NEW YORK (360Dx) – Taiwanese pharma firm TaiRx has established a US-based corporation to commercialize a drug and companion diagnostic targeting the nodal protein, which has been linked to aggressiveness and drug resistance in a variety of cancers.
Formed in August, the Rockville, Maryland-based company, called TaiRx US, is a joint venture between TaiRx and BioHealth Innovation (BHI), a public-private partnership organization that promotes the development of biotech and health businesses in the Washington DC region.
TaiRx will work to develop and commercialize an antibody-based drug that blocks the binding of the nodal protein to its receptor. The technology is based on scientific work done by the lab of Mary Hendrix, formerly a researcher at Northwestern University and currently the president of Shepherd University.
According to BHI CEO Richard Bendis, the company is currently focused on humanization of the monoclonal antibody it will use to target nodal and plans to start first-in-human trials in 2020. The companion diagnostic work is still in the "embryonic stage," he said.
The identification of nodal as a potentially important protein in cancer development emerged from work by Hendrix and her colleagues that looked at the behavior of aggressive cancer cells placed into embryonic environments.
In this work, the researchers observed that "not only does the embryonic environment affect the tumor cells, but the tumor cells can also affect the environment," Hendrix said. "An assessment of the major embryonic pathways that might be involved led to the identification of nodal being expressed in the aggressive cancer cell population."
Nodal is a member of the Transforming Growth Factor superfamily of proteins and is involved in cell differentiation during embryogenesis. It is not typically expressed in adults but, Hendrix noted, can be reactivated in some cancers.
Hendrix's lab has published a number of papers on nodal and nodal signaling over the last 10 years demonstrating that the protein is involved in driving cancer stem cell populations and that its expression is correlated with cancer invasion, metastasis, drug resistance, and prognosis.
According to Hendrix, nodal expression has been detected in 10 different cancer types including melanoma, breast, liver, pancreatic, ovarian, and colon, and expression drives the cancer stem cell phenotype, producing subpopulations of tumor cells that are not targeted by existing therapies and so contribute to drug resistance.
In a 2015 study in Molecular Cancer Research, Hendrix and her colleagues found that nodal expressing cells in metastatic melanoma were not targeted by the chemotherapeutic dacarbazine or B-RAF inhibitors. In a 2016 study in Cell Cycle, they found that nodal was not effectively targeted by doxorubicin treatment in triple-negative breast cancer.
The idea underpinning TaiRx US's development of an anti-nodal drug is that the protein could be targeted in combination with existing therapies to improve their effectiveness. Hendrix and TaiRx have demonstrated in mouse models that adding treatment with an anti-nodal antibody to conventional treatments for melanoma reduced the volume of the primary tumor and lung metastases.
Bendis said that, regarding plans for a companion diagnostic to guide treatment with the anti-nodal drug, the company had not yet decided on a particular approach or assay type. Hendrix suggested, though, that "the initial and potentially most beneficial test for nodal in cancer patients would involve an ELISA-like assay for nodal protein in cancer patient serum samples."
She added that she and her colleagues have previously demonstrated the potential utility of measuring nodal expression in patient biopsies. In a 2012 study in Breast Cancer Research that used immunohistochemistry to assess nodal expression in biopsies from 431 drug-naïve patients with either benign or malignant breast disease, the researchers found that higher nodal expression was associated with undifferentiated, advanced stage, invasive breast cancer.
TaiRx is a publicly traded Taiwanese firm that was launched in 2011 to develop and commercialize cancer drugs targeting tumor vasculogenic mimicry, a phenomenon, first observed by Hendrix and her colleagues, in which aggressive tumors form microvascular channels that promote tumor perfusion. The company currently has seven small molecule drugs under development.
According to Bendis, the company was interested in entering the US market, initially for its anti-nodal drug and companion diagnostic and potentially for other products in the future. To do this it formed TaiRx US, partnering with BHI to access the commercial expertise it needed for a US launch.
TaiRx has been pursuing a dual regulatory path in both Taiwan and the US, and so it had "some experience with the [US Food and Drug Administration]," Bendis said.
However, he noted, the company "didn't have any experience in setting up a commercial operation in the United States, nor did they have anyone in Taiwan who could come to the United States and run that operation. And so they needed a business partner with commercial experience in the United States."
BHI "has significant but not controlling equity" in TaiRx US, Bendis said.
The new firm will be led by Stephen Wolpe, an entrepreneur-in-residence at BHI who will serve as president and CEO. Wolpe was previously a biotech consultant and before that an executive at Wellstat, a group of privately-held biopharma firms.
Bendis said that while the TaiRx US headquarters will initially house primarily commercial operations, the company plans to add laboratory space sometime next year.
He added that the company is currently looking to raise around $10 million to support its efforts and is exploring options including public funding like National Institutes of Health Small Business Innovation Research grants, as well as venture capital and deals with potential strategic partners like pharma and biotech firms.