Delta-Fly Pharma wants to make cancer drug development faster, cheaper and more efficient. Using its module technology, the Japanese biotech has bypassed elements of early-stage research to quickly build a broad pipeline of oncology drugs led by a phase 3 leukemia candidate. Now, Delta-Fly is step- ping up its international ambitions with the filing of a new drug application (NDA) and the opening of an office in North America.
These activities build on Delta-Fly’s work to upend cancer research and development (R&D). Conventional drug discovery entails the identification of an enzyme or receptor involved in a disease pathway and the design of a compound against that target. This approach is expensive and time consuming. Millions of dollars and several years are required for a drug to be ready for human testing. Many candidates never reach this stage or are found to be ineffective or unsafe when they do, contributing to the inefficiency of the process.
Seeking a better way to discover and develop medicines, Delta-Fly looked to the assembly approach used by the automotive and smartphone industries. These industries combine modular elements into finished products to accelerate development timelines and facilitate ongoing modifications.
Delta-Fly is applying the assembly approach to drug development through the concept of module technology. Rather than starting with targets, Delta-Fly starts with existing drugs that have suboptimal risk–benefit profiles. Using its experience with polymers and its broad expertise in R&D, Delta-Fly enhances the safety and efficacy of these compounds and quickly modifies them to create new drug variations.
When Delta-Fly began operating in late 2010, it anticipated that the module technology would enable the faster advancement of candidates for less money than is typical. Today, Delta-Fly has a broad pipeline of cancer drugs, led by a phase 3 asset that validates its belief in module technology.
A broad cancer pipeline
The effectiveness of Delta-Fly’s approach is illustrated by the development of the deoxycytidine analog DFP-10917. Physicians have used deoxycytidine analogs, such as gemcitabine, to treat patients with solid tumors or leukemia for years. However, such drugs are rapidly inactivated by enzymes, forcing physicians to deliver high doses to achieve the desired efficacy. DFP-10917, formerly known as CNDAC, was originally developed in the 1990s and underwent studies that suggested it has a different cytotoxic mechanism than that of gemcitabine. These studies found that the drug is a cancer cell cycle checkpoint inhibitor capable of treating hematological cancers.
More recently, Delta-Fly has built on work from the 1990s and early 2000s by running preclinical in vivo studies to investigate the cumulative dose and infusion schedule of DFP-10917. Encouraged by results showing that low doses of DFP-10917 inhibit tumor growth by more than gemcitabine without causing any serious toxicity, Delta-Fly moved the candidate into a phase 1/2 trial in patients with relapsed or refractory acute myeloid leukemia (AML).
The clinical trial validated Delta-Fly’s belief in the anti-tumor activity of DFP-10917, clearing the candidate to move into a late-phase trial in patients with relapsed or refractory AML. The rapid progress of DFP-10917 has put Delta-Fly on track to win approval in around 2021. DFP-10917 is the lead program in a pipeline abundant with assets developed using module technology. Delta-Fly is also evaluating cancer stem cell regulator DFP-14323 in combination with epidermal growth factor receptor tyrosine kinase inhibitors in patients with non-small-cell lung cancer in phase 2 trials, and is running clinical trials of the cancer cell metabolite regulator DFP-11207 in pancreatic cancer. The rest of the pipeline features a clutch of drugs that are in and around clinical-phase development, such as the tumor microenvironment modulator DFP-17729 and liposomal thymidylate synthase-targeting short hairpin RNA molecule DFP-10825 (Fig. 1).
Fig. 1 | Module technology and research and development pipeline for innovative cancer therapy. GLP, good laboratory practice; IND, investigational new drug; ip, intraperitoneal; iv, intravenous; TS-shRNA, thymidylate synthase-targeting short hairpin RNA.
Delta-Fly is planning to test DFP-17729 in combination with gemcitabine in patients with advanced pancreatic cancer and with an anti-programmed cell death 1 antibody in advanced gastric cancer. Intraperitoneal injection of DFP-10825 in patients with intraperitoneal disseminated ovarian, gastric and pancreatic cancers is effective in combination with taxanes.
Taking risk out of R&D
The lead program DFP-10917 and RNA interference asset DFP-10825 are very different drugs but they, and the rest of Delta-Fly’s pipeline, are linked by a common ethos. The ethos is centered on creating effective cancer drugs with tolerable side effect profiles. Module technology is enabling Delta-Fly to create drugs that fulfill this vision.
In creating drugs that better meet the needs of patients, Delta-Fly is also changing the balance of risk and reward in oncology R&D. While conventional R&D forces companies and investors to take a high-risk, high-reward approach, Delta-Fly’s model has spawned assets that offer above-average returns for moderate risk.
These assets have advanced quickly during Delta-Fly’s short history, validating the effectiveness of its module technology and positioning it for success in the years to come.
Kiyoshi Eshima, President
Delta-Fly Pharma Inc.