Alpha TAU Killing Tumors With Highly Targeted Alpha Radiation
Radiation is commonly employed in hospitals around the world to treat tumors, typically using gamma ray beams of high energy photons, with a relatively…
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.
Ronen Segal
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:
Watch Yield Curve For When Stocks Begin To Price Recession Risk
Authored by Simon White, Bloomberg macro strategist,
US large-cap indices are currently diverging from recessionary leading economic data. However, a decisive steepening in the yield curve leaves growth stocks and therefore the overall index facing lower prices.
Leading economic data has been signalling a recession for several months. Typically stocks closely follow the ratio between leading and coincident economic data.
As the chart below shows, equities have recently emphatically diverged from the ratio, indicating they are supremely indifferent to very high US recession risk.
What gives? Much of the recent outperformance of the S&P has been driven by a tiny number of tech stocks. The top five S&P stocks’ mean return this year is over 60% versus 0% for the average return of the remaining 498 stocks.
The belief that generative AI is imminently about to radically change the economy and that Nvidia especially is positioned to benefit from this has been behind much of this narrow leadership.
Regardless on your views whether this is overdone or not, it has re-established growth’s dominance over value. Energy had been spearheading the value trade up until around March, but since then tech –- the vessel for many of the largest growth stocks –- has been leading the S&P higher.
The yield curve’s behaviour will be key to watch for a reversion of this trend, and therefore a heightened risk of S&P 500 underperformance. Growth stocks tend to outperform value stocks when the curve flattens. This is because growth companies often have a relative advantage over typically smaller value firms by being able to borrow for longer terms. And vice-versa when the curve steepens, growth firms lose this relative advantage and tend to underperform.
The chart below shows the relationship, which was disrupted through the pandemic. Nonetheless, if it re-establishes itself then the curve beginning to durably re-steepen would be a sign growth stocks will start to underperform again, taking the index lower in the process.
Equivalently, a re-acceleration in US inflation (whose timing depends on China’s halting recovery) is more likely to put steepening pressure on the curve as the Fed has to balance economic growth more with inflation risks. Given the growth segment’s outperformance is an indication of the market’s intensely relaxed attitude to inflation, its resurgence would be a high risk for sending growth stocks lower.
COVID-19 lockdowns linked to less accurate recollection of event timing
Participants in a survey study made a relatively high number of errors when asked to recollect the timing of major events that took place in 2021, providing…
Participants in a survey study made a relatively high number of errors when asked to recollect the timing of major events that took place in 2021, providing new insights into how COVID-19 lockdowns impacted perception of time. Daria Pawlak and Arash Sahraie of the University of Aberdeen, UK, present these findings in the open-access journal PLOS ONE on May 31, 2023.
Participants in a survey study made a relatively high number of errors when asked to recollect the timing of major events that took place in 2021, providing new insights into how COVID-19 lockdowns impacted perception of time. Daria Pawlak and Arash Sahraie of the University of Aberdeen, UK, present these findings in the open-access journal PLOS ONE on May 31, 2023.
Remembering when past events occurred becomes more difficult as more time passes. In addition, people’s activities and emotions can influence their perception of the passage of time. The social isolation resulting from COVID-19 lockdowns significantly impacted people’s activities and emotions, and prior research has shown that the pandemic triggered distortions in people’s perception of time.
Inspired by that earlier research and clinical reports that patients have become less able to report accurate timelines of their medical conditions, Pawlak and Sahraie set out to deepen understanding of the pandemic’s impact on time perception.
In May 2022, the researchers conducted an online survey in which they asked 277 participants to give the year in which several notable recent events occurred, such as when Brexit was finalized or when Meghan Markle joined the British royal family. Participants also completed standard evaluations for factors related to mental health, including levels of boredom, depression, and resilience.
As expected, participants’ recollection of events that occurred further in the past was less accurate. However, their perception of the timing of events that occurred in 2021—one year prior to the survey—was just an inaccurate as for events that occurred three to four years earlier. In other words, many participants had difficulty recalling the timing of events coinciding with COVID-19 lockdowns.
Additionally, participants who made more errors in event timing were also more likely to show greater levels of depression, anxiety, and physical mental demands during the pandemic, but had less resilience. Boredom was not significantly associated with timeline accuracy.
These findings are similar to those previously reported for prison inmates. The authors suggest that accurate recollection of event timing requires “anchoring” life events, such as birthday celebrations and vacations, which were lacking during COVID-19 lockdowns.
The authors add: “Our paper reports on altered timescapes during the pandemic. In a landscape, if features are not clearly discernible, it is harder to place objects/yourself in relation to other features. Restrictions imposed during the pandemic have impoverished our timescape, affecting the perception of event timelines. We can recall that events happened, we just don’t remember when.
#####
In your coverage please use this URL to provide access to the freely available article in PLOS ONE: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0278250
Citation: Pawlak DA, Sahraie A (2023) Lost time: Perception of events timeline affected by the COVID pandemic. PLoS ONE 18(5): e0278250. https://doi.org/10.1371/journal.pone.0278250
Author Countries: UK
Funding: The authors received no specific funding for this work.
Journal
PLoS ONE
DOI
10.1371/journal.pone.0278250
Method of Research
Survey
Subject of Research
Not applicable
Article Title
Lost time: Perception of events timeline affected by the COVID pandemic
Article Publication Date
31-May-2023
COI Statement
The authors have declared that no competing interests exist.
Hyro secures $20M for its AI-powered, healthcare-focused conversational platform
Israel Krush and Rom Cohen first met in an AI course at Cornell Tech, where they bonded over a shared desire to apply AI voice technologies to the healthcare…
Israel Krush and Rom Cohen first met in an AI course at Cornell Tech, where they bonded over a shared desire to apply AI voice technologies to the healthcare sector. Specifically, they sought to automate the routine messages and calls that often lead to administrative burnout, like calls about scheduling, prescription refills and searching through physician directories.
Several years after graduating, Krush and Cohen productized their ideas with Hyro, which uses AI to facilitate text and voice conversations across the web, call centers and apps between healthcare organizations and their clients. Hyro today announced that it raised $20 million in a Series B round led by Liberty Mutual, Macquarie Capital and Black Opal, bringing the startup’s total raised to $35 million.
Krush says that the new cash will be put toward expanding Hyro’s go-to-market teams and R&D.
“When we searched for a domain that would benefit from transforming these technologies most, we discovered and validated that healthcare, with staffing shortages and antiquated processes, had the greatest need and pain points, and have continued to focus on this particular vertical,” Krush told TechCrunch in an email interview.
To Krush’s point, the healthcare industry faces a major staffing shortfall, exacerbated by the logistical complications that arose during the pandemic. In a recent interview with Keona Health, Halee Fischer-Wright, CEO of Medical Group Management Association (MGMA), said that MGMA’s heard that 88% of medical practices have had difficulties recruiting front-of-office staff over the last year. By another estimates, the healthcare field has lost 20% of its workforce.
Hyro doesn’t attempt to replace staffers. But it does inject automation into the equation. The platform is essentially a drop-in replacement for traditional IVR systems, handling calls and texts automatically using conversational AI.
Hyro can answer common questions and handle tasks like booking or rescheduling an appointment, providing engagement and conversion metrics on the backend as it does so.
Plenty of platforms do — or at least claim to. See RedRoute, a voice-based conversational AI startup that delivers an “Alexa-like” customer service experience over the phone. Elsewhere, there’s Omilia, which provides a conversational solution that works on all platforms (e.g. phone, web chat, social networks, SMS and more) and integrates with existing customer support systems.
But Krush claims that Hyro is differentiated. For one, he says, it offers an AI-powered search feature that scrapes up-to-date information from a customer’s website — ostensibly preventing wrong answers to questions (a notorious problem with text-generating AI). Hyro also boasts “smart routing,” which enables it to “intelligently” decide whether to complete a task automatically, send a link to self-serve via SMS or route a request to the right department.
A bot created using Hyro’s development tools. Image Credits: Hyro
“Our AI assistants have been used by tens of millions of patients, automating conversations on various channels,” Krush said. “Hyro creates a feedback loop by identifying missing knowledge gaps, basically mimicking the operations of a call center agent. It also shows within a conversation exactly how the AI assistant deduced the correct response to a patient or customer query, meaning that if incorrect answers were given, an enterprise can understand exactly which piece of content or dataset is labeled incorrectly and fix accordingly.”
Of course, no technology’s perfect, and Hyro’s likely isn’t an exception to the rule. But the startup’s sales pitch was enough to win over dozens of healthcare networks, providers and hospitals as clients, including Weill Cornell Medicine. Annual recurring revenue has doubled since Hyro went to market in 2019, Krush claims.
Hyro’s future plans entail expanding to industries adjacent to healthcare, including real estate and the public sector, as well as rounding out the platform with more customization options, business optimization recommendations and “variety” in the AI skills that Hyro supports.
“The pandemic expedited digital transformation for healthcare and made the problems we’re solving very clear and obvious (e.g. the spike in calls surrounding information, access to testing, etc.),” Krush said. “We were one of the first to offer a COVID-19 virtual assistant that deployed in under 48 hours based on trusted information from the health system and trusted resources such as the CDC and World Health Organization …. Hyro is well funded, with good growth and momentum, and we’ve always managed a responsible budget, so we’re actually looking to expand and gather more market share while competitors are slowing down.”
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