PRESS RELEASE: Presentation of Phase IIa Results for Cytos Biotechnology's Hypertension Vaccine

Presentation of Phase IIa Results for Cytos Biotechnology's Hypertension Vaccine at the American Heart Association Scientific Sessions 2007

ZURICH, Switzerland and ORLANDO, Florida, November 6  /PRNewswire/ -- Prof. Juerg Nussberger, MD, University Hospital of the Canton of Vaud (CHUV), in Lausanne, Switzerland, presents today detailed results of a placebo-controlled, double-blind phase IIa clinical trial with CYT006-AngQb in 72 patients with mild to moderate hypertension. In addition, the American Heart Association publishes today at the time of presentation an independent News Release about the vaccine CYT006-AngQb. For more information on this report please visit http://www.scientificsessions.org/ [1].

The study was designed to evaluate safety, tolerability, and exploratory efficacy of two dose levels of the vaccine (100 micrograms and 300 micrograms).For efficacy evaluation, the change in blood pressure from baseline to post-treatment was assessed in individual subjects by 24-hour ambulatory blood pressure monitoring.

Both dose levels of CYT006-AngQb tested were safe and well tolerated. The majority of side effects observed were transient and mostly mild local injection site reactions. During the entire safety follow-up period from month 4 to 12 after the first injection, no vaccine-related adverse events were reported. This confirms the excellent safety and tolerability profile of the vaccine and underscores its potential for long-term disease management.

All patients who received the vaccine mounted a strong antibody response against angiotensin II, which was dose-dependent and long-lived but reversible with a half-life of about 4 months. Also efficacy was dose-dependent and a significant reduction of the mean ambulatory day-time blood pressure was observed in the group who received the 300 mg dose of the vaccine. Systolic blood pressure (SBP) was reduced by 5.6 mmHg and diastolic blood pressure (DBP) by 2.8 mmHg from baseline.

Furthermore, strong efficacy of the vaccine was observed in the early morning hours, a critical time period when serious cardiovascular events occur frequently. The early morning rise of blood pressure starting at 5 am was significantly reduced by the vaccine, leading at 8 am to a blood pressure difference from baseline of (SBP / DBP) - 25 / - 13 mmHg compared to placebo.

Prof. Juerg Nussberger comments: "Despite the fact that effective drugs are available to treat hypertension, only about one out of four hypertensive patients has the blood pressure successfully controlled. Once people are aware of the often symptomless hypertension, they have to take their medications daily, and many are apparently unable or unwilling to take pills every day for the rest of their lives. The major remaining medical need in this important therapeutic area is thus improved patient compliance. If we could support or substitute the oral therapy with a vaccine that would need to be given just every few months, I think we could achieve a better control of high blood pressure."

Prof. Nussberger adds: "A particularly interesting finding of this study is the excellent control of the blood pressure in the early morning hours achieved by the vaccine. This is a crucial time period when serious events like myocardial infarction and stroke are more likely to occur than during other times of the day. Since currently available drugs often have too short half-lives to affect the rise in early morning blood pressure, this could become a major advantage of the novel vaccine approach. I am looking forward to the next steps in clinical development for this promising vaccine candidate."

About CYT006-AngQb

CYT006-AngQb is a therapeutic vaccine in development for treatment of hypertension(1). It is designed to instruct the patient's immune system to produce an antibody response against angiotensin II. Angiotensin II is a small peptide in the body and part of the renin-angiotensin system (RAS), which is an important regulator of blood pressure. Angiotensin II causes blood vessels to narrow, resulting in increased blood pressure. Vaccination with CYT006-AngQb has been shown to reduce blood pressure by induction of antibodies that bind angiotensin II. Thereby, binding of angiotensin II to its receptors and subsequent narrowing of blood vessels should be decreased. The RAS has already been successfully targeted by three major classes of antihypertensive drugs on the market: inhibitors of the angiotensin-converting enzyme (ACEI), blockers of the angiotensin II subtype I receptor (ARB) and direct renin inhibitors (DRI). Like other antihypertensive drugs these also come with the need for daily dosing and often fail to provide a good solution for improving patient compliance. Treatment with CYT006-AngQb should allow for convenient dosing schedules and smooth control of blood pressure due to a sustained antibody response induced by vaccination.

About Hypertension

Hypertension, also termed high blood pressure, is a medical condition where the blood pressure is chronically elevated. Although symptomless in nature and in itself rarely an acute problem, persistent hypertension is one of the most important preventable causes of premature death worldwide and contributes to around half of all cardiovascular diseases(2). It is one of the major risk factors for stroke, myocardial infarction, heart failure, and vascular disease, and is a leading cause of chronic renal failure. Genetic predisposition and lifestyle habits such as inadequate physical activity, high fat diet, and high salt intake promote high blood pressure. Up to 30% of adults in most countries suffer from hypertension. Despite effective and relatively inexpensive treatment available, only about one out of four hypertensive individuals in the U.S. have their blood pressure controlled successfully(3). This poor overall treatment success is mainly attributed to the symptomless nature of hypertension and the necessity for long-term treatment with medications that require at least once daily self-administration.

About Early Morning Blood Pressure

Blood pressure is not static but undergoes natural variations which follow a circadian pattern. Highest levels are reached during the morning, which then decline to reach a trough value at about midnight. In the early morning, a steep increase in blood pressure occurs naturally. It has been suggested that this morning rise in blood pressure triggers adverse cardiovascular events. A large study has revealed a marked circadian periodicity in the onset of myocardial infarction with the primary peak incidence being in the morning. At this time, myocardial infarction is three times as likely to onset as during the night(4). The same periodicity was observed in the onset of stroke. Striking evidence suggests that the morning rise in blood pressure is crucial in determining the rupture of critically weakened arterial walls and subjects with a large rise in morning blood pressure have a significantly elevated risk of intracerebral haemorrhage(5) and stroke(6).

Hypertension therapy therefore aims at a full 24-hour blood pressure control. Current small molecule inhibitors of the RAS were reported to achieve an ambulatory blood pressure reduction from baseline in the early morning hours of e.g. (SBP / DPB) - 8.7 / - 5.8 mmHg (valsartan) and - 11.0 / - 7.6 mmHg (telmisartan), respectively. They, however, do not abolish the rise in early morning blood pressure(7,8).
About Cytos Biotechnology AG

Cytos Biotechnology AG is a public Swiss biotechnology company that specializes in the discovery, development and commercialization of a new class of biopharmaceutical products - the Immunodrugs(TM). Immunodrugs(TM) are intended for use in the treatment and prevention of common chronic diseases, which afflict millions of people worldwide. Immunodrugs(TM) are designed to instruct the patient's immune system to produce desired therapeutic antibody or T cell responses that modulate chronic disease processes. Taking advantage of the high flexibility of its Immunodrug(TM) platform, Cytos Biotechnology has built a pipeline of different Immunodrug(TM) candidates in various disease areas, of which 6 are currently in clinical development. The Immunodrug(TM) candidates are developed both in-house and together with Novartis and Pfizer Animal Health. Founded in 1995 as a spin-off from the Swiss Federal Institute of Technology (ETH) in Zurich, the company is located in Schlieren (Zurich). Currently, the company has 130 employees. Cytos Biotechnology AG has been listed on the SWX Swiss Exchange  since October 2002.
  References

  1. Journal of Hypertension, 2007, 25:63.
  2. World Health Organization, Atlas of Heart Disease and Stroke, 2004.
  3. Hypertension 2003; 42:1206.
  4. New England Journal of Medicine, 1985, 313:1315.
  5. Hypertension, 2006, 47:149.
  6. Hypertension Research, 2006, 29:581.
  7. American Journal of Hypertension, 2004, 17:347.
  8. Hypertension, 2003, 42:1137.

Glossary

Ambulatory blood pressure: blood pressure measured continuously during a normally active day; takes numerous automatic readings over a 24-hour period or longer and applies non-invasive ambulatory blood pressure monitoring devices.
Angiotensin II: a molecule of the RAS inducing vasoconstriction of blood vessels and other effects to raise blood pressure.
Antibody: class of blood proteins generated by the immune system.
Antihypertensive drugs: a class of drugs used for treatment of high blood pressure.
Cardiovascular events: refer to conditions affecting the cardiovascular system, which comprises the heart, the blood vessels, and the cells and plasma that make up the blood.
Circadian: a circadian rhythm is a roughly 24-hour cycle in the physiological processes of living beings.
Compliance: a patient's adherence to a recommended course of treatment.
Diastolic blood pressure (DBP): the lowest pressure within the arterial blood stream occurring during each heart beat.
Double-blind: a set-up often applied in clinical trials where neither the doctor nor the patient knows if placebo or the active drug substance is applied.
Half-life: time required in which half the amount of a biological substance (e.g. antibodies) is removed from the organism.
mmHg: blood pressure values are universally stated in millimetres of mercury (mmHg).
Myocardial infarction: commonly known as a heart attack; is a disease state that occurs when the blood supply to a part of the heart is interrupted.
Peptide: a fragment of a protein comprised of two or more amino acids.
Phase IIa: clinical trial that examines a new drug candidate's safety and exploratory efficacy and may involve between 10 and 100 patients.
Placebo: dummy medical treatment.
Renin-angiotensin system (RAS): hormone system that regulates long-term blood pressure and blood volume in the body.
Receptor: a protein molecule that binds and responds to a certain interaction partner such as hormones, immune mediators or other substances.
Small molecule drugs: low molecular weight chemical compounds. Many pharmaceutical drugs are small molecules.
Stroke: a sudden interruption in the blood supply of the brain.
Systolic blood pressure (SBP): the highest pressure within the arterial blood stream occurring during each heart beat.
Therapeutic vaccine: a preparation of disease-related molecules (antigens) of foreign or self origin that is capable of activating the immune system against such antigens with the goal to modulate disease processes.

This foregoing press release may contain forward-looking statements that include words or phrases such as "designed", "potential", "would", "should", "could", "promising", "suggest", "aim", "intend" or other similar expressions. These forward-looking statements are subject to a variety of significant uncertainties, including scientific, business, economic and financial factors, and therefore actual results may differ significantly from those presented. There can be no assurance that any other therapeutic entities will enter clinical trials, that clinical trial results will be predictive for future results, that therapeutic entities will be the subject of filings for regulatory approval, that any drug candidates will receive marketing approval from the U.S. Food and Drug Administration or equivalent regulatory authorities, or that drugs will be marketed successfully. Against the background of these uncertainties readers should not rely on forward-looking statements. The company assumes no responsibility to update forward-looking statements or adapt them to future events or developments. This document does not constitute an offer or invitation to subscribe or purchase any securities of Cytos Biotechnology AG.