By Debbie Strickland
Special To BioWorld Today
ATLANTA ¿ A little-known, privately held Kirkland, Wash.-based company emerged as a leader in the anti-angiogenesis field over the weekend by presenting Phase I/II data at the annual meeting of the American Society of Clinical Oncology here.
Cytran Inc. released positive Kaposi¿s sarcoma (KS) results on IM862, a two-amino-acid peptide that patients can self-administer via nose drops, a delivery option that is possible because the compound¿s small size allows it to traverse the mucosa.
¿It was the feeling of both the management and the board that we should wait until we¿ve got some data that¿s worthwhile, then publish it and go out into the public arena,¿ said Dennis Fill, chairman and CEO, who is a former president of Squibb Corp. ¿Now, we¿ve got good data and know where we¿re going.¿
The drug has moved on to a pivotal Phase III trial in KS, and is in Phase I/II for ovarian cancer and Phase I for metastatic melanoma. The company also is planning trials in breast, prostate, colorectal and kidney cancers.
Cytran¿s goal is first to win an approval for KS ¿ a highly vascular type of tumor in which changes are easily observed and measured ¿ and then expand into other cancer indications.
¿We¿re not aware of anybody being ahead of us [in anti-angiogenesis],¿ said Fill, who did note that there are a few anti-angiogenic products made by other companies that are beginning Phase III testing.
In the Phase I/II trial discussed at ASCO, 36 percent of patients completely or partially responded to the therapy and another 47 percent achieved disease stabilization.
Eleven percent experienced complete response, defined as resolution of Kaposi¿s sarcoma lesions for four weeks or more without evidence of new disease. Partial response was defined as a reduction in the measurements of five target lesions by 50 percent or more, or complete flattening of half or more total lesions. Treatment was well tolerated with minimal side effects.
The trial was conducted at two sites: the USC Norris Cancer Center in Los Angeles, under Parkash Gill, who presented findings at ASCO; and Massachusetts General Hospital in Boston, under David Scadden.
IM862 is a synthetic version of a peptide found naturally in human tissues, Gill said. It appears to inhibit angiogenesis by inhibiting production of vascular endothelial growth factor and augmenting production of interleukin-12. Additional studies to characterize the compound¿s effects in tumor cells are ongoing, he said.
The findings were strong enough, according to Cytran, that the FDA ¿agreed that if the results are repeated in a well-controlled Phase III trial, it would be adequate to support a marketing application leading to a new drug approval.¿
The company¿s pivotal multicenter Phase III trial in the U.S. and Canada is evaluating IM862 in patients with five or more KS lesions. Co-sponsored by the National Cancer Institute and the AIDS Malignancy Consortium, the 200-patient trial is double-blind, randomized and placebo-controlled. Cytran expects to complete enrollment by December.
The dosage is 5 mg every other day, which succeeded in the Phase I/II trial. An open question is whether patients should continue therapy indefinitely or stop when a complete response is achieved.
¿That will be up to the physician to decide,¿ Fill said. ¿A number of clinicians have indicated that because of the lack of side effects, there are some very legitimate questions as to whether patients should consider long-term therapy.¿
Cytran Seeking $15M Private Round, Considering IPO
Cytran has raised $30 million since its founding in 1991, and currently is seeking to raise $15 million in convertible debenture financing as a final round of private funding, in part to fund clinical trials and manufacturing scale-up of IM862, and for research and development of other peptides.
¿We have two alternatives,¿ Fill said. ¿One is to do an IPO [initial public offering]. The other is to form various strategic alliances and licensing agreements. This final round of financing will give us at least two years of funding, taking us more or less to the middle of .¿
The company¿s peptide technology was first developed at the Kirov Medical Military Academy in St. Petersburg, Russia. Cytran¿s rights are worldwide, with the exception of Russia. The firm¿s patent portfolio covers IM862 as a treatment for immune-deficient conditions in the U.S., Europe, Japan, Canada and Australia, and Cytran has garnered patent protection in the U.S. for anti-angiogenic effects, with applications pending in other markets.
¿This is a compound that¿s easy to manufacture,¿ Fill said. ¿We¿re virtually at 300,000 doses.¿
An undisclosed pharmaceutical company is manufacturing the product. Cytran itself is ¿lean and mean,¿ with fewer than 20 employees, Fill said. n