Core Insights - The company presented full 12-month clinical results and new topline data from 18 and 24 months of the INSPIRE Phase 2/3 trial for govorestat, aimed at treating CMT-SORD, at the Peripheral Nerve Society Annual Meeting in May 2025 [2][4][10] Group 1: Clinical Trial Results - Govorestat treatment demonstrated a statistically significant 37% reduction in sorbitol levels in the sciatic nerve of CMT-SORD rats, indicating its potential effectiveness [1] - MRI data at 24 months showed a slowing of disease progression in patients treated with govorestat compared to 12 months [8][9] - Statistically significant improvements were observed in the CMT-Health Index (CMT-HI) at 12 months, correlating with reductions in blood sorbitol levels [11][12] Group 2: Safety and Tolerability - Govorestat remained generally safe and well tolerated throughout the 24 months of treatment, with similar adverse event rates between active and placebo groups [12][11] Group 3: Regulatory Pathway and Future Plans - The company is committed to submitting a New Drug Application (NDA) for govorestat for CMT-SORD treatment in 2025 [2][10] - 90% of remaining patients from the INSPIRE trial have transitioned to an open-label extension study, indicating strong patient retention and interest in continued treatment [10] Group 4: Disease Background - CMT-SORD is a rare, progressive neuromuscular disease caused by genetic mutations affecting the sorbitol dehydrogenase enzyme, leading to high levels of sorbitol in blood and tissues [3][14] - The disease was officially recognized in 2020, and there are now commercially available tests for sorbitol and genetic testing specific to CMT-SORD [3][4]

PART I. FINANCIAL INFORMATION This section details the unaudited financial statements, management's analysis, market risk, and internal controls [Item 1. Financial Statements (Unaudited)](index=7&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) This section presents the unaudited condensed financial statements for Q1 2025, highlighting a net loss of **$(21,825) thousand** and a going concern doubt [Condensed Balance Sheets](index=7&type=section&id=Condensed%20Balance%20Sheets) Condensed Balance Sheet Highlights (in thousands) | Metric | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Cash and cash equivalents** | $50,762 | $79,398 | | **Total current assets** | $53,966 | $83,646 | | **Total Assets** | $56,907 | $86,691 | | **Total current liabilities** | $17,965 | $27,296 | | **Total Liabilities** | $20,239 | $29,685 | | **Total stockholders' equity** | $36,668 | $57,006 | - Cash and cash equivalents decreased by **$28,636 thousand** during the first quarter of 2025, from **$79,398 thousand** at the end of 2024 to **$50,762 thousand**[18](index=18&type=chunk) [Condensed Statements of Operations](index=8&type=section&id=Condensed%20Statements%20of%20Operations) Condensed Statement of Operations (in thousands, except per share data) | Metric | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Total revenue | $0 | $190 | | Research and development | $7,837 | $12,217 | | General and administrative | $17,688 | $9,066 | | Loss from operations | $(25,525) | $(21,093) | | Change in fair value of warrant liabilities | $3,104 | $(63,405) | | **Net loss** | **$(21,825)** | **$(83,938)** | | Net loss per share | $(0.15) | $(0.67) | - The net loss significantly narrowed to **$(21,825) thousand** in Q1 2025 from **$(83,938) thousand** in Q1 2024, primarily due to a positive change in the fair value of warrant liabilities, which was a **$3,104 thousand** gain in 2025 versus a **$(63,405) thousand** expense in 2024[21](index=21&type=chunk) [Condensed Statements of Stockholders' Equity/(Deficit)](index=9&type=section&id=Condensed%20Statements%20of%20Stockholders'%20Equity%2F(Deficit)) - The company's accumulated deficit grew from **$574,200 thousand** at the beginning of 2025 to **$596,025 thousand** by March 31, 2025, reflecting the net loss incurred during the quarter[26](index=26&type=chunk) [Condensed Statements of Cash Flows](index=11&type=section&id=Condensed%20Statements%20of%20Cash%20Flows) - Net cash used in operating activities was **$28,636 thousand** for the three months ended March 31, 2025, an increase from **$18,900 thousand** in the same period of 2024[28](index=28&type=chunk) - There were no financing activities in Q1 2025, in contrast to Q1 2024 when the company generated **$115,500 thousand** from financing activities, including the issuance of common stock and warrants[28](index=28&type=chunk) [Notes to Condensed Financial Statements (Unaudited)](index=12&type=section&id=Notes%20to%20Condensed%20Financial%20Statements%20(Unaudited)) - Management has concluded that substantial doubt exists regarding the company's ability to continue as a going concern for one year from the issuance of these financial statements, based on a net loss of **$(21,825) thousand** for the quarter, an accumulated deficit of **$596,025 thousand**, and cash and cash equivalents of **$50,762 thousand** as of March 31, 2025[35](index=35&type=chunk)[36](index=36&type=chunk) - The company is involved in a securities class action lawsuit and a shareholder derivative lawsuit. As of March 31, 2025, the probability of loss was deemed reasonably possible, but no liability has been recorded as the amount cannot be estimated[127](index=127&type=chunk)[129](index=129&type=chunk)[130](index=130&type=chunk) - Revenue recognized from the Advanz Pharma agreement was **$0 thousand** for the three months ended March 31, 2025, compared to **$200 thousand** in the same period of 2024, as the related research and development services performance obligation nears completion[124](index=124&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=41&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's clinical-stage status, the FDA's Complete Response Letter for govorestat, and the critical liquidity position with a going concern doubt - In November 2024, the FDA issued a Complete Response Letter for the New Drug Application (NDA) for govorestat (AT-007) for Classic Galactosemia, indicating it could not be approved in its current form. The company subsequently withdrew its European Marketing Authorization Application (MAA)[135](index=135&type=chunk) Comparison of Operating Expenses (in thousands) | Expense Category | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | Research & Development | $7,837 | $12,217 | $(4,380) | | General & Administrative | $17,688 | $9,066 | $8,622 | - The **$4,380 thousand** decrease in R&D expenses was primarily driven by a **$5,600 thousand** reduction in clinical and pre-clinical costs for AT-007 and AT-001. The **$8,622 thousand** increase in G&A expenses was mainly due to a **$9,700 thousand** rise in legal and professional fees related to litigation and responding to the FDA's CRL and warning letter[166](index=166&type=chunk)[171](index=171&type=chunk) - The company's cash and cash equivalents were **$50,762 thousand** as of March 31, 2025. Management has concluded there is substantial doubt about the company's ability to continue as a going concern for the next 12 months due to its operating losses and funding needs[170](index=170&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=62&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's market risk is primarily interest rate sensitivity on cash and foreign currency risk, neither of which is considered significant - The primary market risk is interest rate sensitivity on the company's **$50,762 thousand** in cash and cash equivalents. The investment objective is to preserve principal, and the company does not believe there is significant risk of default or illiquidity[191](index=191&type=chunk)[192](index=192&type=chunk) - Foreign currency sensitivity arises from some service agreements denominated in currencies other than the U.S. Dollar, mainly the Euro. The company does not hedge this exposure and believes a hypothetical 10% change in exchange rates would not have a material impact[193](index=193&type=chunk) [Item 4. Controls and Procedures](index=63&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were ineffective due to a material weakness in internal control over financial reporting, despite ongoing remediation efforts - Management concluded that disclosure controls and procedures were not effective as of March 31, 2025, due to a material weakness in internal control over financial reporting[196](index=196&type=chunk) - The material weakness stems from deficiencies in the information and communication component of the COSO framework, specifically a failure to ensure timely and reliable communication between the former CEO, senior management, and the board of directors[198](index=198&type=chunk) - Remediation actions include appointing a new executive chairman and interim CEO, instituting a new disclosure review process, and creating a cross-functional quality council. However, the material weakness cannot be considered fully remedied until the new controls have operated effectively for a sufficient period[199](index=199&type=chunk)[200](index=200&type=chunk)[201](index=201&type=chunk) PART II. OTHER INFORMATION This section covers legal proceedings, risk factors, equity sales, defaults, mine safety, other information, and exhibits [Item 1. Legal Proceedings](index=66&type=section&id=Item%201.%20Legal%20Proceedings) The company is involved in a consolidated securities class action and a shareholder derivative action related to govorestat NDA statements - A consolidated securities class action lawsuit (In re Applied Therapeutics Securities Litigation) alleges violations of the Securities Exchange Act by the company and certain officers/directors regarding statements made about the govorestat NDA[205](index=205&type=chunk) - A shareholder derivative action (Hassine v. Shendelman, et al.) has been filed against certain officers/directors for breach of fiduciary duty and other claims, based on substantially the same facts as the class action. This case has been temporarily stayed[206](index=206&type=chunk) [Item 1A. Risk Factors](index=66&type=section&id=Item%201A.%20Risk%20Factors) This section outlines substantial risks including financial instability, regulatory setbacks for govorestat, operational dependencies, and stock price volatility - **Financial Risks:** The company has a history of significant losses, and its independent auditor's report includes a "going concern" explanatory paragraph. A material weakness in internal control over financial reporting was identified as of December 31, 2024[212](index=212&type=chunk)[225](index=225&type=chunk)[228](index=228&type=chunk) - **Regulatory Risks:** The FDA issued a Complete Response Letter for the govorestat NDA and a Warning Letter related to a clinical study, creating significant uncertainty for the product's approval and the company's future clinical trials[212](index=212&type=chunk)[254](index=254&type=chunk)[257](index=257&type=chunk) - **Operational & Management Risks:** The company relies heavily on third parties for clinical trials and manufacturing. It recently experienced the departure of its founder and CEO, creating leadership uncertainty. The company is also defending against securities class action and shareholder derivative litigation[215](index=215&type=chunk)[216](index=216&type=chunk)[424](index=424&type=chunk) - **Stock Ownership Risks:** The company's stock price is highly volatile. It received a deficiency letter from Nasdaq for its stock price closing below the **$1.00** minimum bid price requirement for over 30 consecutive days[435](index=435&type=chunk)[441](index=441&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=149&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reported no unregistered sales of equity securities during the quarter ended March 31, 2025 - None[461](index=461&type=chunk) [Item 3. Defaults Upon Senior Securities](index=151&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item is not applicable as the company has no defaults upon senior securities to report - Not applicable[464](index=464&type=chunk) [Item 4. Mine Safety Disclosures](index=151&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company's operations - Not applicable[465](index=465&type=chunk) [Item 5. Other Information](index=151&type=section&id=Item%205.%20Other%20Information) The company states that no officer or director adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement during the first quarter of 2025 - During the three months ended March 31, 2025, no officer or director adopted or terminated a Rule 10b5-1 trading arrangement[466](index=466&type=chunk) [Item 6. Exhibits](index=152&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including employment agreements and Sarbanes-Oxley Act certifications - The report includes certifications from the Executive Chairman (Principal Executive Officer) and the Interim CEO/CFO (Principal Financial Officer) pursuant to Sarbanes-Oxley Act requirements[468](index=468&type=chunk)

Financial Performance - Cash and cash equivalents totaled $79.4 million as of December 31, 2024, compared to $49.9 million at December 31, 2023, representing a 59% increase[9] - Research and development expenses for the year ended December 31, 2024, were $48.7 million, a decrease of approximately 10% from $53.9 million for the year ended December 31, 2023[9] - General and administrative expenses increased to $56.0 million for the year ended December 31, 2024, from $20.6 million in 2023, marking an increase of approximately 172%[9] - The net loss for the year ended December 31, 2024, was $105.6 million, or $0.76 per share, compared to a net loss of $119.8 million, or $1.42 per share, for the year ended December 31, 2023[9] - Total revenue for the year ended December 31, 2024, was $455,000, a significant decrease from $9.99 million in 2023[16] - The accumulated deficit increased to $574.2 million as of December 31, 2024, compared to $468.6 million as of December 31, 2023[14] Regulatory and Strategic Developments - The company received a Complete Response Letter from the FDA regarding the New Drug Application for govorestat for Classic Galactosemia, and is evaluating its response[3] - The company is focused on preparing for potential regulatory interactions regarding govorestat in both Classic Galactosemia and SORD Deficiency[2] - The company appointed key senior executives to enhance its regulatory, medical, and quality affairs capabilities, including Todd F. Baumgartner as Chief Regulatory Officer[3] Asset Management - The total assets increased to $86.7 million as of December 31, 2024, from $54.8 million as of December 31, 2023[14]

Core Viewpoint - Applied Therapeutics, Inc. is focused on advancing its lead drug candidate, govorestat, for the treatment of rare diseases, particularly CMT-SORD and Classic Galactosemia, while preparing for upcoming regulatory interactions and clinical data presentations [2][6]. Recent Highlights - The company will present full 12-month clinical data and new topline 18-month and 24-month data from the INSPIRE Phase 3 trial of govorestat at the Peripheral Nerve Society 2025 Annual Meeting [5][6]. - Ongoing reviews of govorestat development programs for Classic Galactosemia and CMT-SORD Deficiency are progressing as planned [5][6]. Financial Results - Cash and cash equivalents and short-term investments totaled $50.8 million as of March 31, 2025, down from $79.4 million at December 31, 2024 [6]. - Research and development expenses for Q1 2025 were $7.8 million, a decrease from $12.2 million in Q1 2024, primarily due to reduced clinical and regulatory expenses [6]. - General and administrative expenses increased to $17.7 million in Q1 2025 from $9.1 million in Q1 2024, mainly due to higher legal and professional costs [6]. - The net loss for Q1 2025 was $21.8 million, or $0.15 per share, compared to a net loss of $83.9 million, or $0.67 per share, in Q1 2024 [6][13].

Core Insights - Applied Therapeutics, Inc. announced the presentation of full 12-month clinical results from the INSPIRE Phase 3 trial of govorestat (AT-007) at the Peripheral Nerve Society 2025 Annual Meeting, along with new topline 18-month and 24-month data [1] - The INSPIRE Phase 3 trial is a double-blind, placebo-controlled study evaluating govorestat's effect on patients with Sorbitol Dehydrogenase (SORD) Deficiency, a subtype of Charcot-Marie-Tooth (CMT) disease [1] - Govorestat is a central nervous system penetrant Aldose Reductase Inhibitor being developed for multiple rare diseases, including CMT-SORD, Classic Galactosemia, and PMM2-CDG [2][4] Presentation Details - The oral presentation titled "INSPIRE CMT-SORD Clinical Trial: Month 18 and Month 24 INSPIRE Trial Results and Designing the Next Randomized Study" will be presented by Dr. Evan Bailey on May 18, 2025 [2] - The presentation is scheduled for 12:25 - 12:40 p.m. BST [2] Regulatory Designations - Govorestat has received Orphan Medicinal Product Designation from the European Medicines Agency for both Galactosemia and CMT disease [3] - It has also received Orphan Drug Designation from the U.S. FDA for Galactosemia, PMM2 deficiency, and SORD Deficiency, along with Rare Pediatric Disease designation for Galactosemia and PMM2-CDG, and Fast Track designation for Galactosemia [3] Company Overview - Applied Therapeutics is a clinical-stage biopharmaceutical company focused on developing novel drug candidates targeting rare diseases [4] - The lead drug candidate, govorestat, is aimed at treating CNS rare metabolic diseases, including Classic Galactosemia, CMT-SORD, and PMM2-CDG [4]

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-38898 Applied Therapeutics, Inc. (Exact name of registrant as specified in its charter) Delaware 81-3405262 (State ...

Core Viewpoint - Applied Therapeutics, Inc. reported its financial results for the fourth quarter and full year ended December 31, 2024, highlighting key leadership appointments and ongoing development programs for its lead drug candidate, govorestat, aimed at addressing unmet medical needs in rare diseases [1][2]. Leadership Appointments - John H. Johnson was appointed as Executive Chairman, and Les Funtleyder was named Interim Chief Executive Officer [5]. - Todd F. Baumgartner, MD, MPH was appointed as Chief Regulatory Officer, and Reena Thomas Colacot was appointed as Vice President and Head of Quality [5]. Development Programs - The company is focused on regulatory interactions regarding govorestat for Classic Galactosemia and Sorbitol Dehydrogenase (SORD) Deficiency [2]. - A Complete Response Letter (CRL) was received from the FDA for the NDA submitted for govorestat for Classic Galactosemia, and the company is evaluating its response [5]. Financial Results - Cash and cash equivalents increased to $79.4 million as of December 31, 2024, from $49.9 million at the end of 2023 [5]. - Research and development expenses decreased to $48.7 million in 2024 from $53.9 million in 2023, primarily due to reduced clinical and drug manufacturing costs [5]. - General and administrative expenses rose to $56.0 million in 2024 from $20.6 million in 2023, largely due to increased commercial and legal expenses [5]. - The net loss for 2024 was $105.6 million, or $0.76 per share, compared to a net loss of $119.8 million, or $1.42 per share, in 2023 [5][12]. Revenue Overview - Total revenue for 2024 was $455,000, a decrease from $9.99 million in 2023, with no license revenue reported for the year [12].

Core Viewpoint - Applied Therapeutics, Inc. has filed a Form 12b-25 with the SEC for a late filing of its Annual Report on Form 10-K for fiscal year 2024, granting an automatic 15-day extension to file the report by April 15, 2025 [1] Company Overview - Applied Therapeutics is a clinical-stage biopharmaceutical company focused on developing novel drug candidates targeting validated molecular pathways in rare diseases [3] - The lead drug candidate, govorestat, is an Aldose Reductase Inhibitor designed for treating central nervous system rare metabolic diseases, including Classic Galactosemia, SORD Deficiency, and PMM2-congenital disorder glycosylation [3] Filing Details - The Form 12b-25 allows the company additional time to finalize its financial statements, with the expectation to file the Form 10-K by April 15, 2025 [1] - The filing is accessible on the company's Investor Relations website under "SEC Filings" [2] - A subsequent announcement will be made to disclose the fourth quarter and full-year 2024 earnings results once the Form 10-K filing date is confirmed [2]

Core Insights - Applied Therapeutics, Inc. has appointed Todd F. Baumgartner, MD, MPH as Chief Regulatory Officer to lead the company's global regulatory strategy [1][3] - Dr. Baumgartner brings over 35 years of experience in drug development and has successfully led 12 New Drug Applications and marketing authorizations [2] - The company is focused on advancing its lead drug candidate, govorestat, for the treatment of rare diseases [4] Company Overview - Applied Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing novel drug candidates targeting rare diseases [4] - The lead drug candidate, govorestat, is an Aldose Reductase Inhibitor aimed at treating CNS rare metabolic diseases [4] Leadership Background - Dr. Baumgartner previously served as Senior Vice President of Global Regulatory Affairs at Ovid Therapeutics, overseeing multiple development functions [2] - He has held senior roles at Acorda Therapeutics, Purdue Pharma, AstraZeneca Pharmaceuticals, and Bristol-Myers Squibb [2]

Core Viewpoint - Rosen Law Firm is reminding investors who purchased securities of Applied Therapeutics, Inc. during the specified class period of the upcoming lead plaintiff deadline on February 18, 2025 [1]. Group 1: Class Action Details - Investors who purchased Applied Therapeutics securities between January 3, 2024, and December 2, 2024, may be entitled to compensation without any out-of-pocket fees through a contingency fee arrangement [2]. - A class action lawsuit has already been filed, and interested parties must move the Court to serve as lead plaintiff by February 18, 2025 [3]. - Investors can join the class action by visiting the provided link or contacting the law firm directly for more information [6]. Group 2: Law Firm Credentials - Rosen Law Firm emphasizes the importance of selecting qualified counsel with a successful track record in securities class actions, highlighting its own achievements in this area [4]. - The firm has secured significant settlements for investors, including over $438 million in 2019 and has been consistently ranked among the top firms for securities class action settlements since 2013 [4]. Group 3: Case Allegations - The lawsuit alleges that Applied Therapeutics made false and misleading statements regarding its clinical trial protocols, which created a false impression of compliance with good clinical practices [5]. - It is claimed that the company's failure to adhere to trial protocols posed a severe risk of rejection of trial data by the U.S. Food and Drug Administration (FDA) during the New Drug Application process [5].