achieved milestones and provide an update on the anticipated timeline associated with the multiple expected clinical trial readouts from REL 1017, our lead product candidate that we are currently studying as a paradigm-shifting novel treatment for patients with major depressive disorder, or MDD.
Three is the ongoing phase III two arm placebo controlled Registrational study evaluating well done 17, 25 milligrams as a potential monotherapy single agent treatment for ended all participant in all over the reliance trials take a loading dose.
On the 175 milligram three tablets overall 10 seven.
Okay.
We are also delighted to share that the FDA recently granted fast track designation to <unk> as a monotherapy single agent for the treatment of major depressive disorder.
Our commercial preparations.
Sergio Traversa: Following my comments, Maggie Chinuda, our chief financial officer, will review our financial results and balance sheet, and we will then take your questions.
<unk> also continued we didnt expansion of our senior management team most.
Sergio Traversa: We are approaching multiple key catalysts from our ongoing late-stage Reliance clinical development program. Specifically, we anticipate completing the enrollment of Reliance 3, the ongoing monotherapy registration of phase 3 trial, shortly. More specifically, we expect to enroll the last patient in this trial before the end of August, probably earlier than that. This will be followed soon, thereafter by a top-line readout of the study in the second half of this year.
Most recently, we are thrilled to welcome John <unk> to remodel head of commercial genre.
John has over 36 years of sales and marketing experience within the biopharmaceutical industry, including a 31.
With Eli Lilly.
John is on the call. So before I go further John would you like to say a few words.
First conference call.
Remind you just joined them.
I'd be happy if you can say a few words.
Sergio Traversa: We also continue to expect top-line results from Reliance 1 and Reliance 2 in the second half of 2022. As a reminder, Reliance 1 and Reliance 2 are two ongoing Phase III sister two-arm placebo-controlled, pivotal studies evaluating Rel 1017-25mg as a potential adjunctive treatment for MDD.
Yeah, Hi, everyone. There Joe it's a real pleasure to be with all of you and I just want to say that I'm thrilled and.
And humbled and excited to be a part of this real motto team so as Sergio said.
I've got a pretty broad background in commercialization, all 31 years with Eli Lilly, we're in commercialization related roles.
Was fortunate to spend eight years outside of the U S and Spain, South Korea, and Australia, while we're in Australia of my team and I launched Zyprexa the atypical anti psychotic and then when I returned to the United States I became the the last.
Mobile marketing director for Prozac as it was late in its product lifecycle and once that role and it shifted over to be the brand launch leader for Cymbalta Lilly's next antidepressants and pain drug.
After launching the drug is being with it for several years post launch I shifted over to new product planning.
I worked with.
Discovery and development scientists and provided assessments of commercial viability of low lease portfolio and also was actively engaged in various business development opportunities.
And so again I just thrilled to have this opportunity I know the depression space well.
Depression is something that like perhaps many of you as impacted members of my family and close friends.
Having this opportunity to bring forward a new approach to treat depression, if the drug is approved.
Exciting for me and one that I'm very passionate about I think the drug has.
Exciting.
It's truly an exciting new treatment options. So again, thank you very much let me turn this back over to Sergio. So we can continue on with you all thank you.
Thank you John and we're really very happy to have you onboard with us.
Sergio Traversa: Reliance 3 is the ongoing Phase III two-arm placebo-controlled registrational study evaluating, Rel 1017-25mg as a potential monotherapy single-agent treatment for MDD.
Moving on to the current status of the Phase III program as I said earlier, we continue to anticipate the completion of enrollment in <unk> three the ongoing monotherapy single agent a registrational phase II trial with the last patient enrolled before the end of August followed by the topline data readout.
Shortly after the completion of the four weeks.
Treatment.
Let me provide an update on the ongoing reliance one and two studies.
Sergio Traversa: All participants in all of the Reliance trials take a loading dose on day one of 75mg, 3 tablets, of Rel 1017.
As a reminder.
Last one and the reliance to design to evaluate <unk> 10, 17, as an adjunctive treatment for MTBE and both include two arms placebo and 25 milligram of <unk> 17. Both studies are studying the use of <unk> 17. In addition to our standard.
Sergio Traversa: We are also delighted to share that the FDA very recently granted fast-track designation to Rel 1017, as a monotherapy single-agent for the treatment of major depressive disorders.
Sergio Traversa: Our commercial preparations have also continued with an expansion of our senior management team.
Sergio Traversa: Most recently, we are thrilled to welcome John Hickson to Relmada's head of commercial. John has over 36 years of sales and marketing experience within the biopharmaceutical industry, including a 31-year career with Eli Lilly and company.
Depressing for participants who are.
I've had inadequate response to at least one and up to three standard antidepressants.
The primary endpoint is the change in my address the scale that is used to evaluate the severity of deflation.
And model score at day 28.
Key secondary endpoints include the change in <unk> score at day, seven and changing clinical global impression of severity scale CGI score at day 28.
<unk> was chosen as the primary endpoints in agreement with the FDA with an understanding common that depression is a chronic disease and but success of eastern points on day 28, with two core <unk> 17 is a chronic treatment for depression.
Both reliance one and reliance too are progressing as planned and we continue to expect the availability of topline data in the second half of this.
The reliance development program also includes reliance O L. S. The long term open label safety study is enrolling both rollover participants from all three people put studies as well as de Novo proteins.
Radar reliance oil is ongoing and continued to enroll RCC pine <unk> Nathan.
Data from these long term open label safety study and we now expect in the first half of 2023 will be part of the plan that rolling NDA filing package.
Finally, while Maggie will review our financials in detail shortly I would like to emphasize how strong.
Our financial position, we are currency you can recall that we completed an oversubscribed follow on offering for gross proceeds of $172 million in late December 2021.
When the capital market for biotech companies, we are heartless challenging they are today these financing <unk>.
Provided us with the maximum financial and operational flexibility as we ended the second quarter with cash cash equivalents and short term investments of approximately 222 with it.
Sergio Traversa: John is on the call, so before I go further, John, would you like to say a few words?
I will now turn the call over to Maggie for a review of the phase <unk>.
Sure.
Sergio Traversa: Is it your first conference call with Relmada?
Thank you Sergio today, we issued a press release announcing our business and financial results for the three and six months ended June 30th two.
Sergio Traversa: You just joined and I'd be happy if you can say a few words.
22, which I will now review the second quarter ended June 30 of 2022 total research and development expense was approximately $39 million as compared to $17 $3 million for the comparable period of 2021. The increase was primarily related to an increase in costs.
Associated with the execution of a broader clinical program for El Pen 17.
Noncash R&D expense for the second quarter of 2022 amounted to $1 $2 million.
Total general and administrative expense for the second quarter ended June 32022 was approximately $14 $6 million as compared to $9 1 million for the comparable period of 2021, an increase of approximately $5 $5 million increase was primarily driven by an increase in stock.
Based compensation this noncash G&A charge totaled $11 $1 million in the most recently completed second quarter.
For the second quarter ended June 32022, the net loss was $39 $9 million or $1 33.
Cents per basic and diluted share compared to a net loss of $26 $6 million or $1 56.
Basic and diluted share in the comparable period of 2021.
Turning to the results for the six months ended June 32022, total research and development expense was approximately $65 9 million as compared to $31 4 million for the comparable period of 2021 again, the increase was primarily related to an increase in costs associated with the execution of our.
A broader clinical program for El Pen 17, noncash R&D expense for the first half of 2022 amounted to $2 $5 million.
For the six months ended June 32022, total general and administrative expense was approximately $27 9 million as compared to $17 $5 million for the comparable period of 2021. The increase was primarily driven by an increase in stock based compensation. This noncash G&A charge totaled 20.
One $7 million in the most recently completed six month period.
For the six months ended June 32022, the net loss was approximately $79 $7 million or 200, or $2 73 per basic and diluted share compared to a net loss of $48 $8 million or $2 90 per basic and diluted share.
In the comparable period of 2021.
John Hickson: Well, hi everyone.
As of June 32022, as Sergio said, we had cash and cash equivalents and short and short term investments of approximately $212 million compared to cash cash equivalents and short term investments of approximately $211 9 million at December 31, 2021.
John Hickson: Thank you, Sergio.
I will now ask the operator to please open the call for questions operator.
Thank you, ladies and gentlemen, if you would like to ask a question. Please seek known by pressing star one on your telephone keypad, if youre using a speakerphone. Please make sure. Your mute function is turned off to allow youll seen it to reach our equipment again press star one to ask the question you posed just for a moment to assemble the queue.
We take our first question from Andrew Tsai with Jefferies. Your line is open. Please go ahead.
Okay. Thank you and good afternoon, and thanks for taking my questions. Thanks for the update so.
John Hickson: It's a real pleasure to be with all of you and I just want to say that I'm thrilled and humbled and excited to be a part of this Relmada team.
John Hickson: As Sergio said, I've got a pretty broad background in commercialization. All 31 years with Eli Lilly, were in commercialization-related roles.
First one is that it sounds like reliance three of the monotherapy.
John Hickson: I was fortunate to spend eight years outside of the U.S., in Spain, South Korea, and Australia.
John Hickson: While in Australia, my team and I launched Zyprexa, the atypical antipsychotic, and then when I returned to the United States, I became the last global marketing director for Prozac as it was late in its product life cycle, and once that role ended, I was shifted over to be the brand launch leader for Cymbalta, Lilly's next antidepressant and pain drug.
John Hickson: After launching the drug and being with it for several, years post-launch, I shifted over to new product planning where I worked with discovery and development scientists and provided assessments of commercial viability of Lilly's portfolio and also was actively engaged in various business development opportunities.
John Hickson: Again, I'm just thrilled to have this opportunity.
He's out in maybe two months give or take I think you've said reliance won the first of two adjunct studies was tracking a few weeks behind airlines three is that still the case and if.
John Hickson: I know the depression space well.
John Hickson: Depression is something that, like perhaps many of you, has impacted members of my family and close friends. Having this opportunity to bring forward a new approach to treat depression, if the drug is approved, is just very exciting for me and one that I'm very passionate about.
John Hickson: I think the drug is truly an exciting new treatment option.
If so would you consider pocketing both datasets together or would you choose to press release, the two data sets at different times.
John Hickson: Again, thank you very much.
Good afternoon Andrew.
For the question, let me ask you for the second part no we are not planning to.
John Hickson: Let me turn this back over to Sergio so we can continue on with you all.
Really rely on the enterprise one together for a couple of reason one that did probably they're not close enough that we could pack all the data together and the second one that is most important is that we.
Sergio Traversa: Thank you.
Sergio Traversa: Thank you, John, and we are really very happy to have you on board, with us.
We want.
To be sure that everybody will have enough time to digest, there's going to be quite a bit of data topline. Your primary secondary endpoint as much as we can disclose.
And the two trial.
They have their own independent life, although down there they are similar but single agent monotherapy needs a different conversation compared to what is called the VB adjunctive treatment.
The therapeutic choice. So we will we will publish the topline data separately.
These couple of reasons.
Thermal timing.
Moving forward I mean, now we do have a pretty.
Sergio Traversa: Moving on to the current status of the Phase III program. As I said earlier, we continue to anticipate the completion of enrollment in Reliance III, the ongoing monotherapy single-agent registration of Phase III trials, with the last patient enrolled before the end of August, followed by the top-line data readout shortly after the completion of the four-week treatment.
Clear idea of what the timing is we expect the last patient to be enrolled.
Reliance <unk>.
We said before end of August probably is going to be.
Not too far away from from from today.
Calculate loss patient named four weeks 20 days.
So you go somewhere in September .
And then two to four weeks after that.
The topline results.
No.
You can do the math, it's going to be end of September maybe October .
Sergio Traversa: Let me provide an update on the ongoing Reliance I and Reliance II studies. As a reminder, Reliance I and Reliance II are designed to evaluate REL-1017 as an adjunctive treatment for MTD, and both include two arms, placebo and 25 mg of REL-1017. Both studies are studying the use of REL-1017 in addition to a standard antidepressant for, participants who have had inadequate response to at least one and up to three standard antidepressant therapies.
Sergio Traversa: The primary endpoint is the change in Madras, the scale that is used to evaluate the severity of the patient, and Madras score at day 28.
Sergio Traversa: Key secondary endpoints include the change in Madras score at day 7, and change in clinical global impression severity scale, CGI, and score at day 28.
The range that we are getting there.
Sergio Traversa: Day 28 was chosen as a primary endpoint in agreement with the FDA, with an understanding common that depression is a chronic disease and that success of different points on day 28 will support REL-1017 as a chronic treatment for depression.
And realise one.
That one is a little bit.
More difficult to time, so precisely, but you can assume that.
I would say six to eight weeks after maybe a little earlier than that we should be done with that same process same process.
Great. Thanks, So we don't know.
Yes, we will announce the last patient out for both trials.
Perfect.
Thanks.
And and that's very clear second question is can you remind us the last time the D. S. N. The left at the blinded safety data I think the last time was March did they happened to look again and if so.
Any updates on that front, I guess and just to be clear if the U.
So D. S. N V did see like I Dunno withdraw your Florida Association any of these across the phase threes in the open label portion. They would have alerted you just to be clear.
Yes, so to say the answer is yes. They would we would know they would have alerted us people that would have been any issue related with.
We drove symptoms.
Anything any safety signal.
It would be signaled.
They they meet regularly on a time base. So sometimes we don't even know it.
If they met the last time I remember was June .
And then and so they but they did.
They meet regularly and we haven't heard anything picks up.
Sergio Traversa: Both Reliance I and Reliance II are progressing as planned, and we continue to expect the availability, of top-line data in the second half of this year. The Reliance Development Program also includes Reliance OLS, the Long-Term Open Label Safety Study.
Sergio Traversa: It is enrolling both rollover participants, from all three peoples of studies, as well as de novo participants.
Sergio Traversa: Reliance OLS is ongoing and continues to enroll participants as planned. Data from this Long-Term Open Label Safety Study we now expect in the first half of 2023 will be part of the planned enrolling NDA filing package.
Continued as planned.
Sergio Traversa: Finally, while Maggie will review our financial in detail shortly, I would like to emphasize, how strong our financial position we are currently in. You can recall that we completed an oversubscribed follow-on offering for gross proceeds of $172 million in late December 2021. When the capital markets for biotech companies were far less challenging than they are today, this financing has provided us with the maximum financial and operational flexibility as we end the second quarter with cash, cash equivalents, and short-term investment of approximately $222 million.
Sergio Traversa: With that, I will now turn the call over to Maggie for a review of the financing.
The recommendation so.
Maggie Chinuda: Maggie, the stage is yours.
It's always I mean, this business biotechnology developing drugs.
Maggie Chinuda: Thank you, Sergio.
Maggie Chinuda: Today we issued a press release announcing our business and financial results, for the three and six months ended June 30, 2022, which I will now review. For the second quarter ended June 30, 2022, total research and development expense was approximately $30.9 million as compared to $17.3 million for the comparable period of 2021. The increase was primarily related to an increase in costs associated with the execution of a broader clinical program for REL 1017.
Maggie Chinuda: Non-cash R&D expense for the second quarter of 2022 amounted to $1.2 million.
Maggie Chinuda: Total general and administrative expense for the second quarter ended June 30, 2022, was approximately $14.6 million as compared to $9.1 million for the comparable period of 2021, an increase of approximately $5.5 million. The increase was primarily driven by an increase in stock-based compensation. This non-cash G&A charge totaled $11.1 million in the most recently completed second quarter.
Maggie Chinuda: The second quarter ended June 30, 2022. The net loss was $39.9 million or $1.33 per basic and diluted share compared to a net loss of $26.6 million, or $1.66 per basic and diluted share in the comparable period of 2021.
You can never make really.
Maggie Chinuda: Turning to the results for the six months ended June 30, 2022. Total research and development expense was approximately $55.9 million as compared to $31.4 million for the comparable period of 2021. Again, the increase was primarily related to an increase in costs associated with the execution, of a broader clinical program for REL 1017.
Maggie Chinuda: Non-cash R&D expense for the first half of 2022 amounted to $2.5 million.
Assumptions.
Maggie Chinuda: For the six months ended June 30, 2022, total general and administrative expense was approximately $27.9 million as compared to $17.5 million for the comparable period of 2021. The increase was primarily driven by an increase in stock-based compensation. This non-cash G&A charge totaled $21.7 million in the most recently completed six-month period.
Maggie Chinuda: For the six months ended June 30, 2022, the net loss was approximately $79.7 million, or $2.73 per basic and diluted share compared to a net loss of $48.8 million or $2.90 per basic and diluted share in the comparable period of 2021. As of June 30, 2022, as Sergio said, we had cash and cash equivalents and short-term investments, of approximately $212 million compared to cash, cash equivalents, and short-term investments of approximately $211.9 million at December 31, 2021.
Is it.
Yeah with zero risk.
Operator: I will now ask the operator to please
We are at the very end of the massive program. We have all the phase one phase two data we need them.
Very large.
Abuse potential with like 100 patient treated with mainly the different doses, we have not seen one simple issue related to safety.
I would say that the.
We feel very very comfortable that safety is now going to be but is it really stool. It would all block safety abuse. All these we have so many formation. They all very consistent suggest that there is no safety for abuse issues.
Fantastic Alright, thanks for taking my questions best of luck.
Scott. Thank you Andrea I'm sure we'll speak soon.
Data.
Of course, we.
Takeaway.
Thank you we think over next question from Yadkin, Tunisia with Guggenheim. Your line is open.
Operator: open the call for questions.
Hey, guys.
Operator: Operator?
Thank you for taking my question I have just one question and this is on the tolerance side. So I think what we have seen from U S. Seven day data can you just put in contact Sergio with this type of mechanism NMDA targeting Michael.
Operator: Thank you.
Operator: Ladies and gentlemen, if you would like to ask a question, please signal by pressing star 1 on your telephone keypad.
Operator: If you are using a speakerphone, please make sure your mute function is turned off to allow, your signal to reach our equipment.
Should we expect any sort of range of development.
Just trying to get a sense that how much more.
Benefit we should expect.
Out to 2008, there is relative to seven days that you have produce anything that you can point out to whether it's ketamine or an M. D channel blocker that produce things.
Yeah. Thank you yeah. Thanks for the question.
Yes, so like.
They are basically historically.
Let me start from life scientifically.
And.
From the science.
There is no indication.
NMDA channel blockers, they generate any color on this or anything like that clinically. There is few example case I mean I would not.
We use it is it like.
Very good comparison as ketamine M S.
That's great I mean, they are given intermittently for practical reason one is amazing.
You can't go to the clinic to take a drug every day and not to drive for 24 hours a day.
The limitation that make the intermittent.
Treatment.
German the one the only one that is really pieces. Both so that's in terms of like the developing tolerance may not be the best comparison.
Dextromethorphan that one of our peers competitor is trying to get approved.
It does didn't show any.
Any sign of any tolerance the efficacy continue to.
To be there.
Improving up to six weeks, if I remember correctly you had if you will.
Not that much better than I do and the program well so dextromethorphan didn't show any doesn't show any any tolerance.
Momentum for whatever.
Very difficult to evaluate the efficacy of xyrem or drug but at least.
It Didnt show really any any parties will also the that'll be it.
Correct.
Maybe.
One of the ones that we are looking into is.
Dextromethorphan combined with Canada, and believe knowledge parcel choke up and it is a chronic treatment for Super Bowl berth syndrome and also <unk>.
Treatment doesn't show any loss of efficacy over time.
All in all we don't expect that Brad Samson in season show anything different clear.
Clearly if we take the phase II data as a proxy and you do.
We should see a very sharp.
Fast effect cut date for a five seven.
That range and.
It cannot continue to increase efficacy.
Beyond much beyond that otherwise the mother would go below zero [laughter] desktop policy bought so but we do expect.
Continuous improvement up to day 28.
Definitely not the loss of that yeah.
Got it one more if I may.
I think in the past you have talked about on a blinded basis, what the dropout rate.
<unk> is for the study could you give us an update now that you are very close to the completion, what it is or how it is trending are there any differences that you're seeing between like junk table versus monotherapy.
And then also if you can comment on the.
Percentage that might be rolling over to the OLED. Thank you so much.
Yeah. Thank you yeah, the oldest person to ask questions.
It's always dangerous to draw any conclusion problems from blinded data.
That better than anybody else, but so we look at the blinded data, mostly almost exclusively for <unk>.
For safety reasons, and we have seen I think as I mentioned few minutes ago.
In terms of efficacy.
Until you know what the placebo effect. These opinion number does not really <unk> tell you. The truth. So what we can tell you that on a blinded basis with all of the caution we're talking about blinded.
The day look somewhat similar.
Very similar to the phase II.
Phase two goes through day 14.
So it goes to the 28, so they're not directly comparable but whatever we have seen it looked very very similar to phase two.
And so that's all we can say look we took a blinded data we get them.
Three months later and so it's not.
These are not the updated the information so that they can change, but the message is that they look very very similar to the phase II.
Now of course, we know what the phase III placebo did because it has been published and we have the unblinded data, we don't know what placebo.
Is doing in the phase III. So that's the big question, but in terms of like overall color.
Very overlapping the phase two data both monotherapy and <unk>.
<unk> jumped in and they look pretty similar.
I Hope I gave you.
Yes, I think that's the best answer I can give you.
Thank you Sacha.
Thank you.
Operator: Again, press star 1 to ask a question.
Take our next question from Andrea <unk> with Goldman Sachs. Your line is open.
Operator: We pause just for a moment to assemble the queue.
Good afternoon, and thanks for taking my question My first one here is just.
But all of that and more on what fast track designation can't stand here as it relates to the monotherapy indication and just remind us maybe the nature of it.
Our conversations with the agency regarding the eastern for Lionsgate to support an expanded label.
Operator: We take our first question from Andrew Tsai with Jeffrey.
Yeah, good afternoon, Andrea and.
Thanks again for the towards the question is actually a very interesting question. This one.
Andrew Tsai: Your line is open.
I don't want to say that came as a surprise.
And because we filed the application because we hope and we expect to.
Andrew Tsai: Please go ahead.
We do get the fast track designation.
But it's very interesting.
Is that there are 28 drugs approved.
In the United States for Depression.
And the fact that <unk> has been awarded fast track designation for indication, where you have a lot of choices that.
Probably.
They are not they are not the idea.
Tells us that the FCA athletes at the very minimum believes that there is.
It need for something new as a single agent treatment of.
But part of depression, and Thats something we are very pleased to see that.
Maybe that they think or whatever it seemed that residents 17 can bring something new and good for our poor patient.
What does that mean.
That had been the only nine I believe if I counted correctly.
Like designation the award.
Awarded this year, so it's not something the FDA gives away.
We easily and that's in some of our advantages is giving us more access to the FDA.
We tend to view it.
And answer quicker and you have some more light.
Formal.
Exchange all the formation in communication with the FDA. So it makes it makes the process I don't want to call it easier, but thats any faster.
And maybe there's more communication with the FDA that he is always good.
Hope I answered your question.
Got it and maybe a follow on there just has the agency I guess, maybe any conversations you've been having with them.
You know maybe suggested that reliance.
Can be used to address them.
I mean, you can it can be used as a pivotal study.
Just a quick expansion into that the monotherapy setting.
Well, yes, we do.
We think it would be a fair assumption that there will.
He will be happy with that trial.
That would support the approval of <unk>.
<unk> as a monotherapy single agent treatment of depression.
And clearly it's yes, we will present to the FDA package.
The.
Reliance one in Atlanta, two they will have a lot of information.
Well enough to make a decision.
What would be the best use for growth in 17.
And a single agent is.
It's important to severity right. The fact that we received this.
Designation request right now.
We see it is a very positive.
The positive signal to get that indication.
Perfect and then maybe if I can ask one question John .
Yeah.
I would be curious to hear your thoughts on the evolving compression landscape just in the context of the new jobs that are potentially going to be a trend given the course of this year curious how you think <unk> 17 can pay for these drugs and your expectations for where it might be if a piece in the treatment paradigm.
Yes, Thanks, Andrea that that's a good question because they're there.
To be a lot of dynamics in the depression market space and.
The way I see things in a lot of my viewpoint is based upon interactions with psychiatrists and Kols in regards to this.
Everybody is looking for new approaches to treat depression, because everyone in the field understand that only so much remission is really truly achievable for so many patients and patients tend to not.
That's the best term, but they do tend to grind through a lot of different treatments to try to get to the one that offers the benefits. So you know.
I think with the other agents that are in a similar phase as ours is and you know.
It's good to bring new options to the marketplace, because it just creates new and better hopefully better opportunities for clinicians and patients to get to get to well truly realizing that that still is a difficult goal and when I look into the future with.
Further developments out there such as the psychedelics that brings another interesting dynamic that I think will be challenging from a payer reimbursement standpoint without a doubt.
But when I look back at where rail 10, 17 is I I just.
Given particularly the phase II data that I've had a chance to dig in on that that data suggests that this drug has the opportunity to truly provide.
Provide fast and.
Depressive relief to patients, who and they've been looking for that since the probably the second year of the ssris being on the market when everyone realized that it really did take a month or more to get any type of a benefit. So I think that rail 10, 17 is going to be able to fulfill that again based upon what ive seen in the phase II data.
And with a strong effect size that could be a game changing out there versus other antidepressants that that's a strong signal and on top of it it appears to be safe and the fact that it can be administered orally just as kind of that that grail that people have been looking for two two.
Be able to really get patients to well so I think the prospects for our drug are very positive based upon that as long as the phase III data comes close to what we've seen in phase two I think we've got a wonderful opportunity to really get patients into a much better situation I hope I didn't rambled too long there and I answered your question sufficiently.
Andrea.
Yeah, great. Thank you so much John .
Thank you.
Yeah.
Thank you we take our next question from Sean Lee, We truly Securities. Your line is open.
Hey, Thanks for taking my questions.
Are you also using.
A loading dose in phase III as you did in phase two and are there other antidepressants and also use loading doses and we're the largest loading doses also used in Europe .
Human abuse potential studies.
Hey, John Good afternoon, and thank you as well for the question, Yes, we do use the loading those than we used in phase two and all the three phase III trial patients. They treat tablets 75 meters on the first day of treatment and the reason.
Andrew Tsai: Thank you, and good afternoon.
Andrew Tsai: Thanks for taking my questions.
Andrew Tsai: Thanks for the updates.
Andrew Tsai: So, first one is that it sounds like Reliance III, the monotherapy, reached out in maybe two months, give or take.
Andrew Tsai: I think you said Reliance I, the first of two adjunct studies, was tracking a few weeks behind Reliance III.
Andrew Tsai: Is that still the case?
We're doing that as it is to shorten the steady state that is.
The longer half life. So if you don't use it loading those it takes four to five days with a loading dose.
It is.
Short term to two to three days that is very important because one of the feature residence 17 rapid acting so the more you get to efficacy in blood levels of plasma levels, then the better.
Okay.
Andrew Tsai: And, you know, if so, would you consider bucketing both data sets together, or would you choose to press release the two data sets at different times?
And your question.
Ed.
Oh no no no. Thanks for the collaboration so Derrick FDA wasn't worried at all that.
Having that.
In terms of dose on the first day might possibly have such an effect that that might lead to an unwinding of randomization.
No no.
No. We haven't we haven't seen nothing in phase two and we have seen nothing in phase II as well, it's a very benign drug and.
The loading those increase too towards the highest those was actually 100 milligram work for tablets are well solution can you speak to what was a correspondent for tablets and there was no sign of anything that could signal an like that you have taken the drug is not that the placebo.
To answer the other part of your question are there other antidepressants that.
Use loading those I don't have anything on the top of my mind I do know that there is few of them of which one John knows very very well there were quite penetration goes if you take the full dose the first day.
You get some you know some some side effects, so you'll need to and to start with a lower dose.
Titrate to the effective dose.
I don't have anybody anything in my mind of audio into question the loading dose, but a tolerability, we see theres a big Atlanta, if you can give.
Three times, the therapeutic dose too fast and we wont do the steady state into fashion.
At the onset of the effect.
I don't think other drugs don't do it.
They don't do it just because we don't have enough safety and Tolerability that can do that there was.
There's no reason not to do it.
Alright, thank you so much.
Thank you John .
Sergio Traversa: Good afternoon, Andrea.
Yes.
Once again, ladies and gentlemen, please press star one to ask a question star one to ask a question.
Our next question from Jay Olson with <unk>.
With Oppenheimer. Your line is open.
Oh, Hey, thanks for taking the question.
Maybe for John I'm, just curious about the due diligence he did and congrats to him.
On joining real model.
If you could please comment on the feedback that you got from from Kols that you spoke to and what are some of the lessons learned from your work yet.
Lilly and elsewhere.
You hope to leverage at <unk> and then what are the greatest challenges you expect to face in the launch of Royal 10, 17, and how do you plan to overcome those obstacles and then I had one follow up if I could.
Sergio Traversa: Thanks for the question.
Jay Thank you very much for the questions.
Sergio Traversa: Let me ask you for the second part.
So the due diligence do due diligence that I did was was extensive and and really the way I did it was since I've been in the space a long time I've been watching real modest data from afar anyway, but then when this opportunity arose for me besides being very excited I spoke to a lot of my psychiatry fresh.
Sergio Traversa: No, we, are not planning to release Reliance 3 and Reliance 1 together for a couple of reasons.
<unk> and I, just said Hey, what are your thoughts about this drug based upon what you know at this point in time, and then I have to say that every single one of them said that this drug looks extremely exciting to them. So I'm, just quoting them and their viewpoint, given what they've seen so far.
Sergio Traversa: One, that probably they are not close enough that we could pack all the data together.
Sergio Traversa: And the second one, which is the most important, is that we want to be sure that everybody, will have enough time to digest.
Sergio Traversa: It's going to be quite a bit of data, top line, primary, secondary, and point as much as we can disclose.
And then when I probe a little bit further as to why that was they say well. It does appear to work rapidly it does appear to be safe and while it.
Sergio Traversa: And the two trials, they have their own independent life, although they are similar.
Sergio Traversa: But single agent monotherapy needs a different conversation compared to what is called the adjunctive treatment therapeutic choice.
Sergio Traversa: So we will publish the top line data separately for these couple of reasons.
It carries the S. Methadone name they said that strong data and safety data will will certainly win out over any type of a reluctance or concern that some clinicians may have because.
The field is still looking for something that really is going to be efficacious and safe and easy from a patient administration standpoint. So.
So that was very consistent.
In terms of the due diligence, which made the decision easy for me and Ive been doing other projects in the depression space. So it it just.
It just cemented the decision that I thought I was thrilled and an easy yes for me to join the team in terms of lessons that I learned from Lilly gosh that there there are a lot.
I would I would draw first on my experience with Prozac, where the company obviously brought forward a revolutionary iconic antidepressant, but it's.
As more and more competitors came in and I have to say I think the organization, particularly my marketing organization, we started to move away from some of the basics of staying with our own positioning with prozac and started to kind of follow what the competitors were doing and what we learned late in the lifecycle was to go back to our knitting and remain with us.
Positioning concept that got prozac to where it was we employ that.
Very same principle with cymbalta as we prepared to launch at realizing we were gonna be antidepressant number 11, 12 or 13 into the U S marketplace and so we needed to have a unique vulnerable and differentiating positioning concept around.
Depression, hurting hurting both emotionally and physically so that's something that I really want to employ with with role models to come up with a positioning concept that will differentiate it from all of the other potential new entrants coming in around the same time period.
And then the challenges to face going back to the.
The S. Methadone, that's something that we know will be something we're going to have to work through and scheduling, but when I look at other analogues such as F. The dialects.
Epilepsy drug.
A derivative of.
Marijuana or it's a cannabinoid it it came out as a as a scheduled five and after about a year or two on the market. It became D schedule and I think that's that that may be a very good analog for us to dig into and understand and to follow I Hope I answered your questions Jay Thank you.
Yeah that was super helpful. Thank you so much and congrats again for joining roam on it if I could maybe squeeze in one follow up question.
For the team since most Registrational MTBE studies have more than 28 days of randomized treatment can you just comment maybe sergio on what sort of guidance you would give to physicians for treatment durations beyond 2018.
17.
Yeah.
Yeah.
Yeah.
Hum.
Turkey.
Yes, it does.
To see the phase II data first and.
But right we discuss it internally the.
There is really no specific in general.
Antidepressant and John can help me.
Kind of help me out on that.
Yes.
Beyond the study period.
A lot of guidance you can give.
Also because every patient is the patient.
That is different from the other one in terms of safety that the guidance that we can create a game. We have the long term safety study ongoing we have quite a bit of patients already completed six months and we have quite a bit the patients have completed 12 months.
And really there is no no.
That's fine.
<unk>.
Long term.
Safety or tolerability issues. So in terms of safety and Tolerability, we will be able to tell the doctor what we have that data at least until 12 months and we feel very we feel very comfortable but nothing surprising will ensure he's done with efficacy.
When you have that kind of safety and tolerability depends on the patients the patients that take the treatment chronically ill patients that when they are out from the depression that because they want the they want to solve.
Eventually.
We take it if they get depressed again, so it's very difficult to answer this question.
And in the very simple way it would be after the doctor what are what they will do.
The breakthrough in great. Thank you very much.
From the conversation with the FDA. They 28, it mean chronic treatment so that will not stop at day 28. So when you had the labor for chronic treatment technically you can do it as long as we would like to as long as that the patients require treatment.
Okay. Thank you that's helpful.
Yeah.
And we can take our next question.
From what we hear with Mizuho Your line is open.
Hey, guys. Thanks for taking my question.
Just wondering if you guys have already.
Or plan to schedule, a pre NDA meeting with the FDA.
And just curious to know if.
There is anything that needs to be.
<unk> aligned in terms of the.
The NDA package, either on the preclinical level or the CMC level. Thanks.
Thank you Lee and thanks for the question, Yes, we will we will schedule a three.
Pre NDA meeting, we would like to have at least one phase III data topline results before we approach the F D. A.
Sergio Traversa: In terms of timing, moving forward, I mean, now we do have a pretty clear idea what the timing is. We expect the last patient, to be enrolled in Reliance 3, we said, before end of August, probably is going to be not too far away from today. So you calculate last patient in four weeks, 20 days treatment. So you go somewhere in September, and then two to four weeks after that, we will have, the top line results.
Sergio Traversa: So you can do the math, but it's going to be end of September, maybe very early October, this range.
Believe that will take us.
A lot more seriously.
Good phase II data, but we will we will schedule a pre NDA meeting.
Sergio Traversa: But we are getting there.
We will provide the old package that will go from preclinical CMC T D to the clinic.
Really.
Sergio Traversa: And Reliance 1, that one is a little bit more difficult to time so precisely, but you can assume that, you know, I would say six to eight weeks after, maybe a little earlier than that, we should be done with that.
Phase III clinical pause would be the one that.
Will be the topic of discussion from communication with the FDA that go back two months ago. We do believe that the preclinical package was done. So there is no more requests for any.
Sergio Traversa: Same process, same process.
Andrew Tsai: Great.
Any.
Non human studies are in vitro studies.
Andrew Tsai: Thanks.
And so in CMC, where magazines and they called magazines actually the lead on the on the manufacturing.
Sergio Traversa: Yeah, we will announce the last patient out for both trials.
We're well advanced we have well enough product to not only to complete the phase III, but also to go beyond that and I.
Sergio Traversa: Perfect.
I believe magnet correct me, if I'm wrong, but we are making the commercial natures batches. So CMC will probably be filed with the FDA. We have a rolling NDA, so I wouldn't be filed.
Andrew Tsai: Thanks.
Andrew Tsai: Yep.
Before we filed the clinical path. That's the magnitude you have anything to add no. That's that's a great summary, Sergio Thank you and thank you for the question.
Andrew Tsai: And that's very clear.
Andrew Tsai: And second question is, can you remind us, the last time the DSMB looked at the blinded safety data, I think the last time was March, did they happen to look again?
Can I sneak in another question if I may can I get just wondering or you are.
The amount of cash during the quarter with could.
Could you remind us what that would take you through.
Sure sure. So we ended the quarter with $212 million.
Andrew Tsai: And if so, any updates on that front, I guess?
And based on our internal estimates that'll take us out to mid 2024.
Andrew Tsai: And just to be clear, if the DSMB did see like, I don't know, withdrawal, euphoria, dissociation, any of these across the phase threes and the open label portion, they would have alerted you, just to be clear?
Sergio Traversa: Yes, the straight answer is yes.
Sergio Traversa: We would know they would have alerted us if there would have, been any issue related with withdrawal symptoms or, you know, anything, any safety signal would be signaled.
Okay. Thanks.
Sure. Thank you for the question.
Thank you. It appears there are no further question at this time I'd like to turn the call back to Sergio point any additional closing remarks.
Sergio Traversa: They meet regularly on a time base.
Sergio Traversa: So sometimes we don't even know if they met.
Sergio Traversa: The last time I remember was June.
Sergio Traversa: And so they, you know, they meet regularly and we haven't heard anything except continued as planned as a recommendation.
Sergio Traversa: We have all phase one, phase two data.
Sergio Traversa: So it's always, I mean, in business and biotechnology and developing drugs, you can never make really assumptions, with zero risk, but we are at the very end of the massive program.
Sergio Traversa: We need this very large abuse potential with like a hundred patients treated with, you know, many different doses.
Sergio Traversa: We have not seen one single issue related with safety.
Sergio Traversa: So I would say that we feel very, very comfortable.
Sure well, thanks, everyone for the time and interest in that.
Sergio Traversa: That safety is not going to be like a real issue or a roadblock.
Sergio Traversa: Safety, abuse, all these, you know, we have so many information and they all very consistent suggest that there is no safety or abuse issues.
Andrew Tsai: Fantastic.
Andrew Tsai: All right.
Andrew Tsai: Thanks for taking my questions.
Program and the <unk>.
Sergio Traversa: With data.
Andrew Tsai: Best of luck.
In closing I.
Andrew Tsai: Fingers crossed.
Sergio Traversa: Thank you, Andrea.
I am and remain very grateful to them for them out of the team for their continued hard work and dedication to executing our mission and.
Sergio Traversa: I'm sure we'll speak soon.
Sergio Traversa: Of course.
Operator: Thank you.
Operator: We take our next question from Tunisia, your line is open.
Tunisia: Hey, guys, thank you for taking my question.
I would like also to extend my sincere thanks to the participants and clinical partners involved in the World 10, 17 clinical trials for the effort and in advancing this important product candidates through the clinic as expeditiously as possible and it was a very it is a very long.
Tunisia: I have just one question and this is on the tolerant side.
Tunisia: So I think what we have seen from you is seven day data.
Tunisia: Can you just put in contact Sergio with this type of a mechanism and MDA targeting mechanism?
Tunisia: Should we expect any sort of tolerance development?
Tunisia: Just trying to get a sense that how much more benefit we should expect out to 28 days relative to seven days that you have produced.
Tunisia: Anything that you can point out to whether it's ketamine or other NMDA channel blocker that have produced.
Tunisia: Thanks.
Sergio Traversa: Look, we look at the blinded data.
Sergio Traversa: Yeah, thank you.
Sergio Traversa: We get them two or three months later.
Sergio Traversa: Yeah, thanks for the question.
Sergio Traversa: And so it's not.
Sergio Traversa: Yes.
Sergio Traversa: These are not very updated information, so they can still change.
Sergio Traversa: So, like, there are data historically, let me start from, like, scientifically and, like, from the science.
Sergio Traversa: But the message is that they look very, very similar to the Phase II.
Sergio Traversa: There is no indication that NMDA channel blockers, they generate any tolerance or anything like that.
Sergio Traversa: Now, of course, we know what the Phase II placebo did because it's been published and we have the unblinded data.
Sergio Traversa: Clinically, there is, for example, I mean, I would not, you know, I would not use it as a, like, a very good comparison.
Sergio Traversa: We don't know what placebo is doing in the Phase III.
Sergio Traversa: As long as ketamine and esketamine, they are given intermittently for practical reason.
Andrea Tan: Maybe a follow on there.
Sergio Traversa: So that's the big question mark.
Sergio Traversa: One is nasal and you can go to the clinic to take a drug every day and not to drive for 24 hours.
Andrea Tan: Just has the agency, I guess, maybe in these conversations, you've been having with them, you know, maybe suggested that Reliance 3 can be used as, I mean, I guess maybe it can be used as a pivotal study to support expansion into the, monotherapy setting.
Sergio Traversa: But in terms of like overall color, they are very overlapping, the Phase II data, both monotherapy and adjunctive. And they look very similar.
Sergio Traversa: So it's that limitation that made the intermittent treatment regimen the one, the only one that is really feasible.
Andrea Tan: Well, yes, we do.
Sergio Traversa: I hope I give you an answer.
Sergio Traversa: So that's in terms of, like, the developing tolerance may not be the best comparison.
Sergio Traversa: I mean, we, I think it would be a fair assumption that Reliance 3 will be a pivotal trial that would support the approval of REL 1017 as a monotherapy single agent treatment of depression.
Sergio Traversa: Yeah, thank you.
Sergio Traversa: Dextromethorphan that one of our peers competitor is trying to get approved, it does, didn't show any, any sign of any tolerance.
Sergio Traversa: And clearly it's, yeah, we will present to the FDA a full package.
Sergio Traversa: That is the best answer I can give you.
Large program and.
Sergio Traversa: The efficacy continued to continue to be there and improving up to six weeks, if I remember correctly.
Sergio Traversa: And with Reliance 1 and Reliance 2, they will have a lot of information well enough to make a decision on what would be the best use for REL 1017.
Sergio Traversa: Thank you, Sergio.
Sergio Traversa: Yeah, you know that much better than I do.
Sergio Traversa: And, you know, single agent is, it's important.
Sergio Traversa: Thank you.
Sergio Traversa: And you know the problem well.
Sergio Traversa: The fact that we received this designation, of a fast drug, you know, that we see it as a very positive, very positive signal to get that indication.
Operator: We take our next question from Andrea Tan with Goldman Sachs.
The question I had.
Sergio Traversa: So dextromethorphan didn't show any, doesn't show any, any tolerance, mementin or whatever.
Andrea Tan: Perfect.
Operator: Your line is open.
Sergio Traversa: But it's very difficult to evaluate the efficacy on Alzheimer's drug.
Andrea Tan: And then maybe if I can ask one question to John, just, I would be curious to hear your thoughts on the evolving depression landscape, just in the context of the new drugs that are potentially going to be approved over the course of this year.
Andrea Tan: Good afternoon.
John Lee: Your line is open.
Sergio Traversa: But at least didn't show really any, any particular loss of the effect.
You asked me the same question like when we have two years ago.
Andrea Tan: Curious how you think REL 1017 compares to these drugs and your expectations for where it might be able to be used in the treatment paradigm.
Andrea Tan: Thanks for taking my questions.
John Lee: Hey, thanks for taking our questions.
Sergio Traversa: Maybe one of the, the one that we have looked into is dextromethorphan combined with kinadine.
John Hickson: Thanks, Andrea.
Andrea Tan: My first one here is just can you speak a little bit more on what FastTrack designation gives you here as it relates to the monotherapy indication?
John Lee: Are you also using a loading dose in phase three, as you did in phase two?
Sergio Traversa: I believe now it's part of Kotsuka and it's a chronic treatment for pseudobulbar syndrome and also chronic treatment doesn't show any loss of efficacy over time.
John Hickson: That's a good question because there continue to be a lot of dynamics in, the depression market space.
Andrea Tan: And just remind us maybe the nature or extent of your conversations with the agency regarding the use of Reliance III to support an expanded label.
John Lee: And are there other antidepressants that also use loading doses?
Sergio Traversa: So, all in all, we don't expect that.
John Hickson: And, you know, the way I see things and a lot of my viewpoint is based upon interactions with psychiatrists and KOLs in regards to this.
Andrea Tan: Good afternoon, Andrea, and thanks again for the question.
John Lee: Are loading doses also used in human abuse potential studies?
Sergio Traversa: Andrea Tan, Uy Ear, Basma Ibrahim, Andrew Cutler, Relmada, Sergio Traversa, Timothy McCarthy, Andrew Cutler, Relmada, Sergio Traversa, Timothy McCarthy, Andrew Cutler, Relmada, Sergio Traversa, And I think in the past you have talked about on a blinded basis what the dropout rate is.
John Hickson: Everybody's looking for new approaches to treat depression because everyone in the field understands that only so much remission is really truly achievable for so many patients.
What do you need it most.
Sergio Traversa: It's actually a very interesting, question.
Sergio Traversa: Hey, John.
Sergio Traversa: Could you give us an update now that you are very close to the completion, what it is or how it is trending?
John Hickson: And patients tend to – it's not really the best term, but they do tend to grind through a lot of different, treatments to try to get to the one that offers the benefits.
Sergio Traversa: This one came, I don't want to say that it came as a surprise, because we filed the application because we hope and we expect to get the fast track designation.
Sergio Traversa: Good afternoon.
Jay Olsen: If I could maybe squeeze in one follow-up question for the team.
Sergio Traversa: Are there any differences that you're seeing between adjunctive versus monotherapy?
John Hickson: So, you know, I think with the other agents that are in a similar phase as ours is in, you know, it's good to bring new options to the marketplace because it just creates new and better – hopefully better opportunities for clinicians and patients to get to well, truly, realizing that that still is a difficult goal.
Yeah, Ken we actually do a program of this size and this complexity right now.
Sergio Traversa: What is very interesting is that there are 28 drugs approved in the United States for depression.
Sergio Traversa: And thank you as well for the question.
Jay Olsen: Since most registrational MDV studies have more than 28 days of randomized treatment, can you just comment, maybe, Sergio, on what sort of guidance you would give to physicians for treatment durations beyond 28 days of Relmada and 17 days of MDV, and how did you understand the period of 28 days?
Sergio Traversa: And then also, if you can comment on the percentage that might be rolling over to the OLE.
John Hickson: And when I look into the future with, you know, further developments out there such as the psychedelics, that brings another interesting dynamic that I think will be challenging from a payer reimbursement standpoint, without a doubt.
Sergio Traversa: And the fact that REL 1017 has been awarded fast track designation for indication where, you have a lot of choices that probably they are not, they are not idea.
Sergio Traversa: Yes, we do use the, loading dose in phase two.
Jay Olsen: How long should a patient be on therapy?
Sergio Traversa: Thank you so much.
John Hickson: But when I look back at where REL 1017 is, I just – given particularly the phase two data that I've had a chance to dig in on, that data suggests that this drug has the opportunity to truly provide fast antidepressant relief to patients who – and they've been looking for that since the – probably the second year of the SSRIs being on the market when everyone realized that it really did take a month or more to get any type of a benefit.
Sergio Traversa: It tells us that the FDA at the very minimum believes that there is a need for something new as a single agent treatment of depression.
Sergio Traversa: And all the three phase three trial patients, they take three tablets, 75 milligrams the first day of treatment.
Sergio Traversa: Yeah, we had to see the phase 3 data first, but we discussed it internally.
Sergio Traversa: Thank you.
John Hickson: So, I think that REL 1017 is going to be able to fulfill that, again, based upon what I've, seen in the phase two data.
Sergio Traversa: And we are very pleased to see that.
Sergio Traversa: And the reason we're doing that is it is, to shorten the steady state that is a long half-life.
Sergio Traversa: There is really no specific, in general, for antidepressants, and John can help me out, on that.
Sergio Traversa: It's always dangerous to draw any conclusion from blinded data.
John Hickson: And with a strong effect size, it could be game changing out there versus other antidepressants.
Sergio Traversa: And, you know, maybe that they think or whatever thing that REL 1017 can bring something new and good for patients.
Sergio Traversa: So if you don't use the loading dose, it takes four to five days.
Sergio Traversa: Beyond the study period, you don't have a lot of guidance you can give, also because, every patient is a patient that is different from the other one.
Sergio Traversa: And you know that better than anybody else.
John Hickson: That's a strong signal.
Sergio Traversa: What does that mean?
Sergio Traversa: With the loading dose, it is shortened to two to three days. That is very important because one of the features of REL1017 is the rapid acting.
Sergio Traversa: In terms of safety, that's the guidance that we can clearly give.
Sergio Traversa: So we look at the blinded data mostly, almost exclusively for safety reasons.
John Hickson: And on top of it, it appears to be safe.
Jay Olsen: That's helpful.
Sergio Traversa: There have been only nine, I believe, if I counted correctly, fast track designation awarded this year. So it's not something the FDA gives away very easily.
Sergio Traversa: So the more you get to efficacy and blood levels, plasma levels, the better.
Thank you Rudy and so we actually did it we are almost there and those.
Sergio Traversa: We have the long-term safety study ongoing. We have quite a bit of patients that already completed six months, and we have quite a, patient that completed 12 months, and really, there is no sign of any long-term safety or tolerability issue. So, in terms of safety and tolerability, we will be able to tell the doctor that we have, that data at least until 12 months, and we feel very comfortable that nothing surprising will show up.
Sergio Traversa: And we have seen nothing, as I mentioned a few minutes ago.
John Hickson: And the fact that it can be administered orally just is kind of that grail that people have been looking for to be able to really get patients to well.
Operator: We can take our next question from Uy Ear with Mizuho.
Sergio Traversa: But some of the advantages, you have more access to the FDA.
Sergio Traversa: Your question, go ahead.
Sergio Traversa: In terms of efficacy, when you have that kind of safety and tolerability, it depends on, the patient.
Sergio Traversa: In terms of efficacy, until you know what the placebo effect is, any number does not really tell you the truth.
John Hickson: So, I think the prospects for our drug are very positive based upon that. As long as the phase three data comes close to what we've seen in phase two, I think we've got a wonderful opportunity to really get patients into a much better situation.
Operator: Your line is open.
Sergio Traversa: They tend to give you an answer quicker.
John Lee: Oh, no, no, no.
Sergio Traversa: There are patients that take the treatment chronically.
Sergio Traversa: So what we can tell you is that on a blinded basis, with all the caution talking about blinded, they look somewhat similar or very similar to the Phase II.
John Hickson: I hope I didn't ramble too long there and I answered your question sufficiently, Andrea.
Uy Ear: Hey, guys.
Sergio Traversa: And you have some more like informal exchange of information and communication with the FDA.
John Lee: Thanks for the clarification.
Sergio Traversa: There are patients that, when they are out from the depression episode, they want to, stop, and eventually, we take it if they get depressed again.
Sergio Traversa: Phase II goes to day 14.
Andrea Tan: Yes, great.
Uy Ear: Thanks for taking my question.
Sergio Traversa: So it makes the process, I don't want to call it easier, but that's something faster.
Sergio Traversa: So the FDA wasn't worried at all that having that three times a dose on the first day might possibly have such an effect that that might lead to an unblinding of the randomization?
Sergio Traversa: So, it's very difficult to answer this question, in a very simple way.
Sergio Traversa: Phase III goes to day 28.
Andrea Tan: Thank you so much, Sean.
Uy Ear: Just wondering if you guys have already sort of or plan to schedule a pre-NDA meeting with the FDA?
Thanks to the team and the patients and the clinicians and help out on this stuff. Thanks, a lot and with that I believe.
Sergio Traversa: And, you know, there is more communication with the FDA.
Sergio Traversa: No, no, we have seen nothing in phase two, and we have seen nothing in phase three as well.
Sergio Traversa: And that's thanks, to the team and the patients and the clinicians that helped out on this.
Sergio Traversa: It will be up to the doctor what, you know, what they will do.
Sergio Traversa: So they're not directly compared, but whatever we have seen, it looks very, very similar to Phase II.
Andrea Tan: Thank, you.
Uy Ear: And just curious to know if there's anything that needs to be aligned in terms of the NDA package, either on the preclinical level or the CMC level?
Sergio Traversa: That is always good.
Sergio Traversa: It's a very benign drug.
Sergio Traversa: So thanks a lot.
Sergio Traversa: The day 28, from the conversation with the FDA, day 28, it means chronic treatment.
Sergio Traversa: And so that's all we can share.
Andrea Tan: Thank you.
Uy Ear: Thanks.
Sergio Traversa: So I hope I answered your question.
Sergio Traversa: And the loading dose in phase two for the highest dose was actually 100 milligrams for four tablets or solution in phase two.
Sergio Traversa: So, that will not stop at day 28.
Operator: We take our next question from
Sergio Traversa: Thank you, Uy.
Andrea Tan: Got it.
Sergio Traversa: It was the corresponding four tablets, and there was no sign of anything that could signal that you are taking the drug, it's not the placebo.
Jay Olsen: So, when it's, you know, you had the label for chronic treatment, technically, you can use it as long as you would like to, as long as the patients require the treatment.
Operator: John Lee with Truist Securities.
Sergio Traversa: And thanks for the question.
Sergio Traversa: To answer the other part of your question, there are other antidepressants that use loading dose.
Jay Olsen: Okay.
Sergio Traversa: Yes, we will schedule a pre-NDA meeting.
Sergio Traversa: I don't have anything on the top of my mind.
Jay Olsen: Thank you.
Sergio Traversa: We would like, to have at least one phase 3 data top line result before we approach the FDA.
Sergio Traversa: I do know that there is a few of them, of which one, John, knows very, very well.
Sergio Traversa: And with that, I believe the call can be concluded.
Sergio Traversa: I believe that will take us a lot more seriously if we have good phase 3 data.
Sergio Traversa: They require titration, because if you take the full dose the first day, you get some side effects. So you need to start with a lower dose so they titrate to the effective dose.
Sergio Traversa: And I wish everybody a wonderful rest of the, day and a wonderful evening.
Sergio Traversa: But we will schedule a pre-NDA meeting. We will provide the old package that will go from preclinical CMC to the clinical.
Sergio Traversa: I don't have anything on my mind of adding antidepressants that use loading dose, but tolerability, we see that as a big advantage.
Operator: Thank you very much.
Sergio Traversa: Clearly, phase 3, the clinical part will be the one that will be the topic of discussion.
The call can.
Sergio Traversa: If you can give three times the therapeutic dose to fasten the steady state and to fasten the onset of the effect.
Sergio Traversa: From communication with the FDA that go back to months ago, we do believe that the preclinical, package is done.
Sergio Traversa: I don't think other drugs don't do it.
Can be concluded and I wish everybody.
Sergio Traversa: So, there is no more request for any non-human studies or in vitro studies.
Sergio Traversa: They don't do it just because we don't have enough safety and tolerability that can do that.
Sergio Traversa: And so, in CMC, well, MAG-IT is on the call. MAG-IT is actually the lead on the manufacturing. We are well advanced.
Sergio Traversa: Otherwise, there's no reason not to do it.
Sergio Traversa: We have well enough product, not only to complete the phase 3, but also to go, beyond that.
John Lee: Thank you so much.
Sergio Traversa: And I believe MAG-IT, correct me if I'm wrong, but we are making the commercial batches.
Wonderful rest of the day and the wonderful evening. Thank you very much.
John Lee: Thank you, John.
Sergio Traversa: So, CMC will probably be filed with the FDA.
Sergio Traversa: Thank you.
Sergio Traversa: We have it all in NDA, so it will be filed, before we file the clinical package.
Operator: Once again, ladies and gentlemen, please press star 1 to ask a question, star 1 to ask a question.
Sergio Traversa: MAG-IT, do you have anything to add?
Operator: We take our next question from Jay Olsen with Oppenheimer.
Operator: And ladies and gentlemen, that will conclude today's conference.
MAG-IT: No, that's a great summary, Sergio.
Jay Olsen: Your line is open.
Yeah.
Operator: We thank you for your, participation.
Sergio Traversa: Thank you.
Jay Olsen: Oh, hey, thanks for taking the question.
You may now disconnect.
Uy Ear: Thank you for the question.
Jay Olsen: Maybe for John, I'm just curious about the due diligence he did, and congrats to him on joining Realmada.
Uy Ear: Can I sneak in another question, if I may?
And ladies and gentlemen that will conclude today's conference. We thank you for your participation you may now disconnect.
Jay Olsen: If you could please comment on the feedback that you got from KOLs that you spoke to, and what are some of the lessons learned from your work at Eli Lilly and elsewhere that you hope to leverage at Realmada?
Uy Ear: Just wondering, you know, the amount of cash, that you ended the quarter with.
Jay Olsen: Then what are the greatest challenges you expect to face in the launch of REL 1017, and how do you plan to overcome those obstacles?
Maggie Chinuda: Could you remind us what that would take you through?
Jay Olsen: Then I had one follow-up, if I could.
Maggie Chinuda: Sure, sure.
Jay Olsen: Jay, thank you very much for the questions.
Maggie Chinuda: So, we ended the quarter with $212 million. And based on our internal estimates, that'll take us out to mid-2024.
John Hickson: The due diligence that I did was extensive. Really, the way I did it was, since I'd been in the space a long time, I'd been watching Realmada's data from afar anyway.
Maggie Chinuda: Okay.
John Hickson: Then when this opportunity arose for me, besides being very excited, I spoke to a lot of my psychiatry friends, and I just said, hey, what are your thoughts about this drug based upon what you know at this point in time?
Uy Ear: Thanks.
John Hickson: I have to say that every single one of them said that this drug looks extremely exciting to them, so I'm quoting them and their viewpoint, given what they've seen so far. Then when I probe a little bit further as to why that was, they said, well, it does appear to work rapidly.
Uy Ear: Sure.
John Hickson: It does appear to be safe. While it carries the S methadone name, they said that strong data and safety data will certainly win out over any type of reluctance or concern that some clinicians may have, because the field is still looking for something that really is going to be efficacious and safe.
[music].
Sergio Traversa: Thank you for the question.
John Hickson: Easy from a patient administration standpoint.
Sergio Traversa: Thank you.
John Hickson: That was very consistent.
Operator: It appears there are no further, questions at this time.
John Hickson: I've been doing other projects in the depression space, so it just cemented the decision that, I was thrilled and an easy yes for me to join the team.
Sergio Traversa: I'd like to turn the call back to Sergio for any additional
John Hickson: In terms of lessons that I learned from Lilly, gosh, there are a lot.
Sergio Traversa: closing remarks.
John Hickson: I would draw first on my experience with Prozac, where the company obviously brought forward, a revolutionary, iconic antidepressant.
Sergio Traversa: Sure.
John Hickson: But as more and more competitors came in, I have to say, I think the organization, particularly, my marketing organization, we started to move away from some of the basics of staying with our own positioning with Prozac and started to kind of follow what the competitors were doing.
Sergio Traversa: Well, thanks everyone for the time and interest in our program.
John Hickson: And what we learned late in the life cycle was to go back to our knitting and remain, with the positioning concept that got Prozac to where it was.
Sergio Traversa: And in closing, I am and remain very grateful to the Relmada team for their continued hard, work and dedication to executing our mission.
John Hickson: We employed that very same principle with Cymbalta as we prepared to launch it, realizing, we were going to be antidepressant number 11, 12, or 13 into the U.S. marketplace, and so we needed to have a unique, ownable, and differentiating positioning concept around depression hurting, hurting both emotionally and physically.
Sergio Traversa: And I would like also to extend my sincere thanks to the participants and clinical partners involved in the REL1017 clinical trials for the effort and in advancing this important product candidate through the clinic as expeditiously as possible.
John Hickson: So that's something I really want to employ with Relmada is to come up with a positioning, concept that will differentiate it from all of the other potential new entrants coming in around the same time period.
Sergio Traversa: And it was a very, it is a very large program.
John Hickson: And then the challenges to face, going back to the S-Methadone, you know, that's something, that we know will be something we're going to have to work through and scheduling.
Sergio Traversa: And the question I had, you asked me the same question like one and a half years ago, what worried me the most was that, you know, can we actually do a program of this size and this complexity?
John Hickson: But when I look at other analogs, such as Epidiolex, the epilepsy drug that's a derivative, of marijuana, or it's a cannabinoid, it came out as a Schedule 5, and then after about a year or two on the market, it became de-scheduled, and I think that may be a very good analog for us to dig into and understand and to follow.
Sergio Traversa: Well, now I can give you the answer.
Jay Olsen: I hope I answered your questions, Jay.
Sergio Traversa: We actually did it.
Jay Olsen: Thank you.
Sergio Traversa: We are almost there.
Jay Olsen: Yeah, that was super helpful.
Jay Olsen: Thank you so much, and congrats again for joining Relmada.