Radiation is commonly employed in hospitals around the world to treat tumors, typically using gamma ray beams of high energy photons, with a relatively long range, that penetrate all the tissues on the way to and from the tumor. This leads to substantial damage to healthy tissues and too often results in poor outcomes. An alpha particle, consisting of two protons and two neutrons bound together and akin to a helium-4 nucleus, is much trickier to work with in medicine because it is extremely powerful, yet has a very short effective range.
We recently visited the offices of Alpha TAU, a company based in Jerusalem, which has implemented alpha radiation in the treatment of solid tumors by utilizing a novel manufacturing process to prepare so-called Alpha DaRT radioactive implants, developed specialty software that plans the treatment, delivery devices that are based on commonly used biopsy tools, and tied together a number of other technologies that help turn exotic radioactive sources into tumor killers.
Thanks to support from Biomed Israel, the leading international Life Science and HealthTech conference in Israel (see more below about the upcoming event), we enjoyed a tour with Ronen Segal, Chief Technology Officer of Alpha Tau, of the company’s headquarters, development, and manufacturing facility.
Ronen told us a story about Prof. Itzhak Kelson, the co-inventor of the core technology that the company relies on, who was the head of the physics department at Tel Aviv University. He had interesting ideas of using alpha radiation during microchip manufacturing, but regulations of radioactive materials put an end to that idea. Prof. Kelson then turned his sights on medicine, together with co-inventor Prof. Yona Keisari, and came up with an idea of diffusing atoms that emit alpha particles throughout a tumor, in essence increasing the effective range of alpha radiation and making it practical for clinical use.
The result was the Alpha DaRT, a stainless steel cylinder seeded with radium-224 atoms. Radium-224 decays through a number of steps during many of which alpha particles are released. While the alpha particles themselves don’t travel past about 50 microns in biological tissue, the atoms in the decay chain are able to diffuse through tissue up to several millimeters, substantially extending the effective range.
The technology had a chance when a company called Althera was founded, but due to an inability to fund clinical trials, the company ceased to exist just as things were getting interesting. Some years later, in 2015, Alpha TAU was founded by Uzi Sofer, the company’s CEO, to give the technology another opportunity to prove itself. The company bought up all the related patents, signed royalty agreements with different research institutions that were involved, and raised substantial funds to move forward. In 2022 the company went public on the NASDAQ and raised about $100 million more. (NASDAQ: DRTS)
The new company developed the Alpha DaRT into a product and organized a manufacturing process at its headquarters in Jerusalem. They source thorium-228 from the U.S. Department of Energy’s Oak Ridge National Laboratory, which is a byproduct of actinium-227 production, and extract radium-224 from the decaying thorium. Using the company’s own process, radium-224 is impregnated into a steel rod to make Alpha DaRT sources, which are then packaged in a custom kit made for treating specific tumors. Special software that takes DICOM images from CT scanners and creates a treatment plan, defines the distribution of the Alpha DaRT sources within the tumor. The goal is to irradiate the entirety of the tumor without causing much damage to healthy tissues beyond the margins. Because alpha radiation leads to double strand breakage of DNA, any solid tumor, regardless of its oxygenation, and even radiation resistant ones, that external beams have trouble managing to destroy, should be treatable using Alpha TAU’s technology. Moreover, due to the different nature of healthy and cancerous tissue, alpha radiation produced by Alpha DaRT sources diffuses about a millimeter into healthy tissue while penetrating at a diameter up to about five millimeters into tumors, providing an automatic safety mechanism.
To make implantation of the Alpha DaRT sources easy and precise, the company developed dedicated applicators andadapted existing biopsy devices, that physicians are already acquainted with, to deliver the radioactive sources. Surgeons, therefore, can be acquainted with how to perform the implantation procedure in a very short time, and the entire workflow doesn’t differ much from doing a biopsy.
Alpha TAU took their technology to clinical trials right around when COVID became a pandemic and patients didn’t want to spend a long time inside a hospital, which helped participating clinics try Alpha DaRT treatment, since it only takes a couple hours in a single visit, compared to surgery, which can involve hospitalization, or external beam radiation, which requires multiple visits.
Results from initial clinical trials were quite impressive. The first human trial done in Israel proved very successful (2017-2018, finalized during COVID), and published in the Red Journal, the official journal of the American Society for Radiation Oncology), involving many patients whose cancer recurred after treatment or whose options were exhausted. In the first study there was a 78% complete response (no residual cancer). The rest of the patients had partial responses. The FDA looked at the data, saw it promising, and asked for a small feasibility study in the U.S. with ten patients to try to duplicate the results. In this trial there was a 100% complete response.
In parallel, the FDA issued a breakthrough device designation to Alpha TAU for its Alpha DaRT technology for the treatment of skin cancer without curative standard of cure and another breakthrough device designation for GBM (glioblastoma multiforme), an aggressive brain tumor, based purely on pre-clinical trials.
Thanks to these designations, the firm is now preparing to commence a pivotal multi-center study with 20 sites around the U.S., which are currently recruiting patients. This will hopefully lead to an FDA approval for its first indication, after which Alpha TAU plans on expanding to other types of cancer and geographic regions such as Europe and Japan. In Israel, the company already has a ministry of health approval to treat patients.
One surprising aspect of Alpha TAU’s technology is that it seems to help the body to develop immunity to the type of cancer that is treated. In animal studies, researchers were unable to reintroduce the same cancer types that were effectively treated earlier, but had no problem at growing other cancer types in the same animals. In humans, the company published a case study of a patient having a number of tumors, that were scheduled to be treated at different times. But, once the first tumor was treated, the others disappeared on their own, demonstrating that there’s a potential systemic effect involving the immune system. Furthermore, a synergetic effect was demonstrated in animal studies which combined the Alpha DaRT with anti PD-1 checkpoint inhibitor immunotherapy.
Indeed, Alpha TAU’s technology is quite exciting and further studies may very well prove that it is highly effective against all solid tumors, and hopefully not just as a last resort. We got to see a bunch of photos of skin and head and neck cases that were treated with the Alpha DaRT, and they were indeed impressive. The company is already scaling up its facility in Israel to be able to supply treatment for 4,000 patients a year, has set one up in Massachusetts, and has longer term plans that involve facilities in Europe, Japan, and more sites in the United States. This will take some time, since there’s substantial regulatory hurdles when dealing with radioactive sources for medicine, but the company already has experience setting up this kind of shop and is doing its best to move forward.
Alpha TAU overcomes the logistic challenge of preparing the Alpha DaRT sources by making the bespoke sources as their software determines and loads these into a number of applicators that will be used during each procedure. These are then express mailed to the hospital with a strict time window during which the treatment must be complete, since the radioactive sources have a short half life and will not be sufficiently active if delivered too late. These factors require the logistics of the company to operate without skipping a beat so that patients are treated in a timely fashion. Sources are produced with the knowledge of when they will be picked up and delivered to their final destination, and their size takes into account this time period so they’re within their optimal effective strength following implantation. Two weeks following implantation, almost all the activity is washed out of the source and the alpha DaRT sources are only a piece inert steel, and can be removed using a reverse procedure.
We hope to see Alpha TAU presenting its technology at Biomed Israel, the leading international Life Science and HealthTech conference in Israel. This year it is scheduled for May 16-18, 2023 in Tel Aviv, and topics range from medical robotics, to bio-convergence, to the impact of AI on biopharma. Over 6,000 industry leaders, scientists, engineers, physicians, and investors will be attending for the 21st consecutive year of this conference. It is the largest event in Israel that brings together Israeli healthcare professionals and industry experts with international colleagues to work for three consecutive days on business opportunities, develop partnerships, and to seek new collaborations. Hundreds of Israeli life science firms will be showing off their products and technologies to attendees from all over the world. More info can be found at the Biomed Israel website. The conference is co-chaired by Ruti Alon, Founder and CEO of Medstrada, Ora Dar, PhD, Senior Expert, Medical Sciences and Health Innovation, and Nissim Darvish, MD, PhD, Managing Partner, Eliraz Ventures.
Here’s a video about the Alpha DaRT:
And an interesting skin care case that was treated with the Alpha DaRT:
Link: AlphaTAU homepage…