Werewolf Therapeutics(HOWL) - 2023 Q4 - Annual Report

PART I Business Werewolf Therapeutics is a biopharmaceutical company developing conditionally activated immunotherapies for cancer using its proprietary PREDATOR platform. Its lead clinical candidates are WTX-124 (IL-2) and WTX-330 (IL-12), both in Phase 1/1b trials. The company has a collaboration with Jazz Pharmaceuticals for JZP898 (IFNα) and a pipeline of preclinical assets including WTX-712 (IL-21) and WTX-518 (IL-18). The business model relies on internal development, strategic partnerships, and robust intellectual property protection, while navigating a competitive landscape and complex regulatory environment Company Overview and Pipeline Werewolf Therapeutics is a biopharmaceutical company developing conditionally activated INDUKINE molecules to treat cancer by stimulating the immune system within the tumor microenvironment (TME). Their proprietary PREDATOR platform engineers these molecules to remain inactive in peripheral tissues, aiming to reduce systemic toxicity. The clinical pipeline includes WTX-124 (IL-2) and WTX-330 (IL-12), both in Phase 1 trials. They have licensed JZP898 (IFNα) to Jazz Pharmaceuticals and have preclinical candidates WTX-712 (IL-21) and WTX-518 (IL-18) - The company's core technology is the PREDATOR platform, used to create conditionally activated INDUKINE molecules designed to be selectively activated in the tumor microenvironment (TME)[23] Clinical and Preclinical Pipeline | Product Candidate | Target | Stage | Rights | |---|---|---|---| | WTX-124 | IL-2 | Phase 1/1b Clinical Trial | Worldwide | | WTX-330 | IL-12 | Phase 1 Clinical Trial | Worldwide | | JZP898 (WTX-613) | IFNα | Phase 1 Clinical Trial (by Jazz) | Licensed to Jazz Pharmaceuticals | | WTX-712 | IL-21 | Preclinical | Worldwide | | WTX-518 | IL-18 | Preclinical | Worldwide | Our Programs The company is advancing several INDUKINE molecules. WTX-124 (IL-2) is in a Phase 1/1b trial, with preliminary data showing tolerability and tumor shrinkage at the 12 mg dose. WTX-330 (IL-12) is in a Phase 1 trial for immunotherapy-resistant tumors, with initial data expected in Q2 2024. JZP898 (IFNα) is in a Phase 1 trial run by partner Jazz Pharmaceuticals. Preclinical candidates WTX-712 (IL-21) and WTX-518 (IL-18) are in development, with data presentations planned for the first half of 2024 - WTX-124 (IL-2): A Phase 1/1b clinical trial is ongoing for advanced solid tumors. Preliminary data from monotherapy cohorts showed the drug was generally well-tolerated up to 12 mg, with tumor shrinkage observed in three of five evaluable patients at that dose level[50][51] - WTX-330 (IL-12): A Phase 1 clinical trial was initiated in February 2023 for patients with immunotherapy-resistant tumors. Initial data is expected in the second quarter of 2024[57] - JZP898 (IFNα): Partner Jazz Pharmaceuticals received IND clearance in Q3 2023 and initiated a Phase 1 clinical trial in Q4 2023[63] - Preclinical data for WTX-712 (IL-21) and WTX-518 (IL-18) are planned for presentation in the first half of 2024[64][65] Competition Werewolf Therapeutics faces substantial competition from major pharmaceutical and biotechnology companies developing immunotherapies. For its lead candidate WTX-124 (IL-2), competitors include companies with approved products like Proleukin and numerous others with clinical-stage IL-2 molecules such as Roche, Merck, and Xilio Therapeutics. For WTX-330 (IL-12), while no IL-12 therapies are currently approved, several companies including Sanofi, Bristol-Myers Squibb, and Xilio Therapeutics have programs in development - WTX-124 (IL-2) faces competition from the approved product Proleukin (aldesleukin) and numerous clinical-stage programs from companies including Anaveon, Ascendis Pharma, BioNTech, Merck, Roche, and Xilio Therapeutics[70] - WTX-330 (IL-12) competes with clinical and preclinical programs from companies such as Sanofi (Amunix), DEKA Biosciences, DragonFly Therapeutics, Juno Therapeutics (Bristol-Myers Squibb), and Xilio Therapeutics[71] Intellectual Property The company's intellectual property strategy focuses on securing patent protection for its PREDATOR platform, product candidates (WTX-124, WTX-330, JZP898, WTX-712, WTX-518), and related technologies. As of February 29, 2024, its portfolio included approximately 6 issued U.S. patents and over 130 pending U.S. and foreign applications, with patents expected to expire between 2039 and 2044. The company also in-licenses key technology from Harpoon Therapeutics related to serum albumin binding domains, which are incorporated into its product candidates and protected by patents extending through 2037 - As of February 29, 2024, the patent portfolio includes approximately 6 issued U.S. patents, 30 pending U.S. applications, 5 pending PCT applications, and 95 pending foreign applications. Patents, if issued, are expected to expire between 2039 and 2044[89] - The company has five patent families for WTX-124 (IL-2), including issued patents in the U.S., Australia, and Europe, with protection running through 2039-2042[92][93] - The company has five patent families for WTX-330 (IL-12), including two issued U.S. patents, with protection running through 2039-2043[94] - The company in-licenses patents from Harpoon Therapeutics for single immunoglobulin variable domains that bind human serum albumin, used in its product candidates. This licensed patent family has protection through 2037[99] Government Regulation The company's operations are subject to extensive regulation by the FDA in the U.S. and similar authorities abroad, covering all stages from research and development to post-approval marketing. Key regulatory frameworks include the FDCA and PHSA, requiring preclinical studies (GLP), IND submissions, and multi-phase clinical trials (GCP) to establish safety and efficacy before a BLA can be submitted for approval. Recent legislative changes like FDORA and the IRA have introduced new requirements for clinical trial diversity, accelerated approval pathways, and Medicare price negotiations, which could significantly impact development timelines, costs, and future revenue - The company must comply with FDA regulations for drug and biologic development, including GLP for preclinical studies, IND submission before human trials, and GCP for all clinical phases[112][113] - The Inflation Reduction Act of 2022 (IRA) introduced significant changes, including authorizing Medicare to negotiate prices for certain drugs (beginning in 2026) and imposing rebates for price increases that outpace inflation, which could impact future product pricing and profitability[203][204] - The Food and Drug Omnibus Reform Act (FDORA) of 2022 requires sponsors to submit a diversity action plan for pivotal studies and grants the FDA more authority over the accelerated approval process, including requiring confirmatory trials to be underway before approval[124][162] Human Capital As of December 31, 2023, Werewolf Therapeutics had 47 full-time employees, with 34 engaged in research and development. The team includes 20 individuals with M.D. or Ph.D. degrees. The company focuses on attracting, retaining, and developing its employees through competitive compensation, equity incentives, and professional development opportunities, while fostering a commitment to diversity, equity, and inclusion - As of December 31, 2023, the company had 47 full-time employees[211] - Of the full-time employees, 34 are engaged in research and development, and 20 hold M.D. or Ph.D. degrees[211] Risk Factors The company faces numerous risks, including a limited operating history, significant financial losses, and the need for substantial additional funding. Its business is highly dependent on the success of its early-stage INDUKINE molecules and unproven PREDATOR platform. Key risks involve clinical trial delays and failures, manufacturing complexities for novel biologics, reliance on third parties for clinical trials and manufacturing, and intense competition. Intellectual property risks include the ability to obtain and enforce patents. Regulatory hurdles, potential healthcare reforms affecting pricing, and the identified material weakness in internal financial controls also pose significant threats - The company has a limited operating history, has incurred significant losses ($37.4 million net loss in 2023), and expects to incur substantial losses for the foreseeable future[217][218] - The PREDATOR platform and INDUKINE molecule approach are unproven, and the business is highly dependent on the success of its early-stage candidates, WTX-124 and WTX-330[235][244] - A material weakness in internal control over financial reporting was identified in Q2 2023 related to the purchasing process, which was not fully remediated as of December 31, 2023[498][501] - The company relies on third parties for conducting clinical trials and for all cGMP manufacturing of its product candidates, making it vulnerable to their performance and capacity[304][310] - The company faces substantial competition from major pharmaceutical companies with greater resources, particularly in the IL-2 and IL-12 therapy spaces[285][291] Cybersecurity The company has implemented processes for managing cybersecurity risks, overseen by the Director of Operations and the audit committee of the board. These processes include technical safeguards, employee training, and third-party penetration testing. The company does not believe any known cybersecurity threats are reasonably likely to materially affect its business, strategy, or financial condition - The company has processes to identify, assess, and mitigate cybersecurity risks, including employee training, technology tools, and third-party penetration testing[513] - The Director of Operations leads cybersecurity oversight, with the audit committee of the board of directors providing overall governance and receiving periodic updates[516] Properties The company's principal facilities consist of 25,778 square feet of leased office and laboratory space in Watertown, Massachusetts. The lease for this facility expires in May 2030 - The company leases 25,778 square feet of office and laboratory space in Watertown, Massachusetts, under a lease that expires in May 2030[517] PART II Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Werewolf Therapeutics' common stock is traded on The Nasdaq Global Select Market under the symbol 'HOWL'. As of March 1, 2024, there were approximately 21 holders of record. The company has never paid cash dividends and does not anticipate doing so in the foreseeable future, intending to retain earnings for business development. No equity securities were repurchased by the company during the reporting period - The company's common stock trades on The Nasdaq Global Select Market under the symbol 'HOWL'[521] - The company has never declared or paid cash dividends and does not intend to in the foreseeable future[522] Management's Discussion and Analysis of Financial Condition and Results of Operations For the year ended December 31, 2023, Werewolf Therapeutics reported revenue of $19.9 million, up from $16.4 million in 2022, primarily from its collaboration with Jazz Pharmaceuticals. The net loss decreased to $37.4 million from $53.8 million in 2022, driven by higher revenue and a $12.0 million reduction in R&D expenses, mainly due to lower manufacturing costs. As of December 31, 2023, the company had $134.3 million in cash and cash equivalents, which, along with subsequent ATM proceeds, is expected to fund operations through at least Q2 2025. The company drew down a $40.0 million term loan in March 2023 Results of Operations For the year ended December 31, 2023, revenue increased to $19.9 million from $16.4 million in 2022, due to achieving a variable consideration component in the Jazz collaboration. Research and development expenses decreased by $12.0 million to $41.8 million, primarily from a $14.3 million reduction in manufacturing costs, partially offset by increased clinical trial and personnel costs. General and administrative expenses remained flat at $18.7 million. The net loss for 2023 was $37.4 million, a significant improvement from the $53.8 million net loss in 2022 Results of Operations Summary (in thousands) | | Year Ended Dec 31, 2023 | Year Ended Dec 31, 2022 | $ Change | |---|---|---|---| | Collaboration revenue | $19,943 | $16,401 | $3,542 | | Research and development | $41,776 | $53,761 | $(11,985) | | General and administrative | $18,670 | $18,696 | $(26) | | Operating loss | $(40,503) | $(56,056) | $15,553 | | Net loss | $(37,368) | $(53,810) | $16,442 | - The $12.0 million decrease in R&D expenses was primarily driven by a $14.3 million decrease in manufacturing costs for WTX-124, WTX-330, and JZP898, and a $2.3 million decrease in contract research organization costs[561][562] - The decrease in R&D expenses was partially offset by a $2.2 million increase in clinical trial costs for WTX-124 and WTX-330, and a $1.1 million increase in personnel costs[562] Liquidity and Capital Resources As of December 31, 2023, the company had $134.3 million in cash and cash equivalents. Operations have been funded through private placements, an IPO, payments from the Jazz collaboration, an at-the-market (ATM) stock offering, and a term loan facility. In March 2023, the company drew down $40.0 million from its term loan with PWB. Through its ATM offering, the company raised net proceeds of $34.0 million as of year-end 2023 and has subsequently raised additional funds. Management expects current cash to fund operations through at least the second quarter of 2025 but will require substantial additional funding for future development - As of December 31, 2023, the company had cash and cash equivalents of $134.3 million and an accumulated deficit of $344.1 million[568] - In March 2023, the company drew down the full $40.0 million available under its term loan facility with Pacific Western Bank (PWB)[571] - As of December 31, 2023, the company had sold an aggregate of 11,259,548 shares under its ATM Offering for net proceeds of $34.0 million. The program was subsequently expanded[577] - The company expects its existing cash and cash equivalents, plus subsequent ATM proceeds, will be sufficient to fund operations through at least the second quarter of 2025[579] Controls and Procedures Management, including the CEO and CFO, concluded that the company's disclosure controls and procedures were not effective as of December 31, 2023. This was due to a previously reported material weakness in internal control over financial reporting related to the purchasing process. Although significant remediation efforts were undertaken in 2023, including hiring personnel and implementing new processes, the controls were not in place long enough to demonstrate operating effectiveness. Management believes the financial statements are fairly presented despite this weakness and is committed to completing remediation - Management concluded that disclosure controls and procedures were not effective as of December 31, 2023, due to a material weakness in internal control over financial reporting[598] - The material weakness, first reported for Q2 2023, relates to design and operating deficiencies in the purchasing process, including invoice application and expense estimation for purchase orders[603] - Remediation efforts in 2023 included hiring additional accounting personnel, reviewing the procurement process, and engaging a professional services firm. However, these measures were not in place long enough to be considered fully remediated by year-end[604][605] PART III Directors, Executive Officers and Corporate Governance Information regarding directors, executive officers, corporate governance, and delinquent Section 16(a) reports is incorporated by reference from the company's definitive proxy statement for its 2024 Annual Meeting of Stockholders. The company has adopted a code of business conduct and ethics, which is available on its website - Required information is incorporated by reference from the company's 2024 Annual Meeting of Stockholders proxy statement[612] - The company has adopted a code of business conduct and ethics applicable to all directors, officers, and employees[613] Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters Information regarding security ownership is incorporated by reference from the 2024 proxy statement. As of December 31, 2023, under the company's equity compensation plans, 6,120,474 securities were to be issued upon exercise of outstanding options and rights, with a weighted-average exercise price of $6.82. There were 2,418,773 securities remaining available for future issuance under these plans Equity Compensation Plan Information as of December 31, 2023 | Plan Category | Number of Securities to be Issued upon Exercise (a) | Weighted-Average Exercise Price of Outstanding Options (b) | Number of Securities Remaining Available for Future Issuance (c) | |---|---|---|---| | Equity compensation plans approved by security holders | 6,120,474 | $6.82 | 2,418,773 | | Total | 6,120,474 | $6.82 | 2,418,773 | PART IV Financial Statements and Exhibits This section contains the company's consolidated financial statements for the years ended December 31, 2023 and 2022, and the report from the independent registered public accounting firm, Ernst & Young LLP. The financial statements detail the company's financial position, results of operations, and cash flows. Key notes to the financial statements provide further detail on the Jazz collaboration, debt facilities, stock-based compensation, and income taxes. The section also includes an index of all exhibits filed with the report Consolidated Financial Statements The consolidated financial statements for the years ended December 31, 2023 and 2022, show a decrease in net loss from $53.8 million to $37.4 million. Total assets increased from $160.2 million to $174.8 million, primarily due to an increase in cash and restricted cash from financing activities. Total liabilities rose from $37.9 million to $63.5 million, largely driven by the drawdown of a $40.0 million note payable. Stockholders' equity decreased from $122.3 million to $111.4 million Consolidated Balance Sheet Data (in thousands) | | Dec 31, 2023 | Dec 31, 2022 | |---|---|---| | Assets | | | | Cash and cash equivalents | $134,343 | $129,315 | | Total current assets | $138,370 | $140,200 | | Total assets | $174,833 | $160,245 | | Liabilities & Equity | | | | Total current liabilities | $19,378 | $23,989 | | Note payable, net | $39,323 | $0 | | Total liabilities | $63,459 | $37,908 | | Total stockholders' equity | $111,374 | $122,337 | Consolidated Statement of Operations Data (in thousands) | | Year Ended Dec 31, 2023 | Year Ended Dec 31, 2022 | |---|---|---| | Collaboration revenue | $19,943 | $16,401 | | Total operating expenses | $60,446 | $72,457 | | Operating loss | $(40,503) | $(56,056) | | Net loss | $(37,368) | $(53,810) | | Net loss per share | $(1.05) | $(1.86) | Notes to Consolidated Financial Statements The notes provide detailed explanations of the company's accounting policies and financial results. Key details include the recognition of $19.9 million in revenue from the Jazz collaboration in 2023, which includes a $5.0 million variable payment. The company drew down a $40.0 million term loan in 2023. As of Dec 31, 2023, the company had $96.6 million in federal NOL carryforwards and a full valuation allowance against its deferred tax assets. Stock-based compensation expense was $8.0 million in 2023. The company also details its lease obligations and license agreements with Harpoon and Adimab - In April 2022, the company entered into a collaboration agreement with Jazz Pharmaceuticals, receiving a $15.0 million upfront payment and a $5.0 million variable payment in July 2023. Revenue is recognized using a cost-to-cost input method[680][681][687] - In April 2022, the company entered a loan agreement with PWB for up to $40.0 million, which was fully drawn down in March 2023. The loan requires interest-only payments until August 31, 2024[700] - As of December 31, 2023, the company had federal net operating loss (NOL) carryforwards of $96.6 million and state NOLs of $44.9 million. A full valuation allowance is maintained against deferred tax assets[747] - Total stock-based compensation expense was $8.0 million in 2023, compared to $7.4 million in 2022[718]