Florida state Representative Chris Sprowls (R) is leading a special panel looking into foreign influences on publicly supported research. AP PHOTO/STEVE CANNON

Florida joins U.S. government in probing foreign ties of researchers
By Jeffrey Mervis

Jan. 9, 2020 , 4:00 PM

Florida lawmakers have begun an investigation into the foreign ties of researchers at the state’s universities and research institutions. The inquiry, the first of its kind at the state level, dovetails with an ongoing federal probe into whether such affiliations, notably with Chinese entities, pose a risk to the U.S. research enterprise.

The Florida effort is triggered by revelations last month that six scientists at the Moffitt Cancer Center had been dismissed for failing to disclose their participation in China’s Thousand Talents Program. The researchers include the center’s CEO, Alan List, and the head of its research center, Thomas Sellers.

“I’m appalled by the actions of the Moffitt CEO and some of its researchers,” says state Representative Chris Sprowls (R), who is chair of a bipartisan select committee created by Republican House Speaker José Oliva. “The question is, has there also been any theft of intellectual property? Clearly, the intent is there.”


The Moffitt case is the latest instance of scientists being ousted from U.S. biomedical research institutions after being accused of failing to disclose foreign research ties or undermining the integrity of the process by which the National Institutes of Health (NIH) funds research. The MD Anderson Cancer Center cut ties with three scientists in April 2019 as part of a larger investigation, and 1 month later Emory University announced it had fired two neuroscientists. All five were Asian Americans.

“No front door”
In the past 18 months, NIH has raised questions about the conduct of nearly 200 NIH-funded scientists at more than 60 institutions it funds. Many of the cases involve researchers who received money from Thousand Talents or another Chinese foreign talent recruitment program and did not report it to their institutions.

A nonprofit privacy entity created by the Florida legislature in 1981, Moffitt is one of 51 NIH comprehensive cancer centers; last year it garnered $36 million in NIH funding. Moffitt did not receive any letters from NIH raising concerns about foreign ties, according to a center spokesperson. Instead, it conducted its own investigation after learning that some scientists had failed to comply with NIH and Moffitt policies.

Moffitt does not prohibit foreign collaborations, according to the spokesperson, “but disclosure is mandatory and the specific arrangements have to comply with Moffitt’s rules and expectations.” Moffitt is reviewing its rules governing such collaborations, the spokesperson adds.

The new special legislative committee “will examine any further improper or illegal activities involving Florida’s research universities, medical research facilities, and individuals associated with such institutions,” Oliva said in announcing its formation on 30 December 2019. Sprowls, who is in line to succeed Oliva as House speaker in 2021, says the panel has carte blanche to request records, hold hearings, and gather evidence of what Oliva called “Chinese meddling in Florida taxpayer-funded research.”

Sprowls says the committee has the authority to examine behavior at any institution that receives state funds, regardless of the type of research it conducts. Its charter runs through November, and its first hearing is scheduled for 21 January. And Sprowls, a 35-year-old Republican who represents a district just north of Tampa, is expected to draw on his experience as a state prosecutor in exploring how research institutions monitor foreign collaborations by faculty members.

“The problem with universities is that there is no front door,” he says. “There are lots of ways that researchers interact with colleagues around the world. And while I think that scientific collaboration is important, the reality is that university research is at risk from interventions by foreign governments. And we know they are already doing it.”

“My concern is making sure that tax dollars benefit the residents of Florida and not some other country,” Sprowls continued. “And at this point, I’m not convinced that simply disclosing those ties is sufficient. Universities have already demonstrated that, left to their own devices, they are not doing enough to protect our investment.”

Increased oversight
At least one research administrator at a Florida university thinks campuses around the state are already doing a pretty good job of following the rules, and he isn’t sure what will come of the state probe. “I don’t know if legislators are aware of how much we are already doing to address their concerns,” says Gary Ostrander, who, as vice president for research at Florida State University (FSU), is responsible for making sure that his institution complies with the myriad policies governing federally funded research.

Ostrander, who also leads a group of a dozen research chiefs from Florida universities that meets regularly, predicts that Florida institutions “will be giving [legislators] a lot of information that will impress and surprise them. And once we do, I hope they will see that Florida [institutions] are on top of this.”

Ostrander acknowledges that current FSU guidelines might not convey that sense of vigilance. “We haven’t put out a policy yet,” he says when asked whether FSU allows faculty members to participate in Thousand Talents. “But Thousand Talents has been identified as a recruitment tool that can be used for espionage. And we’ve made it clear that [faculty] should not be doing it.”

FSU received some $36 million last year from NIH, and Ostrander says the university did not receive any letters questioning the behavior of its faculty members. But that doesn’t mean FSU researchers are free to do as they please.

Participants in the Thousand Talents Program are often expected to spend a few months or more at their sponsoring Chinese institution, an arrangement that can make it impossible for them to carry out the research that NIH or another U.S. agency is funding. To avoid such conflicts of commitment, Ostrander says, FSU faculty are not allowed to hold a position at another institution. Maintaining what NIH calls a “shadow laboratory” in China is also a no-no, he says, and anyone who violates those rules is putting their job at risk.

At the University of Florida (UF), which received $190 million from NIH last year and conducts more research than any other university in the state, officials say NIH asked about the conduct of two faculty members with NIH funding. The university investigated “possible failure to disclose outside research support, relevant affiliations, or foreign components,” says Steve Orlando, assistant vice president for communications, and both faculty members have resigned as a result of the investigation.

UF officials have also tightened rules regarding foreign collaborations. The university now strongly discourages faculty participation in any foreign talent recruitment program, Orlando says, although in rare cases it might approve such a relationship. A faculty member who fails to disclose their involvement in such a program is subject to termination, he adds. At the same time, Orlando says, “Our campus remains an open and welcoming place to students, faculty, and staff from around the world.”

Let the Sun shine in
Despite holding different perspectives on the scope of the problem, Ostrander and Sprowls agree that transparency is the key to preserving research integrity.

“Although some measure of confidentiality may be necessary, it is my intention to make public as much information as is humanely possible,” Sprowls says about the fruits of his committee’s investigation. A Moffitt spokesperson says the cancer center has already shared its findings with state legislators and is preparing to release a “trove” of documents relating to the investigation.

Ostrander says FSU is also eager to work with Sprowls’s panel. “We have a reputation for being transparent,” he boasts. And he has some advice for faculty members who wonder whether they have crossed the line. “Come by and talk to us,” Ostrander says. “Don’t wait until we hear about it from the Department of Homeland Security or the FBI. Because that could be a career-ender.”

The handle always shows a smaller decline from high to low; it represents a final shakeout of uncommitted holders, sending those shares into sturdier hands in the market.

The handle always shows a smaller decline from high to low; it represents a final shakeout of uncommitted holders, sending those shares into sturdier hands in the market.

When To Buy The Best Growth Stocks: How To Analyze A Stock's Cup With Handle


DAVID SAITO-CHUNG 01:30 PM ET 11/27/2019
The cup with handle is to serious investors in growth stocks what the single is to a baseball fan. It's the starting point for scoring runs and winning the investing game.
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Basic Characteristics Of The Cup With Handle
The stock needs to show a 30% uptrend from any price point, but it must be before the base's construction. Or, the stock must show a minimum 20% increase from a prior breakout.

The cup with handle must be at least seven weeks long. If there is no handle, then the cup itself must stretch a minimum six weeks.

The handle alone needs at least five days to form, but it could go on for weeks. Make sure it doesn't exceed the cup portion in time or size of decline. A good cup with handle should truly look like the silhouette of a nicely formed tea cup. The handle always shows a smaller decline from high to low; it represents a final shakeout of uncommitted holders, sending those shares into sturdier hands in the market.

In most cases, the decline from high to low should not exceed 8% to 12%. During bear markets, some good cup with handle bases show a large, double-digit decline within the handle. But again, it should not exceed the drop within the cup.

The handle usually begins with a down day in price. Be aware that the handle itself, which must stretch for a minimum five trading sessions, can morph into a base of its own in certain cases. That's not a problem; it's often a stock's way of offering a buy point that's clearer or lower than that suggested by the larger pattern.

The Handle? It Must Be High Enough
The handle should form in the upper part of the entire pattern. If it's too low, it's flawed.

One way to check if that handle is proper: use the simple midpoint test. Add the highest price and lowest price within the handle and divide by 2. That number should be greater than the midpoint of the actual base itself.

In most cases, the decline from high to low should not exceed 8% to 12%. During bear markets, some good cup with handle bases show a large, double-digit decline within the handle. But again, it should not exceed the drop within the cup.

The handle usually begins with a down day in price. Be aware that the handle itself, which must stretch for a minimum five trading sessions, can morph into a base of its own in certain cases. That's not a problem; it's often a stock's way of offering a buy point that's clearer or lower than that suggested by the larger pattern.

The Handle? It Must Be High Enough
The handle should form in the upper part of the entire pattern. If it's too low, it's flawed.

One way to check if that handle is proper: use the simple midpoint test. Add the highest price and lowest price within the handle and divide by 2. That number should be greater than the midpoint of the actual base itself.

Let's take the cup with handle fashioned by Baidu (BIDU) (see the chart below) in 2007. In the cup base, the high was 134.10 and the low was 92.80. Add the two prices together and divide by 2 and you get a base midpoint of 113.45. The handle showed a high of 132.80 and a low of 120.25, and its midpoint of 126.53 easily exceeded the cup's midpoint.

The handle should also show a downward slope along at least a portion of its price lows, not an upward one.

An upward-sloping handle is flawed; it represents weak demand as new buyers move into the stock at a trickling pace. During the stock's actual breakout, you want to see a new wave of buyers coming in at a torrid pace, not a trickling one.

Also, a steep, high-volume decline should put you on alert. You don't want to buy a stock that institutional investors couldn't wait to unload at any price.

The cup should form smoothly, without major price declines on the left side. Sharp gains on the right side aren't necessarily good, either. You might think that the opposite of a panic-driven exit would be a good thing. Likely not.

Avoid Deep Bases
Try to limit your picks to cups that are no more than 30% or 33% deep, except for those built during a bear market. In that case, an exceptional growth stock can fall 40%, 50% or more and still make a successful breakout.

Still, shallower is better. It shows that the big hands are catching the stock.

Look for volume to dry up along the lows of the base. Volume should be light in the handle, too.

Tighter price action is better. This is true of almost all bases. A loose, choppy base shows the stock needs to go far for price discovery. If institutions are holding on to the stock, it won't fall too far.

The Buy Point
This, of course, is where all the above parameters lead if they appear correctly. The buy point from a cup-with-handle base appears at the highest point of the handle, plus 10 cents. In the case of former big winner Baidu, the proper buy point during its May 14, 2007, breakout was 132.90, a dime above the handle's intraday high of 132.80.

Less than six months later, the leading Chinese web search engine rocketed to 428, up 222%.

Volume On The Breakout
Even if all other parameters come together, you should avoid stocks that break out below their 10-week moving average.

Also, when the stock is breaking out, you should generally see a rush in turnover. Volume should ideally rise at least 40% above its 50-day average. For small and midcap stocks, expect breakout volume to double or triple.

The daily and weekly charts at both Investors.com and MarketSmith make heavy turnover easy to spot. Simply compare the day or week's volume with the moving average line drawn across the volume bars. An Investors.com chart will also tell you in real time how volume is running in comparison with typical level at that time of the trading session.

For the weekly chart, the moving-average line traces 10 weeks' worth of turnover.

What should you do if volume on breakout day is much lighter than usual? Sometimes volume will pick up in the next few sessions. Light volume in the market in general may also be a factor. Also consider that the breakout may have started later in the day.

O'Neil has often said at past IBD seminars that after a stock breaks out, he wants to see weekly volume rise vs. the prior week. This signifies a sudden shift in demand for shares that could continue to build up.

Are quarterly results coming up? If so, traders often hesitate before the news. But if the stock fails to make much headway in price, the relative strength line is fading, and the market itself is not showing positive action then something may be wrong with the timing of the breakout.

At that point, it makes sense to exit the stock, even if the 7%-8% loss-cutting sell rule has not yet been triggered.

https://www.investors.com/how-to-invest/investors-corner/the-basics-how-to-analyze-a-stocks-cup-with-handle/

Moffitt Cancer Center in FL ties to Peregrine Pharmaceuticals KOL Dmitry Gabrilovich / Scott Antonia / Jessica Frakes etc etc etc

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MD Anderson and Sun Yat-Sen University Cancer Center

https://mdanderson.elsevierpure.com/en/organisations/sun-yat-sen-university-cancer-center-sysucc/network-organisations/

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SYSUCC has established collaborative and friendly relationships with many renowned international institutes from around the world.[18]

SYSUCC has been a sister institute with MD Anderson Cancer Center since 2003. The purpose is to create collaborative oncology research projects between MDACC and other sister institutes in the fight against cancer.[19][20][21]

In 2004, SYSUCC set up a joint laboratory with the Karolinska Institutet of Sweden for research in immunotherapy, molecular virology and oncological epidemiology.

SYSUCC signed a Memorandum of Understanding (MoU) with the UK’s University of Warwick in 2015, creating a partnership in cancer diagnosis, care and research. SYSUCC and the University of Warwick are exploring opportunities in regards to digital pathology, nursing, and anti-cancer drug research.[22][23]

In 2017, SYSUCC and Fred Hutchinson Cancer Research Center signed a broad five-year Memorandum of Understanding to carryout research on cancer diagnosis and treatment.[24][25]

https://en.m.wikipedia.org/wiki/Sun_Yat-sen_University_Cancer_Center

http://ir.avidbio.com/news-releases/news-release-details/peregrine-and-oxigene-conclude-arcus-therapeutics-llc-joint


February 28, 2002 at 12:00 AM EST
Peregrine and OXiGENE Conclude ArcusTherapeutics LLC Joint Venture; Companies Reacquire Full Rights to Respective Vascular Targeting Technologies TUSTIN, Calif., Feb 28, 2002 (BW HealthWire) -- OXiGENE Inc. (Nasdaq:OXGN)(SSE:OXGN) and Peregrine Pharmaceuticals Inc. (Nasdaq:PPHM) today announced an agreement to conclude their Arcus Therapeutics, LLC joint venture (Arcus).
Under the terms of the agreement, Peregrine will pay OXiGENE $2,000,000 and will reacquire full rights and interest to the vascular targeting platform it contributed to the joint venture, as well as any new discoveries to its contributed technology.

OXiGENE will reacquire full rights and interest to its vascular targeting technology including any new discoveries based on its contribution. The joint venture will be concluded after all technology has been distributed to its respective owners.
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http://ir.avidbio.com/news-releases/news-release-details/peregrine-pharmaceuticals-announces-three-abstracts-accepted-0


April 14, 2015 at 8:00 AM EDT
TUSTIN, Calif., April 14, 2015 (GLOBE NEWSWIRE) -- Peregrine Pharmaceuticals (Nasdaq:PPHM) (Nasdaq:PPHMP) today announced that two preclinical abstracts and one clinical translation abstract are scheduled for poster presentations at the 106th Annual Meeting of the American Association for Cancer Research (AACR), to be held April 18-22, 2015 in Philadelphia, Pennsylvania. Data to be presented include studies investigating the therapeutic potential of Peregrine's phosphatidylserine (PS)-targeting antibodies when administered in combination treatment regimens with approved and developmental cancer immunotherapies and translation data in patients with lung cancer. Peregrine's lead PS-targeting antibody, bavituximab, is in Phase III development for the treatment of second-line non-small lung cancer (the "SUNRISE trial") along with several investigator-sponsored trials evaluating other
treatment combinations and additional oncology indications.

Abstract details:

Abstract Number: 274

Presentation Title: Bavituximab modulates tumor microenvironment and activates CD8+ tumor infiltrating lymphocytes in a patient-derived 3D ex vivo system of lung cancer
Presentation Time: Sunday, April 19, 2015, 1:00 PM - 5:00 PM Eastern Daylight Time
Location: Section 13
Poster Board Number: 2
Author Block: Soner Altiok1, Melanie Mediavilla-Valera2, Jenny Kreahling2, David Noyes2, Tiffany N. Razabdouski2, Nikoletta L. Kallinteris3, Joseph Shan3, Scott Antonia2. 1Nilogen Oncosystems, Tampa, FL; 2Moffitt Cancer Center, Tampa, FL; 3Peregrine Pharmaceuticals, Inc, Tustin, CA

Check post #'s 319124 & 319120 for a refresher on my personal interactions with government investigative officials...especially on who was mentioned as being the subject of a FDA OCI referral...imao...r

I stated things would get better for CDMO once new management was in place and they shifted..

I would love to see the court transcript...

Jeanette Bleecker's Secret Record keeping on PPHM's sabotaged 2nd ln NSCLC clinical trial.

JB has given her testimony before the court several weeks ago now. One thing that keeps filling my mind is HOW was it found out that JB kept secret records. The only thing we know about that is that she kept them because it is explicitly mentioned in one of the PACER court filings.

And yesterday, while having a drink with a good friend who is also invested in PPHM, we talked about that and he brought up a possibility I didn't evaluate yet.

For starters I keep thinking that PPHM salvaged the Bavituximab 2nd ln NSCLC with the help of the secret records of JB. They recalled tons of vials and must have known what exactly they were looking for and must have been sure they could salvage the trial. The bankers had just recalled the loan due to the sabotage and PPHM had a hard time raising the needed cash for operations and salvaging by using the ATM. So they will have considered the cost of every action before engaging in it.

But to use the secret records they needed to HAVE these secret records. In the past I have been SPECULATING about their origins.

1) Did JB crack in February after the dead of her father and confessed out of some kind of guilt (maybe first to Angela and then to Finken) because she for sure realized that people not getting their due Bavi would die faster and so she provided the records at that time (that would imply that CSM knew about the sabotage at THAT time but did NOT before that time and thus Angela/Finken/etc would not have been involved in the initiative of the sabotage, just helping to cover it up).

2) Did she produce the records when the sabotage was discovered during an investigation (eg: FDA) or internal CSM/PPHM after the sabotage was discovered?

3) Were the records FOUND because she was caught in the act? In her office desk for instance.

4) Were the records found during a house search at JB's as part of a gov investigations? PPHM IR confirmed there was an external party investigating (and what happened to that investigation?). In that case why did she keep these records at home? Was it a COPY? Did someone else get a copy?

5) Did the records come up during a deal negotiations. She says I have the records that can save the PPHM trial in exchange for ...? And if she was willing to do that then she actually confessed and may have told who was behind it. Which brings us to point 6 of yesterday evening.

6) Did a COPY of those records show up due to an investigation and a search at the premisses of the party that JB named to be behind the sabotage? That would be a more expected place to find the records then at JB's place because that would be the party that has USE for those records.

These records and how PPHM came to know of there existence and when they came to know it is a major indicator in this sabotage story. I will again emphasize as I did in the past that there is NO WAY we know about these record when JB would not want anyone to know about it. If she has the intelligence to PREMEDITATE a clinical trial sabotage, prepare soft glue labels that can be changed without a trace, knows how to pass that by CSM's Quality Control who knows the FDA doesn't authorize these labels, if she thinks about keeping records and she managed to do that in a continuous and consistent way in order to temper with 25% of the doses in the control arm and 25% of the doses in the Bavi 1mg/Kg arm, then rest assured she can keep the secret records SECRET.

Yet we know about them! So the only way that we can know about them without JB working with the system is that they were discovered.

Now what does that mean?
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besides blocking just PS binding to its receptors on immune cells, there is an FC- FC gamma -based effector function leading to ADCC and so on and so forth - an immune effector function that other checkpoint inhibitors do not have blocking PD-1 or blocking CTLA-4. So, you’ve got a component here that is beyond other checkpoint inhibitors, that brings in an effector function that others do not have. Looking at that aspect or looking at some of the translational data, do you think that beyond the PD-1, PD-L1 non-immunogenic tumors, there is a possibility that PS blockade will have far more effect potentially driving [ph??] antigen presentation. Any comments on that?” ..

...
The program managers were looking for exciting new scientific results, Lauer says. But they also found troubling discrepancies between the affiliations and funding that a grantee had reported to NIH and what they wrote in their papers.

“It’s fascinating,” Lauer says. The reporting discrepancy “had been going on for a number of years, apparently, but it took a long time before we noticed it. That’s when we decided there was something going on.”

Initial resistance
NIH’s first step was to notify all grantee institutions that it was launching an investigation. That August 2018 letter, from NIH Director Francis Collins, was followed by inquiries from Lauer about specific researchers.

Many universities pushed back, he says, telling him the agency’s suspicions were misplaced. “What we heard was that there’s nothing going on,” Lauer says. A typical response from a senior university official went like this, according to Lauer: “The faculty member says he’s never been to China, he doesn’t receive any support from the government, and he has no affiliation with any Chinese university. They told us we’re just blowing smoke.”

But Lauer says most university officials changed their tune after NIH showed them evidence that included grant numbers from foreign funders and employment contracts with foreign institutions. “So then what happens is that the university digs a bit deeper and finds that, yes, there is a lot going on,” he says.
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AVID new website yet no mention that royalties milestones etc from the IP assets ? Did they mention all the ties to Federal Investigations for which the IP assets was central part as PS Targeting etc is at the heart of most all cancer research ...and those puzzle pieces are all going to resurface

Michael Lauer leads the National Institutes of Health’s extramural research program. NATIONAL INSTITUTES OF HEALTH
NIH probe of foreign ties has led to undisclosed firings—and refunds from institutions

By Jeffrey MervisJun. 26, 2019 , 5:10 PM

An aggressive effort by the National Institutes of Health (NIH) to enforce rules requiring its grantees to report foreign ties is still gathering steam. But it has already had a major impact on the U.S. biomedical research community. A senior NIH official tells ScienceInsider that universities have fired more scientists—and refunded more grant money—as a result of the effort than has been publicly known.

Since August 2018, Bethesda, Maryland–based NIH has sent roughly 180 letters to more than 60 U.S. institutions about individual scientists it believes have broken NIH rules requiring full disclosure of all sources of research funding. To date, the investigation has led to the well-publicized dismissals of five researchers, all Asian Americans, at MD Anderson Cancer Center in Houston, Texas, and Emory University in Atlanta.

But other major U.S. research universities have also fired faculty in cases that have remained confidential, according to Michael Lauer, head of NIH’s extramural research program. And some have repaid NIH “hundreds of thousands of dollars” in grants as a result of rule violations, he says. “I can understand why [the universities] aren’t talking about it,” Lauer says. “No organization wants to discuss personnel actions in a public forum.”

Lauer suspects some of the cases NIH has uncovered may result in the U.S. government banning certain scientists from receiving federal funds, a process called debarment. NIH has referred at least 18 cases to its parent agency, the Department of Health and Human Services (HHS), for further investigation. “We are still reasonably early on in the process,” Lauer says, “and for a number of cases we don’t know where we’ll end up.”

He also thinks other federal agencies that fund academic research may soon copy NIH’s aggressive approach. “I wouldn’t be surprised if other agencies follow our lead and start doing similar things,” he says.

Connecting the dots
This week, Lauer sat down with ScienceInsider at his office on the NIH campus to talk about how NIH became concerned about foreign influence and what it is doing to defend the process used to spend more than $20 billion annually on outside research projects.

He says the agency’s concerns were initially sparked by reports that scientists were violating the confidentiality of NIH’s peer-review process, in which thousands of volunteer reviewers rate tens of thousands of grant proposals every year. In mid-2016, he says, NIH received a report from the HHS Office of Inspector General that a Federal Bureau of Investigation (FBI) probe had uncovered an MD Anderson researcher sharing proposals he had been asked to review with several other people.

That’s a clear violation of NIH rules intended to ensure the confidentiality of every grant proposal, Lauer says. But few such breaches ever trigger an FBI investigation. “There are people who will download an application and share it with a postdoc or a buddy down the hall and ask a question,” he says. “People are not supposed to do that, but maybe that’s not a hanging offense.”

But this was different. “Grant applications were being sent to multiple people at other institutions” in other nations, Lauer says about the case. “It was quite scary. Initially, we thought it was [the work of] a few rogue scientists, very unfortunate, but probably nothing more than that.”

It turned out, however, that such breaches were just one aspect of what Lauer regards as a much larger assault on the integrity of NIH-funded research. Over the next 2 years, he says, NIH grant managers would find numerous examples of NIH-funded scientists at U.S. universities who were publishing papers that listed a foreign institution—often in China—as their primary affiliation and cited foreign funding sources in the fine print. But the scientists hadn’t reported those affiliations and grants to their institutions or to NIH, as required.

The discovery was serendipitous, Lauer explains, and grew out of the agency’s routine monitoring of progress reports filed by grantees. “We have about 1300 people here, fully trained scientists, who oversee our [extramural] scientific programs,” Lauer says. “They are assigned a set of grants. And each year they look at progress reports to make sure things are OK. And one question we ask is, ‘What have you published?’”

The program managers were looking for exciting new scientific results, Lauer says. But they also found troubling discrepancies between the affiliations and funding that a grantee had reported to NIH and what they wrote in their papers.

“It’s fascinating,” Lauer says. The reporting discrepancy “had been going on for a number of years, apparently, but it took a long time before we noticed it. That’s when we decided there was something going on.”

Initial resistance
NIH’s first step was to notify all grantee institutions that it was launching an investigation. That August 2018 letter, from NIH Director Francis Collins, was followed by inquiries from Lauer about specific researchers.

Many universities pushed back, he says, telling him the agency’s suspicions were misplaced. “What we heard was that there’s nothing going on,” Lauer says. A typical response from a senior university official went like this, according to Lauer: “The faculty member says he’s never been to China, he doesn’t receive any support from the government, and he has no affiliation with any Chinese university. They told us we’re just blowing smoke.”

But Lauer says most university officials changed their tune after NIH showed them evidence that included grant numbers from foreign funders and employment contracts with foreign institutions. “So then what happens is that the university digs a bit deeper and finds that, yes, there is a lot going on,” he says.

University officials insisted it was all news to them, Lauer adds. “Some vice presidents for research and deans have told us that they were surprised, shocked, and horrified when they learned about [these arrangements],” Lauer says. “They said they had no idea some of their employees were spending 4, 6, 8 months away from their institution.”

“We found one person with a $5 million startup package from a Chinese university that wasn’t disclosed to anybody, not to his American university, and not to us,” Lauer asserts. “This is not subtle. It’s not an, ‘Oops, I forgot to list it on a form.’ We’re talking about really, really egregious stuff.”

Those absent without leave scientists were not just stiffing their home institutions, Lauer points out. They were also fleecing NIH and, by extension, U.S. taxpayers. The rip-off became clear, he says, whenever their time commitment to funded research projects exceeded 12 months.

“The American institution thinks it has a 12-month employee who’s working for them,” Lauer explains. “And we give them funding for research that will take 8 months of their time. But they already have 9 months of outside time commitments. So it adds up to 17 months. And that’s not possible.”

Uncovering that faulty math has had financial repercussions, Lauer notes. “Several universities have actually refunded us money for salaries paid during times when, as best they could tell, the faculty member wasn’t at the institution and couldn’t have been working on the NIH grant,” he says. Some of the refunds, Lauer says, are for “hundreds of thousands of dollars.” That is money NIH could have spent on other researchers who are playing by the rules, he adds.

What NIH has learned
Lauer says he hasn’t done a thorough analysis of the 180 cases in which NIH believes scientists have withheld information about their foreign ties. But a few things stand out.

“Most of the scientists are well-funded, meaning they have multiple NIH grants,” he says. “Most are ethnically Chinese, although some of our more serious cases are not ethnically Chinese.” Lauer says the scientists work at institutions all over the United States: “We have examples from the northeast, the southeast, Texas, obviously, the southwest, and elsewhere.”

No particular field seems to have attracted more than its share of bad actors, according to Lauer. “All the people at MD Anderson work on cancer,” he says. “But we’ve also seen [cases involving scientists in] mental health, cardiology, neurology, basic cell biology, and so on.”

Lauer declined to speculate on why these scientists chose not to disclose their foreign ties. But he said NIH has found several cases where the omissions were selective. “We’ve seen scientists who reported other foreign grants and affiliations, but not the Chinese grants and affiliations,” he says.

Among U.S. lawmakers and the media, some of the concern about foreign influence in U.S. research has focused on the role of the Thousand Talents Program, part of China’s decadelong campaign to build ties with scientists outside of China. The program provides distinguished U.S.-based scientists with generous packages to set up and operate labs at a Chinese research institution or university.

Lauer says some of those Thousand Talents awards come with very specific instructions to the researcher, including what they are expected to study and the number of papers they must publish in top-tier journals. But the provisions about what activities should and should not be disclosed are not uniform.

“We have seen contracts that say all the intellectual property that this scientist generates must stay in China and cannot be reported to their American university,” he says. “You can imagine that U.S. universities are not happy when they see that. U.S. universities expect to reap the benefits of research done at their institution, and they are losing that [opportunity].”

Other contracts lean in the opposite direction, Lauer says. “They say every paper a scientist publishes must cite the Chinese university,” he says. “Some have gone so far as to say their university must be cited first.” Lauer says those scientists are also required to cite the Chinese entity funding their research funding, “for the same reason we require people to cite their NIH grants: We want to make sure we get credit for the research we have funded.”

Guilt by association?
Many members of the Asian American community believe that U.S. government agencies have been targeting Asian-born scientists simply for their participation in Thousand Talents and similar Chinese foreign recruitment programs. Lauer says NIH has no problem with U.S. scientists who participate in Thousand Talents so long as they disclose that relationship fully in their grant applications and research progress reports.

“Thousand Talents is not a threat [to the United States],” he says. “It’s not the specific conduct we are focusing on, it’s the failure to disclose it.”

To make his point, Lauer offers an alternative scenario of what he considers to be acceptable behavior. “A U.S. scientist goes to their boss and says, ‘I would like to work in China for 3 months a year, and I managed to secure a part-time employment arrangement. I’ll tell you what I’m working on, and how intellectual property will be handled, and how much they will pay me.’ And then they report all of that in their biosketch.”

That should be the norm, he says. But it’s not. “If that is what was happening,” Lauer says, “you and I would not be sitting here today.”

https://www.sciencemag.org/news/2019/06/nih-probe-foreign-ties-has-led-undisclosed-firings-and-refunds-institutions

Moffitt turmoil began with national concern over China, stolen research

Feds say they are just beginning to understand the scope of foreign involvement in U.S.-based research, at Tampa's Moffitt Cancer Center and beyond.

(A worker handles samples in a lab at Moffitt Cancer Center, where officials say concerns over foreign meddling have not affected research. [Courtesy of Moffitt Cancer Center])

By Justine Griffin
Published Yesterday
A sudden change in leadership at Moffitt Cancer Center shook the Tampa Bay medical community last week and quickly prompted the Legislature to take the unusual step of launching an investigation.

But while the news turned heads in Florida, the turnover at Moffitt is part of a national story line that reaches back to the Obama era and has played out with snowballing urgency ever since. In recent months, federal agencies have become increasingly concerned that Americaâ??s investment in top scientific research is being systematically stolen by foreign actors.

At Moffitt, CEO Dr. Alan List, a vice president and four researchers abruptly resigned in relation to possible exploitation of American-funded research by China. Evidence was found that they were compensated by a Chinese talent recruitment program and failed to disclose it, officials at the Tampa-based center said.

The federal government is still trying to grapple with this and instances like it around the country, said Dr. Michael Lauer, deputy director for extramural research with the National Institutes of Health.

"Research has been compromised," he said, though Moffitt claims its own research was not affected.

"Funding went to projects it never should have. Meanwhile, other proposals didn't get the funding they deserved."

The NIH, which gives out $30 billion a year to American scientists and universities for biomedical research, has opened 180 formal inquiries related to instances of foreign meddling in grant research and funding. In some cases, researchers shared peer-reviewed proposals with the Chinese government, and that research was copied verbatim in Chinese laboratories. Other instances include American researchers being paid by both the NIH and the Chinese government for the same work.

"Many of the universities had no clue this was happening on their campuses," Lauer said. "The scientists they employed never told them about any ties to China, or that they were also employed there."

And the interest in American research doesn't stop with medical topics like cancer. It extends to a variety of industries, from energy and the environment to technology, Lauer said.

A team from Moffitt Cancer Center recently met with federal officials to discuss its investigation into how foreign actors might be involved in its research.
[COURTESY OF MOFFITT CANCER CENTER]
The NIH is working with the FBI to continue to identify cases of intellectual property theft, he said. But Congress also has taken a leading role in trying to understand how this is happening and how to stop it.

The federal government has commissioned studies to get to the bottom of the issue, but so far it's been difficult to discern just when the foreign involvement began and how deep it goes. The scale and scope was hard to define even in a study released earlier this month by JASON, an independent group of scientists who advise the U.S. government.

In November, the Committee on Homeland Security and Governmental Affairs in the U.S. Senate released a report titled, â??Threats to the U.S. Research Enterprise: China's Talent Recruitment Plans," which detailed how $150 billion in American grant funding through organizations like the National Science Foundation, the NIH and the Department of Energy's National Labs is at risk.

"China unfairly uses the American research and expertise it obtains for its own economic and military gain," the report reads. "Based on this investigation, the subcommittee finds that the federal government has failed to stop China from acquiring knowledge and intellectual property from U.S. taxpayer-funded researchers and scientists. Nor do federal agencies have a comprehensive strategy to combat this threat."

A joint committee by the National Science and Technology Council held a summit at the White House last month to discuss the issue, Lauer said. A summary of the meeting describes efforts to be taken by the federal government to ensure better security. Among the ideas: better communication between federal agencies, including making FBI threat briefs more widely available.

In Florida, State Rep. Chris Sprowls, R-Palm Harbor, announced he will lead an investigation into Moffitt and other federally and state-funded academic institutions related to this issue.

A team from Moffitt met recently with Lauer and others in Bethesday, Md., to discuss the centerâ??s investigation so far, according to a letter to lawmakers from H. Lee Moffitt, the centerâ??s namesake and a former House Speaker in Florida. The letter also disclosed that the information has been shared with the Legislature's Office of Program Policy Analysis and Governmental Accountability.

"The Tampa Bay community and Florida taxpayers who send millions to Moffitt every year need more than vague assurances," the former speaker wrote.

In a related development, Moffitt officials confirmed this week that List, who initially said he'd continue to treat his current patients at Moffitt, has since cut all ties with the center.

At the national level, meanwhile, academic associations are developing security guidelines for individual colleges to follow regarding security breaches. The Association of American Universities surveyed members to craft the framework. Penn State University, whose research focuses heavily on energy issues, has been recognized as a national leader in its efforts to be transparent through a new website detailing its compliance policies.

The University of Florida also launched a website outlining the proper disclosure requirements for researchers. Spokesman Steve Orlando said the university developed a new international risk assessment process to screen activities with foreign institutions and developed an electronic system to monitor the disclosures of outside activities and interests.

This year alone in Florida, the NIH awarded 1,456 grants totaling more than $705 million to universities, research centers like Moffitt and other entities. The University of Florida received more than $190 million and the University of South Florida nearly $76 million, according to the NIH website.

While research is generally funded by federal grants, universities benefit from the prestige of publishing the findings and collect royalties on patents and other investments under the 1980 Bayh-Dole Act.

Said Lauer: "Perhaps the most serious loss is that this has enabled China to know what is going on inside American laboratories, and get a head start on everyone else."

https://www.tampabay.com/news/health/2019/12/26/moffitt-turmoil-began-with-national-concern-over-china-stolen-research/?outputType=amp

This should break out of these
levels here very soon!

Build Biologics Not Barriers

iBio’s unique partnership with Beijing’s CC-Pharming will bring economical, plant-derived rituximab to China

By Karen Langhauser, Chief Content Director

Feb 19, 2019

The current trade conflict between the world's biggest economies — the United States and China — has resulted in both countries imposing billions of dollars’ worth of tariffs on each other’s goods. At the time of writing, U.S. and Chinese officials are meeting in Beijing, attempting to resolve the damaging trade dispute. But the stakes — and the tension — remain high.

As many larger companies in both countries are cautiously stalling business dealings, a small Chinese Biotech and a small U.S. CDMO have decided to put politics aside and work together for the greater good. iBio, a Texas-based CDMO and CC-Pharming, a Beijing-based biologics development company have joined forces to develop biopharma products and manufacturing facilities in the Chinese market, utilizing iBio’s proprietary technology.

Their novel and unconventional union may prove to be a game-changer for the future of biopharma production in China.

THE NEED

iBIO partners with Porton PharmaRobert Erwin, president, iBio and Dr. Kevin Wang, founder of CC-Pharming, execute a Master Joint Development Agreement for a a plant-derived, bio-better rituximab
Rituxan (rituximab) was first approved by the U.S. Food and Drug Administration in 1997 and was the first new drug for Non-Hodgkin’s Lymphoma (NHL) in a decade. Since then, its clinical uses have expanded to a range of autoimmune diseases including types of rheumatoid arthritis. The drug came off patent in Europe in 2013, and in the U.S. in 2016, paving the way for biosimilars.

But despite the development and approval of biosimilar versions, treatments are still too expensive for many patients. In China especially, there is a severe lack of access to needed therapies such as rituximab.

“The Chinese market is changing because China’s middle class is growing extremely rapidly — and the demand for these products is going to go up over the next few years. Current capacity cannot adequately serve the rising demands of its population in terms of biologics,” says Robert Erwin, president and COO, iBio Inc.

China’s biologics sector has been held back by regulatory backlogs, capacity restraints and quality issues. While things are changing for the better, bioprocessing capacity remains a challenge.

A DIFFERENT APPROACH
Therapeutic antibodies are mainly produced in mammalian host cell lines. For rituximab, Chinese hamster ovary (CHO) cells are used. But in terms of manufacturability and scalability, working with mammalian cells has historically been challenging — and expensive.

In 2017, Dr. Kevin Wang , a Chinese-American biochemist and plant scientist left the U.S. to create CC-Pharming in Beijing. His goal was to apply plant transient expression technology to produce biologic drugs. Wang was enthusiastic about the potential for scientific and manufacturing advances and worked to provide health benefits to the Chinese people — while also offering very attractive business opportunities for a new company. While researching alternatives to CHO, Wang came across iBio and concluded that a collaboration between his new company and iBio accelerate achievement of his goals and be beneficial to both companies.

iBio’s primary research, development and manufacturing system uses vacuum-infiltration to transfect Nicotiana benthamiana plants, grown in a fully contained, hydroponic system. These plants are infiltrated with an agrobacterium vector that “hijacks” the protein-making functions of the plant. The plant leaves replace a traditional bioreactor, becoming a “protein factory” for seven days. The plant biomass is then harvested and the resulting extract is purified through a typical downstream purification as in most biopharma facilities.

Technology transfer and scale-up is vastly simplified because the need to adapt cell lines to the scale of the bioreactor is eliminated in the plant-based process. Simplification equates to cost-savings. The upstream capital required is dramatically less than mammalian cell reactors.

“A main advantage of the iBio manufacturing platform is that you can increase capacity of a fundamental facility at a non-incremental cost. You can double, triple, quadruple facility capacity just by growing more plants — you don’t have to build bioreactors,” says Erwin.

That savings is key for CC-Pharming as they work to introduce a plant-made antibody superior to rituximab in performance and more affordable than rituximab in price to the Chinese market.

COLLABORATION TRUMPS POLITICS
Given the present-day tensions between the U.S. and China, it might seem that it’s a less than ideal time to enter into business deals with Chinese companies. In fact, the political climate is such that when iBio and CC-Pharming tried to assemble for a planning session in Texas in October, several members of CC-Pharming were initially denied visas.

But despite obstacles, the biopharma industry is proving to have some level of immunity to political drama. “Government trade barriers should not stop good business deals in the biotech industry,” says Barry Holtz, president, iBio CDMO.

Biotech investments back Holtz’ opinion. According to a recent Financial Times report, China venture capital investors have become one of the most important sources of capital for U.S. biopharma companies.

And much of this investment is driven by the hope that U.S. drug development wins will be introduced to China’s market.

But the iBio and CC-Pharming partnership takes this a step further, by bringing the technology to China, so that market needs can be met locally.

“Empowerment is a great business model,” says Holtz.

The iBio/CC-Pharming partnership is currently in the conceptual design stage with a timeline that iBio calls “aggressive but reasonable.” The goal is an IND approval in two years for a plant-made monoclonal therapeutic antibody version of rituximab and then to add mutually selected products.

iBio, which has similar partnerships with pharma companies in South Africa and Brazil, believes that there is great value to be gained by collaboration.

“A good business deal makes money, not adversaries, and serves an unmet medical need,” concludes Holtz

Inhibitors of Notch signaling can be used not only as direct anti-cancer agents but also as a sensitizer to current therapy.

Peregrine / CDMO KOL Scott Antonia co patent owner Dr James Mule which were both enticed to sell out their patent ....

Florida House speaker calls for investigation into China-Moffitt ties

Speaker José Oliva taps state Rep. Chris Sprowls to find out whether China benefits from millions spent on medical research at Florida institutions.

Florida House Speaker José Oliva said Thursday that state Rep. Chris Sprowls will investigate ties between China and Tampa’s H. Lee Moffitt Cancer Center & Research Institute following Wednesday’s announcement that the center’s CEO and others have been ousted.

“The news (stories) coming out of Moffitt Cancer Center are of great concern and compel further investigation," Oliva said in a statement. “While Moffitt’s leadership acted swiftly and decisively, a deeper look into this and all of our institutions is in order.”

In an interview Thursday, Sprowls said actions by Moffitt’s CEO, Dr. Alan List, and other center employees had aided infiltration efforts by China and were indefensible. The Palm Harbor Republican, a former prosecutor, said lawmakers should take steps to make sure similar activity isn’t occurring at other academic institutions across the state.

“These research institutions benefit from vast sums of state and federal resources that are funded by American taxpayers,” said Sprowls, who is slated to succeed Oliva as House speaker. “For these researchers to receive monetary gain from the Chinese government and to pilfer our research, that is just alarming news. And I don’t believe it is isolated to Moffitt.”

State Rep. Chris Sprowls greets Florida House Speaker Jose Oliva last year after Oliva was sworn in at the Florida Capitol. On Thursday, Oliva appointed Sprowls to investigate Chinese efforts to benefit from millions spent on medical research at Florida institutions.
[SCOTT KEELER | TIMES]
Moffitt received more than $36 million this year in grants from the National Institutes of Health, one of the federal agencies investigating the extent to which China is benefiting from U.S.-based medical research.

RELATED: Moffitt Cancer Center shakeup: CEO and others resign over China ties

Moffitt’s board of directors announced Wednesday that List, along with Thomas Sellers, a vice president and director at Moffitt, and four of the cancer center’s researchers resigned under pressure because of a controversy that linked them to possible exploitation of American-funded research by China. List will continue to treat his current patients at Moffitt. He did not respond to multiple phone calls and emails requesting an interview.

Moffitt officials did not divulge whether List and others accepted money from China, but said an internal investigation revealed conflicts of interest and a lack of disclosure of international collaborators. Officials said there is no indication that Moffitt research was compromised or that patient care has been affected.

“We found evidence that people were compensated through the Thousand Talents program and failed to disclose that,” Moffitt officials disclosed Thursday.

The reference was to a program China uses as a tool to recruit talent from Western countries. Sprowls said it’s been “widely reported” that Americans involved in Thousand Talents have received monetary gains.

“I plan to take an active role in looking into the firewalls in place to protect our intellectual property and proprietary information,” Sprowls said. “The Legislature funds these institutions and we need to account for the money we’ve already spent. Taxpayers deserve to know that their money is not subsidizing the Chinese government.”

It was unclear whether Moffitt’s 12-year research and education partnership with the Tianjin Medical University Cancer Institute and Hospital, a 2,400-bed hospital outside of Beijing, is also a source of concern. Moffitt officials are reviewing the arrangement and have alerted the federal government of their preliminary findings.

Thousand Talents was one of hundreds of programs created by the Chinese government to lure back esteemed scientists to improve the quality of the country’s research and innovation, said Ross McKinney, chief scientific officer for the Association of American Medical Colleges.

“The problem wasn’t the recruitment. That happens all the time and there’s nothing wrong with it,” he said. “The problem came when scientists didn’t want to come to China, so instead they’d offer them a part-time job and instructed them not to tell anyone about it.”

Researchers would be paid for their work, sometimes in Chinese currency. Others would steal ideas from peer-reviewed proposals. In some cases, Chinese researchers would copy data and install malware on university campuses, McKinney said.

“These researchers were told to lie,” he said. “And all of a sudden, someone in China is doing the very project you proposed to do. It is a very serious structural effort on the part of the Chinese government.”

Oliva alluded to that activity in his statement Thursday.

“Floridians, and all Americans, should be greatly concerned at both the potential theft of intellectual property and the corruption it implies,” the statement said. "Compromising our public health and research institutions puts all of us at risk. The Florida House will do everything in our power to hold people, and institutions, accountable.”

In an email, NIH officials said Moffitt’s review showed “that several individuals involved in NIH grants, some of whom are members of the Moffitt Cancer Center leadership team, failed to disclose substantial contributions of resources from other organizations, foreign affiliations, and financial conflicts of interest.”

The statement also said NIH will work with Moffitt “to determine the extent of the violations and remediation actions.” The response, it said, could include the removal of more researchers and the return of grant money to the government. The agency also commended Moffitt for “identifying and disclosing these violations to NIH.”

The agency, one of the largest funding sources for medical research in the world, has launched 170 formal inquiries into American academic institutions this year where ties to China were unclear. Researchers were fired at Emory University and the University of Texas MD Anderson Cancer Center. In some cases, the FBI is involved.

“China has pioneered a societal approach to stealing innovation in any way it can from a wide array of businesses, universities and organizations," FBI Director Christopher Wray said in April. "They’re doing it through Chinese intelligence services, through state-owned enterprises, through ostensibly private companies, through graduate students and researchers, through a variety of actors all working on behalf of China.”

Wray added: “At the FBI, we have economic espionage investigations that almost invariably lead back to China in nearly all of our 56 field offices, and they span just about every industry or sector.”

But rooting out who is leaking information has been a challenge, McKinney said. The scale and scope of the problem was even difficult to define in a study released in December by JASON, an independent group of scientists which advise the U.S. government.

“We don’t know how deep it goes. We’re not good at this sort of inspection,” he said.

For decades, American medical and research institutions have forged relationships with foreign collaborators to share information and research strategy, said Jay Wolfson, a professor at the University of South Florida’s College of Public Health and an expert on health care policy.

“For years, some of our best and brightest students have come to study in America from China, South Korea, India and South American countries," he said. "Some stay and join faculty. Others return home and want to maintain those relationships. Collaboration like this improves quality of life and science.”

McKinney reiterated the point, saying the U.S. has a rich history of science being done by immigrants and in collaboration with other countries. “It’s a shame that it could be damaged by the effects this program has had on trust,” he said.

Some scientists fear the U.S. government could go too far and create regulations that would stifle future research collaborations, said William Colglazier, a senior scholar with the Center for Science Diplomacy at the American Association for the Advancement of Science.

“There are two sides of this coin," he said. “It’s in everyone’s interest that we can all benefit from any breakthroughs that happen in science, no matter where they are. The other side is that clearly China has not followed the norms and standards of ethical requirements, and they need to understand that this cannot continue.”

Any investigation by state lawmakers would look into other academic institutions in Florida beyond Moffitt, including the Mayo Clinic in Jacksonville, the University of South Florida and the University of Florida, which also receive NIH grants.

UF Health in Gainesville strengthened its processes and protocols recently due to the NIH inquiries, said spokesman Steve Orlando. That included launching a dedicated website to explain new requirements of researchers.

Earlier in the year, Moffitt officials had pitched a multi-million dollar expansion to its Tampa campus to meet greater patient needs. Sprowls said state funding for the cancer center’s expansion project isn’t off the table, but Moffitt leadership has some questions to answer first.

“It’s a separate issue," Sprowls said. “But they have to account for these unanswered questions.”

Revs Guidance
(FY’20 fye 4-30-20): $64-67M. 7-31-19 Backlog=$61M
*Cash: 7-31-19: $28.9M
*As of 8-31-19: 56,237,674 shares o/s.