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Business Update
Final Countdown to April 5, 2022 PDUFA Date for BXCL501
BioXcel Therapeutics, Inc. (NASDAQ:BTAI) is currently awaiting word from the FDA regarding the potential approval of BXCL501 for the treatment of agitation associated with schizophrenia and bipolar disorder. The PDUFA Date set by the FDA for an approval decision is April 5, 2022. In anticipation of potential approval, the company is currently focused on hiring experienced sales representatives, finalizing marketing materials, and developing market access/pricing strategies. In January 2022, BioXcel hired Matt Wiley as Chief Commercial Officer. Mr. Wiley has over 25 years of commercial and industry experience. He was most recently Chief Commercial Officer of VYNE Therapeutics, where he oversaw all commercial objectives related to the launch of the AMZEEO and ZILXI, the company's first two approved dermatology products.
During the company's fourth quarter 2021 earnings call, when asked about label negotiations with the FDA ahead of the PDUFA date, management indicated that it is company policy not to discuss any ongoing discussions with the agency but that they continue to anticipate a decision on or before April 5, 2022. In addition, during the call management discussed a survey of 150 health care providers in which 83% had a positive impression of BXCL501 after reviewing blinded marketing materials and that they would prescribe it to approximately 40% of their schizophrenia and bipolar patients. This is encouraging news and adds to our confidence that BXCL501 will be a commercially successful product.
As the company looks to expand beyond the potential approval of BXCL501, it is focused on a three-prong strategy that includes:
1) Indication expansion – In December 2021, the company initiated the Phase 3 program for BXCL501 in acute agitation in Alzheimer's disease. The TRANQUILITY II trial will focus on patients in assisted living or residential facilities while the TRANQUILITY III trial will focus on patients in nursing homes. In addition, the company filed an investigational new drug application (IND) for BXCL501 to be used as an adjunctive treatment for major depressive disorder (MDD), which is covered in more detail below.
2) Extending the geographic reach of BXCL501 – BioXcel will be filing a marketing authorization application (MAA) with the European Medicines Agency (EMA) in the first half of 2022 for BXCL501 for the treatment of agitation associated with schizophrenia and bipolar disorder. The filing will be completed following the Apr. 5, 2022 PDUFA date. Management indicated that the package that was filed with the FDA was shown to EMA officials, who indicated it was sufficient to file the MAA. The company will then be actively looking for a commercialization partner, particularly one with a neuropsychiatric franchise that will support potential future indications for BXCL501 in Alzheimer's and MDD. After the EU, Japan is the next likely ex-U.S. region the company will target.
3) Growing the medical settings where BXCL501 can be offered – The company would like for BXCL501 to eventually be offered regardless of the treatment setting, which could include at home.
BXCL501 for Major Depressive Disorder
In September 2021, BioXcel held a virtual R&D day to discuss the development of BXCL501 in MDD. MDD is characterized by a number of different symptoms, with clinical data showing that BXCL501 can have a direct impact on many of them, including anxiety, restlessness, irritability, panic, and sleep disturbances.
Analyzing data collected from the SERENITY I and II trials and the RELEASE trial showed that BXCL501 reduced agitation consistently in depressed patients (bipolar), schizophrenia, and opioid withdrawal. As the following graphs show, a significant improvement in agitation was seen in bipolar patients in those that were depressed as well as manic. In addition, there was a significant improvement in the anxiety item of the PANSS for schizophrenic patients and a significant improvement in clinician ratings of anxiety or irritability in opioid withdrawal patients.
Data from SERENITY II (bipolar) also showed that BXCL501 was effective in reducing Tension in patients with depressed mood. The following graph shows a significant change in PEC ‘Tension', which measures apprehension, anxiety, nervousness, restlessness, and panic, in patients with mania and depression treated with BXCL501.
The company will be developing BXCL501 as an adjunctive treatment for MDD with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). SSRIs/SNRIs take approximately 4-6 weeks for the anti-depressive effects to begin, thus the company will be looking at accelerating the effect of those medications with BXCL501.
Additional Data for BXCL701 Presented at ASCO GU
On February 14, 2022, BioXcel announced results from its ongoing Phase 2 clinical trial of BXCL701 in patients with metastatic castration-resistant prostate cancer (mCRPC) with either adenocarcinoma or small cell neuroendocrine carcinoma (SCNC) phenotypes. BXCL701 is an oral innate immune system activator that is designed to turn ‘cold' tumors ‘hot', thus making them better able to be detected by the adaptive immune system. In this trial, BXCL701 is being administered in combination with pembrolizumab.
For the SCNC cohort, of the 15 evaluable patients, 5 (33%) achieved a composite response at the planned interim analysis. For the 12 patients with measurable disease, 4 (33%) achieved a RECIST-defined partial response and the disease control rate (DCR) was 58% (7 patients). DCR is defined as complete responders (CR) + partial responders (PR) + those with stable disease (SD). In regards to safety, 3 (17%) patients experienced serious adverse events (AEs) possibly related to BXCL701 or pembrolizumab and 4 (22%) discontinued treatment due to AEs.
For the adenocarcinoma cohort, of the 29 evaluate patients, 6 (21%) achieved a composite response. There were 18 patients with measurable disease, and 4 (22%) achieved a RECIST-defined partial response. The DCR was 83% (15 patients) with all responders showing a decrease in tumor size from baseline. Of the 29 patients with at least one post-baseline PSA measurement, the PSA50 (at least a 50% decrease in PSA from baseline) was 17%. Five patients experienced declines in PSA of between -100% to -57%. In terms of safety, 5 (12%) patients experienced serious AEs possibly related to BXCL701 or pembrolizumab and 2 (5%) patients discontinued any drug due to AEs.
These data are encouraging, particularly when compared to historic data for single agent pembrolizumab, which showed an objective response rate of 3-5%, a DCR of 12%, and a PSA50 of 6% in patients with adenocarcinoma phenotype (Antonarakis et al., 2020). We anticipate the data reported by BioXcel to be sufficient to warrant moving BXCL701 ahead in development. In addition, we anticipate additional efficacy data from the MD Anderson study of BXCL701 and pembrolizumab in the second half of 2022.
Financial Update
On March 10, 2022, BioXcel announced financial results for the fourth quarter and full year 2021. As expected, the company did not report any revenues in 2021. Net loss in the fourth quarter of 2021 was $26.1 million, compared to a net loss of $21.1 million in the fourth quarter of 2020. R&D expenses in the fourth quarter of 2021 were $12.5 million, compared to $11.4 million for the fourth quarter of 2020. The increase was primarily due to increased personnel costs. G&A expenses in the fourth quarter of 2021 were $13.6 million, compared to $9.7 million for the fourth quarter of 2020. The increase was primarily due to an increase in compensation costs, higher stock-based compensation, increased marketing and commercial costs, and increased legal and professional fees.
For 2021, BioXcel reported a net loss of $106.9 million, compared to a net loss of $82.2 million in 2020. R&D expenses in 2021 were $52.7 million, compared to $58.0 million in 2020. The decrease was primarily due to decreased clinical trial costs for BXCL501 partially offset by increased clinical trial costs for BXCL701. G&A expenses in 2021 were $54.2 million, compared to $24.3 million in 2020. The increase was primarily due to increased headcount along with significant commercial costs in preparation for the U.S. launch of BXCL501.
As of December 31, 2021, BioXcel had approximately $233.0 million in cash and cash equivalents. As of March 1, 2022, the company had approximately 28.0 million shares outstanding and when factoring in stock options a fully diluted share count of approximately 32.0 million.
Conclusion
We eagerly await the decision by the FDA regarding BXCL501 and we remain confident that it will be approved and be a commercially successful therapeutic. The company has a solid plan in place to expand beyond the potential approval of BXCL501, which includes continuing to advance BXCL701 and the addition of BXCL502 to the pipeline. We are also glad to see the Phase 3 program initiated for BXCL501 in acute agitation in Alzheimer's and look forward to updates on the MDD program.
The company's stock has been on a downward trajectory, along with the biotech sector as a whole, for the past few months. However, we continue to remain positive on both the prospects for BXCL501 and the company as a whole. As we await word from the FDA on the fate of BXCL501, our valuation remains at $110.
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