WEBVTT 00:00:00.000 --> 00:00:02.570 align:middle line:84% MELISSA: Greetings and welcome to the Trevena Corporate 00:00:02.570 --> 00:00:03.380 align:middle line:90% Update. 00:00:03.380 --> 00:00:06.650 align:middle line:84% At this time, all participants are in a listen only mode. 00:00:06.650 --> 00:00:08.300 align:middle line:84% A question and answer session will 00:00:08.300 --> 00:00:10.070 align:middle line:90% follow the formal presentation. 00:00:10.070 --> 00:00:12.392 align:middle line:84% If anyone should require operator assistance 00:00:12.392 --> 00:00:13.850 align:middle line:84% during the conference, please press 00:00:13.850 --> 00:00:16.160 align:middle line:84% star-zero on your telephone keypad. 00:00:16.160 --> 00:00:19.230 align:middle line:84% As a reminder, this conference is being recorded. 00:00:19.230 --> 00:00:21.140 align:middle line:84% I would now like to turn the conference over 00:00:21.140 --> 00:00:24.020 align:middle line:84% to your host Mr. Barry Shin, chief financial officer 00:00:24.020 --> 00:00:24.890 align:middle line:90% for Trevena. 00:00:24.890 --> 00:00:25.580 align:middle line:90% Thank you. 00:00:25.580 --> 00:00:26.750 align:middle line:90% You may begin. 00:00:26.750 --> 00:00:27.500 align:middle line:90% BARRY SHIN: Great. 00:00:27.500 --> 00:00:28.557 align:middle line:90% Thanks, Melissa. 00:00:28.557 --> 00:00:30.140 align:middle line:84% Good morning and thank you for joining 00:00:30.140 --> 00:00:34.070 align:middle line:84% us to discuss our proof of concept data for TRV045. 00:00:34.070 --> 00:00:37.220 align:middle line:84% With me today are Carrie Bourdow, our president and CEO, 00:00:37.220 --> 00:00:40.430 align:middle line:84% and our chief medical officer, Mark Demitrack. 00:00:40.430 --> 00:00:42.350 align:middle line:84% We'll also touch on other business updates. 00:00:42.350 --> 00:00:45.110 align:middle line:84% And as a reminder, Olinvyk was approved by the FDA 00:00:45.110 --> 00:00:47.900 align:middle line:84% in August 2020 and contains all the Saridon 00:00:47.900 --> 00:00:50.660 align:middle line:84% an opioid, which is a Schedule II controlled substance 00:00:50.660 --> 00:00:54.050 align:middle line:84% with a high potential for abuse similar to other opioids. 00:00:54.050 --> 00:00:56.150 align:middle line:84% It's indicated in adults for the management 00:00:56.150 --> 00:00:59.570 align:middle line:84% of acute pain severe enough to require an IV opioid analgesic 00:00:59.570 --> 00:01:02.550 align:middle line:84% and for whom alternative treatments are inadequate. 00:01:02.550 --> 00:01:05.280 align:middle line:84% As with all opioids, serious life-threatening or fatal 00:01:05.280 --> 00:01:07.170 align:middle line:84% respiratory depression may occur in patients 00:01:07.170 --> 00:01:10.080 align:middle line:84% treated with Olinvyk as indicated in the boxed warning. 00:01:10.080 --> 00:01:12.360 align:middle line:84% The safety information, including the boxed warning 00:01:12.360 --> 00:01:14.160 align:middle line:84% and full prescribing information are all 00:01:14.160 --> 00:01:17.062 align:middle line:90% available on olinvyk.com. 00:01:17.062 --> 00:01:19.020 align:middle line:84% We'll also be making forward looking statements 00:01:19.020 --> 00:01:20.493 align:middle line:84% under federal securities law, which 00:01:20.493 --> 00:01:22.410 align:middle line:84% are subject to risks and uncertainties related 00:01:22.410 --> 00:01:24.702 align:middle line:84% to our business, including those covered in our filings 00:01:24.702 --> 00:01:25.770 align:middle line:90% with the SEC. 00:01:25.770 --> 00:01:28.140 align:middle line:84% We undertake no obligation to update these statements 00:01:28.140 --> 00:01:30.870 align:middle line:90% beyond today. 00:01:30.870 --> 00:01:33.305 align:middle line:84% I'll now turn the call over to Carrie. 00:01:33.305 --> 00:01:34.680 align:middle line:84% CARRIE BOURDOW: Thank you, Barry. 00:01:34.680 --> 00:01:35.920 align:middle line:90% Good morning, everyone. 00:01:35.920 --> 00:01:37.890 align:middle line:90% Thanks for joining us today. 00:01:37.890 --> 00:01:40.470 align:middle line:84% Trevena is a company with a novel 00:01:40.470 --> 00:01:44.010 align:middle line:84% platform focused on innovative new medicines for CNS 00:01:44.010 --> 00:01:45.030 align:middle line:90% disorders. 00:01:45.030 --> 00:01:47.880 align:middle line:84% All of our assets are new mechanisms wholly owned 00:01:47.880 --> 00:01:50.340 align:middle line:84% by us discovered in our own labs. 00:01:50.340 --> 00:01:52.920 align:middle line:84% Alembic was our first new chemical entity 00:01:52.920 --> 00:01:55.800 align:middle line:84% that we took from discovery to approval. 00:01:55.800 --> 00:01:58.320 align:middle line:84% Today we're focusing on the middle box 00:01:58.320 --> 00:02:01.740 align:middle line:84% on this slide, our novel S1P modulator program. 00:02:01.740 --> 00:02:04.020 align:middle line:84% And it's an exciting day because we're here 00:02:04.020 --> 00:02:07.770 align:middle line:84% to review preliminary results from two proof of concept 00:02:07.770 --> 00:02:13.170 align:middle line:84% studies for TRV045, our novel S1P receptor modulator. 00:02:13.170 --> 00:02:16.470 align:middle line:84% You may be familiar with other blockbuster S1Ps 00:02:16.470 --> 00:02:17.730 align:middle line:90% like fingolimod. 00:02:17.730 --> 00:02:20.880 align:middle line:84% And while TRV045 is part of this family, 00:02:20.880 --> 00:02:23.160 align:middle line:84% it has a unique mechanism of action 00:02:23.160 --> 00:02:25.590 align:middle line:84% that we believe will allow us to target 00:02:25.590 --> 00:02:28.380 align:middle line:90% a range of CNS disorders. 00:02:28.380 --> 00:02:31.710 align:middle line:84% Trevena has been doing work for the last few years 00:02:31.710 --> 00:02:36.400 align:middle line:84% with TRV045 as a non-opioid for chronic pain conditions. 00:02:36.400 --> 00:02:40.830 align:middle line:84% The NIH has been studying 045 in their epilepsy therapy 00:02:40.830 --> 00:02:45.060 align:middle line:84% screening program known as ETSP and has generated interesting 00:02:45.060 --> 00:02:47.940 align:middle line:90% non-clinical epilepsy data. 00:02:47.940 --> 00:02:51.960 align:middle line:84% After we announced positive first in human phase I studies 00:02:51.960 --> 00:02:56.070 align:middle line:84% late last year, we initiated two proof of concept studies 00:02:56.070 --> 00:02:59.220 align:middle line:84% to gain further insight into the unique mechanism 00:02:59.220 --> 00:03:03.030 align:middle line:84% and to evaluate CNS target engagement. 00:03:03.030 --> 00:03:05.010 align:middle line:84% I'm very pleased with these results 00:03:05.010 --> 00:03:08.040 align:middle line:84% because what we've demonstrated in both studies 00:03:08.040 --> 00:03:10.740 align:middle line:90% is evidence of CNS activity. 00:03:10.740 --> 00:03:13.380 align:middle line:84% And despite the small sample size, 00:03:13.380 --> 00:03:17.280 align:middle line:84% we showed a statistically significant analgesic effect 00:03:17.280 --> 00:03:20.880 align:middle line:84% in a validated model for neuropathic pain. 00:03:20.880 --> 00:03:25.140 align:middle line:84% The TMS study showed interesting changes in EEG results 00:03:25.140 --> 00:03:27.870 align:middle line:84% and early reduction in cortical excitability, 00:03:27.870 --> 00:03:31.560 align:middle line:84% as well as additional evidence of CNS activity 00:03:31.560 --> 00:03:35.580 align:middle line:84% that complements the target engagement pain card study. 00:03:35.580 --> 00:03:39.570 align:middle line:84% We now have further insight into the novel mechanism of action 00:03:39.570 --> 00:03:42.780 align:middle line:84% of TRV045 and we believe these results 00:03:42.780 --> 00:03:45.300 align:middle line:84% support future development either on our own 00:03:45.300 --> 00:03:47.300 align:middle line:90% or with a partner. 00:03:47.300 --> 00:03:49.150 align:middle line:84% Let me now turn the call over to Mark 00:03:49.150 --> 00:03:51.580 align:middle line:84% to walk through the results after which I'll 00:03:51.580 --> 00:03:53.860 align:middle line:84% provide some additional business updates. 00:03:53.860 --> 00:03:54.970 align:middle line:90% Mark? 00:03:54.970 --> 00:03:56.740 align:middle line:84% MARK DEMITRACK: Thank you, Carrie. 00:03:56.740 --> 00:03:59.170 align:middle line:84% As Carrie indicated, this has been 00:03:59.170 --> 00:04:02.170 align:middle line:84% an exciting quarter for our clinical development team. 00:04:02.170 --> 00:04:05.170 align:middle line:84% And today I'm pleased to report the preliminary findings 00:04:05.170 --> 00:04:09.310 align:middle line:84% from our two proof of concept studies for TRV045, 00:04:09.310 --> 00:04:13.110 align:middle line:84% our novel S1P receptor modulator. 00:04:13.110 --> 00:04:16.620 align:middle line:84% Before discussing the data I'd like to provide some context 00:04:16.620 --> 00:04:20.940 align:middle line:84% for why we are so excited about the opportunities we see in 045 00:04:20.940 --> 00:04:26.160 align:middle line:84% And what sets it apart from other drugs in this class. 00:04:26.160 --> 00:04:30.630 align:middle line:84% This slide highlights one of the main features of TRV045. 00:04:30.630 --> 00:04:34.620 align:middle line:84% We believe that because of how rapidly the bound drug receptor 00:04:34.620 --> 00:04:37.830 align:middle line:84% complex is internalized and recycled reflected 00:04:37.830 --> 00:04:40.800 align:middle line:84% in the steps shown in the green box at the bottom, 00:04:40.800 --> 00:04:44.850 align:middle line:84% TRV045 should be devoid of any effect on circulating 00:04:44.850 --> 00:04:46.980 align:middle line:90% peripheral lymphocytes. 00:04:46.980 --> 00:04:49.710 align:middle line:84% In our prior phase I study results 00:04:49.710 --> 00:04:53.190 align:middle line:84% we saw no reduction in lymphocyte levels, which 00:04:53.190 --> 00:04:57.960 align:middle line:84% we believe will lead to no long term immunosuppression. 00:04:57.960 --> 00:05:01.890 align:middle line:84% This next slide shows another important property of 045, 00:05:01.890 --> 00:05:07.620 align:middle line:84% namely its targeted specificity for the type I S1P receptor. 00:05:07.620 --> 00:05:11.550 align:middle line:84% We believe this is important since the type I receptor is 00:05:11.550 --> 00:05:14.070 align:middle line:84% highly expressed on cell targets of interest 00:05:14.070 --> 00:05:17.280 align:middle line:84% in the brain, astrocytes and microglia, 00:05:17.280 --> 00:05:21.230 align:middle line:84% both implicated in brain inflammation. 00:05:21.230 --> 00:05:24.490 align:middle line:84% This was a critical aspect of 045 properties, 00:05:24.490 --> 00:05:27.760 align:middle line:84% which led us to investigate its potential application 00:05:27.760 --> 00:05:31.690 align:middle line:84% for disease targets like neuropathic pain and epilepsy 00:05:31.690 --> 00:05:34.750 align:middle line:84% since these cells are believed to play an important role 00:05:34.750 --> 00:05:37.930 align:middle line:84% in the regulation of brain signaling events key 00:05:37.930 --> 00:05:40.000 align:middle line:84% to the development of chronic pain, 00:05:40.000 --> 00:05:43.720 align:middle line:84% and to play key roles in the physiology of how seizures 00:05:43.720 --> 00:05:48.320 align:middle line:84% develop and how they persist in causing epilepsy. 00:05:48.320 --> 00:05:51.050 align:middle line:84% With that as background, we embarked on our clinical proof 00:05:51.050 --> 00:05:54.080 align:middle line:84% of concept study program with two key goals 00:05:54.080 --> 00:05:57.550 align:middle line:90% in mind outlined on this slide. 00:05:57.550 --> 00:06:00.300 align:middle line:84% First, we wanted to provide evidence 00:06:00.300 --> 00:06:05.460 align:middle line:84% that TRV045 penetrates the CNS and engages its target 00:06:05.460 --> 00:06:09.150 align:middle line:84% as demonstrated by appropriately chosen pharmacodynamic outcome 00:06:09.150 --> 00:06:11.620 align:middle line:90% measures in humans. 00:06:11.620 --> 00:06:15.120 align:middle line:84% Second, we plan to measure plasma concentrations 00:06:15.120 --> 00:06:18.060 align:middle line:84% during these studies to help guide future development 00:06:18.060 --> 00:06:20.520 align:middle line:84% of our next generation drug formulation 00:06:20.520 --> 00:06:23.280 align:middle line:84% and to help frame our dose selection 00:06:23.280 --> 00:06:28.270 align:middle line:84% considerations for subsequent phase II development. 00:06:28.270 --> 00:06:31.020 align:middle line:84% Finally, we wanted to provide additional safety 00:06:31.020 --> 00:06:33.960 align:middle line:84% and tolerability data to support what we already 00:06:33.960 --> 00:06:37.170 align:middle line:90% saw in our prior phase I study. 00:06:37.170 --> 00:06:39.210 align:middle line:84% To accomplish these goals, we chose 00:06:39.210 --> 00:06:42.510 align:middle line:84% to pursue two different, but complementary proof of concept 00:06:42.510 --> 00:06:44.940 align:middle line:84% studies, each with different design 00:06:44.940 --> 00:06:47.250 align:middle line:84% features, pharmacodynamic measures, 00:06:47.250 --> 00:06:52.750 align:middle line:84% and clinical targets in mind to help guide our path forward. 00:06:52.750 --> 00:06:54.880 align:middle line:84% The first study, which we've referred 00:06:54.880 --> 00:06:58.780 align:middle line:84% to previously as the target engagement study employed 00:06:58.780 --> 00:07:02.110 align:middle line:84% a variety of human experimental pain models to help 00:07:02.110 --> 00:07:04.390 align:middle line:84% probe the peripheral and central actions 00:07:04.390 --> 00:07:09.150 align:middle line:90% of TRV045 shown on this slide. 00:07:09.150 --> 00:07:13.580 align:middle line:84% This study conducted in 25 male and female subjects 00:07:13.580 --> 00:07:16.660 align:middle line:84% used a placebo-controlled single dose, 00:07:16.660 --> 00:07:19.010 align:middle line:90% dose ranging crossover design. 00:07:19.010 --> 00:07:21.830 align:middle line:84% The dose is chosen based on the PK parameters 00:07:21.830 --> 00:07:25.160 align:middle line:84% we saw in our prior phase I study. 00:07:25.160 --> 00:07:27.950 align:middle line:84% The pharmacodynamic endpoints examined in the target 00:07:27.950 --> 00:07:30.200 align:middle line:84% engagement study are shown on the lower portion 00:07:30.200 --> 00:07:34.100 align:middle line:84% of this slide, an assay at a broad range of pain modalities, 00:07:34.100 --> 00:07:37.400 align:middle line:84% such as pressure, heat, electrical, and cold pain 00:07:37.400 --> 00:07:41.300 align:middle line:84% and also used capsaicin as a skin irritant, which serves 00:07:41.300 --> 00:07:43.025 align:middle line:90% as a model of neuropathic pain. 00:07:43.025 --> 00:07:45.560 align:middle line:90% 00:07:45.560 --> 00:07:49.040 align:middle line:84% Second, proof of concept study used transcranial magnetic 00:07:49.040 --> 00:07:53.600 align:middle line:84% stimulation, or TMS, to probe the potential effect of 045 00:07:53.600 --> 00:07:57.710 align:middle line:84% on cortical excitability in the brain and was conducted in 25 00:07:57.710 --> 00:07:59.630 align:middle line:90% male subjects. 00:07:59.630 --> 00:08:02.750 align:middle line:84% This study used a placebo-controlled multiple 00:08:02.750 --> 00:08:08.210 align:middle line:84% dose crossover design with 045 given over 4 days and measured 00:08:08.210 --> 00:08:11.870 align:middle line:84% outcomes using electroencephalography, or EEG, 00:08:11.870 --> 00:08:16.220 align:middle line:84% and electromyography, or EMG, to track changes in brain 00:08:16.220 --> 00:08:21.430 align:middle line:84% electrical activity after dosing with TRV045. 00:08:21.430 --> 00:08:23.350 align:middle line:84% We announced the preliminary results 00:08:23.350 --> 00:08:25.270 align:middle line:84% from both of these studies today. 00:08:25.270 --> 00:08:28.270 align:middle line:84% And I'm very pleased to report that the results provide us 00:08:28.270 --> 00:08:31.840 align:middle line:84% with a wealth of encouraging information and offer insights 00:08:31.840 --> 00:08:34.780 align:middle line:84% into the potential path forward for our future development 00:08:34.780 --> 00:08:38.130 align:middle line:90% efforts with 045. 00:08:38.130 --> 00:08:41.070 align:middle line:84% I'll summarize the most salient findings now. 00:08:41.070 --> 00:08:43.440 align:middle line:84% While we expect to receive the final safety 00:08:43.440 --> 00:08:46.350 align:middle line:84% and tolerability data by early fourth quarter of this year, 00:08:46.350 --> 00:08:50.460 align:middle line:84% I'll note that there were no SAEs or discontinuations 00:08:50.460 --> 00:08:55.680 align:middle line:84% due to study drug-related adverse events in either study. 00:08:55.680 --> 00:08:59.820 align:middle line:84% In the target engagement study, despite the small sample size, 00:08:59.820 --> 00:09:02.460 align:middle line:84% we saw a statistically significant 00:09:02.460 --> 00:09:05.580 align:middle line:84% dose-dependent treatment effect on the principal model 00:09:05.580 --> 00:09:09.270 align:middle line:84% for neuropathic pain, namely mechanical allodynia 00:09:09.270 --> 00:09:12.090 align:middle line:84% by Von Frey testing measured on skin 00:09:12.090 --> 00:09:16.010 align:middle line:90% exposed to topical capsaicin. 00:09:16.010 --> 00:09:18.500 align:middle line:84% I'd like to note that the results seen with this model 00:09:18.500 --> 00:09:21.800 align:middle line:84% are important since capsaicin irritation of the skin 00:09:21.800 --> 00:09:24.770 align:middle line:84% is recognized as a valid experimental model 00:09:24.770 --> 00:09:28.850 align:middle line:84% of neuropathic pain in humans and therefore, supports 00:09:28.850 --> 00:09:32.540 align:middle line:84% the hypothesis for the potential use of TRV045 00:09:32.540 --> 00:09:36.800 align:middle line:84% for neuropathic pain indications. 00:09:36.800 --> 00:09:40.500 align:middle line:84% The analgesic effect of 045 in this model is shown in two ways 00:09:40.500 --> 00:09:41.540 align:middle line:90% on this slide. 00:09:41.540 --> 00:09:45.230 align:middle line:84% On the left side, you can see that this analgesic effect was 00:09:45.230 --> 00:09:48.200 align:middle line:84% evident when measured in the area surrounding 00:09:48.200 --> 00:09:50.690 align:middle line:84% the region of skin where the capsaicin was directly 00:09:50.690 --> 00:09:54.960 align:middle line:84% applied, the so-called secondary allergenic area. 00:09:54.960 --> 00:09:58.230 align:middle line:84% On the right, we also saw the analgesic effect 00:09:58.230 --> 00:10:01.140 align:middle line:84% when we measured the total surface area affected, 00:10:01.140 --> 00:10:04.080 align:middle line:84% which includes the area of capsaicin application 00:10:04.080 --> 00:10:06.780 align:middle line:90% or the total allergenic area. 00:10:06.780 --> 00:10:10.390 align:middle line:84% For each of these graphs, the surface area of pain is shown. 00:10:10.390 --> 00:10:13.080 align:middle line:84% So as the bars go down, this means 00:10:13.080 --> 00:10:16.650 align:middle line:84% that the area of painful sensation is shrinking. 00:10:16.650 --> 00:10:19.530 align:middle line:84% In both analysis the results show 00:10:19.530 --> 00:10:22.650 align:middle line:84% statistically significant reductions in pain sensation 00:10:22.650 --> 00:10:27.450 align:middle line:84% or mechanical allodynia with both the 150 milligram and 300 00:10:27.450 --> 00:10:29.670 align:middle line:90% milligram doses. 00:10:29.670 --> 00:10:32.610 align:middle line:84% Note also that the effect is evident beginning 00:10:32.610 --> 00:10:35.670 align:middle line:84% 2 hours after dosing and nicely followed 00:10:35.670 --> 00:10:38.550 align:middle line:84% the trajectory of the plasma concentrations of the drug, 00:10:38.550 --> 00:10:41.740 align:middle line:84% which generally show maximal concentrations around 4 00:10:41.740 --> 00:10:45.210 align:middle line:90% to 6 hours after dosing. 00:10:45.210 --> 00:10:47.940 align:middle line:84% The PK exposure we achieved in this study 00:10:47.940 --> 00:10:50.130 align:middle line:84% was consistent with the levels seen 00:10:50.130 --> 00:10:53.550 align:middle line:84% at these doses in our earlier phase one work 00:10:53.550 --> 00:10:56.340 align:middle line:84% and the half-life was comparable to the prior phase I 00:10:56.340 --> 00:10:59.685 align:middle line:84% study, which would support anticipated once daily dosing. 00:10:59.685 --> 00:11:02.410 align:middle line:90% 00:11:02.410 --> 00:11:06.610 align:middle line:84% To summarize, these data on the mechanical allodynia model 00:11:06.610 --> 00:11:10.990 align:middle line:84% were statistically significant, dose-dependent and provide 00:11:10.990 --> 00:11:13.810 align:middle line:84% support for the hypothesis that TRV045 00:11:13.810 --> 00:11:18.610 align:middle line:84% has the potential for use in neuropathic pain in patients. 00:11:18.610 --> 00:11:22.930 align:middle line:84% Also, the outcomes at the 150 milligram and 300 milligram 00:11:22.930 --> 00:11:26.540 align:middle line:84% doses will help to guide future decisions about dose selection 00:11:26.540 --> 00:11:32.380 align:middle line:84% as we advance towards future clinical studies in patients. 00:11:32.380 --> 00:11:35.320 align:middle line:84% In addition to the mechanical allodynia findings, 00:11:35.320 --> 00:11:38.510 align:middle line:84% additional trends were seen in several other pain models, 00:11:38.510 --> 00:11:42.040 align:middle line:84% including on the cold pain test, on measures of heat pain, 00:11:42.040 --> 00:11:44.470 align:middle line:84% and on one of two different measures of electrically 00:11:44.470 --> 00:11:47.740 align:middle line:84% stimulated pain though these results did not achieve 00:11:47.740 --> 00:11:50.070 align:middle line:90% statistical significance. 00:11:50.070 --> 00:11:52.650 align:middle line:84% Some of the pain modalities studied, including pressure 00:11:52.650 --> 00:11:54.780 align:middle line:84% pain and conditioned pain modulation 00:11:54.780 --> 00:11:59.040 align:middle line:84% showed no statistically significant effects or trends. 00:11:59.040 --> 00:12:01.620 align:middle line:84% It's important to note that this pattern of outcome 00:12:01.620 --> 00:12:04.290 align:middle line:84% with a statistically significant effect on the most 00:12:04.290 --> 00:12:08.160 align:middle line:84% relevant model for our intended neuropathic disease target 00:12:08.160 --> 00:12:11.910 align:middle line:84% along with evidence of analgesic effect on select other pain 00:12:11.910 --> 00:12:15.750 align:middle line:84% measures is encouraging as it suggests specificity 00:12:15.750 --> 00:12:18.460 align:middle line:90% in the mechanism of pain relief. 00:12:18.460 --> 00:12:22.150 align:middle line:84% Finally, results of the mechanical allodynia endpoint 00:12:22.150 --> 00:12:25.420 align:middle line:84% indicate that TRV045 is entering the brain 00:12:25.420 --> 00:12:27.790 align:middle line:84% since the pain signals in this model 00:12:27.790 --> 00:12:31.540 align:middle line:84% depend upon central pain signaling processes sometimes 00:12:31.540 --> 00:12:35.400 align:middle line:84% referred to as central sensitization. 00:12:35.400 --> 00:12:38.400 align:middle line:84% We've had the opportunity to discuss these top line results 00:12:38.400 --> 00:12:41.550 align:middle line:84% with several of our external advisors, all of whom 00:12:41.550 --> 00:12:43.560 align:middle line:84% agree that the results are very exciting. 00:12:43.560 --> 00:12:46.360 align:middle line:90% 00:12:46.360 --> 00:12:49.300 align:middle line:84% Results from the second proof of concept study using 00:12:49.300 --> 00:12:54.010 align:middle line:84% TMS to probe brain electrical activity using both EEG and EMG 00:12:54.010 --> 00:12:56.680 align:middle line:90% methods were also encouraging. 00:12:56.680 --> 00:12:58.690 align:middle line:84% While many of the outcomes did not 00:12:58.690 --> 00:13:00.800 align:middle line:84% achieve statistical significance, 00:13:00.800 --> 00:13:03.760 align:middle line:84% the results did provide additional statistically 00:13:03.760 --> 00:13:08.440 align:middle line:84% significant evidence indicating CNS penetrance of TRV045 00:13:08.440 --> 00:13:11.590 align:middle line:84% as shown through measurable changes in select measures 00:13:11.590 --> 00:13:15.760 align:middle line:84% of brain electrical activity on the resting state EEG power 00:13:15.760 --> 00:13:18.670 align:middle line:90% spectral analysis. 00:13:18.670 --> 00:13:22.690 align:middle line:84% Among the EEG-related endpoints measured in the study resting 00:13:22.690 --> 00:13:26.710 align:middle line:84% state EEG obtained before and after administration of 045. 00:13:26.710 --> 00:13:30.160 align:middle line:84% On the first and the last or fourth day of dosing 00:13:30.160 --> 00:13:33.670 align:middle line:84% demonstrated statistically significant increases 00:13:33.670 --> 00:13:36.100 align:middle line:84% in the power spectral density in several 00:13:36.100 --> 00:13:39.520 align:middle line:84% of the middle to higher frequency bands including 00:13:39.520 --> 00:13:42.970 align:middle line:90% alpha, beta, and gamma waves. 00:13:42.970 --> 00:13:45.550 align:middle line:84% These changes were evident on day 1 00:13:45.550 --> 00:13:49.600 align:middle line:84% and became more prominent on day 4 of dosing. 00:13:49.600 --> 00:13:54.520 align:middle line:84% The changes on day 4 are shown on this slide for 045 compared 00:13:54.520 --> 00:13:56.350 align:middle line:90% to placebo. 00:13:56.350 --> 00:14:00.190 align:middle line:84% With 045, an increase in alpha waves was the most notable 00:14:00.190 --> 00:14:04.000 align:middle line:84% observation with increased power evident in the frontal region 00:14:04.000 --> 00:14:07.420 align:middle line:84% and in the parietal regions in the back of the brain in both 00:14:07.420 --> 00:14:11.230 align:middle line:90% the left and right hemispheres. 00:14:11.230 --> 00:14:13.890 align:middle line:84% The increase in beta and gamma wave power spectra 00:14:13.890 --> 00:14:17.680 align:middle line:84% were noted over the frontal regions only. 00:14:17.680 --> 00:14:19.360 align:middle line:84% Alpha waves are generally considered 00:14:19.360 --> 00:14:22.900 align:middle line:84% to be associated with conscious arousal and alertness 00:14:22.900 --> 00:14:25.180 align:middle line:84% while beta waves are thought to be associated 00:14:25.180 --> 00:14:29.380 align:middle line:84% with GABA-mediated inhibitory corticospinal neurotransmission 00:14:29.380 --> 00:14:32.050 align:middle line:84% and gamma waves are generally associated 00:14:32.050 --> 00:14:36.110 align:middle line:84% with cognitive processing, learning, and memory. 00:14:36.110 --> 00:14:38.650 align:middle line:84% In addition to these changes, we also 00:14:38.650 --> 00:14:42.130 align:middle line:84% studied the slower brain wave spectrum in the delta and theta 00:14:42.130 --> 00:14:43.630 align:middle line:90% wavelengths. 00:14:43.630 --> 00:14:46.000 align:middle line:84% These EEG wavelengths are generally 00:14:46.000 --> 00:14:48.550 align:middle line:84% associated with sedation and sleep. 00:14:48.550 --> 00:14:50.590 align:middle line:84% And activity in these power spectra 00:14:50.590 --> 00:14:53.830 align:middle line:84% are increased with some antiepileptic drugs 00:14:53.830 --> 00:14:56.680 align:middle line:84% and are thought to correlate with their reported 00:14:56.680 --> 00:14:59.750 align:middle line:84% adverse effects on cognitive function in patients. 00:14:59.750 --> 00:15:02.230 align:middle line:84% Therefore, we noted with interest 00:15:02.230 --> 00:15:05.050 align:middle line:84% that unlike the changes in the mid to higher frequency 00:15:05.050 --> 00:15:08.650 align:middle line:84% brainwave bands, there was a statistically significant 00:15:08.650 --> 00:15:11.800 align:middle line:84% decrease in the slow delta brain waves, 00:15:11.800 --> 00:15:15.730 align:middle line:84% again, in the frontal region and no difference in slow theta 00:15:15.730 --> 00:15:18.690 align:middle line:90% brain waves. 00:15:18.690 --> 00:15:22.110 align:middle line:84% Among the EMG-related endpoints measured in the study 00:15:22.110 --> 00:15:26.190 align:middle line:84% TRV045 demonstrated evidence of reduction 00:15:26.190 --> 00:15:30.600 align:middle line:84% in cortical excitability on day 1 of drug dosing in response 00:15:30.600 --> 00:15:33.300 align:middle line:90% to single pulse TMS. 00:15:33.300 --> 00:15:35.460 align:middle line:84% The difference in mean peak motor 00:15:35.460 --> 00:15:40.800 align:middle line:84% evoked potential or amplitude was minus 304 microvolts 00:15:40.800 --> 00:15:42.720 align:middle line:84% though this result did not achieve 00:15:42.720 --> 00:15:45.130 align:middle line:90% statistical significance. 00:15:45.130 --> 00:15:49.830 align:middle line:84% This outcome for 045 is shown on the left of this slide. 00:15:49.830 --> 00:15:52.920 align:middle line:84% For context, on the right side are the results 00:15:52.920 --> 00:15:55.170 align:middle line:84% of the study guide in the same laboratory 00:15:55.170 --> 00:15:59.610 align:middle line:84% also using TMS-EMG to monitor amplitude change 00:15:59.610 --> 00:16:03.440 align:middle line:84% in a different population of subjects. 00:16:03.440 --> 00:16:06.380 align:middle line:84% The map decrease, we observed in our study 00:16:06.380 --> 00:16:08.810 align:middle line:84% it's of a magnitude similar to that 00:16:08.810 --> 00:16:11.660 align:middle line:84% seen with other known antiepileptic drugs 00:16:11.660 --> 00:16:14.770 align:middle line:90% in the other study shown here. 00:16:14.770 --> 00:16:17.310 align:middle line:84% Although we can't directly compare these outcomes 00:16:17.310 --> 00:16:19.560 align:middle line:84% as there have not been head-to-head comparative 00:16:19.560 --> 00:16:22.530 align:middle line:84% studies, they do provide some context 00:16:22.530 --> 00:16:26.220 align:middle line:84% for interpreting what we are seeing in our results. 00:16:26.220 --> 00:16:30.330 align:middle line:84% There was no difference in mean peak map amplitude on day 4 00:16:30.330 --> 00:16:33.900 align:middle line:84% and no differences in resting motor threshold on day 1, 00:16:33.900 --> 00:16:37.920 align:middle line:84% or day 4, or on other EMG-related endpoints. 00:16:37.920 --> 00:16:43.410 align:middle line:84% In our study, we examined only one dose of 045 and measured 00:16:43.410 --> 00:16:47.880 align:middle line:84% amplitude and resting motor threshold only at one post-dose 00:16:47.880 --> 00:16:51.510 align:middle line:84% timepoint due to the complexity of the testing demands of this 00:16:51.510 --> 00:16:52.920 align:middle line:90% study. 00:16:52.920 --> 00:16:57.240 align:middle line:84% Overall we believe these early results are encouraging. 00:16:57.240 --> 00:17:00.720 align:middle line:84% We are very pleased with the results of these two studies. 00:17:00.720 --> 00:17:03.270 align:middle line:84% And as I mentioned above, we've received 00:17:03.270 --> 00:17:06.359 align:middle line:84% positive initial feedback from discussions with our advisors 00:17:06.359 --> 00:17:09.589 align:middle line:90% on both of them. 00:17:09.589 --> 00:17:12.200 align:middle line:84% Taken together we believe these data 00:17:12.200 --> 00:17:16.819 align:middle line:84% show that TRV045 gains access to the CNS 00:17:16.819 --> 00:17:19.490 align:middle line:84% and engages the brain in a manner 00:17:19.490 --> 00:17:22.910 align:middle line:84% consistent with the results we observed in our animal models 00:17:22.910 --> 00:17:26.440 align:middle line:84% in both neuropathic pain and epilepsy. 00:17:26.440 --> 00:17:30.400 align:middle line:84% In addition, we demonstrated a statistically significant 00:17:30.400 --> 00:17:33.650 align:middle line:84% treatment effect in the mechanical allodynia model, 00:17:33.650 --> 00:17:37.000 align:middle line:84% which is particularly noteworthy since it is considered 00:17:37.000 --> 00:17:40.360 align:middle line:84% to be a valid experimental model of neuropathic pain 00:17:40.360 --> 00:17:45.010 align:middle line:84% and central sensitization processes in the brain. 00:17:45.010 --> 00:17:48.510 align:middle line:84% We also showed interesting statistically significant 00:17:48.510 --> 00:17:51.120 align:middle line:84% effects on brainwave activity that may 00:17:51.120 --> 00:17:53.550 align:middle line:90% be relevant across indications. 00:17:53.550 --> 00:17:57.540 align:middle line:84% And finally, we showed promising evidence of early reductions 00:17:57.540 --> 00:18:00.870 align:middle line:90% in cortical excitability. 00:18:00.870 --> 00:18:02.880 align:middle line:84% We'll study these preliminary results 00:18:02.880 --> 00:18:05.010 align:middle line:84% in more detail in the coming months 00:18:05.010 --> 00:18:08.820 align:middle line:84% and also expect additional data from the ETSP, which 00:18:08.820 --> 00:18:12.690 align:middle line:84% is studying TRV045 as a potential disease modifying 00:18:12.690 --> 00:18:16.730 align:middle line:84% therapeutic for epilepsy prevention. 00:18:16.730 --> 00:18:20.150 align:middle line:84% We plan to continue to advance toward future clinical studies 00:18:20.150 --> 00:18:24.560 align:middle line:84% in patients either on our own or with a strategic partner 00:18:24.560 --> 00:18:27.500 align:middle line:84% and look forward to updating you soon. 00:18:27.500 --> 00:18:30.020 align:middle line:84% I'd now like to open the call for questions. 00:18:30.020 --> 00:18:32.840 align:middle line:90% Operator? 00:18:32.840 --> 00:18:33.710 align:middle line:90% MELISSA: Thank you. 00:18:33.710 --> 00:18:35.750 align:middle line:84% If you'd like to ask a question, please 00:18:35.750 --> 00:18:38.310 align:middle line:84% press star-one on your telephone keypad. 00:18:38.310 --> 00:18:40.250 align:middle line:84% A confirmation tone will indicate your line 00:18:40.250 --> 00:18:41.780 align:middle line:90% is in the question queue. 00:18:41.780 --> 00:18:44.450 align:middle line:84% You may press star-two if you'd like to remove 00:18:44.450 --> 00:18:45.890 align:middle line:90% your question from the queue. 00:18:45.890 --> 00:18:47.900 align:middle line:84% For participants using speaker equipment 00:18:47.900 --> 00:18:50.090 align:middle line:84% it may be necessary to pick up your handset 00:18:50.090 --> 00:18:52.310 align:middle line:90% before pressing the star keys. 00:18:52.310 --> 00:18:55.040 align:middle line:84% Our first question comes from the line of Jason Butler 00:18:55.040 --> 00:18:56.330 align:middle line:90% with JMP Securities. 00:18:56.330 --> 00:18:58.860 align:middle line:84% Please proceed with your question. 00:18:58.860 --> 00:19:00.860 align:middle line:84% JASON BUTLER: Hi, thanks for taking the question 00:19:00.860 --> 00:19:03.260 align:middle line:90% and congrats on the results. 00:19:03.260 --> 00:19:06.110 align:middle line:84% Maybe just at a high level, can you just give us some thoughts 00:19:06.110 --> 00:19:07.710 align:middle line:90% here on next steps. 00:19:07.710 --> 00:19:11.360 align:middle line:84% How are you going to prioritize the two different settings 00:19:11.360 --> 00:19:13.340 align:middle line:90% chronic pain versus epilepsy? 00:19:13.340 --> 00:19:16.490 align:middle line:84% How you're thinking about the different epilepsy populations 00:19:16.490 --> 00:19:17.390 align:middle line:90% you could study. 00:19:17.390 --> 00:19:21.920 align:middle line:84% And then on the funding side of things, just how you're 00:19:21.920 --> 00:19:24.500 align:middle line:84% thinking about prioritizing partnerships 00:19:24.500 --> 00:19:27.362 align:middle line:84% versus go alone and different indications. 00:19:27.362 --> 00:19:28.320 align:middle line:90% And I have a follow-up. 00:19:28.320 --> 00:19:29.013 align:middle line:90% Thanks. 00:19:29.013 --> 00:19:29.930 align:middle line:90% CARRIE BOURDOW: Great. 00:19:29.930 --> 00:19:30.800 align:middle line:90% Thank you, Jason. 00:19:30.800 --> 00:19:33.450 align:middle line:90% I appreciate the questions. 00:19:33.450 --> 00:19:38.320 align:middle line:84% Yeah, so we are very excited about this data. 00:19:38.320 --> 00:19:44.790 align:middle line:84% And as you heard, we're thinking about how we're 00:19:44.790 --> 00:19:46.810 align:middle line:90% going to approach next steps. 00:19:46.810 --> 00:19:49.200 align:middle line:84% First, I think we need to see the full safety 00:19:49.200 --> 00:19:52.350 align:middle line:84% and tolerability data on the epilepsy side, 00:19:52.350 --> 00:19:55.980 align:middle line:84% we're waiting for the NIH data on seizure prevention. 00:19:55.980 --> 00:19:59.415 align:middle line:84% We're a little bit further ahead as a company 00:19:59.415 --> 00:20:03.330 align:middle line:84% on neuropathic pain and I think this data then 00:20:03.330 --> 00:20:07.890 align:middle line:84% could lead to a more definitive studies in patients 00:20:07.890 --> 00:20:09.040 align:middle line:90% a little bit more quickly. 00:20:09.040 --> 00:20:13.650 align:middle line:84% But the NIH has been really interested in this compound 00:20:13.650 --> 00:20:16.840 align:middle line:84% and has been accelerating some of their work in epilepsy. 00:20:16.840 --> 00:20:19.620 align:middle line:84% So I'd like to see what the seizure prevention data looks 00:20:19.620 --> 00:20:26.280 align:middle line:84% like before we would declare, I think, on what models we might 00:20:26.280 --> 00:20:27.652 align:middle line:90% be wanting to do in epilepsy. 00:20:27.652 --> 00:20:29.610 align:middle line:84% But Mark, certainly has been thinking about it. 00:20:29.610 --> 00:20:33.390 align:middle line:84% As you heard, he's meeting with KOLs both in neuropathic pain 00:20:33.390 --> 00:20:37.980 align:middle line:84% and in epilepsy to prioritize and think about next steps. 00:20:37.980 --> 00:20:42.180 align:middle line:84% As it relates to partnerships or doing on our own, 00:20:42.180 --> 00:20:45.810 align:middle line:84% I think that was your question, there are certainly phase II 00:20:45.810 --> 00:20:48.510 align:middle line:84% type studies that we could do on our own, 00:20:48.510 --> 00:20:53.990 align:middle line:84% very targeted studies that could bring forward 045 and advance 00:20:53.990 --> 00:20:54.490 align:middle line:90% it. 00:20:54.490 --> 00:20:56.865 align:middle line:84% So those are some of the things that we're thinking about 00:20:56.865 --> 00:21:00.810 align:middle line:84% and we'll be back out with our plans here relatively soon. 00:21:00.810 --> 00:21:02.550 align:middle line:84% Mark, anything you want to comment around 00:21:02.550 --> 00:21:05.070 align:middle line:84% the patient populations you're thinking about? 00:21:05.070 --> 00:21:06.750 align:middle line:84% MARK DEMITRACK: Well, we've talked 00:21:06.750 --> 00:21:11.970 align:middle line:84% in the past about the epilepsy targets of interest 00:21:11.970 --> 00:21:14.280 align:middle line:84% and the data that we've assembled 00:21:14.280 --> 00:21:17.610 align:middle line:84% to date we think certainly points us 00:21:17.610 --> 00:21:19.500 align:middle line:84% in the direction of refractory epilepsy, 00:21:19.500 --> 00:21:23.370 align:middle line:84% a lot of the basic models that ETSP has studied 00:21:23.370 --> 00:21:25.380 align:middle line:90% modeled in that direction. 00:21:25.380 --> 00:21:29.400 align:middle line:84% And more importantly, the changes that we've seen that 00:21:29.400 --> 00:21:35.130 align:middle line:84% 045 appears to exert on immune mediators in the brain is one 00:21:35.130 --> 00:21:39.690 align:middle line:84% aspect of that's particularly excited our advisors as it may 00:21:39.690 --> 00:21:44.490 align:middle line:84% play a potential role in actually modifying the course 00:21:44.490 --> 00:21:49.590 align:middle line:84% of the disease and also for some orphan types of epilepsies 00:21:49.590 --> 00:21:53.850 align:middle line:84% where inflammatory process or immune-mediated events play 00:21:53.850 --> 00:21:56.370 align:middle line:84% a role in the propagation of those illnesses. 00:21:56.370 --> 00:21:59.340 align:middle line:84% So there are a couple of different avenues 00:21:59.340 --> 00:22:00.420 align:middle line:90% in front of us. 00:22:00.420 --> 00:22:05.350 align:middle line:84% And I would say for neuropathic pain it's similar. 00:22:05.350 --> 00:22:09.750 align:middle line:84% We've learned and we are learning a tremendous amount 00:22:09.750 --> 00:22:13.890 align:middle line:84% from the data that we've generated here that point us 00:22:13.890 --> 00:22:19.080 align:middle line:84% to particular understandings about the mechanism of 045. 00:22:19.080 --> 00:22:21.660 align:middle line:84% The efficacy and the mechanical allodynia model, 00:22:21.660 --> 00:22:27.780 align:middle line:84% for example, does suggest that receptors like TRPA1 00:22:27.780 --> 00:22:31.050 align:middle line:84% may be an important target for us to think about. 00:22:31.050 --> 00:22:34.020 align:middle line:84% That narrows down a bit the way we 00:22:34.020 --> 00:22:36.870 align:middle line:84% might shape inclusion criteria or even 00:22:36.870 --> 00:22:42.270 align:middle line:84% delete disease selection targets in the neuropathic pain space. 00:22:42.270 --> 00:22:44.590 align:middle line:84% Small fiber neuropathy, for example, 00:22:44.590 --> 00:22:50.250 align:middle line:84% comes up as an area that is, I think, a pretty fruitful for us 00:22:50.250 --> 00:22:51.390 align:middle line:90% to dig into. 00:22:51.390 --> 00:22:56.680 align:middle line:84% Even in some of the larger targets like OA, 00:22:56.680 --> 00:23:04.290 align:middle line:84% for example, or other neuropathy targets, even though large 00:23:04.290 --> 00:23:08.430 align:middle line:84% based on the mechanism we may be able to narrow down our focus 00:23:08.430 --> 00:23:11.610 align:middle line:84% so that we can have an efficient understanding of proof 00:23:11.610 --> 00:23:14.160 align:middle line:84% of concept in that work moving forward. 00:23:14.160 --> 00:23:16.740 align:middle line:84% CARRIE BOURDOW: I think because Mark and his team 00:23:16.740 --> 00:23:21.900 align:middle line:84% studied so many different aspects of pain it really 00:23:21.900 --> 00:23:25.650 align:middle line:84% helped us think about and derisk frankly other 00:23:25.650 --> 00:23:27.233 align:middle line:84% studies that we might want to take on. 00:23:27.233 --> 00:23:29.525 align:middle line:84% So I there are some orphan pain indications you're also 00:23:29.525 --> 00:23:30.720 align:middle line:90% thinking about in addition. 00:23:30.720 --> 00:23:31.440 align:middle line:90% MARK DEMITRACK: That's right. 00:23:31.440 --> 00:23:32.355 align:middle line:90% CARRIE BOURDOW: Yeah. 00:23:32.355 --> 00:23:33.563 align:middle line:90% MARK DEMITRACK: That's right. 00:23:33.563 --> 00:23:35.670 align:middle line:84% There are some orphan pain indications 00:23:35.670 --> 00:23:39.660 align:middle line:84% where the literature suggests that central sensitization may 00:23:39.660 --> 00:23:43.140 align:middle line:84% play an important role in things like sickle cell disease 00:23:43.140 --> 00:23:46.810 align:middle line:84% even some subsets of patients with Ehlers-Danlos syndrome, 00:23:46.810 --> 00:23:50.250 align:middle line:84% for example, are areas that we've been interested 00:23:50.250 --> 00:23:53.167 align:middle line:90% in our discussions. 00:23:53.167 --> 00:23:54.000 align:middle line:90% JASON BUTLER: Great. 00:23:54.000 --> 00:23:58.320 align:middle line:84% And then just on the Capsaicin data, just data model data, 00:23:58.320 --> 00:24:01.080 align:middle line:84% could you just put the magnitude of change 00:24:01.080 --> 00:24:03.510 align:middle line:84% into context used for neuropathic pain 00:24:03.510 --> 00:24:04.410 align:middle line:90% like gabapentin? 00:24:04.410 --> 00:24:06.370 align:middle line:84% And then I know it's still early, 00:24:06.370 --> 00:24:09.990 align:middle line:84% but can you maybe frame the size and scope of a phase II 00:24:09.990 --> 00:24:13.140 align:middle line:84% study in patients that would be informative 00:24:13.140 --> 00:24:16.555 align:middle line:90% or could be a next step? 00:24:16.555 --> 00:24:17.430 align:middle line:90% MARK DEMITRACK: Sure. 00:24:17.430 --> 00:24:20.235 align:middle line:84% Well, I can comment on the size of the effect 00:24:20.235 --> 00:24:21.850 align:middle line:90% in a couple of ways. 00:24:21.850 --> 00:24:26.130 align:middle line:84% One is just the shear strength of the statistical signal. 00:24:26.130 --> 00:24:31.536 align:middle line:84% When you look at it as a stand alone piece of data 00:24:31.536 --> 00:24:35.560 align:middle line:84% it is of a magnitude that in statistical terms, 00:24:35.560 --> 00:24:37.050 align:middle line:90% we would consider large. 00:24:37.050 --> 00:24:41.360 align:middle line:84% You have effect sizes that are approaching on the order of 0.9 00:24:41.360 --> 00:24:45.900 align:middle line:84% or 1 here, that's a very meaningful change 00:24:45.900 --> 00:24:47.250 align:middle line:90% in statistical terms. 00:24:47.250 --> 00:24:51.720 align:middle line:84% The capsaicin model has been used in a variety of ways 00:24:51.720 --> 00:24:54.100 align:middle line:90% and including with gabapentin. 00:24:54.100 --> 00:25:00.040 align:middle line:84% And when we look at data from comparable models of capsaicin 00:25:00.040 --> 00:25:04.000 align:middle line:84% irritation with drugs like that with opioids, 00:25:04.000 --> 00:25:08.410 align:middle line:84% these are the kinds of changes that we see in those models. 00:25:08.410 --> 00:25:12.940 align:middle line:84% I'd also point to some of the more recent data 00:25:12.940 --> 00:25:18.040 align:middle line:84% even with some of the compounds like the nave inhibitors that 00:25:18.040 --> 00:25:22.760 align:middle line:84% use similar types of neuropathic pain model targets. 00:25:22.760 --> 00:25:27.820 align:middle line:84% So we're pretty pleased with the results we've seen here. 00:25:27.820 --> 00:25:32.845 align:middle line:84% In terms of the phase II, like I was saying earlier, 00:25:32.845 --> 00:25:36.130 align:middle line:84% our approach in the near term is going 00:25:36.130 --> 00:25:39.850 align:middle line:84% to be to build on the understanding we have 00:25:39.850 --> 00:25:43.120 align:middle line:84% as to where this data points us mechanistically 00:25:43.120 --> 00:25:48.890 align:middle line:84% and then to think efficiently about clinical targets. 00:25:48.890 --> 00:25:52.990 align:middle line:84% So again, think more selected populations 00:25:52.990 --> 00:25:56.170 align:middle line:84% where we can get a homogeneous patient sample 00:25:56.170 --> 00:26:01.940 align:middle line:84% and get a very robust signal in a quick manner. 00:26:01.940 --> 00:26:04.330 align:middle line:84% So those are the kinds of things we're beginning 00:26:04.330 --> 00:26:05.980 align:middle line:90% to think about at this stage. 00:26:05.980 --> 00:26:08.320 align:middle line:84% CARRIE BOURDOW: Yeah, our plan is 00:26:08.320 --> 00:26:12.175 align:middle line:84% or our thinking is to have a very targeted study 00:26:12.175 --> 00:26:16.600 align:middle line:84% to get this drug into patients, that would be the next steps. 00:26:16.600 --> 00:26:19.990 align:middle line:84% And so that's why Mark's been spending time with KOLs. 00:26:19.990 --> 00:26:23.080 align:middle line:84% Obviously, we just got the data, so he's 00:26:23.080 --> 00:26:25.630 align:middle line:84% been thinking about models by presenting the data now 00:26:25.630 --> 00:26:28.180 align:middle line:84% to the KOLs and think through next steps 00:26:28.180 --> 00:26:32.330 align:middle line:84% to get it a targeted phase II study in patients. 00:26:32.330 --> 00:26:34.360 align:middle line:84% And as I mentioned, we're further ahead 00:26:34.360 --> 00:26:35.980 align:middle line:84% with neuropathic pain, but I'm really 00:26:35.980 --> 00:26:40.405 align:middle line:84% anxious to see the NIH's data on seizure prevention as well. 00:26:40.405 --> 00:26:43.410 align:middle line:90% 00:26:43.410 --> 00:26:44.410 align:middle line:90% JASON BUTLER: OK, great. 00:26:44.410 --> 00:26:45.743 align:middle line:90% Thanks for taking the questions. 00:26:45.743 --> 00:26:47.595 align:middle line:84% And congrats, again, on the results. 00:26:47.595 --> 00:26:48.970 align:middle line:84% CARRIE BOURDOW: Thank you, Jason. 00:26:48.970 --> 00:26:51.838 align:middle line:90% Appreciate it. 00:26:51.838 --> 00:26:52.630 align:middle line:90% MELISSA: Thank you. 00:26:52.630 --> 00:26:54.930 align:middle line:84% Our next question comes from the line of Douglas Xu 00:26:54.930 --> 00:26:56.340 align:middle line:90% with H.C. Wainwright. 00:26:56.340 --> 00:26:59.222 align:middle line:84% Please proceed with your question. 00:26:59.222 --> 00:27:00.430 align:middle line:90% DOUGLAS XU: Hi, good morning. 00:27:00.430 --> 00:27:01.510 align:middle line:90% Can you hear me? 00:27:01.510 --> 00:27:03.780 align:middle line:90% CARRIE BOURDOW: Yes. 00:27:03.780 --> 00:27:05.280 align:middle line:84% DOUGLAS XU: So congrats on the data. 00:27:05.280 --> 00:27:11.730 align:middle line:84% I'm just curious starting on the pain side, 00:27:11.730 --> 00:27:17.250 align:middle line:84% is your inclination to start in broader indications 00:27:17.250 --> 00:27:19.920 align:middle line:84% and then potentially narrow down or take 00:27:19.920 --> 00:27:23.610 align:middle line:84% the opposite because that could potentially be a faster course? 00:27:23.610 --> 00:27:29.430 align:middle line:84% And I guess a similar question in terms of epilepsy, what 00:27:29.430 --> 00:27:30.970 align:middle line:90% are the immediate next steps? 00:27:30.970 --> 00:27:33.390 align:middle line:84% I mean, is there anything that you can do or are you 00:27:33.390 --> 00:27:36.840 align:middle line:84% really waiting to see what NIH comes up with? 00:27:36.840 --> 00:27:38.490 align:middle line:90% Thank you. 00:27:38.490 --> 00:27:39.750 align:middle line:90% CARRIE BOURDOW: Yeah. 00:27:39.750 --> 00:27:41.960 align:middle line:90% Doug, so good questions. 00:27:41.960 --> 00:27:45.510 align:middle line:84% And as I said earlier, let me take on the pain side. 00:27:45.510 --> 00:27:49.260 align:middle line:84% So there are subsets in the broader markets, 00:27:49.260 --> 00:27:50.620 align:middle line:90% as Mark talked about. 00:27:50.620 --> 00:27:54.240 align:middle line:84% So if you think about OA or back pain, 00:27:54.240 --> 00:27:57.870 align:middle line:84% some of these large markets, there are subsets of patients 00:27:57.870 --> 00:28:00.330 align:middle line:84% within those markets that we think based on the mechanism 00:28:00.330 --> 00:28:04.950 align:middle line:84% of action and the area where we're headed towards 00:28:04.950 --> 00:28:09.360 align:middle line:84% neuropathic pain would be very interesting for 045. 00:28:09.360 --> 00:28:11.730 align:middle line:84% And then as Mark described, there's 00:28:11.730 --> 00:28:18.090 align:middle line:84% even potentially some orphan area like Ehlers-Danlos. 00:28:18.090 --> 00:28:21.572 align:middle line:84% On the pain, I'm sorry, on the epilepsy front 00:28:21.572 --> 00:28:23.280 align:middle line:84% I think it's going to be important for us 00:28:23.280 --> 00:28:24.570 align:middle line:90% to see the seizure prevention. 00:28:24.570 --> 00:28:28.500 align:middle line:84% We certainly could move forward without seeing the ETSP data, 00:28:28.500 --> 00:28:31.470 align:middle line:90% without seeing the NIH data. 00:28:31.470 --> 00:28:34.890 align:middle line:84% And so we're talking with our advisors 00:28:34.890 --> 00:28:36.667 align:middle line:84% on next steps on epilepsy as well. 00:28:36.667 --> 00:28:38.500 align:middle line:84% Mark, I don't know if there's some specifics 00:28:38.500 --> 00:28:41.200 align:middle line:90% you want to give on that. 00:28:41.200 --> 00:28:44.740 align:middle line:84% MARK DEMITRACK: Well, I can echo what I had mentioned earlier. 00:28:44.740 --> 00:28:47.500 align:middle line:84% I think for us right now we've learned a tremendous amount, 00:28:47.500 --> 00:28:52.780 align:middle line:84% we believe, about the mechanism here particularly from the pain 00:28:52.780 --> 00:28:54.100 align:middle line:90% data. 00:28:54.100 --> 00:28:58.180 align:middle line:84% So it points us in a more targeted way 00:28:58.180 --> 00:29:03.310 align:middle line:84% when we think about selection of subjects in our first step 00:29:03.310 --> 00:29:06.466 align:middle line:90% into patient-based studies. 00:29:06.466 --> 00:29:13.420 align:middle line:84% So our goal here is to get a clear, unambiguous, convincing 00:29:13.420 --> 00:29:16.730 align:middle line:84% signal in those next step studies. 00:29:16.730 --> 00:29:22.450 align:middle line:84% So linking the mechanism in that way to selection of patients 00:29:22.450 --> 00:29:26.200 align:middle line:84% is critical and it's an analogous type of approach 00:29:26.200 --> 00:29:28.270 align:middle line:90% when we think about epilepsy. 00:29:28.270 --> 00:29:31.930 align:middle line:84% I think the remaining ETSP data has been informative. 00:29:31.930 --> 00:29:33.497 align:middle line:84% But don't forget that we've already 00:29:33.497 --> 00:29:35.080 align:middle line:84% discussed with you in the past that we 00:29:35.080 --> 00:29:38.350 align:middle line:84% have tremendous amount of data that ETSP has already 00:29:38.350 --> 00:29:41.890 align:middle line:84% generated that we believe is quite informative. 00:29:41.890 --> 00:29:42.400 align:middle line:90% Carrie? 00:29:42.400 --> 00:29:44.817 align:middle line:84% CARRIE BOURDOW: Yeah the only other comment I want to make 00:29:44.817 --> 00:29:47.830 align:middle line:84% is what Mark commented on and I did 00:29:47.830 --> 00:29:50.980 align:middle line:84% as well is that we were talking about this on our own 00:29:50.980 --> 00:29:52.870 align:middle line:90% or with potential partners. 00:29:52.870 --> 00:29:55.930 align:middle line:84% And so some of those larger indications, both in pain 00:29:55.930 --> 00:30:01.240 align:middle line:84% and in epilepsy, we think based on the discussions that we're 00:30:01.240 --> 00:30:02.920 align:middle line:84% having with partners that would be 00:30:02.920 --> 00:30:05.230 align:middle line:84% really interesting for a partner to take this forward. 00:30:05.230 --> 00:30:10.645 align:middle line:84% And now that we've shown CNS target engagement activity, 00:30:10.645 --> 00:30:13.150 align:middle line:84% those are going to make those conversations even more 00:30:13.150 --> 00:30:14.050 align:middle line:90% fruitful. 00:30:14.050 --> 00:30:17.740 align:middle line:84% So think about partners potentially 00:30:17.740 --> 00:30:20.470 align:middle line:84% taking on some of those larger indications 00:30:20.470 --> 00:30:25.570 align:middle line:84% and Trevena thinking about more of a targeted advancement 00:30:25.570 --> 00:30:27.880 align:middle line:90% into a phase IIA type study. 00:30:27.880 --> 00:30:29.695 align:middle line:90% Does that help, Doug? 00:30:29.695 --> 00:30:31.070 align:middle line:84% DOUGLAS XU: Yeah, that's helpful. 00:30:31.070 --> 00:30:32.720 align:middle line:84% Then I guess, Carrie, just maybe it'd 00:30:32.720 --> 00:30:36.530 align:middle line:84% be helpful for everybody just to outline the timelines 00:30:36.530 --> 00:30:40.763 align:middle line:84% that you're thinking about for next steps and milestones. 00:30:40.763 --> 00:30:41.930 align:middle line:90% CARRIE BOURDOW: Yeah, great. 00:30:41.930 --> 00:30:45.680 align:middle line:84% So the NIH data, the epilepsy data, 00:30:45.680 --> 00:30:49.520 align:middle line:84% we're expecting that in the second half of this year. 00:30:49.520 --> 00:30:51.800 align:middle line:84% The full safety, tolerability data 00:30:51.800 --> 00:30:54.140 align:middle line:84% we're expecting that early next quarter 00:30:54.140 --> 00:30:55.340 align:middle line:90% or early fourth quarter. 00:30:55.340 --> 00:30:57.260 align:middle line:90% So those are the two data sets. 00:30:57.260 --> 00:30:59.930 align:middle line:84% We actually have also a non-clinical study running 00:30:59.930 --> 00:31:02.000 align:middle line:84% in infantile spasm, we're expecting 00:31:02.000 --> 00:31:04.260 align:middle line:84% that in the second half of this year. 00:31:04.260 --> 00:31:08.210 align:middle line:84% Those are the, I guess, three big data sets. 00:31:08.210 --> 00:31:11.880 align:middle line:84% And then we announced preliminary data today. 00:31:11.880 --> 00:31:14.330 align:middle line:84% We're not expecting too much more from this study, 00:31:14.330 --> 00:31:17.990 align:middle line:90% but that's part of it. 00:31:17.990 --> 00:31:22.580 align:middle line:84% Mark is already speaking with advisors, showing them the data 00:31:22.580 --> 00:31:26.540 align:middle line:84% and talking about what we've seen 00:31:26.540 --> 00:31:29.220 align:middle line:84% and looking at the CNS target engagement 00:31:29.220 --> 00:31:30.640 align:middle line:90% and moving forward on that. 00:31:30.640 --> 00:31:33.240 align:middle line:84% And so that gives you a sense that we're not 00:31:33.240 --> 00:31:37.530 align:middle line:84% talking about a long time frame here 00:31:37.530 --> 00:31:41.400 align:middle line:84% before we would get back to and let them know next steps. 00:31:41.400 --> 00:31:44.013 align:middle line:90% 00:31:44.013 --> 00:31:44.930 align:middle line:90% DOUGLAS XU: OK, great. 00:31:44.930 --> 00:31:45.542 align:middle line:90% Thank you. 00:31:45.542 --> 00:31:46.625 align:middle line:90% CARRIE BOURDOW: Thank you. 00:31:46.625 --> 00:31:49.528 align:middle line:90% 00:31:49.528 --> 00:31:50.320 align:middle line:90% MELISSA: Thank you. 00:31:50.320 --> 00:31:52.270 align:middle line:84% Ladies and gentlemen, that concludes our question 00:31:52.270 --> 00:31:53.110 align:middle line:90% and answer session. 00:31:53.110 --> 00:31:56.243 align:middle line:84% I'll turn the floor back to Ms. Bourdow for any final comments. 00:31:56.243 --> 00:31:57.160 align:middle line:90% CARRIE BOURDOW: Great. 00:31:57.160 --> 00:31:59.450 align:middle line:84% Well, thank you, again, for joining us this morning. 00:31:59.450 --> 00:32:01.690 align:middle line:84% And as you can hear, we've generated 00:32:01.690 --> 00:32:05.980 align:middle line:84% evidence that supports TRV045 innovative mechanism of action 00:32:05.980 --> 00:32:08.290 align:middle line:90% in CNS target engagement. 00:32:08.290 --> 00:32:10.900 align:middle line:84% As we've talked about in part in the Q&A 00:32:10.900 --> 00:32:15.280 align:middle line:84% the market opportunity for once daily novel solutions 00:32:15.280 --> 00:32:18.410 align:middle line:84% in both chronic pain and epilepsy is large. 00:32:18.410 --> 00:32:20.890 align:middle line:84% And so our next steps, as we've described, 00:32:20.890 --> 00:32:23.218 align:middle line:84% first, we'll provide updates on the full safety 00:32:23.218 --> 00:32:24.760 align:middle line:84% and tolerability results, which we're 00:32:24.760 --> 00:32:26.740 align:middle line:90% expecting early fourth quarter. 00:32:26.740 --> 00:32:29.860 align:middle line:84% We have promising evidence of the therapeutic potential 00:32:29.860 --> 00:32:34.960 align:middle line:84% of TRV045 in neuropathic pain, statistically significant EEG 00:32:34.960 --> 00:32:37.550 align:middle line:84% data now, we have that now in hand. 00:32:37.550 --> 00:32:41.680 align:middle line:84% And as I mentioned, we're waiting for the NIH-ETSP data. 00:32:41.680 --> 00:32:45.130 align:middle line:84% We're already working with our KOLs and potential partners 00:32:45.130 --> 00:32:48.910 align:middle line:84% to plan the additional clinical studies in patients. 00:32:48.910 --> 00:32:52.100 align:middle line:84% Before closing, let me also call your attention 00:32:52.100 --> 00:32:54.890 align:middle line:84% to the business update we issued this morning where we announced 00:32:54.890 --> 00:32:57.590 align:middle line:84% that our partner in China, Nhwa, achieved 00:32:57.590 --> 00:33:00.320 align:middle line:84% the milestone of first commercial sale of Olinvyk. 00:33:00.320 --> 00:33:04.430 align:middle line:84% As a result, we are now in receipt of the $15 million 00:33:04.430 --> 00:33:08.450 align:middle line:84% tranche that was part of our ex-US royalty-based financing 00:33:08.450 --> 00:33:09.560 align:middle line:90% with our bridge. 00:33:09.560 --> 00:33:13.130 align:middle line:84% That funding is in addition to the 28.1 million 00:33:13.130 --> 00:33:15.560 align:middle line:84% in cash we previously reported at the end 00:33:15.560 --> 00:33:17.150 align:middle line:90% of the second quarter. 00:33:17.150 --> 00:33:21.140 align:middle line:84% We also expect new Olinvyk data from the volition study 00:33:21.140 --> 00:33:24.290 align:middle line:84% in the coming weeks and we announced new abstracts 00:33:24.290 --> 00:33:26.090 align:middle line:84% that will be presented at the American 00:33:26.090 --> 00:33:29.300 align:middle line:84% Society of Anesthesiologists next month. 00:33:29.300 --> 00:33:33.278 align:middle line:84% Thank you, again, for calling in today. 00:33:33.278 --> 00:33:34.070 align:middle line:90% MELISSA: Thank you. 00:33:34.070 --> 00:33:35.440 align:middle line:84% This concludes today's conference call. 00:33:35.440 --> 00:33:37.280 align:middle line:84% You may disconnect your lines at this time. 00:33:37.280 --> 00:33:40.500 align:middle line:84% Thank you for your participation. 00:33:40.500 --> 00:33:41.000 align:middle line:90%