BioXcel Therapeutics(US:BTAI)2023-03-15 16:00Forward-Looking Statements This section outlines the forward-looking nature of statements in the 10-K report, based on management's expectations and subject to inherent risks and uncertainties Forward-Looking Statements Content This section outlines the forward-looking nature of statements, emphasizing reliance on current expectations and the presence of known and unknown risks and uncertainties - All statements in this Annual Report on Form 10-K, other than statements of historical fact, are forward-looking statements, based on management's current expectations and involve known and unknown risks, uncertainties, and other important factors4954 - Forward-looking statements cover areas such as ongoing commercialization plans for IGALMI, clinical trials for product candidates, research and development plans, collaboration efforts, regulatory approval timing, market acceptance, manufacturing strategy, intellectual property, financial estimates, and competitive developments82 Summary Risk Factors This section provides a high-level overview of significant risks, including operating losses, product dependence, unpredictable regulatory processes, side effects, and intellectual property challenges Summary Risk Factors Overview This section provides a high-level overview of significant risks, including operating losses, product dependence, unpredictable regulatory processes, side effects, and intellectual property challenges - The company has incurred significant operating losses since inception and anticipates continued substantial operating losses, potentially never achieving or maintaining profitability5786 - The company is dependent on the success of IGALMI and its product candidates BXCL501, BXCL502, and BXCL701; failure to complete clinical development, obtain marketing approval, or successfully commercialize these could substantially harm the business59240 - The regulatory approval processes by the FDA and foreign authorities are lengthy, time-consuming, expensive, and inherently unpredictable, posing a risk to obtaining approval for product candidates60736 - Product candidates may cause undesirable side effects, which could delay or prevent regulatory approval, limit commercial profile, or lead to negative consequences post-approval61752 - The company is substantially dependent on third parties for manufacturing clinical and commercial supplies, and failures by these manufacturers could stop or delay product development and commercialization67950 - Protecting proprietary rights is difficult and costly, and an inadequate patent position could allow competitors to operate more directly, harming the business981000 Item 1. Business This section describes BioXcel Therapeutics as an AI-driven biopharmaceutical company focused on neuroscience and immuno-oncology, highlighting its lead product IGALMI and advanced asset BXCL701 Overview This section describes BioXcel Therapeutics as an AI-driven biopharmaceutical company focused on neuroscience and immuno-oncology, highlighting its lead product IGALMI and advanced asset BXCL701 - BioXcel Therapeutics, Inc. (BTI) is an AI-driven biopharmaceutical company focused on developing transformative medicines in neuroscience and immuno-oncology, utilizing a proprietary AI platform to reduce development costs and accelerate timelines1031158 - IGALMI (dexmedetomidine sublingual film) received U.S. FDA approval on April 6, 2022, for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults, and became commercially available in July 2022731160 - BXCL501 is the most advanced neuroscience clinical program, an investigational orally dissolving film of Dex for agitation in psychiatric and neurological disorders, with ongoing trials for at-home use, Alzheimer's disease, and Major Depressive Disorder (MDD)1041321161 - BXCL701 is an advanced immuno-oncology asset, an investigational oral innate immune activator being developed for aggressive forms of prostate cancer, pancreatic cancer, and other solid and liquid tumors744191163 Neuroscience This section details the company's neuroscience strategy, including its AI-driven drug re-innovation model, commercial progress of IGALMI, and the development pipeline for BXCL501 across various agitation indications Our Novel Drug Re-Innovation Approach The company utilizes its proprietary AI ecosystem, EvolverAI, to rapidly identify new therapeutic uses for existing drugs, aiming to reduce development costs and accelerate timelines - The company's neuroscience strategy involves an AI ecosystem (EvolverAI) to rapidly identify medications for neuroscience and immuno-oncology, leveraging existing drugs and big data with machine learning to find new therapeutic indications75103108 - This drug re-innovation model aims to reduce development costs and accelerate timelines, providing a higher probability of success by combining AI efficiency with human expertise in drug development103108137 Our Neuroscience Programs This section details neuroscience programs, focusing on IGALMI's commercial progress and BXCL501's development for various agitation indications, including Alzheimer's, at-home use, pediatric studies, and MDD - BXCL501, a selective α2a adrenergic receptor agonist, is designed for easy, rapid administration and a calming effect without excessive sedation, differentiating it from current antipsychotics for agitation110148154 - IGALMI's commercial progress since July 2022 includes over 65 formulary wins, 600+ P&T committee reviews scheduled, 70 sales representatives covering 1,700+ hospitals, and nearly 50% of target beds under GPO contracts149118421422 - The TRANQUILITY program (Phase 3) is evaluating BXCL501 for acute agitation in Alzheimer's disease patients (65+), with TRANQUILITY II enrollment complete (top-line data expected Q2 2023) and TRANQUILITY III initiated in December 2022125158127178 - The SERENITY III study for at-home use of BXCL501 in schizophrenia/bipolar agitation initiated in December 2022, with Part 1 enrollment completed in March 2023 (top-line efficacy expected Q2 2023) and Part 2 (at-home safety) expected to initiate in Q2 2023181 - A global clinical trial for acute agitation in pediatric schizophrenia and bipolar disorders was initiated in June 2021 to fulfill FDA requirements161183 - BXCL501 is also being evaluated as an adjunctive treatment for Major Depressive Disorder (MDD) in a multiple ascending dose trial, with top-line results expected in Q2 2023182 - The company identified BXCL502, a second neuropsychiatric drug candidate via its AI platform, for chronic agitation in dementia or stress-related illnesses, with formulation and clinical development planning underway23 - Studies are ongoing to develop algorithms for wearable technologies to detect early signs of agitation, with a robust signal identified in a recent study, aiming for early treatment and prevention22 Neuroscience Competition The neuroscience and rare disease segments are highly competitive, with numerous companies possessing greater resources, where efficacy, safety, convenience, price, and reimbursement are key competitive factors - The neuroscience and rare disease segments are highly competitive, with competition from major pharmaceutical, specialty pharmaceutical, and biotechnology companies, academic institutions, and governmental agencies2526 - Many competitors possess significantly greater financial resources and expertise in R&D, manufacturing, clinical trials, regulatory approvals, and marketing27 - Key competitive factors for product candidates include efficacy, safety, convenience, price, effectiveness of companion diagnostics, generic competition, and availability of reimbursement28 - Current acute agitation treatments include IM antipsychotics (aripiprazole, olanzapine, ziprasidone, haloperidol), oral sublingual atypical antipsychotics (asenapine), and benzodiazepines (lorazepam, midazolam), as well as inhaled loxapine (Adasuve)31 Neuroscience Manufacturing The company relies on third-party partners, primarily ARx, LLC, for the exclusive manufacture and supply of BXCL501 film formulation for commercial and clinical use - The company does not have manufacturing facilities and relies on strategic third-party manufacturing partners, primarily ARx, LLC32 - ARx, LLC has an exclusive agreement to manufacture and supply all worldwide film formulation of dexmedetomidine (BXCL501/IGALMI) for commercial supply and ongoing clinical trials32 - BXCL501 drug product is manufactured using commercially available components and packaging materials, with equipment consistent with standard pharmaceutical production33 Neuroscience Commercialization The company plans to retain worldwide commercialization rights for IGALMI and other neuroscience candidates, leveraging its in-house commercial organization, while considering foreign collaborations - The company plans to retain worldwide commercialization rights for IGALMI and other approved product candidates, but may consider collaboration opportunities to maximize returns or facilitate efforts in foreign jurisdictions3436 - Following FDA approval of IGALMI, the company built an in-house commercial organization and capabilities, which it intends to leverage and expand for additional approved product candidates36 Neuroscience Intellectual Property The company protects its neuroscience portfolio, including BXCL501, through patents, trademarks, trade secrets, and data exclusivity, with key patents for BXCL501 expiring no earlier than 2039 - The company's policy is to protect proprietary technologies, inventions, and product candidates through patent applications in the U.S. and other jurisdictions, as well as relying on trademarks, trade secrets, and data/market exclusivity5 - Neuroscience Patent Portfolio (as of January 31, 2023) | Category | Count | |:---------------------------------------|:------| | PCT applications (not yet national phase) | 4 | | U.S. utility applications | 13 | | Issued U.S. utility patents | 5 | | U.S. provisional patent applications | 4 | | Pending non-U.S. applications | 87 | | Allowed/granted non-U.S. patents | 9 | | U.S. design application | 1 | | Allowed/registered design patents | 34 | - Four U.S. patents (U.S. Pat. Nos. 10,792,246; 11,478,422; 11,497,711; and 11,517,524) directed to the proprietary sublingual film formulation of Dex (BXCL501) were issued between 2020 and 2022, listed in the FDA's Orange Book, and are expected to expire no earlier than 20396 - Patent terms are generally 20 years from the earliest filing date, with potential extensions of up to five years under the Hatch-Waxman Act for regulatory review time and Patent Term Adjustment (PTA) for USPTO delays7910 - Patent positions are generally uncertain and involve complex legal and factual questions, with changes in patent laws or their interpretation potentially diminishing the ability to protect technology or product candidates12259 Immuno-Oncology This section details the company's immuno-oncology focus through OnkosXcel Therapeutics, highlighting BXCL701's development for mCRPC and its mechanism as an innate immune activator OnkosXcel Therapeutics OnkosXcel Therapeutics, a wholly-owned subsidiary, was formed to develop AI-driven immuno-oncology medicines, leveraging EvolverAI for capital-efficient development of anti-cancer therapeutics - OnkosXcel Therapeutics, LLC, a wholly-owned subsidiary, was formed on April 19, 2022, to develop potentially transformative medicines in oncology, utilizing proprietary AI capabilities (EvolverAI) for capital-efficient drug development1314394 - The company's AI-driven platform technologies are central to drug discovery initiatives, identifying novel therapeutic uses for approved therapeutics and candidates, particularly in innate immune modulation, which supported BXCL701 development41 - The company is developing BXCL702, its second AI-driven product candidate, leveraging innate immunity modulation and/or synthetic lethality programs, with a candidate nomination anticipated by 202541170171 Our Immuno-Oncology Programs This section details immuno-oncology programs, focusing on BXCL701's development for mCRPC, its mechanism as an innate immune activator, Phase 2a results, and plans for a Phase 2b trial - BXCL701 is an investigational, oral innate immune activator, an inhibitor of DPP8/9 and DPP4, designed to activate the inflammasome and innate immune system15193 - In a Phase 2a clinical trial, BXCL701 in combination with pembrolizumab demonstrated a 25% composite response rate in mCRPC patients with SCNC phenotype (7 out of 28 evaluable patients), with a median duration of response of 6+ months15449727 - The company intends to initiate a Phase 2b trial in mCRPC patients with SCNC phenotype in the second half of 2023, following planned meetings with the FDA, with the goal for it to serve as a potential registrational trial15472475 - BXCL701 is designed to address multiple components of the immune response, including cancer antigen presentation, T cell priming and activation, infiltration of immune cells into the tumor, and killing of tumor cells, to convert 'cold' tumors into CPI-sensitive ones181920444470471 - BXCL701 has received Orphan Drug Designation for the treatment of AML, stage IIb to IV melanoma, pancreatic cancer, and soft tissue sarcoma730842843 - The company is supporting a Phase 1b IST for BXCL701 in relapsed or refractory Acute Myeloid Leukemia (AML) and a Phase 2 IST for pancreatic cancer, both expected to begin in Q1 and Q2 2023, respectively489520 - Biomarker development initiatives are underway to identify predictive biomarkers, such as DPP9 copy number, to correlate with BXCL701 response rates524525 - Lifecycle management considerations include developing a next-generation BXCL701 molecule with enhanced properties like simultaneous DPP8/9 and DPP4 inhibition, improved pharmacokinetic profile, and anti-cancer activity as monotherapy or in combination with CPIs526 Immuno-Oncology Manufacturing The company relies on third-party CMOs for BXCL701 drug substance and clinical trial supplies, with plans to transfer drug product manufacturing to a larger third-party manufacturer - The company relies on third-party contract manufacturing organizations (CMOs) for the development and manufacture of BXCL701 product candidates for clinical trials494 - Current suppliers include Patheon pharma services division of Thermo Fisher Scientific Inc. and another third-party contract manufacturer for drug substance and clinical trial supplies494 - The company plans to transfer drug product manufacture to a larger third-party manufacturer while maintaining the current drug substance and product manufacturer as part of its supply chain strategy527 Immuno-Oncology Competition The immuno-oncology market is highly competitive, with BTI facing competition from large pharmaceutical and biotechnology companies developing innate immune activators and mCRPC treatments - The biotechnology and pharmaceutical industries have made substantial investments in novel immunotherapies, making the immuno-oncology market highly competitive496529 - Competitors include large pharmaceutical companies (e.g., Amgen, Mirati, Bristol-Myers Squibb, Merck, Novartis, AstraZeneca, Pfizer, Roche) and clinical-stage companies targeting innate immune systems, mCRPC, and synthetic lethality498558 - Many competitors have significantly greater financial resources and expertise in R&D, manufacturing, regulatory approval, and marketing559846 - Key competitive factors affecting success are product safety, efficacy, convenience, and treatment cost532 Immuno-Oncology Intellectual Property The immuno-oncology portfolio includes patents for BXCL701 methods of use with immune checkpoint inhibitors, with granted patents in multiple countries expected to expire no earlier than 2036 - The immuno-oncology portfolio includes a core patent family directed to methods of using BXCL701 with immune checkpoint inhibitors, with granted/allowed patents in the U.S., Japan, Australia, Canada, Russia, China, Mexico, and South Africa, and pending applications in other regions501533 - Patents issued/granted from these applications are expected to expire no earlier than 2036 to 2043501533 - The company expects to file additional patent applications for current and new immuno-oncology clinical candidates, as well as new platform and core technologies562 Relationship with BioXcel LLC This section details the company's relationship with BioXcel LLC, a significant stockholder providing services and AI platform access, noting potential conflicts of interest and the expiration of exclusivity - BioXcel LLC, the company's former parent and significant stockholder, holds approximately 30% ownership in the company502204 - A Separation and Shared Services Agreement (Services Agreement) with BioXcel LLC provides for drug discovery, chemical, manufacturing and controls (CMC), and general and administrative support services5351059 - The company has an option, exercisable until December 31, 2024, to enter a collaborative services agreement with BioXcel LLC for product identification using its EvolverAI platform, requiring a monthly payment of $18,000 to maintain this option5355031493 - Service Charges from BioXcel LLC | Year Ended December 31, | 2022 (in thousands) | 2021 (in thousands) | |:------------------------|:--------------------|:--------------------| | Research and development| $1,151 | $1,184 | | Selling, general and administrative | $250 | $218 | | Total | $1,401 | $1,402 | - The first right to negotiate and exclusivity agreement in neuroscience and immuno-oncology fields with BioXcel LLC expired on March 12, 2023, meaning BioXcel LLC is no longer restricted from using EvolverAI for competitors1493 - Management and beneficial ownership in BioXcel LLC by the company's executive officers and directors (e.g., Vimal Mehta, Krishnan Nandabalan) may create actual or perceived conflicts of interest2071493 Government Regulation and Product Approval This section outlines the extensive U.S. and EU regulatory framework for drug development, approval, and commercialization, including clinical trial processes, expedited programs, and post-market requirements U.S. Drug Development Process The U.S. drug development process, regulated by the FDA, involves preclinical studies, multi-phase clinical trials, NDA submission, and manufacturing inspections to ensure safety and efficacy - The U.S. drug development process involves preclinical studies (GLP compliance), IND submission, human clinical trials (GCPs), NDA submission, FDA review and approval, and satisfactory completion of manufacturing facility inspections (cGMP)538566 - Clinical trials are typically conducted in three phases: Phase 1 (safety, dosage tolerance), Phase 2 (preliminary efficacy, optimal dosages), and Phase 3 (statistically significant efficacy, overall risk/benefit)569570 - The FDA conducts a preliminary review of NDAs within 60 days, followed by a substantive review (goal of 10 months for new molecular entities) and inspections of manufacturing facilities and clinical trial sites574575 - The Pediatric Research Equity Act (PREA) requires pediatric clinical trials for most new drugs, unless a deferral or waiver is granted577 Regulation of Combination Products in the U.S. Combination products (drug-device) are FDA-regulated based on their primary mode of action, subject to cGMP requirements for both drug and device components, including QSR - Combination products (e.g., drug-device) are regulated by the FDA based on their 'primary mode of action,' with a lead center assigned for review578606 - Combination products are subject to cGMP requirements applicable to both drugs and devices, including the Quality System Regulations (QSR) for medical devices552 Expedited Development and Review Programs The FDA offers expedited programs like Fast Track, Breakthrough Therapy, and Priority Review, along with Orphan Drug Designation, to accelerate development and review for qualifying product candidates - Fast Track designation expedites review for product candidates treating serious/life-threatening conditions with unmet medical needs, offering frequent FDA interactions and potential rolling review580608 - Breakthrough Therapy designation is for product candidates showing substantial improvement over existing therapies for serious/life-threatening conditions, providing intensive FDA interaction and expedited development/review58011791184 - Priority Review is granted if a product candidate treats a serious/life-threatening disease and offers significant safety/effectiveness improvement, aiming for FDA action within six months554 - Orphan Drug Designation is for drugs treating rare diseases (<200,000 U.S. patients), providing incentives (tax credits, fee waivers) and 7 years of market exclusivity upon first FDA approval for that indication555583610612871 Post-approval Requirements Post-approval, drug products face continuous FDA regulation, including record-keeping, adverse event reporting, cGMP compliance, and strict marketing rules, with potential for post-market studies or approval withdrawal - Approved drug products are subject to pervasive and continuing FDA regulation, including record-keeping, adverse event reporting, periodic reporting, product sampling, distribution, advertising, and promotion613 - The FDA may require post-market studies (Phase 4), Risk Evaluation and Mitigation Strategies (REMS), or withdraw approval if previously unknown problems or non-compliance occur, leading to fines, recalls, or marketing restrictions584585605614616822823 - Marketing, labeling, advertising, and promotion of drug products are strictly regulated, allowing claims only for FDA-approved safety and efficacy, with active enforcement against off-label promotion586824850851 Hatch-Waxman Act The Hatch-Waxman Act establishes generic drug pathways, patent certification requirements, and regulatory exclusivity periods to balance innovation and generic competition - The Hatch-Waxman Act establishes pathways for drug approval (505(b)(1) NDA, 505(b)(2) NDA, ANDA), allowing 505(b)(2) applicants to rely on FDA's prior findings of safety and efficacy for existing products or published literature587 - Applicants must certify patents listed in the FDA's Orange Book; a Paragraph IV certification challenging a patent can trigger a 30-month stay on approval if a patent infringement lawsuit is filed618620 - Regulatory exclusivity periods include five years for new chemical entities (preventing ANDA/505(b)(2) acceptance for the same active moiety) and three years for new conditions of approval or changes to marketed products based on new clinical studies590 FDA Approval and Regulation of Medical Devices and Companion Diagnostics The FDA regulates in vitro and companion diagnostics as medical devices, requiring marketing clearance or approval, often concurrently with therapeutic products, with similar regulations in the EU - In vitro diagnostics, including companion diagnostics, are regulated as medical devices by the FDA, requiring marketing clearance (510(k)) or premarket approval (PMA) prior to commercial distribution591622593594 - If a companion diagnostic is essential for the safe and effective use of a novel therapeutic product, the FDA generally requires its approval or clearance concurrently with the therapeutic product591788816 - Medical device manufacturers must comply with Quality System Regulations (QSR) covering design, testing, production, and quality assurance, and are subject to periodic FDA inspections594595626 - The EU's In Vitro Diagnostic Medical Devices Regulation (IVDR), fully effective May 2022, introduces a new classification system for companion diagnostics, requiring conformity assessment by a notified body and scientific opinion from the EMA673674790817818 International Regulations The company navigates diverse international regulations, including EU clinical trial harmonization, marketing authorizations, data exclusivity, and the regulatory divergence caused by Brexit - Clinical research in the EU is governed by EU and national regulations, ICH GCP guidelines, and ethical principles from the Declaration of Helsinki, requiring a Clinical Trial Application (CTA) submission599630 - The EU Clinical Trials Regulation (CTR), applicable since January 2022, harmonizes clinical trial assessment and supervision across the EU via a centralized portal and database600630660661662771 - Marketing Authorization (MA) in the EU can be obtained through a Centralized MA (valid throughout EU, compulsory for certain products) or National MA (member state specific, with mutual recognition or decentralized procedures)603633 - EU market exclusivity includes 8 years of data exclusivity and an additional 2 years of market exclusivity for reference products, extendable to 11 years for new therapeutic indications with significant clinical benefit666 - Orphan Medicinal Product designation in the EU provides 10 years of market exclusivity for the approved therapeutic indication, extendable by two years for pediatric investigation plans, but can be reduced or lost under certain conditions638667668871898 - Brexit has led to the UK operating under a distinct regulatory regime since January 2021, creating political and economic uncertainty, increasing costs and complexity for business operations and clinical trials, and requiring separate MAs for Great Britain671830832859 Pharmaceutical Coverage, Pricing and Reimbursement Pharmaceutical sales depend on third-party reimbursement, facing challenges from payors and complex U.S. government pricing programs and healthcare reform laws that impact revenue and profitability - Sales of pharmaceutical products depend significantly on the availability of reimbursement from third-party payors (government, managed care, private insurers), who are increasingly challenging prices, medical necessity, and cost-effectiveness648675877904 - The company participates in U.S. government pricing programs, including the Medicaid Drug Rebate Program (MDRP), 340B program, and VA Federal Supply Schedule (FSS), which require rebates or discounts649202916941 - Healthcare reform laws, such as the Affordable Care Act (ACA) and the Inflation Reduction Act (IRA), have significantly changed healthcare financing, imposing new fees, discounts, rebates, and price negotiation requirements on pharmaceutical manufacturers651678709880909 - Individual states and foreign governments are implementing legislation and measures to limit healthcare costs, including drug price transparency laws and price ceilings, which could limit pricing and payment for products203647912913 - Failure to comply with reporting and payment obligations under government pricing programs can result in additional reimbursement requirements, penalties, sanctions, and fines888890941 Other Health Care Laws and Compliance Requirements The company is subject to federal, state, and foreign healthcare fraud and abuse laws, including anti-kickback and false claims statutes, with violations leading to significant penalties - The company is subject to federal, state, and foreign healthcare fraud and abuse laws, including anti-kickback statutes, false claims laws, consumer fraud laws, and transparency laws (e.g., Physician Payment Sunshine Act)683835861655836 - The federal Anti-Kickback Statute prohibits offering or paying remuneration to induce referrals for federal health care programs, and the False Claims Act imposes liability for presenting false or fraudulent claims654712862835 - HIPAA created federal crimes for healthcare fraud and false statements related to healthcare matters, with violations not requiring actual knowledge or specific intent684863 - Violations of these laws can result in significant civil, criminal, and administrative penalties, including fines, imprisonment, exclusion from federal healthcare programs, product recalls, and reputational harm714822823866 Data Privacy & Security The company navigates evolving data protection laws (HIPAA, GDPR) across jurisdictions, facing risks from data breaches, cyber-attacks, and potential new regulations for AI and machine learning - The company is subject to numerous evolving state, federal, and foreign laws and regulations governing personal data, including HIPAA, CCPA, CPRA, GDPR, and UK GDPR, which impose strict requirements and vary significantly across jurisdictions228715967995 - Data breaches or cyber-attacks on the company's or third parties' IT systems could disrupt business operations, adversely impact financial results, and lead to the loss or exposure of confidential or sensitive information, resulting in legal claims and liability226250251965991992 - The use of AI and machine learning may be subject to new and evolving regulations regarding data bias and anti-discrimination228715 - Non-compliance with data protection laws can result in significant civil and/or criminal penalties, government investigations, and damage to reputation (e.g., GDPR fines up to €20 million or 4% of global annual revenues)228995 Human Capital The company prioritizes attracting and retaining skilled employees through competitive compensation, evidenced by low turnover and significant headcount growth in 2022, while valuing diversity and inclusion - The company grew its overall headcount by over 100% in 2022, reaching 183 full-time employees as of December 31, 2022, primarily expanding its commercial team and general and administrative functions716 - The company believes its success in human capital management is evidenced by low employee turnover and its ability to attract and retain highly skilled employees through competitive salaries, bonuses, equity ownership, and benefits688689 - The company values diversity and inclusion at all levels, focusing on extending these initiatives across its workforce, believing that a diverse workforce brings different perspectives and contributes to a strong, inclusive culture691 Corporate Information BioXcel Therapeutics, Inc. was incorporated in Delaware in March 2017, with headquarters in New Haven, Connecticut, using its website for material information distribution - BioXcel Therapeutics, Inc. was incorporated in Delaware on March 29, 2017, with its principal executive offices located at 555 Long Wharf Drive, New Haven, CT 0651169247 - The company's website, www.bioxceltherapeutics.com, serves as a distribution channel for material information, including financial and other important company information, and SEC filings56326693719 Item 1A. Risk Factors This section details various risks, including financial instability, development uncertainties, commercialization challenges, reliance on third parties, intellectual property issues, and stock ownership risks Risks Related to Financial Position and Need for Additional Capital The company faces risks from significant operating losses, the need for substantial additional funding, considerable indebtedness, and reliance on financial institutions for cash - The company has a limited operating history and has incurred significant operating losses since inception ($165.8 million in 2022, $106.9 million in 2021), anticipating continued substantial losses and uncertainty regarding future profitability86331332 - Substantial additional funding will be required for product development, clinical trials, commercialization, and operations; failure to raise capital when needed could force delays, reductions, or elimination of programs8730330530710101068 - The company has significant indebtedness and other contractual obligations, including $100.8 million outstanding under OFA Facilities as of March 13, 2023, which could impair liquidity and restrict business operations58278279318319 - The company maintains significant amounts of cash and cash equivalents in accounts with major financial institutions that exceed federally insured limits, posing a risk of loss in the event of institutional failure3081084 Risks Related to the Discovery and Development of Product Candidates Risks include limited drug development experience, reliance on unproven AI, expensive and uncertain clinical trials, potential for side effects, and challenges in meeting regulatory requirements for approval - The company has limited experience in drug discovery and development, relying on BioXcel LLC's EvolverAI, a novel and unproven AI-based platform, which may not successfully identify commercially valuable compounds or achieve expected efficiencies8823963115779806807808 - Clinical trials are expensive, time-consuming, and difficult to design and implement, with inherently uncertain outcomes and high failure rates, potentially leading to delays or termination due to various factors including patient enrollment, regulatory authorizations, and manufacturing issues90745764766772773776 - Undesirable side effects from product candidates could interrupt, delay, or halt clinical trials and regulatory approval, or result in a more restrictive label or denial of approval61752777 - The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, expensive, and unpredictable, with no guarantee of approval, and may involve disagreements over data interpretation or trial design60736766767768739746 - If the FDA does not allow the company to pursue the 505(b)(2) regulatory pathway for product candidates, it could significantly increase the time and financial resources required for approval and adversely impact competitive position78511791183 - If approval of a companion diagnostic device is required for any product candidate, delays or failure to obtain such approval could prevent commercialization and materially impair revenue generation93788789815816 - Data from clinical trials conducted outside the U.S. may not be accepted by the FDA, potentially requiring additional costly and time-consuming trials828 Risks Related to Commercialization of Our Product Candidates Commercialization risks include uncertain market acceptance, intense competition, unpredictable third-party reimbursement, impacts from healthcare reform and pricing regulations, and penalties for non-compliance with government programs - Market acceptance of the company's products and product candidates is uncertain and depends on factors such as perceived effectiveness, safety, price relative to alternatives, and the strength of sales and marketing efforts6566841868869903904 - The biopharmaceutical industry is highly competitive, with many companies possessing significantly greater financial resources and expertise in R&D, manufacturing, and marketing, potentially leading to competitors developing more effective or less costly products846874875900901 - Significant uncertainty exists regarding coverage and reimbursement status from government and private third-party payors, which is critical for commercial sales and profitability, as products may not be deemed cost-effective or receive adequate reimbursement rates648675877904 - Healthcare reform measures, including the ACA and the Inflation Reduction Act (IRA), along with state-level legislation, could limit product pricing, reduce reimbursement, and impose new regulatory requirements, adversely affecting commercial success649651677678709878880881882884885905907908909910911912913 - Failure to comply with reporting and payment obligations under government pricing programs (e.g., Medicaid Drug Rebate Program, 340B program) could result in substantial penalties, sanctions, and fines888890941 - Orphan Drug Designation, while offering incentives and market exclusivity, does not guarantee protection from competition by different drugs for the same condition or prevent approval of the same drug if clinically superior557612842871898 Risks Related to Our Relationship with BioXcel LLC Risks stem from BioXcel LLC's significant influence, potential conflicts of interest, reliance on their AI platform and services, and the expiration of exclusivity, allowing them to work with competitors - BioXcel LLC, owning approximately 30% of the company's common stock, has significant influence over business direction, and the concentrated ownership may prevent other stockholders from influencing decisions204918324339 - Commercial terms of agreements with BioXcel LLC were not negotiated by solely disinterested directors, and shared management/ownership (e.g., Vimal Mehta, Krishnan Nandabalan) may create conflicts of interest2079199211493 - The company relies on BioXcel LLC for certain services and access to its EvolverAI platform for product identification and R&D; limitations or failures in these services could adversely affect future operating results962061493 - The exclusivity agreement with BioXcel LLC in neuroscience and immuno-oncology expired on March 12, 2023, allowing BioXcel LLC to use EvolverAI for direct competitors, which could harm the company's competitive position1493 - Disputes between the company and BioXcel LLC regarding their past and ongoing relationships could harm business operations209923948 - BioXcel LLC may experience challenges with the acquisition, development, enhancement, or deployment of technology necessary for EvolverAI, potentially limiting the company's ability to identify new product candidates210923 Risks Related to Our Reliance on Third Parties The company faces risks from heavy reliance on third-party manufacturers for supplies and CROs for clinical trials, with potential for manufacturing failures, supply disruptions, and non-performance, exacerbated by the COVID-19 pandemic - The company is substantially dependent on third-party manufacturers, including ARx, LLC, for clinical and commercial supplies of its product candidates and approved products like IGALMI67211950 - Biotechnology and pharmaceutical manufacturing is complex, involving difficulties in sourcing raw materials, technology transfer, scaling, quality control, and compliance with cGMP, which third-party manufacturers must adhere to212724 - Failure by third-party manufacturers to successfully scale up production, maintain quality, or comply with regulations, or disruptions due to external factors (e.g., labor disputes, natural disasters, COVID-19), could delay or prevent product development and commercialization214926927951953 - The company relies on third-party Contract Research Organizations (CROs) to conduct preclinical and clinical trials; their failure to perform contractual duties, meet deadlines, or maintain data quality could significantly harm development efforts217930931 - The COVID-19 pandemic and its variants continue to pose risks, potentially causing disruptions to preclinical studies and clinical trials, including diversion of healthcare resources, supply chain interruptions, and delays in regulatory review219220243932934 Risks Related to Our Business and Industry Business and industry risks include managing organizational growth, attracting talent, potential disruptions from acquisitions, employee misconduct, data breaches, cyber-attacks, and increased ESG scrutiny - The company needs to increase its organizational size and scope of vendor relationships to manage growth, requiring effective management of consultants and attracting/retaining highly skilled personnel in a competitive market221245935936961986987 - Future acquisitions or investments in businesses/technologies could divert management attention, result in stockholder dilution, incur unanticipated costs, and pose integration challenges, potentially disrupting operations and adversely affecting financial results224247248256938939962963998 - The company is exposed to risks of employee fraud or misconduct, including non-compliance with regulatory standards, which could result in regulatory sanctions and serious harm to its reputation225248963 - Business interruptions from natural disasters, system failures, or pandemics could adversely affect operations, revenues, and financial conditions, and increase costs249964 - Data breaches or cyber-attacks on information technology systems could disrupt business operations, adversely impact financial results, and lead to the loss or exposure of confidential data, resulting in legal claims and liability226250251965991992 - Increased scrutiny and evolving expectations for Environmental, Social, and Governance (ESG) initiatives may impose additional costs, negatively impact reputation, and affect the ability to attract employees or investors68231254969996997 - The utilization of federal and state net operating losses (NOLs) and tax credits may be limited by ownership changes (Section 382 of the U.S. Tax Code) and depends on achieving future taxable income23323497297311891277 Risks Related to Our Intellectual Property Intellectual property risks involve the difficulty and cost of protecting proprietary rights, challenges to patent validity, reliance on trade secrets, and the potential for costly litigation and loss of rights - Protecting proprietary rights is difficult and costly due to the highly uncertain and complex legal and factual questions in biotechnology and pharmaceutical patent law, with no consistent policy on claim scope982352582591000 - The company's ability to prevent third parties from infringing its product candidates depends on valid and enforceable patents, which may not adequately cover similar compounds or may be designed around by competitors236283284285974975976 - Maintaining patent protection requires compliance with various procedural, document submission, and fee payment requirements; non-compliance can result in abandonment or lapse of patent rights2613141003 - Failure to comply with obligations under intellectual property license agreements or disputes with licensors could lead to the loss of rights critical to the business262287288977978979980 - The use of the 505(b)(2) regulatory pathway subjects the company to patent infringement lawsuits, which could delay or prevent the review or approval of product candidates267289982 - Litigation or other proceedings relating to patents and intellectual property rights are costly, time-consuming, and can divert management attention, potentially leading to substantial monetary damages or inability to commercialize products269270272274286292293984985 - Reliance on trade secrets carries risks of disclosure, as confidentiality agreements may not effectively prevent unauthorized disclosure, and others may independently discover proprietary information275296 Risks Related to Owning our Common Stock Risks to common stock ownership include price volatility, concentrated ownership, no anticipated dividends, reduced disclosure as an emerging growth company, potential for class action litigation, and anti-takeover provisions - The price of the company's common stock may fluctuate substantially due to factors such as financial performance, market conditions, competition, analyst reports, and speculative trading3153353633651182 - Concentrated ownership by directors, executive officers, and BioXcel LLC (approximately 37% of outstanding shares) gives them significant control over stockholder approval matters and management, potentially discouraging potential acquirers204324339918 - The company does not intend to pay cash dividends on its common stock in the foreseeable future, meaning any returns to stockholders will be limited to increases in share price325367413 - As an 'emerging growth company' and 'smaller reporting company,' the company benefits from reduced disclosure requirements, which could make its common stock less attractive to some investors, potentially leading to a less active trading market and more volatile stock price344346369370372 - The company is at risk of securities class action litigation, particularly given the stock price volatility common in the biotechnology and pharmaceutical industries, which could result in substantial costs and diversion of management attention347373 - Provisions in the company's certificate of incorporation, bylaws, and Delaware law could make it more difficult for a third party to acquire the company, even if beneficial to stockholders, by discouraging acquisition proposals or delaying changes in control348373374340366 Item 1B. Unresolved Staff Comments This section confirms the absence of any unresolved staff comments Unresolved Staff Comments Content This section confirms the absence of any unresolved staff comments - There are no unresolved staff comments357 Item 2. Properties The company's corporate headquarters are in New Haven, Connecticut, under a lease expiring in February 2026, with existing facilities deemed suitable for current needs Properties Overview The company's corporate headquarters are in New Haven, Connecticut, under a lease expiring in February 2026, with existing facilities deemed suitable for current needs - The company's corporate headquarters are located at 555 Long Wharf Drive in New Haven, Connecticut, occupying 18,285 square feet3831071 - The lease for the headquarters expires in February 2026, with a renewal option for one additional five-year term3831071 - Existing facilities are considered suitable and adequate for current needs, with plans to add new facilities or expand existing ones as employees are added383 Item 3. Legal Proceedings The company is not currently involved in any material legal proceedings, nor is it aware of any pending or threatened actions that could adversely affect its business Legal Proceedings Overview The company is not currently involved in any material legal proceedings, nor is it aware of any pending or threatened actions that could adversely affect its business - The company is not currently a party to any material legal proceedings3584111281 - There are no pending or threatened legal proceedings against the company that are believed to have a material adverse effect on its business, operating results, cash flows, or financial condition4111281 Item 4. Mine Safety Disclosures This item is not applicable to the company's operations Mine Safety Disclosures Content This item is not applicable to the company's operations - This item is not applicable3841100 Part II Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities The company's common stock trades on Nasdaq under 'BTAI,' with 11 stockholders of record as of March 2023, and no cash dividends are anticipated as earnings are retained for business development - The company's common stock is traded on The Nasdaq Capital Market under the symbol "BTAI"47360192 - As of March 13, 2023, there were 11 stockholders of record of the company's common stock386 - The company has never paid or declared any cash dividends on its common stock and does not anticipate paying any in the foreseeable future, intending to retain all available funds and future earnings for business development325367413 Item 6. Reserved This item is reserved - This item is reserved415 Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations This section analyzes the company's financial condition and operations, detailing increased R&D and SG&A expenses, higher net losses, and the ongoing need for substantial additional funding Overview This overview describes BioXcel Therapeutics as an AI-driven biopharmaceutical company, highlighting IGALMI's FDA approval, ongoing BXCL501 clinical trials, and the formation of OnkosXcel Therapeutics for immuno-oncology - BioXcel Therapeutics is an AI-driven biopharmaceutical company focused on developing transformative medicines in neuroscience and immuno-oncology417 - IGALMI (dexmedetomidine sublingual film) was approved by the U.S. FDA on April 6, 2022, for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults3921160 - Clinical trials are ongoing for BXCL501 for at-home use in agitation associated with bipolar disorders and schizophrenia, acute treatment of agitation in Alzheimer's disease, and adjunctive treatment for Major Depressive Disorder (MDD)39311611162 - OnkosXcel Therapeutics, LLC, a wholly-owned subsidiary, was formed on April 19, 2022, to develop immuno-oncology medicines, including BXCL701 and BXCL7023941159 - The