Foresee Pharmaceuticals Co., Ltd. announced the primary endpoint data of FP-025 in an allergic asthma Phase 2a trial. Date of occurrence of the event: April 4, 2023. New drug name or code: FP-025, a Matrix metalloproteinase-12 (MMP-12) inhibitor.

Indication: Planned development stages: Phase 2b clinical trial, followed by a phase 3 clinical trial, and New Drug Application submission. Current development stage: Application submission/approval/disapproval/each of clinical trials (include interim analysis): (A) Clinical Study Design: Protocol Title: The effect of FP-025, an MMP-12 inhibitor, on allergen-induced airway responses, airway inflammation, and aspects of airway remodeling in subjects with mild eosinophilic house dust mite (HDM)-allergic asthma. Study Purpose: To evaluate the efficacy and safety of FP-025 in subjects with allergic asthma.

Phase of Clinical Study: Phase 2a clinical trial, a first-in-patient, proof-of-concept (POC) study. Investigational product: FP-025, a Matrix metalloproteinase-12 (MMP-12) inhibitor. Indication: Allergic asthma.

Endpoints: Primary endpoints: The effect of FP-025 treatment versus placebo on LAR (late asthmatic response), defined as FEV1 (Forced Expiratory Volume in 1 second) AUC3-8h (AUC from 3 to 8 hours post allergen challenge). Secondary endpoints: (a) Pharmacodynamic endpoints include the effect of study treatments on allergen-induced changes in (FP-025 versus placebo): i. Measurement of LAR is defined as max% fall in FEV1 from post-diluent baseline 3-8 h post-allergen. ii.

Measurement of EAR (early asthmatic response) is defined as FEV1 AUC0-3h (AUC from 0 to 3 hours post allergen challenge) iii. Measurement of EAR is defined as FEV1 AUC0-3h post-allergen and in max% fall from post-diluent baseline 0-3 h post-allergen. iv.

Joint HDM-induced airway response expressed as FEV1 AUC0-8h post-allergen. v. Changes in allergen-induced AHR (airway hyper-responsiveness) as measured by PC20FEV1(Meth) or PC20FEV1 (Hist) pre or post allergen (Day 10 versus Day 12). vi.

Small airway parameters measured by IOS (i.e. R5, R20, R5-R20, AX, X5, Fres) during LAR and during EAR and over 0-8h post-allergen challenge. vii. Changes in FeNO (fractional exhaled nitric oxide) and blood eosinophils pre or post allergen (Day 10 versus Day 12).

(b) Potential treatment effect on baseline parameters (i.e. Day 1 versus Day 10), through measurement of blood eosinophils, PC20FEV1 (Meth) or PC20FEV1 (Hist), and FeNO. Number of subjects randomized: (a) This was a randomized, double-blind, placebo-controlled, 2-way crossover, phase 2a study to evaluate the effect of FP-025 in patients with allergic asthma. (b) There were two identical study periods of 12 treatment days each, separated by a washout period of at least 3 weeks (and no more than 7 weeks).

The subjects were treated with either FP-025 (400 mg BID) or matching placebo in a randomized cross-over fashion. (c) 29 subjects were enrolled in this POC clinical study, including 19 evaluable subjects, of which completely adhered to the treatment protocol (per protocol), those subjects with protocol violation/deviation or early termination were excluded from the statistics. Primary endpoint and the statistical results: (a) During this clinical trial, incoming data from experimental HDM-sensitized mice showed long-lasting anti-inflammatory efficacy as well as disease-modifying effects.

In view of these findings and given first-in-class intervention in asthma patients using a cross-over design, the presence of a possible treatment carry-over effect has been assessed. Indeed, at the treatment sequence of FP-025 followed by placebo, even though there was a washout period of 3 to 7 weeks between the two study periods, a statistically significant carry-over effect of FP-025 was found between the two sequences (P-value = 0.0340), suggesting that FP-025's effect may persist into treatment period 2 when subjects were receiving placebo. As a follow-up on the unexpected carryover finding, the statisticians proceeded with analysis to calculate the primary end-point using the following 3 methods: Sequence: the effect on LAR (AUC3-8h) in subjects who received Placebo during Periods 1 versus FP-025 during Period 2 (N=8):FP-025 treatment group (-84.005), and placebo group (-113.429).

The results of FP-025 treatment group demonstrated statistically significant benefit versus placebo (P-value = 0.0161). The 2 airway response curves are generated from the same individuals, with internal control and higher power of detecting significance. Period: the effect on LAR (AUC3-8h) in subjects who received FP-025 during Periods 1 (N=11) versus placebo during Period 1 (N=8):FP-025 treatment group (-79.443), and placebo group (-113.429).

The results of FP-025 treatment group demonstrated no statistically significant benefit versus placebo (P-value = 0.1302), but showed a positive trend. Mixed effects model ANOVA: the effect on LAR (AUC3-8h) in subjects who received FP-025 during Periods 1 and 2 (N=19) versus placebo during Period 1 (N=8), using the mixed effects model ANOVA method:FP-025 treatment group (-81.358), and placebo group (-113.429). The results of FP-025 treatment group demonstrated statistically significant benefit versus placebo (P-value = 0.0149).

Secondary endpoint and the statistical results: Due to the complexity of trial design, huge amounts of data and variety, secondary endpoints results, safety and tolerability data are expected to be available in May. The results of a single clinical trial (including the p value or whether there are statistical significance in primary, secondary endpoints) shall not be sufficient to reflect the success or failure of the new drug in the future development. The investors shall be careful in judgement and investment.