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Sunday, March 31, 2019

Circassia Pharmaceuticals: FDA approval of Duaklir for treatment of COPD

Duaklir® launch planned H2 2019
Duaklir® to join Tudorza® in Circassia’s portfolio of US COPD products
Circassia Pharmaceuticals plc (‘Circassia’ or ‘the Company’; LSE: CIR), a specialty pharmaceutical company focused on respiratory disease, today announces the US Food and Drug Administration (FDA) has approved Duaklir® for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Duaklir® is a fixed-dose combination of the long-acting muscarinic antagonist (LAMA) aclidinium bromide (400 mcg) and long-acting beta-agonist (LABA) formoterol fumarate (12 mcg) administered twice-daily via the breath-actuated inhaler Pressair®. Circassia is on track to launch Duaklir® in the United States in the second half of 2019 via its dedicated COPD sales force.
In 2017, Circassia and AstraZeneca established a collaboration for the commercialisation of Tudorza® and Duaklir® in the United States. At the end of 2018, Circassia exercised its option over Tudorza® and the Company now has the full US commercial rights to both products. Under the companies’ agreement, a contingent option fee of $20 million becomes due to AstraZeneca within 30 days of the FDA approval of Duaklir®, and final deferred consideration of $100 million is due by 30 June 2019. The Company is in discussions with third-party finance providers to satisfy all or part of these payments. If this financing is not forthcoming, Circassia plans to use a loan facility provided by AstraZeneca under the companies’ agreement to satisfy the outstanding amount.
Duaklir® and Tudorza® are registered trademarks of Almirall S.A.
Pressair® is a registered trade mark of the AstraZeneca group of companies

NY accuses opioid maker Purdue of illegal fund transfers to Sacklers

Purdue Pharma LP fraudulently transferred funds to members of the wealthy Sackler family who control the OxyContin maker despite knowing it faced major liabilities that had made it already insolvent, New York’s attorney general alleged on Thursday.

New York Attorney General Letitia James made the claims in a revised lawsuit already pending against Purdue over its role in the opioid epidemic that added members of the Sackler family and other drug manufacturers and distributors as defendants.
The lawsuit alleged Purdue and other manufacturers engaged in deceptive marketing that downplayed the dangers of the addictive painkillers and accused distributors of failing to detect the diversion of the drugs for illicit purposes.
“As the Sackler family and the other defendants grew richer, New Yorkers’ health grew poorer and our state was left to foot the bill,” James said in a statement.
The revised lawsuit also added as defendants units of opioid manufacturers Johnson & Johnson, Endo International Plc, Teva Pharmaceutical Industries Ltd and distributors McKesson Corp, Cardinal Health Inc and AmerisourceBergen Corp.
In a statement, the Sackler family called the lawsuit “a misguided attempt to place blame where it does not belong for a complex public health crisis.”
Representatives for the other defendants did not respond to requests for comment.
The case is among roughly 2,000 lawsuits filed by state and local governments seeking to hold Purdue and other pharmaceutical companies responsible for the U.S. opioid crisis.
Opioids were involved in a record 47,600 overdose deaths in 2017 in the United States, according to the U.S. Centers for Disease Control and Prevention.
The complaint came after Purdue and the Sacklers on Tuesday reached a $270 million settlement with Oklahoma resolving similar allegations. Purdue had been exploring filing for bankruptcy prior the accord’s announcement.
In her lawsuit, James accused Purdue of seeking to “intimidate” states pursuing lawsuits against it by threatening bankruptcy, which would hinder their cases and limit their ability to recover damages.
Yet James said Purdue, which is fighting lawsuits by 34 other states and hundreds of localities, has continued in the face of its liabilities to pay millions of dollars to the Sacklers.
The lawsuit argued Purdue was either insolvent or near insolvency when it transferred those funds, making the transfers illegal under New York law.
The payments meant Purdue, which had average annual sales of $3 billion, no longer had assets that could satisfy the state’s claims, the lawsuit said.

AstraZeneca Selumetinib Designated as Breakthrough Therapy

AstraZeneca said Monday that its Selumetinib drug has been granted a breakthrough therapy designation in the U.S. for neurofibromatosis type 1, a genetic condition which causes tumors to grow in the nervous system.
The drug company said the designation is for treatment of pediatric patients aged three years and older, and means Selumetinib could get an expedited regulatory review.
The designation is based on a phase 2 trial for Selumetinib. The drug is being jointly developed by AstraZeneca and Merck & Co. Inc. (MRK).

Novartis pays $310 million upfront for inflammation specialist IFM

Novartis on Monday said it had agreed to pay $310 million (£238 million) upfront, with the possibility for more later, for some assets of Boston-based inflammation specialist IFM Therapeutics as the Swiss drugmaker seeks to expand its immunology pipeline.

The deal for the IFM subsidiary IFM Tre could eventually reach nearly $1.6 billion, IFM said in a statement, should the portfolio of clinical and preclinical molecules meet milestones. IFM has one molecule, IFM-2427, in an early Phase 1 trial, as well as other less-developed assets.

FDA Action Alert: Evoke Pharma, IntelGenx and ADMA Biologics

Three companies are looking for decisions by the U.S. Food and Drug Administration (FDA) this week. All three drugs are either resubmissions or have had to deal with various problems related to manufacturing or incomplete data. Here’s a look.
Evoke Pharma’s Gimoti Runs Into Trouble
Evoke Pharma’s Gimoti has a target action date of April 1. On March 4, the Solana Beach, Calif.-based company received a multi-disciplinary review (DR) letter from the FDA in association with its New Drug Application (NDA) for Gimotti. A DR letter is used by the FDA to communicate its early thinking on deficiencies observed in an initial review of an NDA. Gimotti is designed to treat gastroparesis, a debilitating, episodic condition characterized by slow or delayed gastric emptying of the stomach after meals, often resulting in symptom flare-ups that include nausea, vomiting, abdominal pain and bloating. It occurs disproportionately in adult women.
There were three sections of the NDA that the agency had concerns about. They were chemistry, a combination of product quality control and reproducibility connected to the commercially available sprayer device used with the drug; clinical—lack of enough data to support sex-based efficacy differences; and clinical pharmacology, specifically that the maximum concentration wasn’t within the parameters of the bioequivalence for abbreviated NDAs.
In theory, the DR letter doesn’t reflect a final FDA decision, but it does throw the April 1 target action date into a cloud of uncertainty.
On March 14, Evoke submitted a response to the DR and requested a meeting with the agency over the April 1 target action date. The meeting was held on March 21, but at this time no information has been released about the content of that meeting.

IntelGenx’s Rizaport for Acute Migraine
Saint Laurent, Quebec-based IntelGenx Corp. has an April 1 target action date for the resubmitted NDA for Rizaport, a VersaFilm oral soluble film to treat acute migraines. The company has five inspectional observations from a January Pre-Approval Inspection as part of the company’s Health Canada-certified cGMP manufacturing facility in Montreal by the FDA. At the time, Horst G. Zerbe, president and chief executive officer of IntelGenx said, “We appreciate the thoroughness of the FDA’s review of our facility, and we are confident that we will be able to address the FDA’s observations within the 15-day response timeframe.” As we continue to advance through the NDA process, IntelGenx is excited to have completed another important milestone toward U.S. approval.”
Rizaport is a proprietary oral thin film formulation of rizatriptan benzoate, a 5-HT1 receptor agonist and the active drug in Merck & Co.’s Maxalt.
ADMA Biologics’ Resubmission of Bivigam
ADMA Biologics, headquartered in Ramsey, NJ, has a target action date of April 2 for Bivigam for the treatment of Primary Immunodeficiency Disease (PIDD). PIDD is a class of inherited genetic diseases that result in a deficient or absent immune system. The FDA issued a Complete Response Letter (CRL) on December 19, 2018 for Bivigam. On January 7, 2019, ADMA submitted its response and provided supplemental information.
Bivigam is an intravenous immune globulin indicated for the treatment of primary humoral immunodeficiency. That includes agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome and severe combined immunodeficiency. Bivigam holds a broad range of antibodies similar to those observed in normal human plasma. The antibodies are directed against bacteria and viruses, and help protect PIDD patients against serious infections.

Opioid Crisis: Action News investigates safe injection sites

Safe injection sites are places for opioid addicts to go use their drugs in a controlled environment.
There is a push to bring such sites to Philadelphia, but not everyone is on board with the idea. So Action News traveled to Toronto, Canada where safe injection sites are already up and running to get a first-hand look.
We found a mixed reaction.
There are still many hurdles before they become reality here in Philly, but they’ll be largely modeled after sites in Canada.
There’s no question these sites save lives and prevent disease, but their location can create concern from residents. We met Farrah Morrison in one of those sites. She was getting a fix with a clean needle inside a sterile room, all while being monitored in case of an overdose.
“You cannot use alone because you will die,” she said. “You will die.”

It’s been nearly a year since Toronto opened its first federally approved safe injection site.
“We offer all the supplies that they’d need: tourniquet, sterile water, cookers, and then they can select the needle that most meets their needs,” said Shaun Hopkins, who runs a site in the heart of Toronto’s tourism district. “We intervened, so far, from August 2017, in about 170 overdoses either with Naloxone or oxygen. So you could say we’ve saved those lives,” she said.
In Toronto, roughly 300 people died from an opioid-related overdose in 2017. Not one of those deaths happened in one of these facilities. Naloxone, commonly known by the brand name Narcan, is readily available. After a user injects, they’re urged to go to an observation room.
When asked about public support for the facility, and whether it has increased or decreased, Hopkins said, “I think public support for this facility is difficult.”
And this is why: Over the two days we sat outside several of Toronto’s safe injection facilities, we witnessed prevalent drug use out front, drug deals, and even violence. We watched as one man harassed several people passing by on the sidewalk, even putting one in a chokehold. One guy decided to fight back and security arrived.
Christine Wittick owns the Football Factory, a bar neighboring one of the city’s half-dozen operational safe injection sites. She understands the need, but feels the rights of the addicts often come before those in the community.
“We started to have drug dealers and prostitutes across the street. Crime started to escalate, neighbors have had their homes broken into, my husband has been punched in the face by a man who was very, very high in front of customers,” Wittick said.
In Moss Park, we met a woman named April. Like many users, she’s addicted to both crack and heroin. We found her using just a few hundred feet from a supervised injection site.
“I go and get a lot of supplies and don’t stick around,” she said. April admits that the site attracted more users and dealers, but said the impact is worth it to save lives.
“If you use alone, you die alone,” she said. “You’ve got to weigh the negative with the positive. Saving a life is a lot more important that the other things that come along with it.”

Bill Coldin lives across the street from the park. He admits there was drug usage there before the facility opened last year, but says it’s increased since. We asked: What would your message be to Philadelphians?
“Be careful where you put them,” he said. “You are going to need increased policing around them.”
He says the site in his neighborhood is not being used for its intended purpose.
“What bothers me is no one is using is the facility. And if they are using it, they are using it to socialize and talk right there,” said Coldin.
Toronto City Councilor Giorgio Mammoliti is an outspoken critic of the safe injection sites. He believes the facilities should be placed in hospitals and have a greater emphasis on treatment. But Canadian health officials say you can’t push addicts into treatment.
If you do, they say, addicts won’t use the sites. First, they say, trust needs to be established and it’s inside these walls where that will happen.
Here in Philadelphia, city leaders have been selling the public on the idea that so-called comprehensive user engagement sites will be a bridge to rehab.
“Every city is going to address this in a different way. We believe strongly in getting people in treatment is our goal, and pushing that at every step in the process,” said Philadelphia Health Commissioner Tom Farley.
Farley said he hopes to open a supervised injection site within the year, but says the biggest obstacles are the legal issues and whether the United States Attorney General’s office will take action if one opens.
Research on the effectiveness of supervised injection sites being a path to treatment have been inconclusive. Toronto was unable to provide any statistics regarding its sites. However, the city of Vancouver’s original facility, Insite, reports out of 7,300 users in 2017, just six percent accessed its detox treatment facility, and the average stay was just 11 days.
After shooting up her latest hit, Farrah Morrison said she was ready to get off drugs and connect with her three children. She’s using this site as the road to that recovery, but where it ends is unclear.
“Wish me luck,” she said.

Bayer downgraded to Hold from Buy at Deutsche Bank

CD40 antibody combination therapy can shrink pancreatic tumors

A new combination of immunotherapy and chemotherapy for pancreatic cancer caused tumors to shrink in the majority of evaluable patients—20 out of 24 as of an interim analysis of the phase 1b trial data. The early findings provide hope that this strategy involving a CD40 antibody, a checkpoint inhibitor, and standard-of-care chemotherapy could be effective for treating the nation’s third deadliest type of cancer. Researchers from the Abramson Cancer Center at the University of Pennsylvania will present the findings today in a clinical trials plenary session at the American Association for Cancer Research 2019 Annual Meeting in Atlanta (Abstract #8060). The ongoing study is being conducted in collaboration with the Parker Institute for Cancer Immunotherapy and its other member institutions and partners. These are the first clinical trial data ever presented as a result of this collaboration.
“These findings give us clues that this new and innovative combination therapy can be effective against ,” said the study’s co-lead author Mark H. O’Hara, MD, an assistant professor of Hematology-Oncology at Penn. “Although only time and further research will truly tell, our data are a reason for optimism.” O’Hara will present the plenary at 12:45 p.m. in Marcus Auditorium, Bldg A-GWCC.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic , and it kills more Americans each year than any cancer type other than lung and colorectal. Despite the fact that it only accounts for about three percent of new cancer cases, it is responsible for more than seven percent of all cancer deaths, and just 8.5 percent of patients survive five years with the disease. Previous research has shown PD-1 inhibitors are ineffective on their own against PDAC, but preclinical data showed combining PD-1 inhibitors with antibodies that target a different antigen known as CD40 can trigger an .
For this study, patients with metastatic PDAC who were previously untreated received combinations of four different therapies. Each patient received gemcitabine and nab-paclitaxel, which are standard-of-care chemotherapies, as well as an experimental antibody targeting CD40 called APX005M. Half the patients also received the PD-1 inhibitor nivolumab. As of the data cutoff for the interim analysis, 20 of 24 patients (83 percent) saw their tumors shrink. Overall, although the majority of the patients experienced side effects from the treatment, they were expected and manageable, with several patients continuing on treatment for more than a year, which also suggests the combination treatment can produce a durable response.
“Seeing patients continue treatment for this length of time does give us hope that this combination approach holds promise, especially when you consider that for stage 4 pancreatic cancer, the median survival is just two to six months,” said senior author Robert H. Vonderheide, MD, DPhil, director of the Abramson Cancer Center and a Parker Institute member researcher. Vonderheide previously led the first-in-human clinical trial of APX005M reported in 2017 that enabled the current study.
The Parker Institute holds the Investigational New Drug application from the U.S. Federal Drug Administration. Patients on this trial were treated at seven Parker member institutions, leveraging a unique ability to develop faster and more efficient clinical studies.
“This study represents the first illustration that our unique collaborative model, which we used to bring together partners from across academia, pharma, and biotech, can help speed the process of translating laboratory findings into efficient, impactful  in areas with high unmet medical need,” said Ramy Ibrahim, MD, the chief medical officer at the Parker Institute for Cancer Immunotherapy. “Based on these early but promising findings, we are excited to see results from the next phase of the study.”
In addition to Penn, Parker member institutions who treated  on this study were Memorial Sloan Kettering Cancer Center; The University of Texas MD Anderson Cancer Center; University of California, Los Angeles; University of California, San Francisco; Stanford University; and Dana-Farber Cancer Institute.
The randomized phase two portion of the trial evaluating chemotherapy, APX005M, and/or nivolumab is currently underway. Apexigen, which manufactures APX005M, and Bristol-Myers Squibb, which manufactures nivolumab, each supplied the drugs for this study. Additional support was provided by the Cancer Research Institute.

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Bristol-Myers Squibb’s Opdivo-Yervoy duo provokes response in rare tumors

Bristol-Myers Squibb has found success with its Opdivo-Yervoy combo in treating various common tumors. But it turns out the duo can help some patients with rare tumors, too.
Sunday at the American Association for Cancer Research annual meeting, researchers unveiled data from an investigator-sponsored phase 2 study showing that Opdivo and Yervoy could produce a benefit in patients with neuroendocrine tumors in various parts of the body.
In a study of 33 patients, 24% responded to therapy, with one patient’s cancer disappearing completely. But among patients with high-grade cancer cells—which tend to grow and spread more quickly—response figures were higher: 42%, or 8 of 19 patients, recorded a response to the combo, while none of the patients with low- or intermediate-grade cancer did.
Based on those numbers, researchers concluded that ”further investigation of this combination is warranted,” they said in the study abstract. And meanwhile, they have an idea as to why the BMS pairing only turned up a benefit in high-grade patients.
“One preliminary hypothesis for this finding is that high-grade neuroendocrine carcinomas may have a higher tumor mutational burden, which is an indicator of better response to immunotherapy,” lead study investigator Sandip Patle, M.D., said in a statement.

Bristol-Myers itself has been working to prove the link between TMB and Opdivo-Yervoy efficacy as it chases an indication in previously untreated non-small cell lung cancer, which is considered immuno-oncology’s largest market. After trumpeting positive data at last year’s AACR meeting, the company last October acknowledged that in a new analysis, the combo’s survival benefit in patients with high TMB and low TMB appeared “quite similar (based on hazard ratios compared to chemotherapy),” as Credit Suisse analyst Vamil Divan put it.
“This leads us to wonder why regulators would approve the regimen strictly for patients with high TMB as per the current filing,” he wrote at the time. And Bristol didn’t wait to find out: It pulled its application in January, citing a need for more data.

Meanwhile, though, Patel and his colleagues say they’ve already scored with the study. “Our study highlights the feasibility of performing clinical trials among patients with rare cancers,” he said, noting that rare tumor types represent “nearly a quarter of all cancers.”
The study will “hopefully will help dispel the belief that clinical trials are not feasible for this patient population,” he added.

#AACR: Neon Therapeutics trial shows benefit in melanoma vaccine

Post-Vaccine Immune and Pathologic Markers Associated with Durable Clinical Benefit in Metastatic Melanoma Patient Cohort
Top-line Results, Including 52-Week Clinical Outcomes, from Full NT-001 Trial in Melanoma, Non-Small Cell Lung and Bladder Cancers Expected Later in 1H 2019
Neon Therapeutics, Inc. (Nasdaq: NTGN), a clinical-stage immuno-oncology company developing neoantigen-based therapeutics, today presented updated data describing the immune and pathologic markers associated with durable clinical benefit in patients enrolled in NT-001, an ongoing Phase 1b clinical trial evaluating NEO-PV-01 in combination with nivolumab (OPDIVO® or anti-PD-1 therapy). The data were highlighted in an oral presentation titled, “The Personalized Vaccine, NEO-PV-01 with Anti-PD-1, Induces Neoantigen-Specific De Novo Immune Responses in Patients with Advanced or Metastatic Melanoma: Association with Clinical Outcomes,” at the American Association for Cancer Research (AACR) Annual Meeting in Atlanta.
NEO-PV-01 is a personal neoantigen vaccine custom-designed and manufactured based on the neoantigens identified by Neon’s proprietary bioinformatics engine, RECON®, as being the most therapeutically relevant for an individual patient. The data presented today, which reflect a cutoff date of August 31, 2018, include 23 patients with metastatic melanoma who received at least one dose of NEO-PV-01 and who either remained progression-free or had progressed by week 36 after the initiation of anti-PD-1 therapy. Patients who did not progress by 36 weeks were classified as having durable clinical benefit (DCB). The data indicate that RECON-based prediction of neoantigen quality correlates with DCB and serves as clinical validation for RECON’s ability to identify therapeutically relevant neoantigens.
“Our new analysis has shown two post-vaccine markers, epitope spread and tumor pathology, that clearly associate with durable clinical benefit. Of the patients tested, we observed epitope spread – which is a cascade of neoantigen recognition beyond those included in the vaccine – in all patients with DCB. Furthermore, the majority of patients with DCB displayed marked reductions in tumor content only after vaccination. We are encouraged by these associations and look forward to evaluating patient outcomes, including clinical responses and progression-free survival, in the more mature 52-week topline data set expected mid-year,” said Richard Gaynor, M.D., President of Research and Development at Neon Therapeutics.

#AACR: Positive Data From Astra, Hutchison China Cancer Drug Trial

Interim results from a phase 1 clinical trial, titled Patton, show that Savolitinib combined with an already-approved medicine, Tagrisso, yielded positive results.
Savolitinib is an investigational therapy under development by AstraZeneca in partnership with Hutchison China MediTech.
Data presented at the 2019 annual American Association for Cancer Research meeting showed that lung cancer patients are responding to the combined treatment.
The study looked at the effect of Savolitinib and Tagrisso in patients with non-small cell lung cancer with a mutation in the EGFR gene.
The objective response rate of the drug combination–a measure of how many patients see a reduction in tumor size–ranged from between 28% and 52%, based on what therapies they had previously undergone.
Dr. Lecia Sequist, who presented the results, said the findings show the benefit of adding a MET inhibitor–the class of drug to which Savolitinib belongs–to already established therapies like Tagrisso in patients whose cancer has acquired drug resistance.
However, she cautioned that this is still early-stage data and the findings need to be confirmed in larger trials.

Dem Candidates Woo Farm Belt Voters by Taking Aim at Agriculture Firms

Democratic presidential candidates pitched voters in this farm-heavy state on their plans to stir up competition in the agriculture industry and stem the conglomeration of corporate power in the U.S.
Sens. Elizabeth Warren of Massachusetts and Amy Klobuchar of Minnesota, as well as former U.S. Housing and Urban Development Secretary Juli├ín Castro, took aim at Bayer AG’s more than $60 billion purchase of Monsanto Co., a deal unpopular with many farmers here.
“We have got to fight back against consolidation, and I’ll make you a promise: you put me in the White House and I will unwind the Bayer-Monsanto” deal, Ms. Warren told a group of farmers here Saturday.
The deal made Bayer the world’s biggest supplier of pesticides and seeds. A flurry of consolidation in the global crop seeds and chemicals market has worried U.S. growers, who are battling a crop glut that has crimped prices.
Candidates are eager to win the support of Iowa’s farmers, a powerful constituency in the state that holds the first-in-the-nation primary caucuses in February. The candidates are also betting their focus on antitrust can attract progressive voters generally uneasy with the concentration of wealth and the power of corporations more broadly.
Ms. Warren has pledged to break up “companies where mergers have reduced competition,” pointing to the Bayer-Monsanto deal in particular in her proposal outlined last week. She has also suggested a nationwide ban on foreign individuals or entities from purchasing farmland for the purpose of farming.
Ms. Klobuchar takes a more measured approach. In an interview with The Wall Street Journal earlier in March, she said it was premature to call for breaking up big companies. But she has introduced several bills in Congress that would update U.S. antitrust law, including by tweaking legal standards to make it easier to challenge mergers successfully in court.
Introduced Saturday as “our neighbor to the north” at the Heartland Forum in Storm Lake, Ms. Klobuchar pitched herself as a can-do Midwesterner who would be a seasoned advocate for rural America.
The Minnesotan said her antitrust proposals would spur competition in agriculture.
“We need to take on the power of these monopolies,” she said. “I just think we’re getting to the point where you know you’re not going to get a fair deal.”
Republicans have traditionally favored giving business a free rein, but some were skeptical of the Monsanto-Bayer deal. Iowa’s Republican Sen. Chuck Grassley, when he was chairman of the Judiciary Committee in 2016, pressed the Justice Department to study how the deal would affect competition. “Competition is critical in this sector. It is essential for the American farm economy,” Mr. Grassley said last year after the department ultimately cleared the deal.
In a statement Saturday evening, Bayer said the deal with Monsanto brings together a robust portfolio to offer more choices for farmers. The company also said there are hundreds of companies competing for farmers’ business.
The consolidation in corporate agriculture is playing out as U.S. growers in recent decades swallowed up acreage to survive a harsh downturn in crop prices, squeezing smaller operations in the process. Ms. Warren has argued that big agriculture buyers and sellers make it even harder for owners of smaller farms to get by.
“Small and even medium-sized farms get caught between the giants…that determine the price that the farmers are going to have to pay for seed,” Ms. Warren told reporters Friday. “On the other end, there may be only one or two buyers for farmers’ product, and so profits get sucked out in the other direction.”
That message has resonated in the nation’s heartland, where many farmers say trends in the industry are pushing farms to merge or fold.
“Extracting wealth, taking opportunities out of rural regions. That’s what this consolidation has done to us,” said Wes Shoemyer, a Missouri farmer and board member of Family Farm Action, a progressive nonprofit, at a different event in Storm Lake on Saturday.
President Trump appeared to back the Monsanto-Bayer deal after executives assured him the postmerger company would invest in the U.S. and maintain American jobs.
Mr. Trump has said his trade policies will boost farmers’ incomes, but some say they are feeling the pinch from his broad trade campaign against China and Beijing’s retaliation against American crops and meat. “The farmers love me. They voted for me,” he said last year in Iowa, a state he flipped into the GOP column in 2016. President Obama won the state twice.
Beyond agriculture, Democratic candidates and progressive voters have taken aim at large financial-services firms and tech giants.
Ms. Warren has also proposed breaking up Facebook Inc., Inc. and Alphabet Inc.’s Google. Vermont Sen. Bernie Sanders, another presidential hopeful, has long called for breaking up the largest U.S. banks — something other candidates also support.
Officials within the Justice Department’s antitrust division and the independent Federal Trade Commission are tasked with enforcing U.S. antitrust law.
Assistant Attorney General Makan Delrahim, Mr. Trump’s appointee who runs the antitrust division, said at a conference Friday in Washington that antitrust proposals by presidential candidates are generally misguided, without naming specific candidates or policies. He said regulators must stake out firm positions based on legal arguments, adding that officials in his agency “can’t just walk into court and say company X should be broken up because it’s too big.”
A Justice Department spokesman said that the department is aware of the Democratic proposals but declined to comment on them.

Walgreens Boots Alliance Isn’t Ready to Quit Cigarette Sales Yet

Under pressure from federal regulators and some investors, Walgreens Boots Alliance Inc. is testing tobacco-free stores in the U.S., but the pharmacy chain’s leader has no plans to quit selling cigarettes entirely.
“The safety of our patients is very important, but we also have to do what our customers are requiring us to do,” Walgreens Boots Chief Executive Stefano Pessina said in a recent interview. “We see that when we don’t sell tobacco, we have a lot of [negative] reactions.”
The issue came up at the company’s annual shareholder meeting in January and again in February, when the U.S. Food and Drug Administration called out the company for selling tobacco products to minors. That month, a group of U.S. senators sent the Walgreens chief and other retailers letters urging them to stop selling tobacco products in stores.
While it continues to sell cigarettes in the vast majority of its stores, Mr. Pessina said Walgreens is trying to help smokers quit by also making smoking cessation products widely available. Employees are encouraged to direct customers seeking cigarettes to cessation products. The pharmacy chain has also reduced the visibility of tobacco products in some stores.
“Our objective is to convince people not to smoke, so we give them a cigarette and we ask them whether they want to stop smoking,” Mr. Pessina said. The Italian-born CEO took over as permanent CEO in 2015 after the merger of Alliance Boots and Walgreens.
Walgreens doesn’t sell tobacco products at a test store in Deerfield, Ill., near its headquarters, as well as 17 stores in Gainesville, Fla., as part of a 12- to 18-month pilot program it started last year. It also doesn’t sell cigarettes in Massachusetts, New York City and San Francisco, which have banned pharmacies from selling them.
Outside North America, the company’s Boots pharmacies don’t sell tobacco products. But unlike rival CVS Health Corp., which stopped selling tobacco products in 2014, Walgreens sells cigarettes, electronic cigarettes and other tobacco products in most of its roughly 9,600 U.S. stores.
Still, most cigarettes in the U.S. are sold at gas stations and convenience stores. Drugstores accounted for 1.7% of cigarette volume sales in the U.S. in 2017, and 39% of the dollar sales of smoking cessation products in 2018, according to market research company Euromonitor International.
Activist shareholders and antitobacco advocates have been asking Walgreens to discontinue sales of tobacco products in its North American stores. Some investors argue the company’s tobacco sales are putting their money at risk with threats of lawsuits, while activists say that tobacco products don’t belong in a health store.
“There is no reason that anyone needs tobacco products, so we do not think that they need to sell tobacco at all,” said Donna Meyer, director of shareholder advocacy for Mercy Investment Services Inc., which manages funds for a Roman Catholic order of nuns. Ms. Meyer raised the issue with Walgreens executives during the company’s shareholder meeting in New York in late January.
Walgreens says its tobacco sales provide customer choice. Executives said at the January meeting that they wanted to see how customers responded in its Gainesville test market to determine how the chain can reduce its reliance on the products.
Walgreens doesn’t disclose how much revenue it gets from selling tobacco products, but Mr. Pessina said its tobacco sales are decreasing. CVS quit selling cigarettes and other tobacco products in 2014 and added “health” to its name in an attempt to create a healthier image. CVS estimated the tobacco move cost about $2 billion a year in lost revenue.
Outgoing FDA Commissioner Scott Gottlieb called out Walgreens in February for selling tobacco products to minors after the agency conducted undercover checks. About 22% of the more than 6,000 Walgreens stores the FDA inspected sold to minors, the agency said. By contrast, 17.5% of Walmart Inc. stores and 9.6% of Rite Aid Corp. stores inspected had illegally sold tobacco products to minors.
In response, Walgreens said that it has a zero-tolerance policy on selling tobacco to minors and any employee violating its policy is subject to termination.
There is pending legislation in a number of states to raise the legal age to use tobacco to 21, and Walgreens has been publicly supportive of those efforts.
Walgreens is scheduled to release its second-quarter earnings results on Tuesday.

#AACR: After blood cancer wins, CAR-T treatments see inroads for solid cancers

CAR-T has seen a host of successes in blood cancers, but translating that into solid tumors has proven much more difficult. Now, early data out of the AACR cancer conference (and all the caveats that brings) may be offering some hope for that direction.
Two separate, small trials out of the American Association for Cancer Research (AACR) show that CAR-T therapy could impact several types of cancer: HER2-positive sarcomas and the difficult-to-treat pleural disease from mesothelioma, typically associated with asbestos-related disease.
First up is a small phase 1 for younger patients and adults with HER2-expressing sarcoma, which can affect bone and soft tissues.

Typically, when you think of HER2-positive cancers you tend to think of breast cancer, but it’s believed that around 40% of osteosarcomas, the most common kind of sarcoma, can harbor this expression.
You’d think you could turn to Roche’s long-standing HER2-positive stalwart Herceptin, but it has no effect on this particular patient population, with treatment usually consisting of chemotherapy agents, which have high side effects and often low treatment success.
So, Shoba Navai, M.D., assistant professor of pediatrics at the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital, and Houston Methodist Hospital in Houston, and her team used HER2-targeted CAR-T cells, combined with a form of chemo. The result, Navi said, was found to be safe and effective in some patients.
It’s still early doors: The test was in just 10 patients, aged 4 to 54, with refractory/metastatic HER2-positive sarcoma (five with osteosarcoma, three with rhabdomyosarcoma, and one each with Ewing sarcoma and synovial sarcoma). These patients had already been through the ringer, receiving up to five prior salvage therapies.
The investigators found that the CAR-T cells expanded in all but two patients, with a median peak expansion after a week, and that they could detect the CAR-T cells in all patients six weeks after infusion.
One pediatric patient whose rhabdomyosarcoma had spread to the bone marrow had a complete response (CR) for 12 months, but relapsed later; retreatment with CAR-T cells resulted in a CR that has been ongoing for 7 months.
And one pediatric patient with osteosarcoma that had metastasized to the lungs has an ongoing CR for 32 months. Three patients had stable disease, and five had progressive disease.
The team acknowledged the limitation of the study, given its size, but were still encouraged by some of the activity; they also note that safety appeared strong, with no pulmonary toxicities detected, something that can occur with CAR-T cells infusion.
In another, separate trial, Prasad Adusumilli, M.D., deputy chief of thoracic surgery at Memorial Sloan Kettering Cancer Center, and his team focused their small phase 1 (of 21 patients) on a particularly aggressive form of lung cancer: malignant pleural disease from mesothelioma, essentially a cancer of the protective lining of the lung, which comes typically from inhaling asbestos and has a poor prognosis.
The MSK team tested mesothelin-targeted CAR T cells called IcasM28z, using completely human components, which includes the so-called safety “suicide” switch that can be activated to kill all CAR-T cells in case of a spike in toxicity.
The investigators recruited 21 patients with malignant pleural disease (19 with malignant pleural mesothelioma, one with metastatic lung cancer, and one with metastatic breast cancer), with 40% of them having had received three or more lines of prior therapy.
This approach saw the CAR T cells to be persistent in the peripheral blood of 13 patients during the 38-week evaluation, and their presence was associated with more than 50% decrease in the levels of a mesothelin-related peptide in the blood and evidence of tumor regression on imaging study.
One patient with mesothelioma underwent curative-intent surgery followed by radiation therapy to the chest.  “Twenty months from diagnosis, the patient is doing well, with no further treatment,” Adusumilli noted.
Meanwhile, 14 patients were given PD-1 checkpoint inhibitors. This is because CAR-T cells can get dampened, or functionally exhausted, in large tumors; preclinical tests show they can be reinvigorated by PD-1 agents.
This only worked in mice, but Adusumilli said they would take try this out on the patients to see its effect. After up to 21 cycles of treatment with an anti -PD1 agent, two patients had complete metabolic response on PET scans at 60 and 32 weeks, respectively, and these responses are ongoing; five patients had partial response, while four had stable disease.
“Combining rationally developed strategies—such as interventional radiology, T-cell genetic engineering, and newer immunotherapy agents—has produced encouraging results and provides rational to further investigate this approach in aggressive, therapy-resistant cancers such as mesothelioma, for which the currently available treatment options are not optimal ,” Adusumilli  concluded.

Atara’s collaborator presents Phase 1 study results in Advanced Mesothelioma

Atara Biotherapeutics announced that the company’s collaborators at Memorial Sloan Kettering Cancer Center presented encouraging results from an ongoing MSK investigator-sponsored Phase 1 clinical study of a mesothelin-targeted CAR T immunotherapy for patients with mesothelin-associated malignant pleural solid tumors, primarily mesothelioma, who progressed following prior standard platinum-containing chemotherapy. Mesothelin-targeted, autologous CAR T cells delivered regionally were well-tolerated and showed anti-tumor activity in combination with pembrolizumab, a PD-1 checkpoint inhibitor. The Phase 1 clinical study recruited 21 patients, 19 with malignant pleural mesothelioma, one with metastatic lung cancer and one with metastatic breast cancer, who received a median of 3 prior treatment regimens, to evaluate the safety and potential anti-tumor activity of a CD28-costimulated, mesothelin-targeted autologous CAR T immunotherapy. The study included six dose cohorts with administration directly to the tumor site using regional delivery techniques, initially at a low CAR T dose without lymphodepleting chemotherapy, followed by increasing CAR T dose cohorts with lymphodepletion. A subset of these patients was subsequently treated with pembrolizumab, a PD-1 checkpoint inhibitor. Mesothelin-targeted, autologous CAR T administration was found to be generally well-tolerated with no CAR T-related toxicities higher than grade 2 observed based on monitoring multiple clinical, radiological, and laboratory parameters. CAR T cells were found to be persistent in the peripheral blood for 13 of the 21 patients during the 38-week evaluation, and their presence was associated with evidence of tumor regression on imaging studies. Best overall response rate for a subset of 11 MPM patients with minimum follow-up time of 3 months who also received pembrolizumab and lymphodepleting chemotherapy was 72% including 2 durable complete metabolic responses on PET imaging and 6 partial responses. Six of the 11 patients in this subset were programmed cell death ligand 1 negative, defined as undetectable expression of PD-L1 in tumor cells by immunohistochemistry, with 4 of the 8 total responses observed in PD-L1 negative patients. Following progression on standard platinum-containing chemotherapy, the expected ORR for patients with MPM treated with a checkpoint inhibitor is estimated between 5%-29% with one patient achieving a CR across multiple studies. MSK is also investigating mesothelin-targeted CAR T cells for patients with mesothelin-associated advanced breast cancer. Additional results from these ongoing studies are expected to be presented at upcoming scientific congresses.

Psychological Dangers Of A Sedentary Life

The central predicament of human life is that we neither possess completely free will, nor are we completely determined by external circumstances. We set and pursue goals, only to become waylaid by habits and distractions. Often we know the patterns in our lives that we would love to change–from overeating to taming our tempers–but still find ourselves falling into old ruts. There are many seemingly different approaches to counseling and psychotherapy, but at a high level all of them represent ways of increasing our self-awareness and, ultimately, control over our thoughts, feelings, and actions.
When I reviewed evidence-based short-term approaches to therapy with two colleagues at SUNY Upstate Medical University in Syracuse, a surprising conclusion stood out. Every effective approach utilizes shifts in states of consciousness to facilitate change. These shifts may be quieting, as in the case of meditation, or they may be activating, as in the case of experiential and behavioral therapies. Across the modalities, there is an understanding that, in our routine states of awareness, we tend to fall into routine. Changing and expanding our consciousness is a portal to expanding our willpower, our capacity for self-determination.
The quest for peak performance is, at root, an effort to become more fully self-determining. Might we explore peak performance practices the way we’ve looked at evidence-based therapies to uncover insights into willpower?
One fascinating finding from a survey of writings on peak performance is that many of them emphasize the relationship between physical and mental conditioning. In pushing the body, we expand the mind. Overcoming physical obstacles strengthens our willpower muscles, extending our capacity to master other life challenges. Emilia Lahti describes the Finnish concept of sisu, which embraces an action mindset that embraces and tackles goals that seem to be beyond our reach. She has embodied sisu in her determination to overcome experiences of abuse, in part by tackling daunting distance running challenges. In pushing herself mentally and physically, she has found a way of accessing “an extra gear of psychological strength.”
A similar use of the body to extend performance is illustrated by David Goggins, who has been described as “the toughest man alive”. A graduate of NAVY SEAL and U.S. Army Ranger training, Goggins decided to raise money for the Special Operations Warrior Foundation by running a race in which he had to cover at least 100 miles in 24 hours. Goggins was not a distance runner, but he tackled the challenge of the distance race and successfully persevered despite multiple injuries. In his book Can’t Hurt Me, Goggins explains, “You are in danger of living a life so comfortable and soft that you will die without ever realizing your true potential.” His approach to peak performance is to “callus your mind the same way you do your hands. Take the path of most resistance every day of your life.” Indeed, when we listen to Goggins’ self-talk, it becomes clear that he utilizes the achievement of one challenge as a prod to tackle a new one. There is no finish line, no easing up, in his sisu.
Most of us are familiar with research that links sedentary lifestyles to poor health outcomes. Less well appreciated is that being sedentary also comes with increased odds of stress, depression, and diminished well-being. Among adolescents, increased screen time is associated with poorer mental health. Sedentary lifestyles are also associated with elevated levels of anxiety. From the perspectives of Lahti and Goggins, the comfortable, sedentary life may in fact serve as training for non-effort and avoidance, preventing us from tackling challenges and attaining peak performance. By challenging the body, we inevitably encounter mental, emotional challenges–and we learn how to overcome them. As in the short-term therapies, positive change follows from an enhanced state of consciousness. The demands of physical activity stimulate our emotional resilience and ability to persevere under duress.
Fergus Connolly, who has worked with elite athletes and special forces operators, quotes Irish politician Terence MacSwiney, who died after a hunger strike initiated while he was incarcerated: “It is not those who can inflict the most, but those that can suffer the most who will conquer.” Peak performers, he finds, “make their game face their everyday face”. Like Goggins, Connolly notes that the key to high levels of achievement is a self-talk that embraces the discomfort of extraordinary efforts. He explains that “the potency of self-talk extends to self-projection.” Our internal dialogues become destiny.
The psychological dangers of a sedentary lifestyle is that comfortable bodies never allow us to exit the routine. Without the immediacy of daily challenges, we fail to exercise the will and thus never find the resources to persist and achieve great things. Lahti, on her site, quotes William James: “Do something every day for no other reason than you would rather not do it, so that when the hour of dire need draws nigh, it may find you not unnerved and untrained to stand the test.” It is in embracing the “path of most resistance” that we cultivate the will to sustain extraordinary efforts.

What Is YOUR Self-Talk?

The latest Forbes article makes the case that self-talk is destiny.  How we process the world–and how we talk to ourselves about ourselves and world–shapes our reality.  That, in turn, defines what we experience as possible and impossible and shapes our actions.  Nowhere is this more true than in trading, where we are constantly dealing with issues of being right and wrong, uncertainty, and making/losing money.
In the above graphic, you’ll see a matrix that describes four styles of self-talk.  These styles can be positive or negative in their emotional tone and they can either increase or reduce the energy available to us.  Let’s take a look at the four styles and what they might mean for you:
Challenging – This is self-talk that pushes us to do better, do more, and tackle new and larger goals.
Worrying – This is self-talk that anticipates negative outcomes in the future, triggering fight or flight responses.
Calming – This is self-talk that reassures and puts things into perspective, dampening negative feelings and keeping us focused.
Self-Blaming – This is negative self-talk directed against oneself, dampening initiative and generating depressed feelings.
Clearly, at different times we may engage in different self-talk.  Much of trading psychology talks about dealing with negative emotions (worry, frustration, self-blame) and ways of sticking to trading plans (calming, focusing).  That is an important shift.
The Forbes article adopts a different perspective, however.  Just as we are in danger of living lives that are too sedentary (creating health risks), we can adopt mindsets that are too sedentary.  Many of us can deal with adversity by calming ourselves and avoiding undue worry and self-blame, but not many of us consistently talk to ourselves in challenging and energizing ways.
Take a look at the work of Emilia Lahti and David Goggins cited in the Forbes article.  These are peak performing professionals who have used unusual physical challenges to push their mindsets to redefine what is possible.  A useful exercise is to listen to a David Goggins video clip and think of his talk as your self-talk.  This kind of challenging talk is often found in athletic settings and in the military, but rarely do we see it in office settings–and rarely do I find it on trading floors.
It’s great to reassure ourselves, accept losses, and find learning lessons in our setbacks.  That is necessary for a solid trading psychology, but is it sufficient?  If our self-talk is not intensely challenging, how will we intensively tackle new challenges?  A calm mindset is helpful at times, but sedentary calm will never rouse us to do better, do more, and throw ourselves into challenges that expand who we are and what we can do.
How inspiring and challenging is your self-talk?

Legal Cannabis Fuels US Job Boom: Florida, Nevada Are The Biggest Gainers

One sector that has been a silent contributor to the U.S. labor market — but hasn’t been recognized yet due to the stigma of being a federally illegal business — is the cannabis industry, according to a report by Leafly.

A Major Industry Left Out Of Jobs Data

The number of full-time jobs in the legal U.S. cannabis industry is now at 211,000, courtesy of an addition of 64,389 jobs in 2018, according to Leafly.
The total number of full-time legal cannabis jobs in the U.S. would likely to soar to 296,000 if indirect and induced jobs were also taken into account.
To put things in perspective, the report said there are now more legal cannabis industry workers in the U.S. than dental hygienists. Among other industries, coal mining jobs currently number 52,000; brewery jobs stand at 69,000; and textile manufacturing jobs total 112,000.

The federal government excludes cannabis from jobs data due to it being a federally illegal substance. States that have legalized cannabis also exclude cannabis jobs, as the model used to count jobs uses the NAICS code, and one does not exist for cannabis, according to Leafly.
How did Leafly arrive at the numbers? The website said it collaborated with economists, who correlated job numbers to cannabis sales.

State-By-State Breakdown

Florida topped the states in terms of the absolute number of jobs added, as the state added 9,068 cannabis jobs in 2018, a 703-percent increase to 10,358, Leafly said. The Sunshine State is followed by Nevada, which has seen a 181-percent increase to 7,573 jobs.
In terms of percentage growth, Pennsylvania recorded a 4,208-percent increase from 90 in January 2018 to 3,878 one year later.
Infographic: The States Getting High On Marijuana Jobs | Statista
Source: Statista
Despite the double-digit percentage gains in legal cannabis jobs in Washington and Colorado, the gains in those states represented a slowdown or a leveling off as opposed to the overall triple-digit percentage growth of the industry.

What’s Fueling The Job Growth?

The legalization of recreational marijuana in 10 U.S. states and Washington D.C. and medical marijuana in 34 states led to a 34-percent jump in legal cannabis sales in 2018, creating incremental job opportunity in the sector.

What The Future Holds

From early 2017 to January 2020, cannabis jobs are estimated to increase by 110 percent, Leafly said.
Oklahoma is likely to experience a boom like the ones witnessed in California and Colorado when the first dispensaries opened in those states, the report said.
In Michigan, where recreational marijuana was legalized with a November vote, a concurrent spike in job gains may not be seen until 2020, Leafly said.
“In the near term, we expect Massachusetts to double its cannabis jobs in 2019, from 3,020 to around 6,000,” the report added.