Trevena Inc (TRVN) 2023 Q3 法說會逐字稿

Greetings and welcome to Trevena Inc, third quarter 2023 Earnings Call. At this time, all participants are in a listen only mode. (Operator Instructions) As a reminder, this conference is being recorded and it is now my pleasure to introduce the host, Barry Shin Chief Financial Officer. Thank you, Mr. Barry Shin, you may begin.

Good morning and welcome, everyone. With me today are Carrie Bourdow, our President and CEO, Patricia Drake, our Chief Commercial Officer, and Mark Demitrack our Chief Medical Officer. We're also joined by Dr. Daniel Clauw, a key opinion leader and paid scientific consultant with Trevena to provide his views on our recent TRV over five proof-of-concept data.

Dr. Clark is a rheumatologist, a leading expert of CNS mechanisms in pain and Professor of Anesthesiology medicine and Psychiatry at the University of Michigan. We'll 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, OLINVYK was approved by the FDA in August 2020 and contains all the Caridine and opioid, which is a Schedule two 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.

As with all opioids, serious life-threatening or fatal respiratory depression may occur in patients treated with OLINVYK as indicated in the box warning. The important safety information, including the box warning and full prescribing information, are all available on OLINVYK.com. I'll now turn the call over to Carrie for an overview of our third quarter and recent business accomplishments. Carrie?

Thank you, Barry. Good morning, everyone, and thank you for joining. We're pleased to report a quarter of significant milestones achieved. Let's start with TRV04545, our novel S1P receptor modulator that we're studying for potential use in chronic pain and epilepsy, two large market opportunities.

During the quarter, we released very promising top line results from two Phase 1 proof-of-concept studies where we demonstrated a statistically significant dose-dependent effect in a validated model of neuropathic pain and statistically significant EEG changes and evidence of early reduction in cortical excitability in the TMS study, a biomarker for epilepsy.

Both studies highlighted TRBO45'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 TRV04545 as a non-opioid with a novel mechanism of action, expected once-daily dosing and a favorable safety tolerability profile. Mark will provide more details from the studies during his comments.

We're also pleased to be joined today by Dr. Daniel Clark, who will provide his thoughts on TRV04545 and its potential fit in the therapeutic landscape.

In addition, as we previously mentioned, the NIH continues to study TRV over five procedure prevention, and we're expecting data from their nonclinical study by the year-end. We're actively planning next steps to advance TRV04545 in patients on our own or with a strategic partner for the potential treatment of neuropathic pain, epilepsy, and other CNS disorders.

Turning to OLINVYK, 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.

OLINVYK was featured in three abstracts at the meeting, including a podium presentation. Our US OLINVYK 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 OLINVYK.

Lastly, related to OLINVYK. During the quarter, we received $15 million as a result of the first commercial sale of OLINVYK by [new off] our licensee in China in connection with the our bridge financing agreements.

Let me now turn the call over to Mark to provide more details on TRV04545.

Mark?

Thank you, Gary. Today I'd like to spend time providing an update on TRV045, which continues its exciting progress in clinical development.

I'm also pleased to be joined by Dr. Daniel Clauw of the University of Michigan Medical Center, a renowned expert on chronic pain, who will provide his own perspective on our recent accomplishments with 045. I'd like to begin by reiterating some of the key features that sets TRV045. four five.

Apart within the class of medications that target the S1P receptor. First TRV045 is potent and selective in its action at the type-1 S1P receptor subtype. That is highly expressed on T cells of interest in the brain, namely astrocytes and microglia.

Second, data from our nonclinical studies, we believe shows that TRV045 action on these cells modulates their inflammatory signals in the brain with a net action to potentially reduce inflammation. We believe this property of 045 effects is particularly relevant to central pain signaling to the control of seizures and may play a role in how seizures develop in the first place, a process known as epilepsy Genesis.

Finally, in our clinical studies, TRV045 has shown no evidence of lymphopenia. A known on-target effect of existing S1P modulating drugs and has shown a favorable safety and tolerability profile, with respect to cardiac and pulmonary function and an ophthalmologic 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 TRV045 action on the brain and to assess pharmacodynamic outcomes relevant to our interest in chronic neuropathic pain and epilepsy.

As I mentioned previously, we've been pleased with the outcome of these studies. Among the most important findings from that work in our pain cart target engagement study, we showed that 045 had a statistically significant dose-dependent action to reduce the mechanical allodynia evoked by topical application of the neurotoxic irritants, Kip Saizen.

These data are important since this validated model provide strong support for the potential efficacy of 045 in the treatment of chronic neuropathic pain in patients. In a new analysis we compared the results of (technical difficulty) work with similar published data from the same testing laboratory using standardized effect size estimates of valid statistical method used to compare results across studies.

By this measure, our data shows a statistically large effect size. The effect size for 045 is also comparable in magnitude to outcomes seen in published data with known analgesics, including pregabalin. And with Vertex's investigational compound VX150 of sodium channel blocking drugs.

There are limitations of this method of using standardized effect sizes to compare data as there are with all comparisons across studies. Given that these different treatments were studied in different experiments, these comparison 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. a noninvasive method to electrically stimulate the brain. The most interesting finding in this study was that 045modulated the resting state EEG with a statistically significant increase in the power spectral analysis among the mid to higher frequency EEG bands, alpha beta and gamma, which are thought to be correlated with arousal alertness and higher odor cognitive processes like learning and memory.

At the same time, we saw no increase in slow wave activity in the delta and theta bands changes which are seen with some antiepileptic 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 showed no clinically significant findings, including an ophthalmologic exam. There were also no drug-related changes on total circulating lymphocyte levels, vital signs, or interval measures on ECGs.

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's epilepsy therapy screening program on our seizure prevention model, which will provide additional insight into 045 potential to exert a disease-modifying effect in epilepsy and we believe could make TRV045 unique among antiepileptic drugs.

We're now continuing development of 045 with ongoing work to develop an optimized formulation that will improve bioavailability parameters observed in Phase-1 and provide a potential commercial ready formulation that could be used in Phase-2 studies.

In addition, our nonclinical toxicology program is progressing well with ongoing reproductive toxicology and some chronic toxicology studies, which will allow us to study an extended treatment duration in phase-2, 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 Clauw. Dr. Clauw is an internationally recognized expert in the clinical path physiology of chronic pain. Doctor Clauw has published 450 peer-reviewed articles in his area of expertise. He's received over $100 million in federal funding through his career and currently serves as [KOBI4NIAH] center grants and 2RO1's studying various aspects of chronic pain. Dr. Clauw will offer his perspectives on the TRV045 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 TRV045. Let me start by providing some context for why a novel treatment for chronic pain is needed. The current landscape of drug treatment options for chronic pain is that we have marginally effective drugs and have lots of side effects.

In the FDA registration trials for these drug, they only had modest effects offering clinically meaningful improvement in a small portion of those who take the drug, even fewer patients continue to use drugs long term because of all the side effects, especially issues with cognition and sedating side effects. It's 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 TRV045 to be very intriguing. I will start with some of the comments on the pain current results, which included 25 individuals. What I find really notable is that 045 had a large statistically significant effect on the mechanical allodynia endpoint.

This and other favorable quantitative sensory testing profiles makes me think that this is a true clinical signal. The particular outcomes seen in this study, namely a reduction in mechanical allodynia is also an accepted marker of the central action of the drug.

It effects demonstrate what I believe to be strong evidence that 045 is exerting an effect and 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 hyper excitability of cortical and some cortical regions in the brain involved in pain signaling.

This is important since we know that the development of central hyper excitability. These brain regions is one of the main ways in which chronic pain develops in the first place and why it persists over time. While we have (technical difficulty) much and about the specific mechanisms of old clarified.

I suspect that these effects are somehow being driven by modifying the balance in the brain between glutamatergic associated neuronal excitation and Gabon mediated inhibition of brain function. Of central nervous system, chronic pain states in some manner of dysregulation in the central neuro chemical events as do seizure disorders, which is why I feel you're 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 studies it's been discussed. These data provide further evidence that 045is potentially modifying the excitability of the brain itself. These changes fit nicely with the analgesic effects observed in the first study and reinforce the idea, in my opinion that 045principal actions are to reduce central hyper excitability.

It's important that TRV045's actions in both the pain card study and the EEG. study are occurring in what appears to be a favorable safety and tolerability profile, including, again, with respect to cognition and sedating side effects.

As previously noted, that 045 had a large effect size on the pain, curt findings. But I want to emphasize that even if TRV045 only has a small or moderate effect size on pain in clinical trials. If it continues to demonstrate this favorable safety profile, it would still have the potential to be an important addition to the current option. And it's especially appealing that 045 is not an opioid which have limited utility and significant toxicity when used in chronic pain. While the Company is currently pursuing the development 045 for chronic pain in epilepsy.

I'd like to make a few comments to broaden and understanding of the opportunity that this compound could offer. As I mentioned in my opinion, and these data (technical difficulty) are working to reduce central neuro hyper excitability, which we know plays a significant role in chronic pain caused by the nervous system now referred to as no surprise to pain.

And also plastic pain is certainly present in chronic neuropathic pain, but it's also an important underlying path of physiologic 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 and conditions such as fibromyalgia. In addition to oncoplastic pain being a primary mechanism and these common pain conditions. There are also significant orphan disease opportunities since this type of plane plays a major role in conditions such as sickle cell disease and hyper mobility syndromes, such as earlier scandal syndrome.

In short, given this early phase of development, this compound looks (technical difficulty) as part of any centrally acting analgesic. But I've seen I believe the Parallel evidence of potential benefit in both pain and epilepsy models indicate that the drug is somehow modulating a central hyper excitability of the brain, which supports its therapeutic potential.

Again, this is accompanied by what initially looks like a favorable safety and tolerability profile. I also believe there's potential broader applicability for a compound with these attributes for a wide range of central nervous system disorders characterized by central hyper excitability. I look forward to the next chapter in this 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 $0.57 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 OLINVYK, TRV045 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. (Operator Instructions)

Jason Butler, GMP Securities.

Hi, great. Thanks for taking the questions. And appreciate all of the detailed comments this morning. And just in terms of TRV045, can you speak to your current views on partnership prioritization? Are you looking for something that's regional 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 and can you just give us a little bit more detail on what the bioavailability you've seen so far? Is this bioavailability? The only thing that you're optimizing for are there other parts of the PK profile you're looking to optimize? And then just lastly there, how should we think about penetration into the brain versus plasma bioavailability? Thanks.

Great. Thanks, Jason. Appreciate I appreciate the question. So I'll start with the partnership question, then I'll turn it over to Mark to talk about the formulation and the bioavailability and the penetration, brain penetration.

So we're flexible as it relates to partners and partnerships. And we have if there are partners that are potentially interested in both epilepsy and pain. So we're looking for the best way to advance TRV045 in patients. Mark, you want to talk a little bit more about formulation and I can circle back.

Yes, sure, Jason. Thank you for the question, and I'll try and remember all of the points that you raised such as ours,-- (multiple speakers)

Formulation and all the trying to improve it.

Yes. So as you know, in early Phase-1 work. We use a very basic formulation, which has been a API. in capsules. So we're proceeding with based on that data. We proceed then with an optimized formulation to bring forward into further development and for commercial use.

The bioavailability domain, the main topic that we want to address in an improved formulation is we have a moderate food effect with dosing. We'd obviously like to change that and allow administration with or without a meal. So that's an important observation from our early phase-1 work. The other thing that we'd like to do is increase the headroom.

So to speak in terms of the plasma exposure, we're 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-2 to do full dose ranging of work that we'd that we'd like to do.

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 it to the tune of about a four-to-five-fold ratio of brain to plasma concentrations.

So the separate penetration of the compound is clear from that work. And that's why we think of 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 my questions.

Sure.

Douglas Tsao, H.C. Wainwright.

Hi, good morning. Thanks for taking the questions. Just maybe just starting point to Dr. Clauw. I'm just curious within the -- sort of potential indications or application of TRV045? Just curious which ones would you prioritize and (inaudible) 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. Clauw only. And that's I think what's helpful is that we have an opportunity in neuropathic pain and Dr. Clauw and some of the broader applicability and within non-opioid space and then also epilepsy by now you're more focused, 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 has prominence. No ceroplastic pain or CMS driven pain. And that's why duloxetine, for example, worked on those conditions before it ended up patent expired.

So we know that they're strong CNS components, 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 do it's not secondary to something else. So the new ICD-10 classifications for primary pain would include things like fibromyalgia, irritable bowel tension, headache, again, really common chronic pain conditions, all of which have a big unmet need.

So I think it's really more of a corporate decision. I think there's any number, some sort of CNS driven pain conditions that this may very well work in as the drug gets further out in development. That's just a decision the Company will have to make.

Okay, great. That's helpful. And Carrie. I know you mentioned epilepsy and obviously you still are sort of waiting some of the data from on the NIH work. I'm just curious, Tom, you know, is that is there a gating item in terms of potentially seeking partners and figuring out what direction you want to go on from a corporate development standpoint? Thank you.

Yes, great question. No, it's not a gating item. I think it will add to the story, we'll see what the data looks like, but I think it is an important part of the story is related to epilepsy because certainly we are worth thinking about treatments.

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 those. The considerations that we have and frankly, the conversations that we're having with partners. But it is not a gating factor. Maybe I'll just add to the overall story for TRV045.

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.

Yes, so I'm probably not. -- well, not in the first part in that we would have a scenario where you would have different partners in pain. There are, of course, as you might imagine, different partners currently that are interested in either pain or epilepsy.

But there are no, there are partners that are also interested in, but given how interesting this dataset is and so we would two the 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 in pain versus epilepsy. How you think about the indications of development program forward but it's certainly terrific right now to have these choices in front of us.

Okay, great. Thank you.

Thank you. There are no further questions at this time. I would now like to turn the floor over to Carrie Bourdow for closing comments.

Great. Thank you, operator, and thank you, everyone, for joining the call today. As you as you heard from Mark, we are actively advancing TRV045 working to optimize the formulation in 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 partners in both epilepsy and pain. And as we said, these are two large markets where a novel mechanism of action like TRV045 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.