By Debbie Strickland

In what the company's CEO is calling "the very small tip of a very large iceberg," Human Genome Sciences Inc. (HGSI) filed its first-ever investigational new drug application (IND) and launched clinical trials of the genomics-derived therapeutic protein.

"It's one small step for a biotechnology company to file a new IND," said William Haseltine, chairman and CEO of the Rockville, Md., genomics firm. "But this event is like the first snowflake in a snowstorm: It's the first tangible conversion of cDNA analysis into development of a product with tangible benefit for patients."

The drug in question is myeloid progenitor inhibitory factor-1 (MPIF-1), a potential chemoprotectant that in preclinical animal studies succeeded in shielding hematopoietic progenitor cells in the bone marrow from the destructive effects of several common chemotherapeutic agents.

MPIF-1 is one of 23 new members of the chemokine/ interleukin family HGSI has identified and tested for activity and specificity as part of a broader program focusing on more than 300 full-length genes corresponding to potential therapeutic proteins.

FDA acceptance of the company's second IND application, for the wound-healing agent keratinocyte growth factor-2 (KGF-2), could follow within two weeks, Haseltine said.

The company was to report today that enrollment is beginning in a multicenter Phase I trial of MPIF-1 to test the protein drug in an undisclosed number of patients. The formulation is an injectable one, to be administered three times per chemotherapy treatment.

The protein works by inhibiting proliferation and differentiation of early progenitor cells. The reversible inhibition accelerates the recovery of white blood cells and enhances the recovery of platelets to normal levels. The company has tested MPIF-1 in more than 70 different cell types and with such chemotherapies as 5-fluorouracil, cytosine arabinoside, paclitaxel and daunorubicin.

Drug Could Reduce Bone Marrow Transplants

For Haseltine, who witnessed the harsh effects of chemotherapy during his days at Harvard University's Dana Farber Cancer Institute, MPIF-1 could be the elusive "dream drug" that would eliminate in many cases the need for post-chemotherapy bone marrow transplants.

"This could be a major breakthrough to protect bone marrow cells from the toxic effects of cancer therapy," he said.

If approved, such a product would tap into markets worth billions of dollars, Haseltine said, quickly adding that "we're a long way from that day."

As a further benchmark, the project establishes five-year-old HGSI as an integrated drug discovery company, Haseltine said.

"All of the work has been done entirely at Human Genome Sciences, from massive gene discovery through the formulation and bottling of the product. We drove that entire effort ourselves without help from another pharmaceutical company."

HGSI, he said, has over the last three years built an internal drug discovery infrastructure, at the same time it provided genetic information to a group of partners that includes SmithKline Beecham plc, of London.

"This is [a rarity] in biotech, to do all the elements of discovery," said Haseltine. The company will complete its integration next year when it opens the doors of a $40 million, 80,000-square-foot manufacturing facility.

That capacity could get a workout, since MPIF-1 and KGF-2 could soon be joined by one or more of 20 HGSI proteins that have demonstrated activity in animal models of human disease.

In addition, the company's patent-pending vascular endothelial growth factor-2 gene, under development through a joint venture, could enter clinical trials in 1998 for critical limb ischemia and other peripheral arterial diseases. (See BioWorld Today, Nov. 11, 1997, p. 1.)

HGSI's shares (NASDAQ:HGSI) closed Wednesday at $40.875, up $1.375. *