Building Blocks of a Biotech: CytRx Executives Talk About 3 Agents for Multiple Tumors

Published: Friday, Jul 29, 2011
Steven A. Kriegsman

Steven A. Kriegsman, president and chief executive officer of CytRx

Amid growing cost pressures in the pharmaceutical industry, many small companies are playing an increasingly active role in drug development. One such company is CytRx Corporation, based in Los Angeles, California.

CytRx, which is traded on the Nasdaq, recently completed several transactions, including the sale of its molecular chaperone technology, which have the potential to generate more than $120 million for its oncology research. The company’s pipeline consists of 3 oncology drugs: INN0-206, under investigation in soft-tissue sarcomas; tamibarotene, under study in a placebo-controlled, double-blind study for non-small cell lung cancer (NSCLC) and a pivotal phase II trial in acute promyelocytic leukemia; and bafetinib, under study in a phase II proof-of-concept trial for relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL) and in clinical trials in advanced prostate cancer and brain cancer. The FDA approved orphan drug status for INNO-206 in July, which carries potential tax credits and extended patent rights.

Steven A. Kriegsman, a former certified public accountant and healthcare investor, is the president and chief executive officer of CytRx. Daniel Levitt, MD, PhD, chief medical officer, has more than 24 years’ experience managing clinical trials and drug development programs for several major pharmaceutical companies. They discuss CytRx’s research and the challenges of oncology drug development.

Daniel Levitt, MD, PhD

Daniel Levitt, MD, PhD, chief medical officer of CytRx

OncLive: How does INNO-206 work?

Levitt: The drug INNO-206 is a tumor-targeted conjugate of the commonly prescribed chemotherapy drug doxorubicin, which is used to treat a number of different types of cancer. In the INNO-206 formulation, doxorubicin is chemically linked to a second molecule that, when administered into the body, will bind very specifically to albumin, the major protein in the human circulation system.

Albumin is known to concentrate in tumors. In this situation, it acts as a carrier for INNO-206. Tumors have been shown to have a very acidic environment. They receive less oxygen and metabolize sugar to lactic acid, which leads to a higher acid content and a lower pH inside the tumor. At a lower pH, the doxorubicin is released from the albumin and from the linker, and then enters the tumor cell where it achieves a much higher concentration than if you administer just the free doxorubicin by itself.

What would be the advantages of INNO-206?

Levitt: You can administer much higher doses of the drug doxorubicin using this linker, which leads to greater activity. You get less toxicity and a lower side-effect profile. Basically, there’s a chance of actually creating a much greater destructive impact at the site of the tumor. This all leads to boosting the activity of the doxorubicin, increasing the tumor’s exposure to the drug by 300 to 400%.

Kriegsman: INNO-206 is really our first platform technology, and what makes it unique is that we have the ability to take that acid-sensitive linker and apply it to other chemotherapeutics.

INNO-206 MOA and moleculer structure

The molecular structure of INNO-206, and an illustration of its mechanism of action.

Please discuss tamibarotene.

Levitt: Tamibarotene is being developed in a pivotal trial for acute promyelocytic leukemia as a third-line drug. And perhaps more excitingly, it has just entered into a placebo-controlled, double-blind phase II trial for NSCLC.

We believe that its potential to improve overall survival, progressionfree survival, and tumor response for patients with stage IV lung cancer is the real opportunity here, based on very encouraging preliminary results with a far less potent drug in the same class as tamibarotene.

We’re focused on our 140-patient phase IIB clinical trial that compares adding tamibarotene to a standard chemotherapy regimen versus a placebo added to a standard chemotherapy regimen in patients who have stage IV NSCLC, the most aggressive or late stage of this cancer. And we hope to have some of these results the latter part of next year.

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