Ontario-based biotech company partners with academia to use machine learning to rationalize the development of biologics for infectious diseases

Collaborators: Abcelex Technologies, University of Toronto, University of Guelph

AbCelex  is collaborating with Southern Ontario academics to utilize machine learning to rationalize the development of next generation biologics for infectious diseases.

Leading the research team is Dr. Mauricio Terebiznik with University of Toronto Scarborough’s Department of Biological Sciences. Dr. Terebiznik is working with AbCelex Technologies to empower the development of a unique, fully integrated single domain antibody discovery and development platform that addresses challenges of both drug discovery and development across a range of therapeutic indications.

The SOSCIP R&D project is using advanced computing to design next generation antibodies that will reduce foodborne illnesses commonly found in broiler chickens.

AbCelex has been utilizing this platform to develop orally available antibodies to treat and prevent bacterial infections in livestock.  The translation of these capabilities by AbCelex will enable the biopharmaceutical industry access to AbCelex’s discovery and development technologies, including the company’s proprietary platform for human therapeutic drug discovery. AbCelex’s experience and track record is in successfully developing orally available antibodies for infectious disease targets principally for animal health and food safety applications.

These single domain antibodies can be delivered as feed additives in livestock to prevent bacteria such as Salmonella and Campylobacter from colonizing the chicken and swine GI tract. The research could support more than 4,000 Canadian chicken and piglet producers deliver millions of safe food products for Canadian consumers, as well as abroad.

According to the Government of Canada, there are about 1.6 million foodborne-related illnesses (https://www.canada.ca/en/public-health/services/food-borne-illness-canada/yearly-food-borne-illness-estimates-canada.html)  every year, hundreds which can lead to death in individuals who are immunosuppressed, which makes the science behind their prevention critical to the health and well-being of Canadians. Salmonella and Campylobacter are bacterial diseases commonly found in poultry[i]. They act as colonizers in poultry which means it does not impact the health of chickens, however, bacteria acts as a pathogen if transferred to humans. If contracted, it can cause severe food poisoning and could be fatal for those with compromised immune systems.

This industry-academic collaboration is exploring a biologic solution to what was formerly solved by antibiotics. Antibiotics have been responsible for helping to fight against various diseases and illnesses, however overuse has led to the rise of antibiotic resistance. When antibiotics are overused for growth promotion (90% of total historical antibiotic use by Public Health Agency of Canada), their ability to kill microbes such as bacteria, viruses, fungi become ineffective.

“We have two goals,” explained Dr. Dea Shahinas, a senior scientist with AbCelex. “One goal is to support the poultry market. Now that antibiotics are banned worldwide for growth promotion due to increased resistance, we need viable alternative solutions. A synthetic, biologic solution is attractive.

“Our second long-term goal is to conduct animal trials and clinical data and translate our findings and technologies to human applications. Considering the delivery is oral, that could include any infection or virus that affects the GI tract, such as C. difficile, E. coli and others.”

The project involves understanding potentially millions of peptide interactions with the target protein. Through computation, the team can identify selected peptides that would provide target specificity and cross-reactivity across different clinical and environmental strains of the same bacterial pathogen.

“Our application develops specific proteins belonging to the antibody family, known as single domain antibodies (sdAbs). The project is based on generating libraries of these antibodies, says Dr. Shahinas. “We can harness a lot of information from the interactions between the antibodies and our compendium of targets that can be achieved through molecular simulation and machine learning approaches.”

“The number of biotech companies in Ontario, Canada and worldwide is growing, particularly in the biologics space, and there’s a lot of pressure to be competitive”

The single domain antibodies are different from both antibiotics and hormones in that they are protein molecules that work by targeting and inactivating bacterial diseases from entering the food stream. The project will support AbCelex’s proprietary sdAb platform technology which is based on camelid antibodies. Due to the small size of the camelid antibody, they can be easily engineered for higher thermal and protease stability and increased protein yield. The easy engineering and recombinant expression of the camelid antibodies make them ideal for the food safety market, which is a very cost sensitive market. AbCelex’s ability to manufacture these antibodies at an attractive cost of goods with tight margins is key to the success of this application.

“The project requires high compute power to be able to make predictions on a single antibody structure that will address interstrain variability of the target proteins,” explains Dr. Shahinas. “Access to SOSCIP’s GPU system and Blue Gene/Q enables our team to speed up the process, particularly with the maturation of antibodies and stability. On top of that, SOSCIP was also able to pair us with expert talent in data science technologies.”

Dr. Jen Huen is a SOSCIP post-doctoral fellow leading experimental research on the antibodies. “We are conducting computational modeling of identified sequences and molecular simulations of the modeled antibodies and the respective antigen,” she says.

Mostafa Nategh is a post-doctoral fellow from the University of Guelph leading the machine learning efforts. “I came from a small academic lab prior to this project. This project is my wish list. The work is challenging but meaningful. SOSCIP’s mandate to help industry and academia collaboration and provide access to computational infrastructure is critical to supporting new ideas and innovation.”

The project will help AbCelex respond to a competitive and in-demand market. Recognized as an innovative biotech in the field, AbCelex has developed single domain antibodies for C. jejuni and S. enterica that can be expressed in large quantities at a low cost compared to traditional antibodies.

“The number of biotech companies in Ontario, Canada and worldwide is growing, particularly in the biologics space, and there’s a lot of pressure to be competitive,” says Shahinas. “Collaborations with academia help to increase the speed and efficiency of moving our products to market in a competitive space.”

Huen agrees. “Sometimes discovery companies lack the gritty, intense technical expertise that the academic world immerses themselves in. Projects and ideas turn over relatively quickly in industry and they need academic partners to to carry out in-depth research to rationalize and validate their findings. Having SOSCIP to bridge the academic realm with industry has been so important for accelerating our work.”

 

 

 

 

[i] https://www.canada.ca/en/public-health/services/food-borne-illness-canada/yearly-food-borne-illness-estimates-canada.html

**Pictured in top photo L to R: Philbert Ip, Saumil Patel, Jen Huen, Mike Jones and Anam Faheem