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Tekmira Moves Cancer Drug into Phase I/II, Working on Subcutaneous Delivery

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Tekmira Pharmaceuticals announced this week that it has launched a phase I/II clinical trial of its siRNA-based cancer therapy TKM-PLK, focusing on two forms of cancer that were particularly responsive to the drug in a previous study.

During a conference call, Tekmira officials also provided updates on its other research and development efforts — including its Ebola infection treatment TKM-Ebola and efforts to develop its lipid nanoparticles, or LNPs, for subcutaneous siRNA delivery — and broke out the company’s second-quarter financial results.

TKM-PLK comprises LNP-formulated siRNAs against polo-like kinase 1, a serine/threonine kinase that is key to cell progression and is overexpressed in a number of cancer types.

Earlier this year, Tekmira presented data from a phase I study indicating that the drug was safe, establishing a maximum tolerated dose, and showing hints of efficacy (GSN 4/11/2013).

Specifically, three patients — one with metastatic appendiceal carcinoid cancer, another with metastatic colorectal cancer, and a third with metastatic adrenocortical carcinoma, or ACC — achieved stable disease. Another patient with metastatic appendiceal carcinoid, or neuroendocrine, cancer experienced a significant reduction in tumor burden.

During this week’s call, Tekmira President and CEO Mark Murray noted that the company also completed a phase I expansion cohort study further evaluating the maximum tolerated dose of TKM-PLK.

“To date, four out of 12 patients are evaluable having received two cycles” of the drug, he said. “Of those four patients, one with adrenocortical carcinoma … achieved stable disease.”

Buoyed by the data, Tekmira has now initiated a phase I/II trial of the cancer treatment in patients with either ACC or advanced gastrointestinal neuroendocrine tumors, also known as GI-NETs. The open-label, single-arm study will enroll around 20 patients, who will receive TKM-PLK in four-week cycles consisting of three once-weekly doses followed by a rest week.

A minimum of 10 GI-NET patients will be enrolled, and data is expected to be available by mid-2014. Assuming a positive outcome, the company aims to begin phase III testing before the end of next year.

Murray said that Tekmira is also planning to test the drug in an open-label, dose-escalation phase I/II trial of hepatocellular carcinoma patients. That study is expected to begin in the first half of 2014.

Meanwhile, Tekmira continues to advance an Ebola virus treatment, which is being developed under a contract with the US Department of Defense under its Transformational Medical Technologies program.

Although TKM-Ebola had already moved into phase I testing, Tekmira opted to reformulate the drug with a next-generation LNP.

“The new LNP formulation … is more potent than any LNP currently in clinical development and it has demonstrated significant increased potency in non-human primates infected with the Ebola virus,” Murray said. “At 0.5 milligrams per kilogram, 100 percent of the infected animals survived after receiving TKM-Ebola daily for seven days. The previous LNP formulation provided that same level of protection … at 2 milligrams per kilogram.

Tekmira expects to complete all necessary preclinical studies with the new version of TKM-Ebola and submit it to US regulators by the end of 2013, he added.

In addition to its pipeline of intravenously administered RNAi candidates, Tekmira has been exploring the use of its LNPs for subcutaneous drug delivery, Murray noted.

“The data we have generated indicates that [our LNP] is more potent when compared to other published data using conjugate delivery systems,” he said, ostensibly referring to one-time partner Alnylam Pharmaceuticals, which is developing its own subcutaneous delivery technology. “LNPs administered subcutaneously in a rodent model can knockdown a liver target by 96 percent at 1 milligram per kilogram with a single administration.”

Tekmira also said that it plans to nominate its next product candidate before the end of this year. Among the programs under preclinical development are ones targeting TKM-ALDH2, which inhibits aldehyde dehydrogenase 2, for alcohol dependence; and an siRNA cocktail designed against the cancer targets Wee1 and CSN5.

2Q

For the three-month period ended June 30, Tekmira’s net loss jumped to $3.1 million, or $0.22 a share, from a year-ago loss of $1.9 million, or $0.14 a share.

Contributing to the increased loss was a rise in research, development, collaboration, and contract spending to $5.1 million from $3.6 million. General and administrative expenses fell to $900,000 from $2.4 million.

Revenues in the quarter arrived at $2.9 million, down from $3.6 million the year before. During the conference call, Tekmira’s Murray noted that the company is currently in a dispute with Alnylam over a $5 million milestone payment.

The companies had been embroiled in a lawsuit over Alnylam’s alleged misuse of Tekmira trade secrets related to its LNP technology. Late last year, the companies settled, agreeing to a cross-licensing arrangement that would see Tekmira receive payments as Alnylam advanced drug candidates that used LNPs.

According to a filing with the US Securities and Exchange Commission, Tekmira was supposed to have received the $5 million upon providing Ascletis Pharmaceuticals, which licensed the Asian rights to Alnylam’s LNP-enabled liver cancer drug ALN-VSP, with the manufacturing know-how for the drug.

Tekmira believes that it has done so, but Alnylam disagrees, according to the SEC document. Alnylam has requested the matter go into arbitration, pursuant to the terms of the companies’ 2012 settlement deal.

Looking ahead, Tekmira said that it expects to end the year with $30 million to $35 million in cash.

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