MinIon handheld sequencing device (Oxford Nanopore Technologies)
15 May 2015. University of Oxford in the U.K. is creating a capital investment fund to help launch spin-off companies based on research from university labs. The £300 million ($US 472 million) fund will be managed by a new enterprise, Oxford Sciences Innovation plc, which will be the university’s preferred capital financier for businesses generated from science, engineering, and mathematics discoveries.
So far the fund attracted some £210 million from six investors: Invesco Asset Management Limited, IP Group plc, Lansdowne Partners (UK) LLP, Oxford University Endowment Fund, the Wellcome Trust, and Woodford Investment Management LLP. The fund expects to raise the remaining £90 million by the end of 2015.
Oxford Sciences Innovation is chaired by David Norwood, founder of IP Group plc that has an 18 percent stake in the enterprise. IP Group plc is an intellectual property commercialization company that says it so far helped finance and build some 20 spin-off businesses from Oxford.
The university is contracting with Oxford Sciences Innovation as its preferred financier for new companies created from labs in its mathematics, physical sciences, life sciences, and medical sciences departments. Isis Innovation, the university’s technology transfer subsidiary, is a partner in creating Oxford Sciences Innovation, and is expected to collaborate with the new entity in bringing new research discoveries to market.
Isis Innovation says it helped create some 100 new enterprises since the year 2000, with 5 of those companies listed on the AIM, a division of the London Stock Exchange for emerging businesses, and 2 companies on the NASDAQ. Among the companies created from University of Oxford labs is Oxford Nanopore Technologies, a developer of portable disease surveillance systems that analyze DNA from blood samples in the field. In March 2015, the company published research showing its MinIon hand-held sequencing device is able to identify a number of bacteria and viruses, and discriminate between closely related species in about 6 hours.
Oxford Nanopore was founded in 2005, which licensed its technology from research by Oxford biochemistry professor Hagan Bayley. The company’s technology is based on straining and isolating individual DNA strands through nanoscale pores in a membrane that allows for electronic sequencing processes to identify the base components of DNA passing through the pore. These nanopores were originally formed in proteins in a lipid membrane, but the company since introduced synthetic materials for nanopores, including graphene.
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Scanning electron micrograph of a human T-cell lymphocyte (National Institute of Allergy and Infectious Diseases, NIH)
14 May 2015. Sanford-Burnham Research Institute and Eli Lilly and Company are collaborating on discovering new therapies for immune system disorders using biotechnology tools. Financial and intellectual property aspects of their agreement were not disclosed.
The partnership aims to combine Sanford-Burnham’s experience in cell communication pathways with Eli Lilly’s work in biotechnology applied to immunological diseases. The organizations expect the collaboration to yield targets for therapies addressing conditions such as lupus, inflammatory bowel disease, Sjogren’s syndrome, and other autoimmune diseases, where the immune system is tricked into attacking healthy tissue and cells.
Lupus — more formally known as systemic lupus erythematosus — is an autoimmune disease that leads to inflammation in the joints, skin, and other organs including heart, lungs, and kidneys. The disorder is more common in women than men, mainly affecting individuals between the ages of 10 and 50. Inflammatory bowel disease results in inflammation of the digestive tract, and includes Crohn’s disease and ulcerative colitis. Sjogren’s syndrome affects the mucous membranes and moisture-secreting glands of the eyes and mouth, causing reduced production of tears and saliva.
The partnership will engage Sanford-Burnham’s Infectious and Inflammatory Disease Center in La Jolla, California, led by molecular biologist Carl Ware. The lab studies intercellular communication pathways controlling immune responses, particularly cell-signaling proteins regulating lymphocytes, white blood cells involved in immune responses, and inflammation. Work by Ware and colleagues led to discovery of therapy targets for immunological and inflammatory diseases and cancer.
Thomas Bumol, Eli Lilly’s senior vice president for biotechnology and immunology research, will co-chair the partnership with Ware. The company says it has therapies in the pipeline for immunological disorders including psoriasis, rheumatoid arthritis, lupus and inflammatory bowel disease. In March 2015, Eli Lilly acquired from Hanmi Pharmaceutical in Korea, an experimental drug that blocks the actions of an enzyme associated with rheumatoid arthritis and other autoimmune diseases.
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Tuberculosis bacteria (DoE.gov)
14 May 2015. A new clinical trial is underway in South Africa testing a regimen of three drugs to treat extensively drug-resistant tuberculosis, a form of the disease that does not respond to normal or even back-up treatments. The trial is sponsored by Global Alliance for TB Drug Development, or TB Alliance, an international consortium of government agencies and foundations.
Extensively drug-resistant tuberculosis is a strain of TB that is airborne and infectious, and develops a resistance to both the normal medications to treat the disease, as well as second-line drugs that are more expensive and come with serious side effects. When faced with extensively drug-resistant TB, patients and physicians face long treatment times trying out drugs that may be more toxic or those not designed to treat TB, often resulting in more serious side-effects and limited chances for success, as well as high rates of death.
While cases of extensively drug-resistant TB are considered rare, TB Alliance says cases have been reported in 100 countries. Centers for Disease Control and Prevention considers extensively drug-resistant TB a risk in the U.S., although a low risk, especially for people with HIV or others with compromised immune systems.
The trial is testing three drugs believed to work differently than earlier medications:
- Bedaquiline, marketed as Sirturo by Janssen Pharmaceuticals
- Pretomanid, a generic anti-bacterial compound
- Linezolid, another antibacterial compound, marketed as Zyvox by Pfizer, but also in generic form
Janssen, a division of Johnson & Johnson, granted a royalty-free license to TB Alliance in 2009 for bedaquiline, which received regulatory approval in some regions as a treatment for TB. Pretomanid is being tested in clinical trials, while linezolid is being used off-label to treat some cases of TB, according to TB Alliance.
The late-stage clinical trial is recruiting 200 patients, age 14 or older, at 3 sites in South Africa with extensively drug-resistant TB or multi-drug resistant TB that does not respond to treatment. The trial is looking primarily at the ability of the drug combination to prevent TB bacteria from reappearing in cultures taken up to 24 months following the treatments. The study is also tracking serious adverse effects of the drugs and activity of the drugs in the body.
TB Alliance is funded by contributions from health, foreign affairs, and assistance agencies in the U.S., Australia, Ireland, U.K., and European Commission, as well as the Bill and Melinda Gates Foundation, UNITAID, and Global Health Innovative Technology Fund. The organization says the new trial is funded by its current donors, but is still seeking contributions to expand the study to more sites.
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DNA molecule display (Christian Guthier, Flickr)
13 May 2015. Mayo Clinic and Baylor College of Medicine are beginning a study of 10,000 human genomes to reveal drug safety problems and highlight where drugs may not work for some people. Financial aspects of the collaboration, involving Mayo Clinic’s Biobank and Baylor’s Human Genome Sequencing Center, were not disclosed.
The research aims to learn more about the role of genes in determining drug safety and effectiveness. Baylor’s Human Genome Sequencing Center will sequence the DNA from blood samples stored in Mayo Clinic’s Biobank, concentrating on 69 genes most associated with the metabolism of drugs in the body. Baylor’s researchers will start with 500 cases to refine the process, then expand to the full 10,000 cases.
The Biobank stores blood samples with associated health and lifestyle information of de-identified Mayo Clinic volunteer patients regardless of their health conditions and makes the data available for researchers. Results of the DNA sequencing will then be added to the health records of the individuals taking part in the study.
The findings aim to highlight genomic factors influencing a person’s reaction to drugs, known as pharmacogenomics, and include those findings in health records to warn of possible adverse reactions to drugs. Results of the analysis will also be tracked for an extended period of time to determine if including pharmacogenomic data in health records improves patient care.
Richard Weinshilboum, who heads the pharmacogenomics program at Mayo Clinic calls the study “a huge step toward bringing knowledge of pharmacogenomics into patient care,” in a Mayo Clinic statement. “Most importantly,” adds Weinshilboum, “it has the potential of preventing errors and identifying the most appropriate drugs and individualized treatments for thousands of patients, thanks to research on the human genome.”
A similar study underway at Mayo Clinic is using data from the Biobank to identify genetics factors to help physicians refine their prescriptions to the right drug in the right dose at the right time. The researchers in this study are recruiting 2,000 Biobank participants to provide a new blood sample for analysis to reveal genetic variations affecting drug absorption, activation, and metabolism.
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Electrostatic image of adeno-associated virus (National Institute of General Medical Sciences, NIH)
13 May 2015. A collaboration between a U.S. biotechnology company and French research institute is enhancing current techniques to allow patients with rare diseases to receive multiple doses of gene therapies. Selecta Biosciences in Watertown, Masachusetts and Généthon in Evry, France plan to co-develop and co-own the results of their partnership, but financial details of the agreement were not disclosed.
Généthon is a research institute developing gene therapies for rare inherited disorders. Gene therapy involves inserting healthy genes into the diseased cells to generate proteins not being produced from mutated genes, or replace defective proteins. According to the institute, as many as 30 million people in Europe suffer from some kind of rare disease.
The collaboration plans to help make gene therapies using current delivery mechanisms more tolerable for patients, thus enabling repeated doses. Those mechanisms harness adeno-associated viruses to deliver healthy genetic material for expressing proteins missing from the mutated or damaged genes causing the disorder. Adeno-associated viruses are benign, naturally occurring microbes that can infect cells. While the viruses do not integrate with the cell’s genome nor cause disease, they can generate a mild immune response.
The Selecta-Généthon partnership aims to eliminate the antibodies and immune responses generated by viral delivery mechanisms, which will make it possible to give patients gene therapies in repeated doses. Under the agreement, Généthon plans to combine Selecta’s synthetic vaccine particle platform with its gene therapies using adeno-associated virus delivery.
Selecta says its synthetic vaccine particle technology generates biodegradable nanoparticles that direct the immune system to prevent and suppress immune responses to specific antigens, thus blocking specific immune responses without compromising an individual’s entire immune system. The company says it successfully tested the technology in preclinical proof-of-concept studies.
Selecta and Généthon believe their approach can be applied to therapies for children, whose organs are still developing. They plan to focus first on therapies for muscular dystrophies and pediatric liver metabolic diseases that use adeno-associated virus deliveries. Muscular dystrophies are a collection of diseases causing progressive weakness and loss of muscle mass, where mutations in genes interfere with production of proteins needed to form healthy muscle. Genetic pediatric liver diseases include hereditary hemochromatosis, Wilson’s disease, and alpha1-antitrypsin deficiency.
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Stéphane Bancel (Brenda Bancel, Wikimedia Commons)
12 May 2015. Moderna Therapeutics, a developer of RNA-based treatments, is starting a new company to design therapies with its technology to address rare diseases. Financial details of the spin-off company Elpidera LLC, the third such venture launched by Moderna, were not disclosed.
Moderna, a biotechnology enterprise in Cambridge, Massachusetts, develops medications that use genetic material to produce therapeutic proteins in the body, with a technology is 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 bodily functions. Moderna designs what it calls modified messenger RNA to produce proteins that act like drugs as treatments for diseases, creating antibodies, and in regenerative medicine, with the potential to cut the time and expense for creating therapeutic proteins over current recombinant methods.
Elpidera LLC plans to apply Moderna’s messenger RNA technology to rare diseases, which Moderna says is a vastly underserved field in pharmaceuticals, with some 7,000 rare diseases identified and few of those adequately addressed by current therapies. In January 2014, Moderna agreed to provide Alexion Pharmaceuticals with 10 product options for treating rare diseases, for which Moderna received $100 million as well as a $25 million equity stake from Alexion. Moderna says the activities of Elpidera LLC will be separate from and not conflict with the work being undertaken for Alexion.
Elpidera is the third spin-off company from Moderna, itself founded in 2010, and the second spin-off in 2015. Moderna says it creates new ventures to allow the enterprises to concentrate on a single clinical area. In January 2015, Moderna started Valera LLC to apply messenger RNA technology to vaccines and infectious diseases. In January 2014, Moderna created a spin-off subsidiary Onkaido Therapeutics that applies messenger RNA technology to cancer treatments, including an early-stage drug discovery partnership with Karolinska Institutet in Sweden.
“The creation of new venture teams is critical to advancing our decentralized drug development business strategy at Moderna,” says CEO Stéphane Bancel in a company statement. “Ventures are the other leg of our strategy to add to the efforts of our pharma and biotech partners. In total, we are driving more than 50 preclinical mRNA programs across cardiovascular, infectious diseases, oncology, and rare diseases.”
Since its founding, Moderna attracted some $600 million in two venture funding rounds, as well as executing license agreements with AstraZeneca, Alexion Pharmaceuticals, and most recently with Merck that will collaborate with Valera LLC on vaccines and infectious diseases. In January 2015, Fortune magazine estimated Moderna has $800 million in cash and is valued at about $3 billion, with none of its therapies yet in human clinical trials.
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Acute myeloid leukemia cells (Cancer Genome Atlas, NIH)
12 May 2015. Researchers from Cold Spring Harbor Lab in New York developed a technique that reveals targets for leukemia drugs with an emerging gene editing technology. A team from the lab of geneticist Christopher Vakoc published its findings yesterday in the journal Nature Biotechnology (paid subscription required).
Vakoc and colleagues study proteins regulating chromatin, the substance of DNA and proteins in the nucleus of cells that form chromosomes, and their role in cancer. In 2011, a team from the lab identified a protein that supports production of acute myeloid leukemia cells, as well as a pocket on the surface of cancer cells where the protein binds. Their discovery led to identification of an existing drug on the market — JQ1, a male contraceptive — that blocks the protein from binding, thus preventing the growth of that type of leukemia and causing the death of cancer cells.
While that discovery highlighted the role of identifying proteins that bind to pockets on cancer cells, the team sought a more scalable process for screening genes and proteins than the one used in the first study. That search led to CRISPR, short for clustered regularly interspaced short palindromic repeats, working with CRISPR-associated protein 9 or Cas9, an emerging technology that makes it possible to identify and repair specific genes needing repair, such as those causing inherited diseases.
In this case, the researchers were more interested in identifying proteins associated with binding to pockets on cell surfaces, which is why they found CRISPR-Cas9 is attractive. In editing genomes, CRISPR-Cas9 identifies specific genes and variations of those genes, especially disease-causing mutations, needing repair. The Cold Spring Harbor team used that same capability to identify genes encoding protein chemistries that bind to the pockets on specific cancer-causing cells.
The technique devised by the researchers alters DNA codes to simulate mutations in the gene changing the pockets used by proteins to bind to cells, and screening for proteins that fit into those pockets. Those proteins could either encourage proliferation of cancer cells or block the binding of cancer-supporting proteins. “If you change the pocket so the protein is no longer functional and you find the cancer can’t survive, then you have a good shot at a useful drug target,” says Vakoc in a Cold Spring Harbor statement. “We can’t tell if any particular pocket will lead to a fully effective drug; but this is a way to annotate every critical pocket in cancer cells.”
The researchers tested the concept on 192 chromatin protein collections from mouse models of acute myeloid leukemia cells. The team identified 6 known proteins associated with the disease. But the researchers also identified 19 other proteins with at least the potential of blocking cancer-supporting proteins from binding to cells. The 19 targets were not previously known to have these binding-blocking properties.
Vokoc’s lab is now applying this technique to targets of greatest interest to pharmaceutical companies. “We want to have an impact on cancers in the near-term,” says Vakoc. “We want to provide pharmaceutical companies the kind of targets that they have extensive experience figuring out how to hit.“
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(Aweisenfels, Wikimedia Commons)
11 May 2015. A clinical trial testing an experimental neurostimulation device to treat obstructive sleep apnea implanted the device in its first two test patients. The trial is sponsored by ImThera Medical Inc. in San Diego, the developer of the aura6000 device being tested.
Obstructive sleep apnea is a disorder where muscles in the throat intermittently relax and block the airway during sleep, causing snoring and repeated stopping and starting of breathing. The pattern of repeated breathing stoppages can interrupt regular sleep, resulting in disrupted sleeping routines. The condition can lead to daytime fatigue from lack of sleep and cardiovascular complications, such as high blood pressure and abnormal heart rhythms. The disorder can also make it more difficult to administer sedatives and general anesthesia.
ImThera Medical developed the aura6000 system, a device using electronic pulses to stimulate the nerve in the brain controlling the tongue. The system uses principles of neurostimulation to prevent the tongue from falling back and blocking the airway. The company says the short bursts of electronic pulses are delivered to an electrode positioned under the skin near the lower jaw, from a pulse generator implanted in the chest, to stimulate the hypoglossal nerve controlling tongue muscle movements.
The clinical trial is testing the aura6000 device among 141 individuals in the U.S. and Europe with moderate to severe obstructive sleep apnea, who did not respond or cannot tolerate usual therapies, such as positive airway pressure and oral appliances. All participants will have the device surgically implanted, but the half of the group, randomly selected, will have the system turned on after 1 month. The other half of the group will receive the usual standard of care for sleep apnea. Participants will be evaluated after 4 months, on the number of sleep interruption events per hour and blood oxygen levels, as well as safety indicators, including serious adverse events.
ImThera conducted two previous clinical trials for safety and efficacy of the aura6000. The company received a CE mark in March 2012, clearing the device for marketing in Europe. The new clinical trial is aimed at providing evidence to support an application for similar approvals from the U.S. Food and Drug Administration.
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Scanning electron micrograph of HIV particles infecting a human T cell (NIH.gov)
11 May 2015. Pharmaceutical maker GlaxoSmithKline and University of North Carolina in Chapel Hill are establishing a joint research center and spin-off company to develop new treatments for HIV and AIDS. GSK says it plans to invest $20 million over 5 years for a new HIV Cure Center on the Chapel Hill campus to conduct research, and to start Qura Therapeutics, the spin-off company to take the discoveries to market.
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.
The HIV Cure Center is expected to build on advances in finding treatments for HIV and AIDS that go beyond management of the disease to removal from individuals of all traces of the virus. Recent research in the university’s Collaboratory of AIDS Researchers for Eradication aims to find residues of the virus left behind from previous treatments that can linger in the body, causing long-term health problems. Therapies based on this approach seek to strengthen the immune system to enable the individual to remove these residual traces the virus and infected cells.
For the HIV Cure Center, the university will provide lab space at its medical school in Chapel Hill where researchers from the company are expected to work with scientists on campus. GSK will offer its expertise in drug discovery and development, while the university provides its experience in basic and translational research, as well as access to patients.
The partners created Qura Therapeutics to handle business aspects of turning lab discoveries into therapies. Qura is expected to be responsible for issues involving intellectual property, commercialization, manufacturing, and governance. GSK is also part-owner of Viiv Healthcare in Brentford, U.K., with Pfizer and Shionogi in Japan, developing antiretoviral treatments for HIV that is expected to advise Qura Therapeutics.
The partners say the combination of academic and commercial approaches is a new and badly needed model to go beyond management of HIV. “After 30 years of developing treatments that successfully manage HIV/AIDS without finding a cure,” says David Margolis, director of Collaboratory of AIDS Researchers for Eradication in a joint statement, “we need both new research approaches to this difficult medical problem and durable alliances of many partners to sustain the effort that will be needed to reach this goal.”
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Mars surface and atmosphere, from NASA’s Mars Atmosphere and Volatile EvolutioN, or MAVEN, mission. (NASA.gov)
8 May 2015. NASA is asking the public for ideas on ways to establish a long-term presence of Mars in a new challenge offered by InnoCentive. The competition has a total purse of $15,000 and a deadline for submissions of 6 July 2015. InnoCentive in Waltham, Massachusetts conducts open-innovation, crowdsourcing competitions for corporate and organization sponsors, in this case NASA.
NASA is well underway developing systems for reaching Mars, and technologies for orbiting the planet and exploring its surface. Once on Mars, the space agency plans to establish a presence in what it calls “pioneering space,” and is seeking new techniques and methods that can enable crews to function independently from Earth. Innovative solutions are needed, says the agency, because of infrequent resupply schedules — a minimum of 500 days between resupply opportunities — and size limitations of space craft.
To address these limitations, NASA is looking for technical proposals to establish or enhance a sustained human presence on Mars describing the capabilities to be developed and the steps needed in the short and long terms, to achieve those capabilities. Proposals can include approaches, individual systems, or sets of integrated systems.
The space agency says submissions should include assumptions, analyses, and data to support them. Submissions should also include processes to develop, test, implement, and operate the proposed systems. Proposals will be evaluated on relevance, creativity, simplicity, resource efficiency, feasibility, comprehensiveness and scalability.
InnoCentive calls this type of competition a theoretical-licensing challenge, where the sponsor is looking for ideas that are not yet at the proof-of concept stage, but participants still need to provide enough details in their proposals to describe the feasibility of their ideas. As the sponsor, NASA is seeking a non-exclusive license to implement ideas in participants’ proposals; participants do not need to relinquish all intellectual property rights. Nor does NASA seek rights to any ideas not winning awards.
Prizes will be awarded in increments of $5,000, up to a total of $15,000. Up to 3 prizes will be awarded, but NASA says no number of prizes is guaranteed.
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