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Archive - Jan 3, 2019


Jazz Pharmaceuticals & Codiak BioSciences Announce Strategic Collaboration to Research, Develop, and Commercialize Engineered Exosomes to Create Therapies for Hard-to-Treat Cancers; Codiak to Receive $56 Million Upfront & Up to $1 Billion in Milestones

On January 3, 2018, Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and Codiak BioSciences, Inc., announced that the companies have entered into a strategic collaboration agreement focused on the research, development, and commercialization of exosome therapeutics to treat cancer. Codiak granted Jazz an exclusive, worldwide, royalty-bearing license to develop, manufacture, and commercialize therapeutic candidates directed at five targets to be developed using Codiak’s engEx™ precision engineering platform for exosome therapeutics. The targets focus on oncogenes that have been well validated in hematological malignancies and solid tumors, but have been undruggable with current modalities, including NRAS and STAT3. Under the terms of the agreement, Codiak is responsible for the execution of pre-clinical and early clinical development of therapeutic candidates directed at all five targets through Phase 1/2 proof-of-concept studies. Following the conclusion of the applicable Phase 1/2 study, Jazz will be responsible for future development, potential regulatory submissions, and commercialization for each product. Codiak has the option to participate in co-commercialization and cost/profit-sharing in the U.S. and Canada on up to two products. As part of the agreement, Jazz will pay Codiak an upfront payment of $56 million. Codiak is eligible to receive up to $20 million in preclinical development milestone payments across all five programs. Codiak is also eligible to receive milestone payments totaling up to $200 million per target based on Investigational New Drug application acceptance, clinical and regulatory milestones, including approvals in the U.S., European Union and Japan, and sales milestones.

WGS of Bulldogs, French Bulldogs, & French Terriers IDs 1 Mutation in 12 Million Variations That Causes “Screwtail”-- Mutation Is in DISHEVELlED 2 (DVL2), Gene Similar to DVL1 & DVL3 That Are Mutated in Rare Human Disease Robinow Syndrome

With their small size, stubby faces, and wide-set eyes, bulldogs, French bulldogs, and Boston terriers are among the most popular of domestic dog breeds. Now, researchers at the University of California (UC), Davis, School of Veterinary Medicine have found the genetic basis for these dogs' appearance, and linked it to a rare inherited syndrome in humans. Bulldogs, French bulldogs and Boston terriers aren't the only dogs with short, wide heads, but they do share another feature not found in other breeds: a short, kinked tail or "screwtail," said Professor Danika Bannasch, Department of Population Health and Reproduction in the UC Davis School of Veterinary Medicine. These three breeds all lack the vertebrae that make up the tail bone, she said. The researchers sequenced the whole genome -- the entire DNA sequence -- of 100 dogs, including 10 from screwtail breeds. All the participating dogs were privately owned pets seen at the UC Davis Veterinary Medical Teaching Hospital, whose owners agreed to participate. Graduate students Tamer Mansour and Katherine Lucot, with Dr. C. Titus Brown, Associate Professor at the School of Veterinary Medicine and Genome Center, searched through the DNA sequences to find changes associated with screwtail breeds. From more than 12 million individual differences they were able to identify one mutation, in a gene called DISHEVELLED 2 (DVL2). This variant was found in 100 percent of the bulldogs and French bulldogs sampled, and was very common in Boston terriers. This kind of whole genome comparison is relatively new, Dr. Bannasch said. "Normally, we would have first had to identify a region of DNA and work from there," she said. "We could look at breed-specific traits, but not as well as we can now." Professor Henry Ho at the UC Davis School of Medicine studies similar genes in humans.

Altering Activity of Brain Development Gene Cdk5 Causes Breakdown in Autophagy, Prompting Hyperactive Innate Immunity Attack That Destroys Dopamine-Releasing Neurons in Fly Brains; Similar Process May Occur in Several Neurodegenerative Diseases

In a study of fruit flies, NIH scientists sugges that the body's immune system may play a critical role in the damage caused by aging brain disorders. The results are based on experiments in which the researchers altered the activity of Cdk5, a gene that preclinical studies have suggested is important for early brain development and may be involved in neurodegenerative diseases, such as Lou Gehrig’s disease (ALS), Alzheimer's, and Parkinson's disease. Previously, they found that altering Cdk5 sped up the genetic aging process, causing the flies to die earlier than normal and have problems with walking or flying late in life and greater signs of neurodegenerative brain damage. In the current study, published in the January 2, 2019 issue of Cell Reports, the researchers suggested that altering Cdk5 resulted in the death of dopamine-releasing neurons, especially in the brains of older flies. Typically, Parkinson's disease damages the same types of cells in humans. Further experiments in flies suggested the neuron loss happened because altering Cdk5 slowed autophagy, a cell's waste disposal system that rids the body of damaged cells in a contained, controlled fashion, which, in turn, triggered the immune system to attack the animal's own neurons. This immune system attack is a much "messier" and more diffuse process than autophagy. Genetically, restoring the waste system or blocking the immune system's responses prevented the reduction in dopamine neurons caused by altering Cdk5.