Good morning, and welcome to BioXcel Therapeutics' first quarter earnings conference call and audio 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 for questions and answers after the presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Just to remind everyone, certain matters discussed in today's conference call, or answers that may be given to questions asked, are forward-looking statements that are subject to risks and uncertainties relating to future events and/or the future financial performance of the company. Actual results could differ materially from those anticipated in these forward-looking statements.
The risk factors that may affect results are detailed in the company's most recent public filings with the U.S. Securities and Exchange Commission, including its quarterly report on Form 10-Q for the quarterly period ended March 31st, 2020, which can be found on its website www.bioxceltherapeutics.com or on www.sec.gov. I would now like to turn the conference over to Vimal Mehta, Chief Executive Officer of BioXcel Therapeutics. Please go ahead.
Thank you, operator. Good morning, everyone, and thank you for joining our conference call to discuss BioXcel Therapeutics' financial results and business highlights for the first quarter 2020. We appreciate everyone's time and attention. Joining me for the call today are Richard Steinhart, Chief Financial Officer, Frank Yocca, Chief Scientific Officer, and Vince O'Neill, Chief Medical Officer. Before we begin, I want to take some time to address these unprecedented times. The COVID-19 pandemic, a crisis that has created uncertainty around the world, has truly affected each and every one of us. I personally want to thank all healthcare workers who are tirelessly fighting on the front lines, caring for patients and preventing the further spread of the virus. Their hard work deserves our everlasting gratitude.
Following the guidance from the U.S. Centers for Disease Control and Prevention and the State of Connecticut, we have made vital adjustments across our company aimed at protecting our employees' health and safety while maintaining key activities needed to advance the development of our clinical programs. The BioXcel team remains motivated and on track to reach our 2020 milestones. In order to monitor the potential impact of this pandemic on our ongoing trials, we have been in close contact with our clinical sites. To date, we have not experienced any significant delays in our ongoing clinical trials and have made great strides with our clinical programs. We will continue to closely monitor the COVID-19 situation and provide any updates as needed. Shifting our discussion back to our corporate highlights, I would like to first discuss our lead neuroscience clinical program, BXCL501.
As a reminder, BXCL501 is our proprietary thin film formulation of dexmedetomidine or dex for the treatment of acute agitation. We have designed this candidate to be easily administered and have a rapid onset of action in order to produce a calming effect without excessive sedation. We have made key advances this quarter in our pivotal trial, SERENITY I and II, which are phase III studies of BXCL501 for the acute treatment of agitation in patients with schizophrenia and bipolar disorder. Back in March, we announced that more than 1/3 of the patients in both trials had been enrolled and treated. Enrollment continues to be progressing as planned, and we have not observed a change in enrollment rates due to the COVID-19 pandemic.
We are on track to report top-line data from the SERENITY program in mid-2020 and will communicate updates as we get closer to our clinical data readout. It is important to note that all schizophrenia and bipolar patients enrolled have successfully self-administered the BXCL501 treatment guided by a healthcare provider. With our pivotal program readouts only a few months away, we are hopeful that we will be able to submit our first NDA for BXCL501 during the first half of 2021, bringing a non-invasive, fast-acting treatment to the millions of patients who suffer from acute agitation associated with neuropsychiatric disorders. Our clinical progress continued with the initiation of TRANQUILITY. This study, a phase I-B/II trial for the treatment of acute agitation in geriatric dementia, highlights the potential versatility of our neuroscience program in treating disorders beyond neuropsychiatric conditions.
Since the TRANQUILITY trial has an adaptive design, we are currently reviewing safety and tolerability data in order to choose the next tested dose. This trial's enrollment is on track, and top-line data is expected in mid-2020.With off-label drugs having a black box warning for the elderly and no FDA-approved therapies to treat agitation in geriatric dementia, there is a desperate need for a safe and effective treatment for patients that struggle with this psychological behavior. We designed BXCL501 to be a fast-acting, easy-to-administer therapy to try to fill this unmet need and provide a treatment, if approved, for caregivers that have trouble managing dementia-related agitation. In parallel, we continue to investigate the use of wearable digital device technology, such as the Apple Watch, to hopefully enhance the prevention and treatment of dementia-related agitation.
Considering this patient population is among the highest risk category for severe illness and death associated with COVID-19, we have taken precautionary measures to preserve the safety and health of our elderly patients. For the TRANQUILITY trial, all BXCL501 doses have already been manufactured and have been provided to the long-term care facilities running the TRANQUILITY study, reducing the risks of exposing the patients. We are continuing our investigation of BXCL501's calming capabilities through the initiation of a phase II study being performed by researchers at Yale University. The aim of this study is to assess biomarkers associated with agitation, such as skin conductance response, heart rate variability, and blood pressure in patients with schizophrenia and their response to treatment with BXCL501.
Managing agitation is a challenge for both physicians and caregivers, and being able to use these biomarkers as an initial signal prior to the onset of visible symptoms could be very beneficial. These bodily signals could provide sufficient time for caregivers to deliver BXCL501 to patients before an agitation episode becomes dangerous. Even though this study is being performed only on schizophrenia patients, we believe this trial will help open the door to investigate the potential use of BXCL501 in additional indications that exhibit similar physiological signals of hyperarousal, expanding the potential market of this candidate into chronic agitation. To wrap up this quarter's neuroscience highlights, we received FDA clearance of our IND application for BXCL501 for the treatment of opioid withdrawal symptoms, a potential fourth indication for this candidate.
As the number one cause of death in the U.S. for individuals under the age of 50 years old, accidental drug overdose is rampant in this country with a majority of fatalities opioid-related. Opioid withdrawal can be very debilitating and uncomfortable, and many addicts continue to take these drugs or relapse to avoid feeling these distressing symptoms. There is a desperate need for new, efficacious treatment options to help aid this underserved population from continuous abuse. Due to BXCL501's intrinsic potency, favorable delivery method, and mechanism of action, we feel this candidate has the potential to offer advantages to treating withdrawal symptoms, helping to combat an abuser's urge to relapse.
We are encouraged by the promising results we witnessed with intravenous drugs in alleviating withdrawal symptoms, and we are planning to initiate the RELEASE trial, a Phase I-B/II trial for the treatment of patients experiencing symptoms of opioid withdrawal shortly. This past quarter, we have focused our efforts on expanding our neuroscience program's clinical development strategy, exploring numerous indications in hopes of reaching an extensive patient population. We believe BXCL501 offers a differentiated therapy to treating the millions of patients that suffer from hyperarousal and lack effective alternatives. We are focused on increasing the commercial value of this candidate and plan on exploring BXCL501 as a potential treatment for acute agitation in hyperactive delirium, as well as for chronic agitation. Turning the conversation over to our immuno-oncology clinical candidate, BXCL701, our orally available systemic innate immunity activator designed with a dual mechanism of action.
Recently, we announced that we are initiating the phase II efficacy portion of the phase I-B/II trial of BXCL701 in combination with KEYTRUDA for treatment-emergent neuroendocrine prostate cancer or tNEPC. Results from the phase I-B safety lead-in showed that a split dose totaling 0.6 mg per day is the recommended dose when used in combination with KEYTRUDA. This split dose has shown on-target side effects consistent with cytokine activation and has an improved safety profile. In the phase II efficacy trial, approximately 30 eligible men with tNEPC will receive 0.3 mg of BXCL701 twice daily on days 1- 14 of each 21-day cycle, plus 200 mg of KEYTRUDA administered intravenously on day one, and then every 21 days. We expect to report initial interim data from the phase II trial in the fourth quarter of 2020.
Currently, there are no approved treatments for tNEPC, a rare and highly aggressive form of prostate cancer. We believe BXCL701 has the potential to be an effective treatment for this subpopulation, as it creates an aggressive adaptive immune response, making tumors more reactive to immunotherapies, including KEYTRUDA. Furthermore, the company is also advancing the clinical evaluation of BXCL701 via the ongoing open label phase II basket trial conducted at the MD Anderson Cancer Center. This study is evaluating the combination of BXCL701 and KEYTRUDA in patients with advanced solid cancer that are either naive to or refractory to checkpoint therapy, and is following the dosing schedule used in the phase I-B/II study for tNEPC.
The combination trial of BXCL701, Bempeg from Nektar, and avelumab from Pfizer and Merck KGaA in pancreatic cancer will start following the completion of Nektar and Pfizer's phase I-B safety study of Bempeg and avelumab. The outcome of that trial. In February, we raised net proceeds of approximately $60 million in a public offering, which helped to significantly strengthen our balance sheet. This cash, together with our current reserves, provide BioXcel enough cash runway to fund pre-clinical regulatory and operational milestones into 2021. With that, I would like to turn the call over to our CFO, Richard Steinhart. Richard?
Thanks, Vimal. Once again, thank you all for joining us this morning, and welcome to our shareholders. BTAI reported a net loss of $14.9 million for the first quarter of 2020, compared to a net loss of $7.2 million for the same period in 2019. The first quarter of 2020 results include about $800,000 in non-cash stock-based compensation. The increase in net loss was primarily due to costs associated with our pivotal Phase III trials. Research and development expenses were $12.4 million for this first quarter of 2020 as compared to $5.7 million for the same period in 2019. The increase was primarily due to an increase in clinical trial costs, salaries, bonus, and related costs, professional research, and project related costs, and chemical manufacturing and controls related to our BXCL501 and BXCL701 product candidates.
General and administrative expenses were $2.6 million for the first quarter of 2020, compared to $1.7 million for the same period in 2019. The increase was primarily due to professional fees for legal and patent matters. Total operating expenses for the first quarter of 2020 were approximately $15 million as compared to total operating expenses of approximately $7.4 million for the same period in 2019. We had cash and cash equivalents of $80.1 million as of March 31st, 2020. That concludes the financial review of the first quarter. Now I'd like to turn the call back to Vimal for any further comments. Vimal?
Thanks, Richard. We would now like to open the call to questions. Operator?
Thank you. At this time, we'll be conducting a question- and- answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question today comes from Geoff Meacham of Bank of America. Please proceed with your question.
Hey, guys. This is Scott on for Geoff. Thanks for taking our question. Wanted to ask about the phase I-B/II study for BXCL501 in dementia. It seems the doses are lower at 30, 60, 90 micrograms due to the elderly patient population. In the phase I-B trial in schizophrenia, the 60-microgram dose was not statistically significant. I was wondering if we should anticipate a tighter window for success given the need to balance dosing and efficacy in these patients. As a follow-up, for BXCL701, you recently noted the 0.6 mg dose is recommended and that splitting the dose can be associated with an improved safety profile. There's certainly concerns around the safety for BXCL701 given the drug's prior history.
Can you give us any insight into whether splitting the dose might impact efficacy for any reason and the potential concerns you're seeing around dosing it as a once daily? Thanks.
Thanks, Scott. This is Vimal. I'm going to pass this question to Rob Risinger, who is our VP of Clinical Neuroscience, to answer the 501 question, and then Vince will pick up the question related to BXCL701. Rob?
Sure. Thank you, Scott. Good question. The dose range in schizophrenia. We're not banking, if you will, on it being identical in dementia. As you point out, they are older, they tend to be more frail, and so we are testing a slightly different dose range, simply to determine the doses that may be safe but also effective.
Vince?
Yep. Thanks, Scott, for the question. On 701, it was really around splitting dose versus not, I believe. What we saw on the once-daily dosing, non-split dose at 0.6 mg or 600 micrograms was an event of syncope, and this was presented at the ASCO GU poster just a couple of months ago. That required us to expand the cohort or otherwise essentially identify a better-tolerated dose and schedule. What we found is that by splitting the dose, we no longer saw those types of events. We certainly still saw some on-target toxicity. In oncology, as you know, that's not necessarily a bad thing at all. It states that the drug is doing what it's expected to do, but the events of syncope were simply no longer present. We believe we've fixed the tolerability by splitting the dose. Hopefully, that answers your question.
Got it. Thanks, guys.
The next question is from Robyn Karnauskas of SunTrust Robinson Humphrey. Please proceed with your question.
Hi, guys. Thanks for taking my question. First of all, can you give us some data points on what steps need to be completed in order to start the opioid withdrawal trial? Like, what are the rate-limiting steps? Do you think we'll still could see data this year? On 701, when you think about what you've learned on the safety profile, what does the safety sort of hint to you around the efficacy of the drug? Did you learn anything about if the drug's working in the way it should be working? Just give us some thoughts on what you've learned so far from the early data. Thank you.
Thanks, Robyn. This is Vimal. Regarding the opioid withdrawal trial, we had all the pieces ready to go to initiate the trial. We were running three trials, SERENITY I and II, our pivotal Phase III, and TRANQUILITY trial, and this COVID-19 situation arose. We made a conscious choice as a company to not start the opioid withdrawal trial right in the middle of COVID-19, in the interest of our employees, our partners' employees, as well as for the patient safety. As you might have noticed, that COVID-19 is creating even a bigger opioid crisis, which is in the press all over the place. The number of patients are plenty, and they keep coming to these sites, and that's what we have been advised by our CRO and the clinical site. We could initiate this study anytime.
I don't think there is any rate limiting step, and we will provide the guidance shortly as we indicated that we are about to initiate that trial. We are in a good position to initiate that opioid withdrawal trial. Regarding the 701 question, I will ask Vince to weigh in what we have been able to observe beside the safety, any signals from the efficacy aspect. Vince?
Sure. Thanks, Vimal. Morning, Robyn. Again, I'm going to pivot back to the data that we presented at ASCO GU. In terms of the learnings, I think an important one is that this drug seems to be a strong activator of the innate immune system. I think that's important because thus far, many of the other potential approaches to activating innate immunity have been weak. We do see things like fever and chills, myalgia, some puffy ankles, all of which are actually transient. They tend to settle down after the first or second cycle. What we did see, as I mentioned from the previous question, was hypotension and one episode of syncope. By splitting the dose, the hypotension events seem to have mitigated substantially. Yet we still see the remainder of those on target toxicities.
Our belief is that we have a strong innate activator that is at the same time safe, and of course, you'll know we have a large safety database behind the drug already at this point. That's one important learning. We haven't released any new data from the ASCO GU or since the ASCO GU presentation, I would simply point out that on efficacy, I mean, this is the I-B portion. This is fundamentally a safety study. The majority of patients were stable disease and remained on study at the time of that presentation.
Can you just also give an update on the other trials and going with 701 and if they're proceeding with any issues due to COVID-19 and just the latest update there and when we can see the next data set from 701? Thank you.
Sure. I'll take, Vimal, for me, I'll take the triple combination study first. I think as we'd mentioned, the doublet of bempegaldesleukin NKTR-214 plus avelumab has to be combined before we add in BXCL701. That study is in the hands of Pfizer. Pfizer did announce maybe six weeks ago that they were pausing all trials. They announced approximately one week ago that they're reopening all trials. That study was underway. The patients were enrolled, and it's now reopened again to accrual. Our anticipation is that, as we previously guided, we will add in the BXCL701 portion to that doublet once we have safety data later on this year. That's the triple combination. The MD Anderson study, and that's an important part of the development plan, as you're aware.
That's in hot tumors, both in patients who are KEYTRUDA naive and also patients who fail KEYTRUDA or progress through it. That study is open. It opened just at the turn of the year. That's progressing. Again, consistent with guidance, we are anticipating being able to present data at the end of the year from that trial.
Great. Thank you.
The next question is from Do Kim of BMO Capital Markets. Please proceed with your question.
Morning. Thanks for taking my questions. I was hoping you could review for us what would be considered clinically meaningful in terms of reduction in the SERENITY trials. When you look at the ADASUVE studies, you saw a slightly benefit in bipolar patients versus placebo then for schizophrenia. Is that something you also expect, or is it just within normal variability for agitation studies?
Thanks, Do, for the question. I will ask Rob to answer that question about the schizophrenia versus bipolar. Rob?
Do, the difference between schizophrenia effect and bipolar effect for antipsychotics tends to be relatively minimal. I realize that ADASUVE had a slightly better efficacy in bipolar patients than schizophrenia. We're seeing from the Study 102 data, the phase II or the ascending dose trial that we did, we saw a clinical benefit, so an improvement by CGI, of one point equated to an improvement on the PANSS excitatory component score of around 2-3 points. We expect to see a similar effect for patients with bipolar as schizophrenia. It's possible that it'll be greater, but that remains to be seen. I could wax on about potential reasons why it might be more efficacious in bipolar than schizophrenia having to related to, for example, the autonomic nervous system and the relationship of activation in bipolar patients who are agitated and manic or hypomanic.
We'll know a lot more once we have the actual data. Short answer, don't know if there will be a difference. It would be interesting, but we're not counting on that in terms of the powering of the trial.
Do you still see a - 3 point reduction in PEC score as the bar for clinically meaningful in either patient population?
Yes. We were able to demonstrate that in the smaller study, and we expect that degree of change would represent a clinically meaningful improvement.
Great. Could you also speak to the rising cases in delirium in hospital ER settings due to COVID-19 and whether you should actually start looking at a 501 study in that setting now versus later?
Do, this is Vimal. As there is a lot of press around these COVID-19 patients who are elderly due to pre-intubation as well as post intubation or mechanical ventilators used. They are getting delirium, and there are tons of reason why they are getting it. A lot of patients are getting that. We continuously evaluate how we can help these patients, and we talk to our key opinion leaders and explore those opportunities. In terms of delirium program, it's strategic part of our development. We are trying to speed up that, considering that this is a tremendous need in the hospital settings for treating the agitation resulting from delirium for the benefit of COVID-19 patients as well as for our own strategic reasons. Rob, would you like to add anything on that?
I would just say that the API for BXCL501 dexmedetomidine is already commonly used to treat delirium in the ICU setting. We do see that as a sort of low-hanging fruit. We're exploring potential development options in that area.
Great. Thanks for taking the questions, guys.
Thanks, Do.
The next question is from Sumant Kulkarni of Canaccord. Please proceed with your question.
Morning. Thanks for taking my questions. First one on 501, then I have a follow-up on 701. We've seen some developments on the competitive side in chronic management of agitation in Alzheimer's patients. How specifically do you expect to potentially bridge from acute treatment of 501 to the chronic management side, if that's possible? On 701, we were encouraged to see the progress into the phase II efficacy part of the trial for tNEPC in combination with KEYTRUDA. Could you give us a sense of what to expect in terms of the bar you might need to hit on efficacy, and how to potentially parse out single agent activity of 701 versus activity of the combo?
Thanks, Sumant . Regarding the 501 question, Can you please repeat the question? Just I want to make sure we answer it right.
Sure. The question specifically was, we've seen some developments on the competitive side on chronic management of agitation in Alzheimer's patients. You have a product right now that is in development for acute agitation. How could that potentially be translated to maybe chronic management of agitation also in the longer run?
Great question. I think we see that any success related to treating agitation in dementia/Alzheimer's is a big progress. Currently, as you know, there are no treatments available to treat these patients. Under those circumstances, we all know neurological conditions as they progress, the agitation episode or spectrum start changing. You may be in a pre-agitation state, then you go to a sporadic agitation, then subchronic agitation, and chronic agitation. Any kind of a treatment that can treat chronic agitation will be good, because that can help reduce number of episodes. Still, if you think about the agitation that's happening and the acute agitation that's still happening in these patients. In the beginning, you have sporadic agitation. There's no need to use a chronic agitation when agitation can be treated with something that is acute treatment as well as in subchronic.
The way we think about this is, the sporadic can be two episodes a month, and do you really need a chronic agitation? It could be two episodes a week, still subchronic treatment will be sufficient. Once it does become a chronic and there is a treatment that can be effective in reducing number of episodes, but they're still going to have breakout episodes, that needs where BXCL501 will fit in. Some of these chronic agitation drugs take quite a long time, six to eight weeks, to become effective, and you need to manage the patient. We think that both BXCL501 for acute treatment of agitation will fit in very well with any chronic agitation. It will help, in fact, support and build the market if treatment is available for both kind of situations.
Did it answer your question, or I'm happy to embellish more on it?
Oh, no. That's great. Thanks.
Okay. Regarding the 701 question, I will pass it on to Vince to describe what the bar is and what to expect from our neuroendocrine prostate cancer trial.
Sure. Thanks, Vimal. Morning, Sumant. I think the question was really twofold. One is, what might the bar be and how will we know the contribution of 701 or the individual contribution, right? I'll take the latter question first. There has been a study with single agent KEYTRUDA. This was really why we did not include an internal KEYTRUDA alone control arm. In a similar, not identical, but similar population. In that setting, this was a castrate-resistant prostate cancer group of patients who'd had treatment with ADT, so androgen blockers. In that setting, the response rate is very low indeed. It's between 3% and 5%. I think we have a reasonable handle on what KEYTRUDA can do in this classic cold tumor.
Given the fact that there is no standard of care here, we believe that a response rate, provided it's durable, okay, and that's a feature obviously of immuno agents. A response rate in the teens, typically 15% or above, would be of interest to the field and actually would move the field on quite substantially.
Thank you.
The next question is from Samir Devani of Rx Securities. Please proceed with your question.
Hi, everyone. Thanks for taking my questions. It's good to see that the trials are on track despite these challenging times. My question is actually on the delirium study you're planning. Looks like, again, coming back to dosing, looks like you're exploring 20 and 60 micrograms in that study. I guess, could you perhaps just elaborate on how that compares to what's currently being used with the intravenous product currently? Also, whether there are any extra R&D costs associated with that program this year. Thanks very much.
Samir, thanks for your question. Regarding the delirium, we have not spelled out what the plan is, what doses we will be using, because that's still in a planning stage. Dementia, obviously, is on the clinicaltrial.gov, and delirium is in a planning stage. Considering that there is such a big pandemic situation with COVID-19 and these patients are in need, we are kind of speeding up development. As part of our overall strategy, we always do a phase I-B/II. These trials don't tend to be that much capital intensive, and we do it on short number of patients, as you have seen with our schizophrenia and dementia. These trials tend to be enrolled rapidly and finish fast. Because of all those reasons, we don't see much impact on our clinical trial spend, but there will be some. We are still in the planning stage.
We will provide the guidance once we have all pieces come together, when this trial will start and when we can provide the data readout on delirium.
Thanks very much.
Thank you.
There are no additional questions at this time. I'd like to turn the call back to Vimal Mehta for closing remarks.
Thank you again for joining our call today. During the first quarter of 2020, we remain focused on advancing the development of our two clinical programs, BXCL501 and 701, with key data readouts occurring in the coming months. Have a great day, and please reach out to us if you have any additional questions. Thank you.
This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.