William Le brings nearly 20 years of experience in drug development in oncology and immunotherapy to his role as Vice President of Operations for ImaginAb. We recently spoke to William about the future of immunotherapy technologies, and how ImaginAb is using imaging to change how cancer and autoimmune disease are managed. The following is a selection of excerpts from our conversation.
Keosys: Can you tell us how you came to your current role with ImaginAb?
WL: I’ve managed multiple programs throughout my career, from Phase I through commercialization, where I was involved in the filing of two NDAs, which in 2014 resulted in FDA market approval for a treatment of a rare cancer.
I joined ImaginAb in 2017 as the company shifted its development strategy to the CD8 ImmunoPET technology we’re currently working on. They reached out to me based on my expertise in clinical research and drug development. As VP of Operations, I oversee clinical development, regulatory, CMC, program management, and QA.
Keosys: The radiopharmaceutical industry has grown tremendously in recent years. What advantages and challenges do these therapies offer versus other types of therapies?
WL: A key advantage is that these therapies are precision medicine: directly targeting cancerous tumors with the right medical isotope to kills cancer cells while limiting damage to the surrounding healthy cells. They have a shorter treatment duration as compared to conventional chemotherapy or immunotherapy.
There are also challenges. Adoption is not yet widespread due to limited knowledge on efficacy and toxicity, as opposed to surgery/chemotherapy or the emerging immunotherapy in the past 20 years.
Another challenge is the availability of radioligands and medical isotypes; the material to generate these isotopes is still limited, and the global community is still building the infrastructure to address the supply chain. Because radiation is involved, regulation is very strict and delivery logistics are complex.
Another aspect is the short life of the isotopes. Sometimes they have to be manufactured on-site, which creates challenges for the hospital. Most radiopharmaceutical doses require a central manufacturing facility where they could be shipped out within days.
At ImaginAb we are working tirelessly with our industry colleagues to address these challenges. There are a lot of exciting things happening.
Keosys: What role can imaging play in immune-oncology?
WL: The conventional follow-up method involves a biopsy or resection of the tumor for lab analysis: an invasive procedure with lots of risks, including infection. Imaging, even conventional imaging like CT scans, MRIs or FDG PET scans, allows the ability to see the tumor, measure it, and correlate with historical data to help understand if the treatment is effective.
In an invasive biopsy, the clinician only sees a representative region of the tumor itself. Imaging technology captures the whole tumor to provide a better understanding of the tumor microenvironment and heterogeneity so it can help determine the best approach in managing the treatment.
Especially in immuno-oncology, where CD8 cells are involved, imaging of the tumor microenvironment is crucial for the clinician to understand how the drug is working.
Keosys: ImaginAb has developed an antibody fragment known as a ‘mini body’ to scan the physical immune response. What can you share about this CD8 imaging innovation?
WL: Our scientists take an intact antibody and remove certain functions to reduce it to about half the size. We label this ‘mini body’ with an isotope (Zirconium-89) so that when the product is injected we can identify the location of the CD8 cells under a PET/CT scanner. Once inside the human body the CD8 cells attach to it, but the mini body does not alter the cells or impact their biological function.
Immunotherapy modulates the CD8 cells to migrate to the tumor environment, infiltrate it, and kill the tumor, and so we build our development so we can correlate the changes in CD8 cell concentration. ImaginAb technology enables the clinician to see the CDA cell concentration around the tumor and within its microenvironment before and after treatment. If the drug is working, we will expect the concentration of CD8 cells around or in the tumor to increase.
Conventional imaging techniques require the patient to come back every three months for a CAT scan or MRI, and can take about six months to confirm because of the phenomenon of pseudo-progression—where the tumor is enlarged but isn’t actually progressing because of the influx of the CD8 cells.
But with ImaginAb CD8 imaging technology, we are able to eliminate that time burden. We are able to predict if the tumor would respond to immunotherapy and we can predict if it is just pseudo-progression. Instead of waiting months for conventional imaging techniques, our technology can help predict and respond within five or six weeks. For oncology patients, every minute counts. I think that our technology can be a game changer to help clinicians better manage patient treatment.
Keosys: You’ve mentioned the unique supply chain challenges posed by radiopharmaceuticals. ImaginAb recently announced numerous strategic partnerships to ensure reliable distribution of the CDA immunoPET agent. What role do strategic partnerships play in ensuring delivery and distribution?
WL: When you deal with radiation, there's a lot of caution from the custom authority. When you ship it from the U.S. to Europe, it has to clear the border. When they get to the airline, the dangerous goods officer has to clear it. Then it has to clear custom again to be delivered to the hospital.
For years, we have worked through these challenges and made significant improvements to the logistics and the distribution of radiopharmaceuticals, especially our CD8 imaging agent. We localized our manufacturing capability. We’ve built a network of manufacturing sites in the United States, Europe, and Australia, and continue to add more sites. We also signed a manufacturing contract with DuChemBio in South Korea, we’re working with a partner called Dongcheng for the Chinese market, and we’re exploring possibilities for the Japanese markets.
Keosys: Is there anything else that we should know about yourself, ImaginAB, immuno-oncology or CDA immunoPET that you think we should know?
WL: This is an investigational product, and we’re working tirelessly to bring it to the market as a clinical utility for medical oncologists to help improve the management of patient treatment. However, because it is already approved by health authorities for research purposes, we are allowed to license the product to other pharmaceutical companies to use in clinical trials.
In 2021 alone, there were more than 1,000 clinical trials working on developing immunotherapies. With ImaginAb technology, they can evaluate the CD8 cells before and after the patient receives the immunotherapy agent, meaning they can make a determination about its efficacy months or even a year earlier than conventional imaging methods.
Saving six months or a year in the development cycle saves a lot of money for the pharmaceutical company, and I hope it will lower costs for the final product when marketed for use. A shorter development cycle can help bring effective and proven products to patients faster.