AstraZeneca to seek FDA authorization for vaccine based on foreign trial data

The company also said it would work with the agency to adjust the design of its late-stage U.S. trial to test the half-dose regimen, rather than the higher dose that proved less effective in the U.S and Brazil studies. That U.S. trial has enrolled about 10,000 of a planned 40,000 participants, but the company has not released any data from that study.

The U.K. and Brazil studies have enrolled about 24,000 participants — fewer than the 30,000 participants that the FDA is requiring for late-stage coronavirus vaccine trials.

The initial findings were based on 131 infections among trial participants. The company did not break down how many cases were reported among those who got a placebo versus those who got the vaccine, and within that vaccine group, how cases split among the two doses tested.

AstraZeneca also said that none of the infected people had severe Covid-19 or were hospitalized, but offered no further safety information.

Promising logistics: The AstraZeneca vaccine is cheaper and easier to distribute than the other two shots that have proven effective. It can be transported and stored under refrigerated conditions for at least six months, and the company says it can make up to 3 billion doses next year.

Vaccines from Pfizer and Moderna, which have each proven about 95 percent effective, must be frozen during distribution and kept at very cold temperatures.

“AstraZeneca and Oxford have developed an affordable, scalable vaccine that crucially can be stored and shipped in a regular refrigerator,” said Richard Hatchett, CEO of the Coalition for Epidemic Preparedness Innovations, said in a statement. “This makes it appropriate for use and easy to deliver almost anywhere in the world, including in low-resource settings.”

But questions remain: Others doubt whether the FDA will authorize the vaccine.

“We believe that this product will never be licensed in the US,” investment bank SVB Leerink analyst Geoffrey Porges said in a note on Monday. “This belief is based on the design of the company’s pivotal trials (which does not appear to match the FDA’s requirements for representation of minorities, severe cases, previously infected individuals and elderly and other increase risk populations), and based on the occurrence of severe safety events (why take the risk) that resulted in the extended clinical hold on enrollment into the trials in the US.”

The company halted its U.S. trial in early September over safety concerns, after a trial participant reported neurological problems. The study resumed earlier this month after FDA concluded that no evidence linked the volunteer’s symptoms to the shot.

Background: The AstraZeneca vaccine was developed by scientists at Oxford University, and uses a different technology than the Moderna and Pfizer vaccines. It uses a weakened version of the common cold that contains some genetic material from the coronavirus.

U.S. vaccine and therapeutics accelerator Operation Warp Speed paid for some of the clinical development of the AstraZeneca vaccine and purchased 300 million doses for $1.2 billion.

Other clinical trials are ongoing in Japan, Russia, South Africa, Kenya

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Builder, 45, dies in prison days before facing trial for murdering fitness trainer girlfriend

Builder, 45, dies in prison days before facing trial for murdering his ‘beautiful and kind’ ex-army fitness trainer girlfriend, 26

  • Terence Papworth was charged with murder of Amy-Leanne Stringfellow in June
  • The mother-of-one was found critically injured at his flat in Doncaster on June 5
  • Papworth, 45, a builder, was due to face trial over Amy’s death on November 30 
  • He was found dead in his cell at Armley Prison in Leeds on Sunday, November 22 

A builder has died in prison days before he was due stand trial for the alleged murder of his ‘beautiful and kind’ girlfriend.

Terence Papworth, 45, was charged with the murder of mother-of-one Amy-Leanne Stringfellow, 26, in June.

Ms Stringfellow, who served in Afghanistan, was found critically injured in Papworth’s home in Balby, Doncaster, South Yorkshire, on June 5 this year.

Emergency services battled to save the fitness trainer, but she was declared dead at the scene.

Papworth was charged with her murder two days later and was due to stand trial next week.

However, he was found dead in his cell at Armley Prison, in Leeds, West Yorkshire, on Sunday.

Terence Papworth, 45, was charged with the murder of mum-of-one Amy-Leanne Stringfellow, 26, in June and was due to stand trial later this month

He was found dead in his cell at Armley Prison, in Leeds, West Yorkshire, on Sunday ahead of the trial, following Amy's (pictured) death

Terence Papworth (pictured left), 45, was charged with the murder of mum-of-one Amy-Leanne Stringfellow (pictured right), 26, in June and was due to stand trial later this month. He was found dead in his cell at Armley Prison, in Leeds, West Yorkshire, on Sunday

Papworth was found dead in his cell at Armley Prison (pictured), in Leeds, West Yorkshire, on Sunday

Papworth was found dead in his cell at Armley Prison (pictured), in Leeds, West Yorkshire, on Sunday

Papworth had recently appeared in court via video link for a case management hearing and was due to stand trial on November 30 at Sheffield Crown Court.

The Ministry of Justice said: ‘Terence Papworth died in HMP Leeds on 22 November.

‘The Prisons and Probation Ombudsman has been informed.’

Papworth and Ms Stringfellow, who has a young daughter, had been in a relationship since last October but they had not moved in together.

She had travelled the four miles from her home in Doncaster to see Papworth during lockdown.

After her death, South Yorkshire Police referred itself to the Independent Office for Police Conduct (IOPC) over prior contact they had with Ms Stringfellow.

Private Stringfellow enlisted in the Army in 2010 and completed assignments with 3rd Battalion the Rifles 3 RIFLES in Edinburgh and Chilwell.

She also served a tour of duty in Afghanistan in 2012 as part of the Operation Herrick 16 deployment.

Amy-Leanne Stringfellow, 26, was found critically injured at a house in Doncaster in June. She died a short while later, despite efforts to save her

Amy-Leanne Stringfellow, 26, was found critically injured at a house in Doncaster in June. She died a short while later, despite efforts to save her

Papworth was charged with murder and appeared at Doncaster Magistrates' Court in June. He was due to stand trial on November 30

Papworth was charged with murder and appeared at Doncaster Magistrates’ Court in June. He was due to stand trial on November 30

Amy had been promoted to Lance Corporal but was discharged before taking up the post.

The fitness fanatic rejoined as a Volunteer Reservist in 2017 and also worked as a personal trainer.

Tributes

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University of Chicago Medicine looking for 2,000 participants for COVID-19 vaccine trial

University of Chicago Medicine will soon begin testing another potential COVID-19 vaccine, and is looking for up to 2,000 people to enroll in the phase three clinical trial.



Medical assistant Debbie Turrise assists patients driving thru with self administered COVID-19 tests at a COVID-19 drive-thru testing site at Rush University Medical Center in Chicago, Tuesday, Oct. 20, 2020. University of Chicago Medicine will soon begin testing another potential COVID-19 vaccine, and is looking for up to 2,000 people to enroll in the phase three clinical trial.


© Antonio Perez / Chicago Tribune/Chicago Tribune/TNS
Medical assistant Debbie Turrise assists patients driving thru with self administered COVID-19 tests at a COVID-19 drive-thru testing site at Rush University Medical Center in Chicago, Tuesday, Oct. 20, 2020. University of Chicago Medicine will soon begin testing another potential COVID-19 vaccine, and is looking for up to 2,000 people to enroll in the phase three clinical trial.

The trial is designed to evaluate the safety and efficacy of a single dose of a vaccine produced by Janssen Pharmaceutical Companies of Johnson & Johnson. The trial began enrolling 60,000 adults across the world in September.

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It’s one of a handful of potential vaccines now in advanced clinical trials in the U.S.

The international trial of the Janssen vaccine was temporarily paused in October after one participant developed an unexplained illness.

“Such pauses are not uncommon in vaccine trials, and late last week the FDA approved the resumption of the trial after an independent committee found the vaccine did not cause the illness,” University of Chicago Medicine leaders wrote in an email sent Monday to faculty, staff and students.

This is the second COVID-19 vaccine trial University of Chicago Medicine has offered. Since mid-September, the system has also been enrolling subjects in the Moderna COVE trial.

To participate in the Janssen trial and future research, people can join UChicago Medicine’s registry.

Other large hospital systems in Chicago are also participating in COVID-19 vaccine trials, including the University of Illinois at Chicago, which is part of the Moderna trial, and Northwestern Medicine, which is part of a trial of the AstraZeneca Oxford vaccine.

———

©2020 the Chicago Tribune

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First-Ever Positive Phase III Trial in Epidermolysis Bullosa

A topical treatment derived from tree bark significantly increased healing of epidermolysis bullosa (EB) lesions versus standard care in an international multicenter clinical trial.

After 45 days of treatment, 41.3% of patients randomized to oleogel-S10 (Filsuvez) had complete wound closure as compared with 28.9% of the control group. A subgroup analysis showed that the beneficial effects were limited to patients with recessive dystrophic, which accounted for almost 80% of the study population.

The wound-healing advantage of oleogel-S10 emerged at about 30 days and persisted out to 90 days, when the proportion of patients with healing became similar in the two treatment groups, reported Dedee Murrell, MD, of the University of New South Wales in Kensington, Australia, during the European Academy of Dermatology and Venereology virtual conference.

“The time to event, which is wound healing over 90 days … was not statistically significant overall,” she said. “The wound healing trajectories demonstrated that oleogel-S10 accelerates wound healing in a subset of the wounds. However, as expected, with good wound care, the control group begins to catch up later by 90 days. The difference in the proportion of healed target wounds had narrowed between treatment groups at 90 days, but the control group never overtook the oleogel arm.”

“This is the first time that a phase III trial in EB has met its primary endpoint,” she added.

Background of Development

A rare genetic skin-fragility disorder, EB characteristically emerges as a pattern of recurring healing and break-down wounds, along with chronic slow-healing or nonhealing wounds. The condition has no approved therapy, and standard of care consists of nonadhesive bandages, topical antimicrobial agents, topical steroids, and various unapproved therapies that are not specific for EB, Murrell noted.

The primary active ingredient in oleogel-S10 is betulin, a naturally occurring triterpene found in the bark of certain types of birch trees. Dry betulin extract is mixed with sunflower oil to form a gel, which is applied directly to EB lesions and to the contact surface of bandages. The mechanistic rationale for its use in EB includes evidence that triterpenes help modulate inflammation and are involved in keratinocyte proliferation, migration, and differentiation.

Preliminary clinical research provided evidence of accelerated wound healing in patients with dystrophic EB. The work subsequently led to the international phase III EASE trial. Investigators at 58 sites in 28 countries enrolled 223 patients, primarily with dystrophic EB but also junctional EB or Kindler syndrome. Eligible patients had a partial thickness wound 10-50 cm2 in size, persisting for 21 days to 9 months.

Patients were randomized to oleogel-S10 or control gel, each in addition to standard dressings changed at least once every 4 days. The primary endpoint was the proportion of patients who had a first complete closure of a target wound within 45 days. Secondary endpoints included time to wound healing, proportion of target wounds healed within 90 days, incidence and severity of wound infections, change in total body wound burden, change in itching, and adverse events.

Patients ages 4-12 years accounted for

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Trial targets deadly lung cancer

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IMAGE: Associate Professor Sonja Klebe, leader of Asbestos Associated Disease research at Flinders University
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Credit: Flinders University

With more than 650 Australians diagnosed with malignant mesothelioma last year, Flinders University is leading new research to discover alternatives to chemotherapy and even prevent deaths by early detection in future.

One novel approach, using natural therapeutic benefits of curcumin, a key component of the spice turmeric, will be put to the test in a clinical trial in 2021 as part of world-leading research at Flinders University.

While asbestos is now banned from being used for new buildings, many houses still contain asbestos, so exposure during renovations is common. Australia has one of the highest per-capita rates of asbestos-related disease in the world.

Flinders University researchers are studying the safety and feasibility of using a form of intrapleural liposomal curcumins to benefit patient survival and quality of life – with fewer toxic side-effects than chemotherapy.

“That’s why it’s important to explore alternative therapies and facilitate early diagnosis to reduce suffering and support early intervention measures,” says Flinders University lead researcher Associate Professor Sonja Klebe.

As well, the researchers are looking for early diagnostic methods with a special lung fluid test. “In most cases, malignant mesothelioma is not diagnosed until it is in the late stages,” she says. “We’re hoping to find a way to test for the disease before it becomes invasive.”

Patients diagnosed with malignant mesothelioma, the cancer caused by asbestos exposure, experience poor survival of 6-12 months following diagnosis and a five-year survival of less than 5%. Therapeutic options are limited due to high resistance rates to chemotherapy and the advanced age of patients (median age 75).

Associate Professor Klebe’s team will test the safety and feasibility of intrapleural liposomal curcumin to benefit patient survival and quality of life. Future treatments are expected to have fewer toxic side-effects than chemotherapy.

In addition, the researchers are investigating methods to facilitate early diagnosis, using novel techniques on the lung fluid that is drained in the early stages of diagnosis.

“In most cases, malignant mesothelioma is not diagnosed until it is in the late stages,” she says. “We’re hoping to find a way to test for the disease before it becomes invasive.”

In time for Asbestos Awareness Month in November, the experts warn the high number of cases could persist for years with hundreds more cases of the deadly disease possible after latency of more than 30 years from work-related (builders, plumbers, gasfitters, mechanics and marine engineers) or other exposure. Firefighters may also be at risk after the devastating bushfires razed old buildings and sheds across Australia.

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See the latest research publications:
‘Malignant mesothelioma in situ: diagnostic and clinical considerations’ (2020) by E Pulford, DW Henderson and S Klebe published in Anatomical Pathology (Vol 52, Iss 6, page 635-642)
DOI: 10.1016/j.pathol.2020.06.010

See also:
The potential utility of GATA binding protein 3 for diagnosis of malignant pleural mesotheliomas (2020) by S Prabhakaran, A Hocking, C Kim, M Hussey and S Klebe has

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Japan’s Shionogi readies COVID-19 vaccine for December trial: CEO

By Rocky Swift

TOKYO (Reuters) – Shionogi & Co is planning clinical trials by year-end for what may be one of Japan’s first domestically produced COVID-19 vaccines to reach the market, as the globe races to secure enough doses to battle the pandemic.

The company plans to put its vaccine candidate into Phase 1 clinical trials in December and shift into Phase 2 by January and apply for tentative approval from the government, Shionogi chief executive Isao Teshirogi told Reuters in an interview.

But a Phase 3 trial would likely be done overseas due to the relative lack of COVID-19 cases in Japan, he said.

Shionogi’s plan to have enough doses to inoculate 30 million people by the end of next year means its impact will be much larger than that of first mover Osaka-based AnGes Inc, which expects to have its first doses ready by March.

“For almost national security reasons, having good capacity in Japan makes a lot of sense,” Teshirogi said.

While Shionogi lags global front runners that are now conducting mass final-stage clinical trials, it is betting on a proven platform to help it become Japan’s biggest home-grown COVID-19 vaccine producer. French drugmaker Sanofi SA and Novavax are using a similar process in their COVID-19 candidate.

“I think our recombinant protein vaccine, method wise, has more accumulated data on efficacy and safety than the novel methods,” Teshirogi said.

Newer methodologies like mRNA vaccines may end up being the solution, “but as of today, we don’t know anything”, he said.

Prime Minister Yoshihide Suga has pledged to provide enough vaccine for the populace by mid-2021, and Japan has struck deals for hundreds of millions of doses with companies including AstraZeneca Plc and Pfizer Inc.

Shionogi has received about $400 million from the Japanese government for its COVID-19 vaccine research.

But the world will need several different vaccines to fight the pandemic, given the sheer size of global demand, effects on different populations, and possible limits of effectiveness in the first vaccines.

Teshirogi said holding the postponed Tokyo Summer Olympics in 2021 is “still possible”, but it will depend more on high-rapid-diagnostic testing and logistics than vaccines.

“Receiving the vaccine is not a so-called safe license,” he said.

(Reporting by Rocky Swift in Tokyo; Editing by Miyoung Kim and Michael Perry)

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CLINUVEL to Trial Innovative Drug in Stroke

Acute Ischaemic Stroke

A clot in the brain vessel of a stroke patient leads to instant death of brain tissue closest to the clot, shown in dark pink. The larger area surrounding the core (shaded) is characterised as the penumbra, tissue which can still be rescued.
A clot in the brain vessel of a stroke patient leads to instant death of brain tissue closest to the clot, shown in dark pink. The larger area surrounding the core (shaded) is characterised as the penumbra, tissue which can still be rescued.
A clot in the brain vessel of a stroke patient leads to instant death of brain tissue closest to the clot, shown in dark pink. The larger area surrounding the core (shaded) is characterised as the penumbra, tissue which can still be rescued.

MELBOURNE, Australia, Oct. 28, 2020 (GLOBE NEWSWIRE) — The drug afamelanotide will be used for the first time in patients with acute stroke. The study will evaluate the safety and efficacy of afamelanotide, developed by Australian company CLINUVEL, in arterial ischaemic stroke (AIS). The aim is to offer a treatment for patients suffering a stroke who are unable to receive treatment to dissolve or remove the underlying blood clot. AIS accounts for approximately 85% of the 15 million strokes suffered worldwide each year.

“Stroke is most commonly caused by a clot in a patient’s brain which starves surrounding tissue of blood and essential oxygen, causing the destruction of brain cells,” CLINUVEL’s Chief Scientific Officer, Dr Dennis Wright said. “This brain damage can have an irreversible effect on a patient’s ability to speak, move, and function, and tragically leads to an early death for more than 5.5 million people per annum. It is our aim to show that treatment with afamelanotide can safely reduce and prevent brain damage in the majority of stroke patients who cannot be offered standard therapy.”

Strokes cause death of brain tissue at the site of the clot and lead to a shortage of oxygen in a larger area of the brain, known as the penumbra, which is salvageable brain tissue if treated quickly. The longer the delay in a stroke patient receiving treatment, the greater the potential threat to their life and overall prognosis as tissue within the penumbra becomes irreversibly damaged.

Current stroke therapies rely on early intervention to restore blood flow to the brain by either chemically dissolving or physically removing the clot. In Europe, no treatment can be offered to over 85% AIS patients due to a critical delay between the start of the stroke and presentation of the patient to a hospital. Additionally, the location of the clot within the artery is also an important factor impacting the possibility to offer treatment.

Research has indicated that afamelanotide – which is approved in Europe and the USA for patients with a rare metabolic disorder called EPP1 – may rapidly exert its effects to protect brain tissue, act on blood vessels to optimise blood flow, and reduce the size of swelling in the brain following a stroke. More than 10,000 doses of afamelanotide have been administered to over 1,400 individuals during its development and use across a period of nearly two decades.

The pilot Phase IIa clinical study (CUV801) will be conducted

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Novavax delays U.S. trial of COVID-19 vaccine to November

FILE PHOTO: A woman holds a small bottle labeled with a “Vaccine COVID-19” sticker and a medical syringe in this illustration taken April 10, 2020. REUTERS/Dado Ruvic

(Reuters) – Novavax Inc on Tuesday delayed the start of a late-stage U.S. trial of its experimental coronavirus vaccine by roughly a month to the end of November, citing delays in scaling up the manufacturing process.

The U.S.-based drug developer said data from a separate Phase III trial being conducted in Britain was expected by the first quarter of 2021 and could be the basis for global regulatory approvals although it did not elaborate. Shares of the company rose nearly 3%.

It is not immediately clear whether that could apply in the United States. Novavax did not respond to a request for clarification.

“I think the FDA has generally been loathe to approve vaccines for Americans that haven’t been tested in Americans, historically,” Dr. Paul Offit, an infectious disease expert at the University of Pennsylvania and a member of the U.S. Food and Drug Administration’s vaccine advisory panel, said on in an interview with the editor of JAMA medical journal on Tuesday.

Data from an early-to-mid stage trial of the vaccine is expected on Friday, the company said. Earlier data had showed the vaccine produced high levels of antibodies against the novel coronavirus.

A handful of companies, including larger rivals Pfizer Inc and AstraZeneca Plc, are conducting late-stage trials of their experimental COVID-19 vaccines, though none have reported pivotal data that would be used to seek emergency authorization or approval.

The companies, including Novavax, have already made distribution deals with several countries for the vaccines, once approved.

Novavax in August said it will supply 60 million doses of its coronavirus vaccine to the UK from as early as the first quarter of 2021.

The company is also preparing to deliver 100 million doses to the United States by January after it was awarded $1.6 billion for its potential vaccine, and has also signed supply agreements with Canada and Japan.

Reporting by Manas Mishra in Bengaluru and Julie Steenhuysen in Chicago; Editing by Arun Koyyur and Bill Berkrot

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Lilly Stops Antibody Trial in Hospitalized COVID-19 Patients

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

Eli Lilly announced it will halt its ACTIV-3 trial evaluating the antibody bamlanivimab in combination with remdesivir for people hospitalized with COVID-19, after new evidence regarding efficacy emerged.

The new data from the National Institutes of Health suggest that the experimental neutralizing antibody therapy does not offer significant clinical benefit for people with more advanced COVID-19 illness, according to a company statement.

Eli Lilly also announced it plans to continue its other trials evaluating the antibody, including those assessing a potential role in treating people in the earlier stages of COVID-19.

“While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19,” the statement reads.

The ACTIV-3 trial was paused on October 13 after a data and safety monitoring board cited safety concerns.

The most recent data update that triggered an end to the trial did not reveal any significant differences in safety, though.  

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and rheumatology. Follow Damian on Twitter:  @MedReporter.

For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.

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Study in Nature Medicine shows superior patient outcomes in LLS’s Beat AML clinical trial

Rye Brook, NY (Monday, October 26, 2020) – Patients participating in The Leukemia & Lymphoma Society’s (LLS) groundbreaking precision medicine Beat AML Master Clinical Trial had superior outcomes compared to acute myeloid leukemia (AML) patients who opted for standard chemotherapy treatment, according to findings published today in the prestigious Nature Medicine journal.

The Beat AML trial achieved its primary endpoint by showing genomic analysis of the leukemia cells to identify AML subtypes can be completed within an unprecedented seven days, giving patients, caregivers and their doctors ample time to make a more personalized treatment decision without risking the patient’s chance for survival.

In other key findings, the study demonstrated a paradigm shift in how patients diagnosed with AML should be treated, proving that using genetic information to match patients to targeted therapies leads to better survival rates than the traditional one-size-fits all treatment approach.

AML is an extremely fast-moving cancer of the marrow and blood, affecting 21,000 people in the U.S. a year, and killing 10,000. For decades patients have been given the same treatments almost immediately upon diagnosis because waiting allows the cancer cells to grow out of control. This standard of care involves either infusion of a combination of two chemotherapies, cytarabine and daunorubicin, or treatment with a so-called hypomethylating agent, a drug that unleashes signals allowing the cancer cells to die.

“The study shows that delaying treatment up to seven days is feasible and safe, and that patients who opted for the precision medicine approach experienced a lower early death rate and superior overall survival compared to patients who opted for standard of care,” said John C. Byrd, MD, D. Warren Brown Chair of Leukemia Research of The Ohio State University, and one of the Beat AML leads and corresponding author of the study. “This patient-centric study shows that we can move away from chemotherapy treatment for patients who won’t respond or can’t withstand the harsh effects of the same chemotherapies we’ve been using for 40 years and match them with a treatment better suited for their individual case.”

Going on the Offensive Against AML


Recognizing the urgent need to do better for AML patients, LLS launched this clinical trial in fall 2016 to test multiple novel targeted therapies at major cancer centers across the U.S., in newly diagnosed AML patients aged 60 and older. In a historic first for cancer clinical trials, LLS is the first non-profit health organization to sponsor a trial and hold the IND (Investigational New Drug) application from the U.S. Food and Drug Administration. Beat AML partnered with Foundation Medicine Inc. to employ next generation genomic sequencing to rapidly analyze the patients’ cancer cells, and identify the patients’ AML subtype so they can be given a targeted therapy within a safe timeframe.

“The breadth of this collaboration, with every clinician, cancer center, pharmaceutical partner and all of the many operations and technical support companies, all unified in working toward the common goal of building a new model for tackling this challenging

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