MeiraGTx Holdings plc  announced positive clinical data from the ongoing Phase 1 AQUAx study of AAV2-hAQP1 for the treatment of grade 2/3 radiation-induced xerostomia (RIX). AQUAx is an open label, multi-center, dose escalation study of a single administration of AAV2-hAQP1 to one or both parotid glands in patients with radiation-induced salivary hypofunction and grade 2/3 xerostomia. Enrollment of the AQUAx study was completed in the first quarter of 2022 and consisted of four unilaterally treated dose escalating cohorts with 3 subjects per cohort and four bilaterally treated dose escalating cohorts with 3 subjects per cohort.

As of the cutoff date of November 30, 2022, all 12 unilaterally treated participants have undergone their 12-month assessment, with 3 having completed their 24-month assessment and one having completed their 36-month assessment in the long-term follow-up study. All 12 bilaterally treated participants have undergone their 6-month assessment. To date, treatment has been well tolerated with no dose limiting toxicity (DLT) or treatment-related serious adverse events (SAEs), and improvements have been seen in validated patient reported assessments of xerostomia symptoms and in whole salivary flow rate.

The study is being conducted at 4 centers, 3 in the US and 1 in Canada. All participants are to be followed for 1-year post-treatment and will then enter a long-term follow-up study for an additional 4 years. The study's primary endpoint is safety.

Secondary endpoints include change from baseline in patient reported measures of xerostomia symptoms as well as whole salivary flow rates. Efficacy Data presented from the24 participants treated in the AQUAx study Clinically meaningful improvements in xerostomia symptoms reported consistently across two validated PROs assessing xerostomia symptom severity Meaningful increases in whole saliva flow rates observed post-treatment, providing objective evidence of biological activity of AAV2-hAQP1 treatment Early long-term follow-up data suggest durability of improvement 2+ years post-treatment Bilateral Cohorts (n=12) to 6 Months 10/12 participants reported symptoms of dry mouth as “better” at the 6 month timepoint Each of these 10 participants rated changes in xerostomia scores that were “important” or “very important” (a score of 2 or more) 3 participants rated the change in xerostomia symptoms with the highest improvement scores of 6 or 7 denoting a “very important improvement” No participant reported any worsening of xerostomia symptoms Unilateral Cohorts (n=12) to 12 Months 8/12 participants who reached the 12-month assessment reported symptoms of dry mouth as “better” following treatment Each of these 8 participants rated changes in xerostomia scores that were “important” or “very important” (a score of 2 or more) 4 participants rated the change in xerostomia symptoms with the highest improvement scores of 6 or 7 denoting a “very important improvement” Improvement in xerostomia symptoms can be seen persisting through 2 years in all 3 patients who have reached that timepoint Participant 1-1 reached the 3-year assessment and the maximum score of 7 was maintained No participant reported any worsening of xerostomia symptoms Combined Unilateral and Bilateral Cohorts 18/24, or 75%, of all unilateral and bilateral treated participants reported symptoms of dry mouth as “better” following treatment Each of these 18 participants rated changes in xerostomia scores that were “important” or “very important” (a score of 2 or more) In the overall cohorts the average improvement in scores was greater in bilateral participants compared to unilateral participants Unilateral cohort achieved overall improvement of >3 points at 12 months Bilateral cohort achieved overall improvement of >3 points at 2 months and an overall improvement of 4 points by 6 months A 2 point improvement in the GRCQ is considered clinically meaningful and an improvement of 3 or more is considered a substantial improvement over standard of care and “transformative” by KOLs Overall improvement in scores was maintained and increased over time in both unilateral and bilateral cohorts Xerostomia Questionnaire (XQ): Xerostomia Questionnaire (XQ) PRO measure scoring scale An improvement (decrease) of 8 points or more is considered clinically meaningful A decrease in score of 10 or greater is considered a substantial improvement over standard of care and “transformative” by KOLs Change from Baseline Unilateral and Bilateral Cohorts 7/12 unilateral participants had improvements in XQ severity score of >8 at 12 months 10/12 bilateral participants had improvements in XQ severity score of >8 at 6 months Overall, 17/24 participants showed an improvement following treatment of >8 points in the XQ score 6/12, or 50%, of unilateral participants at 12 months and 10/12, or 83%, of bilateral participants at 6 months achieved 10 point or greater decline Average Change from Baseline Unilateral and Bilateral Cohorts In unilateral participants an average 13-point improvement from baseline in XQ was seen at 12 months In bilateral participants an average 22-point improvement from baseline in XQ was seen at 6 months Improvement in XQ severity score was observed rapidly post-treatment The degree of improvement in scores was greater in bilateral participants compared to unilateral participants Whole Saliva Flow: Bilateral Treated Subjects Meaningful increase in whole saliva flow was seen in bilateral treated patients at 6 months The average percentage change from baseline was 100% in bilateral patients at 6 months The overall flow rate improved to an average of 0.4mL/min which is in the normal range for unstimulated whole saliva production Based on both absolute and percent change from baseline in whole resting saliva, the improvement in unstimulated salivary flow in the bilateral treated patients are of clinically meaningful size Unilateral Treated Subjects Whole saliva was collected using gum stimulation, however this was directly following extensive manipulation and citric acid stimulation and collection from individual glands which confounded the stimulated whole saliva data   Despite this, an increase in the absolute and percentage change from baseline in whole saliva flow was seen in unilateral treated patients following treatment of only one parotid gland Phase 2 Study Plans: Based on the favorable safety and efficacy profile of AAV2-hAQP1 in the AQUAx Phase 1 study, the Company intends to initiate a randomized, double-blind, placebo-controlled, Phase 2 study evaluating the bilateral administration of two active doses of AAV2-hAQP1 in the first half of 2023 Based upon regulatory interactions, The company anticipates the Phase 2 study's primary efficacy endpoints will be the change from baseline to 12 months in salivary flow rate and key secondary endpoints will be the change from baseline to 12 months in the XQ and GRCQ PROs at 12 months.