- PLK1 is a protein involved in tumor cell growth and high expression levels are associated with aggressive disease and poor patient outcomes in a variety of cancer types. In addition to Tekmira's TKM-PLK1 (a.k.a. TKM-080301), several small molecule drugs against PLK1 are in active clinical development for various solid and hematologic cancers including rigosertib (phase 3; Onconova / Baxter International $BAX), volasertib (phase 3; Boehringer Ingelheim), and several other preclinical or phase 1 programs.
Tekmira's phase 1 trial, initiated in December 2010, involves administering a lipid nanoparticle (LNP) formulation containing siRNA directed against PLK1 to patients with advanced lymphoma or solid tumors weekly via IV infusion (3 weeks out of a 4-week cycle). The dose escalation trial has included 23 patients to date at dose levels ranging from 0.15 - 0.9 mg/kg/week (3-6 patients per cohort).
Initial results appear promising. Dose-limiting toxicities were noted in two patients at 0.9 mg/kg/week (hypoxia/dyspnea and thrombocytopenia). As a result, patient accrual and evaluation is being continued at the 0.75 mg/kg/week dose level. Other drug-related adverse events include infusion-site reactions (delayed, with accompanying cytokine elevation), pyrexia, chills, nausea, vomiting, and fatigue.
Preliminary indications of clinical benefit were highlighted in two patients who received at least 6 cycles of TKM-PLK1: stable disease (SD) was noted in a colorectal cancer patient and a durable, confirmed partial response (PR) in a patient with a carcinoid tumor.
The data presented today are consistent with the interim TKM-PLK1 data presented in August 2012. TKMR investors, in fact, may be disappointed that there is relatively little additional information provided given it has been 8 months since the prior update. According to Tekmira's recent annual report, the company expects to initiate a phase 2 trial in 2013.
While limited, these data are key for TKMR as the company looks to move forward after its long and bitter dispute with Alnylam $ALNY over rights to the LNP technology. With ample financial resources, full rights to the LMP delivery technology, and evidence of clinical activity for TKM-PLK1, Tekmira can now seek to appeal to investors with its low market valuation, clinical-stage cancer drug development program (TKM-PLK1) and a U.S. government contract for the development of an Ebola virus therapeutic.
Key TKMR metrics:
- 12/31/2012 cash balance: $47 million
- Year-end 2013 projected cash balance: $35 million (runway into 2015)
- Shares outstanding: 14.3 million
This afternoon, investors, patient advocates, and the cancer research community get their first glimpse at clinical data from an RNAi therapeutic targeting polo-like kinase 1 (PLK1), in development by Tekmira Pharmaceuticals $TKMR. Preliminary phase 1 safety and efficacy data are being presented by Dr. Ramesh Ramanathan at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC.