Lots of companies are working on the discovery side of things, looking for better ways to tackle disease and better drugs to engage targets new and old. What those companies aren’t addressing, says Parallel Bio CEO Robert DiFazio, is the lack of reliable disease models for preclinical work.
Imperfect disease modeling in animals can lead to drugs that work fine in animals but don’t work in people and fail in the clinic. Worse, it could result in drugs that are harmful to people. Think thalidomide, a drug shown to be safe in animals and then marketed as a sedative and a treatment for morning sickness in the 1950s and 1960s before it was linked to severe birth defects.
For DiFazio, who holds a Ph.D. in immunology, the solution is organoids, or 3D mini-organs that look and work just like the organs found in people. Others had worked on this technology, but not at a “commercially relevant scale,” he said. So, he joined forces with Juliana Hilliard, a molecular bioengineer who had worked in the lab of brain organoid pioneer Jürgen Knoblich, Ph.D.
The duo founded Parallel Bio in the midst of the COVID-19 pandemic and started developing an immune organoid to fill a significant gap in disease modeling.
“We believe the immune system is the master regulator of health and disease … People have always understood this about infectious disease, but a lot of people aren’t thinking about the role the immune system could play in other diseases as well,” DiFazio said.
Besides the more obvious areas of cancer and autoimmune disease, the immune system could be tapped to fight heart disease, neurodegeneration and kidney disease as well as help patients recover from surgery, he added.
What’s more, the immune system model is unique among organoids in that it can directly produce human antibodies, eliminating steps in the drug discovery process that are required when working with models of other organ systems.
So, how does one model the immune system? Unlike brain or kidney organoids, which are tiny 3D models of those organs, immune cells such as B cells, T cells and macrophages are found throughout the blood.
Parallel Bio isn’t replicating the entire human circulatory system in a dish, DiFazio said. Instead, it’s modeling the “home of the immune system,” namely the lymph nodes and the spleen, where immune cells go after they are produced in the thymus and bone marrow. These models are being derived from the blood and tissue of actual patients.
“A lot of the human diseases that we still haven’t cured are very complex: There is not necessarily one causative agent or one thing that drives disease,” DiFazio said.
Factors like genetics, environmental exposure and age all play a role in the development of disease. Building models from patients of various ages, racial backgrounds, exposure history and so on allows Parallel Bio to model diseases in ways others can’t, he added.
Besides improving the success rate of drug development, using organoids could reduce the reliance on animal testing for preclinical work.
“Even if animal models were working fine, we should try a lot harder to find better solutions than using animals,” DiFazio said.
So far, Parallel Bio has tested 12 drugs and vaccines against eight different diseases in its immune system model. These compounds include experimental immunomodulators that the company can’t disclose, as well as childhood vaccines and those for rabies and COVID-19.
The company received $125,000 in funding from Y Combinator this year and could pick up more after pitching its work to investors at the startup accelerator’s Demo Day this week.
After graduating from Y Combinator, Parallel Bio plans to build its team and start working on partnerships with pharma companies.
“People are very interested in using our system to test a therapy they’ve developed for a particular disease … What we’d like to do is continue with partnerships to generate data and validation for our platforms,” DiFazio said. “Once it’s established, we will use that to develop our own in-house assets.”
The company is keeping mum on specifics but identified cancer, autoimmune disease and aging as broad areas of focus. And it’s not stopping with modeling the immune system: Parallel Bio is already discussing the next generation of organ models with potential partners.