Study Result

May 20, 2019

Press Release

Good morning, and welcome to the BioXcel Therapeutics Phase 1 Pharmacokinetic BioXcel Bioanalytics study results of TXEL-five zero one conference call and webcast. Before we start, I would like to inform you that this conference is being recorded and that all participants are in a listen only mode. At the request of the company, we will open the conference up for questions and answers after the presentation. I will now turn the conference over to Carol Ruth. Please go ahead, ma'am. Thank you, operator. Just to remind everyone, certain matters discussed in today's conference call are answers that may be given to questions at our forward looking statements that are subject to risks and uncertainties relating to future events, including, but not limited to, the advancement and development of VXCL501. Actual results could differ materially than there was anticipated in these forward looking statements. The risk factors and other uncertainties that may affect results are detailed in our most recent public filings with the SEC, including our quarterly report on Form 10Q for the quarter period ended March 31, 2019, which can be found on our website, www.bioexceltherapeutics.comoronwww.sec.com. Before turning the call over to Doctor. Beryl Mehta, Founder and Chief Executive Officer of BioStar Therapeutics, I'd like to point out that we have slides accompanying the presentation that you can access off the Investor Relations site of the company's website. Bill? Thanks, Carol. Good morning, and thank you all for joining us today to discuss the results of our Phase 1 pharmacokinetic and safety study of BACL-five zero one. Our proprietary sublingual thin film formulation of dexmedetomidine, we will refer as Dex for acute treatment of agitation across neuropsychiatric diseases. Joining me on the call today are Doctor. Robert Richtenger, VP of Clinical Development Doctor. Chetan Laksiar, Senior VP and Head of Translational Medicine, Clinical Pharmacology and Regulatory Affairs Doctor. Vince O'Neill, Chief Medical Officer Doctor. Frank Yocca, Chief Scientific Officer and Richard Steinhardt, Chief Financial Officer. Earlier today, we announced positive results from a Phase 1 pharmacokinetic PK and safety study for BXCL501 for the acute treatment of agitation. The study met its primary endpoint for PK and safety and achieved a targeted exposure level. The results of this study have laid the foundation for a Phase 2 efficacy trial, which is anticipated to commence imminently. Results from the Phase 2 study are expected to support statistical modeling of a planned Phase 3 pivotal trial in second half of twenty nineteen. We expect to be in a position to file an NDA in 2020. Earlier this year, we have previously announced encouraging human proof of concept data from the IVF study in patients suffering from acute agitation associated with schizophrenia, Alzheimer's disease and opioid withdrawal symptoms as well as healthy volunteers. On today's call, we will provide an overview of the XTL-five zero one program, review the results of Phase 1 treatment safety study and provide an update on the global development plan for our lead neuroscience program. Following our prepared remarks, we will be happy to answer any questions you may have. With that, I would like to turn the call over to our VP of Clinical Development, Doctor. J. Singer to provide an overview of the XL501 program and results from our current study. As well? Thank you, Vimal. On Slide 4, I want to describe agitation as a global and growing multibillion dollar healthcare issue. For many patients, safer and noninvasive treatment for agitation is desperately needed. Approved anti psychotics are invasive and other agents have major competitive effects. In dementia, for example, treatment choices are extremely limited. Benzodiazepines today cause worsening already impaired memory and the use of antipsychotic drugs carry a black box warning of increased risk of death in the elderly. Experts agree that there is a need for a noninvasive treatment that is easy to administer and provides calmness without sedation along with a good safety profile and tolerability. In DXCL501, we have taken an innovative approach to treating agitation using a 1st in class agent that targets a core causal agitation mechanism and created a noninvasive, easy to administer, sublingual film designed for rapid onset of action. The FDA has acknowledged that this is a significant unmet medical need in granting us the fast track regulatory path for our development stance in agitation. On the next slide, there is a spectrum of agitation encountered by providers that start with mild severity where relatively cooperative patients are able to take pills. The goal of treatment is to deescalate emerging agitation and keep patients from becoming more agitated. At the opposite end of the spectrum are patients with severe agitation that are uncooperative, open to the point of requiring seclusion, even physical restraint and are unable to take a pill. These subjects require urgent treatment to keep them from hurting themselves or others and in this condition, as you might imagine, a nurse approaching them with a needle risks even further escalation. For escalating patients, the effect of pills may be too gradual and slow, while using an injection is too invasive and with further escalation. We believe the greater unmet need is providing a treatment option that rapidly intervenes before the patient is fully uncooperative and out of control, which likely fits into existing treatment guidelines designed to identify and deescalate before patients get out of control. On the next slide, today, we are announcing the top line results of our 1st in human study of this sublingual cell. To describe the study, I'd like to introduce Doctor. Chetan Laffia, the Senior Vice President of Pharmacokinetics and Head of Regulatory Affairs, who will elaborate the study design, objectives and our pharmacokinetics front. Thank you, Rob. I'm now going to Slide number 7, which describes the study design. We conducted a first in hand study to evaluate the PK and safety of the sublingual symptom formulation. This was designed as a standard single ascending dose study. The key purpose of this study was to evaluate doses that would yield target exposures. This was a double blind, placebo controlled, single ascending dose PK study. It enrolled healthy adult volunteers ages 18 through 65 with 23 males and 22 males. This was a single center study and 3 doses were evaluated in this study, 10 micrograms, 20 micrograms and 40 micrograms. The primary objective of this study was to determine the PK, safety and tolerability of the doses that were administered in this study. Now I'll go to slide number 8, which is which describes the PK results. On the left side of the slide is a plot of the immune concentration time data. Observed immune concentrations from the 10, 20 and 40 microgram doses are shown in this plot. The data from the IV Dex study in schizophrenia patients show that the lowest efficacious exposure is 22 nanogram per ml. This is shown as the dotted line from the plot. Data from the film formulation shows that the film rapidly delivered targeted exposures. These targeted exposures are consistent with the therapeutic responses seen in the schizophrenia study. Half of the subjects in the schizophrenia study who demonstrated a clinically significant reduction in test scores achieved exposures that were consistent with those observed with the 40 microgram film. These data shows that PXCL501 offers predictable and post proportional pharmacokinetics, which in turn enables using the film to achieve targeted exposures. Pharmacodynamic data evaluated in this study show that the effects last 4 to 6 hours. These data are consistent with the duration of action data from approved therapeutic agents in this setting. With this, I'll turn it back over to Ram. Thank you, Chetan. So on Slide 9, let's review our top line findings by describing the safety and tolerability from this first in human study. We found that dosing with CXCL501 was safe and well tolerated across the range of tested doses. There were no serious adverse events reported. The severity of adverse events was mild to moderate, meaning grade 2 or below. All adverse events were transient and required no intervention and completely resolved. The most common adverse event reported was drowsiness and the rates of drowsiness in the treatment group were similar to that reported by the placebo group. Cardiovascular changes were not clinically meaningful. Further, we saw no clear sensitive effects in comparison with placebo. A maximum tolerated dose was not reached. On these results and the PK observations, we are confidently advancing clinical development to dose agitated patients with CXCL501. Before I describe our development plans, however, let me share the context as to why we are so excited to have achieved these results with the film. On Slide 10, in order to develop rapid proof of concept in agitation, we generated IV Vex data across 4 diseases and healthy volunteers. In schizophrenia, on the top left, we saw a 90% response rate with a reduction in agitation using the PANS excitatory component or PEC scale without excessive sedation as measured by the RASP Are we on? Yes. You're on. Go ahead. Thank you. I believe we were disconnected in the middle of my description of description of my education scale. So let me start again at Slide 10. In our DRAM trial studies in agitation, we generated high suggest data of 4 diseases and healthy volunteers. In schizophrenia, we saw a 90% response rate with a reduction in agitation using the PAMC 20 20 2 component or FRET scale without excessive sedation as measured by the RASP scale. In dementia, we saw 70% response. In opioid withdrawal, we saw 100% response. And in a separate public study of agitated delirium, there was a 100% response. Pharmacokinetics and patient profile from these 3 studies are remarkably consistent across the disease population. Let me detail the proof of concept study completed in agitated patients with schizophrenia on Slide 11. In our IG proof of concept study, agitated subjects with schizophrenia demonstrated a clinically significant reduction in text scores, had exposures that were consistent with those observed our film formulation. Recall that TEC is an FDA agreed upon regulatory endpoint or registration trial to obtain the indication of treatment of acute agitation associated with the dynefinib bipolar disorder. In this process trial, HECT scores were reduced before sedation was evident, providing us with plasma levels to calm patients without inducing limited effects. This degree of calming was robust, not just a few points on a scale, but the degree of calming that clinicians like to see as a result of treatment. When developing the film formulation, we targeted exposure to producers from cost reduction in text form. We don't achieve this closure that equate with clinical test reduction in vegetative skin of patients. And that is why we are confident don't just provide exposure to their potentially therapeutic in the patient population. Reassuringly, the PKAN safety profile at Janssen's birthday across schizophrenia, dementia and opioid recall. So moving to Slide 12. As a well deserved data, let me describe at a high level our plans to progress to our first NDA. Slide 13. We have a Phase II study in a total of 200 agitated patients with hemophilia prednis, which we'll initiate soon. This is a 2 part study. The first half of the study will trial in the doses and the second half will allow us to characterize efficacy. Following this, we will initiate 2 Phase 3 registration trials later this year for a total of about 700 patients, 1 in buisoprenia and 1 in bipolar disorder. These trials use the same endpoints and design as previously successful registration studies. We expect to complete registration trials in the first half of twenty twenty, enabling NDA submission in the second half of twenty twenty. Designs and endpoints are comparable to other agents, which have achieved regulatory success. We have considered multiple options and we believe this plan robustly increases the potential probability of success in separating commercial T cell in Phase 3 while gaining regulatory approval. We believe that Phase 2 trial potentially derisk development in the most capital efficient manner without any impact on time lines. Now let me outline the development timeline on Slide 14. This is the development for acute agitation associated with schizophrenia and bipolar disorder in terms of catalyst. We will initiate our Phase II trial in the first half of twenty nineteen. These are short trials to execute and rapidly enroll simply because of agitation is a commonly encountered condition. We expect to have data readout in the Q3 of 2019 and that enables us to initiate our Phase III trial in the Q4. Data from global Phase III trial will readout in the first half of 2020 and that enables filing our first NDA in the second half of twenty twenty. Finally, let me point out that in parallel, we have staggered development plans in agitated dementia, opioid withdrawal and delirium, which we'll be rolled out throughout 2019. Now let me hand it over to Doctor. Mehta. Thanks, Rob. This slide shows that agitation is a clear unmet medical need for the U. S. Population. There are 19,000,000 in including schizophrenia, bipolar disorder, dementia, opioid use disorder and anemia. KBC, our product addressed as real and medical need and could bring relief to patients and has brought market potential. Let me remind you to join us for our GXL501 investor achievement for an in-depth covering of the Phase 1 CCL safety study results on this Wednesday, May 22nd at the Fort Eagle Hotel in New York, DC. You can find the event about our event in the press release issued on May 13. If you would like to attend the event, please contact Jan D. Moir at the Arun Group at 646-536-7027. To summarize, we believe the data results we have reported today are highly promising and positive. We remain on track to launch a Phase 2 trial called GXCL501, which is expected to support the strategic recovery of a planned Phase 3 pivotal study. As previously mentioned, this timeline would optimistically position us substantially by an FDA in 2020. We are optimistic that Biorextel's DxCL501's anti aliasing properties, which appears to be independent of underlying disease pathologies over the product's broad market potential. This concludes our prepared remarks. We would like to open the line for questions. Operator? Thank you, sir. Ladies and gentlemen, Hey, guys. Congrats on the data. I have a couple of questions. One of them is, as I think you guys have talked about 2 hours being the effect, and this is a little longer, 4 to 6. But am I remembering incorrectly? Or maybe just help us put these results in context maybe of what you view as a meaningful sedation compared to time and I have one follow-up. Yes, Geoff. This is Chetan Lach here. To answer your question, we have It's observed in the plot on Slide 8. And what I mentioned slide 8 is that our cyclical dynamic effects last between 4 to 6 hours. So we have a duration of action of 4 to 6 hours. So hopefully that clarifies the point that you are trying to make. Okay. Makes sense. And then I just saw something in the press release. It said cardiovascular changes were not clunky. So I wasn't sure what this meant. Was there something that you guys saw in this study on the Cardio side that was numerically different? Or maybe just help put that into context. Thank you. Sure. There not clinically meaningful. There were 3 total events in the study, 2 were on drug, 1 was on placebo. We don't believe this was any really was any different from placebo. We will now take our next question from Joe Kim from BMO Capital Markets. Good morning, guys. This is Keith on for Joe. I have two quick questions. The first, I think you kind of touched upon this a little earlier, but did you see any variation among patients presenting with different neuropathology or demographics in terms of age, gender, weight, etcetera? And was the variation related to both Amazons, heterozygous or none? And then I have one more to follow-up. Yes. This is Jason Lakia again. So in the PK study, we evaluated the effect of age, gender, ethnicity, etcetera, on pharmacokinetics, and we did not see any effect of those variants in pharmacokinetics. Okay. Okay. That's helpful. Thank you. Yeah. Yeah. Sure. And then just one more. Can you talk a little bit about how the sublingual film is unique to, for example, monolithic film? I understand that it attaches to the oral mucosa. Is there any concern if the film lands somewhere else like the furrows with respect to numbing effect? And that's all. Let me take that question. This is Frank Yatra, the CSO. The film is different than a monolithic film in that the drug substance is micro deposited onto the film. So as soon as the film touches the mucosa, it's delivering the drug rapidly. So we look at that as a distinct advantage. Not only that, the drug had to be given in such small quantities that we needed to come up with a different way of property that's associated with it. So as soon as it's property that's associated with it. So as soon as it touches the or what have you, it's sick. And people have tried placebo. And we can tell you that this works quite well. Okay. That's great. And if I could ask one more. Any reason you're looking into schizophrenia for the Phase 2 rather than bipolar? There's far more data in patients with schizophrenia, and therefore, it makes sense from a development standpoint to initiate with patients in schizophrenia. There's precedent, multiple trials, and so we feel it's the lowest risk for us to proceed into the premia. Okay. That's great. And congrats again, guys. Hi, good morning. Thanks for taking my questions. Now that you have more info on your PK and T profile of the film, how should we think about timelines on the other agitation indications that you might be going after? I developed a plan for the other indications because each indication will be different. The plans are slightly different and we're going to outline those plans in greater detail at the upcoming Investor Day on Wednesday. We would like to thank you again for participating in this call and for your continued support of biopsy therapeutics and our innovative program. We look forward to sharing further updates on VHCL501, our lead neuroscience candidate as well as other clinical tests as we move forward with the development. Thank you.