Tekmira Pharmaceuticals this week released interim results from an ongoing phase I trial of its siRNA-based cancer treatment TKM-PLK1, which showed the drug to be well tolerated despite an “aggressive” dosing regimen, with some signs of clinical activity.
Tekmira's top official, speaking during a conference call held to discuss the company's second-quarter financial results, also said that the firm remains committed to working with the US Department of Defense should the agency decide to maintain their now-halted Ebola collaboration.
Still, President and CEO Mark Murray added that Tekmira has not made any plans regarding what it will do about the effort should the arrangement be terminated.
TKM-PLK1 is comprised of siRNAs targeting polo-like kinase 1, delivered using Tekmira's lipid nanoparticles, or LNPs. The drug entered phase I testing in advanced solid tumor patients in late 2010, with a second phase I trial launched the next year in patients with primary liver cancer or liver metastases.
According to Tekmira, in the first phase I study, 21 patients have thus far been treated at doses ranging from 0.15 mg/kg to 0.9 mg/kg, with a total of 105 doses administered.
“Unlike other RNAi oncology clinical trials, where patients are treated every two weeks, we have taken a more aggressive approach with patients treated once a week with each cycle consisting of three doses followed by a rest week,” Tekmira CSO Ian MacLachlan noted during the call.
Interim data show that the peak serum concentration of drug and area under the curve were dose proportional, Tekmira said, with no evidence of drug accumulation. Additionally, the pharmacokinetic profile of the drug is maintained through multiple cycles of treatment.
“Importantly, the data [confirm] that the drug exposure levels achieved in this trial are several fold greater than were achieved in clinical trials using earlier LNP formulations,” MacLachlan said.
The most common adverse events were nausea and fever/chills, and there were no observable dose-dependent changes in liver function. Dose-limiting toxicities included transient thrombocytopenia in one patient and hypoxia/dyspnea in another, both at the highest dose level, Tekmira said.
“Based on these data, patient enrollment is ongoing at 0.75 milligram per kilogram, where we plan to enroll a number of additional patients to generate additional pharmacokinetic, safety, and drug-activity data, including data acquired through the analysis of tumor biopsies,” MacLachlan said.
As for the potential therapeutic activity of TKM-PLK1, he said that “one patient has achieved a 63 percent reduction in tumor burden … and remains on study after receiving 15 treatments over five months. Another patient achieved stable disease and received 18 … treatments over the course of six months.”
The company plans to present the data at a scientific meeting once the trial has been completed, he added.
The future of Tekmira's other clinical candidate, the Ebola treatment TKM-Ebola, remains in question, however.
The drug has been under development for years in collaboration with the US government, and in 2010, the company was awarded a contract through the DoD's Transformational Medical Technologies program to bring it to market. The arrangement was valued at up to $140 million to Tekmira.
As reported by Gene Silencing News, last week Tekmira disclosed that the DoD issued a temporary stop-work order on the Ebola program due to budgetary constraints (GSN 8/9/2012). Tekmira said that by Sept. 1 it will know whether the order has been extended or lifted, or whether the contract has been terminated altogether.
During this week's call, Murray stressed that the Ebola work thus far conducted has had broad benefits to the company, “fostering innovations in manufacturing scale up and LNP lyophilization — advances [that] can be applied to all LNP products.”
At the same time, the work is expected to help Tekmira's efforts in other viral disease indications, he said, adding that “we do have some other hemorrhagic fever research going on that's supported by other branches of the US government.” According to MacLachlan, this includes work on siRNAs against other strains of the Ebola virus, as well as the Marburg and Lassa viruses.
“Over the next month, we will work closely with the TMT team as they complete their assessment of their ongoing programs,” Murray said. “If the stop-work order is lifted … we are fully prepared to move quickly and proceed with our work. If the stoppage period is extended or the contract is terminated, we will provide more guidance on the impact to our business at that time.”
The Second Quarter
For the three-month period ended June 30, Tekmira's net loss dropped to $5.1 million, or $0.38 a share, from a year-ago loss of $6.6 million, or $0.63 a share.
Revenues in the period were $3.6 million, down from $4.4 million in the second quarter last year.
Research, development, collaboration, and contract expenses dipped to $3.6 million from $6.2 million, reflecting a focus on clinical candidates TKM-PLK1 and TKM-Ebola, rather than preclinical efforts.
General and administrative spending in the quarter jumped to $2.4 million from $1.6 million, in part related to Tekmira's legal fees incurred in its ongoing litigation with Alnylam Pharmaceuticals and AlCana Technologies (GSN 5/17/2012).
As of June 30, Tekmira had cash and cash equivalents totaling $6.9 million. The company said that its funds on hand, plus expected income from partners and an active $3 million loan facility, are expected to fund its operations into the second half of 2013.