EX-99.2 6 tm2313498d1_ex99-2.htm EXHIBIT 99.2
Exhibit 99.2

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ACTION-Galactosemia Kids (AT-007-1002) Clinical Trial Update April 24, 2023

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Disclaimer The information contained herein is strictly confidential and is being provided to you solely for your information and to assist you in making your own evaluation of Applied Therapeutics, Inc. (the “Company”). For the purposes of this disclaimer, the presentation includes all statements made orally by any representative or advisor of the Company at any meeting where the slides accompanying this disclaimer are provided as well as the slides themselves. Your acceptance of these materials constitutes your agreement to hold the information contained herein in strict confidence. This presentation has been prepared for informational purposes only. By attending or receiving this presentation you acknowledge that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of our business. This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 about the Company that involve substantial risks and uncertainties. All statements, that are not statements of historical fact, regarding the strategy, future operations, prospects, plans and objectives of management, including words such as “may,” “will,” “expect,” “anticipate,” “plan,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are forward-looking statements. The Company cautions that these statements are subject to a number of known and unknown risks, uncertainties and other factors, many of which are beyond the Company’s ability to control or predict, and any forward-looking statements in this presentation and any accompanying oral presentation are not a guarantee of future performance and actual results may differ materially from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, without limitation; our plans to develop, market and commercialize our product candidates; the initiation, timing, progress and results of our current and future preclinical studies and clinical trials and our research and development programs; our ability to take advantage of expedited regulatory pathways for any of our product candidates; our estimates regarding expenses, future revenue, capital requirements and needs for additional financing,; our ability to successfully acquire or license additional product candidates on reasonable terms and advance product candidates into, and successfully complete, clinical studies; our ability to maintain and establish collaborations or obtain additional funding; our ability to obtain and timing of regulatory approval of our current and future product candidates; the anticipated indications for our product candidates, if approved; our expectations regarding the potential market size and the rate and degree of market acceptance of such product candidates;) our ability to fund our working capital requirements and expectations regarding the sufficiency of our capital resources; the implementation of our business model and strategic plans for our business and product candidates; our intellectual property position and the duration of our patent rights; developments or disputes concerning our intellectual property or other proprietary rights; our expectations regarding government and third-party payor coverage and reimbursement; our ability to compete in the markets we serve; the impact of government laws and regulations and liabilities thereunder; developments relating to our competitors and our industry; our ability to achieve the anticipated benefits from the agreements entered into in connection with our partnership with Advanz Pharma and; other factors described in our Annual Report on Form 10-K for the fiscal year ended December 31, 2022, as filed with the Securities and Exchange Commission on March 23, 2023, and our subsequent filings with the SEC. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. Although we believe that we have a reasonable basis for each forward-looking statement contained in this presentation, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur at all. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise.

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Overview • We believe that govorestat (AT-007) impacts clinically meaningful aspects of the Galactosemia disease phenotype alongside a favorable safety profile, and we plan to seek approval in both US and EU based on current data. • Govorestat has previously demonstrated a significant reduction in galactitol level (a toxic metabolite formed in Galactosemia patients), which has now translated into consistent improvement on clinical and functional endpoints, including behavior, daily living skills, cognition, fine motor skills, adaptive skills and tremor over 18 months of treatment compared to placebo. • The primary endpoint and pre-specified sensitivity analysis including cognition showed clinically meaningful trends toward improvement with p-values of 0.1030 and 0.0698, respectively. • All components of the primary endpoints are positively impacted with govorestat treatment, except for speech; post-hoc analysis of primary endpoint without speech showed statistical significance (p= 0.0205 at 18 months). • Key secondary endpoints of adaptive behavior skills and tremor achieved robust and clinically meaningful improvement with p-values of 0.0265 and 0.0428, respectively, over 18 months of treatment compared to placebo. • Govorestat was safe and well-tolerated with no serious adverse events (SAEs) in the trial and no imbalance in adverse events (AEs) or lab values between the active and placebo groups in the pediatric study.

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Next Steps and Market Opportunity • If approved, govorestat will be the first and only treatment for Galactosemia, a devastating rare neurological disease that progressively worsens over time; dietary restriction prevents death, but does not prevent progression of long-term complications of Galactosemia due to endogenous synthesis of galactose by the body. • Galactosemia affects approximately 3,000 patients in the US and 4,000 in Europe, with a growth year over year of approximately 200 patients (due to new births); the patient population is well-identified and diagnosed in the US and Europe due to mandatory newborn screening. • Govorestat treatment for Galactosemia represents a substantial revenue opportunity. • The European Medicines Agency (EMA) has already provided feedback supportive of potential approval in Europe for govorestat for Galactosemia based on existing data; an MAA submission is planned for Q3 2023 • The Company will request a pre-NDA meeting as soon as possible to discuss an FDA submission based on the current data; if acceptable to the FDA, will target NDA submission in Q3 2023 • The Company also plans in the near-term to request a pre-NDA meeting with the Neurology Division regarding SORD approval based on existing sorbitol reduction data. We believe SORD 12 month clinical outcomes data and DbCM Phase 3 data also provide meaningful catalysts towards the end of the year.

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5 AT-007 ACTION-Galactosemia Kids Pediatric Registrational Clinical Study (47 Children Age 2-17) AT-007 Dose Escalation Biomarker Assessment of Galactitol Placebo cross to active once treatment effect on outcomes is demonstrated PK/PD Dose Range Finding & Biomarker Data Long-Term Clinical Outcomes Placebo Screening/ Baseline 2:1 Randomization to Active or Placebo Clinical Outcomes Assessed Every 6 Months by Firewalled Committee Baseline Clinical Outcomes Pediatric Study OWLS 2 Oral Expression Listening Comprehension Speech NIH Toolbox Cognition Battery Cognition BASC-Behavioral Symptoms BASC-Daily Living Skills Behavior NIH Toolbox 9-Hole Pegboard Test Motor Primary Endpoint: Global Assessment of Change (Global Statistical Test) Composite Sum of Change in CNS function BASC-Adaptive Skills Index Adaptive Skills Archimedes Spiral Drawing Test Tremor Primary Sensitivity Analysis Key Secondary Endpoints Changes in primary endpoint (movement of cognition and motor skills to sensitivity analyses) was based on recent FDA advice letters Weight-based dosing: 15mg/kg>40kg; 20mg/kg 20-40kg; 30mg/kg<20kg

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6 Activities of Daily Living (BASC-ADL); Behavior (BASC-Behavioral Index); Speech includes Expressive Language (OWLS-OE) & Receptive Language (OWLS-LC) Sensitivity analysis including 9-Hole PegBoard Test p = 0.0937 at 18 months) Baseline Month 6 Month 12 Month 18 Mean Composite Score (Scaled) Baseline Month 6 Month 12 Month 18 Mean Composite Score (Scaled) Compelling Improvement in Primary Endpoint over 18 Months Across Multiple Clinical Domains Primary Endpoint: Global Statistical Test (Composite Sum of Change): Activities of Daily Living, Behavior, and Speech Primary Sensitivity Analysis: Primary Endpoint + Cognition Baseline Month 6 Month 12 Month 18 Mean Composite Score (Scaled) Post-hoc analysis of primary endpoint without speech (Activities of Daily Living + Behavior) govorestat placebo p=0.1510 p=0.0803 p=0.0205 p=0.1030 p=0.1503 p=0.2886 p=0.2448 p=0.1715 p=0.0698

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Improvement in Galactitol Biomarker Translates into Consistent Clinical Benefit Across Activities of Daily Living, Behavior, Cognition, Adaptive Skills and Tremor 7 Weight Group AT-007 Dose (QD) % Reduction From Baseline >40kg 15mg/kg 38.29% 20-40kg 20mg/kg 41.43% <20kg 30mg/kg 39.83% All groups 15-30mg/kg 40.19% (p<0.001) • Significant improvement in galactitol biomarker vs. placebo • Sustained over time through 18 months of treatment • No compensatory increase in galactose or Gal-1p Daily Living Behavior Adaptive Skills Cognition Receptive Language Expressive Language Tremor Mean difference between govorestat vs. placebo (Standard scores or T scores) Speech endpoints were not impacted by govorestat treatment, which is suspected to be due to lack of progression in the placebo group and concomitant speech therapy received by almost all children in the trial. Of note, patients with severe speech deficits showed a favorable trend towards improvement with AT-007 vs. placebo. Tremor is measured on a different scale vs. other tests, and is referenced by the right hand y axis Fine Motor Mean difference between govorestat vs. placebo (tremor rating scale)

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Consistent Improvement on Activities of Daily Living with Govorestat vs. Placebo 8 Biomarker Activities of Daily Living Behavior Cognition Adaptive Skills Tremor Baseline Month 6 Month 12 Month 18 Mean Change From Baseline Score p= 0.0519 Improvement in Activities of Daily Living (ADL) as Measured by Behavioral Assessment Scales for Children (BASC) govorestat placebo

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Consistent Improvement in Behavioral with Govorestat vs. Placebo 9 Biomarker Activities of Daily Living Behavior Cognition Adaptive Skills Tremor Baseline Month 6 Month 12 Month 18 Mean Change From Baseline Score p=0.1045 Improvement in Behavioral Symptoms Index as Measured by BASC govorestat placebo

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Consistent Improvement in Cognition with Govorestat vs. Placebo 10 Biomarker Activities of Daily Living Behavior Cognition Adaptive Skills Tremor Baseline Month 6 Month 12 Month 18 Mean Change From Baseline Score Improvement in Cognition as Measured by NIH Toolbox Cognition Battery p= 0.2625 govorestat placebo

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Consistent Improvement in Adaptive Skills with Govorestat vs. Placebo 11 Biomarker Activities of Daily Living Behavior Cognition Adaptive Skills Tremor Improvement in Adaptive Skills as Measured by BASC Baseline Month 6 Month 12 Month 18 Mean Change From Baseline Score p= 0.0265 govorestat placebo

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Consistent Improvement in Tremor with Govorestat vs. Placebo 12 Biomarker Activities of Daily Living Behavior Cognition Adaptive Skills Tremor Baseline Month 6 Month 12 Month 18 Mean Change From Baseline Score Improvement in Tremor as Measured by Archimedes Spiral Drawing Test p= 0.0428 Note: Spiral drawing is scored on a much smaller scale of 0-4; as compared to other tests (BASC is scaled on a T score of 0-50 and NIH Cognition is scaled on a standard score of 0-100) govorestat placebo

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Safety Summary 13 • All AEs were mild to moderate • AEs & lab values between AT-007 and placebo groups were balanced Placebo (N=16) Number (%) of Subjects Govorestat (N=31) Number (%) of Subjects Subjects Reporting at Least One TEAE 16 (100%) 30 (96.8%) Gastrointestinal disorders 11 (68.8%) 23 (74.2%) Hepatic enzyme increased 2 (12.5%) 8 (25.8%) Urine albumin/creatinine ratio increased 7 (43.8%) 5 (16.1%) Urine protein/creatinine ratio increased 3 (18.8%) 2 (6.5%) Renal & Urinary Disorders 1 (6.3%) 3 (9.7%) Infections and infestations 10 (62.5%) 18 (58.1%) • AT-007 was safe and well-tolerated with no serious adverse events Refers to patients having reported at least 1 term in AE category; AE, adverse event

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Full Enrollment Completed 15 Month Clinical Outcomes Primary Endpoint Peak VO2 27 Month Clinical Outcomes including morbidity/ mortality DbCM DbCM Phase 3 Key Projected Milestones by Program 14 2022 2023 2024 3 Month Biomarker Data – Sorbitol & NFL 12 Month & Clinical Outcomes Data 24 Month Data Clinical Outcomes SORD SORD Phase 3 6 Month Clinical Outcomes 12 Month Clinical Outcomes 18 Month Clinical Outcomes Open Label/ Compassionate Use Galactosemia Galactosemia Pediatric Phase 3 Potential MAA and NDA Submissions Potential MAA and NDA Approvals

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Appendix 15

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16 Expressive Language (OWLS-OE) Baseline Month 6 Month 12 Month 18 Mean Change From Baseline Score Baseline Month 6 Month 12 Month 18 Receptive Language (OWLS-LC) Mean Change From Baseline Score p=0.8169 p=0.8536 Speech Endpoints Were Not Impacted by Govorestat Treatment, Likely Due to Speech Therapy Across Both Active and Placebo Groups govorestat placebo Note: for 9-Hole Pegboard test, a baseline imbalance existed between the govorestat and placebo group with more patients on speech therapy in the placebo arm at baseline; additionally children who were not on speech therapy at baseline started speech therapy over the course of the trial in both active and placebo groups