Applied Therapeutics SORD 12 Month Interim Data Analysis March 2024

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INSPIRE Trial 12 Month Interim Topline Data 3 Co-primary endpoints at 12 month analysis: • Primary clinical efficacy endpoint: Statistically significant correlation between sorbitol levels and change in clinical outcomes at 12 months of treatment on combined measures of the CMT Functional Outcome Measures (CMT-FOM) lower limb domain (10 meter walk-run test, 4 stair climb, and sit to stand test), 6-minute walk test and dorsiflexion (p=0.05) • Primary pharmacodynamic/ biomarker endpoint: Sustained reduction in sorbitol level in patients treated with govorestat at 12 months, which was statistically significant compared to placebo (p<0.001). Secondary Endpoints • Highly statistically significant effect (p=0.01) impact of govorestat on the CMT Health Index (CMT-HI), an important patient-reported outcome measure of disease severity and well-being; aspects of the CMT-HI that demonstrated a treatment effect included lower limb function, mobility, fatigue, pain, sensory function, and upper limb function. • Trends (not statistically significant) on CMT-FOM measures linked to walking ability, such as 10MWR, dorsiflexion and 6 minute walk test o No substantial effect on stair climb or sit-to-stand test Safety • Govorestat was safe and well tolerated, with similar incidence of adverse events between active and placebo-treated groups Study will continue in blinded format to 24 months

4 Correlation of Sorbitol with CMT-FOM Lower Limb Measures sorbitol (ng/ml) Sum of change (z-scores) on 5 lower limb measures Lower sorbitol level at 12 months correlated with greater improvement in clinical outcomes (sum of change from baseline to 12 months across 10MWR, 4 stair climb, sit-to-stand test, 6-minute walk, dorsiflexion) • Correlation analysis performed on govorestat treated patients • *improved to p=0.03 when 3 patients with major protocol deviations were removed from analysis • Directionality of 10MWR and 4-stair climb was flipped so that improvement aligned with other tests • Statistical threshold defined as p<0.10 in statistical analysis plan p=0.05* 10,000 15,000 20,000 25,000 -0.5 -0.0 0.5 1.0 Lower Limb Composite sorbitol (ng/ml) 10MWR speed (seconds) 10 Meter Walk/Run Test p=0.03 10,000 15,000 20,000 25,000 1.0 -0.0 -1.0 -2.0

5 Govorestat Treated Patients Demonstrated a Statistically Significant Improvement in CMT-Health Index (CMT-HI) Scores at 12 Months (p=0.01 vs. placebo) Lower score (negative change from baseline) represents improvement in disease symptoms; measures with “8” were statistically significant vs. placebo with p<0.05

6 CMT-HI Change from Baseline at 12 Months (Lower Score is Improvement) CMT-HI Total Score Mobility Foot and Ankle Strength Fatigue Numbness Shoulder/Arm Function p=0.012 p=0.196 p=0.055 p=0.064 p=0.020 p=0.047 Govorestat treated group improved over 12 months, while placebo group generally worsened

7 Govorestat Treated Patients Demonstrated Trend Towards Improvement in 10MWR, Dorsiflexion and 6 Minute Walk at 12 Months For foot Dorsiflexion, the estimate and the CI were divided by 10 in order to present within the x−axis range (actual values are 10X the values on the slide); For 6-minute walk, the estimate and the CI were divided by 50 in order to present within the x−axis range (actual values are 50X the values on the slide). For 10 Meter Walk/Run and 4 Stair Climb, the 'change from baseline' value has been reversed (multiplied by -1) in order to maintain consistency of direction of interpretation in the forest plot

8 CMT-FOM Change from Baseline at 12 Months 10MWR Mean Change from Baseline (seconds, +/-SE) Mean Change from Baseline (Newtons, +/-SE) Dorsiflexion 6 Minute Walk Mean Change from Baseline (meters, +/-SE) p=0.258 p=0.314 p=0.606 Govorestat treated group improved compared to placebo on 10MWR, dorsiflexion and 6 minute walk; no effect on 4- stair climb or sit-to-stand test (not shown)

9 Placebo N=18 n (%) Govorestat N=38 n (%) Combined N=56 n (%) Age Mean (SD) 36.0 (9.23) 33.6 (11.70) 34.4 (10.94) BMI Mean (SD) 23.9 (3.57) 24.3 (4.15) 24.2 (3.94) Race White 16 (88.9%) 36 (94.7%) 52 (92.9%) Asian 1 (5.6%) 1 (2.6%) 2 (3.6%) Black 1 (5.6%) 0 (0.0%) 1 (1.8%) Other 0 (0.0%) 1 (2.6%) 1 (1.8%) Sex Male 12 (66.7%) 25 (65.8%) 37 (66.1%) Female 6 (33.3%) 13 (34.2%) 19 (33.9%) Stage of Disease Progression (defined by 10MWR speed at baseline) Mild (<5s) 12 (66.7%) 23 (60.5%) 35 (62.5%) Moderate (5.1-7.5s) 3 (16.7%) 9 (23.7%) 12 (21.4%) Severe (7.6-15s) 3 (16.7%) 6 (15.8%) 9 (16.1%) Sorbitol* 27,971ng/ml (SD=5,950) 30,934ng/ml (SD=4,360) 29,965ng/ml (SD=5,074) Baseline Demographics *For sorbitol values at baseline N=52, as samples for 4 patients were missing (not processed correctly)

10 Placebo N=18 n (%) Govorestat N=38 n (%) Combined N=56 n (%) Randomized 18 (100.0%) 38 (100.0%) 56 ( 100.0%) Ongoing 17 ( 94.4%) 34 ( 89.5%) 51 ( 91.1%) Discontinued 1 (5.6%) 4 (10.5%) 5 (8.9%) Reason for Discontinuation: Adverse Event 0 ( 0.0%) 3 (7.9%) 3 (5.4%) Reason for Discontinuation: Withdrawal By Subject 1 (5.6%) 1 ( 2.6%) 2 ( 3.6%) Patient Disposition

11 Placebo (N=18) n (%) Govorestat (N=38) n (%) Overall (N=56) n (%) Treatment Emergent Adverse Events (number of patients reporting any adverse event during the study)1 15 (83.3%) 34 (89.5%) 49 (87.5%) Mild 12 (66.7%) 33 (86.8%) 45 (80.4%) Moderate 5 (27.8%) 8 ( 21.1%) 13 (23.2%) Severe 0 (0.0%) 1 (2.6%)2 1 (1.8%) 2 Serious Adverse Events 0 (0.0%) 1 (2.6%)3 1 (1.8%)3 Deaths 0 (0.0%) 0 (0.0%) 0 (0.0%) Safety 1.Some patients reported more than one adverse event, so the sum of mild, moderate and severe is larger than the number of patients reporting an adverse event; 2. The severe adverse event was a recurrence of a pre-existing condition; 3. The serious adverse event was a motorcycle accident. Safe and well-tolerated; adverse events were well-balanced between govorestat and placebo treated groups