Intensive Search for Novel Antiviral and Antibacterial Agents

Given the rise of resistance towards commonly used antibacterial and antiviral drugs, AiCuris' research & development (R&D) strategy is based on the urgent need for novel and resistance-breaking therapies. Therefore, AiCuris' R&D portfolio exclusively comprises compounds with a novel mechanism of action and/or originating from new chemical classes. AiCuris has a broad clinical portfolio, currently developing one project in phase II, two projects in phase I, and two further projects that are proceeding into first-in-man trials in 2008. Four additional research projects in virology and bacteriology which are in late preclinical development will sustain a continuous and balanced pipeline of innovative drug candidates.

It is AiCuris' vision to combine innovative science and accelerated clinical development to create resistance-breaking therapies to fight bacterial and viral infections. To realize this vision, AiCuris has implemented a culture of performance- and data-driven decisions to increase project success rates and reduce overall development time.

A key component of this culture is AiCuris' R&D strategy based on the following principles:

Research & Preclinical Development

The "learn and confirm" concept - AiCuris' asset in the clinical development process - is supported by preclinical activities aiming at an early understanding of the efficacy and safety profile of a drug candidate. Therefore, preclinical development at AiCuris is linked seamlessly to the learning phase in clinical development and provides essential data 1) on the mechanism of action of a drug candidate allowing a high likeliness to demonstrate higher efficacy over available therapies; 2) to improve understanding of the exposure-response relationship and predict human drug exposure; 3) to identify the toxicity profile and the risk for drug-drug interactions early.

In order to maintain a continuous pipeline and a balanced portfolio of innovative drug candidates, AiCuris' research activities are focused on identifying novel mechanisms of action. AiCuris then evaluates whether these mechanisms possess distinct advantages over available antibacterial and antiviral therapies, such as greater efficacy especially against resistant organisms, and better safety, particularly decreased toxicity and a lower risk of drug-drug interactions. These activities are realized with AiCuris' in-house expertise in the fields of antiviral and antibacterial research and through collaborations with external partners.

Clinical Development

Due to a rapidly changing pharmaceutical environment characterized by increasing pricing pressure for prescription drugs and stronger regulatory as well as compliance requirements worldwide, AiCuris follows new ways to develop urgently needed medicines. Instead of using a traditional phased approach to clinical development, separated into three phases (phases I to III), AiCuris has adopted a "learn and confirm" paradigm as its clinical development model.

The "learning phase" replaces the traditional phases I and II in clinical development. In the learning phase, understanding of a new drug candidate is optimized to maximize its medical value and determine if it justifies continued investment. Among other parameters, the optimal dosage range is determined and the drug's safety and efficacy profile in humans established. The learning phase ends with a proof-of-concept trial designed to demonstrate that the drug candidate is capable of meeting the specific medical need and the critical value drivers for the targeted disease in a representative patient population. The "confirm(ation) phase" replaces the traditional phase III. It focuses on operational and cost-effective confirmation of the drug's safety, efficacy, and value for successful registration and market launch.

Immunology

Besides its key R&D areas, virology and bacteriology, AiCuris also works on new therapies to help the body's immune system defeat viral and bacterial infections as well as cancer.

Today it appears that the present highly active antiretroviral therapy (HAART) is unable to reconstitute HIV-specific immunity and eradicate the virus. Several observations in primate models and in humans support the notion that cell-mediated immunity can control viral replication and slow disease progression. This positive effect of the immune defence mechanisms has also been shown in other diseases, such as cancer.