Rain Therapeutics Inc. (Fremont, Calif.) closed a tranched $18.4 million series A round led by Biotechnology Venture Fund (BVF), with participation from fellow new investors Perceptive Advisors, Auckland UniServices' Inventors Fund and FMB Research’s Franklin Berger. Other undisclosed private investors also participated.
Rain co-founder, CEO and Chairman Avanish Vellanki told BioCentury the series A funding will provide about three years of cash, enough to complete a Phase II proof-of-concept trial of Rain's sole candidate, tarloxotinib, in non-small cell lung cancer patients with EGFR and ErbB exon 20 insertion mutations. Rain expects to begin the trial in 1H19.
The Phase II trial represents another chance for the hypoxia-activated prodrug of an EGFR inhibitor. Threshold Pharmaceuticals Inc. discontinued development of tarloxotinib in 2016 after reporting interim data from two Phase II trials, including the TH-CR-601 trial in patients with EGFR-mutant, T790M-negative advanced NSCLC. In TH-CR-601, tarloxotinib led to no confirmed partial responses (PRs) and seven cases of stable disease in 21 evaluable patients, missing the primary interim response rate threshold to expand enrollment into the next stage of the trial.
Vellanki said most patients with EGFR-mutant, T790M-negative NSCLC "are likely to have" oncogenic drivers not based on EGFR signaling.
"We believe the prior clinical study did not include patients with tumors that relied on EGFR signaling, and hence included patients that would have been unlikely to have demonstrated a response to any EGFR inhibitor therapy," he added.
Last year, Rain reported preclinical data showing shRNA targeting EGFR or HER2 decreased cell proliferation in three patient-derived EGFR exon 20 insertion mutant cell lines resistant to approved EGFR inhibitors compared with control shRNA, suggesting those tumors rely on EGFR signaling. In a xenograft mouse model of EGFR exon 20 insertion mutant lung cancer, tarloxotinib decreased tumor growth compared with EGFR inhibitors Gilotrif afatinib from Boehringer Ingelheim GmbH (Ingelheim, Germany) and Erbitux cetuximab from Eli Lilly and Co. (NYSE:LLY) or Gilotrif plus Erbitux. Rain presented the data at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics meeting in Philadelphia.
Vellanki noted tarloxotinib led to one confirmed response in Threshold's Phase II TH-CR-602 trial to treat recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) or skin (SCCS). Interim data showed the prodrug led to no confirmed PRs and eight cases of stable disease in 22 evaluable SCCHN patients, and one confirmed PR in seven evaluable SCCS patients.
Vellanki said tarloxotinib could be evaluated in other cancer populations. Rain also plans to develop or in-license additional assets to treat cancer with a single oncogenic driver in patients unresponsive to current therapies.
Rain has worldwide, exclusive development and commercial rights for tarloxotinib from University of Auckland, which previously licensed the candidate to Threshold under a 2014 deal.
Rain has raised a total of $19.4 million, including a $1 million seed round from individual private investors in December, Vellanki said.
BVF's Gorjan Hrustanovic will join Rain's board.