Q4 2021 Aptinyx Inc Earnings Call
Good afternoon, and welcome to that next fourth quarter and year end 2021 financial results conference call. At this time all participants are on a listen only mode. Following the formal remarks, we will open up the call for your questions. Please be advised the call with me.
<unk> recorded at the company's request at this time I would like to turn the call over to Pat Flabby Senior manager of corporate development and Investor Relations at <unk>.
Please proceed.
Good afternoon, everyone and thank you for joining us on today's conference call to discuss <unk> fourth quarter and year end 2021 financial and operating results.
We invite you to visit the investors section of <unk> website to view, our press release, describing our financial results and business highlights.
On today's call Andy Kidd, our President and Chief Executive Officer will discuss our business and clinical development progress that I'm Ashish Carter, our Chief Financial Officer, and Chief Business Officer will review our financial results.
I'd like to remind everyone that statements made during this conference call will include forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995, which involve risks and uncertainties that can cause actual results to differ materially.
Any forward looking statements are made only as of today and we disclaim any obligation to update these forward looking statements.
Please see the forward looking statement disclaimer in our financial results release issued this afternoon and the risk factors in the company's current and subsequent filings with the SEC.
It's now my pleasure to turn the call over to Andy.
Thank you Pat and good afternoon, everyone. We appreciate you joining us on today's call.
21 March a year of significant progress for <unk>. Our mission is to develop transformative therapies for challenging disorders of the brain and nervous system and over the course of the past year, we've taken major strides towards that goal.
We are on track for a series of catalytic milestones and data readouts across our pipeline.
<unk> receptor positive allosteric modulators and expect that 2022 will be a pivotal year for the company.
And the next few months, we expect Readouts from our two phase <unk> studies in chronic pain with NY extra around two five starting with diabetic peripheral neuropathy or APM data very shortly in April the fibromyalgia data than expected in the July to August timeframe.
In addition, we expect the readout from our exploratory study of NY next four or five H cognitive impairment associated with Parkinson's disease, and dementia with lewy bodies within the next 12 months.
Finally, we've been initiating two phase III studies with Atlanta 783 in PTSD and expect data from those studies starting in the second half of next year.
We're supported by a balance sheet that fuels. These development programs and is expected to provide operational runway well into 2023.
Let's discuss our clinical development programs in more detail beginning with NY <unk> 95 in chronic pain.
As I mentioned each of our chronic pain indications VPN and fibromyalgia will read out in the next few months.
The challenging external environment throughout 2020, and 2021, our phase II study in DPM completed enrollment well within schedule last October with a 12 week treatment period, and 30 day follow up we've completed last patient last visit and are expecting to receive and communicate data during April .
The study design integrates several key lessons from our prior phase Iia study and VPN.
In 2019.
Firstly, we're focusing on a patient population with four years or more of DPM disease duration we.
We observed a stronger response in patients with longer disease duration in our prior study.
We believe this is because the abnormalities and grain processing within the prefrontal cortex of the brain that are mechanism targets take time to become manifest.
In addition, we are assessing N Y X 295 at the mono therapy without any concomitant analgesics and with a 12 month trailing period.
We expect these design choices will increase the chances of a separation from placebo and are in line with regulatory requirements for approval.
The VPN study evaluating 12 weeks of daily dosing with 50 milligrams of NY X 295, or placebo. The primary endpoint is the change from baseline to week 12, and patient reported average daily pain averaged over a week and evaluated using the zero to 10 numeric rating scale or <unk>.
The study is powered to detect an effect size that is clinically meaningful.
Pending on the degree of variation seen with pain score differences the lower bound of what is needed to achieve statistical significance would be somewhere between five and seven difference between NY. After <unk> 95, and placebo on the zero to 10 and our scale.
Next steps following the study would include an end of phase two meeting with FDA to discuss requirements for phase III and NDA.
Our phase II study in fibromyalgia completed enrollment at the end of February . So it was just a few months behind our timeline for DPM.
We expect to have data reading out in July or August .
This phase <unk> study in fibromyalgia is similar in design to our DPM study.
Valuation N Y X 295, as a monotherapy with no concomitant analgesics and with a 12 week treatment period.
Primary endpoint is the change from baseline to week 12, and patient reported average daily pain averaged over a week and evaluated using the heroes of Tang at Rs.
In this study as well as the 50 milligram dose were also evaluating 100 milligram dose since we saw promising effects with a higher dose level in a prior neuro imaging study in fibromyalgia.
We believe based on this new imaging study and the underlying disease biology that the abnormalities in pain processing within the prefrontal cortex of the brain that are mechanism targets, our presence in fibromyalgia and at the start of the conditions. We therefore do not have a disease duration requirement as we do for DPM.
The study is powered in a similar way to the DPM study and the next steps would include meeting with FDA to determine the requirements for phase III and the NDA.
Both programs advancement to phase III, we expect there will be synergies and clinical safety and non clinical development work between the two.
We would also consider further indication expansion with chronic pain.
A number of other neuropathic pain conditions, and muscular skeletal pain conditions, which we think of our mechanism is relevant.
Finally, we expect the positive data in one or both of these studies would unlock very significant value for academics and clinical unmet need in chronic pain are substantial.
The drug with evidence of efficacy and a strong safety profile, we have a potential commercial opportunity well into the billions of dollars of annual sales in the U S market alone.
Next we'll discuss NYSE seventy-three, our product candidate in development for the treatment post traumatic stress disorder for PTSD.
In December we commenced phase III development of <unk> 73 in patients with PTSD with the first of two phase III studies.
In the first phase <unk> study approximately 300 patients with PTSD will be randomized to placebo or 50 milligrams of <unk> 73, and evaluated over a 10 week treatment period.
We anticipate reporting data from this first phase II study of NY at 73 in the second half of 2023.
The second Phase <unk> study is the same design as the first except critical test of 150 milligram dose level of NYSE 73.
This dose has not been tested in patients before but based on recent preclinical data. We think there is potential for this higher dose to be effective.
We had been planning to initiate the 150 milligram phase two b. During Q1, we have completed all of the operational steps required.
Works to activate the first group of sites, we now expect to begin screening patients in April .
The two study approach in PTSD is among a range of measures we are employing to minimize and mitigate the placebo response and variability during phase G V.
Having two studies for two different dose levels limits. The number of arms per study factor, which is correlated with lower placebo effect.
In addition to studies limits the number of sites and clinical investigators per arm, which should help to control the variance and measuring clinician assessed endpoints.
We're also not allowing concomitant PTSD pharmacotherapy in either of these studies.
Finally, let's discuss N Y X 458, and cognitive impairment.
We're currently evaluating NY X 458 in an exploratory phase II study of cognitive impairment associated with Parkinson's disease dementia with Lewy bodies. This double blind placebo controlled study evaluates a 30 milligram dose in N Y X 458 versus placebo in approximately 100 patients over 12 weeks of treatment.
This is our first study in patients with cognitive impairment and is primarily meant to detect and characterize signals of activity.
As well as safety and Tolerability, we're evaluating the effects of N Y X and Y X 458 across a battery of neurocognitive tests able to measure changes in attention memory and executive function.
Cognitive domains are impacted in Parkinson's disease, and dementia with lewy bodies, and our NMDA receptor dependent phenomena.
As we mentioned during our portfolio day in February we did see a slowdown in clinical trial enrollment in the U S. After Thanksgiving and continuing into January at least partially related to the omicron variant of Covid.
We've seen activity returned to normal since then and we still expect to be able to read out data from this study late in the fourth quarter of 2022 or in the first quarter of 2023.
In addition to the progress we've made in advancing our pipeline. We recently hosted a portfolio day for investors on February 19th.
Included a review of the chronic pain treatment landscape by Dr. Richard wrap a board certified physician and pain medicine, and anesthesiology, but the Carolinas paying Institute and an investigator in our DPM study.
This event is available for review on our website.
We also announced the formation of a scientific advisory board, comprising leading researchers and physicians in the areas of neuropsychiatry, neurology and chronic pain, including Chatty Abdullah MD from Baylor College of Medicine widely Arnold M. D from the University of Cincinnati College of Medicine Pizza law with MD from Wayne State University School.
With Madison and Jerry Santa Clara M D ph D from Yale University School of Medicine.
The scientific Advisory Board will work closely with us to establish scientific and clinical input as we advanced our pipeline.
Before I hand over to Ashish to review, our fourth quarter and year end 2021 financials I'd like to take a moment to acknowledge and thank our <unk> employees and our external partners for their tireless work over the past year, we have fewer than 40 internal employees, who are successfully manage the ever fluctuating external landscape working closely with them.
Multiple external partners vendors clinical trial sites and investigators and challenging circumstances.
It has been a difficult time for our clinical trial sites and of course for patients and we're very appreciative to all of those contributed to our clinical research efforts.
It is only because of the dedicated efforts in the service of our mission to patients we've been able to advance our pipeline to this critical point and are able to look forward to the data Readouts. We expect both in the next few months and over the next two years Ashish.
Thank you Andy.
Beginning with the balance sheet, we ended the fourth quarter of 2021 with $106 million in cash and cash equivalents compared to $141 million at the end of 2020.
At year end 2021 cash figure does not include $10 million from the second tranche of our capital credit facility, which.
Which we drew down earlier this month and reported today in our 10-K filing.
With respect to our income statement as expected we had zero revenue in the fourth quarters of both 2021 and 2020.
We did have $1 million in revenue over the full year 2021, 2021 as compared to $1 $6 million in revenue for the full year 2020.
And both of those years the revenues were related to our research collaboration agreement with Allergan now a subsidiary of Abbvie.
That research collaboration came to its contractual conclusion early in 2021, and we have not been reliant on it or any other source of income.
And our operations.
The majority of our spend remains heavily concentrated in research and development.
R&D expenses totaled $14 $1 million and $55 4 million for the fourth quarter and full year 2021, respectively, as compared to $6 $8 million and $32 8 million for the same periods in 2021.
The rise in R&D expenses was in 2021 and was primarily driven by increased spending related to clinical development across each of our phase II programs during the year.
This followed a period in 2020 during which we temporarily paused patient enrollment in three of our four then ongoing phase II studies contributing to less than expected R&D spend during that year.
We reported G&A expenses of $5 1 million.
And $20 1 million for the fourth quarter and full year 2021, respectively.
As compared to $4 8 million and $19 5 million for the same periods in 2020.
Finally, we reported a net loss of $19 6 million and $74 9 million for the fourth quarter and full year 2021, respectively.
Compared to a net loss of $11 5 million and $50 $1 million in the same periods in 2020.
I'll now turn the call back over to Andy.
Thanks Ashish.
As we approach a steady cadence of important data readouts. The first of which is expected in the next few weeks, we look forward to moving into our next stage of growth as a company we're.
We're pleased to be well positioned both financially and operationally to continue to advance our pipeline towards the patients desperately need better therapies we.
We are happy to begin taking your questions now.
Thank you if you'd like to ask a question. Please press star one on your telephone keypad if for any reason like to remove that question. Please press star followed by Q.
Wassy question Crestar one.
As a reminder, if you are using a speaker phone. Please remember to pick up your handset before asking your question, we will call to briefly ask questions are registered.
The first question comes from Chris Raymond with Piper Sandler. Please proceed.
Hey, Thanks for taking the question I just have maybe one and then one follow up so I guess just guys.
Hum on the 295 data.
You, obviously had the DPM data coming first that's next month.
And then the fibromyalgia data, obviously I think you said Andy it's now in July or August . So you know this question's come up before but I just wanted to maybe ask it again since we're so close here.
Two of these events.
These are obviously different disease states.
But there are similarities I guess in terms of the clinical measure within our S and what's considered clinically relevant maybe just frame for us the differences between these two programs and why maybe or why not investors should see the outcome and DPM is a direct read through to fibromyalgia.
Yeah. Thanks, Chris.
Great question.
Fortunately.
One that will have a limited.
Shelf life, because as you pointed out I think that between the data from the two studies.
It is about three or four months and so we will know the answer before too long, but I think I think it would be helpful to frame either he suggested that the key differences and similarities we of course think there will be some read through but we do not think it's the absolutes read through there. There are some important differences I think you know the.
The difference between the two conditions really is that obviously DPM begins as a peripheral neuropathic conditions in fact, it's classified by FDA.
Plus a fight in their chronic pain guidance as the peripheral neuropathy. It clearly starts with nerve damage in the periphery and as I mentioned in my remarks, the kinds of centralization of pain processing abnormalities that our mechanism targets take a while to become established and VPN.
There isn't a fibromyalgia based on imaging and based on <unk>.
Studies that had been done by others in the disease State, we think that the central pain processing abnormalities kind of characterize the conditions are an inherent part of the condition. So there's some different underlying biology of course, we tried to take the kinds of that study design, but nonetheless different underlying biology, there's also different extent to which I think are precedent.
Data informed specific elements such as dose we think we have good clinical proof of concept in both indications, but obviously, we're looking at two different doses in fibromyalgia versus one in D. C and so I think those are a couple of reasons why.
Both biology and dosing wise.
There's less than 100% read through between the two indications substantially lastly, I think I would say.
But clearly on the similarity side as you mentioned some of the study design elements are very similar and also of course ultimately our drug as we think acting in the prefrontal cortex to establish better.
Poland modulation of abnormal and in the brain. So there's a clear similarity with with which part of the brain where targeting so yeah. I think we as we've consistently said we believe there is read through but we do not believe there is a complete read through there is still a reasonable amount of independence between the risk in these two indications.
Thank you for that and maybe just a quick follow up.
Andy I think you highlighted with the timelines.
And in your prepared comments I think I heard $4 58, the cognitive impairment data could now slip into next year.
Can you maybe.
Put some color around that is what's what's the what's the driver for that.
I think the last update it was.
End of year thing or maybe I'm misreading.
Okay. So Chris.
It partially right I think in our last quarterly call. We were saying end of year. When we did our portfolio day in February and kind of updated across the pipeline. We provided a modification to still potentially possible by end of year, but may may move into Q1 as well. So I think it's somewhere between the two right now the reason for that that we outlined.
The portfolio day, an item I very briefly recap that in my remarks today, but I can explain it more is we saw probably not surprisingly.
After Thanksgiving.
Omicron wave starts to take effect in the U S.
Sort of broader environment, we did start to see a slowdown in enrollment now you often see a slowdown in enrollment in clinical trials over the holidays anyway.
We do think it was exacerbated a little bit by omicron potentially affecting patients' willingness to.
Enrolling study, but potentially also we know in some cases affecting clinical trial sites. So of course that issues with staff, having a quarantine or isolate and so on.
We were tracking that of course through January and when we did the portfolio day in February we provided the update I think as I mentioned since then it looks as though enrollment has returned back to its prior level.
So I think we're now still comfortable to guide that.
That slowdown caused a delay, but theres not an ever increasing delay. So therefore, we would expect to have data again potentially by the end of this year or into Q1 of next year.
Got it thank you.
Thank you Chris. The next question comes from Charles Duncan with Cantor Fitzgerald. Please proceed.
Yeah.
Hi, yes good.
Good afternoon, Andy NFC.
And team congratulations.
And progress in the chronic pain programs looking forward to seeing that data soon.
I had a couple of questions on.
<unk> hundred 92 sides in DPM and in particular I just wondered if you could.
For us a little bit of.
Perspective.
What is 0.5 to 0.7 N. R. S difference means in terms of clinical meaningfulness in terms of your feedback from investigators and clinicians.
Okay.
Yes, certainly Charles.
So when we talk to clinicians about what is clinically meaningful in pain studies or chronic pain studies in general.
I think it is a little bit of a complicated question and they have a couple of different ways of thinking about it so on the one hand.
A lot of times when people are asking they're trying to get at what you. Just described which is what degree of separation between active and placebo is considered meaningful I think that generally comes in the range that we just described.
5.7, or higher would be clinically meaningful I would say that a lot of pain clinicians and Richard Radcliffe was on our portfolio day. It was one of them would say you know I really want to be convinced that the drug is not the same as placebo I want to see statistical significance in the separation.
Some margin, but I'm not too focused on actually exactly what that is.
Because I really because I know that the clinical study environment is an artificial environment. We know that placebo effects are a significant issue and I think in addition to field now generally viewed as placebo and drug effects does not always purely additive, but actually potentially somewhat overlapping phenomena and so so so that's sort of tends to be the answer.
On separation.
Can you then talk about.
Other indicators of clinical meaningful clinical meaningfulness.
We'll say well what I would look at generally if I'm deciding whether to give this drug to a patient as the reduction from baseline since that's what a patient will experience in the real World and then potentially also as you're considering a population or what are they might go to therapies that I'll prescribed frequently what's the expected response rate for a given.
Our minds of pain reduction and 30% is a threshold that's commonly used what percentage of my patients would I expect to see getting a 30% or so reduction in pain and I think those two measures of change from baseline on average and then the responder.
The responder rate.
Put into context of the safety and Tolerability profile and of course, the Bachelor and the safety and Tolerability profile.
More probably margin there is or potentially lower the bar would be for clinical meaningfulness on the efficacy side. Because there are so few options out there that provide a good risk benefit profile to a lot of these patients. So it gets a little more nuanced and I think that.
Our sensors.
As we look at the data will be it's important to show separation from placebo, but there's also some focus in the real world on the magnitude of response and the consistency of the response.
Okay and response rate picked on site and then second question regarding <unk> and this kind of points to next steps, but just regarding the definition of the period for chronic vacation or centralizing the pain being four years I'm sure it's not a hard hard.
In time.
Maybe three year patients have that as well, but how how did you find that how do you practically define that in terms of symptom presentation. How do you. How do you ensure that you know the majority of your patients have had.
No.
Sufficient time to see centralization of the pain is it true prescribing pattern or how is it done in this trial and how would you anticipate it going forward.
It's actually quite a tricky question Charles there, but a lot of people who've tries to use clinical measures to characterize the centralization of pain and of course, there are some symptoms like hypersensitivity Japan.
Allegheny and so on that that should be characteristic of centralized pain.
It tends to be a little difficult, though using kind of a real pain measurement instruments to come up with.
Good consistent.
Screening approaches so we don't have a lot to work with there I think in addition, there's better characterized timeframe for some kinds of centralization, but sort of amplification of pain and spinal cord. For example, it might start to happen around six months, but for the kind of chronic pain that where our quantification of pain that we're looking at involving.
The critical Olympic parts of the brand, including the prefrontal cortex, and maybe does that take longer.
And then the changes in the spinal cord due its not an area that's been extensively studied.
I think we are.
Turning to advanced the two ideas in parallel so on the one hand and the study we're really just using duration of disease and of course patients have to have enough pain.
The magnitude of pain to get into the study and then I think in parallel working with our scientific Advisory board working with others to try to clarify in advance the understanding of exactly.
What there could be that is a sign of the prefrontal cortex hypofunction that our mechanism can work against and it's not just using using the passage of time as a way to try to get to get to those patients. So there's a little bit of a work in process and it has I think for the field in general better relatively difficult area to sort of.
Produce a clear are measurable biomarker or something of that nature.
Yes, but it's a really interesting hypothesis last question in terms of next steps could you imagined.
This particular phase to be could be one of two potential pivotal studies or would you anticipate.
Wanting or needing to conduct two additional pivotal studies should the data readout cleanly and you move forward and in.
DPM.
It certainly I think possible that this data could serve as a pivotal study we did design trying to follow as far as we could be their requirements that had been previously laid out by FDA for chronic pain.
We didn't meet with FDA in advance to you know to clarify or confirm that so I would say it is a possibility we consider it really an upside scenario.
And even if it doesn't turn out to be the case that this could serve as a pivotal.
Certainly give us a very good guide as we design our pivotal since we'd expect again the designed to follow very closely our phase III.
Perfect. Thanks for taking my questions. Good luck with the upcoming data.
Thanks Charles.
Thank you Charles the next question comes from Ritu <unk> with Cowen. Please proceed.
Hi, guys. Thanks for thanks for taking the question.
The fibromyalgia trial, Andy you mentioned Youre looking at the 50 and 150.
On that score.
<unk> analysis plan was otherwise very similar to the DPM study, that's going to be reading out.
Next month can you talk about I guess, the the primary analysis between the 50 and the 150 in fibromyalgia is it going to be sort of a blended analysis versus.
<unk> versus placebo or.
Are you taking to look at taking them alcohol between the key difference.
Thanks, Ritu, yes, fibromyalgia, I think it's $50 100, or the two doses the one five.
For PTSD.
So yes, hundreds look I don't think at this stage, we really want to.
Get into too much detail and our statistical analysis plan I think it is certainly all pre specified and clearly laid out.
I guess as a main objective I would say we are interested to see which of these two doses performs better with a view to then what would our strategy would be in phase III. So I think I'll just restrict my comments there.
Wouldn't expect anything out of the ordinary and.
Everything is certainly will be very clearly pre specified in our in our SAP Hayward for just not sharing too many details about the S right now.
Okay, and then you made a very intriguing comment about other pain condition.
Terry.
With with unmet need with rationale can you talk about some of those conditions that you're at least considering.
Especially the ones that have a rationale around NMDA modulation.
Yeah, absolutely so.
You know a lot of pain conditions will have a rationale based on simply the experience a prolonged pain, causing some of these are chronic abnormalities.
It is a fairly wide open.
I think that we will be looking at the data from these two indications to try to help us prioritize.
Certainly there are other types of neuropathy that we're very interested in and we have conducted preclinical studies and published preclinical data in some of those in particular in chemotherapy induced neuropathic pain, where we published preclinical data in the last year or two and I think on the muscular skeletal side.
We are certainly interested in a range of different conditions, including osteoarthritis and so on I think I think where we go and highway prioritize those indications will be driven somewhat by by the data that we see in these two studies.
Got it and very last quick question.
Is there anything significant in the.
Delay in screening start for the 150 milligram PTSD study, but that was that COVID-19 related.
Were there any were there any IRB issues et cetera.
Yeah. Thanks Ritu.
Our entire be issues, but again like I said, we actually had everything in place on our side.
And with the key external partners to operationally be ready. It really was just driven by taking not very much longer obviously, just a few weeks longer to get the first wave of sites.
She says and up and running it's hard to tell to your question what is the Covid related delay at this point because as.
As I mentioned, the Covid has impacted clinical study sites from particularly a stopping point of view.
So there is that as a backdrop to everything.
There is in the U S. Obviously, you know reasonable amount of other studies.
And that's a change from a few years ago, and I think a welcomed one because it shows a much greater attention on PTSD and many other therapies that are being developed but there are a few more studies out there and so it just means that the process of prioritizing the sites.
It's a little bit more complex because there's a few other studies out there. So it's probably a combination of those things not really very.
Significant delay, we don't think and we look forward to getting up and running and screening.
Great. Thanks for taking all the questions.
Thanks Rajiv.
Thank you Richie.
The next question comes from Gary Nachman with BMO. Please proceed.
Okay. Thanks, guys also on 292, five will you have to separate end of phase II meetings for each of the indications and DPM and fibro or will it make more sense for them to be considered together when planning the phase III program.
And if both fibro doses, the 50 and the 100 milligram show efficacy or the 100 milligram is better since.
Since DPM is just 50 would that complicate going for a single chronic pain indication with 295.
Yeah. Thanks, Thanks, Gary.
So on the first point around the meeting.
Were planning right now to have two separate FDA interactions.
We think it probably makes more sense to keep moving with DPM as opposed to waiting for fiber data.
Given the likely timing of FDA meetings and fiber data, though we certainly wouldn't anticipate kicking off a DPM study before we had seen the fiber data and would be able to make sure. If there were.
There wasn't anything that would inform the protocol that there would be time to incorporate that so I certainly wouldn't take away from that it will be rushing to too far ahead with VPN, but we do think it makes sense to meet separately and capture a little bit of the timing upside.
On VPN.
With respect to the ultimate question off label and dosing.
It's it's difficult to say I think that would be a question to discuss with FDA I would say the pasta a broader label is something that we would like to clarify with the FDA. It was we believe one of the reasons why the prior chronic pain drug development guidance was actually pulled back.
Not many sponsors had availed themselves of the framework that was in that guidance for achieving broader label language.
It's possible that there are some different thinking that FDA has on that and I think it would be difficult to comment on whether different doses being optimally affective in different indications.
Would be any kind of a challenge there I'm not sure I would foresee that being a challenge but.
I think that whole question would be something that we'll watch we'll discuss with FDA.
Yeah.
Okay great.
And then for four or five eight and cognitive impairment what do you think the rough split will be on the 100 patients between Parkinson's in lewy body dementia.
I know you've been asked that in the past, but maybe what you're thinking at this point.
And any issues from Covid with those patients.
Either patient group.
And then just explain a little bit more what youre, hoping to show on the efficacy side in terms of what kind of signal, we might be able to see.
Yeah. Thanks, Thanks, Gary So I think on the split we don't have a very specific preformed goal around that split.
And in terms of the expectations.
It depends a little bit if you can look at the different prevalence, but you also have to consider who's likely to step forward and participate in our clinical trial, and then possibly inclusion exclusion criteria. So other than saying I think we would certainly hope that there is a reasonable representation of all of the different groups of patients and that's Parkinson's NCI.
It looked like an enrollment with the omicron wave over December and January it's a little difficult for us to tell exactly how much of that as it relates to do with patient behavior, though versus sites. But then also have issues with with stopping as I mentioned, we generally been a little we're cautious and restarting the study and it didn't reach.
Darts it until after the vaccine rollout in 2021 to have more vulnerable populations, including obviously those over the age of 65. The age range. In the study is 50 585 with the majority of the subjects, we'd expect would be towards the higher end of that range and so we we I think generally been.
<unk> sensitive to that and how we've set up the protocol and tried to make the site patient interactions as efficient as possible and we haven't had I think any sense that there there is an issue.
The patients are willing to take part in the study and.
Other than that slight slowdown over the holidays, it seems to be going well.
In terms of efficacy signal the.
Yeah, the the efficacy and points that will be paying the most attention to our series of six different neurocognitive test things like the growth amazed the two back to ask the international shopping list and so on that are fairly well known have been used in cognitive studies quite widely and our target date of measuring different domains.
Executive function working memory and attention in particular that are known to be NMDA dependent phenomena also characterized.
[noise] types of cognitive impairment you see in Parkinson's disease, and I think we're really looking on those different tests for a signature of how does this drug improve cognitive performance and these patients and see what that profile looks like and I think that will then help us as we move forward into phase two be in phase three studies as we're trying.
To select the right endpoints, which will need for those studies, which will have to be more straightforward easy to implement cognitive tests and also probably some measures of function and we can come to the recommendation on how to do that based on the profile that we see with these more sensitive more specific neurocognitive testing.
Okay. That's helpful and just last quick ones Crunchies uhm, how much more flexibility do you have to tap into the credit facility with key to how much is left on it after.
Taken down in the last 10 million.
Yeah. Thanks, Gary Uhm, so the entire facility was $50 million. The first tranche, we took down shortly after signing a $15 million we've taken down in March and I noted another time that rain that leaves 25 million that would be accessible upon.
Positive data milestones in mutual agreement with the lender.
Okay, great. Thank you.
Thank you theory. The next question comes from Mark Bittman with S. E. B Leerink. Please proceed.
Alright. Thanks for taking my question is Rudy on the line from work. So I have a question regarding a 458. So there are several other M D products entering missed a study <unk>.
For calling me to impairments can remind us about and then my 450, a <unk> have you done to support a U F C N be syndication and how could it be differentiated what what's this other than M. D. Upon us.
And the technique may remind the these continuation here, so far and I'm going to U P. N trial, there any new 56 <unk>.
Okay, great. Thank you uhm, yes, so let's start with four.
458, so the evidence for efficacy we have here of course, so far is all preclinical aware in our first and patient study right now the most I think interesting piece of preclinical evidence that we have is from a study in non-human primates using a neurotoxin called M. P. T P to create Ah cognizant.
Deficit.
It's caused by dopaminergic cell depletion and so are very similar to what is seen in Parkinson's disease.
And in that study and we saw a marked and and.
Sustained cognitive deficit that was created by this neurotoxin, but that was largely very rapidly reversed by it's just a single dose of N Y X four or five eight.
Cross a range of different measures of cognitive performance and the improvement with sustained actually for a few weeks before returning back to.
Impair impairment level. So I was very encouraging very exciting preclinical data. We also have some data from rodent models various different kinds, but that was probably the most translatable preclinical data. So we were very excited to take the drug into the clinic. We did the site and it was a conscious decision that our first study in patients would be.
Be robustly designed double blind randomized placebo controlled study of 12 weeks duration, partly because.
We couldn't convince ourselves that any kind of shorter or less robust task would really be meaningful.
So as a result of that you know as you mentioned there are a few other compounds out there.
That are targeting NMDA modulation in cognitive impairment, but so far the only dancing machine from any of those as from these smaller I often open label studies and so it looks promising but it's difficult to say I think really what the degree of of efficacy is so in terms of differentiation of course, we know more about our call Panther.
But those others, we certainly know with our compounds that the safety and Tolerability profile has been very good across all of our clinical stage compounds.
All of the studies so far that we've conducted so we would certainly hope that that would continue and in addition, I think the the targeted effects that are drug seems to have on areas of NMDA Hypofunction. Many may enable a.
Fairly clean you know focus our ability to improve cognitive symptoms without impacting anything else. So I think I think that's as much as we can really say because we don't know a lot of bikes those other compounds, but where again, mostly focused on four or five eight and and certainly think that the study that's in process will be a really good.
First off of what the drug can do to improve cognition.
With respect to 295, we haven't talked specifically about discontinuation rate 42925, and D. P. N I think what what I would say is we of course had projected Ah plans discontinuation right at the beginning of the study and actually we projected to before the pandemic because technically the study kicked off right before the patent.
And we have seen discontinuation broadly in line with that so I think from an operational perspective, we've been pretty comfortable with either study has has proceeded.
Okay, that's very helpful.
Thank you Mark. Your next question comes in January two insecurities. Please proceed.
Good evening. This is the last one for you and thank you for taking my questions I have to first on the 783 any notable differences India P. T. S D patient screening criteria that you've plant in the seat next month for that 150, Meg those that you've learned from initiating the 50 uhm milligram dose.
And then second under 2925 pending data and D P and they're probably going to college out would you consider a partnership for dependable pivotal studies or or your development plans to strictly internal and is it possible that you could have b P. N data as early as the a N meetings next <unk>. Thank you.
Okay. Thanks, a lot so 783, I'll I'll I'll take the 783, and then I'll have a she she actually answer your question on 295, Iran partnerships for 73 screening.
Sure.
Trying to make sure that the two studies and P. T S D R.
Essentially the same so there are very minor differences are really the dose obviously is the principal one.
The the the main design elements, particularly in terms of inclusion exclusion criteria, we want to be the same so are as close to the same as possible. So I don't think we've learned anything yet and the 50 milligram dose that we weren't expecting to see I think that studies been progressing well in.
So we we we certainly we haven't made any changes to 150 milligrams protocol and I do think thrive both of those studies, where are we to make any tweak store modifications, we would likely make them to both but we haven't seen the need to do that yet, but she shall I'll. Let you answer the 295 partnership question.
Yeah. Thanks, Andy you know I think we've been pretty clear and consistent before that that we believe that if if we see the third big profile that we hope to show in in in the face to be that this is Ah Ah Ah pain therapy that has a broad application.
And would probably be best best be served with the assistance of a commercial partner with larger more will establish commercial capabilities and and in front of me I think that would be something we would explore at some point.
Or two commercialization, we have a team that is well poised I'm prepared to take the next steps in development. After phase to be we are already underway with those preparations and is Andes noted before the phase three we don't anticipate would be dramatically different from from what we've already done it.
It has to be we're always open to partnerships that can add value to the programs that can advanced these programs toward patients more rapidly or more responsibly.
And those that that after offer optimal value to shareholders. So will engage in the wake of the data and an evaluation of whether you know.
Near term partnership opportunity Ah represents that but high value juncture or whether that's something down the road and on the R&D path, but I'm certainly open to it.
Great. Thank you for that clarification.
Thank you. The next question comes from Laura to go with the.
Security. Please proceed.
Good afternoon. Thanks for taking the question and I might just ask this one a little bit differently than previously asked but I guess with reset the 295, when you're thinking about <unk> portfolio allocation I'm wondering how much of a consideration safety data might come into play when we get the D. T N N F N Readouts, obviously efficacy is gonna be essential.
But many chronic pain agents have rems program. So I'm curious if there's anything in the face to read at that might be informative in terms of differentiating 29825.
Safety Tolerability perspective, and then I have one follow up for Ya.
Yeah Tomorrow, Yeah, I think you're right they're definitely it is a concern in general with the current chronic pain treatments about some some of the side effects and safety issues and there are a range of those and then they range from you know some some things that are more serious choose some things at all.
Are you you know when he left Syria, very common and can be quite bothersome for patients like dizziness or driving us and then also some issues with with dependence, obviously and and abuse potential. So I think those are the main things that will be looking at the data of course as usual will be looking to make sure you know.
There aren't.
Any concerns with serious or severe adverse events, we haven't had those obviously in our prior studies and so that'll be an important thing to look at but also then even in the mild and moderate you know adverse events or anything that is you know that is that is more common that is a concern. We we we again expect and hope that that will not be.
It takes I think generally are mild and moderate adverse event profile and prior studies has been very similar to what we've seen in the placebo group and so we would certainly hope to see a continuation of that that would be for those two findings together I think would be a huge you know potential differentiator provided of course that.
We see a good efficacy as well, but that would be are you really important for.
Persistence with therapy for the willingness of physicians to prescribe broadly out of course for patients to perceive that there's a risk benefit from their point of view.
An abuse potential and so forth. We do you know openness data you do look quite carefully at any of the adverse events that are reported to determine that there's no underlying potential for you know for for abuse liability or anything like that so that's another thing that we'd be looking at as well and again in the past we haven't seen anything there.
So we'd we'd be hoping for is clean bill of health as possible on those three areas and if we if we got that that would as you mentioned that would certainly be a very important factor in this disease area.
Okay. That's super helpful and <unk>, maybe that's the quick follow up and would just be you know in a best case scenario you get positive Readouts from F. M from D. P and while the 73 program is progressing I guess, you know fast forward I had a a year or so how do you prioritize pivotal advancement if you're successful.
With 290, 573 should we presume all the indications are proceeding or would there be kind of a more closer assessment and allocation of resources in terms of the dancing programs. Thank you.
[noise] thankful right, Yeah, I I would have certainly assume that we will we will make it happen in terms of you know finding between is Ashish mentioned external partnerships and of course further financing by ethnic we will make the the make it half.
And it the pipeline can can inbox you know so there there shouldn't be any concern about.
Having to prioritise or reduce the number of studies that are in process or anything like that I think quite the country I think as I mentioned in my remarks, we would view positive data and VPN and and or fibromyalgia is hugely catalytic for the company.
And we went absolutely expect to move forward as quickly as we can in in in both of those indications and continue to keep the rest of the pipeline M. P. T S D and cognitive impairment moving as well and in addition, I think we do still want to make sure. It is understood by investors in the longer term and the timing of this.
Is probably more of a of.
Have a question because I think that would probably not be an immediate priority in the way that moving to 95 into phase three and making sure that 73, and four or five eight keep progressing as quickly as possible would be but in the longer run we do have over a thousand other molecules in our P. I N D pipeline, we still have I think a lot of potential with our mechanism.
That we can apply in other areas and in the longer run. That's also something we would we became too to find out.
Thanks <unk>.
Thank you mirror. The next question comes from miles Minter with William Blair. Please proceed.
Hi, This is Sarah on the line for miles. Thanks for taking my questions I've got two quick one first can you come in and if you're monitoring the blinded data in a chronic pain trials and if so are you seeing an improvement in pain scores from week to week 12, and then I've got a second after that.
Thanks that Sarah So no no we are not scrutinizing, the blinded data and trying to draw conclusions from that so that's a fairly quick answer I think we'll we'll draw the conclusions when we eventually get to see the the online debate.
Got it things and then the second one was was the powering for the secondary outcome measure and fibromyalgia study factored into the study design or was that study powered only for the primary endpoint.
Yeah, the the the power and was primarily for the the primary endpoint.
Got it thank you.
Okay. Thank you.
The next question comes from them, so far as you with each C. Wainwright. Please proceed.
Afternoon, and the and the teams is months on full ROM. So first you have forgot 22925, and painful deacon and fibromyalgia [noise] do you think returned to more physically active work for some patients as the pandemic receipts.
Has kind of a meaningful bearing on average daily pain school was paint on walking.
And is there something you want a drink.
Thanks, a lot.
Yeah, I I don't know that we've heard you know widespread reports of that as a phenomenon that would hit in a specific way in within a specific you know three months time period for each.
Each patient that is obviously at the study you know the course of the pandemic for March 20th 20 to today has I think been quite different for different individuals and different types of jobs, including those that aren't working in in different parts of the country. So I think it's very difficult to kind of generalized Ah.
On on that.
Some some people have been working as normal somehow not and and at the time of course has been very different we haven't heard anything that's been a consistent concerned about a widespread or mainstream change in activity patterns that was kind of synchronized enough to cause of concern in a clinical trial. So it's it's a good question.
But it's not something that we have really been concerned about it or that's been put on our radar as a concern.
Okay. Good to know and then secondly was there a reason you staggered the initiation of the 2783 trials. The two doses I'm kind of concerned about the patients and no 150 milligram dose knowing there on a high dose.
His previous patients or you know when they all blinded to this.
[noise] so yeah, so the the.
The.
The process will be at each site that only one of the studies will be in process. So it won't be something that's you know that's a factor we don't think an an enrollment of the patience or anything like that I think in terms of the staggering it it it.
It was partly to do with the fact that is cause cause you may recall going back to kind of when we kicked off the study we already have tested the 50 milligram dose we were already anticipating that we will move forward with that dose and we were able to move more quickly we have that.
Among other things just fairly mundane matter of actually having existing physical supplies of the drugs ready to go and things like that so so we certainly felt as though it would be more efficient and quicker to start one study as quickly as possible and then the other study later and it made sense to speak with him. She comes from this way.
Cause of that because of that [noise].
Factor with the investigational product.
So yeah. So it was it was partly a decision and partly actually more an upside that we were able to move more quickly with the 50 milligram dose.
And so far as I mentioned, although you know they were staggered and although the 50 milligram 150 milligrams study, we think will start screening in April we really don't have any longer term concerns I think it's taken slightly longer than we had thought to get some of the sites activated but we don't see we don't really have a concern at this point.
On the most important goal which of course is to is to get the the majority of the sites up and running and get the study enrolled in complete it.
Okay, great. Thanks for clarifying Uhm, and if I can squeeze one more and I was interested in Parkinson's patients and you know a large percentage of them ripple pain. So I was wondering if you've experienced pain reporting by U P. D patients in that trial and if you think.
You know any significant paint improvements are possible M. P. D patients with 458, and giving you have kind of a similar hypothesis that we've hypoactive regions, the prefrontal cortex being taunted with 2925.
Yeah. It's a interesting question was we we aren't obviously we're not.
Well I shouldn't say, obviously, we were not screening for the presence of pain in the study of course, and we don't have a specific measure for soliciting changes in pain in that study, but it will be interesting. It's the kind of thing that there may be reports up in the study we may get some sense as to whether that sort of overlapping.
This so yeah, it's an interesting interesting and you're gonna have to look at it.
Fantastic Thanks for taking my questions root beer in.
That was.
Thank you we have no further questions at this time I would like to turn the call back over to Andy for any closing remarks.
Thank you usually and thank you to everybody on the line for your thoughtful questions. We appreciate your time and attention and we wish everyone a very pleasant evening.
That concludes the afternoon one corner in your in 2021 financial results Conference call. Thank you for your participation you may now disconnect to your line.
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