Q3 2023 Trevena Inc Earnings Call
Greetings and welcome to Sabrina, Inc. Third quarter 2023 earnings call. At this time all participants are in a listen only mode. A brief question and answer session will follow the formal presentation if anyone should require.
Operator assistance during the conference. Please press Star Zero on your telephone keypad. As a reminder, this conference is being of the contract. It is now my pleasure to introduce your host Babish and Chief Financial Officer. Thank you. Mr. Chen you may begin.
Good morning, and welcome everyone with me today are Terry Bordeaux, our president and CEO, Patty Drake, our Chief commercial officer, and Mark <unk>, Our Chief Medical Officer.
We're also joined by Dr. Daniel Claw, a key opinion leader in pain scientific consultant with Trevino provide his views on our recent T. R. V 045 proof of concept data.
Dr. Claude is a rheumatologist, a leading expert a CNS mechanisms in pain and professor of Anesthesiology medicine, and psychiatry at the University of Michigan.
We will also be making forward looking statements under federal Securities Law. These statements are subject to risks and uncertainties related to our business, including those covered in our filings with the SEC. We undertake no obligation to update these statements beyond today.
As a reminder, Olympic was approved by the FDA in August 2020, and contains all the charity and opioid which is scheduled to controlled substance with a high potential for abuse similar to other opioids is indicated in adults for the management of acute pain severe enough to require an IV opioid analgesic and for whom alternative treatments are inadequate.
All opioids serious life threatening our payroll respiratory depression may occur in patients treated with the Olympics as indicated in the box warning the important safety information, including the box warning and full prescribing information are all available on the Olympics dot com.
I'll now turn the call over to Gary for an overview of our third quarter and recent business accomplishments.
Three.
Thank you Barry.
Everyone and thank you for joining we're pleased to report a quarter of significant milestones achieved let's start with TRT 045, our novel <unk> receptor modulator that we're studying for potential use in chronic pain in epilepsy to large market opportunities.
During the quarter, we released very promising top line results from two phase one proof of concept studies, where we demonstrated a statistically significant dose dependent effect in a validated model of neuropathic pain and statistically significant <unk> changes and evidence of early reduction in cortical.
Inability in the Tms study a biomarker for epilepsy.
Both studies highlighted T. R V O 40, five's unique mechanism of action and CNS target engagement.
In addition last month, we also announced favorable top line safety and Tolerability data from these studies.
We believe the data generated to date supports the therapeutic potential of T. R. V 045, as a non opioid with a novel mechanism of action expected once daily dosing and a favorable safety and Tolerability profile.
Mark will provide more details from the studies during his comments.
We're also pleased to be joined today by Dr. Daniel Claw, who will provide his thoughts on <unk> five and its potential fit in the therapeutic landscape.
In addition, as we previously mentioned the NIH continues to study T. I D 045, prestige or prevention, and we're expecting data from their non clinical study by year end.
We're actively planning next steps to advance <unk>, four five and patients on our own or with a strategic partner for the potential treatment of neuropathic pain epilepsy and other CNS disorders.
Turning to Olympic we announced the completion of the initial analysis of respiratory data from the 200 patient Volition study that was generated at Cleveland clinic, and Wake Forest Baptist Health.
The results were presented at the recent American Society of Anesthesiologists meeting last month.
Olympic was featured in three abstracts at the meeting, including a podium presentation.
Our U S Olympic commercial business remains challenging.
We're efficiently deploying resources and pursuing our contracting strategy and we'll continue to assess performance and the best path forward for Olympic.
Lastly related to Olympic during the quarter, we received $15 million as a result of the first commercial sale of Olympic by Noah our licensee in China in connection with the <unk> financing agreement.
Let me now turn the call over to Mark to provide more details on tier four five mark.
Thank you Terry.
Today I'd like to spend time, providing an update on <unk> four five which continues its exciting progress in clinical development.
I'm also pleased to be joined by Dr. Daniel Claw of the University of Michigan Medical Center.
Renowned expert on chronic pain, who will provide his own perspective on our recent accomplishments within four five.
I'd like to begin by reiterating some of the key features that sets <unk> apart within the class of medications that target the <unk> receptor.
First <unk> five is potent and selective in its action at the type one S Y <unk> receptor subtype that is highly expressed on T cells of interest in the brain, namely astrocytes and microglia.
Second data from our non clinical studies, we believe shows the tier B O four fives action on these sales modulates there inflammatory signals in the brain with a net action to potentially reduce inflammation.
We believe this property above four fives effects is particularly relevant to central pain signaling to the control of seizures.
And may play a role and how seizures developed in the first place a process known as epileptic Genesis.
Finally in our clinical studies <unk> has shown no evidence of Lymphopenia.
None on target effect of existing S. One P modulating drugs.
<unk> has shown a favorable safety and tolerability profile with respect to cardiac and pulmonary function.
And on ophthalmologists examination.
Taken together, we believe these features position 045, as a compound, especially well suited to explore its potential use in the treatment of chronic neuropathic pain and epilepsy.
With these features in hand, we embarked on a targeted proof of concept study program to further evaluate <unk> five's action on the brain.
And to SaaS pharmacodynamic outcomes relevant to our interest in chronic neuropathic pain and epilepsy.
As I've mentioned previously we've been pleased with the outcome of these studies.
Among the most important findings from that work in our paint car target engagement studies.
We showed that <unk> five had a statistically significant dose dependent action to reduce the mechanical allodynia.
Look by topical application of the neurotoxic Ayrton capsaicin.
These data are important since there's validated model provides strong support for the potential efficacy of <unk> 45 in the treatment of chronic neuropathic pain in patients.
And a new analysis, we compared the results of our work with similar published data from the same testing laboratory using standardized effect size estimates are valid statistical method used to compare results across studies.
By this measure.
Our data shows a statistically large effect size.
The effect size for <unk> five is also comparable in magnitude to outcomes seen in published data with known analgesics, including Pregabalin.
And with vertex as investigational compound VX 150, sodium channel blocking drugs.
There are limitations of this method of using standardized effect size is to compare data.
As there are with all comparisons across studies given that these different treatments were studied in different experiments.
These comparisons should be confirmed through head to head clinical studies in the future.
In the second study, we examined EEG and EMG measures in association with Tms Noninvasive method to electrically stimulate the brain.
The most interesting finding in this study was that 045 modulator the resting state E G.
With a statistically significant increase in the power spectral analysis, among the mid to higher frequency EG bands Alpha beta and gamma.
Which are thought to be correlated with arousal alertness and higher order cognitive processes like learning and memory.
At the same time, we saw no increase in slow wave of activity in the delta or feeder bands changes, which are seen with some anti epileptic drugs and are thought to be associated with their cognitive and sedating adverse effects.
The safety and Tolerability data from these two studies is consistent with the safety and Tolerability data seen in our prior first in human work.
In particular, there were no serious adverse events.
Most events were mild and transient and were not related to study drug administration.
Physical exams before and after drug exposure.
No clinically significant findings.
Including on Ophthalmology exam.
There were also no drug related changes on total circulating lymphocyte levels vital signs or integral measures on <unk>.
In short we are very pleased with the outcome of our proof of concept study program.
We also expect a readout shortly from the NIH is epilepsy therapy screening program on our seizure prevention model.
Which will provide additional insight into <unk> five's potential to exert a disease modifying effect in epilepsy.
And we believe could make <unk> unique among anti epileptic drugs.
We're now continuing development of about four five with ongoing work to develop an optimized formulation that will improve bioavailability parameters observed in phase one.
And provide a potential commercial ready formulation that could be used in phase II studies.
In addition, our non clinical toxicology program is progressing well with ongoing reproductive toxicology and sub chronic toxicology studies.
Which will allow us to study an extended treatment duration in phase two critical to defining the value proposition.
We expect all of this work to be completed in the second half of 2024.
I'd now like to introduce Dr. Daniel Claw.
Dr. Clark is an internationally recognized expert in the clinical pathophysiology of chronic pain.
Dr. Claw has published 450 peer reviewed articles in his area of expertise. He has received over $100 million in federal funding through his career and currently serves as co Pi for NIH Center grants and two are ones studying various aspects of chronic pain.
Dr. Kerr will offer his perspectives on the TRP 045 data and its potential implications for future development.
Dan.
Thanks, Mark and thanks for inviting me to join this call and have an opportunity to comment on CRB over five.
Let me start by providing some context for why a novel treatment for chronic pain as needed.
The current landscape of drug treatment options for chronic pain is that we have marginally effective drugs can have lots of side effects.
And the FDA registration trials for each drug they only had modest effects offering clinically meaningful improvement in a small portion of those who take the drugs.
Even fewer patients continue to strive for long term because of all the side effects, especially issues with cognition and sedating side effects.
It is clear that more treatment options are needed, especially non opioid options that have novel mechanisms and offer potential improvements in any of these areas.
With that in mind I find that the data Mark described with your view of four five to be very intriguing I.
I will start with some of the comments on the Pink hurt results, which included 25 individuals.
What I find really notable is it 045, you had a large statistically significant effect on the mechanical Allegheny to endpoint.
And other favorable quantitative sensory testing profiles makes me think that this is a true clinical signal.
The particular outcome seen in this study, namely a reduction in mechanical allodynia.
We wont accepted marker of the central action of the drug.
Thats demonstrate what I believe to be strong evidence that <unk> five is exerting an effect on central pain processing with a favorable safety and Tolerability profile.
These data also support the notion that the drug is working in part by dampening Central Hyperexcitability are critical in some critical regions in the brain involved in pain signaling.
This is important since we know that the development of Central Hyperexcitability. These green region is one of the main ways in which chronic pain develops in the first place and why it persists over time.
While we have much more about the specific mechanism a ballpark I suspect that these effects are somehow being driven by modifying the balance in the brain between glutamatergic associated neuronal excitation and Gaba mediated inhibition of brain function.
The central nervous system chronic pain states in some manner.
Dysregulation in the central Neurochemical events. He has to do with seizure disorders, which is why I feel youre seeing parallel signals in these two different types of disorders.
Let me turn to the EEG and EMG data seen in the second proof of concept study that's been discussed.
These data provide further evidence that all four or five is potentially modifying the excitability of the brain itself.
These changes fit nicely with the analgesic effects observed in the first study and reinforced the idea in my opinion that all four of five principal actions are to reduce central hyperexcitability.
It is important that <unk> actions in both the paint card study in the EG study are occurring in what appears to be a favorable safety and tolerability profile, including again with respect to cognition insulating side effects.
I previously noted <unk> had a large effect size on the pain, Kurt findings, but I want to emphasize that even if to your view of four five only guys.
Small or master it effects.
Pain in clinical trials.
It continues to demonstrate this favorable safety profile it would still have the potential to be an important addition to the current options.
And it's especially appealing that all four or five is not an opioid which have limited utility and significant toxicity when used in chronic pain.
While the company is currently pursuing the development of a four five for chronic pain and Epsilon. Please I'd like to make a few comments to broaden and understanding of the opportunity that this compound could offer.
As I mentioned my opinion and these data.
To reduce central neuro hyperexcitability, which we know it plays a significant role in chronic pain caused by the nervous system now referred to as noted the plastic <unk>.
It's a classic pain is certainly present in chronic neuropathic pain, but it's also an important underlying pathophysiological mechanism across a range of other pain conditions, including seemingly disparate conditions like osteoarthritis chronic low back pain and rheumatoid arthritis for example.
This is also the primary pain mechanism in conditions such as fibromyalgia.
Just to note the plastic pain being a primary mechanism in the salmon pain conditions. There are also significant orphan disease opportunities. Since this type of plane played a major role in conditions, such as sickle cell disease, and Hypermobility syndrome, such as early scandals syndrome.
In short given this early phase of development.
Compound it looks as if any.
Any centrally acting analgesic that ive seen I believe the parallel evidence of potential benefit in both pain and epilepsy models indicate that the drug is somehow modulating.
Central hyperexcitability of the brain, which supports its therapeutic potential again. This is accompanied by what initially looked like a favorable safety and Tolerability profile. I also believe there is potential broader applicability for a compound with these attributes for a wide range of central nervous system disorders characterized by center.
Troll Hyperexcitability I look forward to the next chapter in the story and with that I will turn the call back to Mark.
Thank you Dan we certainly appreciate your insight and perspective on the data.
I'll now turn the call over to Barry to review, our third quarter financials Barry.
Thanks Mark.
In the third quarter, our net loss was $7 9 million or 57 per share compared to $15 3 million or $2 24 per share for the same period last year.
This reduced net loss was largely due to cost savings we implemented in 2022.
We finished the quarter with $35 million in cash and marketable securities, which we believe will fund our operations into the third quarter of 2024.
We continue to investigate partnering and other opportunities for Olympic TRP 045, and our other pipeline candidates, which would provide additional resources and build shareholder value.
We'll now open the call for questions after which Carol will provide some closing remarks.
Operator.
Thank you.
We will now be conducting a question and answer session.
If you would like to ask a question. Please press star one on the telephone keypad.
A confirmation tone will indicate your line is in the question queue.
You May press Star two if you would like to remove your questions from the queue for participants using speaker equipment. It may be necessary to pick up your handset before pressing the star keys, one woman please poll for questions.
First question comes from the line of Jason Butler with JMP Securities. Please go ahead.
Hey, great. Thanks for taking the questions and I appreciate all of the detailed comments this morning.
Just in terms of Tivo's four five can you speak to your current views on partnership prioritization are you looking for something that's regional or or indication specific or just what would you view as an optimal outcome. If you chose to partner the asset and then.
On the on the formulation work.
Can you just give us a little bit more detail on what the bioavailability you've seen so far is this bio availability the only thing that you're optimizing for are there other parts of the PK.
Profile, you're looking to optimize and then and then just lastly, there how should we think about penetration into the brain versus plasma bioavailability. Thanks.
Thanks, Jason appreciate I appreciate the question. So I'll start with the partnership question and then I'll turn it over to Mark to talk about the formulation and the bioavailability and the penetration brain penetration.
We're flexible as it relates to partners and partnerships and we have.
Yes.
Partners that are potentially interested in both epilepsy and pain. So.
We're looking for the best way to to advance <unk> four five and in patients.
Mark you want to talk a little bit more about formulation and I can circle back yeah sure.
Jason Thank you for the question and I'll try.
And remember all of the points that you raised so soon as ours formulation and trying to improve there. Yes. So as you know in early phase one work and we use a very basic formulation, which has been a.
In capsules, so we're proceeding with.
Based on that data. We proceed then with.
And optimized formulation to bring forward into further development and for commercial use the bioavailability the main.
A topic that we we want to address in an improved formulation as we have a moderate food effect.
With <unk>.
With dosing.
We'd obviously like to.
To change that.
And allow administration with or without <unk>.
So that's that's an important observation from our early phase one where the other thing that we'd like to do is increase the.
The headroom so to speak in terms of the plasma exposure were well within our targeted efficacy range, we'd like a little more ability to maneuver in terms of plasma.
Exposures that gives us a better opportunity as we proceed into phase III do full dose ranging.
Work that we have that we'd like to the other question. You asked was regard to CNS penetration in our animal studies, we see good penetration of the compound into the brain and we've seen that in multiple.
Studies.
To the tune of about a 4% to five fold ratio of brain to plasma concentrations. So the central penetration of the compound as is clear from that work and that's why we think.
The Pharmacodynamic data that we see in the proof of concept studies is consistent with that it reflects brain presence and engagement of the compound with relevant targets in the in the CNS I think that covers the topics that you raised.
Yes, that's really helpful. Thanks for taking the questions.
Sure.
Yeah.
Thank you <unk>.
Question comes from the line of Douglas Tsao.
Excuse me. Please go ahead.
Hi, Good morning, Thanks for taking my questions just maybe it's a starting point for Doctor Claw I'm, just curious within the sort.
Sort of potential indications or application of Cherokee 045, I'm, just curious which ones would you prioritize or thinks he has the most compelling in the near term for the drug and would you like to see first sort of begin clinical data or work with patients. Thank you.
Thanks, Doug.
So let me let me just start and then I'll turn it over to Dr. Carl only and that's I think what's helpful is that we have an opportunity.
Neuropathic pain and Dr. Carl mentioned some of that.
Broader applicability and within non opioid no non opioid space and then also epilepsy.
But that's fine.
Focus of course on pain. So please.
Yes, I mean, I think the company will have a lot of options I think that this may be effective.
In a large subset of people with really common chronic pain conditions, such as osteoarthritis or chronic low back pain, because we know that at least 30 or 40% of people with either of those conditions is permanent.
No, it's a plastic pain or CNS, driven pain, and that's why I Duloxetine for example worked.
And those conditions.
Before it ended up patent expired.
So we know that Theres strong CNS component, even in even in conditions like low back pain, and osteoarthritis, but often start out as being more nociceptive pain and then you have all these other.
Conditions like fibromyalgia that are now actually being called primary pain conditions, because that the pain is the primary problem. It's not it's not secondary to something else. So the new ICD 10 classifications for primary pain would include things like fibromyalgia irritable bowel attention headache, again really common chronic pain conditions all of it.
Which have a big unmet need so I think it's really more of a corporate decision I think there is any number of.
Sort of CNS, driven pain conditions that may very well working in.
As the drug gets further on in development. That's just a decision the company will have to make.
Okay, Great. That's helpful. And then carry I know you mentioned epilepsy, and obviously you still are sort of waiting some of the data from from Yeah. NIH work I'm. Just curious you know is that it.
A gating item in terms of potentially seeking partners partners in figuring out what direction you want to go from a corporate development standpoint. Thank you.
Yeah, Great question no no its not a gating item I think it will add to the story, we will see what the data looks like but I think it is an important part of the story as it related to epilepsy, because certainly we are worth thinking about treatment.
But given some of the interesting characteristics of the data that we've seen so far having the seizure prevention data would really help broaden knows.
The considerations that we have and frankly, the conversations that we're having with partners, but it is not a gating factor.
Just add to the overall story for <unk>.
And Carrie could you envision a scenario, where you have partners for epilepsy and a different partner for pain or are you generally looking for somebody who would be able to help.
Support the program across all indications. Thank you yeah, yeah, so probably.
Probably not.
Well not in the first part in that we would have a scenario where you would have different partners in pain and there are of course as you might imagine different partners. Currently that are interested in either pain or epilepsy, but there are you know.
The partners that are also interested in <unk>.
Given given how interesting is that this data set is.
So we would see.
She was a path.
As it relates to moving forward and some of that is also of course, Doug as we've talked in the past around the commercial assessment right. The pricing models are different and paying versus epilepsy. How you would think about the indications in development program forward, but it's certainly terrific right now to have these choices in front of us.
Yeah.
Okay, great. Thank you.
Yeah.
Thank you.
There are no further questions at this time I would now like to turn the floor over to Katie Bordeaux for closing comments great.
Great. Thank you operator, and thank you everyone for joining the call today as you as you heard from Marc we're actively advancing TRL four five working to optimize the formulation and our and on our toxicology studies with the expected completion in the second half of next year. We're also continuing to talk with interested strategic partner.
In both epilepsy and pain.
As we said these are two large markets, where a novel mechanism of action like T. RVO for five can potentially have a significant impact. So we look forward to providing you with additional updates on our progress and thank you again.
Thank you. This concludes today's teleconference. You may disconnect. Your lines at this time. Thank you for your participation.
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