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Genome Editing Company Adds $38M in Venture Funds

Gene editing illustration

(NIH.gov)

24 June 2016. A company creating treatments for disease that edit the human genome is raising another $38 million in its second venture financing round. Crispr Therapeutics in Basel, Switzerland says with the new funding, it gained nearly $140 million in the entire round.

The Crispr Therapeutics technology is based on the research of Emmanuelle Charpentier, now a professor at the Max Planck Institute for Infection Biology in Berlin and a scientific founder of the company. Her research discovered the capability of Crispr — short for clustered regularly interspaced short palindromic repeats — to alter human genomes with an enzyme known as Crispr-associated 9, or Cas9. The Cas9 enzyme can program RNA to silence genes and provide immunity against invading genetic material. Cas9 also harnesses RNA to cut DNA at precise points in genomes, making it possible to delete, insert, or correct defects in human genomes. Charpentier led research teams that published their findings in the journal Science in 2012, and an article in Nature a year earlier.

The company is developing treatments that work either outside or inside the body. In some cases, cells will be removed from individuals, with their genes edited in lab cultures, then reinserted back into patient. In other cases, gene-editing mechanisms will be delivered with natural lipid nanoparticles directly to organs or through injections into the blood stream, where they can work inside the body.

Crispr Therapeutics says it is developing treatments for mutations in somatic or existing cells in the body, but not germline modifications that develop through reproductive processes and passed on to successive generations. The company signed a joint statement with Intellia Therapeutics in December 2015 limiting their work to “to discovering and developing gene editing-based treatments for serious diseases using only non-germline somatic cells.” Diseases being considered by Crispr Therapeutics include the inherited disorders sickle cell disease and beta thalassemia, certain types of immunodeficiencies, and immune therapies for cancer.

Participating in the latest financing are Franklin Templeton Investments, New Leaf Venture Partners, funds advised by Clough Capital Partners L.P. and Wellington Capital Management L.L.P., and other undisclosed life sciences funds. Earlier second-round funders were Bayer Global Investments, an affiliate of Bayer AG, and Vertex Pharmaceuticals.

Crispr Therapeutics was founded in April 2014, and as reported in Science & Enterprise, raised $25 million in its first venture funding round. The company opened a research office in Cambridge, Massachusetts a year later, and plans to use the new funding to expand that facility, as well as advance its current and future treatment programs.

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Hat tip: Fortune/Term Sheet

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Start-Up Developing Nanomedicines for Transplants

Ann-Marie Broome and Satish Nadig

Ann-Marie Broome, left, and Satish Nadig, two of the founders of ToleRam Nanotech (Sarah Pack, Medical University of South Carolina)

24 June 2016. A spin-off enterprise from Medical University of South Carolina is creating drug delivery techniques that make it safer for patients needing organ transplants. The company, ToleRam Nanotech LLC in Charleston, was recognized for one of the top new innovative technologies at last month’s TechConnect World Innovation Conference in Washington, D.C.

ToleRam Nanotech is developing a system for packing drugs in nanoscale particles — 1 nanometer equals 1 billionth of a meter — with its first application delivering drugs that better target immune-system rejection of transplanted organs. Three faculty members at Medical University of South Carolina founded the company: immunologist Carl Atkinson, biomedical engineer Ann-Marie Broome, and transplant surgeon Satish Nadig. They formed Toleram Nanotech in January 2014.

The founders say immune-system rejection is a widespread problem for organ transplants, with as many as 20 percent of kidney transplants rejected in 3 to 5 years, and about half of lung transplants overall. Current drugs, such as rapamycin, also known as sirolimus, can suppress immune-system rejection, but come with serious adverse side effects, including increased risk of infection and skin cancer.

The ToleRam Nanotech technology breaks up and packages rapamycin into nanoscale particles called micelles that make it possible to deliver much lower doses of the drug precisely to the target sites. “We encapsulate the drugs to put them in stealth mode and deliver them specifically to a localized region,” says Broome in a university statement. “They are released only to that area, eliminating the adverse side effects.”

Nadig adds, “It potentially will lower rejection of a transplanted organ while allowing the patient to be able to fight off infection and go about a normal life.”

The targeted rapamycin micelles are now in preclinical testing. The university says the team demonstrated the technology in lab mice with transplanted kidneys, where the micelles delivered the drug only to the transplanted kidneys and adjacent environment, leaving the rest of the recipients’ immune systems unaffected.

ToleRam Nanotech was recognized at the 2016 TechConnect World Innovation Conference, held 22-25 May, as one of the winners of its TechConnect Innovation Awards. The awards go to the top 15 percent of entries, judged by the potential impact on their industry sectors, in this case, medical devices.

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App Evaluates Chest Pain Patients for Discharge

Heart Pathway app screens

Heart Pathway app screen excerpts (Decision Point Informatics)

23 June 2016. A new iPhone app helps emergency physicians decide whether a patient with chest pain can be safely discharged from a hospital or needs further tests. The Heart Pathway app, developed by Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, is available for free from the iTunes App Store.

Chest pain is among the most frequent reasons for visiting hospital emergency rooms, accounting for some 8 million visits each year in the U.S., with physicians in almost every shift called on to diagnose patients with chest pain. In most cases, say the app’s developers, patients with chest pain receive lengthy cardiac evaluations, but only a small percentage of patients are at risk for serious cardiac events. Nonetheless, the fear of missing serious heart problems and threat of malpractice litigation results in patients often receiving extensive tests.

Heart Pathway incorporates a protocol developed at Wake Forest Baptist to more efficiently evaluate patients complaining of chest pain and provide emergency room clinicians with better information to make their decisions. The protocol considers 5 variables: patient history, electrocardiogram or ECG, age, other risk factors, and levels of troponin in the blood. Troponin is a protein released when heart muscle is damaged.

A Wake Forest Baptist team led by emergency medicine professor Simon Mahler converted the protocol to digital logic for coding into the Heart Pathway app. The app and protocol compute a composite score from the history, ECG, age, and risk factors to a scale of 0 to 7, with a recommendation to test for troponin. If the patient shows normal troponin levels after a series of tests, and the composite score is 3 or less, the risk of a major cardiac event within 30 days is less than 1 percent. Individuals meeting those conditions are recommended for discharge.

Mahler and colleagues tested the Heart Pathway protocol in a clinical trial with 282 patients admitted to Wake Forest Baptist’s emergency department complaining of chest pains, randomly assigned for evaluation by Heart Pathway or usual care procedures following professional guidelines. The results show patients evaluated with Heart Pathway experienced shorter hospital stays, 12 percent fewer cardiac tests, and 21 percent more early discharges. In addition, no patients identified for early discharge had major adverse cardiac events within 30 days.

Mahler says in a Wake Forest Baptist statement that the “app is the manifestation of our validated patient protocol in digital form.” He adds,”This gives emergency department providers an easy way to apply an already proven method for evaluating patients who present with chest pain in a way that reduces length of stay and unnecessary testing.”

Data from the app can be integrated into some electronic medical record systems with a package written by Decision Point Informatics, a partner company licensing the Heart Pathway technology.

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Celgene, Medical Centers to Partner on Cancer Therapies

Breast cancer cell proteins

Multiplexed ion beam image of six proteins found in breast cancer cells. (Michael Angelo, NIH.gov)

23 June 2016. Biopharmaceutical company Celgene Corporation and a consortium of four medical research institutes are collaborating on new diagnostics and treatments for cancer. The four cancer centers will divide a $50 million initial payment from Celgene for the option to license future research technologies from their labs.

The consortium includes the cancer research institutes at University of Pennsylvania in Philadelphia, Columbia University in New York, Johns Hopkins University in Baltimore, and Mount Sinai medical school in New York. Celgene says each institution is committed to delivering new programs that can alter the course of the disease for individual patients and the public at large. However, no specific new treatments or technologies were announced.

Each institution is designated as a cancer center by National Cancer Institute, and conducts basic research, translational studies, and clinical trials, including advanced technologies such as immunotherapies and precision medicine. The medical centers have nearly 800 faculty conducting research or caring for more than 30,000 patients.

Each cancer center also has a technology transfer or research commercialization office. Under the agreement, each institution will receive an upfront payment of $12.5 million, with Celgene gaining the option to license research discoveries from the cancer centers over the next 10 years. The company says research programs at the four cancer centers could each be worth hundreds of millions of dollars.

Cancer treatments are a major focus of Celgene’s research and development, with programs underway investigating therapies for solid tumor — breast, lung, and pancreatic — cancers, as well as blood-related cancers such as leukemia and multiple myeloma. As reported in Science & Enterprise, Celgene often collaborates with academic institutions and biotechnology companies on cancer treatments. In September 2015, the company began a partnership with academic protein engineering labs, and in June 2015 announced a $1 billion licensing deal for immunotherapies with Juno Therapeutics.

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Immunotherapy Company Raises $70 Million in IPO

NASDAQ display

(bfishadow, WikimediaCommons)

22 June 2016. Selecta Biosciences Inc., a biotechnology company developing treatments harnessing the immune system, is raising $70 million in its initial public offering, or IPO, of company shares. The Watertown, Massachusetts enterprise, trading on the Nasdaq exchange under the symbol SELB, issued 5 million shares at $14.00. At the closing bell today, Selecta shares were unchanged trading at $14.00. The Nasdaq composite index today lost nearly 10.5 points, or 0.22 percent.

Selecta develops treatments and vaccines for triggering an immune response, from a platform called synthetic vaccine particles. These biodegradable nanoscale particles are taken up by dendritic cells in the immune system that are then presented to T-cells for an immune response. Synthetic vaccine particles are designed either to prevent an unwanted immune response from biologic drugs or activate a therapeutic immune response against a harmful invader.

The company first discovers new therapies or vaccines based on this platform, then takes the most promising candidates through clinical trials. As reported in Science & Enterprise, Selecta’s lead product code-named SEL-212 is in an early-stage clinical trial as a treatment for gout, a complex form of arthritis, marked by sudden and severe episodes of pain, with tenderness and redness in the joints.

SEL-212 is designed to work with uricase, an enzyme found in some animal species, but not humans, that oxidizes uric acid making it more soluble, so uric acid can be removed from the body. However, uricase also causes an immune system reaction, which sharply limits its use in natural form as a gout treatment.

Also reported in Science & Enterprise, Selecta is in a partnership with Généthon, a research institute developing gene therapies for rare inherited disorders. To deliver gene therapies, Généthon uses a technique known as adeno-associated viruses, 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 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. They plan to focus first on therapies for muscular dystrophies and pediatric liver metabolic diseases.

In addition, Selecta is developing treatments for type 1 diabetes and food allergies, including celiac disease, with drug maker Sanofi and, for type 1 diabetes with the foundation JDRF. The company is also developing a vaccine to prevent relapse from smoking cessation for National Institutes of Health, now in preclinical testing, as well as cancer from human papillomavirus and a malaria vaccine with the Bill and Melinda Gates Foundation.

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Hat tip: Fortune/Term Sheet

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Wearable System Devised for Stroke Rehab at Home

Stroke rehab jacket

Jacket with sensors for stroke rehabilitation (New York University)

22 June 2016. Two engineering students designed a wearable system connected to a smartphone that enables stroke patients to perform some of their rehabilitation program at home. The team from the lab of New York University engineering professor Vikram Kapila won a top prize at a recent biomedical technology competition, and the student inventors are forming a company to take their system to market.

Stroke occurs when blood flow to the brain is interrupted, cutting the oxygen needed by brain cells to function. The vast majority (85%) of strokes are caused by blood clots, while many other strokes are caused by blood vessel leakage in the brain. Nearly 800,000 people in the U.S. have a stroke each year, with paralysis and weakness in the limbs among the results. Recovery, often in rehabilitation clinics, can take months or years of continuous exercises.

Kapila’s lab studies mechatronics, a field combining mechanical engineering and computer science, with a wide range of applications, including biomedical. Graduate students Ashwin Raj Kumar and Sai Prasanth Krishnamoorthy are seeking to provide stroke patients effective ways of performing rehabilitation exercises, while reducing their dependence on visiting rehab clinics. To meet this need, the students are developing a virtual-reality gaming system, with devices worn by the patient connected to a smartphone that provides instant feedback.

Their system consists of a jacket sensing arm orientation, and a glove to sense wrist and finger joint angles. Microcontrollers in the device measure the movements of the arms, hands, and fingers, offering quantifiable progress results for physical therapists and physicians, as well as motivational feedback for the patient. The exercises are performed as part of a training course structured in a virtual reality experience.

“Smartphone-integrated stroke rehabilitation is a marked improvement over the conventional treatment programs of the past,” says Kapila in a university statement. “Providing patients with immediate feedback and placing that feedback in the context of a virtual reality game that they can use within their own homes is definitely encouraging and motivational.”

Raj Kumar and Krishnamoorthy worked with rehabilitation physician Preeti Raghavan at NYU medical center to design the system and build a working prototype, which they entered in the 2016 BMEidea biomedical engineering competition. Entries in the contest must meet an immediate clinical need and are judged on their feasibility, contribution to health, and commercial potential. The winners, announced last week, included the NYU team that took third place and an award of $2,500.

The inventors believe they can develop a commercial product that can sell for under $1,000, which would compete against devices now selling for 8 times that amount. A patent has been filed for the technology, and Raj Kumar and Krishnamoorthy are forming a company to develop a marketable product in NYU’s start-up business incubator.

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C. Difficile Infection Tested with Synthetic Gut Microbe

C. difficile bacteria

Yellow-green fluorescence of C. difficile bacteria (Centers for Disease Control and Prevention)

20 June 2016. A biotechnology company reported results from tests in mice of a synthetic treatment derived from gut microbes that prevents recurrence of Clostridium difficile or C. difficile infections, caused by bacteria often contracted in hospitals or clinics. A team from Seres Therapeutics in Cambridge, Massachusetts presented the findings in a poster session on Saturday at a meeting of American Society for Microbiology in Boston.

According to Centers for Disease Control and Prevention, almost a half-million C. difficile infections occurred in the U.S. in 2011, leading to 29,000 deaths within 30 days of diagnosis. The infections are often contracted in health care facilities, such as clinics and hospitals, causing inflammation in the colon, and symptoms including watery diarrhea, abdominal pain, nausea, loss of appetite, and fever. People who have other illnesses or conditions requiring prolonged use of antibiotics, and the elderly, are at greater risk of this disease.

Seres Therapeutics discovers and develops therapies related to disruptions in the microbiome, the complex aggregate community of diverse intestinal microbes associated with a wide range of health conditions. These disruptions to the microbiome known as dysbiosis  — resulting from pathogens, antibiotics, diet, or inflammation — are increasingly connected or contribute to many chronic and degenerative diseases.

The company’s technology is based on a library of some 9,000 microbial strains collected from healthy human donors. From this library, Seres uses computational techniques to identify microbial communities in the gut associated with healthy and diseased states, then zeroes-in on specific microorganisms, which in the right combinations, can restore healthy functions in the gut from a state of dysbiosis. The company purifies these target microbial combinations into therapy candidates for testing in lab cultures and animals, and later in clinical trials.

The new data report on a synthetic treatment for C. difficile that Seres code-names SER-262 and calls a second-generation therapy for microbiome disruptions. SER-262 is designed to prevent recurrences of C. difficile infections that the company says happens in about a quarter of cases, resulting from damage to the microbiome in dysbiosis. SER-262 is derived through fermentation from strains of microbes similar to the company’s lead product SER-109, an earlier treatment for C. difficile infections now in clinical trials.

In the poster, the Seres team described the process of deriving and distilling the more than 100 candidate bacterial strains for their relatedness to SER-109 and spore-forming potential, as well as safety. From this original collection, the researchers selected 15 strains from which they fermented SER-262, with a genetic and functional similarity to SER-109. In tests on lab mice induced with C. difficile, the team found SER-262 treatments prevented characteristic symptoms of C. difficile, as well as loss of body weight and death.

Seres considers SER-262 a second-generation microbiome treatment, since it does not require donated human material. The company is developing SER-262 into an oral capsule. David Cook, Seres’s chief scientist, says the company is planning the first clinical trials for SER-262 later in 2016.

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Report from Maker Faire: Wrist Band Takes Blood Pressure

Slapband device inventors

Nicole Mendoza, left, and Kimberly Veliz with their Slapband devices at Maker Faire (A. Kotok)

20 June 2016. Editor’s note: Science & Enterprise visited the National Maker Faire, a celebration of inventors and tinkerers that took place this past weekend (18-19 June) in Washington, D.C. While some corporate giants were there — e.g., GE, Microsoft, Intel — and most exhibits were aimed at hobbyists and school kids, we found a few science-based small businesses with good stories to tell. Here’s the second of two reports.

Taking blood pressure, a routine task in clinics, gives a one-time snapshot of an individual’s condition, but people who need frequent monitoring of blood pressure must return continuously to the clinic or take their blood pressure at home. In addition, devices that measure blood pressure, known as blood pressure cuffs, can be uncomfortable for some individuals. Two engineering students invented a device that makes possible continuous blood pressure monitoring.

Kimberly Veliz and Nicole Mendoza are two recent University of California – Irvine biomedical engineering graduates who designed Slapband, a wristband that measures blood pressure. The device is still in prototype, which they say is being prepared for clinical trials needed to get FDA approval, expected in about a year.

Veliz and Mendoza, now a graduate researcher at UC-Irvine, got the idea for Slapband from working with polymer sensors in their research lab. They found the flexible polymer sensors could fit over arteries in the wrist and measure physiological functions like blood pressure at least as well as conventional blood pressure cuffs. Unlike the conventional cuff, the Slapband — so named because it’s literally slapped on the wrist for wearing — is worn continuously, so it also captures blood-pressure continuously.

Slapband’s sensor circuits are embedded into flexible plastic. Veliz and Mendoza designed the sensors with Arduino, an open-source electronic prototyping platform, then ported the circuits to the wearable device. Algorithms in the device convert the sensor readings to electronic signals sent to a smartphone, for review by the wearer, or uploaded to the cloud for clinicians.

The inventors anticipate adding other monitoring functions to their device, including other vital signs, electrocardiograms, and tracking baby kicks in pregnant women. They are seeking financing for further development, scaling up, and clinical trials. The decision of starting their own company to commercialize Slapband or licensing their technology to another enterprise is still up the air.

Veliz and Mendoza recently demonstrated Slapband in the first season of the reality TV show America’s Greatest Makers on the TBS network. On the show, the inventors told how they’re first-generation university students, the first in their families to go to college, where they took part in UC-Irvine’s program encouraging minority student interest in biomedical science.

Also from Maker Faire: Plastic Recycling Made in Space

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Report from Maker Faire: Plastic Recycling Made in Space

Plastic recycler

Amanda Manna of Lowe’s Innovation Labs with plastic recycler mock-up at the 2016 National Maker Faire (A. Kotok)

20 June 2016. Editor’s note: Science & Enterprise visited the National Maker Faire, a celebration of inventors and tinkerers that took place this past weekend (18-19 June) in Washington, D.C. While some corporate giants were there — e.g., GE, Microsoft, Intel — and most exhibits were aimed at hobbyists and school kids, we found a few science-based small businesses with good stories to tell. Here’s the first of two reports.

For space travelers, 3-D printing meets a critical need to make items on the spot, without calling back to Earth. And since there’s no trash pick-up in space, recycling is just as important, if not more. The company Made In Space, an enterprise with about 30 employees in Silicon Valley working largely under contracts with NASA, aims to fill both of those needs.

The International Space Station now has a zero-gravity 3-D printer developed by Made In Space delivered in late 2014 , that crew members tested for a year. In November 2015, the company was chosen by NASA to lead development of a space-based additive manufacturing technology for space station crews to make more of the larger, more complex items they need.

Since space station systems must also consider waste handling, Made In Space is developing a zero-gravity material recycler. That technology got the attention of Lowe’s home improvement stores, which already partners with Made In Space on 3-D printing projects. The companies saw an opportunity to design a system that recycles waste household plastic right in Lowe’s stores.

The store-based recycling system, which had a full-size mock-up on display at Maker Faire, is an outgrowth of the Made In Space zero-gravity recycling technology. The prototype system recycles polyethylene plastic bags and bottles into plastic filament for 3-D printers and household items like water buckets.  Mike Pless, an engineer for Made In Space, says the device — about the size of a small car — grinds up the discarded bags and bottles, and under heat and pressure converts the plastic into reusable material, in this case printer filament. On the space station, waste plastic would go back into filament for the station’s 3-D printers.

Amanda Manna of Lowe’s Innovation Labs says her company began partnering with Made In Space about two years ago. She notes that the collaboration resulted in a commercial 3-D printer now in use on the space station.  Earlier in June, the companies announced that 3-D printer made its first tool,  a wrench custom designed for use on the space station.

Also from Maker Faire: Wrist Band Takes Blood Pressure

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Trial Shows Personalized Alzheimer’s Treatment Effects

Brain wiring illustration

Brain wiring illustration (Courtesy, Human Connectome Project and NIH)

17 June 2016. A small-scale clinical trial offers early evidence of a personalized treatment combining changes in diet, exercise, brain stimulation, and medications can reverse cognitive decline leading to Alzheimer’s disease. Results of the trial were published this week in the journal Aging.

The trial tested a treatment approach for Alzheimer’s disease known as metabolic enhancement for neurodegeneration or MEND. The MEND protocol addresses 36 factors affecting brain chemistry related to metabolic deficiencies affecting maintenance of synapses, the junctions in nerve cells that send and receive signals. The program is tailored for each individual following a detailed diagnosis, and can include changes in diet and exercise routines, improved sleep, meditation, or brain stimulation.

The study was a pilot test of the MEND protocol conducted at the Buck Institute in Novato, California led by the institute’s founder and CEO Dale Bredesen, and Easton Laboratories for Neurodegenerative Disease Research at University of California in Los Angeles. Bredesen is also on the UCLA faculty.

Some 10 individuals took part in the trial, who ranged from people with subjective cognitive impairment — early-stage memory problems and loss of mental sharpness — or mild cognitive impairment, with a few participants already diagnosed with Alzheimer’s disease. Of the 10 participants, 9 had a higher genetic risk for Alzheimer’s, carrying 1 copy of the APOE4 gene variation associated with a greater likelihood of developing memory loss or Alzheimer’s. They ranged in age from 54 to 74, and were divided evenly between men and women.

Participants in the trial were given quantitative MRI, positron emission tomography or PET scans, and a battery of neurological and psychological tests before and after their treatments, which lasted from 5 to 24 months.  The research team also followed-up with participants 6 to 9 months after the trial to gauge any continuing effects of the treatments.

The immediate results of the treatments show participants reported improvements in at least some cognitive measures, as well as quantitative MRI indicators. Follow-up inquiries, reported as case studies, were made to the participants, as well as spouses, family members, and work colleagues. The team reports participants experienced personal, business, and professional improvements, such as returning to jobs they had to quit before the treatments, or improving performance on the job where they retained their jobs.

Bredesen says larger trials are planned for the MEND protocol, but the early results are encouraging, particularly for catching cognitive decline early, and the earlier the better. “The old advice was to avoid testing for APOE because there was nothing that could be done about it,” notes Bredesen in a Buck Institute statement. “Now we’re recommending that people find out their genetic status as early as possible so they can go on prevention.”

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