Q4 2022 NRX Pharmaceuticals Inc Earnings Call
Good afternoon, and welcome to the Inter X Pharmaceuticals full year 2022 results conference call. All participants will be in a listen only mode should you need assistance. Please signal a conference specialist by pressing the star key followed by zero.
After todays presentation, there will be an opportunity to ask questions to ask a question you May Press Star then one on your telephone keypad to.
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Please note this event is being recorded.
I would now like to turn the conference over to Suzanne.
Missouri Stern Investor Relations. Please go ahead.
Thank you Danielle.
Before we proceed with the call I would like to remind everyone that certain statements made during this call.
Looking statement.
Under U S Federal Securities Law.
These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations.
Additional information concerning factors that could cause actual results to differ from statements made on this call is contained in our periodic reports filed with the SEC.
The forward looking statements made during this call speak only as of the date hereof and the company undertakes no obligation to update or revise the forward looking statements.
Information presented on this call is contained in the press release issued earlier today and then the company's Form 10-K planned to be filed tomorrow.
May be accessed from the Investor Relations section of the editor X Pharmaceuticals website.
Joining me on today's call from an Rx Pharmaceuticals are Steven Willard Chief Executive Officer, and Seth Van Voorhees, Chief Financial Officer and Treasurer.
Steven will provide a summary of the company's progress South will review the company's financial results and then Steven will review upcoming milestones before making closing comments.
Following their prepared remarks, Steven and staff will be joined by Jonathan job at the company's Chief scientist and Matthew Duffy, The company's Chief business Officer to address your question.
I will now turn the call over to Steven.
Thank you Suzanne.
Good afternoon, everyone and thank you for joining us.
We scheduled this conference call to coincide with World bipolar day.
As you know bipolar depression is a lethal condition that affects 2% of Americans nearly 7 million people and a similar percentage of the world's population.
With the commitment of our investors our team and our researchers we aim to literally bring hope to the millions of patients with suicidal bipolar depression, and PTSD, who had been systematically excluded from the trial previous anti depressant.
Today, we will discuss full year 2022 results and provide a business update.
As you can see from our filing 2022 was a pivotal year for <unk> when.
When we filed our 2021 earnings the Covid pandemic was just winding down and we announced our intention to redirect our energy and our.
<unk> core business the development of life saving drugs for lethal central nervous system conditions with an initial focus on suicidal bipolar depression.
We promised to investors a year ago, we have now completed manufacturer of N. R X, one or one and aligned with the SBA on a path to commercial stage product.
We've reinstituted, our clinical trials for <unk> hundred one for patients with suicidal treatment resistant bipolar depression, we've continued to align with F. D. A N a paas to approve.
And our X one on one and this week, we announced encouraging findings from the first evaluation of unblinded data by our independent.
Data safety monitoring board.
As you know from the online publications, we have posted this D. S. M. B initiative is being led by a highly experienced executive team together with leading psychiatrists from around the world.
Today, we are delighted to announce the appointment of two world class psychiatrists, who are advisory board.
Professor Andrew Nurenberg chaired professor of Psychiatry at Harvard Medical School is the director of the <unk> family Center for bipolar research at the Massachusetts General Hospital.
And one of the world's most public scientists in the area of psychiatric research, particularly as it relates to bipolar disease.
We are honored to have him as principal investigator of our ongoing clinical trials.
Professor Marianne on literally a.
Is one of France's leading psychiatrist and then extensively published researcher in the field of neuropsychiatry, particularly as it relates to bipolar disease.
In addition to her academic achievements professor Luckily a chance the phone does seem a fundamental.
And has facilitated an important collaboration with French psychiatry, researchers that I will describe in a few moments.
Their biographies on our website.
I'll begin by reviewing our lead development program and our X 100 Watt.
And our X 101 is a fixed dose combination of <unk> with theory and N M. D. A receptor modulator and lurasidone or standard of care medicine for treating bipolar depression.
We initially introduced in our S. 101 is a drug that showed benefit in conjunction with ketamine in acute care patients and this week announced encouraging findings from our outpatient trial within our X. One on one versus the rest of them that may offer a path to a far broader indication.
And our X 101 means to target a critical area of unmet need among patients with bipolar depression P. T. S T.
And as you can see in our filings, possibly chronic pain.
Multiple investigators around the world have published encouraging findings on the use of recycled serine in these areas.
However, the N. Iraq discovery is a unique synergy between an MTA and five H T to a targeted drugs together with the discovery of the critical doses dosages at which dissect with theory may be effective in these conditions.
As a result within a portfolio of 90 patents around the world 48 of which have now been issued.
All related to the treatment of bipolar depression major depressive disorder, PTSD and the other central nervous system conditions.
It is well established that patients with bipolar depression, alright, far greater risk of self harm than that.
With major depressive disorder.
Tragically, however, patients with suicidal bipolar depression had been excluded from the clinical trials known anti depressant.
To our knowledge and our acts as the first company.
To attempt to bring medicines to people, whose only F. D. A approved treatment alternative is currently electroshock therapy piece.
Cyclists series has been shown to reduce suicidal ideation.
Stake will be trial, and similarly had been shown to reduce suicidal ideation by independent investigators in a peer reviewed studied reproduced in our 10-K filing.
The tragic reality of bipolar depression is that if you know two people with this condition.
Does that one will attempt suicide.
And if you know five people with this condition.
That one will die from suicide.
As the first potential oral NMDA antagonist target bipolar depression suicidality.
Our X 100 one's proof of concept data from the phase two stable B trial has shown me highly differentiated therapeutic profile.
Impaired to the other commercial therapies and investigative drugs under development.
Our phase two data showed a statistically significant reduction in both depression suicidality compared to standard therapy in patients with bipolar depression, who were acutely suicidal.
And those who are initially stabilize with Kennedy.
To our knowledge no oral drug therapy has ever demonstrated a reduction in both depression and suicidal tendencies in this patient population.
This is a potentially lifesaving events, because antidepressants carry black box warning labels regarding the potential for an increased risk of suicide in vulnerable populations.
Based on an Rx 100 one's differentiated therapeutic profile, we believe that we have the potential to address a significant unmet need for patients who are currently underserved by available treatment options.
Based on our phase III results. The S. T. A granted breakthrough therapy designation and a special protocol agreement for <unk>, 101, and bipolar depression with acute suicidality.
The breakthrough therapy designation allows for an expedited rolling submission of a new drug application for investigational drugs that have demonstrated substantial improvement over existing approved therapies.
And the special Protocol agreement allows for a single Registrational trial.
101 in this indication after stabilization with ketamine using a protocol similar to the stable B trial with a patient population that fewer than 100.
During 2022, we made substantial progress in advancing our development plans for <unk> hundred one for the treatment of bipolar depression, Suicidality and as well as the new area P. T. S T.
As you recall from our initial public filings our psychiatry drugs development program was halted by the closure of Psychiatry study sites during the Covid pandemic.
This time last year, we advised investors that we were re initiating our psychiatry program.
Our first order of business was to transfer our manufacturing analytic technology to the United States and.
And we were fortunate to secure alchemy headquartered in North Carolina.
Neatly manufacturing partner.
Over a period of six months, we transferred our manufacturing and analytic methods to alchemy and by September manufactured our first phase III and potentially commercial scale batch about Iraq's one on one.
We submitted our manufacturing and stability data to the S. T E. In October 2022, and in January 2023, we reached alignment with FDA on our proposed manufacturing plan based on the type C meeting to review, our chemistry manufacturing and controls.
As a result, and Iraq is now positioned to conduct registrational trials of <unk> 101, and able to make in our X 101 available through expanded access and right to try programs for patients who have exhausted approved treatment options.
We're excited about this milestone in particular as we believe that adopting a commercial ready manufacturing process at this stage of our development and lease it to a more seamless NDA submission review and approval process under our breakthrough therapy designation without the need for bridging studies.
In January 2023, we initiated the phase III Registrational clinical trial of <unk> 101 for the treatment of severe bipolar depression with acute suicidal ideation and behavior and.
And contracted the first study sites.
The study was designed to show that the four following stabilization in the acute care setting treatment with <unk> 101 is superior to La Raza duck and maintaining improvement in symptoms of depression as measured by the Montgomery Asbury Depression rating scale total score.
We met with the U S. FDA earlier this year to discuss.
The design of this phase III trial, then our X 101 in patients with bipolar depression suffering from acute suicidality and are following FDA suggestion to pursue the indication.
Treatment of recently suicidal patients with bipolar depression.
We conducted our initial stable B trial, and our X 101 versus Lovaza down.
Lee suicidal patients following the acute stabilization with ketamine.
However, both F D E and prospective commercial partners has suggested broadening broadening the indication to test the use of <unk>. One on one as a means of maintaining remission for acute suicidality and patient stabilized by variety of standard inpatient and approaches.
In order that our label should we prove safety and efficacy not be dependent on prior use Academy.
Although he's not actively researching we use academy a potent NMDA antagonist.
We do recognize its role as a potential agents are stabilizing acutely suicidal patients and recognize the fda's desire for more data on its efficacy.
Therefore, we have partnered with a leading psychiatrist and perhaps who conducted what we believe to be the most comprehensive study academy for treatment of acute suicidality among hospitalized patients, particularly patients with bipolar depression.
Their study, which is summarized in Tomorrow's 10-K filing demonstrates that patients with bipolar depression had a seven fold greater response to ketamine and reducing suicidality than did those with major depressive disorder.
Our colleagues have provided us with detailed clinical study reported that we have now translated into English and are submitting to the F. D. A.
To our knowledge. This is the first multi center placebo controlled trial that shows an enhanced benefit of N. M. D. A targeted drugs in patients with bipolar depression compared to those with major depressive disorder.
We look forward to having professor liberally and her colleagues explain the importance of this study in greater detail in the company as to the F D. A to discuss the findings.
And the January 2023 type B meeting with the S. T. A psychiatry division to align on the registration strategy for an Rx 101.
F D. A suggested a potential expanded indication for <unk> hundred one in addition to reaffirming in our X one of the ones Special Protocol agreement, which was originally granted in April 2019.
The FDA suggested that <unk> clinical development program be enlarged to allow for the chronic treatment of patients with bipolar depression and intermittent suicidality.
Update with broadening the addressable population indication under the spa or otherwise to patients with chronic intermittent episodes of bipolar depression and will then enable the use of NR X 101 on a long term basis.
Broader segment of the approximately 7 million individuals in the United States with bipolar disorder.
Prior to pursuing this extremely broad indication, we are focused or outpatient clinical trial first on those of greatest unmet medical need specifically those with suicidal treatment resistant bipolar depression.
In other words, we are enrolling patients who are under the care of a physician for bipolar depression and have ongoing depressive symptoms and actually start to sell farm despite treatment with available medicine.
The object is the double blind study is to demonstrate in our X 100 one's ability to significantly improved symptoms of depression suicidality over six weeks when taken twice daily.
<unk> spaces.
Duration is significantly larger than the severe bipolar depression population with the acute suicide as suicidal ideation and behavior seen in the hospital emergency setting.
And does not require initial stabilization academies or other treatments.
This study has the potential to expand the use of our medicine to the nearly 1 million people, who currently suffer from severe depression and suicidal ideation. Despite expert medical care with currently available medicines.
Are the patients who are targeted by the recently funded $50 million patient centered outcomes research initiative, which documents the extraordinary unmet medical need in this area.
Yeah.
We announced the initiation of this clinical trial, when we met with you a year ago.
And this week announced guidance to continue enrolling patients by our independent data safety monitoring board, what I call. The D F N b.
Examine unblinded data from the first 50 patients.
N B found no futility signal at this stage of the trial.
Similarly, no safety signals were identified in association with that are excellent award and the D. S. M. B recommended that the enrollment of the trial continue as planned.
According to the study's statistical analysis plan.
Failure to identify its utility requires that an advantage, though not yet a statistically significant advantage.
The investigational drug relative to the comparator treatment must be observed by the D. S M B I.
<unk> will continue to monitor safety and efficacy in the trial.
Based on the D. S N B's findings together with the recent completion of phase III anticipated commercials page manufacturer event. Our X 101. The company has upgraded the ongoing trials will cease to be slashed III trial with.
Our results may be used in a future registrational filing should the primary endpoint to met.
With the guidance of the DSM V. At hand, the company is now requested a comprehensive breakthrough therapy planning meeting for <unk> 101, as was suggested by S. P. A and that recent correspondence.
Based on the comments and guidance from the FDA and its recent type B meeting regarding the Registrational acute suicidality trial, and a potentially broader indication as well as the guidance. We received from the DSA B regarding our currently enrolling phase two b stroke C tablets.
Sorry to be slashed C.
Uh huh.
Three clinical study of <unk> 101, the company is evaluating changes towards Registrational program for <unk> 101, and we'll seek to consolidate the current clinical trials.
This broader indication.
Also offer significant advantages in commercialization.
Data is expected by the end of this year.
We are evaluating the potential of <unk> hundred one and post traumatic stress disorder or PTSD. Another area of high unmet need which is also associated with suicidality.
Approximately 9 million individuals in our country expect experienced P. T. S T and one third have severe P. T S T with 10% experiencing suicidality.
Between 17, and 22 members of our armed forces and veterans are lost every day to suicide.
Depression, and PTSD may be driven by pathways that are similar to those that drive depression and other conditions.
However, an M D a antagonist class and decide with Syria and in particular may have a more specific effect in the treatment of PTSD.
And our preclinical PTSD study described in todays filing.
Ooh Tomorrow's Boeing decide considering and demonstrated the ability to extinguish recurring images of traumatic events also known as peer memory in a validated W. K Y model P. T S T.
This model has similarly been used by others to document of PTSD specific effect as ketamine.
Repeated IV ketamine.
<unk> also been demonstrated to improve PTSD scores in a randomized controlled trial.
Unlike ketamine, however, an Rx winter when he is not neurotoxic is not addictive.
Has not caused psychedelic side effects in clinical trials.
Yeah.
We anticipate that our investigational drug will show anti depressant effect in P. T S T compared to placebo and we hope that it will demonstrate specific effects a fear of memory components of PTSD and directly reduce symptoms of PTSD itself.
Today, There is no approved medicine for the specific PTSD symptoms. We are on track to initiate a phase two study of <unk>, one O N P. T S T and the second quarter of 2023.
We are incredibly excited about the potential lifesaving effect in our X 101.
And in order to continue to support the clinical development of these programs, we announced the close of the $2 9 million registered direct offering to support our pipeline efforts and more specifically the.
The initiation of an expanded access protocol and safety database for <unk> one on one.
Treatment resistant bipolar depression with risk of self harm.
This database allows us to investigate the expanded indication put forth by the FDA is like Theatrics Division.
And our type B meeting.
Registrational trials and we look forward to providing you all with an update of our clinical activities in the months to come.
The continued financial support from our existing shareholders based on our existing data and ongoing clinical trials demonstrates their commitment to people living with serious CNS disorders, and the potential within our X 101 to become commercially successful.
Finally, we achieved a number of significant corporate milestones in recent months in February we received notice of the issuance of a U S patent for our X 101, which covers the use of <unk> 101 to treat patients suffering from depression, including bipolar depression, or major depression with or without <unk>.
Modality.
Patent strengthens the company's intellectual property position until at least 2030 free.
We are pleased to announce that Matthew Duffy has joined US as chief business Officer of the company. Many of you may know him from his time at leading pharmaceutical and biotechnology companies, including Pfizer at Medimmune and his efforts in Investor Relations and investment Bank.
Matt will be responsible for a range of duties, including Investor Relations.
Similarly, Dr. Martin pressure, a distinguished psychiatrists, who has held leadership positions at the S. T. A astrazeneca Johnson and Johnson and other leading corporations.
I mean, it's medical director for our clinical trial.
These milestones achieved in the year since we reentered psychiatric drug development establish a strong foundation for on Iraq that enables us to efficiently advance our clinical trials and make a difference in the lives of patients with life threatening psychiatric diseases.
I'd like to express my gratitude to the patients.
The N R S team.
Clinical trial investigators and shareholders for their continued support.
With that I will turn it over to <unk> for a review of our financial results.
Thank you Steven and good afternoon, everyone.
I will now review the highlights of our fiscal year 2022 financial results and our expectations for 2023.
For the year ended December 31, 2022, interacts pharmaceuticals recorded 17.0 or $1 million in R&D expenses compared to $23 million for the year earlier.
<unk> of $3 2 million as it related primarily to the decrease of $2.5 million in clinical trial and development expenses related to our discontinued clinical work.
For the year ended December 31, 2022, we also recorded $27 4 million of general and administrative expenses compared to $74 9 million for the year earlier.
A decrease of $47 6 million was primarily related to a decrease of $53 $3 million in consulting fees of which $41 million was related to the fair value of common stock issued.
For the 12 month period ended December 31, 2022, our resulting net loss was $39 8 million.
Which was $53.3 million in place compared to the net loss of $93 1 million for the 12 months ended the prior year.
Yeah.
In fiscal year 2023, we expect our annual R&D expenses to decrease.
Increased further from both fiscal year, 2021, and 2022 levels as we focus solely on the development of <unk> one on one.
Furthermore, we expect our annual G&A cost will decrease in 2023 due to a number of factors, including reduced legal costs related to the relief therapeutic.
Political settlement.
Which has the potential for significant royalty payments to us in the future.
Lower insurance costs, especially related to D&O coverage.
Well, there's other cost initiatives that we've undertaken.
Now I'd like to comment on our cash resources.
At year end, we had $20 1 million in cash.
Our cash resources were enhanced several weeks ago, when we entered into a securities purchase agreement with a credit of investors who had previously established ownership positions in the company.
The transaction involved the sale of approximately $3 9 million shares of the company's common stock combined with.
Five year once in a registered direct offering priced slightly above market at 75 cents per unit for the securities.
The investors agreed not to sell the shares of common stock or exercise. These warrants for six months following the issuance of this one state.
The aggregate gross proceeds to the company from the offering was approximately $2 9 million.
As of the 10-K filing we evaluated and if there is our ability to fund our operations for the next 12 months.
We have the right to make required payments for our current indebtedness and common stock subject to certain ownership and trading volume limitations.
If we were not able to make the required payments for this indebtedness, we will need to raise additional capital to support our currently anticipated operations for the next year.
To strengthen our.
To strengthen our balance sheet.
He was dealt with.
This successful offering done several weeks ago.
In addition, we may consider additional cost savings initiatives to further extend our cash resources.
With that I will turn it back to Steve for closing remarks, Steve.
Thank you Seth.
Over the past year, we have built strong momentum as we advance our N. Our X 101 program in two indications.
We're also positioning in Iraq for future growth with the potential for both the broader bipolar depression population as well as additional indications.
Building on that momentum 2023 promises to be an even more productive year.
As we continue to execute on multiple regulatory and clinical catalysts.
We believe that <unk> 101, as a potentially lifesaving medicine that could change the treatment paradigm for individuals with bipolar depression, who are experiencing suicidality, which is the driving force behind our mission is meeting the needs of underserved patients with serious CNS disorders.
We look forward to updating you on our near term milestones, which are on track for the coming year.
I'm, assuming that efficacy endpoints and safety are met in our phase III trial, we plan to initiate the rolling submission of a new drug application by the end of this year with potential through drug approval by the end of 2024.
Operator, Danielle we're ready to take questions from the audience.
We will now begin the question and answer session to ask a question you May Press Star then one on your telephone keypad, if youre using a speakerphone. Please pick up your handset before pressing the keys.
To withdraw your question. Please press Star then two.
We will pause momentarily to assemble the roster.
The first question comes.
Hello Hello.
Hello.
The first question comes from Jason Kolbert Dawson James Please go ahead.
Hi, guys. Thanks, Jason appreciate it Hey, how are you. Thank you for the very comprehensive update I mean that it was really really good very detail, which is what we need.
Just wanted to understand a couple of comments you made the D. S M b lack of utility.
Switching five that the active drug is showing.
Let's see.
Equivalent to work, even better than comparator, although not yet statistically significant can you just talk a little bit about that statement and kind of the math behind it that would be helpful.
Yeah.
Sure Jonathan.
Sure.
So Jason as you know it's critical.
Critical that we keep the.
Blinding for the trial in place.
Little calls for the trials and the statistical analysis plan are up on clinical trials like Dove.
And all we've been authorized to say, but the D. S N b.
Is that no futility signal was identified.
And lead methodologies start to live in.
<unk> said that we could offer the additional comment.
In this trial the way this is set up.
For that conclusion to be reached a numerical superiority does not a statistically significant superiority would have to be identified there are some trial decides where.
As long as you're not worse than the placebo.
You're still not futile.
<unk>.
We put in place a stricter futility rule than that.
But that's really all we're at Liberty to say right, but actually that's very critical that last sentence. When you talk to that because that's what I was familiar with it in most clinical trials.
Our design that if you're a quiver lens to the comparator that you're or non inferior to the comparator. That's how they're mostly designed and what I didn't understand until this moment was that if your trial design is a little bit different and in fact, you're not futile.
File because of the powering and I'm, assuming because of the powering differences in the assumptions around.
Around the effect between active and comparator that in fact, if no futility as shown it suggests that there is a superiority.
Otherwise because the numbers are stacked against you because it's a tough trial design does that kind of layman's interpretation about right.
Well I don't think I'd want to yeah.
Two wax overly optimistic I think we're delighted that we deemed it a futility signal given that we had a fairly strict rule in place I don't think it would be necessarily care for as I talked about in the most Ah trial designs, but we did get one of them.
Yes.
Well, let me say the second half of it.
Sure I understand that so I don't want to beat up this point because you are limited by what you can say, but I was also very interested from a clinical perspective, when you talked about potential modifications of the phase III trial and the combination of the two trials together.
Can you talk a little bit about what that might mean and particularly I was.
Yeah, particularly.
But how we got to where we are.
When when when this began.
Began because people were using ketamine.
To treat it.
Acutely depressed patients.
And yeah, everybody saw that ketamine wears off after a couple of days to a week.
And you know a lot of people thought that repeat use academy it wasn't a great idea.
So people suggested course.
<unk> developed in our X 101, as a maintenance therapy.
Prolong the effect of ketamine.
And that's what we did in the stable <unk> study.
We thought with results that was quite encouraging.
As you know are.
Lurasidone was originally approved on a 3.9.
Point difference between.
La Raza one placebo.
And yet we'd be lurasidone, a known good drugs by seven seven points.
Yeah pretty pretty impressive effect.
Yeah.
Remember our ability just got approved on a four point difference between <unk> and placebo.
Bold and we didn't go against placebo because.
It wouldn't be appropriate to do that and soon a subtle patience. We went against the best available standard of care drugs. So that's how we got into this and that's why we got the breakthrough therapy designation.
Along the way, we said well what if an Rx 101 is actually good enough to.
Could be a benefit to patients without prior use of academy.
And.
We ask that question just as we were getting back into psychiatry a year ago.
Where we had just enough of our old fees too material to do a a smallish study like this we said, let's test analytics 101 against slower as his own without prior Academy.
And see if there's a signal it see if it's not futile and and that's where we are at this point.
And based on having reached that point and based on.
Having now the availability of newly manufactured.
Three and potentially commercial scale drugs were enlarging this to a registration study.
Because we now believe that there is a real potential for this home use oral pill actually capsule.
To be effective in its own right not just as a drug to take after caterpillar.
So that's how we got to where we are.
That makes perfect sense, and then last question and you just kind of touched on it also was a breakthrough designation.
Is that something that you feel you've been encouraged to go after.
Well, we've been awarded breakthrough therapy designation for the original indication.
Interacts one on one T use after.
Oh Geez after Academy.
And that gives us the ability is the important part of breakthrough therapy designation.
Is it gives you a.
Dedicated resource at F D a.
A program manager who is.
Committed it's at all possible to helping the drug through the approval process.
So we have that.
In place now.
And the other key benefit of breakthrough therapy designations that it gives you the right Keith.
To submit your knee drug approval application.
On a rolling basis. So we've said by the end of the year, where we're gonna start submitting we're gonna submit the manufacturing data.
Clinical data so that the whole file is reviewed by the time, we finally have the efficacy data.
Submit.
So those benefits of breakthrough therapy designation or already in place got.
Got an edge and that.
Well.
We may we may have a conversation with FDA with more data are available.
About specifically.
Extending the breakthrough designation to this use of N. R X one on one but I'm not sure that that would really change your path to approval in any meaningful way.
Perfect. Thank you and in that answer actually answered some of my timeline question. So.
Really the only.
The critical hurdle for you is gonna be if I'm right is just patient enrollment and then data analysis once you.
<unk> completed treating relapsed patient right.
Patient enrollment data analysis, and we announced after the type C meeting with FDA that they want to see.
Our safety database of 1500 patients. So if you look at recent approvals approvals.
Approvals actually happened at a smaller <unk>.
Safety database than that but 1500 is the easy one.
Any target.
In the United States and other countries all sort of agreed on the safety database size.
For drugs to treat non lethal conditions.
Of course, there's a lethal condition.
Uh huh.
And you've seen us talk about how we're going to start building that safety database not only through our clinical trials, which take a while to enroll and are expensive to enroll but also through.
An expanded access program.
Would allow doctors, who have patients with bipolar depression and have exhausted.
Whose medications for the treatment of bipolar depression.
<unk> access to 101, and there's a fair amount of precedent for the use of such funds at axis.
Programs in this way.
So to the extent that people imagine.
Yeah, the safety database will be horribly horribly expensive.
Recognize that when we did expanded access in in Covid.
Yeah. It was on the order of C L.
<unk> 4000.
<unk> thousand dollars a patient.
As opposed to the kind of costs, one was associated with a formal.
Randomized controlled trial now we don't know what expanded access is going to cost us.
In our S 101, yet we don't know, whether we're going to be able to gain reimbursement for extended access which silicon the FDA guidance can be applied for.
But we do see it as an efficient way.
To get to the M D a.
While at the same time.
Continuing our clinical trials for safety and efficacy full speed ahead.
Thank you Dan just that thank you.
The next question comes from Vernon.
Bernardino from H C. Wainwright. Please go ahead.
Hi, everyone.
Congratulations on the progress and thanks for taking my question.
Hey, Jeff and Steve and myself.
What is important for me to perhaps ask about us.
Is that the current trial being upgraded to a phase two b three study.
That may be used for registrational filing.
With the nuances of this patient population and how they're treated are there any specific changes that.
Are going to occur or need to occur such that.
It has been upgraded.
Two a registrational study or is it just purely an upgrade because that's something that you asked for an August already fulfilled the requirements.
Well one of the things we did is posted the the protocol.
On clinical trials that clause.
And that's an important thing to do because when.
And we certainly hope the trial will show efficacy.
The reviewers for the scientific journals wants to see that we were transparent upfront about what our end points how are we measuring them.
So that to the extent that there were changes along the way, but those are our known in a transparent manner.
The main difference for us between simply phase two and change to be three.
Is it.
So Jason when we started this all we had in our warehouse was phase two investigational medicine that was made five years ago.
In China.
Our partnership with Wuxi upset.
No that's not.
That's not investigational product that can be used for registrational purposes registration study means that you're doing in your clinical trial with medicine that is essentially identical to the medicine that you intend to put on the shelf with a pharmacy.
So we're now at that point, where.
We did the hard work to do the tech transfer to bring the analytic methods over.
From China to North Carolina, and validate those methods.
Oh.
Upgraded our control of impurities from.
Phase two level to a phase three level.
So now that we actually have medicine that we believe is substantially identical to the medicine that we would hope to put on a pharmacy shelf and a couple of years.
We're able to make this a phase two b three registrational.
Trial.
So that that's not really a protocol change.
Per se and I think Austin.
Investors don't realize how.
These days in biotech.
You'll failures in manufacturing and CMC or possibly more likely to bring down our promising drug then you'll failures in an efficacy trial.
And that's why we're so fortunate to have Dr. Panic, Gucci, who as you know one of the world's more experienced drug.
Drug manufacturing exports as our Chief Technology Officer.
Okay.
That's important because conceivably if it's a studied a very successful you could also and I say conceivably use the phase III material for commercial supply I guess, what I was specifically getting at is.
Is there going to be any change to pass the screening of patients.
Such that it's fine tunes those that would enter a phase three level type of a study that is registrational.
Well one of the things that we're intensely focused on.
Is ensuring that the psychometric ratings achieved in this study.
Are as accurate as possible.
A lot of talk in the psychiatry space.
The study sites that yield surprising results and getting on top of study sites.
And one of the things we've done that we think is a little different from you.
What what some have done is we've built a team of experts at the metric graders.
Within the company.
Who are evaluating in real time.
The ratings that are being achieved at the study sites. So they get an audio recording of each rating session as it happens.
And we're constantly looking at concordance between.
People, who are being rated by the site later on the mattress score on the CGI Suicidality scale.
And those same session is being evaluated by our in House Master Raiders and we've set up an adjudication system. So that if there's more than three points of disagreement.
That waiting session immediately goes out to an independent.
Judicator.
If you look on clinical trials Gov, we published some of our information about how we do that.
And I think in the coming.
We're going to hope to get a scientific publication out.
That will give the investment community.
Sense of how we approach. This this whole process of trying to keep our clinical trial under control, where you you don't win or lose based on a blood test or examining a piece of tissue.
When you win or lose based on what's inherently a subjective process where an expert.
Settling the psychologist is asking structured questions and assigning a score.
And Keith you need the risks between study sites down as low as possible just the difference between having a.
You know a very high standard deviation.
A great deal of difficulty improving statistical significance.
Versus having a tighter standard deviation and an easier ability to prove statistical significance. So that's that's where we're focusing every day.
We try to do our job to tripling this medicine to market.
Sure. Okay. That's helpful information.
And because of the placebo effect as you know the problem flip that in these kind of studies.
That's why I asked the question before.
Because unfortunately.
Sometimes it's impossible to know if somebody's suicidal unless they actually have kind of.
Suicide.
But in the screening process you can fine tune the.
Like I said, our second Mexico, as well as possible and you know increase the chances for success. So I appreciate you.
Providing that additional information and.
Wish you the best of luck for the study thanks for taking my question.
You just said something very important.
And it's one of the early things that FDA guided us on when we first met with them.
It's pretty well known that suicide gallery.
Comes and goes.
And it may not be something that patients talk about as readily as are symptoms of depression.
So the guidance, we got from FDA early on because our original thought was that our primary.
Indication would be the suicidology score the Titans, we got from FDA was.
To make the primary endpoint for studies, the mattress depression scale.
And the exact words.
Okay. If you can.
If you're able to prove that.
Got you improved depression in this population of patients who have suicide reality.
Excluded from previous trials, where.
Yeah, there's no anti depressant, that's indicated for use.
No oral anti depressant, because there's been some encouraging data with Johnson <unk> Johnson's S ketamine product.
But theres no oral anti depression, which indicated for use.
In these patients with suicidology, that's great that's that's enough to win.
And if at the same time, we're able to show that the secondary end points of improvement on the CGI Suicidology scale is.
<unk> also significantly better than the comparator drug well.
It's even better.
But that's that's why our primary endpoint is the mattress depression scale.
Thank you I appreciate that and I am very hopeful for you and.
The patients out there. Thanks again for taking my question.
You bet.
Okay.
As a reminder, if you have a question please press star one.
The next question comes from Ed Woo from <unk> Capital Capital. Please go ahead.
Yes, congratulations on the progress and also on the D. S. M. B a readout do we anticipate any more readouts or any interim data for either one of those studies this year.
We do expect that the D. S N b when I looked at the data again.
At some point.
I would guess before the end of Q3, but.
<unk>.
They haven't told us exactly when that readout is gonna be but theyre going to be monitoring. This study in an ongoing way to the extent that there are no safety signals emerge they might look sooner.
Uh huh.
But yeah, they're working with us very closely because this is a population of patients who are actively risk of self harm which is why.
Why they've been excluded from trials of ordinary antidepressants.
Great well, thanks for answering my questions and I wish you guys. Good luck. Thank you. Thank you.
This concludes our question and answer session I would like to turn the conference back over to Suzanne, Missouri for closing remarks.
Thank you Danielle and thank you everyone for participating that is all the time we have for questions. Thank you again. This concludes the interacts pharmaceuticals full year 2022 results conference call.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.