Nanobiotix Radiotherapy Enhancer for Tumors Also Primes Immune System

 Nanobiotix is developing a way for its locally-injected radioenhancer for solid tumors to treat metastasized cancers, in combination with checkpoint inhibitors, and also deliver results distally. The news was announced at the American Society for Clinical Oncology (ASCO) Annual Meeting June 4-8.

As Nanobiotix CEO and co-founder Laurent Levy, Ph.D. told BioSpace, the therapy, NBTXR3, is injected into local solid tumors once, and then activated by radiotherapy. By absorbing energy from radiotherapy, it amplifies the dose of radiation within the tumor cells without increasing the dose in surrounding healthy tissue.

NBTXR3 is composed of hafnium oxide nanoparticles that, once injected, float inside tumor cells and aggregate into highly dense, inert clusters. When radiation is administered, these nanoparticles absorb energy, generating photons and secondary electrons. The hot spot created by these clusters inside the tumors punches holes in the tumor’s subcellular structure that cause the cells to die. When the radiation is not active, the nanoparticles become inert.

That’s step one. It is being evaluated for head and neck, lung, esophageal and other tumors than can be treated with radiation. In the Nanobiotix Phase I extension trial in head and neck cancer, recently released ASCO data suggested durable signs of efficacy at the 8.1-month follow-up, with an overall objective response rate of 82.5% and a complete response rate of 62.5%.

Step two is a systemic approach that can help destroy the local tumor as well as metastatic tumors.

“Working with clinical investigators, we are evaluating the potential of this therapy to kill tumor cells and then trigger an immune response against the tumor,” Levy said. “We believe the way NBTXR3 destroys these cells actually primes the immune system to recognize tumors so it can fight the injected tumor as well as distant metastases.”

“Immuno-oncology (IO) has been revolutionary for patients, but only a small number can benefit. That’s why there are so many IO approaches. For anti-PD-1 inhibitors to work, you need an immune response,” he elaborated. To get that immune response, priming the immune system is important, and that is where our physics-based approach could intervene.”

As researchers also noted in NBTXR3 preclinical data presented at ASCO, treatment with NBTXR3 and radiation “increased CD8+ T cells and improved local and systemic control in mice and induced immune response that was not observed with radiotherapy alone” with PD1-resistant tumors. In humans, new ASCO data indicated clinically meaningful tumor regression in 10 of 13 patients, including 6 of the 8 whose tumors had previously showed resistance to checkpoint inhibitors.

By physically destroying the tumor, Levy explained, “NBTXR3 also appears to activate multiple immune pathways – even if the checkpoint inhibitors previously failed.”

As such, this therapy could have enormous potential to enhance the efficacy of immune checkpoint inhibitors as a first-line therapy, overcome resistance for refractory patients, and transform some cold tumors into hot tumors.

According to Levy, IO typically only provides a meaningful benefit for 15% of patients, but half of the refractory patients in the Nanobiotix ongoing immunotherapy study treated with NBTXR3 transformed into responders thus far.

“This is an ongoing study reporting on only 16 patients overall across 3 cohorts so far, but we believe this is a very big signal for overcoming resistance to anti-PD-1, and that the combination could be effective for anti-PD-1 naïve patients, too,” Levy said. “In the treatment naïve group, 4 of 5 patients had clinically meaningful tumor regression. For me, these data show promising signs that our product candidate may do something others can’t.”

According to the ASCO poster, the combination therapy suggests deep, sustained responses that extended survival time for some patients to 12 or more months.

“If we can replicate these results in 40 patients, I would call them revolutionary,” Levy said. “We are extremely excited.” 

Two Phase II studies evaluating NBTXR3 in combination with anti-PD-1 in head and neck cancer are already underway as part of the company’s clinical collaboration with The University of Texas MD Anderson Cancer Center. Levy said those results will be reported as they become available.

Several other studies are being planned using NBTXR3 as a single agent activated by radiotherapy, in combination with IO, and in combination with chemotherapy. These include ongoing phase I studies in non-small cell lung cancer, pancreatic cancer, and esophageal cancer at MD Anderson. Additional indications may be included.

Levy believes the early success of NBTXR3 is based upon the physics-based nature of the therapy.

“Physics is universal. It doesn’t change from one patient to another,” Levy said. In contrast, “If you take 100 cancer cells from 100 different patients and apply a therapy, some cells die, some don’t, and some develop resistance because of variable biology…but a physics-based approach does not depend on biology. That’s why physics is so powerful.”

The primary focus, currently, is getting the product candidate approved and available to patients. The company received its first market approval from European authorities to treat patients with soft tissue sarcoma (which has a high amputation rate) in 2019 and is now focused on demonstrating a clinically meaningful benefit versus standard of care in head and neck cancer for global registration. Nanobiotix plans to launch a phase III study this year and received a Fast Track designation from the FDA in 2020 for the patient population in the study.

In Asia, Nanobiotix has partnered with LianBio to develop and commercialize NBTXR3 for head and neck cancer patients, who often are frail and elderly and, eventually, a minimum of four other indications. “LianBio is committed to helping us develop NBTXR3 in China and other Asian markets. They will also participate in our global Phase III clinical trials, recruiting 100 patients.

“Our strategy is to go where we can do the most good, with the aim of treating millions of patients around the world” Levy said.

https://www.biospace.com/article/nanobiotix-s-radiotherapy-enhancer-for-tumors-also-primes-the-immune-system/

How Google is making more money than ever off the sick and vulnerable

 In 2019, Google embarked on a mysterious-sounding venture. 

Called Project Nightingale and carried out in secret, the tech giant teamed up with St. Louis-based Ascension, one of the largest private health-care companies in the country. Google was granted complete access to 50 million patients’ names, lab results, diagnoses and hospitalization records, as well as their home addresses and places of employment. Even more worryingly, at no time did Ascension or Google make an attempt to inform the patients or ask for their consent. 

Despite patient privacy concerns, this partnership has only grown with Google boosting its electronic health-record search tool, likely resulting in the accumulation of even more patient data. 

Now, hungry for even more medical data, Google has signed a multiyear deal with HCA, an American for-profit operator of medical facilities with 2,000 health-care sites across 21 different states. The agreement will give Google access to millions more patient records — enabling its advertisers to specifically target even victims of sexual abuse as well as those struggling with severe eating disorders. 

Google has said it will use the sensitive data to develop health-care algorithms that it could hand off to HCA to test on its own. “We want to push the boundaries of what the clinician can do in real time with data,” Chris Sakalosky, managing director of healthcare and life sciences at Google Cloud, told The Wall Street Journal. 

In 2019, Google brokered a deal with Ascension and gained access to 50 million patient names, lab results, diagnoses and hospital records.

Getty Images (2)

But the recent HCA deal is almost a carbon copy of the one struck with Ascension — except it’s even bigger. While Ascension has 165,000 employees and 151 hospitals, HCA boasts 280,000 staff and 186 hospitals. Considering Google earns more than 80 percent of its revenue from targeted ads, the monetization of medical records is just another step in its inexorable march toward data domination. 

Yet again, one of the wealthiest companies in the world has gained access to highly personal medical data without the consent of patients. Executives at Google claim to care about your privacy, but the reality paints a very different picture. 

According to a Consumer Watchdog report, Google collects information without people’s knowledge or consent. And the company currently faces a suit in California, which claims it collects and breaks data into categories like sexuality, ethnicity, religion, health conditions, etc., which are then “broadcast to hundreds of bidders,” with the highest bidder “winning the auction.”

The accumulation of data pays handsomely: Google’s profits more than doubled last quarter. 

Experts are now sounding alarm bells about the new HCA venture. The idea of Google selling patients’ data is not beyond the realm of possibility, argues Arthur Kaplan, professor of ethics at NYU’s Grossman School of Medicine. After all, this is the very same company that, just a few years ago, removed the “don’t be evil” clause from its code of conduct. 

Also, if Google is going to use highly sensitive data to generate profits, shouldn’t the affected people at least receive proper compensation? 

Google exec Chris Sakalosky (right) says the tech giant will use HCA patient data to create health-care algorithms — but really, this is about profit.

Alamy; LinkedIn

Last year, researchers at the University of Chicago Booth School of Business and Northwestern University’s Kellogg School of Management asked Americans if they were willing to share their health data with Big Tech companies. Unsurprisingly, 90 percent of respondents said no. 

How much, they asked, was the average person willing to accept in exchange for their data? The answer was $100,000. Multiply that figure by 50 million (the number of peoples’ records accessed in 2019) and you get $5 trillion. Enough to end the $1-trillion-worth Google as we know it, five times over. 

Sadly, the idea of each patient being compensated doesn’t seem likely. So what, if anything, can be done? 

According to the Health Insurance Portability and Accountability Act of 1996 (HIPAA), patients have a say in how their health information is handled. If a patient requests that their information not be shared with third parties without their consent, then, according to HIPAA guidelines, this request, under law, must be respected. 

If you happen to be a HCA patient and are concerned by what you have read, the company’s ethics line number is 1-800-455-1996. Why not give a call and make sure that your data is not being abused? You might not receive any compensation, but you most certainly deserve to have your questions answered. 

John Mac Ghlionn is a researcher and essayist. His work has been published by The South China Morning Post, Sydney Morning Herald, and Townhall. Twitter: @ghlionn 

https://nypost.com/2021/06/05/how-google-exploits-the-sick-and-vulnerable-for-a-profit/

China Port City Imposes COVID-19 Restrictions

 China’s Guangzhou city, a port city of more than 13 million people, on Saturday ordered more restrictions due to a rise in COVID-19 cases that began in late May.

Of the 24 new cases of COVID-19 reported in China on Saturday, 11 were transmitted in Guangzhou province, where the city is located.

Authorities had imposed restrictions earlier in the week but sought additional limits on business and social activities. Authorities closed about a dozen subway stops, and the city’s Nansha district ordered restaurants to stop dine-in services and public venues, such as gyms, to temporarily close.

Officials in the districts of Nansha, Huadu and Conghua ordered all residents and any individuals who have traveled through their regions to be tested for COVID-19, the disease caused by the coronavirus, Reuters reported.

Also, Sinovac Biotech’s COVID-19 vaccine has been approved for emergency use for young people between the ages of 3 and 17, the company’s chairman, Yin Weidong, said on state television Friday. China’s current vaccination program is restricted to those 18 and older.

As Afghanistan attempts to beat back a surge in COVID-19 cases, it has received the news that the 3 million doses of vaccines it was expecting from the World Health Organization in April will not arrive until August, according to the Associated Press.

Afghan health ministry spokesman Ghulam Dastagir Nazari told AP that he has approached several embassies for help but has not received any vaccines. “We are in the middle of a crisis,” he said.

On Saturday, India’s health ministry reported 120,529 new COVID-19 cases in the previous 24 hours period, the lowest daily count of new infections in 58 days. More than 3,000 deaths were also recorded.

Britain’s Medicines and Healthcare products Regulatory Agency Friday approved the Pfizer-BioNTech COVID-19 vaccine for 12- to 15-year-olds.

The decision follows similar approvals by U.S. and European Union regulators.

Johns Hopkins Coronavirus Resource Center reported early Saturday more than 172 million global COVID infections. The U.S. has the most cases with 33.3 million, followed by India with 28.7 million and Brazil with nearly 17 million.

https://www.voanews.com/covid-19-pandemic/china-port-city-imposes-covid-19-restrictions

Taiwan says it is discussing making COVID-19 vaccines for U.S. firms

Taiwan is in talks with U.S. companies about making their COVID-19 vaccines, following similar talks with European firms, Health Minister Chen Shih-chung said on Saturday.

Taiwan, like much of the world, has been trying to speed up its vaccination programme following a spike in domestic cases, but has been stymied by global supply shortages.

Chen told reporters that they previously had talks with European companies he did not name about producing their vaccines under licence.

"Only recently have we started to have talks with U.S. companies, to see if it's possible or not to carry out relevant subcontracting work," he added, without providing details.

Taiwan has ordered around five million shots from U.S. firm Moderna Inc, of which 150,000 have arrived. It has ordered 10 millions shots from British-Swedish firm AstraZeneca PLC.

Taiwan, also in talks with BioNTech SE, blames China - which claims the island as its own territory - for blocking a deal with the German company earlier this year.

Johnson & Johnson said on Friday it has been in talks with Taiwan about providing its COVID-19 vaccine to the island since last year.

Around 3% of Taiwan's 23.5 million people have received at least one shot of a vaccine. Japan on Friday donated 1.24 million doses of AstraZeneca's COVID-19 vaccine.

Although Taiwan's domestic cases have not exploded, they are not falling dramatically either. Chen announced 511 new domestic infections on Saturday.

While cases have been concentrated in Taipei and its neighbouring city, health authorities are trying to stop an outbreak at two chip packagers in Miaoli, in the north of the island, King Yuan Electronics and Greatek Electronics.

While case numbers in Taiwan's main chip hub of Hsinchu have remained low, the government, working with the military, has set up testing sites there to ensure they can identify any rapid increase.

In a live broadcast from her office on Saturday, President Tsai Ing-wen said she had asked the Hsinchu and Miaoli governments to set up an "anti-epidemic combat alliance" to protect production.

"Every second counts, and we must guard the line of defence against the epidemic," she said.

However, the government has signalled it is not planning for now on further raising the alert level, now one rung below full lockdown.

"Discussions are continuing with experts, but at present there have been no suggestions for a lockdown," Chen said.

Taiwan has reported 10,956 cases since the pandemic began, with 225 deaths.

https://news.yahoo.com/taiwan-reports-more-500-domestic-061417256.html

ADC Therapeutics Presents Updated Clinical Data at 2021 ASCO

 ZYNLONTA™ LOTIS-2 updated data includes median duration of response of 13.4 months in heavily pre-treated patients with relapsed or refractory DLBCL

Subgroup analyses include patients with double- / triple-hit, advanced stage or transformed DLBCL, DLBCL refractory to first-line therapy, and patients older than 65

ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug conjugates (ADCs) to treat hematological malignancies and solid tumors, today announced updated clinical data from the ZYNLONTA™ (loncastuximab tesirine-lpyl) Phase 2 LOTIS-2 trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, which is being held virtually June 4-8, 2021.

"The maturing duration of response from the ZYNLONTA Phase 2 trial reported at ASCO reflects the strong data set that served as the basis of the accelerated FDA approval in April," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "We are especially encouraged to see this positive trend continue to strengthen in a heavily pre-treated patient population, including patients with double- / triple-hit, advanced stage or transformed DLBCL, DLBCL refractory to first-line therapy, and patients older than 65."

https://finance.yahoo.com/news/adc-therapeutics-presents-updated-clinical-175200695.html

S. .Korea's IP laws key to expanding coronavirus vaccine partnership - U.S. senators

 

South Korea's respect for intellectual property rights makes it an ideal partner for the United States as it seeks to decouple its supply chains from China and forge partnerships to manufacture coronavirus vaccines, a trio of U.S. senators said on Saturday during a visit to Seoul.

Democrats Tammy Duckworth and Chris Coons, and Republican Dan Sullivan, were in South Korea as part of their first official overseas trip since the pandemic began.

After last month's summit in Washington between U.S. President Joe Biden and South Korean President Moon Jae-in - who was only the second international leader to be welcomed by Biden - the senators said their visit was sign of the importance Washington places on South Korea's role in countering China and shoring up global supply chains amid the pandemic.

"We can trust in the legal system here, and we can trust that our intellectual property rights will be protected," Duckworth told a group of reporters. "South Korea is a logical partner. This is critical whether it is manufacturing (computer) chips or pharmaceuticals."

A day after Biden and Moon met, U.S. drugmakers Moderna Inc and Novavax Inc entered into a deal with South Korea for their COVID-19 vaccines to be manufactured in the country, which has been seeking to secure more and faster deliveries of U.S.-made vaccines.

When asked about criticism that Moderna's vaccine would not be fully manufactured in South Korea, Duckworth said the arrangement was the first of its kind for the United States.

"Remember we're not doing this anywhere else in the world," she said. "Let's make that clear."

Coons said the deals did not appear to be small or temporary, and were just the beginning.

The U.S. government's recently created International Development Finance Corporation may be involved in funding the partnerships, alongside South Korean sources, he said.

"They are going to be ... ramping up production, not just for South Korea, but for the entire region," he said.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/S-Korea-s-IP-laws-key-to-expanding-coronavirus-vaccine-partnership-U-S-senators-35529745/

G-7 Nations Agree on New Rules for Taxing Global Companies

 The Group of Seven leading rich countries agreed to back new rules for taxing businesses that operate internationally in a significant step toward a global agreement that would deliver the minimum rate sought by the Biden administration.

The agreement, reached by treasury chiefs during a meeting in London on Saturday, resolves long-running tensions between the U.S. and large European economies that have at times threatened to push the international tax system into chaos and spark a trans-Atlantic trade conflict.

Under the deal, G-7 members will back a global minimum tax rate on company profits and a new way of sharing the revenues from taxing the world's largest and most profitable companies.

The G-7, which comprises Canada, France, Germany, Italy, Japan, the U.K. and the U.S., agreed that businesses should pay a minimum tax rate of at least 15%.

"The G-7 finance ministers have made a significant, unprecedented commitment today that provides tremendous momentum towards achieving a robust global minimum tax at a rate of at least 15%," said Treasury Secretary Janet Yellen.

There are still significant details to be worked out, and the deal isn't sufficient to see the new rules applied globally. For that to happen, it would need support from the Group of 20 leading economies--which includes China and India, among other developing economies -- as well as the backing of the 135 countries that have been negotiating the new rules as part of what is known as the Inclusive Framework. G-20 treasury chiefs are due to meet in Venice on July 9-10.

"G-7 finance ministers have reached an historic agreement to reform the global tax system," said Rishi Sunak, the U.K.'s treasury chief.

The U.S., which already has a form of minimum tax on companies based in the country, wants to make that levy tougher and raise domestic tax rates to pay for the Biden administration's new programs. Doing so unilaterally would increase the cost of having a U.S. headquarters, but if other countries imposed similar taxes on their companies, the benefits of escaping the U.S. would shrink. To prod other countries toward a deal, the U.S. has proposed denying certain tax deductions to the U.S. operations of companies based in countries that don't impose minimum taxes.

The main aim of European countries has been to increase taxes on large digital businesses such as Alphabet Inc. and Facebook Inc., most of which are based in the U.S. To do that, an overhaul of the existing rules is needed, because they were designed for an age in which businesses had to have a large physical presence in a country -- such as a factory -- to be able to make profits there.

"Just because their business is online doesn't mean they should not pay taxes in the countries where they operate and from which their profit derives," the treasury chiefs of France, Germany, Italy and Spain said in a joint statement Friday. "Physical presence has been the historical basis of our taxation system. This basis has to evolve with our economies gradually shifting online."

A number of European countries raised the stakes in the long-running talks by announcing separate, national levies on digital businesses, hoping that would pressure the U.S. to agree to an international deal. In retaliation for what it saw as discrimination against U.S. companies, the U.S. government announced a series of punitive tariffs on imports from those countries, although it suspended those tariffs until the end of this year.

The G-7 agreement brings a possible increase in tax bills for a number of digital businesses a step closer. The alternative to an agreement was likely to be an overlapping series of national levies that could have seen the same profit taxed multiple times in different locations, an outcome digital businesses were keen to avoid.

Large tech companies have long expressed support for an international resolution on how to divvy up their taxes among countries. Executives at the companies argue that they need certainty in tax rules, rather than a patchwork of national taxes like those passed in some European countries -- and some privately accept that a global deal may mean an increase in their tax bills.

The toughest question in the tax talks has been the handling of the largely American cadre of tech giants. European countries wanted those companies to pay more taxes in countries where they do business. But the U.S. had rejected a deal that focused only on tech companies as both discriminatory and outdated given the increasingly digital nature of most sectors, and that has been a consistent position under both the Trump and Biden administrations.

Instead, G-7 countries have agreed to focus the new tax rules on large, "global" businesses that have a profit margin of at least 10%. They agreed that the right to tax 20% of profits above that threshold would be shared out among governments.

That new approach, suggested by the U.S., may run into opposition in Congress, where some lawmakers are wary of moving before other countries. Some of the changes could require the U.S. Senate to ratify changes to tax treaties, which would take a two-thirds vote and thus at least some Republican support.

https://www.marketscreener.com/news/latest/G-7-Nations-Agree-on-New-Rules-for-Taxing-Global-Companies-2nd-Update--35529787/