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With Alnylam Settlement Money in Hand, Tekmira Plans 'Aggressive' Pipeline Advancement

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Emboldened by a $65 million payout from Alnylam Pharmaceuticals as part of a litigation settlement, Tekmira Pharmaceuticals this week offered a pipeline update that includes the “aggressive advancement” of a number of drug candidates.

“We recognize that we must demonstrate the clinical value of our pipeline in a range of therapeutically important, commercially attractive markets,” Tekmira President and CEO Mark Murray said during a conference call held to discuss the firm's third-quarter financial results. “Our now-strengthened balance sheet provides added fuel for Tekmira to have a number of therapeutic candidates in various stages of clinical development by 2015.”

As reported by Gene Silencing News, this week Alnylam and Tekmira agreed to settle their longstanding technology-misappropriation and patent-infringement lawsuits, with Alnylam paying Tekmira $65 million now and potentially another $10 million in milestones next year.

According to Tekmira CFO Ian Mortimer, the initial payment, minus attorneys' fees, is expected to push the company's cash runway into 2015. “Our assumptions include aggressive advancement of our product pipeline whereby we could have multiple products in clinical development,” he noted during the call.

Tekmira's lead program is focused on TKM-PLK1, an siRNA-based cancer drug targeting the cell cycle protein polo-like kinase 1 and formulated with the company's proprietary lipid nanoparticles, or LNPs. This summer, Tekmira released interim data from an ongoing phase I trial that showed the compound to be well tolerated despite what was characterized as an “aggressive” dosing regimen (GSN 8/16/2012).

“To date, TKM-PLK1 has been administered to 23 patients, with 128 doses administered ranging from 0.15 milligrams per kilogram to 0.9 milligram per kilogram,” Murray said during this week's call. “Even in this very heavily pretreated patient population, all of whom have advanced disease, we have seen encouraging signs of drug activity. One patient achieved a 63 percent reduction in tumor burden, with partial response … [while] another patient achieved stable disease and received 18 treatments over the course of six months.”

Based on these interim data, he said, patient enrollment is continuing in an expansion stage of the phase I study at the 0.75 mg/kg dose. The trial is expected to wrap up in the first half of 2013, with full data presented at an undisclosed scientific meeting, he added.

“This puts us on track to initiate phase II in the second half of next year,” Murray said. “Based on the data to date, the most likely indications for phase II development include colorectal carcinoma, hepatocellular carcinoma, and neuroendocrine tumors.”

Next up in Tekmira's pipeline is TKM-Ebola, a phase I treatment for Ebola infection that is being developed in collaboration with the Department of Defense. In 2010, the company received a $34.7 million, three-year contract through the agency's Transformational Medical Technologies program. The contract includes an option allowing the DoD to extend the arrangement through US Food and Drug Administration approval, which would result in roughly $140 million in funding to Tekmira.

In August, the DoD issued a temporary stop-work order on the Ebola contract due to budgetary constraints, but last month the program was restarted (GSN 10/4/2012).

With the program again up and running, Tekmira aims to incorporate advancements made with its LNPs into TKM-Ebola, Murray said this week.

“We have submitted a request to modify our existing contract with TMT in order to integrate advancements in LNP formulation and manufacturing technology made by us since the start of the TMT-funded program,” he said. “It is anticipated that this program will utilize a new LNP formulation that is 10-fold more [potent] than the previous formulations and more potent than all other LNP formulations currently being evaluated in clinical trials.”

He added that the final touches on the new LNPs will be completed in the second half of next year. Pending FDA approval, a new phase I trial with the improved drug will begin shortly thereafter.

Murray noted that Tekmira has “a number of other preclinical candidates in our pipeline addressing a wide range of therapeutic needs,” including TKM-ALDH2, which targets aldehyde dehydrogenase 2, for alcohol dependence, and an siRNA cocktail designed against the cancer targets Wee1 and CSN5.

“We will continue to generate data to support the advancement of the most promising of these targets, and we expect to be in a position to nominate our next product candidate for development in the coming months,” he said.

No mention was made of the hypercholesterolemia drug TKM-ApoB, however, even though it was at one point Tekmira's lead candidate.

The drug is designed to inhibit apolipoprotein B and was the first drug Tekmira moved into the clinic with a 2009 phase I trial. But early the next year, the company said that it had halted that study after a patient receiving the highest dose under investigation experienced flu-like symptoms consistent with stimulation of the immune system caused by the siRNA payload.

At that time, the company indicated that it planned to try a new siRNA and delivery formulation, with the program resuming by mid-2010. This goal was not met, and earlier this year Murray said that clinical testing wouldn't restart any time soon.

“We have been waiting for the development of a next-generation formulation,” he said at the time. “We believe that we have that now, but at least for this year, with PLK1 and the Ebola program, we have enough on our plate. We're not likely to initiate another clinical trial with ApoB this year, unless something materially changes in our business.”

Tekmira officials were not available for comment on the cholesterol candidate.

The Third Quarter

For the three-month period ended Sept. 30, Burnaby, BC-based Tekmira's net loss rose to C$8.5 million ($8.5 million), or C$0.63 a share, from C$8.1 million, or C$0.73 a share, in the year-ago period.

Revenues in the quarter slid to C$3 million from C$4.2 million.

Research, development, collaboration, and contract expenses dropped to C$3.1 million from C$4.4 million the year before, while general and administrative spending edged up to C$1.5 million from C$1.2 million.

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