- Potential effectiveness of OATD-01 in the treatment of pulmonary fibrosis is based on a unique mechanism of inhibiting a new biological target – chitotriosidase 1 (CHIT1)
- Linking COVID-19 infection to pulmonary fibrosis where CHIT1 plays a role will increase the value of OATD-01 and other chitinase inhibitors for potential partners
The main cause of death in patients infected with the new coronavirus (COVID-19) is the acute respiratory distress syndrome (ARDS), caused by severe inflammation in the lungs that leads to loss of their function. Depending on the sources, the observed mortality in patients infected with COVID-19 ranges from 3 to 8% and increases proportionally to the age and inversely to health status of the infected person.2 Therefore older people with coexisting chronic diseases (including lung diseases) face the highest risk of developing serious or critical symptoms of COVID-19 infection.
Pathological changes in the lungs including pulmonary fibrosis were observed in those who died of COVID-19. In addition, changes in the lungs were observed in a significant proportion of patients undergoing radiological examination after recovery, which also indicated fibrosis. Furthermore, new scientific reports indicate the accumulation of pro-inflammatory and pro-fibrotic cells in the lungs of COVID-19 patients.
These preliminary observations during a rapidly spreading global pandemic clearly demonstrate the coexistence of COVID-19 and pulmonary fibrosis.
It should be noted that high mortality resulting from inflammation, which causes lung lesions and ultimately ARDS, has also been associated with previous coronavirus outbreaks such as SARS or MERS, where 30% of surviving patients have had fibrotic changes in their lungs. Similar outcomes can therefore be expected with other coronavirus outbreaks, including COVID-19.
There are two drugs approved worldwide for the treatment of idiopathic pulmonary fibrosis (Ofev by Boehringer Ingelheim and Esbriet by Roche) with limited clinical efficacy and burdensome side effects. In addition, two companies (Galapagos and Fibrogen) have experimental drugs in phase 3 clinical trials.
Roche and Genentech have recently announced the launch of Esbriet tests as part of an open-label clinical trial in patients with acute or critical course of COVID-19, registered by the Tongji Hospital (a hospital belonging to the Medical University of Tongji, China).
There are currently only about 20 clinical trials registered worldwide for idiopathic pulmonary fibrosis (IPF). The only Polish company with a drug candidate for the treatment of pulmonary fibrosis in clinical development is OncoArendi Therapeutics SA. OATD-01 is currently nearing completion of phase I clinical trials, which so far has confirmed drug safety in healthy volunteers. These studies are carried out in Germany. In addition, last year OATD-01 obtained an orphan drug designation (ODD) from the Drug and Food Agency (FDA) in the US in for treatment of IPF.
Potential efficacy of OATD-01 in treatment of human pulmonary fibrosis is based on a completely new, unique mechanism of action, consisting of blocking the activity of the chitotriosidase 1 (CHIT1) enzyme in pathologically activated inflammatory cells that produce increased amounts of this protein. In laboratory experiments, blocking of CHIT1 activity after OATD-01 administration resulted in documented anti-inflammatory and anti-fibrotic activity.
– The postulated therapeutic effect of OATD-01 in patients who have undergone coronavirus infection (COVID-19) or other viral infections resulting in similar progression of the disease could be to slow down or prevent progressive fibrotic changes in the lungs and, consequently, improve patients’ respiratory performance – comments Rafał Kamiński, MD, PhD, OncoArendi’s new Chief Scientific Officer.
OncoArendi’s research team is currently in the process of establishing scientific collaborations to verify whether lung tissues from patients who died of COVID-19 have a higher CHIT1 expression and whether induction of CHIT1 occurs in the inflammatory cells that infiltrate the lungs. If the Company confirms its upregulation and determines a safe dose for administration to patients, along with the orphan drug designation from the FDA, it will be able to seek regulatory clearance (as early as in phase II clinical trials) to administer OATD‑01 to COVID-19 survivors, in whom pathological lung changes have been observed. The combination of an orphan drug designation and confirmed presence of an elevated level of the therapeutic target (CHIT1) in patients, can significantly reduce the time of clinical development to pre-marketing approval, from the typical 3-5 years to as little as 2 years.
– A growing number of patients due to the current pandemic will drastically increase the demand for drugs treating inflammation-driven pulmonary fibrosis. To date, idiopathic pulmonary fibrosis has been considered a rare, but fatal disease with an expected survival of 3-5 years from diagnosis. A rapid growth in the number of patients is expected to increase the value of OATD-01 for potential industry partners, since it is anticipated that the effective treatment will likely require a combination of different therapies based on complementary mechanisms of action – explains Rafał Kamiński.
If the hypothesis of increased CHIT1 activity in the lung tissue after a coronavirus infection is proven true, OncoArendi plans to raise funds in the form of grants and subsidies, as well as from cooperation agreements with partners abroad, including in the US and EU (especially in Germany) to combat the potential long-term consequence of the COVID-19 pandemic. It is worth mentioning that the US government has announced an allocation of more than 8 billion dollars to fight coronavirus, of which 3 billion will be earmarked for research on novel therapies.
– OncoArendi does not plan to develop new drugs that directly fight or prevent the new coronavirus infections, but it may contribute to combating potentially fatal complications of this disease, which according to current forecasts may affect several million people around the world – adds Rafał Kamiński.
 Raport Lancet z 24 stycznia – 3%; raport WHO z 3 marca – 3.4%, liczba zgonów dzielona przez sumę zgonów i wyzdrowień – 8%: https://www.worldometers.info/coronavirus/coronavirus-death-rate/
 Thorac Oncol. 2020 (in press, Feb 27); J Forensic Med 2020; 36: 1–3;
 Lancet Infect Dis. 2020 (in press, Feb 24)
 medRxiv 2020 (https://www.medrxiv.org/content/10.1101/2020.02.23.20026690v1)