- OxSonics Therapeutics is a clinical-stage oncology company that has developed an ultrasound-based drug delivery platform.
- Their SonoTran Platform uses low-intensity focused ultrasound combined with injectable ‘SonoTran Particles’ to enhance the dose and penetration of unmodified cancer drugs into solid tumors to enable more effective therapies for cancer patients.
OxSonics Therapeutics is a clinical-stage oncology company that has developed an ultrasound-based drug delivery platform called ‘SonoTran.’ With a vision to maximize the therapeutic potential of a wide range of existing and emerging cancer drugs, OxSonics’ SonoTran Platform uses low-intensity focused ultrasound combined with injectable ‘SonoTran Particles’ to enhance the dose and penetration of unmodified cancer drugs into solid tumors to enable more effective therapies for cancer patients.
We interviewed Co-Founder and CEO, Colin Story, PhD, to learn more.
What is the name of the company, and where is located?
OxSonics Therapeutics is headquartered in Oxford, United Kingdom (UK). Our address is The Magdalen Centre, Oxford Science Park, Robert Robinson Avenue, Oxford, OX4 4GA, UK.
How was the company started?
OxSonics is a spinout company from the University of Oxford’s Institute of Biomedical Engineering, where the Biomedical Ultrasonics, Biotherapy, and Biopharmaceuticals Laboratory (BUBBL) is internationally recognized for its work using therapeutic ultrasound for drug delivery. They set about researching ways of overcoming the widely renowned challenge of poor drug penetration into solid tumors to treat cancer. Solid tumors consist of tightly packed cells and are characterized by being less well vascularized compared to ‘normal’ tissue, and these features combine to hinder drug delivery by diffusion alone – particularly for larger biologic drugs such as antibodies, antibody-drug-conjugates, bi-specifics, and oncolytic viruses.
There were two main areas of original intellectual property generated at Oxford: The spatial detection of ultrasonically induced inertial cavitation in real time (also called ‘passive acoustic mapping’ or ‘see-as-you-treat’ technology) and a novel type of injectable cavitation nuclei. We call these “SonoTran Particles,” and they have a mean diameter of 480 nm that carry 200-nm-sized air bubbles on their surface. OxSonics has four co-founders who worked together to raise capital to spin-out the company in January 2014.
How did you get involved in starting or joining the company?
I am one of OxSonics’ four co-founders. The others are Professor Constantin Coussios, FREng, Dr. Christian Coviello, and Professor Robert Carlisle. I’ve been in industry for over 25 years – mainly in commercial roles. Before that, I earned my PhD in the field of molecular biology. When I first was introduced to the academic team and what they had invented, I was struck by how innovative the technology was and how broadly it could be applied, particularly to help patients tackle tough-to-treat cancers.
Tell us about your company structure: ownership, lead executives, and their roles. In general, what is the current status of your company?
OxSonics is a privately held, venture capital and angel investor–backed clinical stage company with a vision to maximize the potential of existing and emerging cancer therapies for the benefit of cancer patients worldwide. We are currently a group of 30 employees, and 18 of those have earned a PhD. On the technical side, the multi-disciplinary team includes acoustic engineers, electrical engineers, software engineers, chemists, and biologists. We also have very experienced regulatory, operational, commercial, and administration teams in the company.
Our lead executives are:
- Colin Story, PhD, Chief Executive Officer, Executive Director, and Co-Founder
- Christian Coviello, PhD, Chief Technology Officer and Co-Founder
- Nicholas Adams, Chief Business Officer
- Andrew Mullen, MBA, Senior Director, Operations
- Cliff Rowe, PhD, Development Director
- David Preston, Finance Director
How many years has your treatment platform been in development, and what are its origins? Does it have a name?
The SonoTran Platform has been in development since January 2014 within the company. The company’s development built on original research conducted at the Institute of Biomedical Engineering, University of Oxford, from as early as 2007.
Are SonoTran Particles microbubbles?
No, they’re not. In fact, the limitations presented by the use of microbubbles as cavitation nuclei is the very reason why the SonoTran Particles were conceived at the university and further developed within the company. Firstly, microbubbles have a relatively poor pharmacokinetic profile, meaning that infused microbubbles only circulate for a few minutes before being cleared via the lungs, whereas an infusion of SonoTran Particles in preclinical pig studies enabled a full hour of treatment time. Secondly, unlike microbubbles, due to the manufacturing process of SonoTran Particles, bubble size is relatively small and very uniform. Microbubble formulations tend to be heterogenous, ranging from 2-10 microns, whereas SonoTran Particles have a very tight size distribution at 480 nm carrying 200-nm-sized air bubbles. This means that cavitation response is much more consistent and controlled. Also, with bubbles expanding by roughly 10-fold their original size during inertial cavitation, SonoTran Particles present an inherently safer cavitation nucleation agent in the context of the blood vessel. Thirdly, because SonoTran Particles are solid phase and smaller than microbubbles, it has been shown that SonoTran Particles penetrate the tumor mass: Their action is not confined to the blood vessel, where microbubbles are destroyed. Last but by no means least, a higher density of cavitation nuclei is available when using SonoTran Particles compared with microbubbles, further enhancing drug delivery capability. This has been demonstrated in several publications comparing the two types of cavitation nuclei head-to-head.
Tell us about your SonoTran ultrasound System
In parallel with developing a clinical scale manufacturing process for the SonoTran Particles, the company has also developed its own dedicated ultrasound system with a novel ultrasound probe design fully optimized for therapeutic use in an oncology ward setting. The SonoTran System is a mobile unit that incorporates the company’s ‘see-as-you-treat’ technology, providing the operator with on-screen feedback as to the location and extent of inertial cavitation in real-time. This means the operator can review treatment progress and help ensure they cover the entire treatment region of interest with confidence. This feature, combined with the potential to co-register with previously acquired high-resolution, patient-specific diagnostic CT or MR to real-time ultrasound, makes the system intuitive to use by more junior hospital staff aiding adoption and reducing costs.
What are the benefits of your technology over other companies?
There are several drug delivery approaches that involve cancer drug encapsulation or chemical modification of a given cancer drug to alter its pharmacokinetic profile. In each of these cases, the manufacturing process involving the drug is modified and has to be further optimized from a regulatory perspective, because the cancer drug is classified as a new chemical entity. SonoTran does not require any costly or time-consuming drug modification whatsoever.
Both the SonoTran Particle and the ‘see-as-you-treat’ technologies cover the unique benefits as described above. The technologies are novel, proprietary, and protected by granted patents in the major territories.
Overall, OxSonics is the only company we are aware of that provides a complete solution combining the injectables and the ultrasound system fully optimized for therapeutic use in the oncology ward setting.
What are some of the technical challenges your group has had to overcome to develop this system?
We have invested significant time and capital in developing an at-scale, good manufacturing practice (GMP) procedure for SonoTran Particles. The other significant technical achievement has been to develop a tri-functional ultrasound probe that performs diagnostic ‘B-mode’ imaging, delivers a therapeutic pulse to cause inertial cavitation, and detects inertial cavitation in real-time all in the same size and form factor of a standard diagnostic ultrasound probe. Last but not least, the SonoTran ultrasound System as a whole has been a major achievement, with much of the software and functionality designed by the OxSonics team through consultation with leading oncology radiologists.
Who will be your users – what type(s) of clinicians?
The decision to use SonoTran will rest with the medical oncologist based on our marketing claims being drug performance/efficacy based.
Because the SonoTran ultrasound System is so intuitive to use, it has the potential to be operated by trained and certified sonography nurses or junior radiologists as opposed to senior consultant radiologists. The SonoTran Particles are compounded into standard infusion bags and infused into the patient by an oncology nurse in the same way as many oncology drugs.
What challenges do you have to tackle moving forward?
Because we have taken the time to develop an optimized and scalable product offering for both the SonoTran Particles and SonoTran ultrasound System, provided we succeed in achieving clinical trial endpoints, we have a market-ready product.
The same as any clinical-stage company, we need to continue to recruit patients into our clinical development programs as fast and as efficiently as possible.
Tell us about your clinical studies.
Our own preclinical studies and those of our collaborators have generated compelling delivery and corresponding efficacy data across several drug classes and cancer types. OxSonics is now a clinical-stage company having commenced the enrollment and dosing of patients in a first-in-human clinical investigation in January 2022. SonoTran is being evaluated in a phase I/IIa multicentre clinical investigation in patients with metastatic colorectal cancer (mCRC) funded by the National Institute for Health Research (NIHR).
The clinical investigation includes three patient cohorts to evaluate:
- The safety of the SonoTran Platform;
- SonoTran’s ability to enhance the delivery of cetuximab and irinotecan into tumours in resectable mCRC patients; and
- SonoTran’s ability to enhance tumour response to standard of care first-line chemotherapy (cetuximab + FOLFIRI) in unresectable mCRC patients.
Can the SonoTran platform be used to treat multiple metastases at the same time?
Due to the superior pharmacokinetic and performance characteristics of SonoTran Particles, they should be able to be used to treat patients for periods of around one hour. This means there is time to treat multiple metastases in the liver – and even in other parts of the body – during a single treatment session.
You mentioned delivering antibodies. Will your platform be used to deliver cancer immunotherapies?
In collaboration with the University of Oxford, data were generated with an immunotherapeutic anti-PDL1 antibody, and that preclinical study demonstrated a significant enhancement in dose and distribution of the antibody, which in turn correlated with a doubling of median survival.
Do you partner with other companies?
Yes, we’re building a pipeline of ‘in-house’ and partnered development programs. We are currently participating in a number of preclinical evaluation programs with biotech and pharmaceutical companies. In each case, we have generated profound enhancements in efficacy when combining SonoTran with the partner drug. Interested companies should check out our website and dedicated partnering page.
Which health conditions or diseases will your technology be used for?
Solid tumor cancers account for 90% of all adult cancers. SonoTran has the capability to be used in many solid tumor cancers, such as head and neck cancer, breast cancer, pancreatic cancer, liver cancer, bladder cancer, prostate cancer, ovarian cancer, renal cancer, and soft tissue sarcoma.
The SonoTran Platform also has potential applications beyond oncology. For example, we envision its use to enhance the delivery of drugs into heart tissue or to enhance the delivery of thrombolytic agents into blood clots.