Kalos Therapeutics Inc. is gearing up to begin clinical trials with KT-220, an atrial natriuretic peptide with a history in cardiovascular disease and a future in cancer.
Natriuretic peptides are known for their cardiovascular applications. The heart produces the peptides in response to conditions like congestive heart failure, and recombinant brain natriuretic peptide (BNP) is marketed for heart failure by Johnson & Johnson subsidiary Scios Inc. under the trade name Natrecor (nesiritide)
Like BNP, atrial natriuretic peptide (ANP) has shown cardiovascular efficacy. David Vesely, a professor at the University of South Florida College of Medicine, found the drug to be effective in heart failure clinical trials. But Vesely also discovered that ANP inhibited the mitogen-activated protein kinase (MAPK) pathway and had broad anticancer potential.
Through a number of in vitro studies, ANP eliminated anywhere from 63 percent to 97 percent of pancreatic, lung, prostate, breast, ovarian, colon and melanoma cells. In animal studies, between 33 percent and 71 percent of breast, lung and pancreatic cancer xenographs were eliminated after a four-week treatment period, and responsive animals were followed for up to a year with no recurrence.
Those data caught the eye of George Colberg , founder and chairman of San Diego-based Kalos. After selling off a previous health care start-up, Colberg founded Kalos in late 2005 to address what he saw as wasteful spending in the biotech industry. He felt he could put together a company capable of developing drugs better-faster-
Two years later, he found Vesely. Colberg told BioWorld Today he was "a bit skeptical at first because the results [in cancer] were absolutely amazing." So he took ANP on a trial run with oncology expert Daniel Von Hoff, professor at the University of Arizona Health Sciences Center and chairman of Kalos' scientific advisory board. ANP passed the test, and Kalos licensed the intellectual property.
Colberg noted that while plenty of companies are using small molecules to target the MAPK pathway, small molecules are synthetic chemicals foreign to the body and thus often plagued by side effects. KT-220, on the other hand, is a natural hormone that has produced no known adverse effects in preclinical or clinical trials, he said.
"It's not a cytotoxic - it's more like a cytostatic: We put the cells into a prolonged nondividing state," Colberg explained.
The next step is to prove KT-220's safety and efficacy in the clinic. But to do that, Kalos needs money.
The company has thus far raised $700,000 in seed funding from friends and family, including a few high net worth individual investors and industry executives. Plans for a Series A financing were put on hold while last year's financial crunch limited venture activity, but as of last week, Kalos is back on the financing trail.
Colberg said $8 million will get KT-220 through an investigational new drug application filing and into Phase I trials, both of which could be completed within a year of closing the round. But "in a perfect world," Colberg said, Kalos would like to raise $25 million, which would allow the company to complete a controlled Phase II trial for pancreatic cancer.
That Phase II trial could be completed within three years and potentially could provide the basis for accelerated approval based on the unmet need in pancreatic cancer, Colberg said.
Late-stage pancreatic cancer patients are given a 20 percent chance of living a year and a 4percent chance of surviving five years. As of now, treatment options include chemotherapy or EGFR-inhibitor Tarceva (erlotinib, Genentech Inc./Roche AG and OSI Pharmaceuticals Inc.), which was approved based on a 13-day increase in survival. Many drug developers have tried and failed to improve the grim statistics, with Regeneron Pharmaceuticals Inc. and partner Sanofi-Aventis Group pulling the plug on a Phase III trial of aflibercept (VEGF Trap) just a few months ago. (See BioWorld Today, Nov. 4, 2005, and Sept. 14, 2009.)
Colberg said that even if Kalos needed to conduct a Phase III trial for KT-220, a new drug application could be filed within seven years at a fraction of the cost of traditional drug development programs, thanks to the significant existing data with the compound and tight cost control. "We're very attuned to spending as little money as possible," Colberg said.
Beyond pancreatic cancer, Kalos plans to develop KT-220 in ovarian cancer, and Colberg sees applicability as a front-line treatment for certain untreatable breast cancer patients. He said the company also has plans for pegylation and other approaches to "evergreen" the intellectual property.
But if a potential partner wants to take over development of KT-220, Colberg said he'd be happy to hand over the reins in cancer and start studying the compound for other hyperproliferative diseases.
About Kalos:
Kalos Therapeutics (http//:www.kalostpx.com)
