November 18, 2015
By Mark Terry, BioSpace.com Breaking News Staff
South San Francisco-based Threshold Pharma announced today that it had signed a co-promotion deal with Darmstadt, Germany-based Merck KgaA . This deal is an extension of a 2012 License and Co-Development Agreement worth up to $540 million.
The new deal is for evofosfamide, previously dubbed TH-302, which is currently being studied in two Phase III clinical trials. Both trials are fully recruited. One is studying the drug in combination with doxorubicin versus doxorubicin alone in patients with locally advanced unresectable or metastatic soft tissue sarcoma (STS). The second trial studies evofosfamide in combination with gemcitabine versus gemcitabine and placebo in patients with locally advanced unresectable or metastatic pancreatic cancer. Top-line data for the two trials are expected by the end of the year.
This new deal gives Threshold the right to develop its own sales to collaborate in the U.S. with Merck’s U.S. sales force. Merck will otherwise hold all other commercial and regulatory functions associated with the launch and promotion. The milestone payments related to development and royalties stay the same.
“We are pleased to have reached an agreement with our partner Merck KGaA, Darmstadt, Germany on definitive terms for our option to co-promote evofosfamide in the U.S.,” said Barry Selick, Threshold’s chief executive officer, in a statement. “The ability to co-promote and field a sales force represents one of two key options allowing Threshold to participate in the commercial phase of evofosfamide’s lifecycle should it receive FDA approval. Importantly, the license agreement also provides us with an option to co-commercialize evofosfamide in the U.S., depending upon achieving certain milestones, which would allow us to share in up to fifty percent of the profits from the sale of the drug. Threshold is well positioned to integrate a commercial arm to its oncology discovery and development organization.”
Threshold Pharmaceuticals has been on a more or less upward trend with some volatility this year. Shares traded on Feb. 11, 2015 for $3.62 per share, rose to $4.61 on Mar. 4, sagged back to $3.49 on May 4, then spiked to $5.11 on Sept. 18. Shares dropped again to $3.62 before recovering. They currently trade for $4.03 per share.
A recent overall rating gave an average rating of a “Strong Buy” by Sacks in Chicago, Ill. All eight analysts polled gave the company a “Strong Buy.” In its third-quarter earnings, the company indicated actual sales of $3.68 million, very close to the consensus project of six analysts, which had been $3.705 million.
On Nov. 6, the company indicated promising preclinical data for tarloxotinib for the treatment of EGFR inhibitor resistant cancers. “Our preliminary findings suggest that tarloxotinib may be able to overcome wild-type EGFR-driven resistance to TKI therapy,” said Adam Patterson, a researcher at the University of Auckland in a statement. “We believe this is related to the role of hypoxia in driving wild-type EGFR signaling within tumors coupled with the hypoxia-activation of tarloxotinib.”
“This important translational work continues to support our ongoing proof-of-concept Phase II trials in patients with non-small cell lung cancer (NSCLC) and in patients with squamous cell carcinomas head and neck (SCCHN) and squamous cell carcinomas of the skin (SCCS),” said Tillman Pearce, Threshold’s chief medical officer, in a statement. “Initial PET imaging using our proprietary hypoxia imaging agent, [18F]-HX4, shows that imaging hypoxia in these tumors is possible. We hope that by combining imaging with response data we can start to determine which patients would benefit most from tarloxotinib therapy. We look forward to having preliminary results from these studies in the first half of 2016.”
This is an area of research that Threshold is focused on. When tumors grow rapidly, they outgrow their blood supply, which means they are deprived of oxygen, or are hypoxic. As a result, some cancer cells change their metabolism in order to continue to grow and proliferate in a low-oxygen environment. Drugs such as evofosfamide can be activated under those low-oxygen microenvironments, which the company believes will allow them to be effective in a wide range of cancer types.
