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RATIONALE FOR IMMUNIZATION WITH MPL(R) AGAINST SEPTIC SHOCK SUPPORTED BY NEW SCIENTIFIC DATA FROM RIBI IMMUNOCHEM

RATIONALE FOR IMMUNIZATION WITH MPL(R) AGAINST SEPTIC SHOCK SUPPORTED
 BY NEW SCIENTIFIC DATA FROM RIBI IMMUNOCHEM
 HAMILTON, Mont., May 26 /PRNewswire/ -- The prophylactic use of MPL(R) immunostimulant may have distinct advantages over certain other products under development as therapy for septic shock, according to an analysis of a controlled challenge study, Ribi ImmunoChem Research Inc. (NASDAQ: RIBI) announced today.
 During a seminar yesterday on prevention of septic shock, sponsored by Ribi ImmunoChem as part of the Society of Critical Care Medicine's 21st Educational and Scientific Symposium in San Antonio, Texas, Ribi reported that its MPL beneficially regulates four key cytokines involved in septic shock. As a result, clinical testing of a multiple-dose regimen of MPL immunostimulant is planned for mid-1992, to be followed in early 1993 by activity testing in patients at high risk of developing sepsis and septic shock.
 Septic shock is the 13th leading cause of death in the United States. More than 400,000 cases of septicemia, the precursor of septic shock, are reported in the United States annually, resulting in more than 100,000 deaths. Over the last 10 years, the incidence of septicemia has more than doubled. An estimated $5 billion to $10 billion is spent annually in the United States on health care costs associated with septicemia and septic shock.
 The prophylactic use of MPL immunostimulant is in direct contrast to, and may have significant advantages over, certain other products under development as therapy for septic shock. MPL immunostimulant is administered prior to the onset of sepsis and shock. This prophylactic use of MPL, based on the human data reported yesterday, may reduce the degree of infection and/or substantially reduce or prevent the effects of sepsis and septic shock in a significant percentage of patients at risk. By comparison, certain other products under development which include anti-endotoxin antibodies and anti-TNF antibodies as well as other products to block the activity of IL-1 and TNF, are used after sepsis, and in some cases shock, sets in. Further, published clinical data indicate that some of these other products are useful in only a narrow subsegment of sepsis and septic shock patients.
 "We are very excited about this analysis and the evidence it provides to support our rationale for preventing septic shock with MPL," said Robert E. Ivy, chief executive officer, president and chairman of Ribi ImmunoChem. "Successful development of MPL to safely protect patients against septic shock may reduce if not eliminate the suffering of patients subjected to this sometimes deadly sequel of infection. In light of this preliminary evidence that MPL beneficially regulates four of the key factors involved in septic shock, we plan to accelerate our clinical testing in order to acquire the definitive evidence required to support a license application.
 "It should also be noted that certain other products under development to treat septic shock have been criticized for their apparently high cost per patient," Ivy said. "We anticipate that, pending approval, the cost of MPL per patient will be equal to or less than a standard course of antibiotics. Also the potential of MPL immunostimulant to prevent or reduce complications of sepsis and septic shock carries with it the potential to reduce health care costs by shortening hospital stays. Thus, MPL may eventually be clinically and economically significant to human health care."
 The analysis reported yesterday found that a single dose of MPL immunostimulant administered to healthy volunteers prior to an endotoxin challenge significantly reduced production of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF) and significantly enhanced production of interleukin-1 receptor antagonist (IL-1ra) which blocks the effects of interleukin-1 (IL-1). This beneficial regulation of these four key cytokines was not observed in healthy volunteers who received a placebo prior to the endotoxin challenge.
 The interleukins and TNF are among the cytokines, or stimulatory and inflammatory substances, produced by white blood cells during an immune response. The presence of endotoxin, a bacterial by-product, in the bloodstream tends to stimulate overproduction of certain cytokines, particularly IL-1 and TNF. This cytokine overproduction leads to damage to the circulatory and respiratory functions as well as damage to other vital organ functions, in some case resulting in shock and death.
 The development of MPL immunostimulant to prevent or reduce the effects of septic shock is based on considerable experimental evidence showing that the use of minute, sub-toxic amount of endotoxin renders the immune system unresponsive, or insensitive, to subsequent challenge with lethal amounts of endotoxin. However, the narrow difference between a sub-toxic and lethal dose of endotoxin makes it unsafe to use outside of a carefully controlled, experimental situation. As a non-toxic derivative of endotoxin, MPL retains the beneficial properties that desensitize the immune system to the presence of endotoxin without the lethal consequences of endotoxin.
 Ribi ImmunoChem Research Inc., a biopharmaceutical company founded in 1981, is a leader in the development of immunostimulants for use in preventing and treating human and animal diseases.
 -0- 5/26/92
 /CONTACT: Robert E. Ivy or Jeffrey S. McDowell of Ribi ImmunoChem Research, 406-363-6214
 (RIBI) CO: Ribi ImmunoChem Research Inc. ST: Montana IN: MTC SU:


JH-LM -- SE001 -- 3603 05/26/92 08:43 EDT
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Date:May 26, 1992
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