Orion Biotechnology
Precision Engineered G Protein-Coupled Receptor Targeted Immunotherapies for Cancer and other Serious Diseases

Over the past several years we have witnessed some exciting, yet somewhat inconsistent, results in the field of immunotherapy. While some of the outcomes of these promising therapies have been remarkable, only a small percentage of patients have benefited, with many types of cancers failing to respond at all. In order to address this gap Orion Biotechnology has focused on an important range of G Protein-Coupled Receptors (GPCRs), which includes promising immunotherapeutic targets. GPCRs are a major focus for drug developers since these receptors regulate a wide variety of human physiological processes, including growth, metabolism, and homeostasis, and have been implicated in many serious diseases, such as cancer. Around 30 percent of medicines used today target GPCRs, but despite this success, a range of GPCR targets (including those activated by natural peptides and proteins) have proven to be very difficult to drug effectively with traditional drug classes, and as a result, have gone largely unexploited. Targeting these GPCRs represents an enormous untapped opportunity to deliver effective treatment for many different types of serious disease.

With its novel approach to engineering analogs of natural ligands that can effectively target GPCRs, Orion Biotechnology has not only created a promising immunotherapeutic with best-in-class potency but has also developed a powerful platform for precision engineering drug candidates for GPCR targets. The company’s drug discovery platform effectively overcomes the barriers to better exploit this promising range of drug targets. “Orion is focused on unlocking the potential of GPCRs for cancer treatment, as well as other serious diseases,” adds Mark Groper, president and CEO of Orion.

So how does Orion’s Precision Engineered Analogs of Small Proteins (natural ligands) differ from the traditional modalities?

“We have a unique binding mechanism when compared to small molecules and monoclonal antibodies that allows us to target these receptors more precisely,” Dr. Oliver Hartley, VP of drug discovery at Orion Biotechnology. Let’s consider a scenario where you have found a locked treasure chest. You decide to call in a locksmith. He brings a stock key, masterfully measures the insides of the lock, and grinds away unnecessary parts, sculpting a key that perfectly fits the lock. The same holds for Orion Biotechnology with its precision engineering of natural ligands. Like a skillful locksmith, Orion utilizes the natural ligand like a stock key, and then uses its patented technology to optimize the ligand interaction surface with the receptor ‘lock’. The result increases binding affinity between the ligand and receptor and also fine-tunes signaling activity of the natural ligand, which would typically be an agonist, into an antagonist, a pure antagonist or a partial agonist, or biased agonist or a superagonist.

We are focused on the development of GPCR targeted therapeutics for cancer treatment, as well as other serious diseases

“We start with what nature has provided, and then we make significant improvements on it according to the kind of drug we need,” enthuses Dr. Hartley.

The company’s discovery platform enables it to systematically generate new peptide and protein (ligand) analogs much more rapidly and cost-effectively than would otherwise be possible.

Orion’s lead drug candidate - OB-002 - falls within a unique class of Immunotherapeutics referred to as Chemokine Analogs, which are being developed using Orion Biotechnology’s drug discovery platform. Specifically, OB-002 is an analog of CCL5, a CCR5 antagonist. As such, it involves a proven mechanism of action, which reduces drug development risk. Moreover, this mechanism of action has demonstrated broad applicability to a range of serious disease types in both pre-clinical as well as clinical contexts.

OB-002 interrupts the binding of the GPCR receptor CCR5 and its ligand CCL5 to slow down the growth of a tumor and prevent metastasis. “OB-002 reduces tumor growth and metastasis, particularly in colorectal and breast cancer” explains Dr. Ian McGowan, CMO of Orion Biotechnology. When OB-002 enters clinical trials in 2021 it will be used on its own and in combination with checkpoint inhibitors in order to confirm the potential benefits for treating advanced colorectal and gastric cancer. “We are beyond excited by the potential of OB-002 to provide an effective therapy for cancer patients, especially those who have exhausted their treatment options” adds Groper.

Through these initiatives, Orion is actively positioning itself as the “go-to” technology company for pharmaceutical companies interested in developing GPCR targeted therapeutics. Orion is backed by an impressive team that includes not only world class scientific and clinical expertise, but the business, financial and legal skills and credentials necessary to build a successful pharmaceutical technology company. “I’m so proud of the talent that we have attracted to Orion. It is a diverse team of professionals, each of whom are leaders in their respective fields” says Groper. Additionally, Orion has strong collaborations and partnerships with different academic organizations, such as the University of Geneva, for research guidance. “Our COVID-19 program, aimed at developing treatments for severe coronavirus patients, is being undertaken in collaboration with a leading Canadian university, remarks Groper. With such relentless efforts, Orion is currently focused on leading the world of precision medicine and discovering new drugs that will improve and save lives.