By Frances Bishopp

Since its founding in 1993, Milkhaus Laboratory Inc. has made impressive progress on less than $5 million of invested capital.

Milkhaus, which uses its signaling-inducing technology to develop therapeutic agents for the treatment of chronic diseases, has six clinical trials under way, as well as three preclinical trials.

On four separate occasions, the company has begun Phase II trials for less than $500,000 per product, compared to an estimated $10 million to $15 million per product for most biotechnology companies.

It adds up to a lot of work by 14 industrious employees (seven full-time and seven part-time), who work out of their homes, and a strategy built on a series of findings that relate the importance of specific molecules to specific diseases.

Milkhaus, of Boxford, Mass., uses naturally occurring molecules as its therapeutic agents, which reduces the time and cost tof developing drugs in two ways.

First, the molecules are well characterized with regard to their toxicity, so the FDA has granted permission for Phase I/II trials without the time-consuming Phase I dose/toxicity studies usually required.

Second, because these molecules are already available, there is no cost or time involved in the screening, synthesis or development of the manufacturing process.

Milkhaus perceives a wide number of chronic diseases as reflecting regulatory dysfunction. The company's therapeutic products act by inducing signals that drive regulatory cells to regain their normal activity and thereby restore health.

In effect, the technology seeks to "short circuit" a disease process and prevent it from reaching completion, John Glass, vice president of corporate development at Milkhaus, explained to BioWorld Today.

For example, the company's approach to cancer began with the observation that almost all cancer cells in almost all species of animals have chorionic gonadotropin (CG) or CG-like molecules on their surfaces.

"Because it's half-foreign, a fetus is protected from rejection by the mother's body by gonadotropin and is therefore immune from attack by the immune system," Glass said.

"Curiously enough, in all cases of cancer, the cells of the tumors are surrounded by CG, which is the genesis of our work on cancer. This is an event that is appropriate to the fetus, but Nature has gone awry in the case of a non-fetus," he continued.

Glass said the data are good, but not exhaustive, that the surrounding of cancer cells by CG can be attributed to a gene, bcl2, which is stuck "on," thereby inducing the cells to produce the gonadotropin as well as preventing natural cell death, or apoptosis.

To remedy this, Milkhaus gives CG, the thing that is aberrant in the cell, to the patient, causing a cascade of signals that end up at the bcl2 gene and turn it "off," so the gonadotropin is no longer expressed. The cells are then subject to normal maturation and attack by the immune system and, through apoptosis, mature and die normally.

Milkhaus has completed a Phase I/II trial of its investigational agent, LDI-200 (the active ingredient is gonadotropin), for acute myelogenous leukemia that demonstrated significantly positive results.

Based on the outcome of this trial, the company has begun a Phase III trial in a pre-leukemic condition known as myelodysplastic syndrome, for which there is no available therapy.

Milkhaus also is conducting a Phase I/II trial with LDI-200 for solid tumors, as well as a Phase II trial with another product, HP-4 (a naturally occurring molecule), for benign prostatic hyperplasia, and a Phase I/II trial LDI-200 for cancer-associated pain.

This June Milkhaus was granted FDA authorization to begin a Phase II trial of yet another product, HP-3 (another naturally occurring molecule), for the treatment of cystic fibrosis.

Cystic fibrosis produces thick, sticky mucus that builds up in the lungs and gastrointestinal tracts. HP-3 works to relieve congestion of the respiratory and gastrointestinal tracts by preventing the mucus from forming and breaking it up after its appearance.

Milkhaus completed a Phase II trial for chronic fatigue syndrome which demonstrated that patients treated with 2CVV (a mixture of two naturally occurring molecules that act as antiviral agents) have more improvement in a combined score of physical, cognitive and social evaluations than patients on placebo.

The differences between placebo and control group were not significant as a consequence of the small number of patients enrolled in the study. A second Phase II clinical trial is being organized.

The privately held company, which is actively seeking corporate partnerships, also is doing preclinical work in cardiomyopathy, urinary incontinence and herpes infections. *