Fred’s (NASDAQ:FRED) reports comparable-store sales down 5.3% in Q3.
Gross margin rate leveraged 353 bps to 25.1%.
Adjusted SG&A expense improved 50 bps to 33.6%.
Joe Anto, Fred’s Interim CEO and CFO, stated “We have made significant progress against our goal of strengthening the balance sheet and as of December 12, 2018 our ABL balance stood at $51.9M vs. $153.4M as of the beginning of this Fiscal Year. As of December 12, 2018 we completed the sale of script files associated with approximately 138 locations to Walgreens and expect to complete the remaining 41 location transfers to Walgreens by the end of January 2019. As we have stated in the past, we are continuing to evaluate potential opportunities to monetize all our non-core assets including our retail pharmacy script portfolio as well as our real estate.”
Health Insurance Innovations (HIIQ+25.9%) is up on double normal volume in response to its disclosure that it has agreed to pay $3.4M to settle an investigation into its business practices by insurance regulators. Under the terms of the agreement, it has also agreed to:
Submit a third-party administrator license application in any jurisdiction where required and where it is not already licensed.
Improve its monitoring of sales calls via the recording and retention of all internal and external calls. This requirement will apply to external distributors as well.
Periodically submit reports to monitoring regulators.
Prepare and implement a “disclosure plan” to ensure that all customers are fully aware of policy details and fees, a “compliance plan” aimed at monitoring and improving sales practices and a “training plan” for internal and external sales personnel and related parties regarding compliance with applicable insurance laws. Monitoring regulators will approve all plans.
Failure to comply with any aspect of the above items will subject the company to further enforcement and administrative actions.
The FDA has cleared an augmented reality navigation system from Mariner Endosurgery that provides surgeons a view similar to a heads-up display, warning them of potential problem areas during minimally invasive procedures.
The company’ s LaparoGuard system can allow surgeons to designate three-dimensional safety zones and areas of risk, which are then integrated and overlaid within their own surgical visualization equipment. The system can also track the locations of multiple tools during a procedure.
LaparoGuard works without the use of an AR headset, and provides real-time feedback through a customizable mix of audio and visual cues. Surgeons can also annotate areas during the operation to help guide their tools.
In addition, instrument movements are recorded for postoperative playback, providing training opportunities.
Mariner plans to further support the system with additional visualization and laparoscopic instrumentation currently under development, according to the Hamilton, Ontario-based company’s president, Mitch Wilson.
Irisin, the once much-hyped but controversial “exercise hormone” that researchers had hoped would be an effective obesity treatment, could make a comeback—this time in bone strengthening.
In a study published in the journal Cell, a team led by scientists at Harvard University Medical School found that injections of irisin in mice increased sclerostin, a protein produced by osteocytes that regulate bone formation. The team argued the findings could lead to future treatments for osteoporosis.
“These results are potential game changers in the fields of metabolism, muscle-bone biology, and exercise,” said the study’s senior author, Bruce Spiegelman, in a statement. “We show that irisin works directly on osteocytes, the most abundant cell type in bone.”
A paper that Spiegelman published in Nature in 2012 triggered the initial excitement over irisin. In that study, Spiegelman and colleagues identified irisin as a cleaved version of the FNDC5 membrane protein. The team showed that irisin, which is produced during exercise, could help turn unhealthy white fat into calorie-burning brown fat.
The study laid the groundwork for Ember Therapeutics, a FierceBiotech Fierce 15 winner in 2012. The company initially raised $34 million from venture capital bigwig Third Rock Ventures. Spiegelman himself came on board as chair and scientific founder as the company, which aimed to turn irisin into an anti-obesity treatment.
However, controversy soon followed. Questions mounted about the very existence or the hormone in people, even though Spiegelman later used mass spectrometry to prove in a Cell Metabolismstudy that irisin does exist. Third Rock eventually pulled away from Ember, which merged with Mariel Therapeutics.
Mariel ultimately returned the intellectual property around irisin back to Harvard. The new company, taking Ember’s name, recently voluntarily deregistered from the stock market.
Based on its last public statement, Ember is now focused on developing bone therapeutics. And that’s where Spiegelman and his team intend to revive hope for irisin.
Mammalian bones go through constant remodeling, swapping in new bone cells for old or damaged ones. It starts with the breakdown of old bone cells, a process that modulated by the protein sclerostin. Some recent studies have shown that very low doses of irisin can improve bone density and strength in mice. But the underlying mechanism was unclear.
In the new study, Spiegelman’s team found that irisin functions through a receptor called aV/b5 integrin to boost bone cell survival and production of sclerostin. Discovering the irisin receptor marks a step toward finding new cells that respond to the hormone, Spiegelman said.
What’s more, after injecting mice with irisin intermittently for six days, the researchers observed higher levels of sclerostin in the animals’ blood and increased bone mass. Mice genetically modified to lack irisin were also found to be resistant to ovariectomy-induced bone loss, the team reported. Irisin could “also act on remodeling in a favorable manner with intermittent pulse dosing,” the researchers wrote in the study.
The Harvard-led team now plans to focus on optimizing irisin and antibodies to irisin, said Spiegelman. They haven’t given up on obesity, however, so they’re still examining the hormone’s effects on fat, and they’re also testing it in nervous-system disorders.
Human growth hormone samples extracted from cadavers decades ago were able to “seed” amyloid beta pathology in mice, researchers reported.
While these findings do not demonstrate that Alzheimer’s disease can be transmitted, they provide experimental evidence for the hypothesis that amyloid beta pathology can be transmitted by iatrogenic means, said John Collinge, MD, of University College London, and colleagues, in Nature.
“This represents a new way of thinking about Alzheimer’s disease,” Collinge said in a press briefing. “There may be certain circumstances — hopefully, they’re rare medical circumstances — in which transmission of the pathology can occur.”
In 2015, Collinge’s group reported evidence of early amyloid beta pathology in the brains of seven people who had died of iatrogenic Creutzfeldt-Jakob disease (CJD). These patients had been treated with human growth hormone from cadaveric pituitary glands, a practice that was stopped in 1985 when some recipients were found to have developed CJD. What was unknown at the time was whether these patients developed amyloid beta pathology from the cadaveric samples or whether the samples contained amyloid beta.
Since then, Collinge and colleagues obtained vials of the growth hormone the patients were exposed to and found a number of them tested positive for both amyloid beta and tau protein. They injected samples into mice models of Alzheimer’s disease and found that the animals developed accelerated amyloid deposition in the brain parenchyma and around the cerebral vessel walls over time. These deposits were almost completely absent in control mice, including mice that received synthetic recombinant human growth factor.
“This data indicate that the vials used for human treatment indeed contained amyloid beta material that was competent to seed the accumulation of pathological amyloid,” said Claudio Soto, PhD, of the University of Texas McGovern Medical School at Houston, who was not involved with the study. “This study, added to the previous one, strongly suggests that amyloid beta deposition seen in patients was induced in a manner reminiscent to prions.”
More than 15 years ago, Soto had developed a hypothesis that beta-amyloid plaques were a disorder of protein folding, analogous to prion pathology, such that one misfolded amyloid protein could catalyze misfolding of others to form toxic aggregates.
The question still remains whether transmission of Alzheimer’s pathology is restricted to these rare conditions — such as the use of human-derived products for treatment — or can occur under more common medical practices like blood transfusions, Soto told MedPage Today.
Concerns about transfusions have been around for some time, noted Bart De Strooper, MD, PhD, of the University College London in England. “Several studies using mice that were similarly genetically primed to develop Alzheimer’s disease-like symptoms have shown that this route of transmission is theoretically possible,” he told the U.K. Science Media Centre. These findings prompted a large retrospective study in Sweden and Denmark that found no evidence for increased rates of Alzheimer’s or Parkinson’s disease in patients who received blood from donors who went on to develop those diseases. “Those results provided real-world evidence that any such risk is extremely small,” De Strooper said. “Nevertheless, it is worth monitoring these risks.”
While Collinge emphasized there is no suggestion Alzheimer’s disease is contagious or transmissible by blood, he noted it’s important to evaluate the risks of iatrogenic transmission of amyloid beta pathology.
“We have now provided experimental evidence to support our hypothesis that amyloid beta pathology can be transmitted to people from contaminated materials,” he said. “It will be important to review risks of transmission of amyloid pathology by other medical procedures still done today, including instruments used in brain surgery, drawing on other research and what we already know about accidental CJD transmission.”
Mice in this study received samples injected directly into their brains, while people who received the cadaveric human growth hormone preparations decade ago had injections intravenously or intramuscularly, observed Tien-Phat Huynh, MD-PhD candidate, and David Holtzman, MD, both of Washington University in St. Louis, in an accompanying editorial.
“Future studies in animals should assess whether the route of administration influences the ability of material containing misfolded amyloid beta to cause brain amyloid beta pathology, and should investigate the minimum amount of material that has pathological effects,” they wrote.
It’s worth noting that the stored vials had been maintained at ambient temperature since the mid-1980s, they added. “Their ability to transmit amyloid beta pathology seen in this study corroborates the idea that amyloid beta seeds are remarkably stable,” they noted. “This property of amyloid beta seeds emphasizes the importance of not using biological material prepared from the human central nervous system for injection or transplantation into patients during neurosurgical or medical procedures, unless these materials are adequately screened or there is no other option.”
The mice in this study were genetically modified to be prone to amyloid beta pathology, but not tau. The samples of human growth hormone people were exposed to also contained tau, Collinge said, and future studies will assess whether the tau in these vials can seed aggregation in other mice.
This study was funded by the U.K. Medical Research Council, the National Institute of Health Research, University College London, the Leonard Wolfson Experimental Neurology Centre, and the National Institute on Aging.
Collinge is a shareholder and director of D-Gen Limited. No other researchers disclosed competing interests.
Clovis Oncology, Inc. (NASDAQ: CLVS) today announced that the European Union’s (EU) European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending an additional indication to include rucaparib as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. EC approval is anticipated in the first quarter of 2019.
Once approved, Rubraca’s indication will expand beyond its initial Marketing Authorization in Europe granted in May 2018 for adult patients with platinum-sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.
The CHMP’s positive opinion for this additional indication was based on data from the phase 3 ARIEL3 clinical trial, which found that rucaparib significantly improved progression-free survival in all ovarian cancer patient populations studied.
