BioXcel Therapeutics(BTAI) - 2019 Q4 - Annual Report

Part I Business BioXcel Therapeutics, Inc. (BTI) is a clinical-stage biopharmaceutical company leveraging an AI platform to re-innovate existing drugs for neuroscience and immuno-oncology applications - BTI is a clinical-stage biopharmaceutical company using AI to identify new therapies in neuroscience and immuno-oncology[11] - The company's drug re-innovation approach leverages existing approved drugs and clinically validated candidates with its proprietary AI platform, EvolverAI, to identify new therapeutic uses, aiming to accelerate time to market[11][13] - The two most advanced programs are BXCL501, a sublingual film for acute agitation, and BXCL701, an oral innate immunity activator for cancers like tNEPC and pancreatic cancer[11][12] Our Clinical Programs and Strategy The company's strategy focuses on advancing BXCL501 and BXCL701 through clinical trials, regulatory approval, and market expansion, utilizing biomarkers and its AI platform - Advance BXCL501, a sublingual thin film of dexmedetomidine (Dex), for acute treatment of agitation through the 505(b)(2) regulatory pathway[16] - Complete Phase 2 trials for BXCL701 for first-line treatment of tNEPC and second-line treatment of pancreatic cancer, and pursue breakthrough therapy designation[21][25] - Utilize biomarkers to identify patient subsets most likely to respond to product candidates, thereby increasing the probability of clinical trial success[27] - Plan to build a specialty sales force in the United States for commercialization and seek collaborations for ex-U.S. markets if products are approved[31] BXCL501 Program BXCL501, a sublingual film for acute agitation, is progressing through pivotal Phase 3 trials with an expanding development program for additional indications U.S. Market for Treating Agitation | Indication | Patients at Risk | Patients Experiencing Agitation | Potential Annual Doses | | :--- | :--- | :--- | :--- | | Schizophrenia & Bipolar Disorder | 7,800,000 | ~3,000,000 | ~36,000,000 | | Dementia | 5,700,000 | ~4,000,000 | ~96,000,000 | - BXCL501 has received Fast Track Designation from the FDA for the treatment of acute agitation[65][66] - Phase 1b trial in schizophrenia patients met its primary endpoint, showing a statistically significant reduction in agitation scores (PEC score) at multiple doses (80 mcg, 120 mcg, 180 mcg) compared to placebo[72][73] - Two pivotal Phase 3 studies, SERENITY I (schizophrenia) and SERENITY II (bipolar disorder), were initiated in December 2019, with topline data expected in mid-2020[79][80] - The development program is expanding to include a Phase 1b/2 trial for agitation in dementia and a Phase 1b/2 trial for opioid withdrawal symptoms[82][83] BXCL701 Program BXCL701, an oral immuno-modulator, is in Phase 1b/2 trials for tNEPC and pancreatic cancer, holding three FDA Orphan Drug Designations - BXCL701 is an oral small molecule designed to stimulate the innate immune system by inhibiting DPP 8/9 and FAP[94] - A Phase 1b/2 trial combining BXCL701 with pembrolizumab (Keytruda®) in tNEPC patients is ongoing, with topline data expected in the second half of 2020[117][118] - A triple combination trial of BXCL701, bempegaldesleukin (Nektar), and avelumab (Merck KGaA/Pfizer) is planned for pancreatic cancer, expected to start in H2 2020[120][126][127] - BXCL701 has received three FDA Orphan Drug Designations: for pancreatic cancer, acute myeloid leukemia, and melanoma[26][114][128] Competition, Manufacturing, and Commercialization The company faces intense competition, relies on third-party manufacturing, and plans a U.S. specialty sales force with international partnerships - Competitors in the acute agitation space include atypical antipsychotics like aripiprazole and olanzapine, as well as non-invasive treatments like Adasuve (inhaled loxapine)[141] - The immuno-oncology field is highly competitive with major players like AstraZeneca, Bristol-Myers Squibb, Merck, and Roche[143] - The company relies on third-party manufacturing partners for both BXCL501 and BXCL701 clinical supplies and considers them suitable for potential commercial supply[147][148][149] - Commercialization plans include retaining U.S. rights and building a specialty sales force, while exploring partnerships for European and Japanese markets[151] Intellectual Property The company protects its technology and product candidates through patent filings in key jurisdictions, with expected expirations between 2036 and 2041 - The core patent family for BXCL501 has been filed in the U.S., Taiwan, and as a PCT application, with expected patent expiration no earlier than 2039[154][156] - The core patent family for BXCL701, covering its use with immune checkpoint inhibitors, is filed in the U.S. and 17 other countries, with expected expiration no earlier than 2036[157] Our Relationship with BioXcel Corporation BTI is a 45.5% subsidiary of BioXcel Corporation, with an ongoing services agreement and an option to continue using the EvolverAI platform - BTI is a 45.5% owned subsidiary of BioXcel Corporation[162] - Under the Asset Contribution Agreement, BTI made milestone payments of $500,000 each in April 2019 and July 2019 to BioXcel[163] - A Services Agreement allows BTI to use BioXcel's services and provides an option (until Dec 31, 2020) to enter a collaborative agreement for continued use of the EvolverAI platform, which would include royalties and milestone payments to BioXcel[164][165] Government Regulation The company navigates extensive FDA regulations, utilizing expedited pathways like 505(b)(2) and Fast Track, while facing post-approval compliance and reimbursement challenges - The FDA drug approval process requires extensive preclinical and clinical trials to establish safety and efficacy before an NDA can be submitted and approved[170] - The company intends to use the Section 505(b)(2) regulatory pathway for BXCL501, which allows an NDA to reference data from studies not conducted by the applicant, potentially streamlining the approval process[213] - The company has obtained FDA Fast Track designation for BXCL501 and may seek other expedited programs like priority review or breakthrough therapy designation for its candidates to accelerate development and review[198][202] - BXCL701 has received Orphan Drug Designation for pancreatic cancer, melanoma, and acute myeloid leukemia, which can provide benefits like market exclusivity and financial incentives[196][197] - Commercial success depends on securing adequate coverage and reimbursement from third-party payors, a process challenged by increasing cost-containment pressures and healthcare reforms like the ACA[227][229] Risk Factors The company faces significant risks including operating losses, capital needs, dependence on lead candidates, reliance on its parent, third-party manufacturing, and intellectual property challenges - The company has a history of significant operating losses ($33.0 million in 2019) and has never generated revenue, raising substantial doubt about its ability to continue as a going concern without additional funding[257][262][263] - The business is highly dependent on the success of its two lead product candidates, BXCL501 and BXCL701; failure or significant delays would substantially harm the company[273][274] - The company relies on its parent, BioXcel Corporation, for its core EvolverAI technology and other services, creating risks related to conflicts of interest, service continuity, and reputational harm[369][376][377] - There is a substantial risk of reliance on third parties for manufacturing clinical supplies and conducting clinical trials; failure by these third parties to perform could delay or halt development programs[386][394] - The use of the 505(b)(2) pathway for BXCL501 creates a risk of patent infringement lawsuits from holders of patents on the referenced drug, which could trigger an automatic 30-month stay on FDA approval[448][452] - As of February 24, 2020, BioXcel Corporation owned approximately 45.5% of the company's common stock, giving it significant influence over business direction and corporate actions[370] Unresolved Staff Comments The company reports no unresolved staff comments from the SEC - None[507] Properties The company leases 11,040 square feet of office space for its headquarters in New Haven, Connecticut, under a seven-year lease with a five-year renewal option - The company leases 11,040 square feet of office space for its headquarters in New Haven, Connecticut[508] - The lease term is for seven years with an option to renew for one additional five-year term[508] Legal Proceedings The company is not currently a party to any material legal proceedings and is unaware of any pending or threatened claims - The company is not a party to any material legal proceedings[509] Mine Safety Disclosures This item is not applicable to the company - Not applicable[510] Part II Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities The company's common stock trades on Nasdaq, has never paid dividends, and recently repurchased shares from its parent company - Common stock is traded on the Nasdaq Capital Market under the symbol "BTAI"[513] - The company has never paid dividends and does not plan to in the foreseeable future[514] - In February 2020, the company purchased 300,000 shares of its common stock from its parent company, BioXcel, at a price of $30.08 per share[517] Selected Financial Data The company reported no revenues for 2019 and 2018, with net loss increasing to $33.0 million in 2019 due to higher operating expenses Selected Financial Data (in thousands, except per share data) | Metric | 2019 | 2018 | | :--- | :--- | :--- | | Results of Operations | | | | Revenues | $0 | $0 | | Research and development | $25,797 | $14,558 | | General and administrative | $7,804 | $5,404 | | Loss from operations | $(33,601) | $(19,962) | | Net loss | $(32,968) | $(19,270) | | Net loss per share | $(2.02) | $(1.32) | | Balance Sheet Data (as of Dec 31) | | | | Cash and cash equivalents | $32,426 | $42,565 | | Total assets | $36,392 | $43,549 | | Total stockholders' equity | $26,895 | $38,889 | Management's Discussion and Analysis of Financial Condition and Results of Operations The company's net loss increased to $33.0 million in 2019 due to rising R&D and G&A expenses, with current cash and recent financing expected to fund operations for at least one year Results of Operations The company's net loss increased to $33.0 million in 2019, driven by a $13.6 million rise in total operating expenses, primarily R&D and G&A Comparison of Operating Expenses (in thousands) | Expense Category | 2019 | 2018 | Change | | :--- | :--- | :--- | :--- | | Research and development | $25,797 | $14,558 | $11,239 | | General and administrative | $7,804 | $5,404 | $2,400 | | Total operating expenses | $33,601 | $19,962 | $13,639 | - The $11.2 million increase in R&D expense was primarily driven by a $4.1 million increase in clinical trials expense, a $2.2 million increase in professional research costs, and a $1.7 million increase in chemical, manufacturing, and controls (CMC) costs, reflecting the acceleration of development activities[565][569] - The $2.4 million increase in G&A expense was mainly due to a $0.9 million increase in salaries and related costs from higher headcount and a $0.8 million increase in professional fees for legal, audit, and investor relations services[570][571][575] Liquidity and Capital Resources As of December 31, 2019, the company had $32.4 million in cash, with recent financing expected to fund operations for at least one year, though substantial additional funding will be required Cash Flow Summary (in thousands) | Activity | Year Ended Dec 31, 2019 | Year Ended Dec 31, 2018 | | :--- | :--- | :--- | | Net cash used in operating activities | $(27,280) | $(13,509) | | Net cash used in investing activities | $(870) | $(340) | | Net cash provided by financing activities | $18,011 | $55,527 | | Net (decrease) increase in cash | $(10,139) | $41,678 | - In September 2019, the company raised approximately $17.4 million in net proceeds from a public offering of common stock[583] - In February 2020, the company raised approximately $60.0 million in net proceeds from a registered offering of common stock[583] - Management believes existing cash and a review of project timing will fund operating expenses and capital requirements for at least one year from the report's filing date[578] Critical Accounting Policies The company's critical accounting policies involve significant judgment in expensing R&D costs, valuing stock-based compensation, and estimating accrued clinical trial expenses - Research and development costs, including patent-related costs, are expensed as incurred[599] - Stock-based compensation is measured at fair value on the grant date using the Black-Scholes option-pricing model, which involves significant estimates for inputs like stock volatility[604][605] - The company estimates accrued expenses for clinical trials based on services received and efforts expended under contracts with CROs and research institutions, which requires judgment on the progress of work performed[608][610] Quantitative and Qualitative Disclosures About Market Risk The company's primary market risk relates to its $32.4 million in cash and cash equivalents, with no foreign currency hedging or derivative financial instruments used - The company's cash and cash equivalents of $32.4 million are subject to market risk, though it believes the risk of default or illiquidity is not significant[615][619] - The company does not participate in foreign currency hedging or use derivative financial instruments[615] Financial Statements and Supplementary Data This section indicates that the company's financial statements are appended to the Annual Report on Form 10-K - The financial statements required by this item are appended to the Annual Report[621] Changes in and Disagreements with Accountants on Accounting and Financial Disclosure The company reports no changes in or disagreements with its accountants on accounting and financial disclosure - None[622] Controls and Procedures Management concluded that the company's disclosure controls and internal control over financial reporting were effective as of December 31, 2019 - Management concluded that as of December 31, 2019, the company's disclosure controls and procedures were effective[624] - Management concluded that as of December 31, 2019, the company's internal control over financial reporting was effective[625] - The report does not include an auditor's attestation on internal control over financial reporting, as permitted for an "emerging growth company" under the JOBS Act[626] Other Information The company reports no other information for this item - None[628] Part III Directors, Executive Officers, Corporate Governance, Compensation, Security Ownership, and Related Transactions Information for Items 10 through 14 is incorporated by reference from the company's 2020 proxy statement - Information for Items 10, 11, 12, 13, and 14 is incorporated by reference from the company's 2020 proxy statement[631][632][633][634][635] Part IV Exhibits, Financial Statement Schedules This section lists the financial statements, notes, and key exhibits filed as part of the annual report, including corporate documents and material contracts - The financial statements and their schedules are filed as part of the report[642] - A list of exhibits is provided, including key corporate documents and material contracts[643][644][648] Form 10-K Summary This item is not applicable to the company's filing - Not applicable[653] Financial Statements Report of Independent Registered Public Accounting Firm BDO USA, LLP issued an unqualified opinion on the company's financial statements for 2019 and 2018, confirming fair presentation in accordance with U.S. GAAP - The auditor, BDO USA, LLP, expressed an unqualified opinion on the financial statements[659] - The financial statements are deemed to be presented fairly in accordance with U.S. GAAP[659] - The company was not required to have, nor was the firm engaged to perform, an audit of its internal control over financial reporting[661] Financial Statements Tables The financial statements show a net loss of $33.0 million for 2019, with total assets of $36.4 million and total stockholders' equity of $26.9 million as of December 31, 2019 Balance Sheet (in thousands) | | Dec 31, 2019 | Dec 31, 2018 | | :--- | :--- | :--- | | Assets | | | | Cash and cash equivalents | $32,426 | $42,565 | | Total current assets | $34,107 | $43,171 | | Total assets | $36,392 | $43,549 | | Liabilities & Equity | | | | Total current liabilities | $8,468 | $4,660 | | Total liabilities | $9,497 | $4,660 | | Total stockholders' equity | $26,895 | $38,889 | | Total liabilities and stockholders' equity | $36,392 | $43,549 | Statement of Operations (in thousands) | | Year Ended Dec 31, 2019 | Year Ended Dec 31, 2018 | | :--- | :--- | :--- | | Revenues | $0 | $0 | | Research and development | $25,797 | $14,558 | | General and administrative | $7,804 | $5,404 | | Loss from operations | $(33,601) | $(19,962) | | Net loss | $(32,968) | $(19,270) | | Net loss per share | $(2.02) | $(1.32) | Statement of Cash Flows (in thousands) | | Year Ended Dec 31, 2019 | Year Ended Dec 31, 2018 | | :--- | :--- | :--- | | Net cash used in operating activities | $(27,280) | $(13,509) | | Net cash used in investing activities | $(870) | $(340) | | Net cash provided by financing activities | $18,011 | $55,527 | | Net (decrease) increase in cash | $(10,139) | $41,678 | Notes to Financial Statements The notes detail accounting policies, including milestone payments to BioXcel, lease accounting adoption, deferred tax assets with a full valuation allowance, and a significant February 2020 public offering - The company made two milestone payments of $500,000 each to its parent, BioXcel, in 2019 under the Asset Contribution Agreement[706] - The company has significant clinical trial commitments, with one trial for BXCL701 expected to cost approximately $10 million over two years, and a second trial expected to cost approximately $8 million over three years[718][719] - As of Dec 31, 2019, the company had federal and state net operating loss carryforwards of approximately $16.4 million and R&D tax credits of $1.3 million, but a full valuation allowance has been recorded against these deferred tax assets[431][748] - In February 2020, the company completed a public offering, raising gross proceeds of approximately $64 million[757]