Jazz Pharmaceuticals will use Codiak BioSciences’ engEx™ precision engineering platform to research, develop, and commercialize exosome therapeutics for cancer through a collaboration that could generate more than $1 billion for Codiak, the companies said today.

Codiak has granted Jazz an exclusive, worldwide, royalty-bearing license to develop engineered exosomes to be applied as therapeutic candidates directed at five targets.

The targets will focus on oncogenes that have been well validated in hematological malignancies and solid tumors but have been undruggable with current modalities, including neuroblastoma-RAS (NRAS) and signal transducer and activator of transcription 3 (STAT3), according to the companies.

The therapeutics will be engineered through Codiak’s engEx, a platform for exosome design and manufacturing designed to allow for precise targeting of key molecular pathways involved with human disease.

Codiak reasons that two inherent characteristics of exosomes—their membrane composition and immune-silent nature—offer opportunities for their application as drug delivery vehicles. The membrane composition of exosomes allows them to deliver various molecules from cell to cell by efficiently entering target cells or by interacting with proteins on the cell’s surface.

Because exosomes are believed to evade the immune system, they can elude the various sensors the body uses to detect and halt the spread of foreign substances.

Using engEx, Codiak plans to modify exosomes to express and deliver therapeutic drug candidates of various classes—including small molecules, proteins, peptides, cytokines, and nucleic acids—onto the surface or in the lumen of its therapeutic exosomes. The platform allows for exosomes to be either loaded inside with potent and specific payloads, or for producing cells to be programmed to secrete exosomes carrying drug on their surface or in their interior.

According to Codiak, the engineered “messages” become instructions for recipient cells. Instructions encoded within the luminal cargo of the exosome are taken up by the cell cytosol. Instructions encoded in the exosome membrane are delivered via a protein/protein interaction at the cell surface.

Relevant but intractable targets

“This collaboration allows Codiak to accelerate the potential of our engEx platform as we advance our lead candidates and core pipeline,” Codiak president and CEO Douglas E. Williams, PhD, said in a statement. “We believe that the Codiak engEx platform, along with Jazz’ insights into relevant but intractable targets, creates a unique opportunity to improve patient outcomes in various cancers.”

Codiak agreed to oversee execution of preclinical and early clinical development of therapeutic candidates directed at all five targets through Phase I/II proof-of-concept studies. Following the conclusion of the applicable Phase I/II study, Jazz will be responsible for future development, potential regulatory submissions, and commercialization for each product, the companies said.

In addition, Codiak has the option to participate in co-commercialization and cost/profit-sharing in the U.S. and Canada on up to two products.

Jazz agreed to pay Codiak $56 million upfront, up to $20 million in preclinical development milestone payments across all five programs, and up to $200 million in payments for each of the five targets tied to achieving milestones. Those include IND application acceptance, clinical, regulatory—including approvals in the U.S., EU, and Japan—and sales milestones, Jazz and Codiak said.

Jazz also agreed to pay Codiak tiered royalties on net sales of each approved product, with percentages ranging from mid-single digits in the lowest tier to high teens in the highest tier.

“The exosome approach is differentiated and represents the ideal complement to our CombiPlex platform and other collaboration programs,” added Jazz chairman and CEO Bruce Cozadd. “The ability to develop multiple new therapies through these technologies is an important advance as we seek to add long-term value for patients and shareholders.”

CombiPlex is designed to enable the design and rapid evaluation of various combinations of enhanced anticancer therapies. The technology seeks to identify the most synergistic ratio of drugs in vitro and fix that ratio in a nano-scale delivery complex that maintains the synergistic combination after administration. CombiPlex uses two nanoscale delivery platforms: liposomes to control the release and distribution of water-soluble drugs and drugs that are both water- and fat-soluble (amphipathic), and nanoparticles to control the release and distribution of non-water-soluble (hydrophobic) drugs.

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