Category Archives: Genetic medicine

A coalition that includes major drugmakers like Pfizer and Johnson & Johnson is running ads featuring workers in hard hats and hiring former labor officials and well-known union lobbyists to deliver their message. Many see the pairing between pharma and the unions as an odd one, because members often struggle with the high costs of drugs. Meanwhile, the White House contends that House Speaker Nancy Pelosi's drug plan will hurt innovation.

The New York Times:Labor Unions Team Up With Drug Makers To Defeat Drug-Price ProposalsHouse Speaker Nancy Pelosis bill to lower drug prices has the backing of many of the nations biggest labor groups, including the United Auto Workers, the A.F.L.-C.I.O., and unions representing teachers and other government workers. But a wave of Facebook ads that ran this fall appeared to suggest otherwise. The ads, featuring a dejected-looking man in a hard hat, warned that the bill threatens thousands of good-paying jobs and restricts access to lifesaving medication. (Thomas, 12/3)

CNBC:White House: Pelosi's Drug-Pricing Bill Would Result In 100 Fewer DrugsDemocratic House Speaker Nancy Pelosis sweeping drug-pricing bill would result in as many as 100 fewer drugs hitting the U.S. market over the next decade, the White House claimed in a report Tuesday. The White House, citing an analysis from the Council of Economic Advisers, an agency within the executive office, also said Pelosis bill would lead to worse health outcomes and cost the U.S. economy $1 trillion per year over that time period. The report from the administration, which has some health policy analysts scratching their heads, suggests far greater consequences than other estimates for both the drug industry and American consumers if the bill is enacted. (Lovelace, 12/3)

And in other pharmaceutical news

Stat:Huntington's Clinical Trial Opens A Door To Hope But Only If Patients Get In[Perry Stewart] is one of about 800 patients around the world enrolled in a final-stage clinical trial of a drug designed to slow maybe even stop the progression of the disease. Though it wouldnt be a cure, its the first time a therapy aimed at the actual root of Huntingtons has reached this far in its development odyssey. And it is one of a wave of therapies to rely on advances in genetic medicine to combat previously untreatable inherited diseases. (Joseph, 12/4)

Stat:4 Questions Key To Making Sense Of New Data On Biogens Alzheimers DrugThe annual Alzheimers research meeting known as CTAD was supposed to be a snoozefest this year. That all changed six weeks ago, when Biogen (BIIB) stunned the medical world by bringing an Alzheimers drug back from the dead and vowed to make a detailed scientific case for the decision at the gathering this week. On Thursday morning, Biogen will give that highly anticipated presentation livestreamed here detailing data from two late-stage clinical trials of its drug, known as aducanumab. (Robbins, 12/4)

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Low-Profile Pharma Group Taps Into Fears That Pelosi's Drug Pricing Bill Will Threaten 'Thousands Of Good-Paying Jobs' - Kaiser Health News

Country doctor James DeLine talks about his work with the Amish

In 33 years at the La Farge clinic, Dr. James DeLine has gained the trust of many Amish. He understands their beliefs and their financial limitations, and he leaves the medical decisions to the families.

Mark Hoffman, Milwaukee Journal Sentinel

MILWAUKEE, Wis.It is 5 degrees below zeroand a light powdering ofsnow swirls across the roads of Vernon County.Afew horses and buggies clop through the chillmorningair, but Perry Hochstetler leaves his buggy at the family farmand has a driver take him to his doctors appointment.

TheHochstetlersare Amish. With no health insuranceanda modest income, they cannot afford most doctors.

They can afford James DeLine, once the lone doctor in the western Wisconsin village of LaFarge. Population 750.

When he became the village doctor in 1983, DeLine had no experience treating the Amish and no idea the crucial role they would play in his work. Today, about 20% of the doctors patients are Amish or Old Order Mennonite, part of a Christian population called Plain People. They are known for their separation from the modern world and adherence to a simple lifestyle and unadorned dress.

Something of a throwback himself,DeLine, 65, is a short,bespectacledman with a walrus mustache, a doctor who carries a brown medical bag to house calls. For years, he carried his equipment in a fishing tackle box.

He knows the families on every local farm and their medical histories. He knows whos beenborn,andcalls on the mothers and infants to make sure they are healthy. He knows whos dying, and looks in on them in their final days, sitting by their bedside, talking in a gentle voice, making sure they have what they need for pain.

Amish farms are clustered together along Highway D between Cashton and La Farge.Mark Hoffman / Milwaukee Journal Sentinel

As a young doctor,DeLine never imagined he would find himselfsomedaywith one foot planted solidly in medicines past, the other in its future.

The doctor who makes housecallsalso collaborates with English and American geneticists studying some of the rarest diseases on Earth. Some occur at much higher levels among the Amish, Mennonites and other closed communities that dont allow marriage to outsiders. This prohibition increases the likelihood that when a rare, disease-causing mutation appears in the community, it will take root and pass from generation to generation.

It has taken DeLine and his staff years to gain the trust of Plain People, some of whom are wary of medicine and technology.Often,theyfear that going to a hospital or clinic will mean surrendering the decision-making to doctors who neither respect their beliefsnor understand their financial limitations.

DeLine, not a religious man himself, accommodates the beliefs of patients and parents; he has always viewed them as the ultimate decision-makers.

At first glance, Hochstetler seems an unlikely candidate for a rare disease or a health problem of any kind. Work at the local sawmill and his family farm has given the 26-year-old father of two a lean muscular frame. Beneath the skin lies another story.

He has the vasculature of an 80-year-old smoker,DeLinesays.

He inherited the genetic mutation that causes an illness most people have never heard of: sitosterolemia. Only 100 cases have been described in the medical literature, but DeLine has 13 patients with the condition, including four of Hochstetlers 10 siblings and their father.

The disease prevents the body from getting rid of lipids from vegetable oils and nuts, causing them to build up and clog the arteries.

Since diagnosing the disease,DeLinehas treated Hochstetler with a cholesterol-lowering drug called Zetia.

Without diagnosis and treatment,Hochstetlercould by now havesuffereda heart attack, a trauma that Zetia should delay, thoughfor how long isuncertain. There is no cure for sitosterolemia.

Im not afraid, he says. If I die young, I guess Im going to die young. I cant do much about it. I cant say I ever get low and have the blues about it.

Saving grace: The story of an Amish community and the fight for their children's lives

A blizzard almost kept the doctor and village from their appointment.

It was February 1983. DeLine drovehis familyover hilly country roads, staring out the windshield into flurries and fearingtheir carmight not makeit to LaFarge.

DeLinehad just completed his residency at the Wausau Hospital Center. Now, a10-membercommitteeof localswas recruiting him to fill LaFargesvacancy for a doctor. Thevillage had beenwithout one for a couple ofyears.

The doctor liked the friendly villagers, a welcome change from the suit-and-tie types hed interviewed with in other places.

He was 28 years oldwith a bad car, a growing family and $30,000 in unpaid student loans. The average salary for a family doctor in America was then around $80,000, enough to settle down and beginpaying offhis debt.

But the people of LaFargewantedDeLine needed him. Their offer: $20,000.

That would have to coverDeLinesannual salary, the salary of an assistant to answer the phones and handle billing, plus all the clinic equipment andexpenses. .

DeLine took the offer.

The photo of country doctor Ernest Guy Ceriani, made famous in a groundbreaking Life Magazine photo essay by W. Eugene Smith, hangs on James DeLine's refrigerator door at his home in La Farge.Mark Hoffman / Milwaukee Journal Sentinel

DeLinegrew up in New Lenox, Illinois, a farming community outside Joliet.

The village of 1,750 was mostly cornfields. DeLine remembers it asthe kind of place where children grew up building forts during the day and watching bonfires at night. DeLine had twin sisters five years younger than him. Their father owned a restaurant.

From an early age, though, itjust seemed like Id be going to medical school. It was meant to be.

DeLineremembers nights when he could hear his mother struggling to breathe. He could hear his father, too, trying to persuade her to go to the hospital.

She had rheumatic heart disease and took blood thinners starting in her 30s. She sometimes joked about needing a valve job.

DeLinewas 17 when his mother went in for the procedure.

He saw her once after surgerybut I didnt like how she looked.About the third day, his mother suffered cardiac arrest. She was resuscitated but had sustained a severe brain injury. Days later, the family shut off life support. She was 42.

One week after her death, JamesDeLineset out to become a doctor,leavinghome for the University of Illinois in Urbana-Champaign.

Physician James DeLine eases into his work day starting at 5 a.m. at his home in La Farge.Mark Hoffman / Milwaukee Journal Sentinel

University life was hard.DeLineremained so miredin grief that when he ate, he suffered terrible abdominal pain and had to lie on his stomach for relief.

Still, he took on a demanding schedule.Driven students tended to enter the more advanced honors program in either chemistry orbiology. DeLine, a physiology major, enrolled in both.

He paid for college through restaurant jobs and financial aid.

He went on to medical school, first in Champaign, then at the University of Illinois campus in Chicago. He lived in the citys Little Italysection on the nearwestside. There he met his future wife, Ann Doherty, who worked in a print shop.

DeLinegraduated from medical school on June 7, 1980. The next day, he and Ann married.

A week later, he started his residency in Wausau.

He would work a 24-hour shift, take 24 hours off, then head back for another 24 hours at the hospital. By the time Id stagger home for some rest, he says, I was sleep-deprived, hungry, with a headache.

The schedule bothered his wife. She missed him.In his next job, she would see even less of him.

Physician James DeLine checks on Dean Pease at Vernon Memorial Healthcare in Viroqua. Pease was admitted to the hospital for breathing difficulties.Mark Hoffman / Milwaukee Journal Sentinel

In LaFarge,DeLineworked harder than he had in his residency.

He was on call 24 hours a day, seven days a week. To make ends meet, both for his family and the clinic,DeLineworked five shifts a month in the emergency room at Vernon Memorial Hospital in Viroqua.

Some days he would work 9 a.m. to 5 p.m. at the clinic, then drive to the hospital and work 6 p.m. to 8 a.m. in the emergency room. He would return to the familys home just in time to shower and get to the clinic by 9.

There were times when he was tired, but it didnt slow him down, Marcia Bader, his now-retired office managersays. It was that deep-seated caring that kept him going.

After a morning of driving around visiting patients, physician James DeLine, right, updates the staff at his clinic.Mark Hoffman / Milwaukee Journal Sentinel

It was his wife,AnnDeLine, too.

The woman who had dreamed of being a mother did everything for the couples four children, all born within a five-year span. She washed cloth diapers and hung them out to dry. Shecooked, cleaned, took the children for walks, helped with school and play, and accepted with grace all the times when her husband was called away from holidays and birthday parties.

"The calendar of holidays does not apply," she says. "He helps people when they need him like the volunteer fireman races off when the alarm sounds; like the farmer plants and harvests when the ground and weather are ready."

"Life is lived by needs, not calendars and time slots."

This drawing is a gift from an Amish patient. James DeLine keeps it on his desk at home.Mark Hoffman / Milwaukee Journal Sentinel

Villagers embraced their doctor. Patients said they were accustomed to physicians who talked at them most of the time;DeLinelistened.

The clinic struggled financially in the early years. Not everybody paid their bills, Bader recalls. But the doctor wasnt going to send them to collection firms, and he wasnt going to stop caring for them.

The doctor and his wife became fixtures ofcommunitylife. They went to their childrens cross country meets and other school events. They attended the annual Kickapoo Valley Reserve Winter Festival.

But it was his presence in the homes of area residents that endeared him to them.

My father was diagnosed with colon cancer in 1994. The thing that always struck me was that Dr.DeLinestopped in to see my mom and dad one night after a basketball game, recalls Bonnie Howell-Sherman, editor and publisher of the weekly Epitaph-News in nearby Viola.

That was just unheard of. My mom is going through dementia now and out of all of the people shes met since shes been here, hes the one she remembers.

The villagers didnt just likeDeLine. They depended on him.

They worried about him, too.

Theres been two things about Dr.DeLinethat the whole community has been concerned about, Steinmetz said. One was, how do we keep him? The other was that hestayhealthy.

From time to time, rumors spread that the doctor was sick, even dying.

In 2007,DeLinehad noticed a problem. He would urinate, only to discover a short time later that he needed to go again.

It was prostate cancer.

Courtesy of the Viola Epitaph-News

Feeling, as he put it, reflective, maybe anxious too,DeLineapproached the Epitaph-News editor. He asked to write a series of columns for the newspaper describing his illness and treatment. He would counter the rumors with transparency. He called the column, From the Other Side.

I decided early on that I was comfortable sharing my experience with our community, he wrote in the first column. After all many of you have shared your concerns, fears and symptoms with me for nearly 25 years. Each of us knows that our turn must come for illness and eventually death.

He discussed his fears about surgery to remove his prostate Would I be able to jog again?He evensharedthe frustration of phoning to make a doctors appointment and going through endless computer prompts before reaching a live human voice.

His columns took readers through his surgery, recovery andreturn home.

The way the whole village shared the doctors illness and treatment, thats part of small-town life, explains Howell-Sherman, the newspaper editor.

Its been 12 years sinceDeLinessurgery. The cancer hasnot returned.

An Amish teen pulls farm machinery down a road in La Farge.Mark Hoffman / Milwaukee Journal Sentinel

Of all the relationships the doctor built in LaFarge, the most challenging involved his Amish patients.

DeLine found his medical work was affected by a deeply held principle among the Amish, expressed in the German wordgelassenheit, which means yielding oneself to a higher authority. Among the Amish, the word encompasses a calmness and patience, as well as a belief that individualism must take a back seatto the good of the community and the will of God.

A sign warns motorists they may encounter horse-drawn vehicles on Highway D between Cashton and La Farge.Mark Hoffman / Milwaukee Journal Sentinel

While some Amish visit hospitals and accept modern medical techniques, others prefer natural methods and traditional treatments: herbs, vitamins, supplements and home remedies. In the LaFargearea, it is not unusual for an Amish family to turn to these methods beforedecidingto see DeLine.

Such was the case with Abie and Edna Yoder when their 8-year-old daughter, Barbara, first grew sick in spring 2015.

The girl had little appetite and suffered from a terrible stomachache and bloody diarrhea. Barbara weighed 38 pounds 19 pounds below average for an 8-year-old.

The Yoders took her to a so-called non-traditional doctor used by some of the Amish; these tend to be herbalists, specialists in natural medicine and others, all of whom lack medical degrees.He viewed her blood under a microscope and told the family she might have colon cancer.

The parents worried terribly about their daughters survival, but worried too about putting her in the hands of a traditional doctor. The scenario that haunted them had happened to a 3-year-old Amish boy with leukemia. The boy was given chemotherapy, they say, despite the excruciating pain andultimate failureof the treatment.

He begged to be released to go to Jesus, Edna Yoder recalls.

The Yoders approached a midwife, whosent her husband to speak with DeLine. The husband explained to the doctor the circumstances and the familys hesitation. Then the Yoders brought their daughter.

"Dr.DeLinemade it really clear that he would respect our wishes,Edna Yoder recalls.

Their daughter was admitted to American Family Childrens Hospital in Madison.DeLineconsulted with a pediatric cardiologist hed worked with at UW, Amy Peterson.

Dr.DeLinehad noticed that she had interesting looking bumps on her arms and on her legs, Peterson recalls. They were deposits of cholesterol. Dr.DeLineand I started thinking along very similar lines very quickly.

Genetic testing confirmed their hunch. The girl had extremely rare sitosterolemia, the same illness that would later be diagnosed in Perry Hochstetler.

Treatment lowered the girls sitosterol levels and helped her gain weight.

DeLineand Peterson have since foundamong the local Amisha dozen othercases the second largest cluster of the disease in the world.

An Amish farmer makes his way to work on a fence along Highway D between Cashton and La Farge.Mark Hoffman / Milwaukee Journal Sentinel

Almost 200 diseases are found in much higher proportions among Plain People. Scientists have developed a special Amish genetics test that screens the blood for more than 120 of them.

DeLine has seen patients with more than 30of the diseases on the testand has at least two patients with diseases neverdescribed in medicine.

Across the globe, there have beenonly20 to 30 cases of a disease called BRAT1; DeLine has seen six. Babies with the illness are born rigid and are prone to frequent seizures.

When the baby is born you cant straighten the baby, DeLine says. The eyes are jerking, face twitching. Some moms say they have felt things that suggest the babies have been seizing in the womb.

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In a Wisconsin village, the doctor makes house calls and sees the rarest diseases on Earth - USA TODAY

IRVING, Texas and ALISO VIEJO, Calif., Dec. 4, 2019 /PRNewswire/ --Caris Life Sciences, a leading innovator in molecular science focused on fulfilling the promise of precision medicine, and Ambry Genetics(Ambry), a leading clinical genetic testing company, today announced that Caris will begin offering Ambry's 67-gene CancerNext-Expanded panel to evaluate the hereditary risks for cancer. Combined with Caris' somatic (tumor) tests that analyze a cancer's detailed molecular makeup, Caris will provide patients and their healthcare providers unparalleled information to more accurately diagnose and treat cancer. This will be the most comprehensive, clinically relevant molecular and genetic offering on the market today to guide treatment and management of cancer.

"We are committed to providing clinicians with high-quality information they can use to inform treatment decisions," said David D. Halbert, Caris Life Sciences Chairman, Chief Executive Officer and Founder. "By partnering with Ambry Genetics to better inform patient care, we are able to provide clinicians a greater ability to learn about a cancer's molecular composition."

Caris currently offers clinicians Caris Molecular Intelligence, a proprietary, comprehensive tumor profiling approach that assesses DNA, RNA, and proteins unique to an individual's cancer to reveal a molecular blueprint in order to guide more precise and individualized treatment decisions.

Through the partnership, Caris will now offer Ambry's CancerNext-Expanded hereditary cancer panel. This panel analyzes 67 genes associated with an increased hereditary risk of cancer, including brain, breast, colon, ovarian, pancreatic, prostate, renal, uterine, and many other cancers. Its comprehensive testing identifies inherited risks for cancer in order for clinicians to accurately diagnose, treat, and manage cancer risks for each patient's needs.

"To best diagnose and treat cancer, clinicians must understand whether patients have mutations in genes associated with an increased risk for hereditary cancer," said Aaron Elliott, Chief Executive Officer of Ambry. "Caris' molecular tests combined with Ambry's germline genetic testing, give clinicians the most comprehensive, clinically relevant molecular profile on the market to guide treatment and management."

The combined Caris and Ambry testing is now available nationwide.

"Being able to simultaneously conduct comprehensive tumor genomic testing and multi-gene germline sequencing is invaluable, especially for sick patients at the beginning of their cancer journey," said Michael J. Hall, M.D., M.S., Chair, Department of Clinical Genetics at Fox Chase Cancer Center. "This is information I can immediately begin using for my patients to more accurately diagnose them and to better individualize their treatments."

About Caris Life Sciences Caris Life Sciences is a leading innovator in molecular science focused on fulfilling the promise of precision medicine through quality and innovation. The company's suite of market-leading molecular profiling offerings assesses DNA, RNA and proteins to reveal a molecular blueprint that helps physicians and cancer patients make more precise and personalized treatment decisions.

Caris is also advancing precision medicine with Next Generation Profiling that combines its innovative service offerings, Caris Molecular Intelligence and ADAPT Biotargeting System, with its proprietary artificial intelligence analytics engine, DEAN, to analyze the whole exome, whole transcriptome and complete cancer proteome. This information, coupled with mature clinical outcomes on thousands of patients, provides unmatched molecular solutions for patients, physicians, payers and biopharmaceutical organizations.

Whole transcriptome sequencing with MI Transcriptome provides the most comprehensive and unique RNA analysis available on the market and covers all 22,000 genes, with an average of 60 million reads per patient, to deliver extremely broad coverage and high resolution into the dynamic nature of the transcriptome. Assessing the whole transcriptome allows us to dig deeper into the RNA universe to uncover and detect fusions, splice variants, and expression changes that provide oncologists with more insight and actionable information when determining treatment plans for patients.

Caris Pharmatech, a pioneer of the original Just-In-Time research system with the largest research-ready oncology network, is changing the paradigm from the traditional physician outreach model to a real-time approach where patient identification is completed at the lab and the physician is informed so that the patient can be enrolled days earlier, and remain in the local physician's care, without having to travel to a large central trial site. This fundamentally redefines how pharmaceutical and biotechnology companies identify and rapidly enroll patients in precision oncology trials by combining Caris' highest quality industry leading large-scale molecular profiling services with Pharmatech's on-demand site activation and patient enrollment system.

Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe, Asia and other international markets. To learn more, please visitwww.CarisLifeSciences.comor follow us on Twitter (@CarisLS).

About Ambry GeneticsAmbry Genetics, as part of Konica Minolta Precision Medicine, excels at translating scientific research into clinically actionable test results based upon a deep understanding of the human genome and the biology behind genetic disease. Our unparalleled track record of discoveries over 20 years, and growing database that continues to expand in collaboration with academic, corporate and pharmaceutical partners, means we are first to market with innovative products and comprehensive analysis that enable clinicians to confidently inform patient health decisions. We care about what happens to real people, their families, and the people they love, and remain dedicated to providing them and their clinicians with deeper knowledge and fresh insights, so together they can make informed, potentially life-altering healthcare decisions. For more information, please visitambrygen.com.

Caris Company Contact & Media:Srikant RamaswamiVice President, Chief Communications Officersramaswami@carisls.com +1-214-769-5510

Ambry Genetics Media Contact:Liz Squirepress@ambrygen.com (202) 617-4662

View original content to download multimedia:http://www.prnewswire.com/news-releases/caris-life-sciences-and-ambry-genetics-partner-to-advance-cancer-care-300968640.html

SOURCE Caris Life Sciences

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Caris Life Sciences and Ambry Genetics Partner to Advance Cancer Care - P&T Community

Tokyo-based Astellas Pharma announced plans to acquire San Francisco-based Audentes Therapeutics for $60 per share in cash, a total equity value of about $3 billion.

Under the terms of the deal, which both companies boards have unanimously approved, Astellas will buy Audentes through Asilomar Acquisition Corp., a wholly-owned subsidiary of Astellas US Holding. The offer represents a 110% premium of Audentes closing share price of $27.61 as of December 2.

The merger is an effort on the part of Astellas to strengthen its genetic medicine and gene therapy business. Hidemaru Yamaguchi, an analyst with Citi, wrote in a note for clients that it was a positive move for Astellas because Audentes had cutting-edge gene therapy modalities. We thought it was only a matter of time before Astellas entered the gene therapy market.

As part of the deal, Astellas gains access to Audentes AT132, which is being developed for XLMTM, a life-threatening, rare neuromuscular disease marked by extreme muscle weakness, respiratory failure and early death. It also picks up a pipeline of possible best-in-class genetic therapies for rare neuromuscular diseases with Audentes AAV gene therapy technology platform, in-house large-scale cGMP manufacturing capabilities and expertise in neuromuscular drugs. It expects to file for regulatory approval for AT312 in mid-2020.

The disease, however, affects only about 40 boys in the U.S. each year. Assuming a maximum price tagconsistent with other approved gene therapiesof about $2 million, that would only generate about $80 million in annual revenue. As such, Stephen Barker, an analyst with Jefferies, notes that, The $3 billion acquisition price is therefore more likely to be mainly predicated on the firms technology platform and manufacturing capabilities.

Recent scientific and technological advances in genetic medicine have advanced the potential to deliver unprecedented and sustained value to patients, and even to curing diseases with a single intervention, said Kenji Yasukawa, president and chief executive officer of Astellas. Audentes has developed a robust pipeline of promising product candidates which are complementary to our existing pipeline, including its lead program AT132 for the treatment of X-Linked Myotubular Myopathy (XLMTM). By joining together with Audentes talented team, we are establishing a leading position in the field of gene therapy with the goal of addressing the unmet needs of patients living with serious, rare diseases.

This is only the most recent of several deals by Japanese biopharma companies in the last year. Most recently, Asahi Kasei Corp. acquired Denmarks Veloxis Pharmaceuticals A/S for about $1.3 billion. Takeda Pharmaceutical Co. closed on its $62 billion acquisition of Shire Plc.

The deal is the second largest for Astellas after its $3.8 billion acquisition of OSI Pharmaceuticals in 2010.

Astellas currently has four Primary Focus Areas, urology, immunology (transplantation), cardiology, and infectious disease. The company indicates that the fifth, with this acquisition, will be Genetic Regulation, with gene therapy viewed as a key driver of future growth.

We are very pleased to enter into this merger agreement with Astellas, said Matthew R. Patterson, chairman and chief executive officer of Audentes. With its focus on innovative science and a global network of research, development and commercialization resources, we believe that operating as part of the Astellas organization optimally positions us to advance our pipeline programs and serve our patients.

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Astellas Buys Audentes for $3 Billion to Expand into Gene Therapy - BioSpace

What happened

Shares of Arrowhead Pharmaceuticals (NASDAQ:ARWR) gained as much as 14.4% today after the company announced a public stock offering. It seems counterintuitive, but investors appear to be excited about a snippet of text listing possible uses for the proceeds.

The company made the standard explanation that the cash will be used for general corporate expenses, to fund maturing clinical trials, and the like. But Arrowhead Pharmaceuticals also included a nonstandard detail in the press release for the public offering: "A portion of the net proceeds may also be used for the acquisition of complementary businesses, products and technologies, or for other strategic purposes."

Investors may be getting a little ahead of themselves here, but if Arrowhead Pharmaceuticals pulls the trigger on any strategic investment, then it's likely to be in one (relatively boring) category in particular.

As of 1:55 p.m. EST, the pharma stock had settled to a 10.2% gain.

Image source: Getty Images.

The developer of precision genetic medicines based on RNA interference (RNAi), a technique used to silence disease-driving genes, ended September with $221.8 million in cash and another $37 million in short-term investments. The proposed public offering of up to 4.6 million shares hasn't been priced yet; that information should be announced after market close today. But assuming an offering price of $60 per share, the business would raise up to $275 million in gross proceeds -- not a bad haul.

What could the cash be used for? Well, Arrowhead Pharmaceuticals decided to account for a $252.6 million up-front payment and equity investment, received from Johnson & Johnson subsidiary Janssen in late 2018, using the proportional accounting method. That allowed the business to count chunks of that total each quarter during its fiscal 2019, which resulted in full-year 2019 operating income of $61 million. It reported an operating loss of $55.9 million in fiscal 2018.

The proportional-accounting-method well will run dry in 2020, as there was just $77.8 million remaining against the up-front payment total at the end of September (the end of its fiscal year). In other words, the business is likely to report operating losses again in the near future.

What about a strategic investment, as hinted at in the press release for the public offering? That could happen, too. It may be a little less exciting than investors are imagining, however, because it's likely to be in drug manufacturing.

Arrowhead Pharmaceuticals spent $22 million on drug manufacturing in fiscal 2019, making it the single largest expense in the research and development category -- even more expensive than running clinical trials. The RNAi company has relatively strict manufacturing requirements, and the expense is starting to grow at a significant rate, so it may make sense to bring some of that expertise in-house with its own facility. Others in the precision-medicine space have done the same to reduce costs and operational risks. In fact, there's a manufacturing arms race in gene therapy right now.

The company is wisely taking advantage of a soaring stock price to pad its balance sheet. It will certainly need the cash to develop a maturing pipeline, and to fund operations once a lucrative collaboration revenue stream runs dry in 2020.

Whether Arrowhead Pharmaceuticals makes an acquisition of new technology or boring old manufacturing assets (or none at all), the company is correctly focused on the long term. That said, the company does appear to be a little expensive right now.

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Here's Why Arrowhead Pharmaceuticals Is Soaring Today - The Motley Fool

Sarepta Therapeutics, Inc.'s (NASDAQ:SRPT): Sarepta Therapeutics, Inc. focuses on the discovery and development of RNA-based therapeutics, gene therapy, and other genetic medicine approaches for the treatment of rare diseases. The US$8.4b market-cap posted a loss in its most recent financial year of -US$361.9m and a latest trailing-twelve-month loss of -US$620.3m leading to an even wider gap between loss and breakeven. The most pressing concern for investors is SRPTs path to profitability when will it breakeven? Ive put together a brief outline of industry analyst expectations for SRPT, its year of breakeven and its implied growth rate.

See our latest analysis for Sarepta Therapeutics

According to the 22 industry analysts covering SRPT, the consensus is breakeven is near. They expect the company to post a final loss in 2021, before turning a profit of US$676m in 2022. SRPT is therefore projected to breakeven around 3 years from now. What rate will SRPT have to grow year-on-year in order to breakeven on this date? Using a line of best fit, I calculated an average annual growth rate of 68%, which is rather optimistic! If this rate turns out to be too aggressive, SRPT may become profitable much later than analysts predict.

NasdaqGS:SRPT Past and Future Earnings, December 3rd 2019

Im not going to go through company-specific developments for SRPT given that this is a high-level summary, though, bear in mind that by and large a biotech has lumpy cash flows which are contingent on the product type and stage of development the company is in. This means, large upcoming growth rates are not abnormal as the company is beginning to reap the benefits of earlier investments.

One thing I would like to bring into light with SRPT is its relatively high level of debt. Typically, debt shouldnt exceed 40% of your equity, which in SRPTs case is 44%. Note that a higher debt obligation increases the risk in investing in the loss-making company.

This article is not intended to be a comprehensive analysis on SRPT, so if you are interested in understanding the company at a deeper level, take a look at SRPTs company page on Simply Wall St. Ive also put together a list of relevant aspects you should look at:

If you spot an error that warrants correction, please contact the editor at editorial-team@simplywallst.com. This article by Simply Wall St is general in nature. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. Simply Wall St has no position in the stocks mentioned.

We aim to bring you long-term focused research analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Thank you for reading.

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Breakeven On The Horizon For Sarepta Therapeutics, Inc. (NASDAQ:SRPT) - Yahoo Finance

Tulane University neuroscientist Dr. Stacy Drury will launch the Telomere Research Network to establish best practices for measuring telomere length and how it can be used as a sentinel of aging-related disease risk. Photo by Jennifer Zdon.

The National Institutes of Health awarded a $2.9 million grant to Tulane University neuroscientist Dr. Stacy Drury to lead a research network that will set methodological standards for studying a part of the chromosome that scientists increasingly recognize as an important biological marker of aging and age-related diseases.

Drury will launch theTelomere Research Network to establish best practices for measuring telomere length in population-based studies. Telomeres are the caps at the end of chromosomes that keep them from shrinking when cells replicate. Shorter telomeres are linked to higher risks for heart disease, obesity, cognitive decline, diabetes, mental illness and poor health outcomes in adulthood.

The network willdefine the extent to which telomere length can be effectively applied as a sentinel of aging-related disease risk and an indicator of environmental and psychosocial stress exposure across the life span, said Drury, the Remigio Gonzalez, MD, Professor of Child Psychiatry at Tulane University School of Medicine. We are charged with bringing together all of the international experts in the field and becoming a central focus for this research across the globe.

There has been an explosion in telomere research within the last decade. But scientists have used different measurement criteria, leading to problems replicating research results in some studies.

As it becomes clearer that it is a very powerful marker, the rigor of the science has to get better, Drury said. Because so many people are studying it in so many different ways, we don't want to dilute the impact by having lots of people using methodology that isnt the best.

The network will define the extent that telomeres can be used as a marker of environmental exposures, psychosocial stress and disease susceptibility. It will also provide a forum for researchers to share samples, research data, study protocols and discussions on best practices for the field.

The network will convene for its first meeting Dec. 5-6 in Washington, D.C. The event will be streamed online athttps://tulane.zoom.us/j/258026269.

Weatherhead Professor of Pharmacology John McLachlan is a co-investigator on the grant. Drury will be working with collaborators at the University of Groningen, University of California at San Francisco, Georgetown University, Pennsylvania State University and Rutgers University.

The NIHs National Institute on Aging and the National Institute of Environmental Health Sciences funded the initiative under grant award No.U24AG066528.

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NIH taps Tulane neuroscientist to lead effort to standardize research in genetic aging - News from Tulane

The human genome was first sequenced in 2003 by multiple research centres across the world. The breakthrough was hailed as the dawn of a new era. Genetics would swiftly transform our response to disease and lead to personalised medicine.

In the past decade there has been substantial progress in terms of studying genetic factors giving rise to disease. But much of this has been focused on European populations. Little progress has been made in examining the factors associated with disease among Africans.

Until very recently, only a few hundred whole genome sequences of individuals within Africa had been completed. Researchers largely relied on genetic data from African-Americans. These have provided many new insights. But they dont reflect the continents full genetic diversity.

Africa is known to be where humans originated. From Africa, they migrated to other parts of the world. This makes it the most genetically diverse region in the world. Diversity among other populations represents a subset of the diversity within Africa.

This genetic diversity provides unique opportunities to examine genetic factors associated with disease that cant be examined in Europeans where diversity is much lower. This highlights the need for much larger studies of genetic causes of disease within Africa.

We conducted a study to build one of the largest genome resources from within Africa. We developed a rich, diverse resource using genome wide data from 6,400 Ugandans the Uganda Genome Resource. It included whole genome sequencing of nearly 2,000 people.

The study built on the long standing research programme of the Medical Research Council Uganda and Uganda Virus Research Institute. Its aim has been to establish a clinical and genomic data resource to understand population health and disease in the region.

The team also incorporated data on 14,000 individuals from different parts of the continent. It did this in collaboration with the University of KwaZulu-Natal and the Centre of Genomics and Global Health, National Institutes of Health. This allowed us to examine genetic determinants of traits within the population.

Around a quarter of the genetic variation identified had not been discovered before. We found a higher level of genetic diversity in the Ugandan population than seen in similar studies of European populations.

Modern Uganda appears to be a complex mosaic of genetic flow from many different communities that have migrated from surrounding regions within Africa and from Europe or the Middle East. This gene flow appears to have occurred repeatedly, dating back from around 100 years ago to as long as 4,500 years ago.

Our work is an important step forward in African medical genetics research. But much more research is needed to understand how these genetic variants affect disease traits. That means looking at the functional effects of genomes on gene expression and protein levels.

In our study, we discovered ten new associations with blood traits, liver function tests and indicators of diabetes. Most of these new associations relate to genetic variants that are unique to the Ugandan population or very rare in non-Africans. These would not have been discovered even in very large studies of Europeans.

For example, we identified an association between a genetic variant that causes alpha-thalassemia, a blood disorder that leads to anaemia, and glycated haemoglobin levels, which are commonly used for diagnosis of diabetes. This genetic variant is found in 22% of Africans. It has become very common in some regions within Africa because it also protects against severe malaria. It remains very rare in other populations where malaria isnt endemic. Our findings suggest that the utility of glycated haemoglobin as a diagnostic tool for diabetes may require re-evaluation in regions where alpha-thalassemia a blood disorder that reduces the production of haemoglobin is common.

The richness of the Uganda resource also offered us other opportunities. For example, we were able to study the extent to which genetic differences influence differences in traits among Ugandans relative to previous studies in European populations. We found that heritability the extent to which genetic differences encode differences in traits or diseases may differ between Ugandans and Europeans.

We also found that height is less genetically determined in rural Ugandans relative to previous European studies. We think that this might relate to differences in the impact of environmental factors between rural Ugandan and European populations. For example, the genetic influences on height might be more limited by nutritional influences in early childhood.

Our findings highlight the usefulness of examining genetically diverse populations within Africa. They underscore how this can lead to new discoveries and help us understand the genetic encoding of traits that may be different within Africa relative to other populations.

Africa is central to our understanding of human origins, genetic diversity and disease susceptibility. There is a clear scientific and public health need to develop large-scale projects that examine disease susceptibility across diverse populations across the continent. That work should be integrated with initiatives to improve research capacity in Africa.

We now need larger and more diverse studies of genetic causes of disease across the region. These will foster the development of new treatments that will benefit people living in Africa as well as people of African descent around the world.

Future work will look at individuals from other parts of Africa. The aim will be to get a deeper understanding of genetic diversity among indigenous hunter-gatherer populations. These include the Khoe-San populations in Namibia and South Africa and the rain forest populations in central Africa. In addition, we will be expanding current studies of genetic causes of disease to 100,000 individuals across the region.

The data was collected by researchers from universities and research institutes from Africa and the UK, including Queen Mary University of London, the University of KwaZulu-Natal, MRC/UVRI & London School of Hygiene & Tropical Medicine Uganda Research Unit, the US National Institute of Health and the University of Cambridge.

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What we've learnt from building Africa's biggest genome library - The Conversation Africa

Washington (AFP)

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome.

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

"I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email.

"Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

"But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

- Cures -

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union.

They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris.

"It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection.

"You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

- Bioterrorism -

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal -- and his excommunication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

"Not everyone is a biologist or scientist," she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops?

Charpentier thinks that technology generally tends to be used for the better.

"I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

2019 AFP

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2019: the year gene therapy came of age - FRANCE 24

Specific patterns of protein levels in our blood could be used to provide a comprehensive liquid health check that gives a snapshot of health and potentially an indication of the likelihood that we will develop certain diseases or health risk factors in the future, according to research by scientists in the U.S. and U.K. working with SomaLogic. The results of their proof-of-concept study involving more than 16,000 participants, and published in Nature Medicine, showed that while the accuracy of models based on specific protein expression patterns varied, they were all either better predictors than models based on traditional risk factors, or would constitute more convenient and less expensive alternatives to traditional testing.

This proof of concept study demonstrates a new paradigm that measurement of blood proteins can accurately deliver health information that spans across numerous medical specialties and that should be actionable for patients and their healthcare providers, said Peter Ganz, MD, co-leader of this study and the Maurice Eliaser distinguished professor of medicine at UCSF and director of the Center of Excellence in Vascular Research at Zuckerberg San Francisco General Hospital and Trauma Center. I expect that in the future we will look back at this Nature Medicine proteomic study as a critical milestone in personalizing and thus improving the care of our patients. The teams published study is titled, Plasma protein patterns as comprehensive indicators of health.

Preventative medicine programs such as the U.K. National Health Services Health Check and Healthier You programs are aimed at improving individuals health and reducing the risk of developing diseases. While such strategies are inexpensive, cost-effective, and scalable, they could also be made more effective using personalized information about an individuals health and disease risk, the authors suggested. The application of big data in healthcare, assessing and analyzing detailed, large-scale datasets, makes it increasingly feasible to make predictions about health and disease outcomes and enable stratified approaches to prevention and clinical management. Protein scanning represents a potential approach to bridging the gap between the need for practicality and low cost, and the potential for personalized, systemic, and data-driven medicine.

Proteins regulate biological processes and can integrate the effects of genes with the effects of environment, age, existing diseases, and lifestyle behaviors, the authors explained. Our genomes contain about 19,000 genes that code for some 30,000 different proteins. Up to 2,200 of these proteins, including hormones, cytokines, and growth factors, are purposefully secreted into the blood, to orchestrate biological processes in health or in disease. Other proteins enter the blood through leakage from damaged or dead cells. Both secreted and leaked proteins can inform health status and disease risk.

In a proof-of-concept study based on five observational cohorts involving 16,894 participants, the researchers scanned 5,000 proteins in single blood plasma samples taken from each participant, to simultaneously capture the individualized imprints of current health status, the impact of modifiable behaviors, and incident risk of cardiometabolic diseases (diabetes, coronary heart disease, stroke, or heart failure).

To analyze the proteins in each sample the researchers used a technique that harnessed fragments of DNA known as aptamers, which bind to the target protein. In general, only specific fragments will bind to particular proteins. Using existing genetic sequencing technology, the researchers could then search for the aptamers and determine which proteins are present and in what concentrations. In total, the study carried out about 85 million protein measurements in the nearly 17,000 participants.

The researchers analyzed the results using statistical methods and machine learning techniques to develop predictive modelsfor example, that an individual whose blood contains a certain pattern of proteins is at increased risk of developing diabetes. The models covered a number of health states, including levels of liver fat, kidney function and visceral fat, alcohol consumption, physical activity, and smoking behavior, and for risk of developing type 2 diabetes and cardiovascular disease.

The accuracy of the models varied, with some showing high predictive powers, such as for percentage body fat. Other models demonstrated only modest prognostic power, such as that for cardiovascular risk, but even this was still modestly better than traditional risk factors and could also add value in overcoming the incomplete utilization of risk calculation in primary care, the team wrote. Many of the proteins measured linked to a number of health states or conditions. Leptin, for example, modulates appetite and metabolism, and was informative for predictive models of percentage body fat, visceral fat, physical activity, and fitness.

The researchers pointed out that a key feature of the study is that it used information from just one source, a single blood draw, for protein-phenotype models, the authors pointed out. This was a key objective of our health check proof of concept. The team didnt include demographic or known risk factors in their modelsunless absolutely necessary. They also didnt test whether they models could be improved by adding in other features, such as history, laboratory tests, or genetic information. It is possible that these multi-source models could improve absolute models performance, although their inclusion has potential implications for increasing costs and loss of convenience.

One difference between genome sequencing and proteomics approaches is that whereas the genome is fixed, the proteome changes over time, possibly as an individual becomes more obese, less physically active, or smokes, for example. These changes in proteins could be used to track changes in an individuals health status over a lifetime.

Proteins circulating in our blood are a manifestation of our genetic make-up as well as many other factors, such as behaviors or the presence of disease, even if not yet diagnosed, said Claudia Langenberg, M.D., from the MRC Epidemiology Unit at the University of Cambridge. This is one of the reasons why proteins are such good indicators of our current and future health state and have the potential to improve clinical prediction across different and diverse diseases.

While this study shows a proof-of-principle, the researchers acknowledged that there were limitations, and suggested that as technology improves and becomes more affordable, it is feasible that a comprehensive health evaluation using a battery of protein models derived from a single blood sample, could be offered as routine by health services. It is thus conceivable that, with further validation and the potential for expansion of the number of tests, a comprehensive, holistic health evaluation using a battery of protein models derived from a single blood sample could be performed. The next step is to test the applicability of the protein models that we have derived and validated in observational cohorts under research conditions in real-world healthcare systems.

Its remarkable that plasma protein patterns alone can faithfully represent such a wide variety of common and important health issues, and we think that this is just the tip of the iceberg, said study lead Stephen Williams, M.D., chief medical officer at SomaLogic, which is developing its SomaScan Platform and SomaSignal tests for a wide range of human diseases. We have more than a hundred tests in our SomaSignal pipeline and believe that large-scale protein scanning has the potential to become a sole information source for individualized health assessments.

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Blood Test that Measures Expression of 5,000 Proteins Shows Potential as Disease Screening Tool - Clinical OMICs News