In-vivo investigators
April 2013
by Ilene Schneider  |  Email the author


SEATTLE—To identify the value of drug combinations in vivo early in the development of cancer drugs, Presage Biosciences, a leader in discovering effective cancer drug combinations, has entered into a strategic collaboration agreement with Celgene Corp., a multinational biopharmaceutical company investigating hard-to-treat cancers.   
Under the terms of the agreement, Celgene will invest $13 million to develop Presage's proprietary technology platform to identify novel drug combinations for solid tumor indications. Presage will receive an upfront payment, an equity investment and potential downstream payments. The eventual goal is to get the drug combinations into the clinic.
"Early in the drug development process, researchers want to screen components to see how the drug knocks down the target," explains Nathan Caffo, president of Presage Biosciences. "By directly placing very small doses of multiple candidate drugs into the tumor, we can see if the target is engaged and if the cells are responding to it. We can also see how the drugs behave in different parts of the tumor, and we can do it in vivo."  
Presage Biosciences' platform enables the controlled delivery of cancer drugs into different parts of the tumor using an array technology that transports the drug through the skin and into the tumor, where the results are analyzed three-dimensionally to determine the effect of the drugs. The platform, which is being used with canine subjects, is the only technology that allows for the direct comparison of multiple drugs or drug combinations in the same living tumor.  
According to Dr. Thomas Daniel, president of research and early development at Celgene, drug development is currently "challenged by heavy reliance on in-vitro test systems and animal xenografts of little relevance to individual patients." He says he believes the Presage platform addresses this challenge, enabling rapid assessment of drug candidates and combinations in relevant models, "with potential to base critical drug development decisions on in-vivo response data."  
The drugs administered into the tumor are at a dosage level that is "a thousand-fold less" than the systemic dosage, Caffo explains, adding, "with late-stage molecules in clinical trials, it only matters what happens in the clinic, but a lot of work goes into the determinations beforehand. There is a very long process to determine the maximum tolerated dosage when doing combinations. It can be an 18-month process. Instead, we deliver the combinations into the tumor in microdose to screen rapidly with less potential for toxic effects."  
According to Caffo, the idea evolved when Presage Biosciences Founder Dr. James Olson, a pediatric oncologist, was treating children with end- stage tumors. During clinical trials, the children were spending their last few months in the Fred Hutchinson Cancer Center. Olson came up with the idea of trying out drugs without exposing his subjects to chemical toxicity. If the tumor resisted therapy, the drug should be eliminated from consideration. He came up with the idea of microdosing lymphomas, resecting the tumor and gradually eliminating ineffective drugs. The company, which was founded in 2008, obtained a $4 million grant from the National Cancer Institute, based on Olson's technology platform.  
Presage Biosciences, which also signed a collaboration agreement with Millennium: The Takeda Oncology Company a year ago to find drug combinations that can be used against solid tumors, encountered Celgene management through Accelerate Brain Cancer Cure, a venture philanthropy organization co-founded by AOL pioneer Steve Case. Celgene officials made it clear that they wanted "to go after tough cancers, such as pancreatic and glioblastoma," Daniel explains.  
Currently, there are more than 300 clinical trials at major medical centers using compounds from Celgene to study patients with incurable hematological 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 the patients, which will be canines that have failed rounds of chemotherapy. Celgene, which intends to "fund the program and then step back," according to Caffo, will provide the drugs.
"We can't control dogs in the clinic the way we control mice in the laboratory, but we're doing something novel, because canines are clinically relevant and similar to humans," Caffo says. "We're also getting patient accrual, because people want to give meaning to their pet's life by advancing science. In fact, the owners of our first patient became investors in Presage."
Code: E041325

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