Covid – 19 Pandamic
In3Bio is working on solutions for Covid-19 affected patients.

Covid - 19 Pandamic

In3Bio’s proprietary molecule has the potential to help post-Covid 19, recovering patients

The Coronavirus

The coronavirus are single-stranded RNA viruses, some of which circulate in the human population causing mild respiratory disease. The coronavirus often jump from animal reservoirs to humans causing emerging infectious diseases. In 2002, the severe acute respiratory syndrome coronavirus (SARS-CoV) originated in China caused a severe atypical pneumonia with a mortality index of 13%. No specific antivirals or approved vaccines are available for the epidemic. Coronavirus disease 19 (COVID-19) is a new infectious disease originated by SARS-coronavirus 2 (SARS-CoV-2), which is closely related to SARS-CoV.

The Threat of Pulmonary Fibrosis

The full spectrum of COVID-19 ranges from mild, self-limiting respiratory tract illness to severe progressive pneumonia, multiorgan failure, and death. Some patients have complications such as acute respiratory distress syndrome (ARDS). Severe ARDS has an estimated mortality of 45% and survivors tend to develop pulmonary fibrotic damage.

 

 What is Pulmonary Fibrosis (PF)?

  • Pulmonary fibrosis is a disease that occurs when fragile parts of the lungs become damaged and scarred
  • The thickened, stiff tissue makes it more difficult for the air sacs to work effectively
  • In some cases, this can lead to breathing difficulties and fatigue, as well as leaving the patient more susceptible to another lung infections in the future
  • It is an irreversible condition and, in some cases, it gets worse over time.

At present, the long-term pulmonary consequences of COVID-19 remains speculative and requires further study. Nonetheless, given the huge numbers of individuals affected by COVID-19, even rare complications have major health effects at the population level. Given these observations, scientists warn that the burden of pulmonary fibrosis after COVID-19 recovery could be substantial.

Reference:

  1. Reed, Jim, and Sophie Hutchinson. “Coronavirus: Warning Thousands Could Be Left with Lung Damage.” BBC News, BBC, 23 June 2020, www.bbc.com/news/health-53065340
  2. Spagnolo, Paolo, et al. Pulmonary Fibrosis Secondary to COVID-19: a Call to Arms? Lancet Respir Med., 15 May 2020, ww.ncbi.nlm.nih.gov/pmc/articles/PMC7228737/

EGF/EGFR Signalling Pathway and Pulmonary Fibrosis

From the historical data, epidermal growth factor (EGF) signalling pathway is found to play an important role in the development of Idiopatic Pulmonary Fibrosis (IPF). EGF receptor (EGFR) are highly overexpressed in IPF patients. The ligands of EGFR activate the pathway and resulting in lung fibrosis. We hypothesized that EGF signalling pathway might contribute to the COVID-19 induced pulmonary fibrosis.

Reference:

  1. Venkataraman, Thiagarajan, and Matthew B Frieman. “The Role of Epidermal Growth Factor Receptor (EGFR) Signalling in SARS Coronavirus-Induced Pulmonary Fibrosis.” Antiviral Research, Elsevier B.V., July 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5507769/.

Potential Solution – IN01 (In3Bio’s Proprietary Molecule)

Being aware that IN01 demonstrated significant immuno modulation in EGFR mutant lung cancer cell lines and safety profile in an animal study, Prof. Rafeal Rosell from Pangaea Oncology, Spain, first brought the idea to our CEO / CSO Dr. Erik D’hondt, for treating pulmonary fibrosis using IN01.

In3Bio’s platform technology molecule, IN01, works by stimulating the patient’s own immune system to recognise, bind and remove EGF growth factor, i.e. ligand that is one of the activators for EGFR. Our hypothesis is that IN01 could effectively prevent SARS-COV-2 lung fibrosis that develops during the long convalescence period after the infection, by blocking the EGF pathway.

Jointly developing the idea and protocol together with Pangaea, In3Bio will start the Phase Ib clinical trial using IN01 in discharged SARS-CoV-2 patients from intensive care units (ICU) and developed fibrotic damage as consequence of the infection. No previous studies have addressed the fibrotic damage resulted from acute COVID-19 infection. Currently therapeutic options to treat fibrotic pulmonary damage are limited.

In3Bio’s Phase Ib trial

This investigator-led trial will be co-sponsored by Pangeae Oncology. The study Principal Investigator is Dr. Pablo Rubinstein, who is the Head of Pneumology Service of General University Hospital of Catalonia, El Pilar Hospital (as part of QuironSalud Group).

In the planned study, 40 ex-acute COVID patied-19 patients with fibrosing lung syndrome will be randomized in the treatment arm (25 patients) and control arm (15 patients). IN01 in the treatment arm, while standard of care will be given to control arm patients.

The aim of the study is to evaluate the safety and efficacy of IN01 vaccine in the recovery from pulmonary fibrosis associated to COVID-19 infection in 1 year after patient is discharged from ICU. There will be 5 clinical centres in Spain for the proposed Phase Ib clinical trial.

Pangaea

Founded in Barcelona in 2007 and listed on the Madrid Stock Exchange, Pangaea Oncology is a medical services company composed of prestigious clinical and research professionals that provide services from pre-clinical cancer research, biomarker discovery and drug development. Prof. Rafeal Rosell whom was recognized by The Lancet as the highest authority in lung cancer in Europe, is the Chief Scientific Officer of Pangaea.

www.panoncology.com