(Suresh Subbaiah, Wikimedia Commons)
14 January 2016. The online company Yahoo is releasing an extensive data set of individual user interactions with some of its popular services to the academic community as raw material for studies of machine learning. The de-identified data sets will be part of Yahoo’s Webscope reference library offered to academic researchers.
The data sets cover individual interactions with Yahoo’s news, sports, finance, movies, and real estate sections, as well as its home page. The collection, says the company, has some 110 billion items accessed by with 20 million users, from February to May 2015. The entire uncompressed file is estimated to be 13.5 terabytes of data.
Items in the data set are identified by their titles, summary, and key phrases. Data on individuals accessing those items give their gender, age range, and generalized geographic location. Interactions with the items show the user’s local date and time, and some data about the device employed.
Yahoo’s Webscope program provides data sets for academic researchers and students covering computer systems, languages, images, graph and social data, ratings and classification data, as well as competition, advertising, and marketing data. The Webscope databases are part of Yahoo Labs, doing research in a range of fields related to the company’s business and services including, advertising, computer science, information and knowledge management, human-computer interactions, and machine learning.
In a statement, the company cites computer scientists planning on using the data sets. Gert Lanckriet at University of California in San Diego says “Access to data sets of this size is essential to design and develop machine learning algorithms and technology that scales to truly ‘big’ data.”
Tom Mitchell at Carnegie Mellon University adds, “Academic researchers everywhere will finally have access to realistic scale data to study how to automatically discover which news articles are of interest to which users, and will be able to compare their methods using this as a shared test case.”
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(Arthur Toga, UCLA/NIH.gov)
13 January 2016. Pharmaceutical companies Boehringer Ingelheim and Arena Pharmaceuticals Inc. are collaborating on discovery of new therapies for schizophrenia and other neurological disorders. The partnership could bring Arena, in San Diego, as much as $262 million.
Arena Pharmaceuticals is a biopharmaceutical company developing therapies for disorders related to G protein-coupled receptors, or GPCRs, proteins that appear on the surface membranes of cells and act as gateways for other proteins, sugar, lipids, and energy. GPCRs are involved in a wide range of biological signaling functions, with about 1,000 of these receptors in humans, each receiving specific signals.
The company’s technology discovers and develops drugs acting on GPCRs with known and unknown connecting molecules, called ligands, resulting in agonists that activate, or inhibitors that block or minimize the receptors. Arena says it can identify both agonist and inhibitor drug leads for specific GPCRs, either with our without knowing the connecting ligands. GPCRs, where the connecting ligands are unknown, are called orphan GPCRs.
The new agreement between Boehringer, in Ingelheim, Germany, and Arena covers an unspecified orphan GPCR associated with central nervous system functions. The deal gives Boehringer exclusive rights to the Arena’s intellectual property related to this GPCR, as well as any compounds developed internally from that intellectual property. Arena and Boehringer will jointly discover additional compounds that may be suitable for development, with Boehringer gaining a global license to develop and commercialize products resulting from the collaboration.
In return, Arena is eligible to receive up to $262 million in research funding, and initial and milestone payments. The companies did not disclose further financial details of the agreement.
Arena already has one product lorcaserin, approved by FDA in 2013 as a weight management drug, and marketed as Belviq. The company is discovering and developing other applications of lorcaserin for cardiovascular conditions related to diabetes and smoking cessation. Other candidates in Arena’s pipeline include drugs for blood clots, pulmonary arterial hypertension, autoimmune disorders, pain, and neurological disorders.
Neurological disorders is one of Boehringer’s four disease research areas, recently expanded to include psychiatric conditions. The company says it plans to discover new drugs for cognitive impairment and negative symptoms associated with schizophrenia, depression, impulsiveness, Alzheimer’s disease, and Parkinson’s disease.
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Gas-sensing intestinal capsule (RMIT University)
13 January 2016. A team at RMIT University in Australia developed a device, swallowed like a pill, that measures gas concentrations in the intestine and sends its data to an outside receiver. Proof-of-concept results from tests with pigs appear in the January 2016 issue of the journal Gastroenterology.
Researchers led by RMIT engineering professor Kourosh Kalantar-zadeh are seeking better techniques for detecting and measuring different gases produced in the gut, which can serve as indicators of disease in the gastrointestinal tract. Current sampling methods involve insertion of tubes that often are invasive and inconvenient. With a less invasive and easy-to-use device, clinicians could get better and earlier indications of disorders such as colon cancer, irritable bowel syndrome, and inflammatory bowel disease.
Kalantar-zadeh — with colleagues from RMIT, Monash University, University of Melbourne, and Australia’s Commonwealth Scientific and Industrial Research Organisation — developed a device about the size and shape of drug capsule. The system features a gas sensor, microcontroller, wireless transmitter, and silver oxide battery, inside a gas-permeable membrane, covered by non-digestible coating. The device transmits data every five minutes to a nearby receiver that analyzes and stores the transmissions, as well as displays profiles of the gases detected.
The device was tested with pigs, which have gastrointestinal organs similar in size and function to humans, feeding the pigs diets either high or low in dietary fiber that the team could compare to published benchmarks. Some of their findings, say the researchers, are quite different from many assumptions about fiber content and digestive gases.
“We found a low-fiber diet produced four times more hydrogen in the small intestine than a high-fiber diet, “says Kalantar-zadeh in a university statement. “This was a complete surprise because hydrogen is produced through fermentation, so we naturally expected more fiber would equal more of this fermentation gas.”
This finding could have implications for people with irritable bowel syndrome, sometimes associated with bacterial overgrowth in the small intestine, who could benefit from a high-fiber diet. Other findings show no change in the ratio of methane to carbon dioxide in the large intestine, between high- and low-fiber diets, suggesting changes in dietary fiber would not help people with disorders linked to excess methane concentration.
The researchers plan to improve and refine their smart pill. adding sensors for oxygen, pH, vapor,and other gases. The device, which the team says could transmit data to a mobile phone, also needs to be reduced in size, and made more reliable and durable.
“We hope this technology,” adds Kalantar-zadeh, “will in future enable researchers to design personalized diets or drugs that can efficiently target problem areas in the gut, to help the millions of people worldwide that are affected by digestive disorders and diseases.”
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RNA molecule illustration (Nicolle Rager Fuller, National Science Foundation)
12 January 2016. The Bill and Melinda Gates Foundation is backing a biotechnology company’s early development of antibodies to treat human immunodeficiency virus or HIV based on RNA, nucleic acids expressed by a person’s genetic code. The foundation is supporting the work of Moderna Therapeutics, in Cambridge, Massachusetts, with an initial $20 million grant, and options for follow-up projects on other infectious disease therapies with additional funding of up to $80 million.
While research over the past 30 years is advancing the understanding of HIV and new treatments are making the condition more manageable, HIV and AIDS continue to be a critical public health problem. In the United States alone, according to Centers for Disease Control and Prevention, some 1.2 million are living with HIV, as some 50,000 new cases are reported each year. The agency estimates 14 percent of people with HIV do not know they have the condition. Worldwide some 35 million people are living with HIV, of which 3 million are children, according to World Health Organization.
Moderna develops medications that use genetic material to produce therapeutic proteins in the body, with a technology based on research licensed from Harvard University and MIT. That technology harnesses messenger RNA, a nucleic acid related to DNA delivering genetic code used by cells to produce the amino acids in proteins for carrying out human functions. Moderna designs what it calls modified messenger RNA to produce proteins that act like drugs as treatments for diseases, creating antibodies with the potential to cut the time and expense for creating therapeutic proteins over current recombinant methods.
The Gates Foundation funding supports Moderna’s work, through the company’s Valera LLC subsidiary formed about one year ago, to test antibodies created with messenger RNA to treat HIV infection. Valera develops vaccines and therapies from engineered messenger RNA designed to express viral antigens and induce an immune response. The new project calls for Valera to test a combination of antibodies as HIV therapies in preclinical studies, as well as conduct early-stage clinical trials.
Yesterday, Moderna and Valera revealed a licensing deal with the pharmaceutical company Merck for a vaccine code-named mRNA 1566 to address an undisclosed viral disease target. Moderna already had a partnership agreement with Merck, which this new deal supplements. Under the new agreement, Merck will lead further development and commercialization, while paying Moderna upfront and milestone payments, as well as royalties on sales.
Moderna and Valera also disclosed yesterday another vaccine candidate code-named mRNA 1440 will soon begin early-stage clinical trials in Europe. The announcement was made in the context of Moderna becoming a clinical-stage biotechnology company in 2015. Science & Enterprise reported on Moderna several times since its founding in 2010.
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12 January 2016. A team from Institut Pasteur in French Guiana sequenced the complete genome of the Zika virus, a mosquito-borne pathogen causing disease outbreaks in tropical regions, including the Americas. Findings from the analysis appeared last week in the journal The Lancet.
The Zika virus causes fever, with rash, joint pain, and conjunctivitis, also known as pink eye. Most symptoms reported are mild, but Centers for Disease Control and Prevention says the virus is linked in Brazil to infections in pregnant women and subsequent birth defects, as well as Guillain-Barré syndrome and other neurological disorders. There are no vaccines to prevent or treatments for Zika virus infections. Avoidance of mosquitoes is the only known control.
The virus is spread by Aedes species mosquitoes, also associated with dengue and chikungunya viruses. Sporadic Zika virus outbreaks were reported in Africa and Asia, but an epidemic broke out in 2013 in French Polynesia, which spread to other Pacific islands. In 2015, outbreaks first occurred in northeast Brazil, and later spread to Colombia and Suriname in the fall of 2015. In Brazil alone, as many as 1.3 million cases are suspected. CDC says Puerto Rico reported its first Zika case in December 2015.
The team from Institut Pasteur’s virology lab in Cayenne, French Guiana, led by biologist Dominique Rousset, confirmed and isolated the virus from the first five cases of Zika in Suriname. Rousset and colleagues analyzed the viral genomes from blood serum in four of the individuals with reverse transcription-polymerase chain reaction, or RT-PCR. This technique detects and quantifies gene expression with micro-RNA, even from samples as small as a single cell.
The team was able to sequence the complete Zika virus genome from one of the individuals. The results show the genome in Suriname is almost completely identical to proteins found in the strain that infected French Polynesia in 2013.
“Until now.” says Rousset in an Institut Pasteur statement, “few complete sequences of this virus and none of the strains currently circulating in South and Central America were available. This complete sequence of the virus is a major starting point for shedding light on how its behavior develops.”
Institut Pasteur says 17 cases of Zika virus are now reported in French Guiana, with 3 more reported in Martinique, a French possession in the eastern Caribbean. A team from Institut Pasteur’s branch in Dakar, Senegal is assisting health authorities in Brazil with that outbreak.
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(AllanAjifo, Wikimedia Commons)
11 January 2016. Two clinical trials testing stem cells to treat amyotrophic lateral sclerosis, or ALS, found the treatments are safe for patients, and can slow progression of the disease. Results of the trials testing the stem cell product known as NurOwn made by BrainStorm Cell Therapeutics in Petach Tikvah, Israel are reported today in the journal JAMA Neurology (paid subscription required).
ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease where neurons or nerve cells controlling muscles in the body begin to waste away, and can no longer send or receive signals from the brain or spinal cord. As the nerve cells stop functioning, the muscles in the limbs, and later speech and breathing muscles, begin weakening and eventually stop functioning. Most people with the disease die of respiratory failure.
BrainStorm’s NurOwn technology extracts stem cells from the patient’s bone marrow that are transformed into cells supporting development of nerve cells. These transformed stem cells, says the company, secrete proteins called neurotrophic factors that protect nerve cells, as well as encourage their growth and interactions with muscles. Because the original cells come from the patient, they have little risk of rejection by the immune system.
The clinical trials are early and intermediate-stage studies testing the safety and clinical benefit of NurOwn, conducted at Hadassah Hebrew University Medical Center in Jerusalem. The studies recruited 12 and 14 patients respectively in the early stages of ALS. The 12-participant trial looked primarily for safety and tolerability of stem cell treatments, but also took note of progression rates of the disease, as well as forced exhaling capacity, muscle strength and bulk, overall survival, and other indicators on a standard scale of ALS functionality. The trial with 14 participants had similar objectives and measures, but also tested three dosage levels of NurOwn treatments.
In the 12-participant study, 6 patients received injections of stem cells, while 6 patients with more advanced cases received stem cell transplants. In the 14-patient study, participants received a combination of injections and transplants. In both studies, participants were evaluated 3 and 6 months after receiving their treatments.
The results show participants in both studies experienced no more than mild or transient adverse effects from the treatments, and were well tolerated. The findings show as well slower progression of the disease, as indicated by a slower declines in forced exhale capacity and scores on ALS functionality rating scales, although the rating scale differences were not large enough to be statistically reliable. The researchers also found slower declines in muscle mass over that period.
BrainStorm today announced plans for another intermediate-stage trial of NurOwn treatments with 24 ALS patients at Hadassah medical center. Dimitrios Karussis, professor of neurology at Hadassah, will lead the study; he was also principal investigator for the earlier trials at Hadassah. The new study will test three dosage levels of NurOwn treatments, to help prepare for a late-stage clinical trial that compares treatment results to a placebo.
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Scanning electron micrograph of a human T-cell lymphocyte (National Institute of Allergy and Infectious Diseases, NIH)
11 January 2016. Juno Therapeutics is gaining single-cell sequencing technology for cancer immunotherapies through the buy-out of biotechnology company AbVitro Inc., and licensing part of that technology to pharmaceutical company Celgene Corp. The AbVitro acquisition is valued at about $125 million, while financial details of the licensing deal with Celgene are not disclosed.
Juno Therapeutics, in Seattle, is a spin-off enterprise from Fred Hutchinson Cancer Research Center in Seattle, Memorial Sloan-Kettering Cancer Center in New York, and Seattle Children’s Research Institute, founded in 2013. The company employs two technologies to encourage white blood cells in the immune system, known as T-cells, to target invading cancer cells without damaging healthy tissue. One process genetically modifies T-cells with molecules called chimeric antigen receptors to better identify and attack cancer cells on their own, without invoking immune-system signals that could target non-cancerous cells.
The second technique, known as T-cell receptors, also reprograms T-cells by adding molecules known as human leukocyte antigens that target corresponding proteins in tumors. The company harvests blood cells from cancer patients and separates their T cells for enrichment with the required genetic sequences in the cells’ DNA, then grown in the lab into dosage quantities for infusion back into the patient. In the body, the engineered T-cells multiply in the presence of target proteins and attack their corresponding tumor cells.
AbVitro, in Boston, is a spin-off company from the Harvard Medical School lab of geneticist and genomics pioneer George Church, a co-founder of the company. Its technology harnesses high-throughput genomic sequencing of millions of tumor and blood cells to identify antigen and T-cell receptors for cancer immunotherapies. This simultaneous, paired identification process, says AbVitro, makes it possible to highlight specific cancer targets and develop more effective therapies with binding molecules that recognize those targets.
Through the acquisition, Juno says it plans to continue development of AbVitro’s cancer immunotherapies, as well as adapt the technology for better tests of immune system responses to cancer, and to track the treatment of patients receiving immunotherapies. Under the deal, AbVitro shareholders receive $78 million in cash, and 1.3 million shares of Juno stock, valued at about $47 million. AbVitro staff are expected to relocate to Seattle, and company founder Church will become an advisor to Juno.
Celgene Corp., in Summit, New Jersey, and Juno are already collaborators on two of Juno’s therapy candidates for blood-related cancers, with Juno gaining access to Celgene’s T-cell programs, in a $1 billion licensing deal last June, reported in Science & Enterprise. Under the new agreement, Celgene receives rights to a subset of the acquired AbVitro single-cell sequencing technology, as well as options on products developed from that technology.
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Cross-section of muscle tissue from a person with Duchenne muscular dystrophy shows extensive replacement of dark colored muscle fiber with light-colored adipose or fat cells. (Centers for Disease Control and Prevention)
8 January 2015. Grünenthal Group, a German pharmaceutical company, is licensing a treatment candidate for Duchenne muscular dystrophy developed by Akashi Therapeutics, a biopharmaceutical company created by organizations advocating for research on the disease. While full financial details of the agreement were not disclosed, Grünenthal says it’s committing more than $100 million to the venture.
Duchenne muscular dystrophy is a rare genetic disorder resulting in progressive muscle degeneration and weakness, primarily in the shoulders, arms, hips, and thighs. The disease affects mainly boys starting at age 3 to 5, and caused by a defective gene that fails to produce the protein dystrophin for strengthening muscle fiber and protecting muscles from injury. While life expectancy can vary, people with Duchenne muscular dystrophy do not often survive past their 20s or 30s, with death caused by respiratory or cardiac failure.
The deal involves Akashi’s drug candidate code-named HT-100. Akashi Therapeutics, in Cambridge, Massachusetts was founded by patient advocacy organizations Charley’s Fund and Nash Avery Foundation expressly to find therapies for Duchenne muscular dystrophy. HT-100 is a delayed release formulation of halofuginone, a derivative the compound febrifugine found in the roots of a Chinese hydrangea plant known as chang sham, long associated with herbal treatments for malaria, fibrosis, and inflammatory diseases.
Akashi designed HT-100 as a small-molecule candidate to reduce fibrosis and inflammation, as well as regenerate healthy muscle fiber in patients with Duchenne muscular dystrophy. HT-100 is in an intermediate-stage clinical trial with 30 participants at 4 sites in the U.S. The drug is designated an orphan therapy by regulators in both the U.S. and Europe, and is granted fast-track review status in the U.S.
Up to recently, Grünenthal Group in Aachen, Germany developed treatments solely for pain and inflammatory disorders, but broadened its focus in 2014 to niche markets addressing unmet medical needs. Under the agreement, Grünenthal is providing Akashi with unspecified initial and milestone payments, and will fund development and commercialization beyond intermediate-stage clinical trials. Akashi will also be eligible for royalties on net sales in the U.S. Grünenthal says it plans to put more than $100 million into the initiative.
Akashi is also working on a muscle-building compound code-named DT-200, which the company says is ready for early-stage efficacy trials. In addition, Akashi is developing AT-300, a modified peptide derived from the venom of the Chilean Rose Tarantula that targets calcium imbalance in muscles, considered an early trigger of later weakening and loss of muscle function. In 2010, Science & Enterprise reported on development of this therapy at University at Buffalo, which was licensed to Tonus Therapeutics, a start-up company for development. Akashi acquired the technology from Tonus in 2014.
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Downtown Vancouver (Magnus Larsson, Flickr)
8 January 2016. Two biotechnology companies in Vancouver agreed to collaborate on developing antibody treatments for cancer, with an option to merge their enterprises later on. The deal calls for Zymeworks Inc. to make an undisclosed equity investment in Kairos Therapeutics Inc. Zymeworks is also receiving $US 61.5 million in its first venture funding round.
Zymeworks creates engineered antibodies that bind to two targets or epitopes, the parts of antigens that generate an immune response. This design concept, says Zymeworks, enables its antibodies to address complex diseases that require more than one line of attack, as well as combining multiple treatments similar to a cocktail in one therapy. Despite the novel design, says the company, these bi-specific antibodies can be made with today’s monoclonal antibody processes.
Zymeworks also develops antibody drug conjugates, the focus of Kairos’s technology. Antibody drug conjugates combine highly targeted antibodies with chemotherapy drugs, with the potential for fewer side effects than traditional chemotherapy. Kairos Therapeutics is a two-year-old spin-off enterprise from the Centre for Drug Research and Development, an applied pharmaceutical R&D lab in Vancouver, that licensed its antibody drug conjugate technology to Kairos for commercial development. The company says its approach to antibody drug conjugates makes them feasible for precision medicine that can target therapies more directly with fewer side effects.
Kairos and Zymeworks will collaborate initially on antibody drug conjugate therapies for cancer. The agreement gives the enterprises an option to merge later on, which would make it possible to combine their respective technologies and pipelines for other cancer therapies. The companies gave no timetable for the current partnership nor a target date for merger.
Zymeworks is also raising $61.5 million its first venture funding round. Up to now, the four-year-old company was funded by private investments and licensing deals with pharmaceutical companies Merck, Eli Lilly and Company, and Celgene. The new financing is a mezzanine investment, a hybrid of debt and equity capital where loans can be converted to equity ownership. The funding round was led by new investors BDC Capital and Lumira Capital, with participation by Eli Lilly, Celgene, and a syndicate of Canadian and U.S. investors.
The new funding, says Zymeworks, is expected to underwrite the company’s lead Azymetric platform developing bi-specific antibodies. The company’s most advanced therapy candidates are ZW25 and ZW33, engineered bi-specific antibodies addressing overexpressed HER2 proteins associated with breast cancer, with ZW33 adding an antibody drug conjugate. Zymeworks expects to file new drug applications to authorize clinical trials later this year.
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Minicare blood analysis device (Royal Phillips)
7 January 2016. A collaboration between electronics manufacturer Royal Phillips and medical diagnostics company Banyan Biomarkers Inc. is developing a handheld blood test for concussions and other mild traumatic brain injuries. Financial and intellectual property aspects of the partnership were not disclosed.
Traumatic brain injury is caused by a blow or jolt to the head, as well as injuries where the skull is penetrated. Not all bumps to the head cause injury, but when normal functions of the brain are affected, traumatic brain injury occurs, with mild injuries, known as concussions, the most common form. Centers for Disease Control and Prevention says some 2.5 million emergency room visits, hospitalizations, or deaths in the U.S. were attributed to traumatic brain injury in 2010, leading to 50,000 fatalities.
Diagnosing concussions quickly and conclusively is difficult, because symptoms are not always evident, and may not be detected even with CT scans. Diagnosis is particularly tricky with athletes. From 2001 to 2009, reports CDC, traumatic brain injuries related to sports or recreation increased by 57 percent among children, age 19 or younger.
Banyan Biomarkers, in San Diego, licenses research from University of Florida to commercialize lab tests that detect brain injury and neurological diseases. The company’s technology assesses proteins in blood and other bodily fluids with antibodies associated with specific disorders, which in this case can also be quantified to estimate the extent of brain injury. Banyan tested the technology in several clinical studies identifying two biomarkers in blood serum and plasma for traumatic brain injury.
Royal Phillips, based in Amsterdam, and Banyan will develop a blood test for mild brain trauma that can be administered and return results at the point of care. The system will adapt Phillips’s Minicare blood testing device that returns results in a few minutes. The device requires a pinprick blood sample analyzed with a sensor in a replaceable cartridge and dedicated software. The sensor in this case will be configured to detect the target molecules identified by Banyan.
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