In-vivo investigators

Presage and Celgene investigate microdoses of drug combos to tackle solid tumors

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SEATTLE—To identify the value of drug combinations invivo early in the development of cancerdrugs, Presage Biosciences, a leader in discovering effective cancer drugcombinations, has entered into a strategic collaboration agreement with CelgeneCorp., a multinational biopharmaceutical company investigating hard-to-treat cancers. 
 
 
Under the terms of the agreement, Celgene will invest $13million to develop Presage's proprietary technology platform to identify noveldrug combinations for solid tumor indications. Presage will receive an upfrontpayment, an equity investment and potential downstream payments. The eventualgoal is to get the drug combinations into the clinic.
 
"Early in the drug development process, researchers want toscreen components to see how the drug knocks down the target," explains NathanCaffo, president of Presage Biosciences. "By directly placing very small dosesof multiple candidate drugs into the tumor, we can see if the target is engagedand if the cells are responding to it. We can also see how the drugs behave indifferent parts of the tumor, and we can do it in vivo."
 
 
Presage Biosciences' platform enables the controlleddelivery of cancer drugs into different parts of the tumor using an arraytechnology that transports the drug through the skin and into the tumor, wherethe results are analyzed three-dimensionally to determine the effect of thedrugs. The platform, which is being used with canine subjects, is the onlytechnology that allows for the direct comparison of multiple drugs or drugcombinations in the same living tumor.
 
 
According to Dr. Thomas Daniel, president of research andearly development at Celgene, drug development is currently "challenged byheavy reliance on in-vitro test systemsand animal xenografts of little relevance to individual patients." He says hebelieves the Presage platform addresses this challenge, enabling rapidassessment of drug candidates and combinations in relevant models, "withpotential to base critical drug development decisions on in-vivo response data."
 
 
The drugs administered into the tumor are at a dosage levelthat is "a thousand-fold less" than the systemic dosage, Caffo explains,adding, "with late-stage molecules in clinical trials, it only matters whathappens in the clinic, but a lot of work goes into the determinationsbeforehand. There is a very long process to determine the maximum tolerateddosage when doing combinations. It can be an 18-month process. Instead, wedeliver the combinations into the tumor in microdose to screen rapidly withless potential for toxic effects."
 
 
According to Caffo, the idea evolved when PresageBiosciences Founder Dr. James Olson, a pediatric oncologist, was treatingchildren with end-stage tumors. During clinical trials, the children werespending their last few months in the Fred Hutchinson Cancer Center. Olson cameup with the idea of trying out drugs without exposing his subjects to chemicaltoxicity. If the tumor resisted therapy, the drug should be eliminated fromconsideration. He came up with the idea of microdosing lymphomas, resecting thetumor and gradually eliminating ineffective drugs. The company, which wasfounded in 2008, obtained a $4 million grant from the National CancerInstitute, based on Olson's technology platform.
 
 
PresageBiosciences, which also signed a collaboration agreement with Millennium: TheTakeda Oncology Company a year ago to find drug combinations that can be usedagainst solid tumors, encountered Celgene management through Accelerate BrainCancer Cure, a venture philanthropy organization co-founded by AOL pioneerSteve Case. Celgene officials made it clear that they wanted "to go after toughcancers, such as pancreatic and glioblastoma," Daniel explains.
 
 
Currently, there are more than 300 clinical trials at majormedical centers using compounds from Celgene to study patients with incurablehematological and solid tumor cancers, including multiple myeloma,myelodysplastic syndromes, chronic lymphocyte leukemia, non-Hodgkin's lymphoma,myelofibrosis, small cell lung cancer and prostate cancer.
 
In the collaboration, Presage Biosciences will evaluate thepatients, which will be canines that have failed rounds of chemotherapy.Celgene, which intends to "fund the program and then step back," according toCaffo, will provide the drugs.
 
"We can't control dogs in the clinic the way we control micein the laboratory, but we're doing something novel, because canines areclinically relevant and similar to humans," Caffo says. "We're also gettingpatient accrual, because people want to give meaning to their pet's life byadvancing science. In fact, the owners of our first patient became investors inPresage."


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