Kalamazoo-based ProNAi Therapeutics Inc., a privately held biopharmaceutical company, announced today dosing of its first patient in an open-label, single-arm, Phase I dose-escalation study of PNT2258 in patients with advanced solid tumors for which no standard therapy exists. The company’s therapy represents a novel way of interfering with genes that are overexpressed in some cancers.
Patients will receive PNT2258 as an intravenous infusion once daily for five consecutive days of every 21-day cycle. The first-in-human clinical trial of PNT2258 has the primary objective to assess the safety and tolerability. The study will also examine the pharmacokinetics of PNT2258 and explore biomarkers with the goal of identifying doses for subsequent efficacy studies in cancer patients.
PNT2258 is the company’s first drug candidate, a 24-base single-stranded oligonucleotide (PNT100), designed to modulate the Bcl-2 oncogene, encapsulated within a proprietary delivery technology called Smarticles. This novel encapsulation of an oligonucleotide was chosen to prolong circulation times and protect PNT100 from premature degradation.
Bcl-2 is a known oncogene that is over-expressed in non-Hodgkin’s lymphoma and many other cancers. PNT2258 therapy will be evaluated used either alone or in combination with other approved cancer therapeutics. ProNAi believes that based on the activity seen in preclinical models, PNT2258 may be promising for the treatment of patients with many solid and hematological cancers such as non Hodgkin’s lymphoma, breast, prostate, lung, ovarian and melanoma.
Smarticles were originally discovered and developed by Novosom AG of Halle, Germany, and further enabled by joint efforts with ProNAi. Wendi Rodrigueza, vice president of product development at ProNAi, led the collaboration of this novel liposome formulation.
Cancer continues to be second leading cause of death and is a serious unmet medical need. In 2010, it is estimated that 1.5 million men and women will be diagnosed and 570,000 deaths will occur in the United States according to National Cancer Institute Surveillance Epidemiology and End Results.
“We are excited to have developed one of the few systemic oligonucleotide therapies that have entered into this phase of human trials,” said ProNAi chairman Donald Parfet, who is also managing partner of the venture capital firm Apjohn Ventures.
The trial is being conducted at South Texas Accelerated Research Therapeutics with a team led by Anthony W. Tolcher, Clinical Director of Research at START.
“Our team at START is an enthusiastic collaborator with ProNAi as they develop this novel class of oligonucleotides for the treatment of cancer,” Tolcher said. “PNT2258 represents a unique approach to potentially silence gene expression and we are very pleased to be part of its first-in-human testing for safety and tolerability in patients with advanced cancer.”
ProNAi is positioned to develop additional cancer therapies from its pre-clinical leads targeting other oncogenes including c-myc, k-ras, and her-2.
The company has successfully raised more than $15 million from Apjohn Ventures, Sigvion Capital, the Michigan Economic Development Corp. on behalf of the State of Michigan, the Biosciences Research and Commercialization Center, Amherst Fund and private investors.
More at www.pronai.com.
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