EXACT Therapeutics AS is a clinical-stage biopharmaceutical company headquartered in Oslo, Norway. The company is developing Acoustic Cluster Therapy (ACT®), a novel, ultrasound-mediated technology platform for delivering targeted therapeutics.
We recently spoke with CEO Per Walday, PhD, about the innovative company and its exciting clinical work testing ACT® in patients with metastatic cancer.
Tell us about EXACT Therapeutics. How was it started?
The company was spun out from GE Healthcare in 2012 by three senior scientists who had worked with ultrasound contrast agents since the early 1990s. This group of scientists wanted to use a unique large microbubble technology for drug delivery, and that is the technology we today call ACT®. This technology platform has since then been refined and patented for use in drug delivery, with solid preclinical evidence established for its utility in tumors and central nervous system (CNS) disorders.
EXACT Therapeutics is based in Norway, a nation with a rich heritage in the field of medical ultrasound. Norway boasts unique expertise in both ultrasound hardware and contrast agents. Pioneers in the medical application of ultrasound, such as Liv Hatle and Bjørn Angelsen, were Norwegian. Their groundbreaking work, along with the contributions of ultrasound experts in the technical and medical community in Trondheim, Norway, led to the establishment of several companies; notably, Vingmed, which was acquired by GE in 1998 to form GE Vingmed Ultrasound. In addition, Nycomed Imaging in Norway played a pivotal role in advancing ultrasound contrast agents. Nycomed currently has two products on the market: Optison and Sonazoid. Nycomed Imaging also became a part of GE Healthcare, underlining Norway’s significant contributions to the global ultrasound industry.
How did you get involved in starting or joining the company?
I joined the company in 2022, after having worked 15 years in the drug delivery field as a biotech CEO. My background is from GE Healthcare, and I was heavily involved in the early development of ultrasound contrast agents, including the development of the product that was later spun out and developed to become the ACT® technology for drug delivery.
Tell us about your company structure: ownership, lead executives, and their roles.
The company was listed on the Euronext Growth Stock Exchange, Oslo, in June 2020. The shareholder base consists of some of the most solid family offices in Norway, institutional investors, and three of the original founders.
We have a four-member board of directors chaired by Mr. Anders Wold, who was until recently the business development and strategic advisor to the GE Healthcare President and CEO. In spring 2021, he left his position as the CEO for GE Healthcare’s Global Clinical Care Solution business unit, which included the ultrasound business.
The Board further consists of:
- Vice Chair Masha Strømme, D.Phil., investor and advisor with more than 20 years of experience in the life sciences sector
- Sir William (Bill) Castell, previous vice chairman of GE and president of GE Healthcare
- Ann-Tove Kongsnes, investment professional and managing director of Investinor
The executive management team at EXACT includes the following:
Per Walday, PhD, Chief Executive Officer
I earned my PhD from the University of Oslo and have more than 30 years of experience developing pharmaceuticals from early preclinical to commercialization. I was previously CEO of PCI Biotech, where I managed the development of drug-device combinations through the US Food and Drug Administration and the European Medicines Agency regulatory paths to late-stage development. I was also formerly global head of project management at GE Healthcare, with responsibility for all development programs of new pharmaceuticals.
Svein Kvåle, PhD, Chief Operating Officer
Dr. Kvåle is a co-founder of EXACT Therapeutics AS and has more than 25 years of experience from pharma research and development (R&D), having worked for Nycomed Imaging, Amersham Health, and GE Healthcare, where he spent ten years as a senior scientist. Dr. Kvåle is also an inventor with more than 10 patents in diagnostics and cancer therapeutics, protecting five commercial products. He earned his PhD from the Norwegian University of Science & Technology.
Amir Snapir, MD, PhD, Chief Medical Officer
Dr. Snapir has extensive experience in global clinical development of novel therapeutics, international regulatory procedures, and business collaborations, alliances, and co-developments. He was previously chief medical officer of PCI Biotech, where he was responsible for the clinical development of drug-device combination products. He has also been the leader of clinical pharmacogenomics and clinical development in oncology at Orion Pharma. Dr. Snapir earned his PhD from the University of Turku, Finland, and his MD from the University of Tel Aviv, Israel.
John M. Edminson, Chief Financial Officer
Mr. Edminson has served in various finance roles spanning more than 20 years, including auditor at KPMG Oslo and KPMG Boston, as well as finance manager roles at Telenor Mobile and Kistefos. Mr. Edminson also held the positions of chief financial officer of PatientSky Group and Questback – both companies that are listed on Euronext Growth.
Caspar Foghsgaard, Senior Vice President, Commercial and Business Development
Mr. Foghsgaard brings broad life science and commercial experience from listed and private companies. His latest roles have been with Nykode Therapeutics, where he has served as Sr. Director of Special Projects and was part of the extended leadership team. Prior to that, he led Nykode’s business development activities as Director Business Development. He has also held business development and strategy roles at Arcus, Elopak, and Novozymes in Denmark, the United States, and the UK.
In general, what is the current status of your company?
We are currently conducting a Phase I clinical study in patients with colorectal cancer that has spread to the liver. The dose escalation part of the study produced highly encouraging safety and efficacy results. We are now recruiting patients for the dose expansion phase of the study. The dose escalation phase of the study was performed at the Royal Marsden hospital in London, while dose expansion is being conducted at several hospitals in Europe. In tandem with completion of the dose expansion phase, the company is planning to initiate a Phase II study in locally advanced pancreatic cancer, including sites in the United States.
We are also working with our partners to expand the applications for the ACT® platform, with preclinical studies ongoing in several potential use areas. Just before year-end 2022, we received a $1.5 million grant to study immunotherapy applications of ACT®. This project is a collaboration with TGen (part of City of Hope), in Arizona, US, Institute of Cancer Research at Royal Marsden Hospital in the UK, and the Norwegian University of Science and Technology.
One of the most exciting applications is in diseases of the brain. We have already shown in preclinical models that ACT® can safely deliver macromolecules across the blood-brain barrier, and we have recently entered into a strategic partnership with Cordance Medical for brain applications.
Tell us about the ACT® platform. How many years has it been in development and what are its origins?
EXACT Therapeutics and our ACT® platform build on decades of R&D efforts within ultrasound and microbubbles performed by the former world-leading diagnostic company, Nycomed Imaging AS (now GE Healthcare). The core technology behind ACT® was developed in the late 1990s and early 2000s, with more than $10 million and 40 man-years invested into establishing formulation, manufacturing line, quality control, preclinical data, and more. In 2012, three senior scientists spun the technology out from GE Healthcare to form EXACT Therapeutics – with the aim to develop ACT® for therapeutic applications.
Which health conditions or diseases will your technology be used for?
We consider ACT® as a platform technology that can be used for multiple diseases and conditions, spanning from oncology to CNS diseases to applications within gene and cell therapy.
Is your system approved for commercial use in any markets? If so, how is it being used in these markets?
No, it has not yet been approved for commercial use.
What are some of the technical challenges your group has had to overcome to develop a fully noninvasive system?
ACT® technology uses low energy levels of diagnostic ultrasound, so the technology is well known. The procedure requires two different transmit frequencies. The ultrasound required to activate the proprietary microbubble-microdroplet clusters can be achieved with any diagnostic clinical ultrasound system, but the low-frequency ultrasound to enhance the therapeutic effect requires a dedicated ultrasound probe. Functioning clinical prototypes have been developed in collaboration with GE Healthcare, but a user-friendly clinical system is required for widespread adoption.
We also have a partnership with Cordance Medical who is developing the NeuroAccess™ device for therapeutic ultrasound CNS applications.
What challenges do you have to tackle moving forward?
The clinical studies needed for approval of the microbubble-microdroplet cluster drug is the biggest challenge in the development of this technology, and it must follow normal regulatory drug development requirements. We already have commercial good manufacturing practice (GMP) production capabilities established in collaboration with GE Healthcare, which is quite unique for an early phase company. The plan is to develop lean user-friendly ultrasound devices in collaboration with existing players in the field.
Tell us about your clinical studies and the results.
We are currently conducting a multisite clinical Phase I/II study in Europe in patients with colorectal cancer that has spread to the liver – the ACTIVATE study. The dose-escalation part of ACTIVATE, performed at the Royal Marsden hospital in London, was completed in August 2023, and the results were released in September. The dose escalation part is mainly for safety, but the implemented intra-patient control design – where the patients receive standard of care treatment, and we use ACT® to enhance the effect in only one of the liver tumors and compare the response to the other liver tumors – allows for a controlled tumor response readout as well. This part of the study included eight hard-to-treat cancer patients that have been through many (up to seven) lines of prior treatment, and safety and efficacy results are available from six patients. The initial safety results suggest a clean safety profile, and the initial tumor response results are highly encouraging, with substantially more shrinkage of ACT®-treated tumors. The dose-expansion part of ACTIVATE started in August, with the aim to include 12–20 additional patients randomized to two different doses of the proprietary ACT® formulation (PS101).
Following this, we are planning to initiate a Phase II study of the ACT® platform with PS101 in combination with standard-of-care therapeutics in first-line treatment of locally advanced pancreatic cancer. This will be a multisite study spanning clinical sites in both Europe and the US. The selection of pancreatic cancer is based on a strong rationale with the mechanism of action of the ACT® technology, as well as convincing preclinical results in relevant pancreatic cancer models with standard-of-care therapeutics. An animal model using patient-derived pancreatic tumor material, which better resembles the dense stroma that severely hampers drug delivery, was published in 2022 by the research group of Professors Dan Von Hoff and Haiyong Han at TGen. In this study, treatment with ACT® was shown to strongly increase tumor shrinkage induced by treatment with standard-of-care chemotherapeutics, with a 7.2-times higher probability of having a complete tumor remission compared with chemotherapeutics alone.
What are the benefits of your technology over companies?
PS101 contains clusters of negatively charged microbubbles and positively charged microdroplets. These highly engineered small (<5μm) clusters are free flowing in the bloodstream until activated with normal diagnostic ultrasound at the target site for drug delivery. The insonation enlarges and deposits the bubbles in capillaries at the target site, allowing for low-frequency manipulation using low-energy ultrasound. The deposited ACT bubbles induce mechanical effects, such as microstreaming and shear stress, on the capillary wall and the surrounding tissue, which increases the local permeability of the vasculature and improves the transport of the co-administered therapy across the capillary wall and through the extracellular matrix, thereby delivering substantially more therapeutic agent directly where it is needed. Ultrasound is applied only for a few minutes and after that the larger bubbles dispatch and dissolve.
PS101 presents three significant benefits: 1) the formulation is activated and thereby deposited at the target site by the use of focused ultrasound, providing an extended time window for manipulation of the vasculature and tissue; 2) the activated ACT bubble is 1,000 times the size of free-flowing bubbles, substantially increasing the biomechanical effect of stable cavitation with low-energy ultrasound manipulation; and 3) ACT bubbles are in direct contact with the endothelial cells after activation, providing a direct effect on the cellular lining of the capillaries. Other standard microbubbles designed for diagnostic use will typically flow straight through the capillaries without much contact with the endothelium.
Since ACT® is only activated by the localized application of ultrasound, it is possible to precisely target therapeutic enhancement where it is required. The ultrasound energy levels used are lower than those commonly applied in fetal ultrasound imaging.
Have you learned any lessons for watching the experience of the other companies?
The key leadership members in EXACT Therapeutics have been involved in similar drug-device combination product development for drug delivery in previous companies, and the company possesses deep domain knowledge and extensive experience on regulatory paths and requirements within this field.
Do you partner with other companies?
EXACT Therapeutics has an open and collaborative approach to the development of ACT®. The technology is well suited for targeted delivery of precision medicine and advanced therapies, and we are seeking collaboration with companies that need improved targeted delivery methods for their innovative drugs.
The company is a spinout from GE Healthcare, and we still have a close collaboration, both for PS101 manufacturing and for ultrasound medical devices.
In September 2023, we announced a strategic partnership with Cordance Medical, which is based in the US.
For preclinical studies, we collaborate with several expert academic centers. We currently have very close collaborations with TGen (part of City of Hope), in Arizona, US, Institute of Cancer Research at Royal Marsden Hospital in the UK, and the Norwegian University of Science and Technology.