Bulgarian drug discovery startup Micar21 has announced it has found a new drug micromolecule that may enhance the fight against coronavirus. The discovery may accelerate the development of a drug that not only prevents or covers the symptoms of COVID-19 but also heals the disease as it targets the root cause.

The results from two of the most respected laboratories in Europe and the US – Eurofins and ThermoFisher Scientific have validated the discovery. “Given the situation with the spread of COVID19, it has been declared that requirements for new drugs in this field are now lower, which means the process for development could be accelerated. Within a year, we could reach Phase II of clinical trials,” explains Dimitar Dimitrov, CEO of Micar Innovation. According to the results validated with the two laboratories, the discovered small molecule could serve as a basis for a pill, that is far less toxic than other similar developments in the segment. It is based on the two proteins CCR5 and CCR7, typically used in respectively HIV and rheumatoid treatments.

INFOBOX Typically Phase II trials are performed on larger groups (100–300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients.

The company is ready to file patents and is already negotiating funding with five of the biggest pharma companies in the world, explains Dimitrov. Given the situation with COVID-19, the drug development process could be accelerated and a coronavirus treatment could reach the mass market within 5 years (it typically takes around 10-15 years to bring a drug to market – ed.n.). The company is now looking for around €3M to enter the pre-clinical phase.

How it works

Already two months ago Micar21 started running virtual screen tests and detected the first class of CCR5 / 7 dual antagonists for COVID-19. To put it simply, the company has managed to discover a small molecule that could be used in non-invasive drugs such as pills and help prevent and treat coronavirus on a DNA level. CCR5 and CCR7 are both proteins involved in the immune system that have certain mutations making individuals with the mutation resistant to some diseases like HIV. A genetic approach involving intrabodies that block CCR5 expression is used as a treatment for HIV infected patients. According to Dimitrov, there are 62 treatments based on CCR5, and no based on CCR7, which makes the discovery a true novelty and may accelerate its path to the mass market. Mutations of CCR7 are typically responsible for psoriasis and rheumatoid diseases. The discovered dual antagonists basically modify cells so they can no longer express CCR5/7 and thus establishes a virus-resistant cell pool in infected individuals.

Currently, in the US there’s one COVID-19 treatment in development that is based on CCR5. It has already reached Phase 2 of clinical trials. Given the fact, however, that there are already another 62 drugs based on the same protein, it will take longer for the company to prove that its development is significantly better than the other drugs. As of Micar21’s discovery, being first in class may accelerate its development. Furthermore, Dimitrov claims a treatment based on the dual antagonists would be far less toxic than current drugs.

The team of Micar21 came to the discovery after running a virtual screen of 4 million compounds. The most promising compounds have been sent to ThermoFisher companies for bioassays to study both their binding capability and biological response. The whole R&D process from 0 to preclinical tests is done within the company. Alongside the human intelligence of 20 scientists, Micar21 is also working on an AI-enhanced discovery and prediction platform. The platform itself, however, is still in its early days.

How could a drug discovery startup monetize the discovery

Micar21 was founded in 2016 by serial entrepreneur Dimitar Dimitrov and scientist Dr. Filip Fratev as a drug discovery factory. The main focus is on non-clinical Proofs-of-Concept (POCs) in preclinical R&D. The company has a team of 20 scientists who work on the discovery of new drug molecules that the company then patents and licenses for big pharma players to help accelerate their own drug development processes. Part of the business model of the company is to spin out new discoveries in separate entities under the Micar umbrella and to fundraise for particular discoveries. Once an asset or a patented discovery is licensed the company receives both cash and between 7% and 9% royalty fee for the next 20 years (as much as the patent is valid). Micar21 has already five patents, says the CEO, and is ready to file another 15 if the right investor appears.

In the case of the CCR5/7 discovery, Micar21 is entering a market of $1trillion – this is how much the direct economic healthcare costs for treating the disease are estimated at.

Putting Bulgaria on the biotech map

For Dimitrov, who is also Chair of the Bulgarian Biotech Cluster, the discovery is important for one more reason: “It could put Bulgaria on the global map as a hub for the development of biotech innovation.” Since its start four years ago, his company, as one of the key players in this domain, has published 30+ papers in respected scientific media such as Nature Scientific Reports and Journal of Biomolecular, Structure, and Dynamics. Micar21 has won numerous recognitions and is one of the world’s 130 companies in Deep Knowledge Analytics report AI for Drug Discovery Landscape in 2018. It is also one of the world’s 198 companies in “In Silico/Computer- Aided Drug Discovery Services Market 2020-2030”. With the new micro molecule discovery, the Bulgarian company has an even bigger chance to put Bulgarian science and technology on the global biotechnology and drug R&D map.