- the report confirms the OATD-01 safety profile which justifies further clinical development of this experimental drug
- In Q1 of 2021 the company plans to file for an approval of the next phase clinical trial in sarcoidosis patients
OncoArendi Therapeutics S.A. (GPW: OAT) — a biotechnology company which specializes in discovery and development of new drugs will continue the clinical development of the OATD-01 molecule — an innovative small molecule chitinase inhibitor — in the treatment of severe pulmonary diseases such as sarcoidosis or idiopathic pulmonary fibrosis (IPF). OncoArendi Therapeutics is the first and so far only biotechnology company in the world, which conducts clinical trials of drug candidates targeting chitinase (first-in-class).
In April 2020 based on the analysis of initial unblinded data and a series of consultations, the Company decided to end OATD-01 phase Ib clinical trial conducted on healthy volunteers due to achievement of full pharmacodynamic effect. The results presented in the final report from the OATD-01 phase Ib clinical trial confirm the initial conclusions and therefore justify further clinical development of OATD-01 in subsequent trials in patients.
– The decision to terminate phase Ib was made after completing the 25 and 50 mg doses in two of the three initially planned healthy volunteer cohorts and the initial analysis of blinded data. The obtained results have suggested a very strong inhibition of the (target) chitinolytic activity, which is a biomarker for the potential therapeutic effect of the OATD-01 drug candidate. The final unblinded results from phase Ib trials have confirmed the safety of the tested doses (25 and 50 mg) and achieving the desired pharmacodynamic effect. What is especially important at this stage (finished phase I trials in healthy volunteers), the observed safety and pharmacodynamic profile of OATD-01 justify further development of this drug candidate in subsequent phases of clinical trials in patients with sarcoidosis and idiopathic pulmonary fibrosis — says Rafał Kamiński, Member of the Board and Chief Scientific Officer at OncoArendi Therapeutics S.A.
Moreover in cooperation with the US company Certara, which specializes in supporting drug development programs with the use of state-of-the-art clinical pharmacology methods, OncoArendi has conducted an initial study of pharmacometric modelling in order to establish the impact of OATD‑01 in healthy volunteers on the biomarker of chitinolytic activity of blood plasma. The results of modelling indicate clearly that in the tested dose of 25 mg, and even in modelled lower doses (10 or 15 mg) a therapeutic effect may be expected in sarcoidosis patients. These conclusions will be subsequently verified in the next stage trials in sarcoidosis patients.
– We already have a comprehensive set of data necessary for the continuation of subsequent stages of OATD-01 clinical trials in patients. We are now finalizing the pharmacometric studies in order to select optimal therapeutic doses and design of the trial and we have initiated the process of selecting the facilities where the next phases of the trial will be conducted. We plan to conduct the phase IIa trial on a small group of patients with diagnosed sarcoidosis, with the goal to assess the safety and tolerability, as well as to demonstrate the initial therapeutic effect of our drug candidate, along with the changes of biomarkers of disease progress. This will hopefully allow us to assess the probability of the clinical efficacy of OATD‑01. We have already obtained financing for conducting the phase IIa trial for sarcoidosis. We intend to file an application to launch the next stage of OATD-01 clinical trials in patients with sarcoidosis in the first quarter of 2021, and the end of the first part of this trial at the end of 2021. We expect that in the first half of 2022 we will be able to commence the second part of the study consisting of a longer administration of the drug candidate to another group of patients — says Marcin Szumowski, Member of the Board of OncoArendi Therapeutics S.A.
The OATD-01 molecule developed by OncoArendi Therapeutics has an Orphan Drug Designation (ODD) status for the treatment of both sarcoidosis and idiopathic pulmonary fibrosis (IPF), awarded by the U.S. Food and Drug Administration (FDA). OncoArendi Therapeutics is the first biotechnology company in Poland with two orphan indications awarded by the FDA.
Having the ODD status in case of development of OATD-01 for the US enables OncoArendi to benefit from scientific advice from the FDA in clinical trials and may significantly reduce the time needed for future stages of clinical trials. Additional benefits involve tax exemptions, a simplified and less costly drug evaluation and registration procedure, an extended period of patent protection as well as an additional seven-year period of exclusivity for its sales.
The clinical part of the phase Ib trial (MAD, multiple ascending dose) of OATD-01 was conducted in a German facility specializing in early stage clinical trials. This was the second stage of phase I after previous successful phase Ia (SAD, single ascending dose).
In phase Ib trial OATD-01 was administered in 25 and 50 mg doses for 10 days to 24 healthy volunteers of both sexes in two study groups. In general, the safety assessment of OATD-01 indicated that the tested doses (25 and 50 mg) were well tolerated. Most laboratory parameters recorded during the trial were within normal limits and did not indicate any clinically significant changes related to time or dose. There were also no serious adverse events (SAE) nor any other adverse events that would justify interrupting the trial (stopping criteria) or lowering the dosage.
In the 25 mg dose group, no clinically significant prolongation of QTc interval was observed in ECG monitoring. In the 50 mg group, the analysis of ECG monitoring indicated a statistically insignificant tendency for slight prolongation of the QTc interval and a few transient arrythmias in Holter ECG records. Such events were also observed in other studies in healthy volunteers without any pharmacotherapy. Therefore at this stage it is not possible to unequivocally establish that these observations may have been drug related. It should be emphasized that the observed adverse events were very mild and all ended before the trial was finished.
The team of doctors supervising the trial has deemed most deviations from normal levels to bear no clinical significance. The trial also has achieved the expected pharmacodynamic effect, that is, nearly complete inhibition of the chitinolytic activity after multiple application of OATD-01 at 25 and 50 mg doses.
OncoArendi has decided not to administer the third, highest dose of OATD-01 (75 mg) originally planned in the phase Ib study protocol. This decision is in line with the guidelines on strategies to identify and mitigate risks for first-in-human and early stage 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) further dose increases are not justified. This effect was fully achieved with the 50 mg dose of OATD-01.
OncoArendi Therapeutics S.A. is an innovative biotech company focused on discovery, development and commercialisation
of novel medicines to treat patients with pulmonary diseases and neoplasms. OncoArendi’s business model is based on discovery and development of new therapeutic compounds with the intention to out-license the medicines to pharmaceutical companies. The company develops potential first-in-class or best-in-class medicines for the treatment of diseases associated with unmet medical need. For the development of current research projects OncoArendi Therapeutics has obtained funds from private investors
as well as from numerous grants co-financed by national funds, EU funds, Horizon 2020 and the US National Health Institute (NIH) following a competitive procedure. In March 2018 OncoArendi Therapeutics successfully conducted the initial public offering (IPO) which resulted in obtaining 58 million PLN for further development of its biotech projects in the future. The company was first listed on the Warsaw Stock Exchange on 19 April 2018.
Sarcoidosis is a rare disease, which significantly impacts the quality of life and presents a globally unmet medical need. So far there is no approved standard of care in the treatment of this disease, and treatment is conducted on an “off-label” basis, that is, drugs are administered that have been approved for other indications. In the treatment of sarcoidosis these include mainly corticosteroids and immunosuppressive drugs with significant side effects.
There are currently approx. 1.3 million patients with sarcoidosis worldwide. OATD-01 has demonstrated effectiveness in an animal model of sarcoidosis, and as an approved drug it should be characterized by a high level of safety, with a therapeutic effect based on a new mechanism – inhibition of the CHIT1 protein, which seems to play a significant role in the pathogenesis of sarcoidosis.
On idiopathic pulmonary fibrosis (IPF)
Idiopathic pulmonary fibrosis is a rare disease. The estimated number of IPF patients worldwide varies greatly between sources from less than 200 thousand diagnosed cases in the 7 major markets to even up to 3 mln worldwide. It may be reasonable to assume that the accessible market for a new drug is on the order of 500 thousand worldwide. After the diagnosis an IPF patient has an average survival of 3–5 years. Patients with IFP frequently develop lung cancer. There are 2 drugs which are currently approved for the treatment of IPF, which have serious limitations caused by their cumbersome side effects.
There are approx. 20 registered clinical trials for idiopathic pulmonary fibrosis worldwide. In Poland the only company with an idiopathic pulmonary fibrosis drug candidate undergoing clinical development is OncoArendi Therapeutcs.
For more information visit: https://oncoarendi.com/
Michał Wierzchowski, cc group
tel. +48 531 613 067
Katarzyna Mucha, cc group
tel. +48 697 613 712