As Amplia Therapeutics prepares to initiate the first of two Phase 2 clinicals trials for its lead asset, FAK inhibitor AMP945, we caught up with Managing Director and CEO, Dr John Lambert, to discuss the considerable work that happens behind the scenes prior to reaching the human trial stage.
Human clinical trials are a complex and necessary part of the process of developing and delivering new pharmaceutical products to patients. They are also a highly regulated research activity to ensure patients are not put at unnecessary risk of harm during the trials process. Before even reaching the clinic, biotech companies invest in years of research and development (R&D), gathering the necessary preclinical evidence to make a compelling case for clinical advancement.
In the case of Amplia’s lead molecule, FAK inhibitor AMP945, the upcoming human clinical trial in pancreatic cancer patients has been more than six years in the making.
“Finding a drug target is the fun bit - it is exciting and full of promise. Then comes the hard work, honing the medicinal chemistry, protecting the intellectual property and conducting the preclinical safety studies. These studies are vital because they provide the pieces of the puzzle that underpin the ethics of conducting clinical trials - we need to be satisfied that the candidate compound we have chosen is not only capable of doing what we want it to, but that we aren’t likely to compromise the health and safety of the patient in the process,” explained John.
This phase is when relationships with expert scientific collaborators, such as FAK researcher Dr Paul Timpson at the Garvan Institute of Medical Research are critical, providing the necessary preclinical data to give human trials a green light.
“It is those early safety and efficacy studies that provide the biggest hurdle to starting clinical development. If the drug we are developing isn’t safe, or has little prospect of being efficacious, then the drug development process comes to a stop.”
In the case of AMP945, numerous preclinical studies conducted both in the laboratory and in animal models demonstrated that the compound was safe enough to advance to a Phase 1 clinical trial. This data will form an important part of the company’s regulatory submission when it comes to meeting the stringent criteria for regulatory approval by agencies such as the US Food and Drug Administration and the Australian Therapeutic Goods Agency in the future.
“The regulatory hurdles are substantial, and with good reason. Patients need to trust that the drugs that are being prescribed to them have been thoroughly tested for safety and efficacy , and the regulatory process provides a structured way to ensure that we are delivering on that promise,” John said.
While achieving regulatory approval is an arduous undertaking, John appreciates the structure that the approval framework provides, and the scientific rigour that is required to gain approval.
“I find the regulatory approval process to be methodical in its approach. It provides a rigorous interrogation of the scientific evidence. Yes, regulatory agencies will pick holes in your data if you leave those open, but that is why the process is effective and our goal is to make sure that there are no holes.”
Amplia has assembled a dream team of employees and collaborators designed to ensure that not only are there no gaps in the science, but that the clinical development process runs as smoothly and successfully as possible.
“Drug development is the ultimate team sport. You need people with all different sorts of experience and expertise along the entire chain of development - from discovery through to commercialisation. It is critical to have people with deep clinical expertise, drug development experience, regulatory knowledge and manufacturing know-how. But it’s equally important to have team members with more generalist skills, who can tie all the different components together, and drive the work operationally from end-to-end.”
With regulatory approval and commercialisation the ultimate goals, Amplia places a lot of emphasis on maintaining meticulous documentation of the entire clinical development journey.
“Documentation can appear to be an administrative burden from the outside, but it is vitally important to the life of the project. It’s about making sure that new team members and regulatory agencies alike can understand the entire development history of our drugs from start to finish, why things were done and where things are going.”
When it comes to ensuring success of the AMP945 clinical trial, there are clearly no guarantees. But there is preparation and process, and scientific rigour is a central part of Amplia’s DNA.
“I think to work in biotech, you need to want to help people, and believe that what we’re doing is worth trying. To some, it can seem like a leap of faith to pursue drug development. While our intuition and commercial acumen both play their roles, our objective is to put as much rigour and ethics around the development process as we can.”