RefleXion Medical Submits IPO Filing for SCINTIX: A Real-Time, PET-Guided Radiotherapy Platform for All-Stage Cancer Treatment

Globally, both cancer incidence and the resulting mortality rates are on the rise. The World Health Organization previously predicted that by 2030, the annual number of new cancer cases worldwide would increase by 69%, reaching 21 million. According to the latest assessment by the International Agency for Research on Cancer (IARC), there were 19.29 million new cancer cases and 9.96 million cancer deaths globally in 2020. During this century, cancer is projected to surpass cardiovascular disease as the leading cause of premature death in most countries.

Compared with the myriad emerging innovative cancer therapies, RefleXion may offer a new approach. By integrating medical physics, nuclear medicine, and radiation therapy, it has developed SCINTIX, a biology-guided radiotherapy method that combines biological targeting with radiation. More importantly, this approach enables systemic radiation therapy for cancer patients at any stage for the first time, pioneering a new paradigm in cancer treatment.

RefleXion, founded in 2009, is a privately held oncology therapeutics company headquartered in Hayward, California, USA. Dr. Sam Mazin, the founder and Chief Technology Officer, was a postdoctoral fellow in radiology at Stanford University and received the Cum Laude Award from SPIE, the International Society for Medical Imaging, for his achievements in PET algorithms. Todd Powell, the President and Chief Executive Officer, brings 29 years of experience in developing innovative products for cancer care. RefleXion’s vision is to provide more effective, innovative treatment options for patients with advanced-stage cancer.

On November 4, 2022, RefleXion received the Pantheon Award for its convergence technology from California Life Sciences (CLS), the largest and most influential life sciences organization in California, in recognition of the company’s breakthrough technology.

For primary and metastatic lung cancer or bone cancer, RefleXion has developed a novel therapy—SCINTIX. Throughout the treatment process, this therapy determines the radiation delivery location using continuous real-time data, providing more comprehensive information and more precise targeting than traditional imaging. SCINTIX was initially approved for use in combination with fluorodeoxyglucose F18 (FDG) and covers all stages of lung cancer and bone cancer.

SCINTIX therapy leverages the gold standard of cancer imaging—positron emission tomography (PET)—to address the challenge of tumor motion. A single injection of a radiopharmaceutical transforms each tumor cell into a biological beacon, transmitting data on tumor cell location via continuous radioactive emissions. As the tracer accumulates in the tumor, onboard PET detectors on the RefleXion X1 system detect these emissions and utilize the data to deliver treatment with sub-second latency.

First, the patient needs to be injected with a drug containing radioactive isotopes, typically fluorodeoxyglucose (FDG). This drug is absorbed by tumor cells, causing them to emit positrons. Then, RefleXion X1 uses PET technology to capture the positron signals emitted by the tumor cells.

The RefleXion X1 integrates PET and CT, enabling real-time construction of tumor location and morphology maps based on detected radiotracer data, which are then combined with tumor imaging to guide radiotherapy.

The RefleXion X1 is equipped with fan-beam kVCT, which provides higher-quality images than cone-beam CT to improve intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT), thereby enhancing the accuracy of radiation delivery. The rotating ring gantry is one of the key components of the RefleXion X1; it can rotate continuously at a speed of 60 RPM, enabling simultaneous radiation delivery and PET emission detection. The PET detector arc consists of state-of-the-art solid-state silicon photomultiplier (SiPM) arrays, capable of collecting tens of thousands of real-time emission events as radiotracers accumulate in tumors. Currently, the RefleXion X1 has been approved for use in stereotactic body radiation therapy (SBRT), stereotactic radiosurgery (SRS), and intensity-modulated radiation therapy (IMRT).

Next, the RefleXion X1 analyzes the tumor’s location, size, shape, and motion based on PET signals, and calculates the optimal radiation dose and direction. Finally, the RefleXion X1 system employs linear accelerator (LINAC) technology, rotating at 60 revolutions per minute to deliver high-energy X-ray beams from multiple angles to destroy tumor cells.

Meanwhile, SCINTIX therapy enables precise and dynamic radiotherapy for multiple tumors simultaneously without the need for separate localization, thereby improving treatment efficiency and accuracy while reducing damage to normal tissues.

During treatment, tumor displacement often poses a significant challenge in determining the precise location and dosage for radiation therapy. As physiological activities such as respiration and cardiac motion occur continuously, the tumor’s position shifts constantly. Compared with conventional imaging diagnostics, SCINTIX offers a distinct advantage by tracking both periodic and non-periodic tumor movements induced by physiological processes. It can even promptly adjust radiation dosage and beam direction in response to sudden changes in patient positioning, thereby addressing two long-standing obstacles in the radiation therapy of metastatic diseases: targeting accuracy and motion management.

On February 2, 2023, RefleXion announced that the U.S. FDA had granted its SCINTIX biology-guided radiotherapy system the first marketing authorization. The SCINTIX therapy had previously received the FDA’s Breakthrough Device designation for the treatment of lung tumors, owing to its breakthrough capability to detect and treat multiple moving tumors. “Autonomous radiotherapy was merely a ‘concept’ more than a decade ago, but today, for the first time in the history of cancer treatment, we have achieved a paradigm where cancer cells themselves guide their own destruction,” said Dr. Sam Mazin, Founder and Chief Technology Officer of RefleXion.

For patients with stage IV cancer, treatment options are generally very limited, and most are not candidates for curative radiotherapy. RefleXion, however, offers these patients a new alternative. Cancer treatment is not a one-size-fits-all approach relying on a single modality; for many patients, the optimal treatment plan involves a combination of therapies. Incorporating SCINTIX therapy into regimens comprising chemotherapy, immunotherapy, and targeted drugs has the potential to improve outcomes for some patients with stage IV cancer.

On June 24, 2023, at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting held in Chicago, RefleXion announced the results of a prospective clinical imaging study conducted by City of Hope using PET on the RefleXion X1 system. These findings lay the groundwork for evaluating the application of SCINTIX therapy in conjunction with prostate-specific PET radiotracers for external beam radiotherapy targeting prostate cancer tumors. The prostate-specific PET radiotracer used in this study, 18F-DCFPyL (PyL), is FDA-approved for the diagnosis and staging of prostate cancer and can accurately localize tumors within the prostate as well as those that may have spread or metastasized to other parts of the body. The results support continued exploration into leveraging the precision of PyL to extend RefleXion’s SCINTIX therapy to patients with prostate cancer.

RefleXion is currently exploring tracers to extend the SCINTIX therapy to other specific diseases. It has entered into a collaboration agreement with a leading radiopharmaceutical manufacturer to develop fluorine- and gallium-based prostate-specific membrane antigen (PSMA) tracers, with the aim of one day expanding SCINTIX therapy to all stages of prostate cancer. The company also plans to broaden its radiotherapy applications to multiple oncologic indications, thereby benefiting more patients with advanced-stage cancers.

According to the latest 2020 global cancer burden data released by the International Agency for Research on Cancer (IARC), China has become a veritable cancer powerhouse. As a country with a large population, China’s cancer statistics are far from optimistic; it ranks first globally in both new cases and deaths.

Suzhou Zhihe Biopharmaceutical Technology Co., Ltd., established in 2015, is a radiopharmaceutical company dedicated to providing innovative radionuclide theranostic drugs to patients worldwide. Its product portfolio covers areas such as thyroid cancer, breast cancer, and radionuclide-based diagnostic and therapeutic agents for tumors. The company’s first independently developed PD-L1-targeted radionuclide imaging agent (SNA002) has received approval for clinical trial applications in both China and the United States. SNA002 is a gallium (Ga)-labeled radionuclide imaging agent targeting PD-L1, developed by Zhihe Biopharma through its proprietary SRC platform. Imaging can be performed just 1–2 hours after injection, enabling rapid differentiation between PD-L1-positive and PD-L1-negative tumor cells. It provides real-time, dynamic, and precise assessment of PD-L1 expression levels across all organs throughout the body, offering an alternative to conventional immunohistochemistry for PD-L1 detection.

Jinghe Biopharmaceutical Technology (Nanjing) Co., Ltd. is developing an integrative, imaging-guided next-generation targeted radionuclide therapy. While most existing radiopharmaceuticals consist of conventional drugs and targeted radioactive tracers, Jinghe Biopharma focuses on bringing theranostic approaches to market to improve treatment outcomes for cancer patients. One of its core technology platforms, J-Linker, enables the rapid and stable conjugation of highly selective and specific targeting ligands with particular radionuclides. Additionally, it allows for flexible modulation of the physicochemical properties of molecules, thereby significantly enhancing their druggability.

With significant improvements in cancer diagnosis and treatment, continuous advancement in the development pipeline of anti-tumor drugs, and an expanding population of cancer patients, the global oncology market is experiencing sustained growth. According to Frost & Sullivan, the global oncology drug market reached $150.3 billion in 2020 and is projected to reach $209.9 billion by 2022, with a compound annual growth rate (CAGR) of 15.2% from 2020 to 2025. Although the global oncology sector is currently highly competitive, the continuous emergence of innovative therapies has indeed bolstered confidence in this field.