Tyra Biosciences(TYRA) - 2022 Q4 - Annual Report

PART I Business Tyra Biosciences develops precision medicines for oncology and genetic conditions, advancing TYRA-300 and TYRA-200 via its SNÅP platform - Tyra Biosciences is a clinical-stage biotechnology company focused on developing precision medicines targeting Fibroblast Growth Factor Receptor (FGFR) biology for oncology and genetically defined conditions[14] - The company's proprietary SNÅP platform enables rapid and precise drug design to address acquired resistance to existing therapies[15][19] - Lead product candidate TYRA-300, an FGFR3 selective inhibitor, is in a Phase 1/2 clinical trial (SURF301) for metastatic urothelial carcinoma (mUC), with the first patient dosed in November 2022[16] - TYRA-300 development is expanding into achondroplasia, with plans to submit an IND for a Phase 2 study in pediatric patients in 2024[17] - Second product candidate TYRA-200, an FGFR1/2/3 inhibitor, received IND clearance in January 2023 for a Phase 1 trial in intrahepatic cholangiocarcinoma, with the first patient expected to be dosed in the second half of 2023[18] Our SNÅP Platform - The SNÅP platform is designed to efficiently identify and target vulnerabilities in mutant proteins that cause acquired drug resistance[19][56] - The platform is built on three key pillars that provide iterative data rapidly and concurrently: protein crystallography, cell-based assays, and in vivo models[22][23] - Proprietary protein crystallography techniques can generate co-crystal structures of compounds in target proteins in as little as three days, enabling rapid structural insights[26][57] - The company utilizes custom cell-based assays to assess inhibitor potency, cell penetration, and target-specific cell killing, generating data in as little as two days[26][60] - In-house animal models provide bioavailability, pharmacokinetic data, and anti-tumor activity in as little as five days, completing the rapid, iterative drug design cycle[26][61] Our Programs Pipeline Overview | Program | Target | Lead Indication(s) | Development Stage | | :--- | :--- | :--- | :--- | | TYRA-300 | FGFR3 | Metastatic Urothelial Carcinoma (mUC) | Phase 1/2 Clinical Trial (SURF301) | | TYRA-300 | FGFR3 | Achondroplasia (ACH) | Preclinical / IND-enabling | | TYRA-200 | FGFR1/2/3 | Intrahepatic Cholangiocarcinoma (ICC) | Phase 1 Clinical Trial (IND cleared) | | FGFR4/FGF19 Program | FGFR4/FGF19 | Hepatocellular Carcinoma (HCC) | Discovery | | RET Program | RET | RET-related cancers | Discovery | - TYRA-300 is designed to be a selective FGFR3 inhibitor that overcomes gatekeeper resistance mutations (e.g., V555M) and minimizes off-target toxicities associated with pan-FGFR inhibitors[28][29] - TYRA-200 is an FGFR1/2/3 inhibitor designed to be potent against activating FGFR2 alterations and key resistance mutations (molecular brake and gatekeeper) that emerge during treatment with other FGFR inhibitors[34] - The FGFR4/FGF19 program is focused on hepatocellular carcinoma (HCC) and aims to address bypass mechanisms and acquired resistance mutations that limited previous FGFR4 inhibitors[35] - The RET program is focused on overcoming acquired drug resistance mutations (e.g., G810 solvent front) observed in response to existing RET inhibitors like selpercatinib and pralsetinib[36][171] Competition - The company faces intense competition from major pharmaceutical and biotechnology companies with greater financial resources and experience[175][176] - Key competitors in the FGFR inhibitor space for oncology include Janssen (Balversa), Incyte (Pemazyre), Taiho Oncology (Lytgobi), Relay Therapeutics (RLY-4008), and Kinnate Biopharma (KIN-3248)[178][182] - In achondroplasia, competitors include BioMarin Pharmaceutical (Voxzogo), BridgeBio Pharma (infigratinib), and Ascendis Pharma (TransCon CNP)[183] - In the RET inhibitor space, competitors include Lilly's Loxo Oncology (Retevmo) and Blueprint Medicines (Gavreto)[185] Intellectual Property - As of March 15, 2023, the company's IP portfolio consists of eight pending U.S. provisional applications, two pending U.S. nonprovisional applications, and three PCT applications, all solely owned, and the company does not own any issued patents[187] - For the FGFR3 program (including TYRA-300), the company owns one pending PCT application and other filings, with any patents issued expected to expire between 2040 and 2043[191] - For the FGFR2 program (including TYRA-200), the company owns one pending PCT application and other filings, with any patents issued expected to expire between 2040 and 2042[192] - The company also relies on trade secret protection for its confidential and proprietary information, including its SNÅP platform, and uses confidentiality agreements with employees, consultants, and collaborators[199] Government Regulation - The company's operations are extensively regulated by the FDA in the United States and comparable authorities in other countries, covering research, development, testing, manufacturing, and marketing[205] - The U.S. drug development process involves preclinical studies, submitting an Investigational New Drug (IND) application, and conducting Phase 1, 2, and 3 clinical trials under Good Clinical Practices (GCPs)[207][213] - The FDA offers expedited programs like Fast Track, Breakthrough Therapy, priority review, and accelerated approval for qualifying product candidates intended for serious conditions[227][228][231] - In the European Union, clinical trials are now governed by the Clinical Trials Regulation (CTR), which harmonizes the assessment and supervision processes via a centralized portal[275] - The company is also subject to healthcare laws concerning fraud and abuse (e.g., Anti-Kickback Statute), pricing transparency (e.g., Sunshine Act), and data privacy (e.g., GDPR, CCPA)[254][294] Human Capital - As of March 20, 2023, the company had 38 full-time employees, with 28 engaged in research and development[295] - The company's human capital objectives include identifying, recruiting, retaining, and incentivizing employees through stock-based compensation and competitive benefits[296] Risk Factors The company faces significant risks from early development, clinical trial uncertainties, capital needs, third-party reliance, and regulatory complexities - The company is in the early stages of development with a limited operating history, no approved products, and a history of significant net losses, making future success difficult to evaluate[303][306] - Substantial additional financing is required to achieve goals, and failure to obtain capital could force delays or termination of development programs[309] - Preclinical and clinical development is a lengthy, expensive process with an uncertain outcome, and the company's SNÅP platform is novel and unproven and may not lead to approved products[323][339] - The company relies on third parties for manufacturing and conducting clinical trials, which increases risks related to supply, cost, quality, and timelines[394][407] - The company faces significant competition from better-funded companies and must obtain and maintain patent protection for its product candidates, which is uncertain[431][497] Properties The company's Carlsbad headquarters occupies 4,734 sq ft, with an additional 7,377 sq ft expansion expected in late 2023 - The company leases approximately 4,734 square feet of laboratory and office space for its headquarters in Carlsbad, California[588] - An expansion is underway to lease an additional 7,377 square feet in an adjacent building, with the new lease expected to commence in the second half of 2023[588] Legal Proceedings The company is not currently subject to any material legal proceedings, though minor matters may arise in the ordinary course of business - The company is not currently a party to any material legal proceedings[591] 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 under 'TYRA', has never paid dividends, and used $61.5 million of its $181.2 million IPO proceeds - The company's common stock is traded on the Nasdaq Global Select Market under the ticker symbol "TYRA"[594] - The company has never declared or paid cash dividends and intends to retain future earnings to finance business operations[596] - The company received net proceeds of approximately $181.2 million from its IPO in September 2021[600][601] - As of December 31, 2022, approximately $61.5 million of the IPO proceeds have been used to fund the development of TYRA-300, TYRA-200, and other programs[602] Management's Discussion and Analysis of Financial Condition and Results of Operations Net loss increased to $55.3 million in 2022 due to higher R&D and G&A expenses, with $251.2 million cash expected to fund operations through 2024 Results of Operations (in thousands) | | Year Ended December 31, | | Change | | :--- | :--- | :--- | :--- | | | 2022 | 2021 | ($) | | Operating expenses: | | | | | Research and development | $43,008 | $20,636 | $22,372 | | General and administrative | $15,919 | $5,652 | $10,267 | | Total operating expenses | $58,927 | $26,288 | $32,639 | | Loss from operations | ($58,927) | ($26,288) | ($32,639) | | Interest income | $3,652 | $13 | $3,639 | | Net loss | ($55,325) | ($26,294) | ($29,031) | - The $22.4 million increase in R&D expenses in 2022 was primarily due to a $15.1 million increase in clinical trial and preclinical study costs for TYRA-300 and TYRA-200, and a $7.3 million increase in personnel-related costs[626] - The $10.2 million increase in G&A expenses in 2022 was driven by a $6.5 million increase in personnel costs (including $4.1 million in stock-based compensation), a $1.8 million increase in professional services, and a $1.9 million increase in other operating expenses[628] - As of December 31, 2022, the company had cash and cash equivalents of $251.2 million and an accumulated deficit of $95.7 million[612] - Existing cash and cash equivalents are expected to be sufficient to fund operations and capital expenditures through at least 2024[614] Quantitative and Qualitative Disclosures About Market Risk The company's market risks are low for interest rates and foreign currency, with inflation noted as a potential future cost factor - The company's cash and cash equivalents are held in checking accounts and money market funds, making the portfolio's fair value relatively insensitive to interest rate changes[655] - Foreign currency exchange risk is not considered material as most expenses are denominated in U.S. dollars, and the company does not have a formal hedging program[656] - Inflation has not had a material effect on financial results but is acknowledged as a factor that generally increases labor and clinical trial costs[657] Financial Statements and Supplementary Data Audited financial statements for 2022 and 2021 show total assets of $266.2 million, a $55.3 million net loss, and $50.3 million net cash used in operations Balance Sheet Highlights (in thousands) | | Dec 31, 2022 | Dec 31, 2021 | | :--- | :--- | :--- | | Assets | | | | Cash and cash equivalents | $251,213 | $302,182 | | Total current assets | $257,288 | $304,057 | | Total assets | $266,181 | $306,701 | | Liabilities and Stockholders' Equity | | | | Total current liabilities | $5,701 | $3,616 | | Total liabilities | $8,352 | $4,964 | | Total stockholders' equity | $257,829 | $301,737 | Statement of Operations Highlights (in thousands) | | Year Ended Dec 31, 2022 | Year Ended Dec 31, 2021 | | :--- | :--- | :--- | | Research and development | $43,008 | $20,636 | | General and administrative | $15,919 | $5,652 | | Loss from operations | ($58,927) | ($26,288) | | Net loss | ($55,325) | ($26,294) | | Net loss per share, basic and diluted | ($1.32) | ($1.91) | Cash Flow Highlights (in thousands) | | Year Ended Dec 31, 2022 | Year Ended Dec 31, 2021 | | :--- | :--- | :--- | | Net cash used in operating activities | ($50,285) | ($23,745) | | Net cash used in investing activities | ($559) | ($645) | | Net cash provided by financing activities | $632 | $311,348 | Controls and Procedures Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2022 - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2022[771] - Based on an assessment using the COSO framework, management concluded that the company's internal control over financial reporting was effective as of December 31, 2022[772] - No changes in internal control over financial reporting occurred during the fourth quarter of 2022 that materially affected, or are reasonably likely to materially affect, internal controls[773] PART III Directors, Executive Officers and Corporate Governance Information on directors, executive officers, and corporate governance is incorporated by reference from the 2023 proxy statement - Information regarding directors, executive officers, and corporate governance is incorporated by reference from the company's definitive proxy statement for the 2023 annual meeting[778] - The company has adopted a Code of Business Conduct and Ethics applicable to all officers, directors, and employees, which is available on its website[779] Executive Compensation Executive compensation details are incorporated by reference from the company's definitive proxy statement for the 2023 Annual Meeting - Details on executive compensation are incorporated by reference from the upcoming Definitive Proxy Statement[780] Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters Security ownership and equity compensation plan information is incorporated by reference from the 2023 definitive proxy statement - Information on security ownership and equity compensation plans is incorporated by reference from the upcoming Definitive Proxy Statement[781] Certain Relationships and Related Transactions, and Director Independence Information on related party transactions and director independence is incorporated by reference from the 2023 definitive proxy statement - Details on related transactions and director independence are incorporated by reference from the upcoming Definitive Proxy Statement[783] Principal Accounting Fees and Services Information on principal accounting fees and services is incorporated by reference from the 2023 definitive proxy statement - Information on principal accounting fees and services is incorporated by reference from the upcoming Definitive Proxy Statement[784] PART IV Exhibits and Financial Statement Schedules This section lists financial statements and exhibits filed with the 10-K, noting that all financial statement schedules are omitted - This section contains the financial statements, notes that all financial statement schedules are omitted, and references the Exhibit Index for a list of all filed exhibits[786][787][788]