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We believe this differentiated approach has the potential to reduce the expense and time associated with drug development in diseases with substantial unmet medical needs.
−Removed: On April 6, 2022, we announced that the United States (“U.S.”) Food and Drug Administration (“FDA”) approved IGALMI TM (dexmedetomidine (or “Dex”)) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.
−Removed: IGALMI TM is approved to be self-administrated by patients under the supervision of a health care provider.
−Removed: On July 6, 2022, we announced that IGALMI TM was commercially available in doses of 120 and 180 microgram (“mcg”).
Our most advanced neuroscience candidate is BXCL501.
−Removed: In indications other than those approved by the FDA as IGALMI TM , BXCL501 is an investigational, proprietary, orally dissolving film formulation of Dex in development for the treatment of agitation associated with psychiatric and neurological disorders.
+Added: In indications other than those approved by the United States (“U.S.”) Food and Drug Administration (“FDA”) as IGALMI ® , BXCL501 is an investigational, proprietary, orally dissolving film formulation of dexmedetomidine (or “Dex”) in development for the treatment of agitation associated with psychiatric and neurological disorders.
+Added: On April 6, 2022, we announced that the FDA approved IGALMI ® sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.
+Added: IGALMI ® is approved to be self-administrated by patients under the supervision of a health care provider.
+Added: On July 6, 2022, we announced that IGALMI ® was commercially available in doses of 120 and 180 micrograms.
+Added: On September 5, 2024, we announced the initiation of our SERENITY At-Home trial, a double-blind, placebo-controlled study to evaluate the safety of a 120 mcg dose of BXCL501 in 200 patients for acute treatment of agitation associated with bipolar disorders or schizophrenia in the at-home setting.
+Added: On November 12, 2024, we announced that the first patient had been randomized in the trial, and on March 27, 2025, that 24 clinical trial sites had been opened and 127 patients had been enrolled.
+Added: Topline data results, which are expected in the second half of 2025, are intended to support a supplemental new drug application (“sNDA”) submission to potentially expand the label of IGALMI® (dexmedetomidine) sublingual film in the at-home setting.
We are continuing to develop BXCL501 for the potential acute treatment of agitation associated with bipolar disorders or schizophrenia in the at-home setting and for the potential acute treatment of agitation (non-daily) associated with dementia due to probable Alzheimer’s disease in the at-home setting and in care facilities.
−Removed: As described further below, we have deprioritized the development of BXCL501 for certain other proposed indications, including development of BXCL501 as a potential adjunctive treatment for major depressive disorder (“MDD”), as well as our BXCL701 program, except as noted under “Immuno-Oncology” below.
+Added: As described further below, we have deprioritized the development of BXCL501 for certain other proposed indications, as a potential adjunctive treatment for major depressive disorder (“MDD”), as well as our BXCL701 program, except as noted under “Immuno-Oncology” below.
+Added: On September 5, 2024, we submitted to the FDA the proposed protocol for our TRANQUILITY In-Care Phase 3 trial designed to evaluate the efficacy and safety of a 60 mcg dose of BXCL501 for agitation associated with Alzheimer’s dementia.
+Added: See further discussion in “Our Neuroscience Clinical Programs” below.
+Added: On October 15, 2024, we announced a U.S.
+Added: Department of Defense grant to the University of North Carolina to fund a study of BXCL501 (sublingual dexmedetomidine) for treating Acute Stress Disorder (ASD).
+Added: See further discussion in “Additional Neuroscience Opportunities” below.
Our most advanced immuno-oncology candidate, BXCL701, is an investigational oral innate immune activator being developed by OnkosXcel as a potential therapy for the treatment of aggressive forms of prostate cancer, pancreatic cancer, and other solid and liquid tumors.
+Added: Nasdaq Notice
+Added: On September 16, 2024, the Company received a letter from the Listing Qualifications Department (the “Staff”) of The Nasdaq Stock Market LLC (“Nasdaq”) that it was not in compliance with Nasdaq Listing Rule 5550(a)(2) because its common stock failed to maintain a minimum closing bid price of $1.00 per share for 30 consecutive business days.
+Added: On February 6, 2025, the Company announced that it would effect a 1-for-16 reverse stock split of its common stock.
+Added: The reverse stock split became effective at 5:00 p.m.
+Added: on February 7, 2025, and the company’s common stock began trading on a split-adjusted basis (above $1 per share) at the opening of the market on Monday, February 10, 2025.
+Added: To regain compliance, the Company was required to maintain a minimum closing bid price of $1.00 per share for at least 12 consecutive trading days.
+Added: This requirement was met on February 26, 2025.
+Added: As previously reported, on September 20, 2024, we received a letter from the Nasdaq Staff notifying us that for the 30 consecutive business days prior to the date of the letter, the Company’s market value of listed securities (“MVLS”) closed below the minimum $35 million requirement for continued listing on The Nasdaq Capital Market under Nasdaq Listing Rule 5550(b)(2) (the “MVLS Requirement”).
+Added: In accordance with Nasdaq Listing Rule 5810(c)(3)(C), the Company was granted a period of 180 calendar days, or until March 19, 2025, to regain compliance.
+Added: As anticipated, on March 20, 2025, the Company received another letter from the Staff stating that, as a result of the Company’s continued non-compliance with the MVLS Requirement, its securities would be delisted from Nasdaq unless the Company appealed the Staff’s delisting determination by requesting a hearing before the Nasdaq Hearings Panel (the “Panel”).
+Added: The Company made timely request for a hearing before the Panel to appeal the Staff’s determination.
+Added: The Company’s common stock will remain listed and eligible for trading on Nasdaq at least pending the ultimate conclusion of the hearing process;
+Added: however, there can be no assurance that the Company will ultimately regain compliance and remain listed on Nasdaq.
+Added: 2024 Clinical Prioritization
+Added: As discussed in Note 4, Restructuring in the notes to the consolidated financial statements included elsewhere in this Annual Report on Form 10-K, on May 8, 2024 the Company took additional actions as part of its continued efforts to preserve cash and prioritize investment in its core clinical programs.
+Added: As part of these actions, the Company initiated a reduction of approximately 15% of the Company’s workforce.
+Added: O n September 17, 2024, the Company approved a plan for an additional reduction in its workforce by 15 employees (including all but one sales and marketing employee), or approximately 28% of the Company’s headcount (the “Clinical Prioritization”), in order to extend its cash runway and prioritize investment on the clinical development of its lead neuroscience asset, BXCL501.
Our Neuroscience Strategy
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We believe that understanding the relation between entities relevant to drug development may lead to novel potential uses for existing drugs.
−Removed: Predictive algorithms or queries of the knowledge graph may uncover not only single drugs but potentially identify new combinations of drugs that we believe may be
−Removed: more effective in treating disorders than single agents.
+Added: Predictive algorithms or queries of the knowledge
+Added: graph may uncover not only single drugs but potentially identify new combinations of drugs that we believe may be more effective in treating disorders than single agents.
New combinations of drugs may lower tolerable doses of drugs and provide the basis for stronger intellectual property positions.
−Removed: Our AI team works closely with our Business Development team to prioritize in a data-driven manner the most valuable external opportunities.
+Added: Our AI team prioritizes the most valuable external opportunities in a data-driven manner.
These opportunities may be found in new potential uses for launched drugs, in drugs that are part of pharmaceutical company pipelines no longer being pursued, or within academic efforts to develop new drug candidates.
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and Karuna Therapeutics, Inc.
−Removed: are based on the re-innovation and combination of existing clinical candidates or marketed drugs to provide novel solutions for patients.
+Added: (acquired by Bristol Myers Squibb) are based on the re-innovation and combination of existing clinical candidates or marketed drugs to provide novel solutions for patients.
Unfortunately, such discoveries have been severely limited in scope due to the lack of a genuinely integrated approach to mining big data and advanced analytics.
Our AI-based discovery and development process is the foundation of our drug re-innovation model for identifying the next wave of potential medicines.
−Removed: Our therapeutic area experts have over 200 years of combined experience across the drug discovery and development value chain.
+Added: Our therapeutic area experts have substantial experience across the drug discovery and development value chain.
We believe that our method of finding potential product candidates gives us a higher probability of success because it combines AI expertise and intuition of human experience in drug development.
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We continue to integrate and evolve our neuroscience and immuno-oncology AI machine learning and drug discovery and development platform.
−Removed: Our platform led to the identification of Dex, the rapid development of BXCL501, and its approval by the FDA as IGALMI TM , as well as the advancement of BXCL501 for other potential indications.
+Added: Our platform led to the identification of Dex, the rapid development of BXCL501, and its approval by the FDA as IGALMI ® , as well as the advancement of BXCL501 for other potential indications.
We are continuing to leverage our platform to identify and develop new neuroscience and immuno-oncology programs.
−Removed: Our Neuroscience Programs
+Added: Our Neuroscience Clinical Programs
The following is a summary of the status of our neuroscience clinical development programs as of the date of this Annual Report on Form 10-K:
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In addition, we estimate that there are approximately 1.6 million Americans diagnosed with schizophrenia or bipolar disorders and that those patients experience agitation at a rate of about three episodes per month, on average.
−Removed: We, therefore, believe there is significant potential market opportunity for BXCL501 if approved for use in these patient populations in the at-home setting.
−Removed: foregoing estimates of the incidence of each patient population and the number of agitation episodes experienced and potential market opportunity are based on management’s estimates and third-party data, which may be materially different from actual agitation episodes and actual treatable patients.
+Added: We, therefore, believe there is significant
+Added: potential market opportunity for BXCL501 if approved for use in these patient populations in the at-home setting.
+Added: The foregoing estimates of the incidence of each patient population and the number of agitation episodes experienced and potential market opportunity are based on management’s estimates and third-party data, which may be materially different from actual agitation episodes and actual treatable patients.
For additional information regarding risks associated with these estimates, see Part I, Item 1A, Risk Factors “— Our estimated number of episodes of agitation and our corresponding estimated total addressable market are subject to inherent challenges and uncertainties.
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Treatments for Agitation
−Removed: Antipsychotics, the current standard of care for acute treatment of agitation in schizophrenia and bipolar disorder, are also used off-label to treat agitation in dementia and other conditions.
+Added: Antipsychotics, the current standard of care for acute treatment of agitation associated with schizophrenia and bipolar disorder, are also used off-label to treat agitation in dementia and other conditions.
Side effects of these medications include movement disorders, including akathisia and extrapyramidal symptoms.
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The sublingual or buccal route of administration is an accepted alternative to oral administration of drug delivery to the central nervous system when rapid onset or more controlled delivery is required.
−Removed: Currently, there are six products approved for film administration, including our product, IGALMI TM .
+Added: Currently, there are six products approved for film administration, including our product, IGALMI ® .
For example, BioDelivery Sciences International, Inc., a commercial-stage specialty pharmaceutical company, has developed a buccal film formulation of buprenorphine for chronic pain management and buprenorphine and naloxone for opioid dependence.
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Given these uses of the IV formulation of Dex, we believe Dex formulated in a sublingual film and at much lower doses allows for ease of administration in settings where rapid acute treatment of agitation is needed.
−Removed: IGALMI TM Commercial Progress
+Added: IGALMI ® Commercial Strategy
We continue to support IGALMI ® in the hospital setting through limited and focused commercial activity.
−Removed: On August 14, 2023, the Company announced it had implemented a shift in commercial strategy for IGALMI TM in the institutional setting, a reduction of in-hospital commercialization expenses, a suspension of programs no longer deemed core to the Company’s business, and a shift to focus on the development of BXCL501 for use in the at-home and care facilities in the treatment of acute agitation in schizophrenia and bipolar disorders, and in the treatment of acute agitation (non-daily) associated with dementia due to probable Alzheimer’s disease (collectively, the “Reprioritization”).
−Removed: Following the Reprioritization, a small Corporate Account Director (“CAD”) team supports current customers and targeted Integrated Delivery Networks (“IDNs”) with educational support and contracting opportunities, while our trade operation supports customers with drug supply.
−Removed: The goal of this approach is to help maintain current business and potentially broaden IGALMI TM utilization through volume contracting.
−Removed: Over time, we believe the revised commercial effort is expected to allow the Company to continue to make inroads into the institutional market in a more cost-efficient manner.
−Removed: Commercial efforts for the IGALMI TM launch were impacted significantly in the six months ended December 31, 2023 due to the reduction in force, which included the elimination of sales, marketing, and commercial operations staff.
−Removed: The realigned CAD team generated $376,000 in net revenue for the three-month period ended December 31, 2023 through legacy sales and volume-based contracts, up from $341,000 for the three-month period ended September 30, 2023.
−Removed: Net revenues from IGALMI™ product sales for the years ended December 31, 2023 and 2022 were $1.4 million and $375,000 respectively.
−Removed: On October 30, 2023, we announced that the Centers for Medicare & Medicaid Services (“CMS”) assigned a new J-Code for IGALMI TM (J1105).
−Removed: J-Codes are permanent codes used by healthcare providers, commercial insurance plans, and government payers to help standardize the reimbursement process.
−Removed: A J-Code can help simplify claims submission as compared to use of a miscellaneous or unlisted code, which in turn can streamline the billing and reimbursement process.
−Removed: The J-Code for IGALMI TM has been published online in the CMS HCPCS Application Summaries and Coding Recommendations, Third Quarter, 2023 HCPCS Coding Cycle.
−Removed: We believe this J-Code, which became effective on January 1, 2024, will facilitate access to IGALMI TM for patients with agitation associated with bipolar disorder or schizophrenia.
−Removed: If IGALMI TM is approved outside the U.S., we would consider launching the product through collaborations with third parties.
−Removed: Our continued commercialization efforts for IGALMI TM are designed to build the foundation to launch additional potential follow-on indications, if any, paving the way for our expanding neuroscience business.
+Added: In the third quarter of 2023, we revised our commercial strategy for IGALMI ® in the institutional setting, reducing in-hospital commercialization expenses, suspending programs no longer deemed core to our business, and shifting focus to the development of BXCL501 for use in the at-home and care facilities in the treatment of acute agitation in schizophrenia and bipolar disorders, and in the treatment of acute agitation (non-daily) associated with dementia due to probable Alzheimer’s disease (collectively, the “Reprioritization”).
+Added: Following the Reprioritization, a small Corporate Account Director team supported existing customers and targeted Integrated Delivery Networks (“IDNs”) with educational assistance and contracting opportunities, while our trade operation supported customers with drug supply.
+Added: The goal of this approach was to help maintain current business and potentially broaden IGALMI ® utilization through volume contracting.
+Added: As part of the Clinical Prioritization announced on September 19, 2024, we made further workforce reductions including sales and marketing employees, as the Company announced it would maintain IGALMI™ in the market with minimal commercial support.
+Added: The Clinical Prioritization staff reductions may have future impacts on net revenue.
+Added: Net revenues from IGALMI ® product sales for the years ended December 31, 2024 and 2023 were $2.3 million and $1.4 million, respectively.
+Added: We are currently seeking potential commercial partners.
+Added: Our continued commercialization efforts for IGALMI ® are designed to build the foundation to launch additional potential follow-on indications.
+Added: If IGALMI ® would be approved outside the U.S., we would consider launching the product through collaborations with third parties.
BXCL501 Development
−Removed: In indications other than those approved by the FDA as IGALMI TM , BXCL501 remains an investigational, proprietary, orally dissolving film formulation of Dex, a selective alpha-2 receptor agonist, targeting symptoms from stress-related behaviors such as agitation.
−Removed: BXCL501 is our most advanced neuroscience clinical program, being evaluated for the at-home acute treatment of agitation related to bipolar disorders or schizophrenia and for the acute treatment of agitation (non-daily) in patients with dementia due to probable Alzheimer’s disease in care facilities and at-home settings.
+Added: In indications other than those approved by the FDA as IGALMI ® , BXCL501 remains an investigational, proprietary, orally dissolving film formulation of Dex, a selective alpha-2 receptor agonist, targeting symptoms from stress-related behaviors such as agitation.
+Added: BXCL501 is our most advanced neuroscience clinical program, being evaluated for the acute treatment of agitation associated with bipolar disorders or schizophrenia in the at-home setting and for the acute treatment of agitation (non-daily) in patients with dementia due to probable Alzheimer’s disease in care facilities and at-home settings.
As a selective adrenergic agent with a sublingual or buccal route of administration, BXCL501 is designed to be easily administered and, compared to medications that may take days or weeks, has shown a relatively rapid onset of action in multiple clinical trials, including those studying patients with bipolar disorders, schizophrenia, and Alzheimer’s disease.
We believe results from these studies suggest that BXCL501 has the potential to reduce agitation without producing excessive sedation.
−Removed: We also believe BXCL501 is highly differentiated from antipsychotics, which are
−Removed: currently used as first-line standard-of-care treatments despite often producing unwanted side effects such as excessive sedation or extra pyramidal motor effects.
+Added: We also believe BXCL501 is highly differentiated from antipsychotics, which are currently used as first-line standard-of-care treatments despite often producing unwanted side effects such as excessive sedation or extra pyramidal motor effects.
Managing patient agitation in neuropsychiatric and neurodegenerative disorders represents a significant challenge for physicians and caregivers.
We believe BXCL501 has the potential to address these challenges while providing an efficient treatment regimen for patients.
−Removed: We also believe that BXCL501, if approved for the respective indications, has the potential to become the standard of care for the acute treatment of agitation arising from diseases such as schizophrenia and bipolar disorder and Alzheimer’s disease.
−Removed: In addition, given the differentiated design of BXCL501 and its potential mechanism of action, we believe BXCL501 has the potential to address several diseases or conditions for which agitation is a symptom of the condition or underlying disease, including opioid withdrawal and post-traumatic stress disorder (“PTSD”), which are being evaluated in clinical trials run by third-parties.
+Added: We also believe that BXCL501, if approved for the respective indications, has the potential to become the standard of care for the acute treatment of agitation arising from diseases such as schizophrenia, bipolar disorder and Alzheimer’s disease.
+Added: In addition, given the differentiated design of BXCL501 and its mechanism of action, we believe BXCL501 has the potential to address several diseases or conditions for which agitation is a symptom of the condition or underlying disease, including opioid withdrawal and post-traumatic stress disorder (“PTSD”), which are being evaluated in investigator-sponsored trials run by several leading academic research institutions.
BXCL501 Clinical Trials
+Added: SERENITY Program:
+Added: Agitation Associated with Bipolar Disorders I and II or Schizophrenia (at-home setting)
+Added: We initiated the clinical study of BXCL501 in patients with agitation associated with bipolar disorders or schizophrenia in SERENITY III, which consisted of two parts.
+Added: The first part was comparable to our pivotal SERENITY I and II studies.
+Added: Using similar inclusion and exclusion criterion under a well-controlled in-patient setting, acutely agitated patients with bipolar disorders or schizophrenia were randomized to self-administer either 60 mcg of BXCL501 or placebo in a double-blind placebo-controlled trial.
+Added: The primary endpoint of Part I was efficacy, as measured by the change in PEC score change from baseline at two hours post-dose.
+Added: The secondary objectives of Part I were safety and tolerability.
+Added: On May 25, 2023, we reported topline results from Part I of the study.
+Added: Although the trial did not meet its primary efficacy endpoint, we believe the efficacy results, observed with the 60 mcg dose, representing half of the lowest approved dose of IGALMI ® for in-patient use (120 mcg), were promising.
+Added: Specifically, greater than 50% of individuals were responders, defined as those patients who achieved a 40% or greater reduction in PEC score.
+Added: Furthermore, this population responder rate was consistent and dose-proportionate to the same response rates observed in the larger SERENITY I and II trials.
+Added: Although the primary efficacy endpoint as a group mean change in PEC score from baseline at 2 hours was not statistically significant at the primary endpoint at 2 hours (p=0.077), BXCL501 statistically separated from placebo at 4 hours (p=0.049).
+Added: Part II of the SERENITY III study was designed to evaluate the same dose tested in Part I, 60 mcg (with an optional additional 60 mcg dose), but in the at-home setting and focusing on safety only.
+Added: However, because the trial did not meet its primary efficacy endpoint using this 60 mcg dose in Part I, we paused continuation of Part II of the study pending feedback from the FDA.
+Added: We held a Type C meeting with the FDA on November 8, 2023 to discuss changes to Part II of our SERENITY III study.
+Added: We proposed the evaluation of an 80 mcg dose based on previous clinical experience with this dose during our Phase 1b trial in schizophrenia patients with agitation, and pharmacokinetic and pharmacodynamic modeling suggesting that use of an 80 mcg dose of BXCL501 could provide an optimal balance between safety and efficacy for at-home use.
+Added: Based on feedback from the FDA during the meeting, we made the decision to evaluate a 120 mcg dose in the at-home setting.
+Added: The 120 mcg dose has already demonstrated efficacy based on the approval of IGALMI ® (when administered under the supervision of a healthcare provider, for a single agitation episode), so we sought further feedback from the FDA regarding the proposed design of this study amendment in a request for a follow-up meeting with the FDA, which was held on March 6, 2024.
+Added: Based on the FDA’s feedback in advance of and during the March 6, 2024 meeting, we moved forward evaluating the use of the 120 mcg dose of BXCL501 in the at-home setting, and amended Part 2 of the SERENITY III study.
+Added: We now refer to this study as the SERENITY At-Home trial, with safety as the primary objective and efficacy measures as exploratory endpoints to support use in the at-home setting.
+Added: This was the FDA’s recommendation in the November 8, 2023 FDA meeting, for the acute treatment of agitation in bipolar disorders or schizophrenia.
+Added: We also plan to initiate a clinical study designed to enroll approximately 30 patient-informant dyads to evaluate the correlation between patient-and informant-reported efficacy measurement and the PEC scale, conducted by trained clinician raters as previously recommended by the FDA.
+Added: IGALMI ® is already approved at the 120 mcg dose based on efficacy data that we previously generated in treating a single episode of agitation.
+Added: Consistent with the data generated to date, the label for IGALMI ® currently includes a limitation on use (“LOU”), noting the lack of efficacy or safety data beyond 24 hours following the first dose.
+Added: During our March 6, 2024 Type C meeting with the FDA, we discussed, among other things, whether evaluating the at-home use of BXCL501 120 mcg, with safety as the primary objective and efficacy measures as exploratory endpoints, if successful, could support the submission of an sNDA seeking expansion of the current label for IGALMI ® 120 mcg to allow at-home use and labeling without the current LOU.
+Added: Based on FDA feedback, we believe that our ability to seek labeling without the current LOU will depend, in part, on the number of agitation episodes we observe during our planned study period.
+Added: On April 22, 2024, we announced our plans, subject to funding, to advance the SERENITY At-Home trial.
+Added: On September 5, 2024, we announced the initiation of our SERENITY At-Home trial.
+Added: The pivotal Phase 3 trial is designed to evaluate the safety of BXCL501 in the at home setting.
+Added: On November 12, 2024, we announced that
+Added: the first patient had been randomized in the trial.
+Added: On March 27, 2025, 24 clinical trial sites had been opened and 127 patients have been enrolled, representing 63% of the total required enrollment in the trial.
+Added: Topline data results, which are expected in the second half of 2025, are intended to support a supplemental new drug application (“sNDA”) submission to potentially expand the label of IGALMI® (dexmedetomidine) sublingual film.
TRANQUILITY Program:
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Randomized patients self-administered 40 mcg or 60 mcg of BXCL501 or placebo for agitation episodes that occurred over a 12-week period.
−Removed: The primary endpoint was the change from pre-dose in PEC total score at 2 hours post-dose for the first treated episode of agitation.
+Added: The primary endpoint was the change from pre-dose in Positive and Negative Syndrome Scale-Excitatory Component (“PEC”) total score at 2 hours post-dose for the first treated episode of agitation.
The key secondary efficacy endpoints were PEC change from pre-dose at 1 hour post-dose of study treatment for the first treated episode of agitation, and PEC change from pre-dose at 30 minutes post-dose of study treatment for the first treated episode of agitation.
The Phase 3 trial met its primary efficacy endpoint with the 60 mcg dose;
−Removed: a statistically significant and clinically meaningful 7.5 point reduction from baseline in Positive and Negative Syndrome Scale-Excitatory Component (“PEC”) total score was observed at 2 hours versus 5.4 with placebo (p=0.0112).
+Added: a statistically significant and clinically meaningful 7.5 point reduction from baseline in PEC total score was observed at 2 hours versus 5.4 with placebo (p=0.0112).
The 60 mcg dose also met the first key secondary endpoint of reducing agitation symptoms at 1 hour during the first episode of agitation (p=0.0185) but did not meet the other key secondary endpoint of change from baseline in PEC score at 30 minutes.
−Removed: Efficacy for this dose was supported by several secondary measures, including CGI-Improvement and Agitation-Calmness Evaluation Scale.
+Added: Efficacy for this dose was supported by several secondary measures, including the Clinical Global Impressions – Improvement Scale (“CGI-I”) and Agitation-Calmness Evaluation Scale (“ACES”).
Most patients (76%) responded to the first 60 mcg dose and were determined to be “Very Much” or “Much Improved” (CGI-I of 1 or 2, respectively) compared to 50% with placebo.
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Based on these steps to date, we believe that there have been no further instances of misconduct or fraud or other findings that adversely impact the data integrity or reliability of the eligibility, safety, and efficacy data obtained at the clinical trial site in question.
−Removed: Our TRANQUILITY III trial was designed to evaluate the safety and efficacy of BXCL501 in patients residing predominantly in nursing homes with moderate to severe dementia due to Alzheimer’s disease who require moderate or greater assistance with activities of daily living.
−Removed: We halted additional enrollment in this Phase 3 after initial enrolled patients were observed to have more frequent episodes of agitation than originally anticipated, suggesting that agitation may present chronically in this population.
−Removed: Due to the chronic nature of agitation episodes observed in this population thus far, we believe that continued evaluation of BXCL501 in this population would require a different development program targeting more frequent or chronic use.
−Removed: We have chosen to focus our development efforts on the urgent need for episodic treatment in the care facility and at-home setting.
−Removed: In a Type B/Breakthrough Therapy designation meeting with the FDA on October 11, 2023, we reviewed our
−Removed: TRANQUILITY clinical trial program and discussed the data package required to support submission of an sNDA for the potential approval of BXCL501 for the acute treatment of agitation in patients with mild to moderate dementia due to probable Alzheimer’s disease in the ALF and at-home settings.
+Added: On March 3, 2025 we announced that the U.S.
+Added: Food and Drug Administration (FDA) concluded that the inspection of a single site in its TRANQUILITY II Phase 3 trial was closed under 21 C.F.R.20.64(d)(3) and released the Establishment Inspection Report.
+Added: The FDA designated “Voluntary Action Indicated” for the site.
+Added: We believe this further supports the reliability of data from the TRANQUILITY II trial of BXCL501.
+Added: In a Type B/Breakthrough Therapy designation meeting with the FDA on October 11, 2023, we reviewed our TRANQUILITY clinical trial program and discussed the data package required to support submission of an sNDA for the potential approval of BXCL501 for the acute treatment of agitation in patients with mild to moderate dementia due to probable Alzheimer’s disease in the ALF and at-home settings.
Specifically, we sought feedback from the FDA as to whether our data package consisting of TRANQUILITY I and II, along with the clinical pharmacology and toxicology programs previously discussed with the FDA, would be sufficient to support an sNDA submission for the potential use of BXCL501 to treat agitation in patients with mild to moderate dementia due to probable Alzheimer’s disease in either the at-home or ALF setting, or, if not, what additional data would be required.
−Removed: Based on the FDA’s feedback in this meeting, we understand that the FDA will require additional efficacy data, including repeat efficacy data, and that it requested long-term safety data.
+Added: Based on the FDA’s feedback in this meeting, we understand that the FDA will require additional efficacy data, including repeat efficacy data, and long-term safety data.
We therefore requested another meeting with the FDA to further discuss the additional data that would be required to support an sNDA submission.
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As a result, we focused on requesting feedback from the FDA regarding our proposal for an at-home clinical study with safety as the primary objective, and to better understand what additional data would be required to submit an sNDA to support labeling for BXCL501 to include the acute treatment of agitation associated with dementia in probable Alzheimer’s disease or, in the alternative, in this population in the care setting only.
−Removed: In its preliminary responses, the FDA reiterated its prior comments that we generate additional efficacy data, including repeat-dose efficacy data, to support an sNDA submission, as the FDA indicated that our proposed efficacy database, which currently includes the 70 patients who have been treated with 60 mcg of BXCL501 in TRANQUILITY I and TRANQUILITY II, would not contain substantial evidence of effectiveness absent additional data.
+Added: In its preliminary responses, the FDA reiterated its prior comments that we need to generate additional efficacy data, including repeat-dose efficacy data, to support an sNDA submission, as the FDA indicated that our proposed efficacy database, which currently includes the 70 patients who have been treated with 60 mcg of BXCL501 in TRANQUILITY I and TRANQUILITY II, would not contain substantial evidence of effectiveness absent additional data.
The FDA advised that we generate the necessary efficacy data in care facilities prior to conducting any trials in the at-home setting.
In addition, the FDA indicated the need to generate long-term safety data to support an sNDA submission, including from probable Alzheimer’s disease patients exposed to BXCL501, for up to one year.
−Removed: We have received the final meeting minutes from the FDA, which we believe are consistent with the FDA’s preliminary responses and the subsequent meeting discussion.
−Removed: Based on the FDA’s feedback, we are currently planning to generate additional Phase 3 efficacy and safety data, in a variety of relevant care-facility settings and across severity of dementia using the Positive and Negative Syndrome Scale-Excitatory Component (“PEC”) as the primary efficacy measure, as used in the prior TRANQUILITY II study.
+Added: Based on the FDA’s feedback, we are currently planning to generate additional Phase 3 efficacy and safety data, in a variety of relevant care-facility settings and across severity of dementia, in our planned TRANQUILITY In-Care Phase 3 trial.
In addition, we plan to discuss the details of the requirement for long-term safety data at a future meeting with the FDA.
−Removed: Also, although we announced in November 2023 that we were planning to conduct a Phase 3 trial in the at-home setting, with safety as the primary objective (TRANQUILITY At Home), given the priority to expand the database to generate additional efficacy and safety data in care facilities, we are re-evaluating the timing for initiating TRANQUILITY At Home.
−Removed: SERENITY Program:
−Removed: Agitation Associated with Bipolar Disorders I and II and Schizophrenia (at-home use)
−Removed: We initiated the SERENITY III clinical study of BXCL501 in patients with agitation associated with bipolar disorders or schizophrenia in SERENITY III, which consists of two parts.
−Removed: The first part was comparable to our pivotal SERENITY I and II studies.
−Removed: Using similar inclusion and exclusion criterion under a well-controlled in-patient setting, acutely agitated patients with schizophrenia or bipolar disorders were randomized to self-administer either 60 mcg of BXCL501 or placebo in a double-blind placebo-controlled trial.
−Removed: The primary endpoint of Part I was efficacy, as measured by the change in PEC score change from baseline at two hours post-dose.
−Removed: The secondary objectives of Part I were safety and tolerability.
−Removed: On May 25, 2023, we reported topline results from Part I of the study.
−Removed: Although the trial did not meet its primary efficacy endpoint, we believe the efficacy results, observed with the 60 mcg dose, representing half of the lowest approved dose of IGALMI TM for in-patient use (120 mcg), were promising.
−Removed: Specifically, greater than 50% of individuals were responders, defined as those patients who achieved a 40% or greater reduction in PEC score.
−Removed: Furthermore, this population responder rate was consistent and dose-proportionate to the same response rates observed in the larger SERENITY I and II trials.
−Removed: Although the primary efficacy endpoint as a group mean change in PEC score from baseline at 2 hours was not statistically significant at the primary endpoint at 2 hours (p=0.077), BXCL501 statistically separated from placebo at 4 hours (p=0.049).
−Removed: Part II of the SERENITY III study was designed to evaluate the same dose tested in Part I, 60 mcg (with an optional additional 60 mcg dose), but in the at-home setting and focusing on safety only.
−Removed: However, because the trial did not meet its primary efficacy endpoint using this 60 mcg dose in Part I, we paused continuation of Part II of the study pending feedback from the FDA.
−Removed: We held a Type C meeting on November 8, 2023 with the FDA to discuss changes to Part II of our SERENITY III study.
−Removed: We proposed the evaluation of an 80 mcg dose based on previous clinical experience with this dose during our Phase 1b trial in schizophrenia patients with agitation, and pharmacokinetic and pharmacodynamic modeling suggesting that use of an 80 mcg dose of BXCL501 could provide an optimal balance between safety and efficacy for at-home use.
−Removed: Based on feedback from the FDA during the meeting, we made the decision to evaluate a 120 mcg dose in the at-home setting.
−Removed: The 120 mcg dose has already demonstrated efficacy based on the approved conditions of use for IGALMI TM (when administered under the supervision of a healthcare provider, for a single agitation episode), so we sought further feedback from the FDA regarding the proposed design of this study amendment in a request for a follow-up meeting with the FDA, which was held on March 6, 2024.
−Removed: Based on the FDA’s feedback in advance of and during the March 6, 2024 meeting, we plan to move forward to evaluate at-home use of the 120 mcg dose of BXCL501, with safety as the primary objective and efficacy measures as exploratory endpoints to support continued efficacy in the at-home setting as recommended by the FDA in the November 8, 2023 meeting, for the acute treatment of agitation in bipolar disorders or schizophrenia.
−Removed: We also plan to conduct a clinical study designed to enroll approximately 30 patients to evaluate the correlation between patient-reported or informant-reported efficacy with trained rater-reported efficacy using PEC measurements, which the FDA had previously recommended.
−Removed: IGALMI TM is already approved at the 120 mcg dose based on efficacy data that we previously generated in treating a single episode of agitation.
−Removed: Consistent with the data generated to date, the label for IGALMI TM currently includes a limitation on use (“LOU”), noting the lack of efficacy or safety data beyond 24 hours following the first dose.
−Removed: During our March 6, 2024 Type C meeting with the FDA, we discussed, among other things, whether evaluating the at-home use of BXCL501 120 mcg, with safety as the primary objective and efficacy measures as exploratory endpoints, if successful, could support the submission of an sNDA seeking expansion of the current label for IGALMI TM 120 mcg to allow at-home use and labeling without the current LOU.
−Removed: Based on FDA feedback, we believe that our ability to seek labeling without the current LOU will depend, in part, on the number of agitation episodes we observe during our planned study period.
−Removed: We plan to provide further guidance regarding our plans for the SERENITY program following receipt of the final meeting minutes from the FDA.
+Added: Also, although we announced in November 2023 that we were planning to conduct a Phase 3 trial in the at-home setting, with safety as the primary objective (TRANQUILITY At Home), given the priority to expand the database to generate additional efficacy and safety data in care facilities, and subject to funding, we are re-evaluating the timing for initiating TRANQUILITY At Home.
+Added: On September 5, 2024, we submitted to the FDA the proposed protocol for our TRANQUILITY In-Care Phase 3 trial designed to evaluate the efficacy and safety of a 60 mcg dose of BXCL501 for agitation associated with Alzheimer’s dementia.
+Added: On November 12, 2024, we announced that we had received FDA feedback on the proposed protocol .
Adjunctive treatment in Major Depressive Disorder (“MDD”)
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The initial clinical study in this program was a double-blind, placebo-controlled, multiple ascending dose (“MAD”) trial to evaluate the safety and tolerability of daily doses of BXCL501 in healthy volunteers.
−Removed: On May 16, 2023, we reported positive topline results from a MAD study.
−Removed: It enrolled 125 healthy adult volunteers across seven different cohorts in a 2:1 randomization to BXCL501 or placebo film.
−Removed: Healthy volunteers were dosed for 7 consecutive days.
−Removed: Both safety and pharmacokinetics were assessed.
−Removed: The study included 7 cohorts.
−Removed: Four distinct cohorts received 30 mcg, 60 mcg, 80 mcg, or 120 mcg doses of BXCL501 or placebo once daily.
−Removed: Two additional dosing cohorts received twice-daily (BID) BXCL501 at either 30 mcg in the morning and 60 mcg in the evening, or 40 mcg in the morning and 80 mcg in the evening.
−Removed: The final escalation cohort evaluated BXCL501 at 60 mcg in the morning and 80 mcg in the evening in combination with 30 mg of duloxetine BID.
−Removed: BXCL501 was generally well tolerated across all dosing cohorts.
−Removed: Based upon pre-specified stopping criteria, a maximum tolerated dose was not reached.
−Removed: All adverse events were reported as mild or moderate.
−Removed: As part of the Reprioritization announced on August 14, 2023, we have paused our plan to develop a Phase 2 human proof-of-concept trial design to investigate BXCL501 as a potential adjunctive treatment and its potential accelerant effect in combination with first-line selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.
+Added: As part of the Reprioritization announced on August 14, 2023, we paused our plan to develop a Phase 2 human proof-of-concept trial design to investigate BXCL501 as a potential adjunctive treatment and its potential accelerant effect in combination with first-line selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.
Pediatric Study
−Removed: In June 2021, we initiated a global clinical trial designed to evaluate the safety and efficacy of BXCL501 in the acute treatment of agitation associated with pediatric schizophrenia and bipolar disorders, in part to fulfill pediatric study requirements agreed to with the FDA in connection with the approval of IGALMI TM .
+Added: In June 2021, we initiated a global clinical trial designed to evaluate the safety and efficacy of BXCL501 in the acute treatment of agitation associated with pediatric schizophrenia and bipolar disorders, in part to fulfill pediatric study requirements agreed to with the FDA in connection with the approval of IGALMI ® .
The trial protocol has been reviewed by the FDA, as well as by the European Medicines Agency, to fulfill potential commitments to study the effects of BXCL501 in pediatric patients ages 13 to 17 with schizophrenia and ages 10 to 17 with bipolar disorders.
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portion of this program remains active following the Reprioritization.
+Added: In October 2024, we submitted a request to the FDA for an extension and plan to submit an updated trial protocol to complete enrollment requirements for pediatric patients with schizophrenia or schizoaffective disorder.
+Added: The FDA granted a 3-year extension to complete the pediatric study.
+Added: IGALMI ® Post-Marketing Requirement Study
+Added: On June 25, 2024, we announced positive topline results from our post-marketing requirement study evaluating whether tolerance, tachyphylaxis, or withdrawal occur following repeat dosing of the 180 mcg (highest approved dose) of IGALMI ® .
+Added: This study was a single-arm, open-label study of 28 inpatient adults with frequent episodes of agitation associated with bipolar disorders or schizophrenia who self-administered 180 mcg dose of IGALMI ® as needed over seven days.
+Added: A total of 83 episodes were treated.
+Added: The study achieved its objective and demonstrated no evidence of tachyphylaxis, tolerance, or withdrawal, and IGALMI ® was generally well tolerated during the study.
Additional Neuroscience Opportunities
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Given the differentiated design of BXCL501 and its selective mechanism of action, we believe BXCL501 has the potential for broad applicability across several indications where agitation is a symptom of a condition or underlying disease.
−Removed: Government-Supported Investigator-Initiated Trial Programs
+Added: Government-Supported Investigator-Sponsored Trial Programs
The Company has been awarded key opportunities for the development of BXCL501 in post-traumatic stress disorder (“PTSD”), alcohol use disorder (“AUD”), and opioid use disorder (“OUD”).
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Clinical and regulatory responsibilities are led by clinical researchers and regulatory staff at the Veterans Affairs Connecticut Healthcare System, Yale University Medical School, RTI International, Columbia University New York State Psychiatric Institute, and NIDA.
−Removed: The Company has retained all rights to commercialization of BXCL501 in all potential indications evaluated in clinical trials supported by the U.S.
Opioid Use Disorder Program
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To date, a ll three initial sites have recruited, enrolled, and dosed patients diagnosed with OUD who are physically dependent on opioids, including prescription opioids.
−Removed: The Company is supplying the drug product for the conduct of this study, which is sponsored by Columbia University .
+Added: The Company is supplying BXCL501 for the conduct of this study, which is sponsored by Columbia University .
We expect that the results from current study will be used to select a recommended dose of BXCL501 to compare to placebo in a later outpatient Phase 3 study sponsored by NIDA.
−Removed: On November 6, 2023, we announced that NIDA has requested Columbia University, the trial coordinator, to add a fourth site to target trial completion in 2024.
−Removed: The patient screening and enrollment process for the fourth site commenced in March 2024.
−Removed: Pending favorable results, after completion of the trial, we plan to seek FDA feedback on potential registrational paths.
+Added: On November 6, 2023, we announced that NIDA requested Columbia University, the trial coordinator, to add a fourth site to expedite trial completion.
+Added: The patient screening and enrollment process for the fourth site commenced in March 2024, a potential mid-study readout anticipated in the first half of 2025.
+Added: Subject to favorable results and available funding, we plan to seek FDA feedback on potential registrational paths.
Alcohol Use Disorder with Comorbid Post-traumatic Stress Disorder Program
In December 2020, the Veterans Affairs Connecticut Healthcare System and Yale University Medical School were awarded a grant by the U.S.
−Removed: Department of Defense’s Congressionally Directed Medical Research Program with the
−Removed: overall objective to evaluate BXCL501 in patients who suffer from AUD with comorbid PTSD.
+Added: Department of Defense’s Congressionally Directed Medical Research Program with the overall objective to evaluate BXCL501 in patients who suffer from AUD with comorbid PTSD.
The Company provided BXCL501 for the inpatient Alcohol Interaction Study, which has been completed.
−Removed: We understand Yale is currently seeking approval from its IRB and allowance from the FDA to proceed with a trial evaluating the effects of up to 80 mcg BID of BXCL501 per day for 28 days on alcohol consumption, PTSD symptoms, cognitive function, memory, sleep, and mood in patients diagnosed with mild, moderate, or severe AUD and who meet Criterion A for comorbid PTSD.
+Added: We understand Yale is currently seeking approval from its Institutional Review Board (“IRB”) and allowance from the FDA to proceed with a trial
+Added: evaluating the effects of up to 80 mcg BID of BXCL501 per day for 28 days on alcohol consumption, PTSD symptoms, cognitive function, memory, sleep, and mood in patients diagnosed with mild, moderate, or severe AUD and who meet Criterion A for comorbid PTSD.
The new outpatient study has received funding approval from the Pharmacotherapies for Alcohol and Substance Use Disorders Alliance (funded through a Cooperative Agreement between the U.S.
Department of Defense Congressionally Directed Medical Research Program and RTI International).
−Removed: We believe the results from this study will be used to inform a Phase 3 study intended to commence with support by the alliance.
−Removed: Algorithms for Wearable Technologies
−Removed: The Company completed a healthy volunteer study designed to train an algorithm to detect a state of hyper-arousal, which often precedes agitated behaviors.
−Removed: In hyper-aroused healthy volunteers, robust signals were measured using wearable technology (phones and watches).
−Removed: As part of the Reprioritization announced on August 14, 2023, we deprioritized our plan to develop wearable technology.
+Added: Patient screening and enrollment began in the fourth quarter of 2024.
+Added: We believe the results from this study may be used to inform a Phase 3 study intended to commence with support by the alliance.
+Added: Acute Stress Disorder (ASD) Program
+Added: On October 15, 2024, we announced a U.S.
+Added: Department of Defense grant to the University of North Carolina (“UNC”) to fund a study of BXCL501 for treating ASD.
+Added: The award provides $2,800 to the UNC Institute for Trauma Recovery from September 15, 2024 through September 14, 2026 to evaluate the potential efficacy of BXCL501 to reduce ASD symptom severity and/or posttraumatic neuropsychiatric symptoms.
+Added: The double-blind, placebo-controlled trial is expected to enroll 100 patients experiencing ASD resulting from motor vehicle collisions, beginning in the first half of 2025.
+Added: We intend to supply BXCL501 for the trial.
BXCL502 Development
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We plan to evaluate BXCL502 initially as a monotherapy and possibly in combination with BXCL501 for the chronic treatment of agitation in patients with dementia and acute stress disorder.
−Removed: The active pharmaceutical ingredient (“API”) underlying BXCL502 is designed to affect serotonergic signaling in the brain.
+Added: The active pharmaceutical ingredient (“API”) underlying BXCL502 affects serotonergic signaling in the brain.
Our preclinical data suggests BXCL502 has the potential to treat stress-related neuropsychiatric symptoms in dementia and other stress-related disorders.
In previously published third-party clinical trial data, daily administration of the API of BXCL502 demonstrated improvement in behaviors using a well-established, clinically validated symptom scale.
−Removed: Formulation and further clinical development planning are currently under way with BXCL502 and are expected to continue in 2024.
+Added: Formulation and further clinical development planning for BXCL502 was paused as part of the Reprioritization.
Other Product Candidates Leveraging the AI Platform
−Removed: We are targeting neuropsychiatric disorders with high unmet medical needs.
−Removed: Our focus is on treating stress-related symptoms, such as agitation, that are responsible for increased levels of healthcare burden.
−Removed: We are also using AI approaches and machine learning to identify new candidates for rare neurological diseases and to re-innovate late-stage drug candidates, such as BXCL503, targeting apathy in dementia, and BXCL504, targeting aggression in dementia.
−Removed: We utilize proprietary algorithms to identify associated mechanisms with existing pharmacology to test whether these agents can improve the disease profile in the animal model either through disease modification or symptomatic manner.
−Removed: The agents identified must be those we believe can enter the clinic with the potential for an efficient development path (similar to BXCL501).
−Removed: We are also developing an AI-based research and development platform to help identify potential product candidates and indications across a range of treatment areas.
+Added: Our AI platform is comprised of a series of customized and specific AI applications aimed at identifying, predicting efficacy and testing of late-stage assets with known mechanisms of action and associated pharmacology and safety data.
+Added: We target neuropsychiatric and neurological rare disorders, where the compounds are either disease-modifying or symptom-mitigating.
+Added: Compounds are tested in relevant models of disease and rank-ordered based on the potential to enter the clinic and ease of development.
+Added: Disease areas of interest are stress related such as agitation, or neuropsychiatric symptoms associated with dementia and responsible for increased levels of healthcare burden.
+Added: For example, our pipeline concepts BXCL503 and BXCL504 putatively have the potential to address apathy and aggression in dementia, respectively.
+Added: These programs were also paused as part of the Reprioritization.
Neuroscience Competition
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Mergers and acquisitions in the pharmaceutical, biotechnology, and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors.
−Removed: These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and in
−Removed: establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to or necessary for our programs.
+Added: These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and in establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies
+Added: complementary to or necessary for our programs.
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
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Any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.
−Removed: IGALMI TM and any of our other product candidates that are approved, if any, will compete with the drugs discussed below, in addition to any other drugs currently in development.
+Added: IGALMI ® and any of our other product candidates that are approved, if any, will compete with the drugs discussed below, in addition to any other drugs currently in development.
Drugs used for the acute treatment of agitation related to schizophrenia and bipolar disorder are antipsychotics frequently administered via IM injection that typically requires patient restraint.
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We currently rely on strategic manufacturing partners, in particular ARx, LLC (“ARx”), and expect to continue to rely on third parties for the manufacture of our product candidates for clinical research and our products for commercialization efforts.
−Removed: ARx has agreed to exclusively manufacture and supply all of our worldwide supply of film formulation of dexmedetomidine to be used for the commercial supply of IGALMI TM and for ongoing clinical trials of BXCL501, subject to certain alternative supply provisions.
+Added: ARx has agreed to exclusively manufacture and supply our supply of film formulation of dexmedetomidine to be used for the commercial supply of IGALMI ® and for ongoing clinical trials of BXCL501, subject to certain alternative supply provisions.
BXCL501 drug product is manufactured using commercially available components and packaging materials.
−Removed: The equipment employed for manufacture and analysis is consistent with standard pharmaceutical production.
+Added: The equipment employed for manufacturing and analysis is consistent with standard pharmaceutical production.
Neuroscience Commercialization
−Removed: We plan to retain worldwide commercialization rights for IGALMI TM and other approved product candidates, if any, but could consider collaboration opportunities to maximize returns or facilitate commercialization efforts in foreign jurisdictions.
−Removed: For additional information regarding our commercialization efforts for IGALMI TM , see above under “IGALMI TM Commercial Progress.”
+Added: We plan to retain worldwide commercialization rights for IGALMI ® and other approved product candidates, if any, but could consider collaboration opportunities to maximize returns or facilitate commercialization efforts in foreign jurisdictions.
+Added: For additional information regarding our commercialization efforts for IGALMI ® , see above under “IGALMI ® Commercial Strategy.”
As product candidates advance through our pipeline, our commercialization plans may change.
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Our policy is to protect and enhance the proprietary technologies, inventions, and improvements that are commercially important to our business by filing patent applications in the U.S.
−Removed: and other jurisdictions related to our
−Removed: proprietary technology, inventions, improvements, and product candidates.
−Removed: We also rely on trademarks, trade secrets, and know-how relating to our proprietary technologies and product candidates, continuing innovation, and in-licensing technology and products.
+Added: and other jurisdictions related to our proprietary technology, inventions, improvements, and product candidates.
+Added: We also rely on trademarks, trade secrets,
+Added: and know-how relating to our proprietary technologies and product candidates, continuing innovation, and in-licensing technology and products.
This reliance is expected to develop, maintain, and strengthen our proprietary position for novel therapeutics and novel formulations of existing therapeutics across multiple therapeutic areas.
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We have multiple patent families filed to protect our Neuroscience program, including BXCL501.
−Removed: As of March 15, 2024, our neuroscience patent portfolio included two Patent Cooperation Treaty (“PCT”) applications not yet in national phase, 19 U.S.
−Removed: utility applications, seven U.S.
−Removed: provisional applications, one allowed US application, ten issued U.S.
+Added: As of February 20, 2025, our neuroscience patent portfolio included five Patent Cooperation Treaty (“PCT”) applications not yet in national phase, 13 U.S.
+Added: utility applications, 16 issued U.S.
utility patents, 76 pending non-U.S.
utility applications, 24 allowed or granted non-U.S.
−Removed: patents (including three in Japan), one pending U.S.
+Added: patents (including four in Japan), one pending U.S.
design patent application, and 39 allowed or registered design patents (including two in Japan).
−Removed: utility patents, directed to our proprietary sublingual film formulation of Dex and methods of treating agitation, are now listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the “Orange Book”) for IGALMI™ with expiration dates between 2039 and 2043.
−Removed: In the formulation family, we also have a granted patent in China, two granted patents in Eurasia, and pending applications in the U.S., China, and other major markets.
+Added: Thirteen U.S.
+Added: utility patents, directed to our proprietary sublingual film formulation of Dex and methods of treating agitation, are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the “Orange Book”) for IGALMI ® with expiration dates between 2037 and 2043.
+Added: In the formulation family, we have granted or allowed patents in China, Europe, Eurasia, Japan, Mexico, and the U.S., and pending applications in the U.S., China, and other major markets.
We expect that patents issued in this family will expire no earlier than 2039.
We have also filed applications in additional patent families that are relevant to BXCL501.
−Removed: We have applications pending in the U.S., Europe and Japan directed to methods of treating insomnia using sublingual Dex.
−Removed: We expect that patents issued from these applications, if any, will expire no earlier than 2035.
−Removed: We also have applications filed in 16 regions/countries, including the U.S., Europe, Japan, and China, directed to methods of treating agitation.
−Removed: We expect that patents issued from these applications, if any, will expire between 2039 and 2043.
−Removed: We also have one PCT application directed to treating mania and another to treating depression.
−Removed: If patents are issued from those cases, we expect them to expire no earlier than 2041 and 2042, respectively.
−Removed: In March 2024, the Company announced that the European Patent Office granted the Company’s European Patent No.
−Removed: 3,562,486 (the “’486 patent”), which covers the use of dexmedetomidine administered sublingually to treat agitation in individuals with dementia.
−Removed: The ‘486 patent encompasses a broad range of dosage forms, including films such as BXCL501 (sublingual dexmedetomidine), wafers, and tablets, at dexmedetomidine doses ranging from 3 mcg to 100 mcg.
−Removed: The ‘486 patent will expire no earlier than December 29, 2037.
−Removed: In February 2024, the Company announced that the United States Patent and Trademark Office (“USPTO”) had allowed U.S.
−Removed: Patent Application No.
−Removed: 17/496,470 with claims pertaining to a method of treating agitation in patients with Alzheimer’s disease using the oromucosal administration of 60 mcg of dexmedetomidine in a water-soluble dosage form.
−Removed: The broad claims encompass film formulations such as BXCL501 (sublingual dexmedetomidine), tablets, or wafers.
−Removed: The patent, when issued, is expected to have an expiration date of December 29, 2037, subject to patent term adjustment (“PTA”), patent term extension (“PTE”) and terminal disclaimers.
−Removed: In February 2024, the Company also announced the USPTO issued U.S.
−Removed: 11,890,272 (the “'272 Patent”) on February 6, 2024.
−Removed: The '272 Patent claims a method of treating agitation associated with schizophrenia or bipolar disorder through oromucosal administration of about 120 mcg to about 180 mcg of dexmedetomidine where the patient has a QT interval of less than 470 msec.
−Removed: The '272 Patent has an expiration date of July 17, 2040, subject to PTA, PTE and terminal disclaimers.
−Removed: The '272 Patent has been accepted for listing in the FDA Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the “Orange Book”).
−Removed: In February 2024, the Company also received notice that the USPTO had allowed U.S.
+Added: We have one granted European patent and applications pending in the U.S.
+Added: and Japan directed to methods of treating insomnia using sublingual Dex.
+Added: We expect that patents issued from these applications, will expire no earlier than 2035.
+Added: We also have granted patents and pending applications filed in major markets, including the U.S., Europe, Japan, and China, directed to methods of treating agitation.
+Added: We expect that patents issued from these applications, will expire between 2039 and 2043.
+Added: We also have four PCT applications directed to treating mania, depression, stress and agitation.
+Added: If patents are issued from those cases, we expect them to expire in 2043 or 2044.
+Added: In August 2024, the Company received a Notice of Allowance from the U.S.
+Added: Patent and Trademark Office (“USPTO”) for U.S.
Patent Application No.
−Removed: 18/216,890 with claims pertaining to a method of treating agitation using an oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof through the administration of an initial dose of 60 mcg, 80 mcg, 90 mcg, 120 mcg or 180 mcg of dexmedetomidine and, after at least two hours, administering an oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof in a second dose of 40 mcg, 60 mcg, 80 mcg or 90 mcg of dexmedetomidine, where the patient has a QT interval of less than 470 msec.
−Removed: The patent, when issued, is expected to have an expiration date of July 17, 2040, subject to PTA, PTE and terminal disclaimers.
−Removed: The Company expects that this patent, when issued, will be submitted for listing in the Orange Book with the eight currently listed U.S.
−Removed: patents for IGALMI™ (dexmedetomidine) sublingual film.
−Removed: Collectively, these nine patents will in general extend patent protection for IGALMI TM until January 12, 2043.
+Added: 18/600,431 (the “’431 Application”).
+Added: The ’431 Application claims methods of treating agitation using an oromucosal formulation of dexmedetomidine.
+Added: The ‘431 Application issued as U.S.
+Added: 12,138,247 (the ‘247 Patent) patent, issued on November 2024, and is expected to expire no earlier than January 12, 2043.
+Added: The ’247 Patent is listed in the Orange Book for IGALMI ® .
The term of individual patents depends upon the legal term for patents in the countries in which they are obtained.
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In the future, we intend to apply for restorations of patent term for some of our currently owned or licensed patents to add patent life beyond their current expiration date, depending on the expected length of clinical trials and other factors involved in the submission of the relevant NDA.
−Removed: The term of a patent can also be extended by Patent Term Adjustment (“PTA”) established in 35 U.S.C.
+Added: The term of a patent can also be extended by PTA established in 35 U.S.C.
The intention of the PTA is to accommodate for delays caused by the USPTO during the prosecution of a US utility or plant patent application.
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In addition, the scope of the rights granted under any issued patents may not provide us with protection or competitive advantages against competitors with similar technology.
−Removed: Furthermore, our competitors may independently develop similar technologies outside the scope of the rights granted under any issued
−Removed: patents that we own or exclusively in license.
+Added: Furthermore, our competitors may independently develop similar technologies outside the scope of the rights granted under any issued patents that we own or exclusively in license.
For these reasons, we may face competition with respect to our product candidates.
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The Company is continuing to evaluate strategic options for OnkosXcel.
−Removed: With the Company’s Reprioritization announcement on August 14, 2023, further work on the immuno-oncology programs described below have generally been paused, except as noted below.
−Removed: Our approach to drug discovery leverages the application and methodology of our proprietary AI-based research and development platform, complemented by EvolverAI, utilized in the successful development of IGALMI TM with the aim of efficiently identifying and developing immuno-oncology product candidates.
+Added: With the Company’s Reprioritization announcement on August 14, 2023, further work on the immuno-oncology programs described below has generally been paused, except as noted below.
+Added: Our approach to drug discovery leverages the application and methodology of our proprietary AI-based research and development platform, complemented by EvolverAI, utilized in the successful development of IGALMI ® with the aim of efficiently identifying and developing immuno-oncology product candidates.
We believe that BXCL701 reflects the potential of this discovery approach in immuno-oncology.
−Removed: BXCL701 is an investigational, oral innate immune activator which demonstrated a 25% composite response rate in a Phase 2a clinical trial to treat patients with small cell neuroendocrine (“SCNC”)-phenotype metastatic castration-resistant prostate cancer (“mCRPC”).
+Added: BXCL701 is an investigational, oral innate immune activator which demonstrated a 25% composite response rate in a Phase 2a clinical trial to treat patients with small cell neuroendocrine carcinoma (“SCNC”) phenotype metastatic castration-resistant prostate cancer (“mCRPC”).
On February 12, 2024, the Company announced that the FDA has designated as a Fast Track development program the investigation of BXCL701 in combination with a checkpoint inhibitor for the treatment of patients with metastatic SCNC with progression on chemotherapy and no evidence of microsatellite instability.
−Removed: We intend to finalize a potential registrational trial design in mCRPC patients with SCNC phenotype following planned meetings with the FDA in the first half of 2024.
−Removed: However, the start of any such trial is paused following our Reprioritization.
+Added: We have finalized a potential
+Added: registrational trial design in mCRPC patients with SCNC phenotype, however in light of our Clinical Prioritization, we have not met with the FDA to discuss this, nor plan at the current time to initiate this trial.
mCRPC is often characterized as a “cold” tumor, which is a tumor with an immunosuppressive tumor microenvironment (“TME”) and poor immune cell infiltration.
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We believe BXCL701 can potentially provide significant benefits for the approximately 20% of the estimated 299,010 men who will be diagnosed with prostate cancer in the U.S.
−Removed: in 2024 and are expected to progress to the more aggressive mCRPC form of the disease, including approximately 20%, or 11,960, of those patients who develop the SCNC phenotype, for which there are currently limited treatment options.
+Added: in 2024 and are expected to progress to the more aggressive mCRPC form of the disease, including approximately 20%, or 11,960, of those patients who will develop the SCNC phenotype, for which there are currently limited treatment options.
Immune checkpoints represent a myriad of inhibitory pathways that act to regulate the duration and intensity of an antigen-induced immune response and factor prominently in mediating immune tolerance.
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As a result, other targets and pathways can be exploited by the tumor to create a TME that can evade the enhanced immunological response enabled by approved CPIs.
−Removed: While numerous agents designed to target the earlier stages of an immune response are in development for use in combination with CPIs, their activity is restricted to a single
−Removed: component of the immune response.
+Added: While numerous agents designed to target the earlier stages of an immune response are in development for use in combination with CPIs, their activity is restricted to a single component of the immune response.
In contrast, we have developed BXCL701 to simultaneously address multiple components of the immune response, including:
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Central to our drug discovery initiatives are proprietary, AI-driven platform technologies we employ to identify novel therapeutic uses for approved therapeutics and candidates in clinical evaluation.
−Removed: The first and most advanced of our AI-driven discovery programs is our innate immune modulation program, which supported the pursuit of BXCL701 as a development candidate.
+Added: The first and most advanced of
+Added: our AI-driven discovery programs is our innate immune modulation program, which supported the pursuit of BXCL701 as a development candidate.
We believe the application of this program provides us actionable insights into the inflammasome, a component of the innate immune system responsible for activation of the inflammatory response.
−Removed: We are working to develop our second AI-driven product candidate, BXCL702, by leveraging our innate immunity modulation program via re-innovation or in-licensing and we intend to nominate a candidate by 2025.
Our Immuno-Oncology Programs
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We believe our product candidates, if successfully developed and approved, have the potential to become compelling treatment options for their respective indications.
−Removed: With our Strategic Reprioritization announcement on August 14, 2023, further work on our immuno-oncology program has been paused, other than as noted below.
−Removed: An Overview of the Immune System
−Removed: The immune system is a host defense system comprised of multiple structures and processes within an organism that protects against disease.
−Removed: As with other mammalian species, the human immune system is comprised of the innate immune system and the adaptive immune system.
−Removed: The innate immune system involves an immediate, non-specific response to infected or diseased cells.
−Removed: Triggering its activation are pathogen-associated and damage-associated molecular patterns recognized by pattern-recognition receptors, which reside on the surface of various types of leukocytes, or white blood cells, making up the innate immune system including phagocytes, eosinophils, and natural killer cells.
−Removed: The innate immune response also participates in promoting activity of the adaptive immune system.
−Removed: The adaptive immune system is made up of special types of leukocytes known as T and B lymphocytes, or T cells and B cells, respectively.
−Removed: T cells participate primarily in the cell-mediated immune response while B cells are involved in the humoral immune response.
−Removed: T lymphocytes can be further segregated into distinct cell types, with the primary types being CD8, or cytotoxic, T cells and CD4 T cells.
−Removed: CTLs directly eliminate cells that are infected with viruses or other pathogens or are otherwise damaged or dysfunctional.
−Removed: Anti-cancer activity is primarily CD8 T cell mediated.
−Removed: CD4 T cells, which have limited cytotoxic activity, mediate the activity of other cells to eliminate pathogens.
−Removed: Activation of a resting CD4 T cell causes it to release cytokines that influence the activity of an array of cell types.
−Removed: Cytokines released by activated Type 1 CD4 T cells enhance the microbicidal activity of macrophages and the activity of CD8 T cells.
−Removed: A critical capability of the immune system is its ability to distinguish between healthy, functioning host cells and either non-self-infectious agents or damaged or dysfunctional host cells.
−Removed: The ability to differentiate between these entities is the central feature of immune tolerance.
−Removed: A significant limitation of currently approved therapeutics against endogenous diseases such as cancer is the inability to overcome host immune tolerance and elicit a strong, target-specific immune response while avoiding off-target complications.
−Removed: Immune Tolerance and the Role of Immune Checkpoints
−Removed: The immune system’s ability to distinguish between a normal, healthy cell and an infected, damaged, dysfunctional, or cancer cell is accomplished through an immunological selection process that occurs in the thymus during early development.
−Removed: Antigen specific immune cells, such as T cells, B cells and NK cells, which recognize molecular markers originating from normal, healthy tissues are eliminated in the thymic medulla to avoid possible autoimmune consequences through a negative selection process.
−Removed: This results in the suppression of immune effector cell activation and proliferation.
−Removed: Immune checkpoints represent a myriad of inhibitory pathways that act to regulate the duration and intensity of antigen-induced immune responses and factor prominently in mediating immune tolerance.
−Removed: checkpoint molecules have been identified and studied in cancer therapy in the past decades.
−Removed: Two of the more well-characterized immune checkpoint molecules are CTLA-4 and PD-1, and its related ligand, PD-L1.
−Removed: As key regulators of the immune system, immune checkpoints are critical gatekeepers that prevent the indiscriminate attack of normal host cells by components of the immune system.
−Removed: Their suppressive function usually depends on ligand-induced signaling, with protein structures on the surface of immune effector cells binding to complementary molecular structures on partnered cells.
−Removed: This signaling not only dampens the generation of co-stimulatory cytokines instrumental in triggering and sustaining a robust immune response, such as interleukin 2 and interferon gamma, but also results in an upregulation of regulatory T cells, which acts to further suppress immune effector cell activity.
−Removed: These factors bias the immune response towards anergy and senescence rather than activation and proliferation.
−Removed: Certain tumors co-opt these pathways and overexpress immune checkpoint molecules on their cell surface to camouflage themselves to evade detection and destruction by the immune system.
−Removed: Immunotherapy and the Emergence of Checkpoint Inhibitors
−Removed: Cancer immunotherapy, designed to harness the intrinsic power resident in the immune system by modulating immune cell function, has proven to be a major advancement in cancer treatment.
−Removed: Immune CPIs have emerged as one of the most promising classes of cancer immunotherapy.
−Removed: CPIs work by disabling the inhibitory function of immune checkpoint proteins.
−Removed: Disabling immune checkpoints allows the immune system to bypass the shield of immune tolerance the checkpoints provide, allowing the tumor-directed immune effector cells to engage the tumor.
−Removed: Seven CPIs targeting PD1/PD-L1 and CTLA-4 have been approved by the FDA to treat more than a dozen different types of cancer.
−Removed: CPIs directed towards other validated checkpoints, including lymphocyte activation gene 3 and T cell immunoreceptor with immunoglobulin and ITIM domain have recently been approved or are advancing through clinical development.
−Removed: These CPIs are largely involved in modulating the activity of the adaptive immune system.
−Removed: Immune checkpoint molecules, such as CD47, which regulate responses mediated by the innate immune system, are also under evaluation as potential therapeutic targets for checkpoint inhibition.
−Removed: CPIs across a spectrum of cancer types are expected to generate sales of more than $50 billion worldwide by 2025, up from sales of $29 billion in 2020.
−Removed: Limitations of Current Approaches
−Removed: While CPIs have proven to be a significant advancement in cancer therapy, those currently approved by the FDA do not produce meaningful results in a majority of patients:
−Removed: clinical benefit is generally viewed to be limited to between 13% and 30% of cancer patients and the duration of response to treatment is often short.
−Removed: CPIs require the infiltration of anti-tumor CD8 T cells for therapeutic activity, and patients whose tumors are characterized by a TME that lacks activated TILs, typically fail to respond to therapy.
−Removed: Moreover, the expression of positive costimulatory signals is critical to the amplification and diversification of a TIL-based response following initial activation, without which treatment durability is limited.
−Removed: We are focused on advancing therapeutic candidates designed to overcome these challenges and
−Removed: enhance the sensitivity of immunologically inaccessible, or cold, tumors to an efficacious immune response.
−Removed: The chart below shows the single agent objective response rate (“ORR”) of CPIs by different cancer types and clinical trial.
+Added: With our Reprioritization announced on August 14, 2023, further work on our immuno-oncology program has been paused, other than as noted below.
Immuno-Oncology Clinical Trials
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● Restore CPI sensitivity to tumors which had previously been responsive.
−Removed: BXCL701 Innate Immune Activator
−Removed: BXCL701 is an oral small molecule inhibitor of a class of enzymes called DPPs, specifically DPP8/9 and DPP4.
−Removed: Inhibition of DPP8/9 initiates activation of the inflammasome and ultimately activation of the innate immune system.
−Removed: Key characteristics of BXCL701 include:
−Removed: ● Orally bioavailable, potentially sole inhibitor of both DPP8/9 and DPP4, key regulators of the inflammasome directed innate immune response, currently in clinical development for cancer.
−Removed: ● Novel proposed mechanism of action may complement CPIs activity, enabling therapeutic access to immunologically cold tumors as well as other difficult-to-treat cancers, including relapsed or refractory tumor types.
−Removed: ● Phase 2 clinical proof-of-concept achieved in treating mCRPC patients with either adenocarcinoma or SCNC phenotype.
−Removed: The initial focus on mCRPC with SCNC phenotype is designed to provide for a more efficient clinical development pathway than current industry standards.
BXCL701 as a Potential Treatment for mCRPC
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The majority of these cases are classified as adenocarcinomas and involve low risk, localized or regional disease for which the five-year survival rate ranges from 60% to 99%.
−Removed: However, an estimated 20% of these newly diagnosed cases will progress to the more aggressive metastatic disease.
+Added: However, an estimated 20%
+Added: of these newly diagnosed cases will progress to the more aggressive metastatic disease.
The five-year survival rate for men with metastatic prostate cancer drops significantly, to approximately 30%.
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We elected to pursue mCRPC as an indication for BXCL701 due to its enrichment for DPP mutations, which are especially prevalent in tumors with SCNC phenotype.
−Removed: BXCL701 is being evaluated in a Phase 1b/2a clinical proof-of-concept trial that we are sponsoring to investigate its potential efficacy when used in combination with pembrolizumab.
−Removed: Enrollment in this trial is complete.
−Removed: We received initial comments from the FDA on our proposed clinical development plan, and we plan to meet with the FDA in an End-of-Phase 2 meeting in the first half of 2024 to discuss the development path forward.
+Added: BXCL701 has been evaluated in a Phase 1b/2a clinical proof-of-concept trial that we sponsored to investigate its potential efficacy when used in combination with pembrolizumab.
+Added: Enrollment in this trial is complete, and the data are described below.
+Added: We received initial comments from the FDA on our proposed clinical development plan and received feedback regarding dose-optimization for use in future studies.
However, the start of any such additional trial is paused following the Company’s Reprioritization.
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Both cohorts employed a Simon two-stage trial design of 15 trial participants followed by 13 additional patients.
−Removed: The primary endpoint of the Phase 2a portion of this trial was a composite response rate, determined as either a RECIST 1.1 response (defined as a reduction in RECIST score of 30% or more), and/or a reduction in prostate specific antigen (“PSA”) level of 50% or more, and/or a conversion in circulating tumor cells (“CTCs”) from 5 or more CTCs/7.5 milliliter (“ml”) to less than 5 CTCs/7.5 ml.
+Added: The primary endpoint of the Phase 2a portion of this trial was a composite response rate, determined as either a RECIST 1.1 response (defined as a
+Added: reduction in RECIST score of 30% or more), and/or a reduction in prostate specific antigen (“PSA”) level of 50% or more, and/or a conversion in circulating tumor cells (“CTCs”) from 5 or more CTCs/7.5 milliliter (“ml”) to less than 5 CTCs/7.5 ml.
Secondary endpoints included duration of response, progression-free survival, overall survival, changes in circulating cytokines, and certain disease-specific biomarkers.
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Pancreatic Cancer
−Removed: The American Cancer Society estimates that in 2024, approximately 66,440 cases of pancreatic cancer will be diagnosed in the U.S.
−Removed: We are supporting a Phase 2 IST sponsored by Georgetown Lombardi Comprehensive Cancer Center (“Georgetown Lombardi”), designed to evaluate the use of BXCL701 along with pembrolizumab to treat pancreatic cancer.
+Added: The American Cancer Society estimated that in 2024, approximately 66,440 cases of pancreatic cancer were expected to be diagnosed in the U.S.
+Added: We are supporting a Phase 2 investigator-sponsored trial (“IST”) sponsored by Georgetown Lombardi Comprehensive Cancer Center (“Georgetown Lombardi”), designed to evaluate the use of BXCL701 along with pembrolizumab to treat pancreatic cancer.
Few therapeutic options are available for patients with this disease, which has a five-year survival rate of less than 10%, among the lowest of all cancers.
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Tumor biopsies and blood samples will also be collected over the course of treatment to better understand the potential mechanism of action for the combination.
−Removed: The human proof of concept portion of the trial is expected to start in the first half of 2024.
+Added: The human proof of concept portion of the trial started in the first half of 2024.
+Added: On April 24, 2024, we announced that an abstract entitled “Phase II trial of BXCL701 and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (EXPEL-PANC):
+Added: Preliminary findings,” was selected for presentation at the poster session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting that took place in Chicago, Illinois from May 31 to June 4, 2024.
+Added: Investigators reported that, as of the applicable cutoff date, one patient was progression-free at 18 weeks, three patients showed substantial reductions in serum CA19-9, a tumor marker that may correlate with increased T-cell infiltration, and one patient showed a best response of partial responses, out of six patients that had been treated with the combination.
Relapsed or Refractory AML
−Removed: The American Cancer Society estimates that in 2024, about 20,800 new cases of AML will be diagnosed in the U.S.
+Added: The American Cancer Society estimated that in 2024, approximately 20,800 new cases of AML were expected to be diagnosed in the U.S.
We are supporting a Phase 1b IST sponsored by the Dana-Farber Cancer Institute (“Dana-Farber”) designed to evaluate the use of BXCL701, along with the current standard of care to treat relapsed or refractory AML.
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The first cohort enrolled patients who previously had not received CPI therapy, with a second cohort consisting of patients that were either refractory to CPI therapy or had relapsed while on CPI therapy, meaning that no further response to CPI treatment is anticipated among patients in the second cohort.
−Removed: Trial participants received 200 mg of pembrolizumab on day 1 of a 21-day cycle, with 0.2 mg of BXCL701 administered twice-daily (“BID”) on days 1 through 7 during the first cycle, the dose increasing to 0.3 mg BID on Days 8 through 14 during the first and the subsequent cycles.
+Added: Trial participants received 200 mg of pembrolizumab on day 1 of a 21-day cycle, with 0.2 mg of
+Added: BXCL701 administered twice-daily (“BID”) on days 1 through 7 during the first cycle, the dose increasing to 0.3 mg BID on Days 8 through 14 during the first and the subsequent cycles.
Evaluable trial participants were required to receive a minimum of two treatment cycles.
A preliminary assessment of BXCL701 dosed in combination with a CPI, as of completion of the first stage, noted responses in one patient in each of the CPI naïve and CPI refractory/relapsed cohorts, including a partial response in CPI-naïve, microsatellite stable endometrial carcinoma, PD-L1 negative (CPS <1) and a partial response in CPI-refractory uveal melanoma.
−Removed: These preliminary results were presented at the 2021
−Removed: American Society of Clinical Oncology annual meeting (ASCO 2021).
+Added: These preliminary results were presented at the 2021 American Society of Clinical Oncology annual meeting (ASCO 2021).
Patient enrollment in this trial was completed in the third quarter of 2022.
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We expect this strategy will enable us to maintain a more efficient infrastructure, avoiding dependence on our own manufacturing facility and equipment, while simultaneously enabling us to focus our expertise on the clinical development and future commercialization of our products.
−Removed: Currently, the Patheon pharma services division of Thermo Fisher Scientific Inc.
−Removed: and another third-party contract manufacturer supply the drug substance and clinical trial supplies for BXCL701, and we expect to enter into commercial supply agreements with such manufacturers prior to any potential approval of BXCL701.
+Added: Drug substance is produced by Aptuit (Oxford) Ltd, an Evotec Company, and drug product by Pharma Services (Patheon) by Thermo Fisher Scientific.
+Added: We expect to enter into commercial supply agreements with these manufacturers prior to any potential approval of BXCL701.
BXCL701 drug product is manufactured via conventional pharmaceutical processing procedures, employing commercially available excipients and packaging materials.
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We believe BXCL701 is the only innate immune system activator in clinical development specifically addressing the cold tumor problem in immuno-oncology.
−Removed: We face substantial competition from multiple sources, including large and specialty pharmaceutical, biopharmaceutical and biotechnology companies, academic research institutions and governmental agencies, and public and private research institutions.
+Added: We face substantial competition from multiple sources, including large and specialty pharmaceutical, biopharmaceutical and biotechnology companies, academic research institutions and governmental agencies, and public
+Added: and private research institutions.
Our competitors compete with us on the level of the technologies employed, or on the level of development of product candidates.
In addition, many small biotechnology companies have formed collaborations with large, established companies to (i) obtain support for their research, development, and commercialization of products or (ii) combine several treatment approaches to develop longer lasting or more efficacious treatments that may potentially directly compete with our current or future product candidates.
−Removed: We anticipate that we
−Removed: will continue to face increasing competition as new therapies and combinations thereof, technologies, and data emerge within the field of immunotherapy and, furthermore, within the treatment of infectious diseases and cancers.
+Added: We anticipate that we will continue to face increasing competition as new therapies and combinations thereof, technologies, and data emerge within the field of immunotherapy and, furthermore, within the treatment of infectious diseases and cancers.
In addition to the current standard of care treatments for patients with infectious diseases or cancers, numerous commercial and academic preclinical studies and clinical trials are being undertaken by a large number of parties to assess novel technologies and product candidates in the field of immunotherapy.
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We seek to protect and enhance proprietary technology, inventions, and improvements that are commercially important to the development of our business by seeking, maintaining, enforcing, and defending patent and other intellectual property rights, whether developed internally or licensed from third parties.
−Removed: We will also seek to rely on regulatory protection afforded through inclusion in expedited development and review, data exclusivity, market exclusivity, and patent term extensions where available.
−Removed: As of February 29, 2024, we have multiple patent families filed to protect our immuno-oncology program, including our core patent family directed to methods of using BXCL701 with immune checkpoint inhibitors, which is granted in the U.S., Japan, Australia, Canada, Russia, China, South Africa, Mexico, New Zealand, and United Arab Emirates, and
−Removed: with at least one pending application in the U.S., China, Mexico, the Republic of Korea, New Zealand, Russia, Australia, Brazil, Hong Kong, and Europe.
−Removed: Patents issued from this family, if any, are expected to expire no earlier than 2036.
−Removed: We have one additional patent issued in the U.S.
−Removed: directed to a method of selecting patients based on a biomarker, with an expected expiration date no earlier than 2039.
−Removed: Additional applications are directed to administering BXCL701 in combinations with various other molecules, biomarkers, and dosing regimens.
−Removed: We also have four provisional applications directed to novel formulations of BXCL701, various dosing regimens, methods of use, and combination therapies.
−Removed: We expect that patents issued from these applications, if any, will expire from 2039 to 2044.
+Added: We will also seek to rely on regulatory protection afforded through
+Added: inclusion in expedited development and review, data exclusivity, market exclusivity, and patent term extensions where available.
+Added: As of February 20, 2025, we have multiple patent families filed to protect our immuno-oncology program, including our core patent family directed to methods of using BXCL701 with immune checkpoint inhibitors, which is granted in the U.S., Japan, Australia, Canada, Russia, China, India, Taiwan, South Africa, Mexico, New Zealand, Europe and United Arab Emirates.
+Added: Additional applications in this family are pending in major markets.
+Added: Patents issued from this family are expected to expire no earlier than 2036.
+Added: We have an additional patent issued in the U.S.
+Added: directed to a method of selecting patients based on a biomarker and methods of treating certain cancers, with an expected expiration date no earlier than 2039.
+Added: A corresponding European Patent case directed to selecting patients is issued and is expected to expire no earlier than 2039.
+Added: Additional applications are directed to administering BXCL701 in combination with various other molecules, biomarkers, and dosing regimens.
+Added: We also have three PCT applications directed to novel formulations of BXCL701, various dosing regimens, methods of use, combination therapies, and to methods of treating small cell lung cancer.
+Added: We expect that any patents issuing from the PCT and provisional applications will expire no earlier than 2043 to 2044.
We expect to file additional patent applications in support of current and new immuno-oncology clinical candidates as well as new platform and core technologies.
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Our Relationship with BioXcel LLC
−Removed: BioXcel LLC currently holds an ownership interest of approximately 29% in the Company and our pipeline compounds were identified by applying our growing internal AI capabilities, along with BioXcel LLC’s EvolverAI, a proprietary pharmaceutical discovery and development engine, for drug re-innovation.
+Added: As of March 21, 2025, BioXcel LLC holds an ownership interest of approximately 8.8% in the Company and our pipeline compounds were identified by applying our growing internal AI capabilities, along with BioXcel LLC’s EvolverAI, a proprietary pharmaceutical discovery and development engine, for drug re-innovation.
We entered into the Amended and Restated Asset Contribution Agreement (the “Contribution Agreement”), pursuant to which BioXcel LLC, agreed to contribute BioXcel LLC’s rights, title and interest in BXCL501, BXCL701, BXCL502 and BXCL702, and all of the assets and liabilities associated in consideration for (i) 592,500 shares of our common stock, (ii) $1 million upon completion of an initial public offering, (iii) $500,000 upon the later of the 12-month anniversary of an initial public offering and the first dosing of a patient in the bridging bioavailability/bioequivalence study for the BXCL501 program, (iv) $500,000 upon the later of the 12 month anniversary of an initial public offering and the first dosing of a patient in the Phase 2 proof of concept open-label monotherapy or combination trial with Keytruda for the BXCL701 program and (v) a one-time payment of $5 million within 60 days after the achievement of $50 million in cumulative net sales of any product or combination of products resulting from the development and commercialization of any one of the contributed product candidates or a product derived therefrom.
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These services include certain intellectual property prosecution and management and research and development activities.
−Removed: The Company has an option, exercisable until December 31, 2024, to enter into a collaborative services agreement with BioXcel LLC pursuant to which BioXcel LLC shall perform product identification and related services for us utilizing EvolverAI, its proprietary pharmaceutical discovery and development engine.
−Removed: To maintain the ability to exercise the foregoing option, pursuant to an amendment to the Services Agreement effective as of April 19, 2022, the Company has agreed to pay BioXcel LLC $18,000 per month from March 13, 2023 to December 31, 2024.
−Removed: The parties are obligated to negotiate the collaborative services agreement in good faith and to incorporate reasonable market-based terms, including consideration for BioXcel LLC reflecting a low, single-digit royalty on net sales and reasonable development and commercialization milestone payments, provided that (i) development milestone payments shall not exceed $10 million in the aggregate and not be payable prior to proof of concept in humans and (ii) commercialization milestone payments shall be based on reaching annual net sales levels, be limited to 3% of the applicable net sales level, and not exceed $30 million in the aggregate.
−Removed: Service charges recorded under the Services Agreement were $1.3 million and $1.4 million for the years ended December 31, 2023 and 2022, respectively.
+Added: The Company had an option, exercisable until December 31, 2024, to enter into a collaborative services agreement with BioXcel LLC pursuant to which BioXcel LLC shall perform product identification and related services for us utilizing EvolverAI, its proprietary pharmaceutical discovery and development engine.
+Added: To maintain the ability to exercise the foregoing option, pursuant to an amendment to the Services Agreement effective as of April 19, 2022, the Company agreed to pay BioXcel LLC $18,000 per month from March 13, 2023 to December 31, 2024.
+Added: This option was not exercised.
+Added: However, BioXcel LLC continues to perform certain administrative services under the terms of the expired contract.
+Added: The parties were obligated to negotiate the collaborative services agreement in good faith and to incorporate reasonable market-based terms, including consideration for BioXcel LLC reflecting a low, single-digit royalty on net sales and reasonable development and commercialization milestone payments, provided that (i) development milestone
+Added: payments did not exceed $10 million in the aggregate and were not to be payable prior to proof of concept in humans and (ii) commercialization milestone payments were to be based on reaching annual net sales levels, were to be limited to 3% of the applicable net sales level, and were not exceed $30 million in the aggregate.
+Added: However, subsequent to December 31, 2024 no development activity has been carried out by BioXcel LLC and none is contemplated.
+Added: Service charges recorded under the Services Agreement were $1.3 million for each of the years ended December 31, 2024 and 2023.
Government Regulation
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The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical studies.
−Removed: The IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product;
+Added: IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product;
chemistry, manufacturing, and controls information;
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In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product.
−Removed: These so-called Phase 4 studies may be conducted after initial marketing approval and may be used to gain additional experience from the treatment of patients in the intended therapeutic indication.
+Added: These so-called Phase 4 studies may be conducted after initial marketing approval and may be used to gain additional experience from the treatment of patients in the intended
+Added: therapeutic indication.
In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA.
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An approval letter authorizes commercial marketing and sale of the product with specific prescribing information for specific indications.
−Removed: A CRL usually describes the specific deficiencies in the NDA identified by the FDA and may require additional clinical data, including additional clinical trials, or other significant and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing.
+Added: A CRL usually describes the specific deficiencies in the NDA identified by the FDA
+Added: and may require additional clinical data, including additional clinical trials, or other significant and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing.
If a CRL is issued, the sponsor must resubmit the NDA or, address all of the deficiencies identified in the letter, or withdraw the application.
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For example, the FDA may approve the NDA with a Risk Evaluation and Mitigation Strategy (“REMS”) to ensure the benefits of the product outweigh its risks.
−Removed: A REMS is a safety strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries, and other
−Removed: risk minimization tools.
+Added: A REMS is a safety strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries, and other risk minimization tools.
The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications.
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Any application for a drug submitted to the FDA for approval, including a product candidate with a Fast Track designation and/or Breakthrough Therapy designation, may be eligible for other FDA review programs intended to expedite the FDA review and approval process, such as priority review.
−Removed: An NDA is eligible for priority review if the product candidate is designed to treat a serious or life-threatening disease or condition, and if approved, would provide a significant improvement in safety or effectiveness compared to available alternatives for such disease or condition.
+Added: An NDA is eligible for priority review if the product candidate is designed to treat a serious or life-threatening disease or condition, and if approved, would provide a
+Added: significant improvement in safety or effectiveness compared to available alternatives for such disease or condition.
For new-molecular-entity NDAs, priority review designation means the FDA’s goal is to take action on the application within six months of the 60-day filing date, or with respect to non-new-molecular-entity NDAs, within six months of the NDA receipt date.
Additionally, depending on the design of the applicable clinical studies, product candidates studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.
−Removed: As a condition of accelerated approval,
−Removed: the FDA will generally require the sponsor to perform adequate and well-controlled confirmatory clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit, and may require that such confirmatory studies be underway prior to granting accelerated approval.
+Added: As a condition of accelerated approval, the FDA will generally require the sponsor to perform adequate and well-controlled confirmatory clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit, and may require that such confirmatory studies be underway prior to granting accelerated approval.
Products receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor fails to conduct the required confirmatory studies or if such studies fail to verify the predicted clinical benefit.
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Post-approval Requirements
−Removed: Drug products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse events, periodic reporting, product sampling and distribution, and advertising and promotion of the product.
+Added: Drug products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse
+Added: events, periodic reporting, product sampling and distribution, and advertising and promotion of the product.
After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval.
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ANDAs are termed "abbreviated" because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and efficacy.
−Removed: Instead, generic applicants must scientifically demonstrate that their product is
−Removed: bioequivalent to, or performs in the same manner as, the innovator drug through in vitro, in vivo, or other testing.
+Added: Instead, generic applicants must scientifically demonstrate that their product is bioequivalent to, or performs in the same manner as, the innovator drug through in vitro, in vivo, or other testing.
The generic version must deliver the same amount of active ingredients into a subject's bloodstream in the same amount of time as the innovator drug and can often be substituted by pharmacists under prescriptions written for the reference listed drug.
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However, an ANDA or 505(b)(2) NDA may be submitted after four years if it contains a certification of patent invalidity or non-infringement.
−Removed: The Hatch-Waxman Act also provides three years of non-patent exclusivity to the holder of an NDA (including a 505(b)(2) NDA) for a particular condition of approval, or change to a marketed product, such as a new formulation for a previously approved product, if one or more new clinical studies (other than bioavailability or bioequivalence studies) was essential to the approval of the application and was conducted or sponsored by the applicant.
+Added: The Hatch-Waxman Act also provides three years of non-patent exclusivity to the holder of an NDA (including a 505(b)(2) NDA) for a
+Added: particular condition of approval, or change to a marketed product, such as a new formulation for a previously approved product, if one or more new clinical studies (other than bioavailability or bioequivalence studies) was essential to the approval of the application and was conducted or sponsored by the applicant.
This three-year exclusivity period protects against FDA approval of ANDAs and 505(b)(2) NDAs for the condition of the new drug's approval.
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In August 2014, the FDA issued final guidance clarifying the requirements that apply to approval of therapeutic products and in vitro companion diagnostics.
−Removed: According to the guidance, if the FDA determines that a
−Removed: companion diagnostic device is essential to the safe and effective use of a novel therapeutic product or indication, the FDA generally will not approve the therapeutic product or new therapeutic product indication if the companion diagnostic device is not approved or cleared for that indication.
+Added: According to the guidance, if the FDA determines that a companion diagnostic device is essential to the safe and effective use of a novel therapeutic product or indication, the FDA generally will not approve the therapeutic product or new therapeutic product indication if the companion diagnostic device is not approved or cleared for that indication.
Approval or clearance of the companion diagnostic device will ensure that the device has been adequately evaluated and has adequate performance characteristics in the intended population.
16 unchanged sentences
PMA applications are subject to an application fee.
−Removed: In addition, PMAs for certain devices must generally include the results from extensive preclinical and adequate and well-controlled clinical trials to establish the safety and effectiveness of the device for each indication for which FDA approval is sought.
+Added: In addition, PMAs for certain devices must generally include the results from extensive
+Added: preclinical and adequate and well-controlled clinical trials to establish the safety and effectiveness of the device for each indication for which FDA approval is sought.
In particular, for a diagnostic, a PMA application typically requires data regarding analytical and clinical validation studies.
4 unchanged sentences
A not approvable letter will outline the deficiencies in the application and, where practical, will identify what is necessary to make the PMA approvable.
−Removed: The FDA may also determine that additional clinical trials are necessary, in which case the PMA may be delayed for several
−Removed: months or years while the trials are conducted and then the data submitted in an amendment to the PMA.
+Added: The FDA may also determine that additional clinical trials are necessary, in which case the PMA may be delayed for several months or years while the trials are conducted and then the data submitted in an amendment to the PMA.
If the FDA concludes that the applicable criteria have been met, the FDA will issue a PMA for the approved indications, which can be more limited than those originally sought by the applicant.
17 unchanged sentences
Non-clinical studies are performed to demonstrate the health or environmental safety of new chemical or biological substances.
−Removed: Non-clinical (pharmaco-toxicological) studies must be conducted in compliance with the principles of good laboratory practice (“GLP”) as set forth in EU Directive 2004/10/EC (unless otherwise justified for certain particular medicinal products, e.g., radio-pharmaceutical precursors for radio-labeling purposes).
+Added: Non-clinical (pharmaco-toxicological) studies must be conducted in compliance with the principles of good laboratory practice (“GLP”) as set forth in EU Directive 2004/10/EC (unless otherwise justified for certain particular
+Added: medicinal products, e.g., radio-pharmaceutical precursors for radio-labeling purposes).
In particular, non-clinical studies, both in vitro and in vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies.
4 unchanged sentences
The regulatory landscape related to clinical trials in the EU has been subject to recent changes.
−Removed: The EU Clinical Trials Regulation (“CTR”) which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became
−Removed: applicable on January 31, 2022.
+Added: The EU Clinical Trials Regulation (“CTR”) which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022.
Unlike directives, the CTR is directly applicable in all EU member states without the need for member states to further implement it into national law.
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are issued by the European Commission through the centralized procedure based on the opinion of the EMA’s CHMP and are valid throughout the EU.
−Removed: The centralized procedure is compulsory for certain types of medicinal products such as (i) medicinal products derived from biotechnology processes, such as genetic engineering, (ii) medicinal products containing a new active substance indicated for the treatment of certain diseases, such as HIV or AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune and other immune dysfunctions and viral diseases, (iii) designated orphan medicinal products, and (iv) advanced therapy medicinal products (“ATMPs”) such as gene therapy, somatic cell therapy or tissue-engineered medicines.
+Added: The centralized procedure is compulsory for
+Added: certain types of medicinal products such as (i) medicinal products derived from biotechnology processes, such as genetic engineering, (ii) medicinal products containing a new active substance indicated for the treatment of certain diseases, such as HIV or AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune and other immune dysfunctions and viral diseases, (iii) designated orphan medicinal products, and (iv) advanced therapy medicinal products (“ATMPs”) such as gene therapy, somatic cell therapy or tissue-engineered medicines.
The centralized procedure is optional for product candidates containing a new active substance not yet authorized in the EU, or for product candidates that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU.
3 unchanged sentences
If the product has not received a national MA in any member state at the time of application, it can be approved simultaneously in various member states through the decentralized procedure.
−Removed: Under the decentralized procedure, an identical
−Removed: dossier is submitted to the competent authorities of each of the member states in which the MA is sought, one of which is selected by the applicant as the reference member state.
+Added: Under the decentralized procedure, an identical dossier is submitted to the competent authorities of each of the member states in which the MA is sought, one of which is selected by the applicant as the reference member state.
Under the centralized procedure, the maximum timeframe for the evaluation of a MAA by the EMA is 210 days.
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Upon grant of a MA, orphan medicinal products are entitled to 10 years of market exclusivity for the approved therapeutic indication.
−Removed: During the 10-year market exclusivity period, the competent authorities cannot accept a MAA, or grant a
−Removed: MA, or accept an application to extend a MA, for the same indication, in respect of a similar medicinal product.
+Added: During the 10-year market exclusivity period, the competent authorities cannot accept a MAA, or grant a MA, or accept an application to extend a MA, for the same indication, in respect of a similar medicinal product.
The period of market exclusivity is extended by two years for orphan medicinal products that have also complied with an agreed pediatric investigation plan (“PIP”).
31 unchanged sentences
The process for determining whether a payor will provide coverage for a drug product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the drug product.
−Removed: Third-party payors may limit coverage to specific drug products on an approved list, or formulary, which might not include all of the FDA-approved drugs for a particular indication.
+Added: Third-party payors may limit coverage to specific drug products on an approved list, or formulary, which might not include all of the
+Added: FDA-approved drugs for a particular indication.
Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy.
24 unchanged sentences
We participate in the Medicaid Drug Rebate Program and other federal and state government pricing programs in the U.S., and we may participate in additional government pricing programs in the future.
−Removed: government and other governments have shown significant interest in pursuing health care reform, which has resulted in changes to these programs and impacts IGALMI TM and our product candidates that may be approved.
+Added: government and other governments have shown significant interest in pursuing health care reform, which has resulted in changes to these programs and impacts IGALMI ® and our product candidates that may be approved.
For example, in March 2010, the Patient Protection and Affordable Care Act (“ACA”) was enacted and substantially changed the way health care is financed in the U.S.
10 unchanged sentences
will continue to consider legislation to limit the growth of health care costs, including the cost of prescription drugs.
−Removed: Future legislation could limit payments for pharmaceuticals such as IGALMI TM and the product candidates that we are developing.
+Added: Future legislation could limit payments for pharmaceuticals such as IGALMI ® and the product candidates that we are developing.
Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers, which will remain in effect through 2032, absent additional congressional action.
10 unchanged sentences
HHS has issued and will continue to issue guidance implementing the IRA, although the Medicare drug price negotiation program is currently subject to legal challenges.
−Removed: impact of the IRA on the pharmaceutical industry and our business cannot yet be fully determined, it is likely to be significant.
+Added: While the impact of the IRA on the pharmaceutical industry and our business cannot yet be fully determined, it is likely to be significant.
In addition, individual U.S.
1 unchanged sentence
Furthermore, there has been increased interest by third-party payors and governmental authorities in reference pricing systems and publication of discounts and list prices.
−Removed: Future legislation could limit payments for pharmaceuticals such as IGALMI TM and the product candidates that we are developing.
+Added: Future legislation could limit payments for pharmaceuticals such as IGALMI ® and the product candidates that we are developing.
We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our products or additional pricing pressures.
5 unchanged sentences
The federal Anti-Kickback Statute prohibits persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, to induce either the referral of an individual, or the furnishing, recommending, or arranging for a good or service, for which payment may be made under a federal health care program, such as the Medicare and Medicaid programs.
−Removed: A person or entity does not need to have actual knowledge of this statute or specific intent to violate it in order to have committed a violation.
+Added: A person or entity does not need to have actual knowledge of this statute
+Added: or specific intent to violate it in order to have committed a violation.
Many states have adopted laws similar to the federal Anti-Kickback Statute, some of which apply to the referral of patients for health care items or services reimbursed by any source, not only the Medicare and Medicaid programs.
9 unchanged sentences
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of this statute or specific intent to violate it in order to have committed a violation.
−Removed: The Physician Payment Sunshine Act (the “Sunshine Act”), which was enacted as part of the ACA, requires applicable manufacturers of drugs, devices, biologicals, or medical supplies covered under Medicare, Medicaid or the Children’s Health Insurance Program, to report annually to the Secretary of the Department of Health and Human Services payments or other transfers of value made by that entity, or by a third-party as directed by that entity, to
−Removed: physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), certain non-physician providers including physician assistants and nurse practitioners, and teaching hospitals, or to third parties on behalf of such providers, as well as ownership and investment interests held by physicians and their immediate family members during the course of the preceding calendar year.
+Added: The Physician Payment Sunshine Act (the “Sunshine Act”), which was enacted as part of the ACA, requires applicable manufacturers of drugs, devices, biologicals, or medical supplies covered under Medicare, Medicaid or the Children’s Health Insurance Program, to report annually to the Secretary of the Department of Health and Human Services payments or other transfers of value made by that entity, or by a third-party as directed by that entity, to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), certain non-physician providers including physician assistants and nurse practitioners, and teaching hospitals, or to third parties on behalf of such providers, as well as ownership and investment interests held by physicians and their immediate family members during the course of the preceding calendar year.
Failure to comply with the reporting requirements can result in significant civil monetary penalties for any payment or other transfer of value that is not reported.
8 unchanged sentences
In addition, certain state and non-U.S.
−Removed: laws, such as the California Consumer Privacy Act (“CCPA”), the California Privacy Rights Act (“CPRA”), and the EU General Data Protection Regulation (“GDPR”), govern the privacy and security of personal information, including health-related information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
+Added: laws, such as the California Consumer Privacy Act (“CCPA”), the California Privacy Rights Act (“CPRA”), and the EU General Data Protection Regulation (“GDPR”), govern the privacy and security of personal
+Added: information, including health-related information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or criminal penalties and private litigation.
5 unchanged sentences
Following a comprehensive review of the business, we determined to focus on high-potential agitation-market opportunities using our innovative, AI-based clinical drug development platforms.
−Removed: We intend to reduce more than 50% of our cash burn, as compared to our cash burn levels during the second quarter of 2023, to approximately $80 million on a go-forward annualized basis.
+Added: Our goal was to reduce more than 50% of our cash burn, as compared to our cash burn levels during the second quarter of 2023, to approximately $80 million on a go-forward annualized basis.
As part of the Reprioritization, our Board of Directors approved a reduction of approximately 60% of our workforce, from approximately 190 to 80 employees.
These actions also included a shift in commercial strategy for IGALMI ® in the institutional setting, a reduction of in-hospital commercialization expenses, a suspension of programs no longer deemed core to our business, and a shift in focus to develop BXCL501 for use in the at-home setting in the treatment of agitation in schizophrenia, bipolar disorders, and in patients with mild to moderate dementia due to probable Alzheimer’s disease.
−Removed: We recorded restructuring costs of $4.2 million in the year ended December 31, 2023, including severance and benefit costs of $4.1 million and contract termination costs of $0.1 million, substantially all of which were paid in 2023.
−Removed: As of December 31, 2023, we had 74 full-time employees.
−Removed: We also leverage certain experts in drug development and AI that are employed by BioXcel LLC to provide flexibility for our business needs.
−Removed: We believe that the success of our human capital management investments is evidenced by our low employee turnover, a number which is regularly reviewed by our Board of Directors as part of their oversight of our human capital strategy.
+Added: In May, 2024 the Company took additional actions as part of its continued efforts to preserve cash and prioritize investment in its core clinical programs.
+Added: As part of these actions, the Company initiated a further reduction of approximately 15% of the Company’s then current workforce.
+Added: The Company recorded total restructuring costs of $0.9 million for the three months ended June 30, 2024.
+Added: These costs consisted of severance and benefit costs, all of which were paid during the three month period ended June 30, 2024.
+Added: In September, 2024, the Company approved a plan for an additional reduction its workforce by 15 employees, or approximately 28% of the Company’s headcount (the “Clinical Prioritization”), in order to extend its cash runway and prioritize investment on the clinical development of its lead neuroscience asset, BXCL501.
+Added: The Company recorded total restructuring costs of $1.6 million for the three months ended September 30, 2024.
+Added: These costs also consisted of severance and benefit costs.
+Added: The Company completed the Clinical Prioritization in October 2024, and commenced payments which are expected to be completed in the first quarter of 2025.
+Added: We recorded restructuring costs of $2.4 million and $4.2 million in the years ended December 31, 2024 and 2023, respectively, including severance and benefit costs of $4.1 million and contract termination costs of $0.1 million, substantially all of which were paid in 2023.
+Added: As of December 31, 2024 and 2023, respectively, we had 37 and 74 full-time employees.
+Added: We believe that the success of our human capital management investments is evidenced by our low employee turnover, despite the difficult restructuring actions recently taken, and is regularly reviewed by our Board of Directors as part of their oversight of our human capital strategy.
Employee Engagement, Talent Development & Benefits
19 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.