Tyra Biosciences(TYRA) - 2023 Q4 - Annual Report

PART I Business Tyra Biosciences develops precision medicines for FGFR-driven cancers and genetic conditions using its proprietary SNÅP platform Overview - Tyra Biosciences is a clinical-stage biotechnology company using its proprietary SNÅP platform to develop precision medicines targeting Fibroblast Growth Factor Receptor (FGFR) biology for oncology and genetically defined conditions[14] - Lead product candidate, TYRA-300, is an oral, FGFR3-selective inhibitor being evaluated in the SURF301 Phase 1 study for advanced solid tumors with FGFR3 gene alterations. The study has completed dose escalation without reaching a maximum tolerated dose (MTD)[16] - TYRA-300 is also being developed for achondroplasia (ACH), the most common form of dwarfism. The FDA has granted it Orphan Drug Designation (ODD) and Rare Pediatric Disease (RPD) Designation for this indication, with an IND submission planned for the second half of 2024[17][18] - Second product candidate, TYRA-200, is an oral, FGFR1/2/3 inhibitor being evaluated in the SURF201 Phase 1 study for cholangiocarcinoma and other advanced solid tumors with FGFR2 alterations and resistance mutations[20] Our SNÅP Platform - The proprietary SNÅP platform is designed to rapidly and precisely design drugs by generating molecular "SNÅPshots" that predict genetic alterations causing acquired resistance[14][21] - The platform is built on three key pillars that provide iterative data concurrently: - Protein crystallography: Generates co-crystal structures in as little as three days - Cell-based assays: Assesses inhibitor potency and cell penetration in as little as two days - In vivo models: Provides bioavailability, PK, and anti-tumor activity data in as little as five days[22][23] Our Programs Development Pipeline Overview | Indication Category | Program | Annual US Addressable Patients | Development Stage | Anticipated Milestone | | :--- | :--- | :--- | :--- | :--- | | Genetic Conditions | | | | | | FGFR3 ACH | TYRA-300 | ~3K | IND-Enabling | Submit IND 2H '24 | | Oncology | | | | | | FGFR3 ONC | TYRA-300 | ~40K | Phase 1 (SURF301) | Ph1 data in 2H '24 | | FGFR2 ONC | TYRA-200 | ~5.5K | Phase 1 (SURF201) | Complete Ph1 | | FGFR4/3 ONC | TYRA-430 | ~9K | IND-Enabling | Complete IND-enabling | - TYRA-300 is designed as a selective FGFR3 inhibitor to treat metastatic urothelial carcinoma (mUC) by addressing gatekeeper resistance mutations (e.g., V555M) and minimizing off-target toxicities associated with pan-FGFR inhibitors[27][28] - TYRA-200 is an FGFR1/2/3 inhibitor with potency against activating FGFR2 alterations and key resistance mutations, initially targeting intrahepatic cholangiocarcinoma (ICC)[35] - TYRA-430 is being developed to address cancers driven by the FGF19/FGFR4 axis, initially focusing on hepatocellular carcinoma (HCC), with a design intended to also inhibit FGFR3 to address bypass mechanisms[37] Our Strategy - Advance next-generation precision medicines through clinical development, focusing on overcoming acquired resistance and off-target toxicities of existing FGFR inhibitors[38] - Utilize the SNÅP platform to rapidly expand the pipeline with additional therapies for oncology and genetically-defined conditions[41] - Leverage recent advances in precision medicine, such as the potential for expedited regulatory pathways, to accelerate product development[41] - Maximize product candidate value across multiple therapeutic areas by retaining worldwide rights and considering strategic partnerships opportunistically[40] Intellectual Property - As of March 15, 2024, the company's IP portfolio, which is solely owned, includes 6 pending U.S. provisional applications, 5 pending U.S. nonprovisional applications, 46 pending foreign applications, and 6 PCT applications. The company does not own any issued patents[181] - For the FGFR3 program (including TYRA-300), the company owns 3 pending U.S. provisional, 2 pending U.S. nonprovisional, 3 pending PCT, and 30 pending foreign applications. Any resulting patents are expected to expire between 2040 and 2045[184] - For the FGFR2 program (including TYRA-200), the company owns 2 pending U.S. provisional, 2 pending U.S. nonprovisional, and 14 pending foreign applications. Any resulting patents are expected to expire between 2040 and 2042[185] Government Regulation - The company's products are subject to extensive regulation by the FDA in the U.S. and comparable authorities in other countries, covering research, development, testing, manufacturing, approval, and marketing[200] - The U.S. drug development process involves preclinical studies, submitting an Investigational New Drug (IND) application, conducting Phase 1, 2, and 3 clinical trials under Good Clinical Practices (GCPs), and submitting a New Drug Application (NDA) for FDA review and approval[201][203] - The FDA offers expedited programs like Fast Track, Breakthrough Therapy, priority review, and accelerated approval for qualifying product candidates intended for serious conditions, which can potentially speed up the development and review process[220][223][225] - The company is also subject to foreign regulations, including the EU's Clinical Trials Regulation (CTR) for clinical studies and the centralized or national procedures for obtaining Marketing Authorization (MA) from the European Medicines Agency (EMA) or member state authorities[265][270][274] Human Capital - As of March 18, 2024, the company had 49 full-time employees, with 37 engaged in research and development. This includes 16 employees with M.D. or Ph.D. degrees[289] - None of the employees are represented by labor unions or covered by collective bargaining agreements. The company considers its employee relations to be good[289] Risk Factors The company faces substantial risks from its early development stage, funding needs, third-party reliance, competition, and IP protection challenges - Financial Risks: The company has a limited operating history, has incurred significant net losses since inception ($69.1 million in 2023), and expects to continue incurring losses. It will require substantial additional financing to fund operations, and failure to obtain it could force delays or termination of programs[299][302][305] - Development and Regulatory Risks: The company is early in its development efforts with only two candidates in Phase 1 trials. Preclinical and clinical development is a lengthy, expensive, and uncertain process. Difficulties in patient enrollment or unexpected adverse events could delay or halt trials[298][315][319] - Reliance on Third Parties: The company relies on third parties for manufacturing its product candidates and conducting clinical trials. This dependency increases risks related to supply sufficiency, cost, quality control (cGMP compliance), and adherence to timelines and protocols[300][396][409] - Commercial and Market Risks: The company faces significant competition from larger, better-funded companies. The commercial success of its products, if approved, will depend on market acceptance, pricing, and reimbursement from payors. Market opportunities may also be smaller than estimated[300][421][434] - Intellectual Property Risks: The company's success depends on obtaining and maintaining patent protection. The patent process is uncertain, and the company may not be able to protect its technology from competitors. The company currently does not own any issued patents[300][501][509] Unresolved Staff Comments The company reports that it has no unresolved staff comments from the SEC - None[597] Cybersecurity The company's cybersecurity risk management program, based on the NIST framework, is overseen by the audit committee, with management handling day-to-day threats - The company has a cybersecurity risk management program guided by the National Institute of Standards and Technology Cybersecurity Framework (NIST CSF)[600] - Oversight is provided by the board of directors, which has delegated the function to the audit committee. The committee receives periodic reports from management[603][605] - A management team including the CFO, General Counsel, and IT Senior Director is responsible for assessing and managing cybersecurity risks[606] - The company has not identified any risks from cybersecurity threats that have materially affected or are reasonably likely to materially affect its business, operations, or financial condition[602] Properties The company leases approximately 13,065 square feet of laboratory and office space in Carlsbad, California for its corporate headquarters - The company leases approximately 13,065 square feet of laboratory and office space in Carlsbad, California for its corporate headquarters[608] - The lease for the combined space commenced in November 2023 and has a term of 120 months (10 years)[608] Legal Proceedings The company is not currently a party to any material legal proceedings - The company is not currently subject to any material legal proceedings[610] Mine Safety Disclosures This section is not applicable to the company - Not applicable[611] 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 used $112.4 million of IPO proceeds for operations by year-end 2023 - The company's common stock is traded on the Nasdaq Global Select Market under the ticker symbol "TYRA"[614] - The company has never declared or paid cash dividends and intends to retain future earnings to finance business operations[616] - The September 2021 IPO generated net proceeds of approximately $181.2 million. As of December 31, 2023, approximately $112.4 million of these proceeds have been used for general corporate purposes and to fund development programs[620][621] Management's Discussion and Analysis of Financial Condition and Results of Operations Net loss increased to $69.1 million in 2023 due to higher R&D expenses; $203.5 million cash at year-end, plus a $200 million PIPE, is expected to fund operations through 2026 Results of Operations Results of Operations (in thousands) | | Year Ended December 31, 2023 | Year Ended December 31, 2022 | Change | | :--- | :--- | :--- | :--- | | Research and development | $62,518 | $43,008 | $19,510 | | General and administrative | $17,427 | $15,919 | $1,508 | | Total operating expenses | $79,945 | $58,927 | $21,018 | | Loss from operations | $(79,945) | $(58,927) | $(21,018) | | Interest income | $10,850 | $3,652 | $7,198 | | Net loss | $(69,134) | $(55,325) | $(13,809) | - Research and development expenses increased by $19.5 million in 2023 compared to 2022, primarily due to a $13.7 million increase in CRO and drug manufacturing costs for ongoing and planned clinical trials, and a $4.0 million increase in personnel costs[648] - General and administrative expenses increased by $1.5 million in 2023, mainly due to a $1.0 million increase in professional services costs and a $0.9 million increase in personnel costs[651] Liquidity and Capital Resources - As of December 31, 2023, the company had cash, cash equivalents, and marketable securities of $203.5 million[633] - In February 2024, the company completed a private placement (PIPE) for gross proceeds of approximately $200 million[634] - Management believes that existing cash combined with the 2024 PIPE proceeds will be sufficient to fund operations and capital expenditures through at least 2026[636] Summary of Cash Flows (in thousands) | | Year Ended December 31, 2023 | Year Ended December 31, 2022 | | :--- | :--- | :--- | | Net cash used in operating activities | $(50,139) | $(50,285) | | Net cash used in investing activities | $(144,605) | $(559) | | Net cash provided by financing activities | $1,537 | $632 | Quantitative and Qualitative Disclosures About Market Risk The company faces immaterial market risks from interest rate fluctuations on short-term investments and foreign currency exchange, with inflation having no material effect - Interest Rate Risk: The company's portfolio of cash, cash equivalents, and marketable securities is exposed to interest rate changes. However, due to the short-term nature of these investments, a hypothetical 10% change in interest rates would not have a material impact[680] - Foreign Currency Exchange Risk: The company has limited exposure as most expenses are denominated in U.S. dollars. A hypothetical 10% change in exchange rates would not have had a material impact[681] - Inflation: The company does not believe inflation has had a material effect on its financial results[682] Financial Statements and Supplementary Data Audited financial statements show a net loss of $69.1 million in 2023, with total assets decreasing to $225.9 million, and an unqualified opinion from Ernst & Young LLP Key Balance Sheet Data (in thousands) | | Dec 31, 2023 | Dec 31, 2022 | | :--- | :--- | :--- | | Cash, cash equivalents, and marketable securities | $203,469 | $251,213 | | Total current assets | $211,671 | $257,288 | | Total assets | $225,857 | $266,181 | | Total current liabilities | $15,333 | $5,701 | | Total liabilities | $21,595 | $8,352 | | Total stockholders' equity | $204,262 | $257,829 | Key Statement of Operations Data (in thousands) | | Year Ended Dec 31, 2023 | Year Ended Dec 31, 2022 | | :--- | :--- | :--- | | Research and development expense | $62,518 | $43,008 | | General and administrative expense | $17,427 | $15,919 | | Loss from operations | $(79,945) | $(58,927) | | Net loss | $(69,134) | $(55,325) | | Net loss per share, basic and diluted | $(1.62) | $(1.32) | - The independent registered public accounting firm, Ernst & Young LLP, issued an unqualified opinion on the financial statements[686] - Subsequent to year-end, in February 2024, the company closed a private placement (PIPE) for gross proceeds of approximately $200 million[799] 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[800] Controls and Procedures Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2023 - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2023[802] - Management concluded that the company's internal control over financial reporting was effective as of December 31, 2023[803] - No changes in internal control over financial reporting occurred during the fourth quarter of 2023 that materially affected, or are reasonably likely to materially affect, internal controls[805] Other Information No officers or directors adopted, modified, or terminated Rule 10b5-1 or non-Rule 10b5-1 trading arrangements during Q4 2023 - During the three months ended December 31, 2023, no officers or directors adopted, modified, or terminated any Rule 10b5-1 or non-Rule 10b5-1 trading arrangements[807] PART III Directors, Executive Officers and Corporate Governance Information for this item is incorporated by reference from the company's definitive proxy statement for the 2024 Annual Meeting of Stockholders - The required information is incorporated by reference from the company's definitive proxy statement for the 2024 annual meeting of stockholders[810] Executive Compensation Information regarding executive compensation is incorporated by reference from the company's definitive proxy statement for the 2024 Annual Meeting of Stockholders - The required information is incorporated by reference from the company's definitive proxy statement for the 2024 annual meeting of stockholders[812] Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters Information regarding security ownership is incorporated by reference from the company's definitive proxy statement for the 2024 Annual Meeting of Stockholders - The required information is incorporated by reference from the company's definitive proxy statement for the 2024 annual meeting of stockholders[813] Certain Relationships and Related Transactions, and Director Independence Information regarding related party transactions and director independence is incorporated by reference from the company's definitive proxy statement for the 2024 Annual Meeting of Stockholders - The required information is incorporated by reference from the company's definitive proxy statement for the 2024 annual meeting of stockholders[815] Principal Accounting Fees and Services Information regarding principal accounting fees and services is incorporated by reference from the company's definitive proxy statement for the 2024 Annual Meeting of Stockholders - The required information is incorporated by reference from the company's definitive proxy statement for the 2024 annual meeting of stockholders[816] PART IV Exhibits and Financial Statement Schedules Financial statements are in Part II, Item 8, with schedules omitted as not applicable, and a list of exhibits is referenced - The financial statements are included in Part II, Item 8 of the Annual Report[818] - All financial statement schedules have been omitted because they are not applicable or the required information is otherwise provided[819] Form 10-K Summary The company has not provided a summary for Form 10-K - None[821]