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We’re not done with chemotherapy, so why not improve it?

While it's hard to get excited about a modified chemotherapy drug in an era of personalized medicine, checkpoint inhibitors, and CAR-T immunotherapies, Modra Pharmaceuticals' modified taxane drugs could make a sizeable impact in the field.

It’s hard to get excited about a modified chemotherapy drug in an era of personalized medicine, checkpoint inhibitors, and CAR-T immunotherapies.

But it would be a mistake to not embrace a potential advance in this field, given the degree to which oncologists (and even some other specialties, such as rheumatology) still rely on this class of drugs.

Based in the Netherlands, Modra Pharmaceuticals is taking aim at a group of chemotherapy agents known as taxanes, which include paclitaxel (Taxol) and docetaxel (Taxotere). Despite their widespread use, taxanes are poorly soluble — a characteristic that has forever restricted them to intravenous (IV) administration.

The company and its platform are built around so-called Modulated Oral Drug Absorption (MODRA) Technology, which is designed to address two primary challenges, explained Eric van der Putten, Modra CEO and a partner at VC firm Aglaia Biomedical Ventures. 

The first hurdle is getting the poorly water soluble molecules into a tablet formulation, he said. At that point, the drug runs into the body’s natural defense mechanisms in the stomach.

“The second invention is that we know how to temporarily block this defense mechanism for an hour or so,” van der Putten said. “To make sure that the nicely water soluble docetaxel also pass the gut and secondly, are not completely broken down by the metabolic system before they reach their effector cells.”

According to van der Putten, both aspects of the approach are backed by a lot of published data, reflecting the company’s strong roots in Dutch academia.

Modra was founded in June 2010 with intellectual property created at the Netherland’s Cancer Institute. For the next six years, the enterprise remained virtual, he said. Its founders chose to continue their work at the academic center and managed to progress Modra’s lead candidate right through to the end of Phase 1 trials using academic and government grants.

Aglaia and van der Putten entered the picture with a Series A financing round that closed in April 2016. From there, the company put its roots down and began hiring its team.

In mid-June, Modra reached another milestone: Enrollment for a Phase 2 trial of its lead compound, ModraDoc006/r, in metastatic castration-resistant prostate cancer patients had begun.

It sounds like the platform is progressing well, but is there a sustainable market for a souped-up chemotherapy agent in this era of precision medicine?

In an interview at ASCO 2017, head of the Prostate Cancer Foundation Jonathan Simons was heralding one of the biggest strides the field has seen in treating the most advanced form of the disease. Simons believes new data on a more targeted therapy, abiraterone acetate (Zytiga), could usher in the demise of chemotherapies as a necessary part of many prostate cancer regimens.

But that was the old taxane drugs, which came with myriad toxicities.

“We have treated about 120 patients up to now with the oral docetaxel formulation and the safety profile of the tablet formulation seems to be distinctly different from the IV docetaxel formulation,” van der Putten said. “It appears to be a much milder cytotoxic agent in its oral form than it is in the intravenous formulation.”

That opens the door to earlier treatment and more combination options, breathing new life into a dying drug. Taxanes have always been effective, van der Putten stressed. Now with an oral formulation and fewer side effects, Modra is hoping to make them more palatable for patients and physicians.

And there is some billion-dollar precedent. Patrick Soon-Shiong’s former company Abraxis BioScience led the way with a modified version of paclitaxel (Taxol), dubbed Abraxane. Celgene subsequently acquired the company for $2.9 billion in 2010.

Photo: YDL, Getty Images

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