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FDA Shown Approving New Drugs Faster than Europe

Watch and money

(TheDigitalWay, Pixabay)

6 April 2017. An analysis of regulatory actions in the U.S. and Europe, shows the U.S. Food and Drug Administration approves more new therapies and faster than the European Medicines Agency. Results of the analysis by a team from Yale University and other institutions appear in today’s issue of New England Journal of Medicine.

FDA is often cited by opponents of regulation in the U.S. as an agency imposing rules that meddle in or even cripple the work of industry. In his speech to Congress on 28 February, President Trump pointed out in the audience Megan Crowley, a student at Notre Dame University, who suffers from Pompe disease, a rare disorder that confines her to a wheelchair. Trump used her story to take a shot at FDA’s regulations …

But our slow and burdensome approval process at the Food and Drug Administration keeps too many advances, like the one that saved Megan’s life, from reaching those in need. If we slash the restraints, not just at the FDA but across our government, then we will be blessed with far more miracles just like Megan.

Not everyone in the pharmaceutical industry holds that view, however. In an essay shared on the Pharmaceutical Research and Manufacturers of America, or PhRMA web site on 22 March, Jim Robinson, president of drug maker Astellas America, notes that “A state-of-the-art FDA helps shepherd innovations from clinical trials to the patient’s bedside, while incorporating unique approaches to drug development and regulatory decision-making.”

To assess the agency’s track record, a research team led by Joseph Ross, a professor of medicine and public health at Yale University, evaluated FDA’s performance in approving new treatments, and compared that record against its European counterpart, the European Medicines Agency. Ross, with Nicholas Downing of Brigham and Women’s Hospital and Audrey Zhang of New York University, reviewed FDA’s and EMA’s approvals of new therapies between 2011 and 2015. The team then classified the approved treatments by disease type and recorded the length of time each agency needed to review the drugs.

The results show in that 5-year period, FDA approved 170 new therapies, compared to 144 for EMA. The two agencies show similar profiles in the diseases addressed by the new drugs, with about one-third of the treatments for cancer, and 14 to 15 percent each for heart disease or diabetes, and infectious diseases. FDA, however, approves a higher percentage of orphan drugs — those addressing small populations, like Pompe disease — with 44 percent of FDA’s approvals going for these rare diseases, compared to 25 percent of EMA’s approvals.

In addition, FDA approves new therapies faster than EMA. The median amount of time needed for FDA approvals in this period was 306 days compared to 383 days for EMA. Approval times were particularly faster at FDA for cancer, infectious disease, and orphan drugs. Ross and colleagues identified 142 new therapies approved by both FDA and EMA, and in those cases FDA needed a median of 303 days for review, compared to 369 for EMA.

The authors note that the current Prescription Drug User Fee Act that authorizes FDA’s drug review processes expires in October 2017 and its reauthorization is being debated in Congress. “This is more information that should inform upcoming debates,” notes Ross in a Yale University statement. “The FDA is already making decisions quickly and increasing its regulatory speed shouldn’t be our number-one priority.”

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Umbilical Cord Blood Evaluated for Autism Treatment

autism spelled in Scrabble tiles

(Blue Diamond Gallery)

5 April 2017. Results from a clinical trial show infusions of a child’s own umbilical cord blood are safe for treating autism spectrum disorder, and provide initial signs of effectiveness. Findings of the study by a team from Duke University and funded in part by ViaCord LLC in Waltham, Massachusetts, a division of the medical technology company PerkinElmer, appear in today’s issue of the journal Stem Cells Translational Medicine.

Autism spectrum disorder is a collection of neurodevelopmental conditions marked by communication difficulties and impaired social interaction, as well as repetitive and stereotyped patterns of behavior. Some 1 in 68 children have autism spectrum disorder, according to Centers for Disease Control and Prevention, with males 5 times more likely to have the disorder than females. Classic autism is considered the most severe form of the syndrome.

The team from Duke University, led by pediatrics professor Joanne Kurtzberg and Geraldine Dawson, professor of psychiatry with the university’s Center for Autism and Brain Development, hypothesized that stem cells derived from a child’s own umbilical cord blood could help alleviate symptoms associated with autism spectrum disorder by controlling inflammatory processes in the brain. In addition, cord blood infusions were shown earlier to be safe for treating cerebral palsy in children.

The early-stage clinical trial recruited 25 children, age 2 to 7, diagnosed with autism spectrum disorder and who had umbilical cord blood previously banked. The study, conducted at Duke University Medical Center in Durham, looked primarily at the safety of cord blood treatments, consisting of single infusions calibrated to the size of the child. However, the trial also evaluated the children on a number of behavioral and developmental assessments, starting with the Vineland Adaptive Behavior Scales that measures personal and social skills of individuals from birth through adulthood. These tests, given up to a year after the infusions, tracked as well changes in attention to social stimuli with eye-tracking and electroencephalography or EEGs that measure electrical activity in the brain.

Of the 25 children, most were male (21), white (22), with moderate to severe autism spectrum disorder symptoms, and a median non-verbal IQ of 65. The researchers report the infusions were well-tolerated with no serious adverse effects in any participants. The children experienced an average 3 mild to moderate side effects during the trial, mainly allergic reactions to the infusions. However, no infections from the infusions were reported.

The team found as well that the children as a group made progress during the trial in the behavioral and developmental measures. These assessments include social communication skills and autism symptoms, expressive vocabulary, and attention to social stimuli as measured by the eye-tracking tests. Kurtzberg notes in a ViaCord statement that, “while small and non-randomized, there were observed improvements in a majority of the children reported by clinicians and parents.” She adds, “We are now hoping to replicate these preliminary results in a phase 2 randomized clinical trial for which enrollment is nearly complete.”

The phase 2 or intermediate-stage trial is enrolling 165 participants that will test cord blood infusions against a placebo among children with autism spectrum disorder. This study is also taking place at Duke University Medical Center.

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Prodrugs Designed to Better Target Cancer Therapies

Lungs illustration

(National Cancer Institute)

5 April 2017. A delivery mechanism is being developed to package cancer drugs in a nanoscale precursor state that reacts only in tumor regions, to protect against adverse effects. Results from a test of this drug-delivery technology by researchers at Oregon State University in Portland and Corvallis appear in the 10 May 2017 issue of Journal of Controlled Release (paid subscription required).

The team led by Oregon State pharmacy professor Adam Alani is seeking safer methods for treating cancer other than conventional chemotherapy that attacks cancer cells, but also healthy proliferating cells and tissue in the body, causing adverse and often severe reactions. One technique for minimizing these adverse effects is to deliver the drugs in an inactive state, with the active chemotherapy released only in the tumor and its supporting environment.

Alani and colleagues are testing a technology by Cascade Prodrug Inc. in Eugene, Oregon that develops a formulation of the chemotherapy drug vinblastine, to treat several solid tumors and lymphomas. Cascade Prodrug’s techniques combine a precursor of vinblastine code-named CPD100 broken down into nanoparticles in liposomes, tiny natural-oil bubbles similar to surfaces of cells. This formulation is designed to keep vinblastine in an inactive state until it reaches tumor regions, where it reacts with the low-oxygen environment of the tumor, known as hypoxia.

“One reason these cancers become very aggressive is the development of this hypoxia,” says Alani in a university statement. “Since the late 1990s, researchers have been trying to take advantage of the hypoxia.” The Cascade Prodrug technology tries to do just that, keeping vinblastine in its precursor or prodrug state until it comes into contact with low-oxygen environments, in which CPD100 metabolizes into vinblastine.

The Oregon State team evaluated two variations of Cascade Prodrug’s CPD100-liposome treatments, one with a coating of biocompatible polymer polyethylene glycol or PEG used in many drugs, and one without a coating. The researchers first determined a maximum safe dose of the drugs in lab cultures, before giving them to lab animals.

In tests with lab mice induced with non-small cell lung cancer, both liposome formulations of the prodrug show greater exposure to cancer cells than CPD100 given alone. This greater exposure is attributed to more assimilation of the prodrug’s active ingredients into the tumors and slower clearance from the body, than CPD100 in its free state. The PEG-coated liposome version lasted 9.5 hours in the test mice, compared to 5.5 hours for the non-coated version.

After 3 months, lung tumors in mice treated with the liposome prodrugs remained shrunk and suppressed. Biomarkers in blood indicating lung cancer also remained low. “The nano carriers performed much better than the prodrug itself,” notes Alani. “We were able to literally cure the tumor.”

Alani’s lab is now working with the university’s veterinary medical school and Cascade Prodrug to test the safety and efficacy of the liposome formulations in dogs, both as a treatment for cancer in dogs, as well as further tests of a proposed therapy for humans.

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Artificial Pancreas Shown Feasible for Young Children

Diabetes Assistant screen

Diabetes Assistant screen (University of Virginia)

4 April 2017. An integrated system combining a glucose monitor and insulin pump to simulate the human pancreas is shown to be feasible for young children with type 1 diabetes. Results of a study with a group of children, ages 5 to 8, were presented on 3 April at a meeting of the Endocrine Society in Orlando, Florida.

Type 1 diabetes is an inherited autoimmune disorder where the body does not produce insulin, and is diagnosed primarily in children or young adults. Autoimmune disorders are conditions where the immune system is tricked into attacking healthy cells and tissue as if they were foreign invaders, in this case, insulin-producing beta cells in the pancreas. About 1.25 million people in the U.S. have type 1 diabetes, about 5 percent of people with diabetes of any kind.

A research team from University of Virginia in Charlottesville, led by pediatrics professor Marc DeBoer, presented findings from a study where they tested an artificial pancreas device developed at the university’s Center for Diabetes Technology. The device combines the functions of a third-party blood glucose monitor and insulin pump, controlled with software called Diabetes Assistant, developed at the university, that resides on a smartphone. As described in Science & Enterprise, a clinical trial is underway testing the device among teens and adults.

An outstanding question, however, is whether a system of this kind can be operated successfully in younger children with type 1 diabetes. To answer the question, DeBoer and colleagues recruited 12 children, divided equally between boys and girls, age 5 to 8, with type 1 diabetes. Participants were randomly assigned to use the artificial pancreas device, with child-proof locked-down screens, for 68 hours or their own blood glucose monitors and insulin pumps at home for the same amount of time, then switching to the other method. The children’s physical activity levels were also measured with Fitbit devices.

The results show the children experienced more time with safe blood glucose levels when using the artificial pancreas. When the children were wearing the test device, their blood glucose levels were within safe ranges — between 70 and 180 milligrams per deciliter, or mg/dL — 73 percent of that time on average. compared to 47 percent of the time for home care with their own blood glucose monitors and insulin pumps.

Children also spent less time with high blood glucose levels when using the artificial pancreas (26%) compared to home care (52%). Amounts of time with hypoglycemia or low blood sugar were about the same for each method, 3 percent for the artificial pancreas and 4 percent for home care.

The team concludes the artificial pancreas, adapted for young children is safe and improves overall diabetes control. Although the number of children in the study was small, the results, says DeBoer in an Endocrine Society statement, “show great promise because similar results have been found in large-scale studies of older individuals with type 1 diabetes.”

DeBoer and several members of the research team are co-founders of the company TypeZero Technologies LLC in Charlottesville, taking the artificial pancreas system to market.

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Triple-Drug Inhaler Shown to Cut COPD Attacks

lung illustration

(Kai Stachowiak, Pixabay)

4 April 2017. Results from a year-long clinical trial show that an inhaler with three types of drugs reduces the number of COPD attacks compared to a common single-drug inhaler. Findings from the trial, led by researchers from University of Manchester in the U.K., appear in the 3 April issue of the journal The Lancet (paid subscription required).

Chronic obstructive pulmonary disease, or COPD, is a progressive respiratory disorder that makes it difficult to breathe, and causes coughing, wheezing, shortness of breath, and tightness in the chest. The leading cause of COPD is cigarette smoking, but other irritants like chemical fumes or air pollution can contribute to the condition.

Two major forms of the disease are emphysema, where walls between air sacs in the lungs are damaged and chronic bronchitis,where  the lining of the airways is constantly irritated and inflamed. COPD is a major cause of disability and the third leading cause of death in the U.S. In the U.K., according to Manchester respiratory medicine professor Jørgen Vestbo who led the research team, COPD exacerbations, or attacks, lead to some 150,000 hospital admissions and 1.2 million bed-days each year.

The clinical trial tested a new type of inhaler designed to deliver drugs directly to the lungs for people with COPD. In this case, the inhaler — made by Chiesi Farmaceutici SpA in Parma, Italy that funded the study — delivers three different drugs to prevent COPD exacerbations: beclometasone, formoterol, and glycopyrrolate. Most of the total sample of nearly 3,700 participants with COPD, age 40 and over, were randomly assigned to test the triple-drug inhaler, used once a day, against a commonly used inhaler with a single drug, tiotropium.

A sub-group of participants, about 500, tested the triple-drug inhaler against a scenario where patients were asked to use two inhalers, one with combination of beclometasone and formoterol, and one with tiotropium. Participants in all groups were asked to use their inhalers for a whole year, where the study team looked primarily at the rate of moderate to severe exacerbations as the main indicator of effectiveness. Researchers also measured forced expiratory volume in 1 second, an indicator of lung performance, and tracked adverse effects.

The results show participants using the triple-drug inhaler had an exacerbation rate of 0.46 compared to 0.57 for tiotropium-only inhalers, a difference large enough to be statistically reliable. After a year, triple-drug inhaler users also had higher forced expiratory volumes than individuals with tiotropium-only inhalers. Exacerbation rates and lung performance were comparable for the triple-drug inhaler and dual-drug plus tiotropium samples; that part of the study looked for equivalence of the treatments, not superiority of one over the other.

Adverse effects rates for all of the inhalers were similar, but high. Between 55 and 58 percent of participants reported some type of adverse effects during the study.

Chiesi Farmaceutici submitted the triple-drug inhaler for approval by the European Medicine Agency in September 2016. The company says it’s the first triple-drug inhaler to seek approval for COPD.

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Enhanced Gene Therapy Boosts Anti-Tumor Response

Sun

(Arun Kulshreshtha, Wikimedia Commons)

3 April 2017. Gene therapies delivered with electronic pulses were shown in lab mice to increase production of natural immune-system proteins and reduce melanoma, or advanced skin cancer, tumors. A team from the biotechnology company OncoSec Medical Inc. in San Diego presented its findings today at a meeting of American Association of Cancer Research in Washington, D.C.

Melanoma is an aggressive type of skin cancer, which while not as common as basal cell and squamous cell skin cancers, is more likely to spread to other parts of the body. American Cancer Society expects more than 87,000 people in the U.S. to develop melanoma in 2017, leading to some 9,700 deaths. If melanoma is caught and treated early, before it spreads or metastasizes, the 5-year survival rate is 98 percent. After the cancer spreads to other parts of the body, however, the 5-year survival rate drops to 16 percent.

OncoSec develops solid tumor cancer treatments that harness the the cancer fighting capabilities of the interleukin 12, or IL-12, a natural protein in the body that fights off invading pathogens, but can also be directed at cancer. When used by itself as a therapy, however, interleukin 12 can cause serious unexpected adverse effects, often as a result of its promoting production of other proteins in the body.

OncoSec overcomes this problem by simultaneously aiming electroporation, or mild electronic pulses, at the tumor as DNA plasmids with genes producing interleukin 12 are injected into the tumor. These pulses, says the company, weaken the tumor cell membranes, making them less resistant to interleukin 12, allowing for smaller and safer amounts of the protein. OncoSec is testing its technology in clinical trials on its own and with other cancer treatments on several kinds of skin cancer, including melanoma, and triple-negative breast cancer.

The company’s treatments are also designed to generate a systemic, or whole-body, response by “training” the patient’s T-cells in the immune system to recognize the cancer, wherever it may spread. To enhance this capability, OncoSec researchers evaluated gene therapies to produce a variation of interleukin 12 known as IL-12 p70, which the team administered with electroporation to the tumors. IL-12 p70 combines the two main components of interleukin 12 and is considered desirable for systemic treatments.

In tests in lab mice induced with melanoma, the gene therapies successfully reduced the size of primary, or original, tumors, with the higher the dose given the mice, the more shrinkage in their tumors. In addition, the results show increased production of CD8 T-cells targeting specific melanoma cells that spread in the body. The findings also show tumors elsewhere in the body shrunk, suggesting a strong systemic response.

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Zika DNA Vaccine Begins Clinical Trial

Testing Zika virus

Testing Zika virus in tissue cultures (Walter Reed Army Institute of Research)

3 April 2017. A new clinical trial is underway testing a Zika vaccine that uses genetically-engineered DNA to generate an immune response against the disease. The intermediate-stage trial is conducted by National Institute of Allergy and Infectious Diseases, or NIAID, part of National Institutes of Health.

The Zika outbreak is a current public health challenge, with cases in Brazil spreading to the Caribbean and the Americas, including the U.S. mainland. The Zika virus is transmitted primarily by aedes aegypti mosquitoes, the same species carrying chikungunya, dengue, and yellow fever pathogens. The virus may also be spread through sexual contacts. Most people contracting the Zika virus report symptoms such as mild fever, conjunctivitis or pink eye, and muscle and joint pain.

The current Zika outbreak, however, is resulting in increasing numbers of cases of birth defects, notably microcephaly and Guillain-Barré syndrome. Centers for Disease Control and Prevention, as of March 2017, counts more than 5,100 Zika cases in the 50 U.S. states and District of Columbia, and 38,300 cases in U.S. territories. As yet, no approved treatments or vaccines are available.

The new trial is testing a vaccine that genetically alters a circular piece of DNA found in bacteria and other organisms called a plasmid, to which the NIAID researchers added Zika genes from the surface of the virus. These genes encode two proteins, which when injected in a human recipient form into particles that appear enough like a Zika virus to stimulate an immune response, but not cause infection. NIAID says initial results from an early-stage clinical study testing the vaccine with 50 healthy individuals indicate the vaccine is safe and able to create an immune response.

The new trial will also test for the vaccine’s safety and immune response, but also in two dosage levels. The first part of the study is recruiting 90 healthy men and non-pregnant women in Houston, Miami, and San Juan, Puerto Rico, who will receive three injections, standard or high-dose, each four weeks apart. Participants will be tracked and evaluated for the next 32 weeks for adverse effects and receive counseling on preventing Zika infections.

The second part of the study plans to enroll 2,400 individuals, all healthy men and non-pregnant women, in the same three locations as the first part, but also from sites in Costa Rica, Peru, Brazil, Panama, and Mexico. In this stage of the trial, participants will be randomly assigned to receive either the test vaccine or a placebo in three injections, each four weeks apart. Persons taking part will be tracked for two years, and evaluated for adverse effects and signs of Zika infection, as well as counseling on preventing Zika infections. The study team will look primarily for confirmed Zika cases among test and placebo recipients to determine if the vaccine is effective.

The Miami segments of the study are being conducted by University of Miami’s medical school, led by Margaret Fischl, an infectious disease expert who heads the school’s AIDS research center. “The vaccine is really important in Miami,” says Fischl in a university statement, “because we saw the nation’s first cases of locally-acquired Zika, which needed a more immediate response.”

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Start-Up Licensing Flexible Genome-Editing Technology

DNA molecules

DNA molecule display (Christian Guthier, Flickr)

31 March 2017. A start-up biotechnology company is licensing techniques from two universities that make genome editing more flexible and better control gene expression. Financial aspects of the agreements between Canopy Biosciences LLC in St. Louis, with Washington University in St. Louis and Johns Hopkins University in Baltimore were not disclosed.

Canopy was formed in 2016 to take a technology to market that adapts emerging Crispr-Cas9 genome editing techniques for better control of the extent of gene expression needed for therapeutics. Crispr, short for clustered regularly interspaced short palindromic repeats, is based on bacterial defense mechanisms that use RNA to identify and monitor precise locations in DNA. The actual editing of genomes with Crispr in most cases uses an enzyme known as Crispr-associated protein 9 or Cas9. RNA molecules guide the editing enzymes to specific genes needing repair, making it possible to address root causes of many diseases.

Up to now, Crispr could entirely knock-out defective genes to remove mutations responsible for disease, but not control the proteins expressed by those defects. Canopy’s technology, however, makes it possible to use genome-editing for situations where completely removing a gene would cause adverse effects. That technology quickly and reliably produces hypomorphic mutations, or genetic alterations that reduce gene expression, on demand, dialing down the extent of proteins transcribed by the gene.

These more regulated mutations are accomplished by adding adenosine nucleotides, components of RNA responsible for energy metabolism in cells, called polyA tracks in Canopy’s technology. PolyA tracks act as control units for genes, with the size of polyA tracks added to a gene in DNA controlling the extent of gene expression and protein production. A research team led by cell biologist Sergej Djuranovic at Washington University demonstrated production and control of hypomorphic mutations using polyA tracks with DNA from 5 model organisms, including E. coli bacteria and fruit flies, as well as human cells in lab cultures, in a paper published in January 2017 appearing in the journal Nature Communications.

The research by Djuranovic and co-author Rachel Green at Johns Hopkins University is the basis of the license from the 2 institutions. Canopy is marketing the technology under the brand name TUNR Flexible Gene Editing System, for 3 types of adjustable gene editing for therapies. The company also established prices for the services, ranging from $1,990 to $4,990.

Canopy’s president Edward Weinstein believes the TUNR system can be useful in situations such as cancer immunotherapy where better control of gene expression may be needed. “Previously, researchers have only been able to completely delete, or ‘knockout’, a particular gene,” says Weinstein in a company statement. “With TUNR, we can dial in the exact level of expression necessary, such as 10, 25, or 75 percent. This has become particularly important for new immuno-oncology drug targets like PDL1, which has a range of expression in cancer patients and is used to predict their responsiveness to the latest promising cancer drugs.”

The company was formed in 2016 and is being incubated at BioGenerator, a life sciences investor and accelerator in St. Louis. In December 2016, Canopy received $2 million in financing from BioGenerator and other angel investors.

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NIH Funds Seen Boosting Industry Patents

U.S. Patent and Trademark Office

U.S. Patent and Trademark Office in Alexandria, Virginia (A. Kotok)

31 March 2017. An analysis of grants issued by National Institutes of Health shows a large percentage of those grants, directly or indirectly, result in patented technologies in industry. The study by management and public health researchers at Harvard Business School, Massachusetts Institute of Technology, and Columbia University appears in the 30 March issue of the journal Science.

National Institutes of Health is the main financial source for life sciences research in the U.S., with a total budget in the current (2017) fiscal year of more than $33 billion. President Trump’s proposed budget for FY 2018 asks for a reduction of $5.8 billion in spending, an 18 percent cut for NIH. Secretary of Health and Human Services Tom Price told a committee of the House of Representatives this week that the cuts would come out of overhead payments to universities, but lawmakers in both parties are complaining about the scale of these reductions.

Danielle Li, a professor of entrepreneurship at Harvard Business School, with management professor Pierre Azoulay at MIT and public health policy professor Bhaven Sampat at Columbia, sought to gauge one economic impact of public spending on life sciences research, the generation of patents by business enterprises from studies funded by NIH. Patents represent a tangible result of the knowledge produced in research, which can be translated into revenues from licensing and royalties for drugs, medical devices, and other biomedical products. For this study, the authors traced NIH funding to patents issued by the U.S. Patent and Trademark Office, or USPTO.

Using natural language processing tools, Li and colleagues examined 365,380 grants funded by NIH from 1980 through 2007. About half of those grants, more than 164,000, supported large renewable research projects, known by the funding code R01. These R01 grants are considered the foundation of NIH’s support, since they often finance the work of entire labs, including postdoctoral researchers and graduate students, for a number of years. The researchers also reviewed nearly 5.3 million patents issued by USPTO between 1980 and 2012, adding another 5 years for research findings to end up in patent documents.

The team found a sizeable effect from NIH funding on patent activity over this period, but largely in indirect ways. The most direct vehicle for turning NIH support into patents is the Bayh-Dole Act of 1980, which gives universities and research institutes the rights to intellectual property produced by studies conducted by their scientists and funded with federal sources. As a result of Bayh-Dole, institutions can file for patents and own the rights for future licensing. Once the initial discoveries are licensed to industry, those enterprises can further develop the findings and file patents for their follow-on technologies.

The researchers in this study focused on patents for industrial technologies, and found only a modest direct output of these patents from NIH funding. The team uncovered 17,093 patents that identified 30,829 NIH grants, about 8 percent of the total, as the source for the research funds leading to discovery or development of private-sector technologies.

The nature of scientific inquiry and discovery however, is rarely direct, with knowledge developed from one scientist often influencing the work of other labs. When adding in all citations of NIH-funded research in patents, the researchers found 81,462 private-sector patents referencing 112,408 NIH grants, or 31 percent of the total.

Another modest output of NIH research is drugs approved by FDA. The team found only 4,414 patents in its sample for FDA-approved drugs directly linked with about 1 percent of NIH grants. When taking in all references to NIH funded research, however, the slice of approved drugs increases to 5 percent. In addition, the analysis found studies considered “basic” or “applied” research had about the same likelihood of appearing in a U.S. patent, leading the authors to conclude, “the basic/applied distinctions may not be so useful in thinking about what types of research funding is more productive.”

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CARB-X Commits $48M for Antibiotic Resistance R&D

Carbapenem-resistant Enterobacteriaceae

Carbapenem-resistant Enterobacteriaceae bacteria (CDC.gov)

30 March 2017. A public-private partnership is spending $48 million in grants to biotechnology companies for research on treatments and diagnostics to counter antibiotic resistance, with half of that amount distributed immediately. The Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, or CARB-X, announced its first portfolio grants for 11 enterprises in the U.S. and U.K.

CARB-X is an initiative of Biomedical Advanced Research and Development Authority, or BARDA, an agency of the U.S. Department of Health and Human Services, National Institute of Allergy and Infectious Diseases, or NIAID, and the Wellcome Trust, a foundation based in London, that provide the funding or in-kind services. Partnering organizations include Boston University law school where CARB-X is headquartered, as well as the Broad Institute of MIT and Harvard, Massachusetts Biotechnology Council, California Life Sciences Institute, AMR Centre in the U.K., and RTI International.

CARB-X was created from initiatives in the U.S. and U.K. in 2015 and 2016 aimed to control the growing global problem of antibiotic resistance. The project plans to invest some $450 million over 5 years to advance 20 new antibacterial products into preclinical testing, and at least 2 new products into clinical trials. Private companies are then expected to finance further clinical testing. Wellcome Trust said today it anticipates contributing $155.5 million over this period.

A total of $48 million is allocated in the first set of grants, with half of the amount on initial awards and the remainder on progress payments as milestones are achieved. The grant recipients are:

Cidara Therapeutics in San Diego, for its immunotherapy discovery platform designed to create compounds that direct a patient’s immune cells to attack and eliminate bacterial, fungal, or viral pathogens. Cidara is receiving $3.9 initially, and eligible for another $3 million in milestone payments.

ContraFect Corp. in Yonkers, New York, for the company’s technology producing lysins, bacteriophage-derived enzymes shown in preclinical studies to act against antibiotic-resistant pathogens. ContraFect is getting $1.1 million at first, and eligible for $1 million later in milestone payments.

Entasis Therapeutics in Waltham, Massachusetts, for its work in developing oral treatments for multi-drug resistant gram-negative bacterial infections, including those caused by carbapenem-resistant enterobacteriaceae, for which many patients now find current oral drugs ineffective. Entasis is receiving $2.1 million immediately, and will be eligible for up to $4.2 million in progress payments.

Forge Therapeutics in San Diego, for the company’s work in blocking metallic-based enzymes found only in gram-negative bacteria and are essential to bacterial growth. Forge is getting $4.8 million initially and is eligible for another $4 million later on.

Microbiotix Inc. in Worcester, Massachusetts for its technology targeting secretions from dangerous bacteria, such as Pseudomonas aeruginosa, that reverse the pathogen’s disruption of the host’s innate immune response to infection. Microbiotix is set to receive $1.6 million upfront, and is eligible for another $1.6 million in milestone payments.

Oppilotech Ltd. in London, for its computational network modeling technology to produce agents known as potentiators that make it possible to penetrate cell membranes, allowing the use of conventional antibacterial compounds against drug-resistant microbes. Oppilotech is getting $0.12 million upfront.

Proteus in Edinburgh, Scotland, for the company’s optical imaging technology for high-speed and accurate visualization of bacterial infections in the lungs, to diagnose infections in critical care units. Proteus is receiving $0.64 million at first and eligible for another $0.48 million in progress payments.

Redx Pharma, in Alderley Park, U.K., for its work with bacterial inhibitors against difficult-to-treat gram-negative pathogens, including drug-resistant strains, as shown in tests with lab animals. Redx is set to receive $1 million.

Spero Therapeutics in Cambridge, Massachusetts, for the company’s combination drugs designed to disrupt the cell membranes of gram-negative bacteria, to treat dangerous infections such as enterobacteriaceae and acinetobacter baumannii. Spero is receiving $1.6 million initially, and eligible for up to $5.4 million later on.

Tetraphase Pharmaceuticals in Watertown, Massachusetts, for its chemistry technology to create new antibiotics for infections, including those active against gram-negative bacteria, such as enterobacteriaceae and acinetobacter baumannii. Tetraphase is expected to receive $4 million upfront.

Visterra Inc. in Cambridge, Massachusetts for the company’s work on antibody-drug conjugates designed as single-cure therapies for multi-drug resistant bacteria and viruses. Visterra is getting $3 million initially and eligible for up to $4.2 million in milestone payments.

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