Skip to main content
Premium Trial:

Request an Annual Quote

Santaris, GSK to Develop, Sell LNA-Based Antiviral Drugs; Santaris Could Gain $700M

Santaris Pharma and GlaxoSmithKline said this week that they will collaborate on the discovery, development, and commercialization of antiviral drugs based on Santaris’ locked nucleic acid technology.
Separately this week, Santaris said it has closed a €20.4 million ($30 million) Series C round of financing, which it said would enable it to remain solvent through the end of 2009.
Under the drug-development arrangement, which could be worth as much as $700 million to Santaris, GlaxoSmithKline has also taken an option to develop and commercialize Santaris’ microRNA-targeting hepatitis C drug candidate SPC3649.
According to the companies, Santaris will grant GlaxoSmithKline options to drug candidates discovered and developed during the collaboration in up to four different viral disease programs. GlaxoSmithKline will participate in this portion of the alliance through its Infectious Diseases Center of Excellence for Drug Discovery.
In each of the programs, Santaris will oversee drug development through the completion of phase IIa clinical trials, at which point GlaxoSmithKline may choose to exclusively license the worldwide rights to the drug candidates for further development and commercialization
In exchange, GlaxoSmithKline will pay Santaris a $3 million upfront fee for the first antiviral program and buy $5 million worth of the Danish company’s shares.
Should drug candidates from this first program reach the market, Santaris could receive milestone payments of up to $140 million. Similar upfront and milestone payments are payable to Santaris for the other three antiviral programs.
If GlaxoSmithKline options SPC3649, it will pay Santaris $5 million upfront, and could pay milestones of up to $122 million based on regulatory approvals in the US and Europe.
Santaris is also entitled to receive high single-digit to double-digit royalties on worldwide sales of products resulting from the alliance.
Additional terms were not disclosed.
According to Henrik Orum, Santaris’ CSO and vice president of business development, the main portion of the deal does not specifically cover miRNA.
“The deal allows for exclusivity on the virus; whatever sequences in the genome of the virus or whatever transcripts that arise from the virus [are] included in the program,” he told RNAi News this week. “If a virus encodes a non-coding RNA, [such as] a microRNA, that could also be a target [covered by the alliance. However], I’m not aware that viruses do that at this point.”
But GlaxoSmithKline’s option for SPC3649 does set up the British big pharma for a foray into the nascent field of miRNA-targeting therapeutics.
SPC3649 is an unformulated, single-stranded oligo based on Santaris’ LNA technology. Essentially, LNA are nucleic acid analogs in which the ribose ring is locked by a methylene bridge connecting the 2'-O atom with the 4'-O atom — features designed to increase the molecules’ affinity and stability. Santaris holds the exclusive, worldwide rights to LNA for therapeutic applications.

“The jury is out … on how miR-122 assists HCV in performing its replication cycle. But there are a couple of putative target sequences for microRNA-122 in the 5’ and 3’ regions of HCV. So [miR-122] definitely has the capability of binding to the HCV genome, and that may be how it permits replication to be completed.”

The drug candidate targets miR-122, the most abundantly expressed miRNA in the liver and one that appears to play a role in cholesterol regulation, lipid metabolism, and HCV replication.
“There are a couple of papers that show if you remove microRNA-122 in hepatocytes, you significantly disrupt the ability of HCV to replicate,” Orum explained. “If you come in with [SPC3649] and bind microRNA-122, you essentially sequester it in a form that is not able to interact directly with the HCV genome, [which] is how we conceive the mechanism of action.”


“The jury is out … on how miR-122 assists HCV in performing its replication cycle,” he added. “But there are a couple of putative target sequences for microRNA-122 in the 5’ and 3’ regions of HCV. So [miR-122] definitely has the capability of binding to the HCV genome, and that may be how it permits replication to be completed.”
Santaris is not the only company that believes miR-122 is a good target for HCV. Regulus Therapeutics, a joint venture between Alnylam Pharmaceuticals and Isis Pharmaceuticals, is also exploring the use of miR-122 antagonists against the virus (see RNAi News, 9/13/2007).


Santaris, however, appears to be the farthest along in its efforts. According to Orum, Santaris has completed non-human primate studies in which low doses of SPC3649, administered intravenously, significantly lowered levels of circulating cholesterol.
“We have just recently submitted a paper on those data … [and] we hope to have that published in the very near future,” he noted.
He said that Santaris has also completed investigational new drug application-enabling toxicology and pharmacokinetic studies on SPC3649 and expects to begin a phase I trial of the drug in healthy human volunteers in the first quarter of 2008.
This clinical study is likely to be run in Europe.
Orum also said that GlaxoSmithKline is currently conducting its own preclinical evaluation of SPC3649 to measure the drug’s efficacy against HCV rather than on cholesterol levels.
Officials from GlaxoSmithKline were not available for comment by press time.
Separately this week, Santaris announced that it has closed a €20.4 million ($30 million) Series C round of financing. As reported by RNAi News last month, the financing is expected to enable the company to fund its operations through the end of 2009 (see RNAi News, 11/15/2007).


The money also gives Santaris the freedom to put on hold its plans to go public, a move the company had been considering in order to raise the capital needed to advance its research and development programs.
Santaris said that the proceeds of the Series C financing will be used to support the development of its drug candidates and bring the company’s cash reserve to more than €40 million.

The Scan

Study Reveals New Details About Genetics of Major Cause of Female Infertility

Researchers in Nature Medicine conducted a whole-exome sequencing study of mote than a thousand patients with premature ovarian insufficiency.

Circulating Tumor DNA Shows Potential as Biomarker in Rare Childhood Cancer

A study in the Journal of Clinical Oncology has found that circulating tumor DNA levels in rhabdomyosarcoma may serve as a biomarker for prognosis.

Study Recommends Cancer Screening for Dogs Beginning Age Seven, Depending on Breed

PetDx researchers report in PLOS One that annual cancer screening for dogs should begin by age seven.

White-Tailed Deer Harbor SARS-CoV-2 Variants No Longer Infecting Humans, Study Finds

A new study in PNAS has found that white-tailed deer could act as a reservoir of SARS-CoV-2 variants no longer found among humans.