19 August 2014. HealthQuest Capital, a spin-off investment firm, says it raised $110 million for funding in technology-based start-ups serving the health care industry. The company was spun off from Sofinnova Ventures in Menlo Park, California and founded by Garheng Kong, a Sofinnova general partner.
HealthQuest plans to invest in companies developing medical devices, diagnostics, patient-care products, mobile health, and health care information technologies. The company says it is particularly interested in new enterprises that can show quantifiable benefits in terms of patient care and health care economics. “It is our strong belief,” says the HealthQuest Web site, “that the winning formula for emerging companies in health care is to have a strong story in both these areas.”
The company aims to target newer enterprises in North America, but those beyond the initial start-up stage, where investments can help grow revenues and scale-up operations for the marketplace. Pre-launch businesses will be considered, if commercial operations are imminent and can show evidence of likely market adoption. Investments will generally be in the range of $2 to $4 million, for companies with capital needs less than $20 million to reach profitability.
HealthQuest started last year, and its portfolio already includes Castle Biosciences developing molecular diagnostics for cancer and First Aid Shot Therapy, commercializing over-the-counter medications as single liquid doses of 40 milliliters or 1.35 ounces (A shot glass holds about 45 milliliters or 1.5 ounces.). A third portfolio company, Vestagen Technical Technologies in Orlando, Florida, develops antimicrobial and other specialized textiles with a process licensed from researchers in Switzerland.
HealthQuest first aimed at raising $50 million in its first fund, but the response from investors was particularly strong, thus the fund remained open until reaching $110 million. The company expects to make a total of 12 investments from that fund. HealthQuest remains affiliated with Sofinnova Ventures that provides back-office support.
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Microscopic view of umbilical cord (Josef Reischig, Wikimedia Commons)
19 August 2014. Gamida Cell, a developer of therapies from umbilical cord stem cells, says the global pharmaceutical company Novartis is buying a 15 percent interest in the company, with an option to acquire the entire company later. The deal brings Gamida Cell, located in Jerusalem, Israel, $35 million immediately, with a total potential return of $600 million if the full acquisition goes through.
Gamida Cell designs therapies based on stem cells derived from umbilical cord blood, a potentially rich source of regenerative cells to treat blood-related diseases including anemia, leukemia, and lymphoma. A limitation of cord blood stem cells is the small number that can be generated at any one time. Gamida’s technology expands the number of available cells with epigenetic techniques — changes in gene expression outside of DNA — and cultures based on low molecular weight compounds.
The company’s lead product is StemEx, offered as an alternative when an exact bone marrow transplant cannot be found. Cord blood transplants do not require the same precise match as bone marrow. StemEx completed a late-stage clinical trial as a treatment for blood-related cancers leukemia and lymphoma.
Gamida Cell’s more recent technology applies nicotinamide, a derivative of vitamin B3 to expand the functionality of cultured cord blood stem cells. This technology is the basis for the company’s NiCord product, currently in early and intermediate stage clinical trials as a treatment for blood related cancers, as well as sickle-cell anemia.
Another nicotinamide-based product, CordBridge, completed preclinical tests as a treatment for acute radiation syndrome. A related NK Cells (for natural killer) product completed preclinical tests as an immunotherapy for solid tumor cancers.
Under the deal, Novartis will acquire 15 percent of Gamida Cell’s stock for $35 million. Should Novartis exercise the option to buy the entire company, Novartis will pay Gamida Cell’s shareholders — mainly other biotechnology and pharmaceutical companies, as well as venture investors — $165 million. The full-acquisition option will be available for a limited, but undisclosed, period of time, and is contingent on the achievement of certain milestones in the development of Gamida’s NiCord product in 2015.
If the full acquisition goes through, Gamida Cell’s shareholders will also be eligible for another $435 million in payments, based on reaching certain development and regulatory milestones, as well as royalties on sales.
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Jennifer Elisseeff (Johns Hopkins University)
18 August 2014. Biomedical engineers at Johns Hopkins University in Baltimore developed a synthetic lubrication fluid for natural or artificial joints in the body that emulates the properties of natural substances. A team led by Johns Hopkins medical professor Jennifer Elisseeff published its results earlier this month in the journal Nature Materials (paid subscription required).
Knees, hips, and elbow joints have a naturally-produced lubricant called hyaluronic acid found in the joints’ synovial fluid, a viscous substance that resembles motor oil. Hyaluronic acid also helps joints protect against inflammation and metabolic damage.
As people age or the joints become damaged, however, concentrations of hyaluronic acid become lower, leading to pain. The lower concentrations are believed to result from the lack of a key protein that binds hyaluronic acid to joint surfaces.
Some patients with osteoarthritis, the common wear and tear on joints as people age, try injections of hyaluronic acid to restore the joints’ natural lubrication, a treatment known as viscosupplementation. The technique, however, often requires several weeks to take effect and in a systematic review of clinical trials, showed little benefit for relieving pain or improving joint function. The review also showed viscosupplementation increases the risk for adverse effects.
One of the reasons for the limited benefit of viscosupplementation is the inability of joints to retain hyaluronic acid, which gets washed away by the body’s natural cleansing process. Elisseeff and colleagues sought to remedy this property by devising peptides, short chains of amino acid molecules, that are tethered to biocompatible polymers, but also bind with hyaluronic acid molecules.
The Johns Hopkins team tested these binding peptides with both natural and artificial cartilage samples in the lab, and later in the knees of lab rats. The tests used the binding peptides with polyethylene glycol, a common biocompatible polymer, to connect the hyaluronic acid with cartilage tissue in both the samples and animal tests.
The researchers found the engineered binding peptides/hyaluronic acid compound reduces friction as well as natural hyaluronic acid. When injected into the knees of lab rats, the tests show the engineered compound lasts 12 times as long as natural hyaluronic acid. The results suggest the compound could be a useful addition to viscosupplementation, as well as a coating for replacement joints.
“What I like about this concept,” says Elisseeff in a university statement, “is that we’re mimicking natural functions that are lost using synthetic materials.” Elisseeff and a colleague filed a patent application last year covering biomaterials combining binding peptides with biocompatible polymers for retaining hyaluronic acid and other tissue engineering applications.
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18 August 2014. A new challenge sponsored by National Institutes of Health is looking for better ways to follow and predict the functioning of a single cell in a complex multi-cell environment, such as in a tumor or a response to treatment. The competition, managed by the open-innovation/challenge company InnoCentive, expects to award prizes totaling up to $500,000. The first deadline for submissions is 15 December 2014 (free registration required).
The challenge, says NIH, is driven by the need to more precisely determine the actions of cells as they behave in the body. The assumption that individual cells of a certain type or in a given population act alike can obscure important differences in functioning, which can have profound implications for detecting and treating diseases. As a result, better techniques are needed to track the behavior and functions of individual cells.
Several methods today can be used to analyze individual cells, says NIH, including mass spectometry, optical technologies, sensors, and electrochemical methods. They generally lack the ability, however, to analyze cell states and performance in a dynamic environment. The challenge, therefore, aims to find new tools for assessing functional changes in individual cells over time as they alter their states, such as becoming cancerous, infected with a virus, or resistant to drugs.
The competition has two stages. In the first stage, participants will submit proposals, due 15 December, outlining their solutions for monitoring meaningful state changes in a single cell over time that can make an impact on at least one biological or clinical issue. A team from NIH’s Single Cell Analysis Program and outside experts will review the proposals and select finalists, who will get a chance to compete in the challenge’s second stage. Up to six awards will be made to finalists from a total first-round purse of $100,000.
In the second stage, finalists will prepare detailed documentation supporting their initial proposals, including data from proof of concept tests. NIH plans to award up to two prizes to the winning entries, totaling up to $400,000. The deadline for second-stage submissions in 30 March 2017, with the winners announced on 31 July 2017. Participants in the challenge will be asked to grant NIH a non-exclusive license to practice their solutions.
One reason for the challenge format, says NIH, is to generate ideas from a larger population than the usual participants in the agency’s grant process. The competition is open to teams from academia and industry, including teams from outside the biomedical field.
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Apostolia M. Tsimberidou (MD Anderson Cancer Center)
15 August 2014. MD Anderson Cancer Center in Houston and Foundation Medicine in Cambridge, Massachusetts are testing the benefit of genetic profiles of tumors in determining personalized therapies for patients with metastatic cancer. The researchers conducting the trial also believe genetic profiling can better match cancer patients to studies of new treatments, and lead to faster and less expensive clinical trials.
The study, called Initiative for Molecular Profiling in Advanced Cancer Therapy or Impact2, aims to enroll 1,362 patients with metastatic cancer, that is spreading from the original tumor to other parts of the body. Patients will have tissue from their tumors analyzed to reveal mutations and other variations in their genetic compositions. Foundation Medicine, a developer of genomic analysis systems, is conducting the profiles to find if any molecular factors are contributing to their cancer.
If any genetic alterations are found in the profile, and an FDA-approved treatment for that type of tumor is available, the patients will receive that treatment. In case genetic alterations are found, but no treatments are yet approved, the patients will be randomly assigned either to take part in a clinical trial of a treatment addressing the alteration, or receive the standard of care.
Likewise, if no genetic alterations are found, patients will receive the standard of care. The primary outcome measure is progression-free survival, the length of time following treatment that the patient survives, but without the cancer getting worse.
The new trial is a follow-up to a study of molecular profiling for cancer therapies conducted by MD Anderson called Impact1 and reported in 2011. That earlier trial enrolled more than 1,100 cancer patients, of which 40 percent were found with some kind of genomic alteration. Of those receiving the targeted treatments based on the genetic analysis, 27 percent of patients responded, compared to 5 percent of those receiving the standard of care.
This approach to identifying patients aims as well to speed up the recruitment process for clinical trials. The analysis by Foundation Medicine is expected to take three weeks following initial enrollment, after which physicians can guide their patients’ treatments, including participation in a clinical trial. Foundation Medicine says its system has a more advanced analytical engine than the system used earlier, thus more patients with genetic variations in their tumors are expected to be found.
“This is a collaborative and institutional-wide effort to improve patient care and accelerate the drug development process,” says Apostolia Tsimberidou, professor cancer therapeutics at MD Anderson and study director. “If the results of IMPACT1 are confirmed, cancer treatment will be transformed and comprehensive molecular profiling will become the standard of care.”
Tsimberidou tells more about the trial in the following video.
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Human embryonic stem cell colony (Clay Glennon/Univ of Wisconsin-Madison, NIGMS)
14 August 2014. Biomedical engineers and systems biologists developed an online system that tests the fidelity of engineered cells and tissue to the real-life properties of the cells they aim to emulate. The system, known as CellNet, is the creation of researchers from Boston Children’s Hospital, Boston University, and the Wyss Institute for Biologically Inspired Engineering at Harvard University, and described in pair of articles appearing in this week’s issue of the journal Cell (paid subscription required).
CellNet tests the quality in induced pluripotent stem cells, those reprogrammed from skin or blood cells, as well as specialized cells, — e.g., liver, heart, or brain cells — derived from induced pluripotent or embryonic stem cells, and specialized cells made from other specialized cells. In addition, CellNet highlights improvements in the engineering process to improve cell quality.
CellNet takes a cell’s gene expression profile and returns its likelihood of being classified into one of 16 human or 20 mouse cell and tissue types, which applies strict criteria to determine how close the engineered cells or tissues resemble the real thing, what CellNet calls “training data.” In this process, an algorithm compares the network of genes activated or inhibited in the engineered cell, known as the gene regulatory network, and returns specific improvements for improving the cell or tissue engineering process.
In one study, the team used CellNet to analyze gene expression data from 56 published studies for assessing the quality of 8 kinds of engineered cells created in those studies. In the second study, researchers tested with CellNet two specialized types of direct cell conversions: (1) skin to liver cells, and (2) immune system B cell lymphocytes to macrophages, white blood cells in the immune system that ingest foreign material. In both articles, the researchers found shortcomings in the conversions and highlighted fixes in the genetic engineering process to plug the gaps.
The team likewise identified a few patterns in the conversions for further gene or tissue engineering initiatives. The gene regulatory networks of engineered cells derived from induced pluripotent stem cells, for example, were very similar to the networks of cells from embryonic stem cells, suggesting induced pluripotent stem cells can provide a feedstock of about equal quality as embryonic stem cells.
In addition, the gene regulatory network of engineered cells grafted into lab mice begins to resemble the network of the target tissue, suggesting the body is sending signals to the engineered cells to enhance their performance. However, most specialized cells made from other specialized cells retain some of the properties of the original cells, which depending on their purpose, can be an advantage or disadvantage.
The team still notes, however, that transforming induced pluripotent stem cells into specific tissues remains a more effective strategy than converting one specialized cell into another, despite the laborious process of first creating pluripotent stem cells. With pluripotent stem cells, the engineered cells or tissue have gene regulatory networks more like the real-life cells or tissue.
“Most attempts to directly convert one specialized cell type to another have depended on a trial and error approach, says Patrick Cahan of Boston Children’s Hospital and the principle designer of CellNet in a Wyss Institute statement. “Until now, quality control metrics for engineered cells have not gotten to the core defining features of a cell type.”
CellNet is freely available online, and can be used as a hosted service or downloaded to run locally.
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EphA3 illustration (Protein Data Bank/Wikimedia Commons)
14 August 2014. Researchers in the U.S. and Australia identified an enzyme found in a range of cancerous tumor cells, but not normal adult tissue, and tested an engineered antibody to fight that enzyme in tumors. The team from the biotechnology company KaloBios Pharmaceuticals Inc. in South San Francisco, California, and Monash University and Ludwig Institute for Cancer Research, both in Melbourne, Australia published its findings in this week’s issue of the journal Cancer Research.
KaloBios develops engineered antibodies to treat cancer, cystic fibrosis, and asthma. One of its therapy candidates, code-named KB004, inhibits the actions of the gene Ephrin type-A receptor 3 or EphA3 that expresses an enzyme active in the development of many fetal organs, but also occurs in some blood-related cancers.
In the study led by Andrew Scott of the Ludwig Institute, the researchers found EphA3 enzymes over-expressed in the internal cellular environment of tumors. In tests where lab mice were grafted with human cancer cells, the team found EphA3 in stem cells derived from the mice’s bone-marrow, where the enzyme contributes to the growth of blood vessels feeding the tumors as well as the tumor’s supporting tissue.
Scott and colleagues also treated the cancer grafts with a specific antibody designed only to combat EphA3. The researchers found the antibody kills the stem cells in the tumors with EphA3. The antibody also severely disrupts the formation of blood vessels and supporting tissue in the tumors from cancer grafts. In addition, the researchers noted EphA3 appears only in the tumor cells and not in other cells in adult mice.
KB004 is now being tested in a combined early/intermediate-stage clinical trial with patients having several types of blood related cancers including various types of leukemia and multiple myeloma. In a company statement, Geoffrey Yarranton, KaloBios’s chief scientist and co-author of the paper, says the results of the study provide a rationale to expand the scope of KB004 to solid tumors as well as blood-related cancers.
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13 August 2014. Otonomy Inc., a biopharmaceutical company in San Diego developing treatments for disorders of the middle and inner ear, raised $100 million in its initial public offering of stock. The company, trading on the NASDAQ under the symbol OTIC, priced its 6.25 million shares at $16.00.
Otonomy was founded in 2008 by physicians and researchers in otolaryngology — ear, nose, and throat specialists — from University of California at San Diego and biotechnology investors, including Jay Lichter from Avalon Ventures, who developed Ménière’s disease, a chronic inner-ear disorder that affects balance and hearing. The company focuses on treatments for middle and inner ear disorders, which it says are not being adequately met with current therapies.
Inner and middle ear conditions include Ménière’s disease, ear infections, tinnitus (ringing in the ears), and hearing disorders. One reason for the lack of adequate therapies, says the company, is the inner and middle ear anatomical structure, including the eardrum and other membranes, that limits access to areas needing the treatments, or prevents fluid treatments from being retained. In addition, treating middle ear infections with repeated antibiotics, the current standard therapy, runs the risk of developing resistance to the antibiotics.
Otonomy’s technology offers a drug delivery system to overcome these limitations that provide therapeutics directly to affected regions and are retained in the ear for a period of time after a single dose. The system combines drug microparticles in a suspension with a heat-sensitive polymer. The polymer is administered as a liquid injected into the middle ear that at body temperature becomes a gel, which is more readily retained.
The company’s lead product is AuriPro, a formulation of the antibiotic ciprofloxacin to treat bacterial infections associated with middle ear effusion, the build-up of fluid in the middle ear, requiring surgical placement of a tube to equalize the pressure. About one million of these surgeries are performed each year, mainly in children age 5 and younger. Ontonomy says two late-stage clinical trials of AuriPro with children show the treatments achieved their desired outcomes compared to a sham procedure, with regulatory filings for the drug expected soon.
The company has two other drug candidates in development. OTO-104 is a treatment for Ménière’s disease currently being tested in an intermediate-stage study of 140 patients in the U.S. and Canada, with results expected in the first quarter of 2015. OTO-311 is a treatment for tinnitus that reformulates gacyclidine, a drug with neuroprotective properties, into a single-dose treatment. Otonomy expects to file a new drug application for OTO-311 next year.
Hat tip: Fortune/Term Sheet
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Mediterranean fruit fly (Oxitec Ltd.)
13 August 2014. Researchers at the biotechnology company Oxitec Ltd. in Oxford and University of East Anglia in Norwich, both in the U.K., created a modified form of the Mediterranean fruit fly that tests show can reduce the population of this pest responsible for extensive crop damage in many parts of the world. Results of the research from the team that includes colleagues in Greece, where field work was conducted, appear online today in the journal Proceedings of the Royal Society B.
Mediterranean fruit fly, known by the short-hand term medfly, infests more than 300 wild and cultivated fruits, vegetables, and nuts worldwide. Damage from medflies affects crops in southern Europe, Middle East, Australia, Pacific Islands, Africa, Central and South America, Caribbean, and parts of the U.S. The pest is difficult to control, and techniques for containing or eliminating medflies — quarantines, baited traps, insecticides, and inflicting natural enemies on the species — return mixed results. Some of these techniques, such as traps and insecticides, can involve dangerous chemicals.
Yet another control method is the sterile insect technique that introduces forms of the male medfly into the population prevent further generations of the pest by producing weakened offspring that die off before maturity or only males. This technique also produces mixed results, with the radiation for generating the sterile forms believed to cause weakened medflies that cannot compete with stronger wild types.
The Oxitec/East Anglia team took a different approach to controlling medflies, creating a robust form of the male insect genetically-engineered to produce only male offspring. The technique, known as release of insects carrying a dominant lethal or RIDL, in this case adds a gene to the males where the RIDL is lethal only to females. Releasing these robust yet engineered male medflies into the wild population, therefore, should over time cause the wild medfly population to collapse.
The researchers tested this premise in greenhouses at University of Crete in Greece, having cages that simulated fruit orchards with a lemon tree and food and water sources. The team released into each cage a precise number of wild-type medflies in the pupal stage, between larva and adult. After 6 weeks, the researchers began releasing genetically engineered male medflies each week into half of the cages, with the other cages serving as controls.
The results show the cages with the modified males experienced declining numbers of wild medflies until the wild types disappeared. The researchers found after 6 weeks, production of eggs in the cages with the engineered males began declining. In addition, more males with the added female-lethal gene increased in the test cages, until the original wild-type form of medfly became extinct by about week 17. At the same time, the number of wild-type medflies in the cages without the modified males remained about the same.
Oxitec is now seeking approvals to carry out open-field studies with engineered medflies. The company develops RIDL-based solutions for medflies and other species: diamond back moth, pink bollworm, mexfly, and olive fly.
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12 August 2014. The pharmaceutical company Pfizer and personal genetics company 23andMe in Mountain View, California are researching genetic factors associated with inflammatory bowel disease, for which Pfizer is testing several treatments. Financial aspects of the collaboration were not disclosed.
Inflammatory bowel disease is the name given to disorders of the digestive tract, such as Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention says the conditions are responsible for 700,000 doctor visits as well as 100,000 hospitalizations each year in the U.S., and because there is no cure, they require a lifetime of care.
Crohn’s disease results in inflammation of the digestive tract lining and can spread deep into affected tissues. The disorder is characterized by diarrhea and abdominal pain, and can lead to malnutrition. With ulcerative colitis, the inflammation usually affects the inner lining of the large intestine and rectum. Symptoms can range from pain, diarrhea, and rectal bleeding to unintended weight loss, dehydration, and shock.
Under the agreement, the companies will explore genetic factors influencing the onset of inflammatory bowel disease, as well as its progression, severity, and variations in response to treatments. Some 10,000 participants residing in the U.S. with inflammatory bowel disease will be recruited for the study. There will be no charge for participants, with all data kept anonymous, according to 23andMe.
Each participant will be asked to provide a saliva sample that 23andMe will analyze for genomic composition. Participants will also be asked to complete a 15-minute online survey about their experiences with the disease. People taking part will receive 23andMe’s standard personal genome analysis, including ancestry, as well as a DNA profile that their physicians can review for medical implications.
Pfizer is testing several compounds and biologics in clinical trials for inflammatory bowel disease. Its current rheumatoid arthritis drug tofacitinib, marketed under the name Xeljanz, is in a late-stage trial as a treatment for ulcerative colitis. Pfizer is also testing tofacitinib for Crohn’s disease in an intermediate-stage study.
The biologics code-named PF-00547659, PF-04236921, and PF-05285401 are likewise in intermediate-stage trials for Crohn’s disease and ulcerative colitis. In addition, the biologic code-named PF-06480605 is in an early-stage trial to treat Crohn’s disease.
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