Current report No. 1/2021 – Positive results of the phase II clinical trial on Celon Pharma’s DPI esketamine in bipolar treatment-resistant depression [03KET2018]

Date prepared: 01/08/2021, 7:23 PM

Legal basis: Article 17 section 1 of the Market Abuse Regulation (MAR) – confidential information.

Content of the report:

In relation to the current report No. 45/2020 regarding the date for the presentation of results of the phase II clinical trial on esketamine-based DPI drug (Falkieri) in bipolar treatment-resistant depression, the Management Board of Celon Pharma S.A. (the "Company") wishes to announce that on January 8, 2021, it received results of the above-mentioned trial.

In the phase II trial on esketamine in bipolar depression, the adopted primary endpoint, defined as a considerable, statistically and clinically significant reduction on the MADRS scale, compared to placebo at week 2, was achieved in all tested doses.

The obtained results indicate that scenario 4 (extremely positive) of the four scenarios listed in the current report no 45/2020 has played out.

The difference on the MADRS scale after placebo deduction on day 14 was -5.9 (95% CI: -10.2 to -1.5; p=0.009) for the 24mg dose; - 6.7 (95% CI: -11.1 to -2.2; p=0.004) for the 36mg dose; and -8.2 (95% CI: -12.6 to -3.7; p<0.001) for the 48mg dose.

Furthermore, patients receiving Falkieri demonstrated a considerable, statistically significant improvement on the HDRS scale, the second depression scale used in the trial, in all tested doses.

Moreover, positive results were observed also with regard to secondary endpoints measuring drug efficacy. Responses to treatment, defined as reduction on the MADRS scale larger or equal to 50% on day 14 were identified in 48%, 52% and 68% of patients receiving 24, 36 and 48 mg esketamine doses, respectively, vs. 23% in patients receiving placebo. Remissions, defined as reaching a value lesser or equal to 10 points on the MADRS scale on day 14 was identified in 44%, 43% and 46% of patients receiving 24, 36 and 48 mg esketamine doses, respectively, vs. 9% in patients receiving placebo.

The drug tolerability was high. No cases of treatment discontinuation connected with the occurrence of adverse reactions in any patients have been reported. No severe adverse reactions have been reported. No deaths or suicide attempts have been reported. No cases of mania induced in patients receiving Falkieri have been reported. The risk is a highly recognized factor accompanying the use of antidepressants in the treatment of bipolar depression.

Dissociation after drug administration was short-term and mild. Sedation after drug administration has not been observed.

The Company expects to receive full clinical data, along with results of an additional 6-week follow-up, within the next 8 to 12 weeks.

In connection with the obtained data, the Company plans to continue talks with the regulators concerning phase III trials, as well as partnering talks in line with its innovative portfolio’s commercialization strategy.

03KET2018 was a multicentre, randomized, double-blind clinical trial, where esketamine was administered in a dry-powder inhaler in 24, 36 and 48 mg doses and was placebo-controlled in patients with bipolar treatment-resistant depression. Esketamine was administered in the above-mentioned trial twice a week over the course of 2 weeks. The study subjects were patients with a history of insufficient response to a stable dose of at least two efficacious therapies approved for bipolar depression treatment.