OncoArendi Therapeutics – a clinical stage biotechnology company specializing in the discovery and development of innovative small molecule drugs continues the clinical development of its first-in-class experimental drug candidate for treatment of sarcoidosis and idiopathic pulmonary fibrosis (IPF). OncoArendi Therapeutics is the first and thus far the only biotechnology company in the world conducting clinical research on new drugs blocking the activity of chitinase proteins.
OncoArendi Therapeutics announces the end of the clinical part of phase Ib trial (multiple ascending dose (MAD)) of the OATD-01 compound after confirming the tolerability of the tested doses and achieving the estimated pharmacodynamic effect. This was the second early phase clinical study after the successfully completed phase Ia “First in Human study” (single ascending dose – SAD).
The clinical part of the phase Ib (MAD) was conducted in Germany at a CRO specialized in early clinical development. In the course of the study, the compound was administered at doses of 25 mg and then 50 mg for 10 days to 24 healthy volunteers of both sexes in two study groups, each consisting of 12 subjects.
A full pharmacodynamic effect was achieved with OATD-01 at the 50 mg dose. Consequently, after conducting a number of analyses and consultations, OncoArendi decided not to test the third, highest dose (75 mg), anticipated in the study protocol. This decision is in line with the guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products issued by the European Medicines Agency (EMA) in early 2018. These guidelines indicate that after achieving a full pharmacodynamic effect (target saturation) no further therapeutic benefit is to be expected by increasing the dose.
– Based on these preliminary data we conclude that our compound is on the right track towards further clinical development in patients. OATD-01 was well tolerated by healthy volunteers, we did not observe any serious adverse events and there were no events that would meet the clinical trial stopping criteria specified in the protocol. Furthermore, no electrocardiographic (ECG) abnormalities were observed that would meet the predefined criteria for adverse proarrhythmic effects. In addition, it is worth emphasizing that in both tested doses (25 and 50 mg), the expected pharmacodynamic effect was achieved, i.e. significant inhibition of chitinolytic activity in plasma, which is a biomarker of the potential therapeutic effect. Therefore, we decided not to continue dosing at 75 mg. In our opinion, increasing the dose administered to healthy volunteers would be unnecessary and non-compliant with the recommendations of EMA, since we have already achieved a full pharmacodynamic effect and we have sufficient data package to continue further clinical development of the compound – says Rafał Kamiński, OncoArendi Chief Scientific Officer and Member of the Board.
– Foregoing dosing of the third cohort of healthy volunteers is also beneficial for us, because we are saving time and money. In our opinion, these funds will be better used for further analyses aimed at determining more precisely the range of therapeutic doses for the phase II study – comments Sławomir Broniarek, Member of the Board (Chief Financial Officer) of OncoArendi Therapeutics.
– Based on the data, which we have collected so far in phase I clinical trials with OATD‑01, we conducted preliminary modeling studies, which indicate that doses lower than 25 mg are likely to have the desired pharmacodynamic effect. Therefore, in the planned phase IIa clinical trial, we want to start administration of the drug to patients with sarcoidosis at lower doses. This will potentially result in an even broader therapeutic window for OATD-01 – adds Rafał Kamiński.
OncoArendi Therapeutics will soon inform both the Federal Institute for Drugs and Medical Devices (BfArM), as well as the Bavarian Bioethics Committee about the termination of clinical phase of the MAD study. The above decision does not require consent of the above institutions, because according to the study protocol is solely the sponsor’s (OncoArendi Therapeutics) decision, which can be made based on scientific merits, as was the case for OATD-01. Formal activities and analyses of the extensive unblinded data from the clinical part of the study will start immediately, as required for generation of the preliminary and final reports from the phase Ib (MAD) study.
The final report from the phase Ib clinical trial is expected in the third quarter of 2020.
After the final confirmation of the safety profile and the desired pharmacodynamic effect of OATD-01 in the MAD study reports, it will be possible to file all required documents as a part of the Clinical Trial Application (CTA) for the planned phase IIa clinical trial. The primary aim of the phase IIa signal seeking study will be to further confirm safety and demonstrate target engagement, while the secondary endpoints will be related potential therapeutic efficacy in patients with sarcoidosis. Possibly, a separate study in idiopathic pulmonary fibrosis (IPF), which is the second indication for OATD-01, may be conducted in the future.
The OATD-01 molecule developed by OncoArendi Therapeutics has the Orphan Drug Designation (ODD) status for the treatment of both sarcoidosis and IPF awarded by the FDA (US Food and Drug Administration). OncoArendi Therapeutics is the first biotechnology company in Poland with two orphan indications awarded by the FDA.
Having the ODD status for OATD-01 enables OncoArendi to benefit from free scientific advice from the FDA and reduces the scope and time of future clinical development. Additional benefits, if the drug is developed for the US market, involve tax exemptions, a simplified and cheaper drug evaluation and registration procedure, as well as an extended period of patent protection as well as additional seven-year period of exclusivity for its sales.