Genevant inks development deal with BioNTech

• Ahead of Roivant Sciences’ pipeline day on Tuesday afternoon, the company announced some of the latest news for one of its “Vants” — the term it uses for its many subsidiaries.
• Genevant, which is meant to be a RNA therapeutic-focused company, has inked a co-development deal with BioNTech to use the German company’s mRNA platform to develop five rare disease products.
• The two companies will co-develop and co-commercialize the products through a 50/50 split, sharing all future costs and profits, with an aim of entering the clinic in 2020.

Genevant, launched in April as a joint venture between Roivant and Arbutus Biopharma, has the goal of bringing five to 10 compounds using mRNA, RNA interference or gene editing to the clinic by 2020. The deal with BioNTech will potentially help it reach that goal.

As part of their pact, the companies have entered into a licensing agreement that uses Genevant’s lipid nanoparticle delivery technology with five of BioNTech’s oncology programs. Genevant is eligible to receive commercial milestones on those products. The platform was developed by Arbutus, another Roivant company, and used in the development of Alnylam Pharmaceutical’s patisiran.

The companies did not elaborate on what diseases they plan to target under the collaboration.

Genevant is just one of twelve subsidiaries under the Roivant umbrella. The business model was designed so that each subsidiary would have a different focus — like RNA therapeutics, dermatology, neurology, hepatitis B, urology or cardiometabolic diseases — and could succeed or fail without affecting the larger company. It also allows Roivant to provide funding and take certain subsidiaries public, while keeping some private. Additionally, the model could allow the parent company to more easily sell off certain assets.

Best-known among the Vants is surely Axovant, the neurology-focused drugmaker that failed at bringing its Alzheimer’s compound forward after an historically large initial public offering. After that failure, Roivant’s unique business model has come under fire. The parent company hosted a pipeline day on Tuesday afternoon to showcase its assets. Stay tuned.

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Medtronic, UnitedHealthcare say value-based pact cut diabetes costs

• Medtronic and UnitedHealthcare said first-year results from a value-based care pact for patients with diabetes showed a 27% reduction in the rate of preventable hospital admissions for Medtronic insulin pump users, compared with patients injecting insulin multiple times per day.
• The analysis included 6,000 plan members using either standalone insulin pumps or pumps integrated with continuous glucose monitors. The first-year data covered July 2016 through June 2017 in the multiyear initiative between the biggest U.S. health insurer and largest medical device maker.
• UnitedHealthcare and Medtronic said their diabetes partnership lowered costs in the first year but did not disclose the amount of savings. UnitedHealthcare said its total payments to physicians and hospitals tied to value-based arrangements have grown in the last three years to $65 billion. The insurer expects that figure to reach $75 billion by the end of 2020.

Health insurers such as UnitedHealthcare are developing value-based programs that reimburse providers or manufacturers based on patient care outcomes rather than volume of services.

The programs are particularly attractive for high cost diseases. The cost of diabetes rose 26% over a five-year period from 2012 to 2017, according to the American Diabetes Association.

CMS backs value-based care and has already converted 30% of its fee-for-service Medicare payments to the model.

Medtronic CEO Omar Ishrak was an early champion of value-based arrangements and has forged a number of partnerships with organizations pursuing similar efforts. The medical device maker last year entered into an outcomes-based agreement with Aetna similar to its partnership with UnitedHealthcare that ties part of the company’s reimbursement to meeting clinical goals for patients who transition to Medtronic insulin pump therapy.

“These positive results provide further evidence of the benefits of both automated insulin delivery and of value-based healthcare models,” said Hooman Hakami, president of the diabetes group at Medtronic in a statement.

JDRF, the diabetes research foundation, launched a campaign called #Coverage2Control after the Medtronic-UnitedHealthcare agreement was announced to advocate for patient choice in insulin pumps, among other goals.

Peter Pronovost, the chief medical officer of UnitedHealthcare called the results encouraging for the first year.

“We will monitor patients using Medtronic pump therapies to ensure we continue to see improved quality of care, fewer hospitalizations, and lower costs,” he said in a statement.

https://bit.ly/2L3sLLF

Stealth STD could become the next superbug

A little-known, sometimes symptomless sexually transmitted disease is set to be the next superbug within a decade — if people don’t wise up about their sex lives, experts are warning.

Mycoplasma genitalium, or MG, is a sexually transmitted bacteria that can cause pelvic inflammatory disease and, ultimately, infertility in women if not treated properly.

Symptoms of MG can be similar to gonorrhea and chlamydia — but often, there are no signs of an infection at all. That means some people may not even be aware they’ve been infected until bigger problems arise.

If left untreated, MG, which was first discovered in the early 1980s and spreads through unprotected sex, can also develop a resistance to antibiotics.

“This is not curing the infection and is causing antimicrobial resistance in MG patients,” Dr. Paddy Horner told the Telegraph. “If practices do not change and the tests are not used, MG has the potential to become a superbug within a decade, resistant to standard antibiotics.”

In women, MG can cause a burning sensation when urinating and pain or bleeding during and after sex. Men might experience watery discharge from their penis.

It’s unclear exactly how many in the US have been infected with MG. In 2015, the Centers for Disease Control and Prevention listed it as an “emerging issue.”

In the UK, health experts launched new guidelines for the treatment and diagnosis of MG, saying around 1 to 2 percent of men and women have contracted the STD, according to the Telegraph. Some clinics, however, have put that number as high as 38 percent.

The new guidelines recommend a specific test for MG and that it be treated with a seven-day dose of antibiotic doxycycline, followed by a course of azithromycin.

“These new guidelines have been developed because we can’t afford to continue with the approach we have followed for the past 15 years as this will undoubtedly lead to a public health emergency with the emergence of MG as a superbug,” said Horner, who helped author the new guidelines.

Dr. Olwen Williams, president of the British Association for Sexual Health and HIV, warned of much greater consequences.

“Potentially up to 3,000 women a year over the next 10 years could become infertile because of MG leading to pelvic inflammatory disease,” she said.

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Athenahealth gathering initial bids this week

Athenahealth, which has said it initiated a process to explore strategic alternatives, is asking for initial bids this week, said Dealreporter, according to contacts.

https://bit.ly/2L9FE3M

Galmed started at buy by Cantor

Galmed initiated with an Overweight at Cantor Fitzgerald. Cantor analyst Elemer Piros initiated Galmed with an Overweight and $59 price target.

https://bit.ly/2L8B2uR

‘Big Bang’ of Alzheimer’s: Genesis of disease, shape-shifting tau IDd

Scientists have discovered a “Big Bang” of Alzheimer’s disease – the precise point at which a healthy protein becomes toxic but has not yet formed deadly tangles in the brain.

A study from UT Southwestern’s O’Donnell Brain Institute provides novel insight into the shape-shifting nature of a tau molecule just before it begins sticking to itself to form larger aggregates. The revelation offers a new strategy to detect the devastating disease before it takes hold and has spawned an effort to develop treatments that stabilize tau proteins before they shift shape.

“This is perhaps the biggest finding we have made to date, though it will likely be some time before any benefits materialize in the clinic. This changes much of how we think about the problem,” said Dr. Marc Diamond, Director for UT Southwestern’s Center for Alzheimer’s and Neurodegenerative Diseases and a leading dementia expert credited with determining that tau acts like a prion – an infectious protein that can self-replicate.

The study published in eLife contradicts the previous belief that an isolated tau protein has no distinct shape and is only harmful after it begins to assemble with other tau proteins to form the distinct tangles seen in the brains of Alzheimer’s patients.

Scientists made the discovery after extracting tau proteins from human brains and isolating them as single molecules. They found that the harmful form of tau exposes a part of itself that is normally folded inside. This exposed portion causes it to stick to other tau proteins, enabling the formation of tangles that kill neurons.

“We think of this as the Big Bang of tau pathology,” said Dr. Diamond, referring to the prevailing scientific theory about the formation of the universe. “This is a way of peering to the very beginning of the disease process. It moves us backward to a very discreet point where we see the appearance of the first molecular change that leads to neurodegeneration in Alzheimer’s. This work relied on a close collaboration with my colleague, Dr. Lukasz Joachimiak.”

Despite billions of dollars spent on clinical trials through the decades, Alzheimer’s disease remains one of the most devastating and baffling diseases in the world, affecting more than 5 million Americans alone.

Dr. Diamond is hopeful the scientific field has turned a corner, noting that identifying the genesis of the disease provides scientists a vital target in diagnosing the condition at its earliest stage, before the symptoms of memory loss and cognitive decline become apparent.

His team’s next steps are to develop a simple clinical test that examines a patient’s blood or spinal fluid to detect the first biological signs of the abnormal tau protein. But just as important, Dr. Diamond said, efforts are underway to develop a treatment that would make the diagnosis actionable.

He cites a compelling reason for cautious optimism: Tafamidis, a recently approved drug, stabilizes a different shape-shifting protein called transthyretin that causes deadly protein accumulation in the heart, similar to how tau overwhelms the brain.

“The hunt is on to build on this finding and make a treatment that blocks the neurodegeneration process where it begins,” Dr. Diamond said. “If it works, the incidence of Alzheimer’s disease could be substantially reduced. That would be amazing.”

Dr. Diamond’s lab, at the forefront of many notable findings relating to tau, previously determined that tau acts like a prion – an infectious protein that can spread like a virus through the brain. The lab has determined that tau protein in the human brain can form many distinct strains, or self-replicating structures, and developed methods to reproduce them in the laboratory. He said his newest research indicates that a single pathological form of tau protein may have multiple possible shapes, each associated with a different form of dementia.

More information: Hilda Mirbaha et al. Inert and seed-competent tau monomers suggest structural origins of aggregation, eLife (2018). DOI: 10.7554/eLife.36584

https://bit.ly/2L34chV

Footwear habits influence child and adolescent motor skill development

New research finds that children and adolescents who spend most of their time barefoot develop motor skills differently from those who habitually wear shoes. Published in Frontiers in Pediatrics, this is the first study to assess the relevance of growing up shod vs. barefoot on jumping, balancing and sprinting motor performance during different stages of childhood and adolescence. The study shows that habitually barefoot children are noticeably better at jumping and balancing compared to habitually shod children, particularly from 6-10 years of age. While these beneficial barefoot effects diminished in older adolescents, the research nevertheless highlights the importance of barefoot exercise for motor development as children grow and mature.

“Walking barefoot is widely thought to be more natural, and the use of footwear has long been discussed as an influencing factor on foot health and movement pattern development,” explains Professor Astrid Zech from the University of Jena, Germany, who led the study.

“A few studies report that barefoot situations change biomechanics in children and adults during running and jumping—but only limited knowledge exists for the clinical relevance of this finding,” she continues. “We wanted to investigate, for the first time, whether changes in foot biomechanics due to barefoot activities are actually relevant for the development of basic motor skills during childhood and adolescence.”

Zech, together with two research teams, assessed three motor skills—balance, standing long jump and a-20 m sprint—in 810 children and adolescents from 22 primary and secondary schools across rural Western Cape South Africa and urban areas of northern Germany. The two groups were selected to represent different footwear lifestyles: children from South Africa are habitually barefoot, while children from Germany wear shoes most of the time.

The habitually barefoot participants scored significantly higher in the balance and jumping tests compared to the habitually shod participants. This difference was observed in both test conditions (barefoot and shod) and across all age groups (6-10, 11-14 and 15-18 years), but particularly evident in 6-10 year-old children. The habitually barefoot children also performed better when barefoot than when shod.

“Most of the primary school children in our study (South Africa) go to school and perform sport and leisure activities barefoot,” says Professor Ranel Venter from Stellenbosch University, who led the South African research team. “Our finding that these children performed better in balancing and jumping supports the hypothesis that the development of basic motor skills during childhood and adolescence at least partly depends on regular barefoot activities.”

The results for the sprint test, however, were different. Here the habitually shod children performed better, particularly those in the 11-14 year age group, and both groups performed better while shod. The researchers explain that environment—the one factor that could not be standardized across the two study locations—may have influenced this result.

“In South Africa, the sprint test took place outdoors—with different weather conditions and surfaces. In contrast, the German children took the sprint test indoors, mostly in a sports hall with a sprung floor,” says Zech. “The type of shoe may also have influenced the results. South African students run in school shoes, while German students use sneakers or athletic shoes in their physical education classes. So while our results suggest that growing up shod may be beneficial for fast sprinting, we need to investigate this further.”

Overall, the researchers’ work emphasises the benefits of barefoot physical activities for motor development.

“Physical education classes, exercise and sport programs, and reactional activities that aim to improve basic motor skills could benefit from including barefoot activities,” says Zech. “Parents could also encourage regular barefoot time at home.”

More information: Astrid Zech et al, Motor Skills of Children and Adolescents Are Influenced by Growing up Barefoot or Shod, Frontiers in Pediatrics (2018). DOI: 10.3389/fped.2018.00115

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