Connective Therapeutics' Collaborator Reports Data on Multiple Sclerosis Vaccine in Nature Medicine.

PALO ALTO, Calif.--(BUSINESS WIRE)--Sept. 30, 1996--Connective Therapeutics, Inc. (NASDAQ:CNCT) announced today that results from Phase I/II clinical testing of T-cell Receptor (TCR) peptide vaccines for the treatment of multiple sclerosis will be published in the October 1996 issue of the journal Nature Medicine.

The results from this pilot study indicated that patients who responded immunologically to TCR vaccines experienced stabilization of disease without side effects during one year of therapy.

The Phase I/II physician-sponsored study was conducted by a team of scientists led by Connective's collaborator, Arthur A. Vandenbark, Ph.D. of Neuroimmunology Research, Veterans Affairs Medical Center, Portland and Oregon Health Sciences University.

The double-blind, placebo-controlled trial involved 23 patients with chronic, progressive multiple sclerosis who were treated for 12 months with a native or substituted version of a V beta 5.2 TCR peptide vaccine or placebo. Successful peptide vaccination boosted protective T-cells and lowered pathogenic T-cells thought to cause the disease.

"These promising early data support our decision to conduct additional studies in a larger population of progressive multiple sclerosis patients," said W. Scott Harkonen, M.D., senior vice president of Product Development and Operations at Connective. "We believe these clinical observations in multiple sclerosis generated by Dr. Vandenbark's group also serve as indications of the potential therapeutic value of TCR technology as a platform to develop vaccines for other autoimmune and connective tissue diseases."

In the Phase I/II study, all TCR peptide vaccine responders (6/6) were clinically improved or stable, while only 7 of 17 non-responders were improved or stable. There were no responders in the placebo group. The vaccines were well-tolerated, with no evidence of adverse events attributable to TCR peptide treatment.

Additional findings in the Nature Medicine report suggest that protective (regulatory) cells elicited by the vaccine not only inhibit their specific target pathogenic T-cells, but also inhibit "bystander" pathogenic T-cells in the area of inflammation in the nervous system.

This information implies that the target T-cells need only represent a fraction of the total pathogenic population for the vaccine to be effective -- an important finding as multiple sclerosis is believed to be caused by a heterogeneic (mixed) population of T-cells.

The publication of this data coincides with Connective's plans to submit an Investigational New Drug Application to conduct a Phase I/II study of native and substituted TCR V beta 5.2 peptide vaccines in progressive multiple sclerosis. The study will be a multicenter, double-blind, placebo-controlled trial which is expected to enroll 100 patients. Connective plans to compare the immunogenicity of the two vaccines against placebo.

Dr. Vandenbark commented, "We are excited about the potential of TCR vaccines as therapies for multiple sclerosis and look forward to participating in Connective's upcoming trial. Boosting the body's natural immunity with vaccines such as these may provide long-term clinical benefit by arresting disease progression."

As with other vaccines, the TCR technology is being developed to help the body recognize and destroy pathogens. In the case of autoimmune diseases, the pathogens are believed to be T-cells. TCR vaccines are manufactured from the receptor portion of pathogenic T-cells and injected into the patient to elicit a heightened immune response against the T-cells thought to cause autoimmune disease.

Connective Therapeutics' TCR peptide vaccines are being designed to boost the naturally occurring control arm of the immune system believed to function inefficiently in immune-mediated diseases. These vaccines are expected to elicit a "regulatory immune response" that can immunize against the activity of disease-causing immune cells, possibly arresting the autoimmune disease process at its earliest stage.

Connective Therapeutics, Inc., headquartered in Palo Alto, California, is focused on the development of novel therapeutics for serious connective tissue disorders. The company has four products in development: gamma interferon for atopic dermatitis and keloids; betamethasone mousse for scalp psoriasis and other scalp dermatoses; ConXn(TM) (recombinant human relaxin H2) for scleroderma and other fibrotic indications; and TCR peptide vaccines for rheumatoid arthritis and multiple sclerosis.

Special Note: This news release contains forward-looking statements that involve risks and uncertainties that could cause actual results or events to differ materially from those in such forward-looking statements. Potential risks and uncertainties include, without limitation, those mentioned in Connective's prospectus dated January 31, 1996 under the heading "Risk Factors" and in Connective's Report on Form 10-Q for the quarter ended June 30, 1996 under the heading "Additional Factors That May Affect Future Results."

CONTACT: Connective Therapeutics Inc.

Sylvia Wheeler, 415/843-2857