Q3 2022 Aptinyx Inc Earnings Call
Executive Officer, who will discuss our business and clinical development progress then Ashish Khanna, our Chief Financial Officer, and Chief Business Officer will review our financial results. In addition, Catherine King Senior Vice President of clinical and CMC operations is on the line for the Q&A portion of the call.
I would 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.
Thanks, Pat and good afternoon, everyone and thank you for joining us on today's call.
Last few months, we've seen several major updates to our pipeline of clinical stage programs and.
In August we announced that Nyse's 295 did not meet its primary endpoint in our phase <unk> study in fibromyalgia and that we do not intend to focus our current resources and further development of <unk> hundred 95 in chronic pain.
Does that have come with obviously disappointing and underscores the significant challenges that exist in chronic pain drug development.
Despite our disappointment in that result, we continue to have confidence in the potential of the remaining programs on which we focus our energy and resources.
We export five eight and cognitive impairment and NYSE 783 in PTSD in opioid use disorder.
We've always viewed our platform and pipeline is providing diversification of clinical risks, while our drugs are all derived from a common chemistry platform focused on NMDA receptor modulation.
MBA receptors play different roles in our different clinical indications.
Therefore, our clinical stage pipeline provides multiple shots on goal with largely independent clinical risks and we're looking forward to all of our remaining data readouts expected in 2023.
I'm happy with the progress we've made over the last few months and positioning ourselves for these <unk>.
In August we completed enrollment in our phase II study of NY X 458, and cognitive impairment and expect to report data from this study in the first quarter of 2023.
This exploratory study is designed to evaluate the role of NY X 458, and improving cognitive function in patients with mild cognitive impairment or dementia associated with Parkinson's disease dementia with lewy bodies given.
Given the huge need for novel therapies. In these disease areas are positive signals should enable us to move into a larger study that we hope could serve as a pivotal trial and with physician NY X 458 is one of the few late stage development programs for Parkinson's cognitive impairment.
In addition, we've made steady progress on enrollment in our phase <unk> study of <unk> 73 in patients with PTSD and remain on track for a data readout in the second half of 2023.
NYSE 73 is also being developed for the treatment of opioid use disorder through research funded by a recently finalized $5 6 million grant from the NIH awarded to researchers at Yale University School of Medicine.
Together with Yale we expect to commence a phase one study of NY at 783 by the end of this year and completed in the second half of next year.
Importantly, we expect our existing cash resources of over $65 million.
To provide operational runway into 2024 and support the data readouts from each of our clinical development programs.
Let's discuss the phase III study of <unk> 458 in cognitive impairment in more detail.
The study completed enrollment in August with a total of 99 patients. The majority of these patients have a diagnosis of mild cognitive impairment or mild dementia associated with Parkinson's disease with fewer patients diagnosed with dementia with lewy bodies.
The study is randomized placebo controlled and double blinded and we will evaluate 30 milligrams QD of NY X 458 versus placebo over a treatment period of 12 weeks.
Since this is the first time, we are evaluating NY export five eight and patients. The primary endpoint is safety and Tolerability and the efficacy endpoints are exploratory.
We're taking a thorough approach to characterizing the efficacy profile of NY X 458 by incorporating a range of cognizant of assessments of secondary and exploratory endpoints each.
Each of these endpoints is designed to measure specific aspects of cognitive function.
The first set of endpoints is based on six computerized neuro cognitive tests provided by <unk> a leader in brain health assessments. These include the following test continuous paired associate learning.
Broken Mays.
Identification test International shopping list and one back on to back test.
This battery of tests was chosen because they focus on specific aspects of cognition that are impaired in Parkinson's disease.
We will assess changes from baseline and versus placebo in each individual test as well as a cognitive composite score for sub scores, reflecting the different cognitive domains assessed by the test.
Ignorant of composite score will combine the results of all six tests and provide a key measure of the overall cognitive effects of NY X 458.
The sub scores are each based on different subsets of data from the six neurocognitive tests. There is a sub score for each of the following cognizant of domains.
<unk> working.
Working memory.
<unk> <unk> memory and executive function.
In addition to endpoints based on the neuro cognitive tests, we're also measuring endpoints related to everyday function.
The <unk> 12 is a simple instrument that measures the patient's assessment of their performance on 12 functional abilities related to cognitive performance.
<unk> is another instrument.
That is the extent to which cognitive impairment from Parkinson's disease, Parkinson's disease impact 15 activity of daily living.
We're also measuring clinicians patients and caregivers assessments of the severity unchanged and overall Parkinson's symptoms using the CGI S and civic plus scales.
Together all of this data will enable us to determine whether NY X 458 shows a signal of improved cognizant performance I will also give us a sense as to what extent this improved cognitive performance impacts patient function.
Our goal is to assess the nature and magnitude of the effect of <unk> 458 in order to guide the design of larger late stage studies.
We hope to see a signal on overall cognitive performance and associated signs of functional improvement that could then be confirmed in future studies.
Our immediate plans if the data are positive would include meeting with FDA to discuss the requirements for an NDA in this area and the design of our next clinical trial.
Mild cognitive impairment and dementia associated with Parkinson's disease represent a significant area of unmet medical need and accordingly commercial potential.
We believe this study will offer key insights and to NY X 40, <unk> therapeutic potential in this area and that the value creation from positive data there should be substantial.
We've worked hard to bring this study close to the finish line and we look forward to reporting these results in Q1 of next year.
Let's move on to <unk> 73, and.
<unk> 708, three is currently being evaluated in a phase <unk> study in patients with post traumatic stress disorder or PTSD.
This study is evaluating 50 milligrams of NY at 780, <unk> QD versus placebo in approximately 300 PTSD patients over 10 weeks of treatment and utilizing the change in caps five total score as the primary endpoint.
Key secondary endpoints include clinicians and patient global impression of disease severity and improvement.
During Q3, we've completed activation of the full complement of study sites all of which are located in the U S and we've seen our enrollment progress at a steady pace.
As such the study remains on track to report data in the second half of 2023.
And we had 73 is also an early clinical development of a novel therapy for the treatment of opioid use disorder or <unk>.
Last week, we announced the Finalization of a $5 6 million NIH grant awarded to our research collaborators at Yale University School of Medicine.
The grant was issued under the NIH is helping to end addiction long term heal initiative and we will fund an upcoming phase one study as well as the subsequent larger proof of concept study to be initiated once the phase one study successfully completed.
Phase one drug drug interaction study, which is being conducted by reached by the researchers at Yale is set to begin by the end of this year and is expected to complete in the second half of 2023. This.
This study is an important safety and regulatory requirements, enabling later stages of development.
It's an inpatient study that will assess the safety tolerability and pharmacokinetics of NYSE 708, three in combination with Oxycodone and individuals who use opioids.
The primary outcomes of this study will.
We'll evaluate a variety of safety related measures.
Andre outcome measures will evaluate opiate withdrawal and symptom scales.
Preclinical data from NYSE 703 in models of <unk>, which served as the foundation for the ground and the Phase one study will be presented at the society for neuroscience or <unk> annual meeting in San Diego next week.
We are excited for this phase one study to commence and are pleased to be expanding the clinical evaluation of the therapeutic potential of <unk> 73 in a capital efficient manner.
I'll now hand, it over to Ashish to review our quarterly financials.
Thanks, Andy.
Starting with the balance sheet, we ended the third quarter of 2022 with $66 $5 million in cash and cash equivalents compared to $106 1 million at the end of 2021.
During this past quarter, we completed a handful of onetime payments related to closeout of our phase III studies of <unk>.
What extra nine to five in chronic pain.
Securing manufacturing capacity.
Payment of major insurance policy premiums and.
And other corporate expenses.
As these were planned and nonrecurring payments during the quarter.
Cash burn over the third quarter of 2022 was higher than our projections for expenditures going forward.
Based on our projected expenditures through the remainder of this year and through 2023, we anticipate our cash cow, our existing cash balance will support operating runway into 2024.
As Andy mentioned this runway should be sufficient to enable data readouts from each of our ongoing clinical development programs.
The majority of our spend during the quarter centered around research and development related to our clinical studies.
<unk> expenses were $10 million for the third quarter of 2022.
Third to $16 2 million for the same period in 2021.
The decrease in R&D expenses was primarily driven by the completion of our phase III studies of <unk>, two five and VPN and in fibromyalgia.
We reported G&A expenses of $4 6 million for the third quarter compared to $4 9 million for the same period in 2021.
Finally, our net loss for the third quarter was $15 3 million compared to a net loss of $21 2 million for the same period in 2021.
I'll now turn the call back over to Eddie.
Thanks Ashish.
Sites it to move into next year with the data readout from our phase III study of NY X 458 in cognitive impairment in the first quarter with two readouts from NYSE <unk> expected later in the year.
We're happy to begin taking your questions now.
If you would like to ask a question. Please press star followed by one of your telephone keypad. If you are using you'd like to remove that question. Please press star followed by two.
To ask a question star one.
Our first question comes from Charles Duncan with Cantor Fitzgerald. Your line is now open.
Super Hi, Andy NFC, Sharon Thanks for taking our questions and congrats on a decent quarter of progress.
I wanted to start with a couple of questions on core Friday, particularly along the lines of if you could characterize the patient or the sample that you enrolled in this study.
Are these relatively late stage patients I think you mentioned that they had mild cognitive impairment, but are then stable.
Aldo and <unk>.
Also do you think that ambulation are on time.
On time rates may maybe a compounding variable.
Yes, Thanks, Charles it's Andy.
So they are patients who will have for the most part as I mentioned mild cognitive impairment or dementia at.
At the milder ended the dimension of scale and Thats kind of consistent with our inclusion criteria. We set a range on the Montreal cognitive assessment of 15% to 25, which is pretty much where that lands mci or mild dementia.
As to.
<unk> motor symptom severity, we did obviously try to exclude patients from the study whose motor symptoms were likely to be.
Severe enough that they would interfere with the conduct of the study or with the administration of the cognitive tests, so that would likely mean that.
There is a range of how long these patients will have had Parkinson's disease and how severe their symptoms are.
But we certainly want to exclude patients that where it might confound the measurement of cognition.
Okay and can I assume that they are all remaining.
Relatively independent or are the long term care patients and then I had a question about the endpoints.
Yes so.
They.
With mild dementia.
They may or may not be fully independent.
Obviously, one of the criteria for diagnosing dementia is that there is some impairment in function, but importantly, all patients in the study have to be have to have a caregiver thats available to provide their assessment.
Also support to the patient so even if they are.
Not.
Independent they will have a caregiver in the study with them.
Okay, and then you talked about Cogs state as well as.
Yes.
Assessments of everyday functional.
I'm kind of wondering if you have with paper it or what you are most intrigued with reading out and then when you think about subsequent steps, let's let's assume the study retail positively.
Is there is there a preferred endpoint for alcohol at registration or registration enabling.
Studies, and and what what would that endpoint.
Yeah, Great question so.
Yes.
From from the different endpoints I think as I mentioned, our hope would be that we see an effect on the Cogs date composite score because that would be the clearest demonstration of an impact on overall cognition and then I think we would like to see some evidence of improvement on the activities of daily living.
The question there is with the sample size high sensitive those instruments are but I think we would certainly like to see at least a trend to improvement on the activities of daily living. So those are the endpoints that we'll probably scrutinized most closely and then related to that the reason for that.
In large part is because of the second part of your question, which is what would the endpoints being a subsequent study and we think that there is a range of different instruments that are all validated that could be used in.
A larger study, but they all.
Have some combination of a.
Tests of cognitive function that is more similar to general cognitive function and that it will not be specific to a particular domain.
And then we'll also have some element of.
Functional improvement our activities of daily living included in it so the likely instruments or endpoints for the next study.
Bear the closest resemblance to the endpoints that I just mentioned that we'd be spending the most timely and then thats exactly which one is most appropriate would be guided by the data we see and then by discussions with FDA.
Okay. That's helpful. I will hop back in the queue on this one but looking forward to seeing those results. It sounds like within a couple of months from now.
Yes into Q1, yes, that's right Charles Thank you.
Thanks.
Our next question comes from Marc Goodman with <unk>. Your line is now open.
Hi, Thanks for taking my question is related on a line per month.
How fertile question for 458.
If you only have 30 million rate goes.
The phase Iia study.
So what kind of data will make you comfortable that this is the right dose to move forward and do we expect to start another dose ranging studies before running a pivotal study.
Yeah. Good question. So of course, we will look at safety, which is the primary endpoint and then as I mentioned in the previous answer.
The key endpoint on efficacy to help us determine what effect size, we see and then I think based on that we will decide if any future dose ranging as warranted.
And also obviously discussions with FDA.
The goal of this study with signal finding and we were I think comfortable to do that with a single dose, but depending on the data and FDA discussion, we have not ruled out doing further dose finding in the future.
Got it that makes sense.
How long are you following those patients after the 12 week treatment do you think that would be the right duration two separately.
58 versus placebo.
We will see what the time series that the data looks like.
Our sense was that it would be based on our mechanism based on our preclinical data based on the fact that it's symptomatic treatment versus a disease modifying treatment.
But we'll be interested to see what the time series looks like in this study. We're following the patients up for a few weeks after treatment, but we'll decide the duration of the next study I think based on again based on the data.
Got it that's very helpful. Thanks.
Thank you.
Yeah.
Our next question comes from Myles Minter with William Blair. Your line is now open.
Thanks for taking the question maybe just following on from Charles's question about the ability of these patients to perform the test like I know you're screening in based on the <unk> and CGI S. But.
You also screening impatience on the Cogs State test performance and is there any safeguards that.
It matches that screening criteria a bit.
Mitering payment means they can't perform like the maze or something like that is the safeguards to rule them out of the trial or do you treat that as missing data for this trial.
Yes, like I said miles there is part of the screening processes to try to ensure that patients are able to complete the tests.
So our from a motor perspective, so our expectation would be that for most patients most of the time in the study they will they will be able to complete the tests at least based on motor capacity and if there are difficulties completed in the past that that might be more related to to cognition.
If there was missing data for any reason then in the study then than it would be treated as missing data.
If we're talking about.
Just sort of a modified intent to treat population.
Okay, and then just a quick follow up I know you've mentioned that the majority of those patients will have Parkinson's disease Lewy body dementia can you.
Classify those numbers for me.
Because I know that a lot of these question as a Parkinson's disease specific in their activities daily locks and what they were impacted and may be different from a patient with lewy body dementia.
Yes, certainly so we'll just a technicality.
The term lewy body dementia, and it is rather confusing nomenclature, but the term lewy body dementia is normally used to include both Parkinson's disease dementia and dementia with lewy bodies DLP. So it's dementia with lewy bodies that I was commenting on that we've seen relatively few patients enrolled in the study I don't think we have the specific numbers to disclose today, but it's a.
It's a low number.
So the majority of patients in the study will either have mci or dementia with with Parkinson's disease and.
We had other youre right that there can be some differences and sometimes between dementia with lewy bodies in Parkinson's disease dementia, we had other inclusion and exclusion criteria in this study two to try to.
Essentially get to the right patient.
And that.
Partly why probably fewer dementia with lewy body patients made it into the study, but those that did were likely to have the right magnitude of cognitive impairment.
Probably on the right domains, and probably not confounded by other symptoms like psychosis. So.
Think we're comfortable with the patient population that we have that we screen.
Okay beautiful thanks for the clarification.
Yes.
Thanks, so much.
Our next question comes from Gary Nachman with BMO. Your line is now open.
Hi, This is Dennis resident on for Gary Nachman, Congrats on the process progress and thank you for taking my questions.
Can you provide context on how many patients will be enrolled in the phase one study for 73 in opioid use disorder and then secondly, now that you are no longer progressing <unk> hundred 19, <unk> forward can you just talk about like some more color on how you're going to be spending moving forward. Thank you.
Sorry, what was the last word Dennis how we're going to be spending did you say.
Yeah, you spend moving forward. Thank you.
Yes, certainly, okay, well I'm actually going to pass the first question over to Katherine and then maybe Ashish can take the second part.
Yes, Thanks, Andy there are nine subjects in the drug drug interaction.
University School of Medicine are conducting.
And with regard to the expenditures.
As you can imagine.
Our projected expenditures going forward will be meaningfully lower than what you've seen in the past several quarters.
We arent.
Actively pursuing further development.
<unk> 95.
And cognitive impairment rather than a chronic pain.
We expect that existing cash flow.
Fund our operations into early 2024, we tend not to give quarter by quarter guidance.
As there are fluctuations along the way of the cloud.
Complete but.
Surely it will be a lower number four.
R&D expense.
And then you have seen in previous quarters.
Thanks, I think I should just maybe add a little bit Dennis.
Two the nine subjects.
Is adequate to meet the goal of this study, which is which is as we mentioned drug drug interaction study with Oxycodone. It is safety on a regulatory requirement you can probably infer from the size of that study that quite a large portion of the ground that we have received will be then available for the subsequent proof of concept study that we could then start.
Once the 90 subject study is complete.
That's very helpful. Thank you.
Our next question comes from <unk>. Your line is now open.
Hi, This is awesome on for Jim Thanks for taking the questions.
A question on historical data points of robotic mine test it out its primary up 24 weeks when it got approved.
I'm just wondering given the dosing of 45 eight for the studies over a shorter period of time, what bar with <unk>. They have to be at the 12 week Mark on any of the Cox the task or other primaries and secondaries.
To be considered signal finding as I stated earlier thank you.
Yes, it's a good question. So rivastigmine was obviously using.
Somewhat different endpoints. There was also I think if I recall correctly, some dose titration involved in the.
Over the weeks of the study.
So.
The bar I think that we.
We'd like to see is partly informed by existing therapies and also partly by the path forward.
Existing therapies and of course, they are used in Alzheimer's as well as in Parkinson's disease.
As well as the what seems to be the emerging regulatory bar for approval in Alzheimer's disease. It is not clear in Parkinson's, obviously, because there haven't been approvals it seems to be standardized effect size of about one point too. So that's essentially the difference between active and placebo divided by the <unk>.
Standard deviation of the sample is just a way to standardize the results from different endpoints.
So we might like to see something a little higher than that simply because we like the clinical trials going forward to be a more manageable size.
But it's difficult to put a very specific cutoff in place because it does depend on which end points, we see those effects.
And and and.
And details like that so, but I think looking at the external.
Benchmarks gives us a little bit of a guide.
Okay, and then just like a bit of a hypothetical follow up now.
Say, if you saw a meaningful improvement.
Say, just one or two of the subsequent years, but.
Not the others, how should we or even the FDA and future interpret that.
Yes, it's an interesting question I think what we would like.
Were to transpire I think we would like to see there be some translation of that.
<unk> on one or two sub scores are domains into functional improvement because I think thats probably.
How FDA would look at it which is to say.
The rubber meets the road essentially in improving the patient's activities of daily living and if that can be done with an effect on a single domain are just a couple of domains then that could be interesting that's to be determined and confirmed in discussions with the agency, obviously, but I think that's how we would look at it.
Thank you.
Our next question comes from Cristina Chen with Cowen. Your line is now open.
Hey, guys.
On for Ritu. Thanks for taking my question I also have a question on slide eight and we see that the secondary endpoints are evaluated.
With that.
Cognitive tests do you anticipate any differences in the composite scores between patients, especially the elderly patients.
I think it's a good question I think that's something we'd be interested to look at it I can't say at the moment that we would anticipate a particular difference because part of the goal of the study was to enroll.
Subjects that met the inclusion criteria in terms of the severity and nature of the cognitive complaint without.
Excluding the diagnosis.
Specific sub diagnosis that got them. There. So I think that certainly will be part of the analysis, we will look at.
<unk> versus Parkinson's dementia versus dementia with lewy bodies.
Got it thank you.
Our next question comes from Google on <unk> with H C. Wainwright. Your line is now open.
Hi, Thanks for taking my questions and congrats on the quarter.
Just a couple for me firstly with respect to $4 58 for CIP D.
Obviously, you are deploying multiple cognitive assessment test.
Evaluate efficacy.
But the beauty of this test as it relates to cases does this progression operator.
Right. So so sensitivity sensitivity in general I think our hope is that the neuro cognitive tests are relatively sensitive to change.
And as I mentioned earlier that as we get into functional test and other endpoints.
The sensitivity and the sample size, maybe a little less but we still think are adequate to see a signal. If there is disease progression over the course of the 12 weeks.
Then.
Since our drug is a symptomatic improvement.
We're assuming that as much as there is disease progression over 12 weeks it should be equally apportioned between drug and placebo group the drug group should be experiencing an improvement over what the symptoms would have been and since we're mostly interested in the delta between the active group and the placebo group unless there was a large imbalance in disease progression between groups then.
That should be that.
Okay.
Okay. Thanks for the color and then with respect to $7 83 for opioid use disorder.
Should we think about the placebo response in the upcoming phase II study.
Just to clarify.
When you say the upcoming Phase II study, you mean, not the phase one drug drug interaction study, but the study after that.
Is that because that study.
Hum.
I have some thoughts on the design of that study but.
But we don't have.
Our study design template that we can really discuss today.
Okay, Yes, yes.
Yes.
So phase one.
So in the face.
Yes go ahead.
Yes go ahead, yes.
Okay. So if you mean the phase one study then it's.
Primarily going to be.
Safety study looking at drug drug interaction.
Let me just check if Catherine Zon, if there is a relevant placebo comparison on any of the key measures Kathryn.
So there certainly is a placebo comparator, but I don't think we expect a placebo response in those endpoints that you could describe the safety Tolerability and PK.
Yes, yes.
Thanks Catherine.
Thank you alright, thanks for taking my questions.
Youre welcome.
There are no further questions waiting at this time, so I'll pass the call back over to management team for closing remarks.
Thank you operator, and thank you everyone for your questions. We appreciate your time and your attention and we wish you all a very pleasant rest of your day.
That concludes the conference call. Thank you for your participation you may now disconnect your lines.