Going Beyond Traditional Diagnostics and Therapies, Delivering Precise Cancer Treatments
In June 2020, Colin Hayward, MBBS, joined Telix Pharmaceuticals as Chief Medical Officer. Dr. Hayward was attracted to the company’s oncology pipeline and the potential of on data-driven diagnostic approaches leading to therapeutic nuclear medicine. Bringing twenty-plus years of global pharmaceutical, biotechnology, and drug development experience, he leads the company’s worldwide medical affairs, regulatory, clinical operations, and pharmacovigilance activities. Indeed, it is under his guidance that Telix moves its product portfolio toward FDA marketing approval. “What I find exciting is that we’re taking a number of promising products further down the development pathway to see how they will address unmet medical needs,” Dr. Hayward says. “The nuclear medicine community is very important to Telix. As a company, showing our commitment to nuclear medicine is critical to fulfilling the utility of these products.”
Committed to molecularly targeted radiation (MTR) for personalized therapy
Telix focuses on products related to molecularly-targeted radiation (MTR). In MTR therapy, a radionuclide is attached to a targeting agent such as a small molecule or antibody. This targeting agent binds to and delivers a highly selective radioactive payload to tumors for diagnosis, therapeutics, or both. MTR offers the potential for better-informed treatment decisions and personalized therapy that, in turn, can lead to better outcomes.
The Telix pipeline currently concentrates on the development and commercialization of several oncologic clinical-stage assets aimed at different molecular cancer targets – PSMA, CA9 and LAT-1. The Australia-based company is also actively exploring indication expansion opportunities for its products including diagnostic and advanced therapeutic approaches. In combination with a network of partners, Telix has investigational products in 60 countries and is running clinical trials in 25 countries, including Mexico, Egypt, Russia, and India.
“Molecularly-targeted radiation is part of our very essence at Telix, and we believe in using radiation to address oncologic therapy. Our products combine the power of precision with the potential power of radiation to target very specific sites within tumors and very specific tumors to deliver intelligent therapeutics,” Dr. Hayward explains.
He believes that molecularly-targeted radiation products can be applied throughout the theranostic pathway, with both imaging and therapeutic potential, an exciting opportunity for pharmaceutical development. “This really has the potential to be made into a backbone of cancer therapy,” Dr. Hayward says. “The applications in diagnostics and therapy are about delivering more precise radiation, which can also help surgical outcomes.”
Pushing boundaries with clinical trials
Telix is entering new frontiers of diagnostic and therapeutic nuclear medicine through a number of significant clinical trials, both company-sponsored and in collaboration with cancer centers around the globe.
The ZIRCON Study is a multi-center phase III study to evaluate the diagnostic performance of 89Zirconium-labeled girentuximab (89Zr-TLX250) to noninvasively detect clear cell renal cell carcinoma (ccRCC) by positron emission tomography/CT (PET/CT) imaging in patients with indeterminate renal masses. 89Zirconium-labeled girentuximab, or TLX-250, is an antibody that targets carbonic anhydrase IX (CA9), an enzyme that, in humans, is encoded by the CA9 gene. CA9 is overexpressed in many types of cancer, including ccRCC and carcinomas of the cervix, breast, and lung, where it promotes tumor growth by enhancing tumor acidosis.
“CA9 is expressed in a number of tumors, so TLX-250 has great potential in renal cancer and more. I think this is a very important, unmet need in the urological community to potentially diagnose patients with girentuximab-based imaging and determine if there’s an underlying malignancy,” says Dr. Hayward.
“The applications go beyond diagnostics and to therapy to help clinicians deliver more precise radiation, which can also help surgical outcomes,” Dr. Hayward adds, noting that recent studies indicate that CA9 could also be a potential marker of resistance to immunotherapy in oncology, opening another application opportunity for TLX-250.
“The potential to identify immune-resistant tumors with imaging is very exciting. We’re just touching the very tip of the iceberg of the potential of using TLX-250 with CA9 expression,” he says.
Telix is also invested in studying its TLX-101 product in diagnosing and treating patients with glioblastoma, the most common and aggressive malignant brain tumor in adults. The IPAX-1 Study is a phase I/II open label trial to evaluate the safety and efficacy of 131I-TLX101 (iodine phenylalanine) in combination with external beam radiation therapy in patients with recurrent glioblastoma.
“Glioblastoma is a huge unmet medical need, and nothing has been licensed in this area for some time,” Dr. Hayward says. “We’re hoping to expand the program more broadly into patients with LAT-1 expressing tumors, while developing an efficacy pathway and proof of concept pathway in glioblastoma.”
Targeting prostate cancer
Currently, the company’s No.1 priority is developing prostate cancer applications.
Prostate cancer is the fourth-most common cancer in the world; 1.3 million initial cases were diagnosed in 2018. Despite treatment advances, prostate cancer still accounts for many deaths---more than 365,000 men died of the disease in 2018.
An estimated 100,000 prostatectomies a year are performed in the U.S., with 50,000 to 60,000 biochemical cancer recurrences. In these settings, prostate specific membrane antigen (PSMA) imaging could help to develop new interventions for post-prostatectomy patients with rising PSA levels, thus improving outcomes.
PSMA is a tumor-associated antigen and type II transmembrane protein, expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells.68Ga-PSMA-11 is a radioisotope that upon intravenous administration, targets and binds to PSMA-expressing tumor cells. Upon internalization, PSMA-expressing tumor cells can be detected during Positron Emission Tomography (PET) imaging.
Telix’s investigational prostate cancer program consists of a companion diagnostic imaging agent (TLX591-CDx) and a therapeutic (TLX591) to improve detection and treatment of metastatic prostate cancer. TLX591 (177Lu-DOTA-Rosopatamab) is an antibody-based therapeutic radiopharmaceutical targeting PSMA and is in pre-Phase 3 development with trials planned to start in Australia and the United States in early 2021 (subject to regulatory approvals).
Gallium PSMA can help cancer patients today
The TLX591-CDx diagnostic imaging agent comes in a “cold kit” for rapid preparation of 68Ga-PSMA-11 injection and is compatible with major commercially available 68Ga generators. It’s currently being used under a U.S. Investigational New Drug application at several leading cancer centers, and in the Novartis VISION trial, a phase III study comparing the efficacy of 177Lu-PSMA 617 plus standard of care, to standard of care alone, in the setting of progressive PSMA positive metastatic prostate cancer.
“Gallium PSMA is potentially more sensitive and specific in terms of evaluating prostate cancer, which could change patient management decisions… made based on traditional imaging,” says Dr. Hayward. He notes that many patients with biochemical recurrence, a rising PSA after initial radical prostatectomy or radiotherapy as potential curative therapy, will go on to have recurrent prostate disease. “Gallium PSMA can help us understand the extent of recurrence and plan appropriate management strategies. We can also use gallium PSMA to potentially detect PSMA-positive lesions earlier as well,” he says. “Gallium PSMA can provide additional information over and above existing CT, MRI, or bone scans alone to understand the extent of disease and to clearly define the stage of that disease.”
“If we gain approval and can fully commercialize gallium PSMA, we'll continue to develop the product and look for new indications with our academic partners, many of which are already working with us to understand how to maximize the utility of the product,” he says.
Readership training is important
With an increase in the utilization of 68GA PSMA-11, Telix recognizes the need to help clinicians develop their skills in reading PSMA imaging. With this prostate cancer MTR agent as their focus, they are committed to delivering targeted readership training designed for the Nuclear Medicine Physician and Radiologist. The overall goal is to prepare the readers with improved confidence and skills, which ultimately aids in treating patients more effectively. “Providing readers with clear training to accurately read these scans is very important so they can support their colleagues in urology and surgery…resulting in a multidisciplinary team that fully understands and appreciates the implications of the reader.” says Dr. Hayward
Citing these efforts as an example of how Telix is leading the way to improved cancer diagnoses, Dr. Hayward says, “the goal is to have a network of experts who are able to support the nuclear medicine community in the future and improve patient care.”
Editor’s Note: Applied Radiology spoke with Colin Hayward, MBBS, Chief Medical Officer of Telix Pharmaceuticals about the company’s growth and targeted focus to help patients with cancer live longer and better lives. This article is based on that conversation.
*No Telix agent has received regulatory authorization in any jurisdiction.