Prodrugs and drugs for selective ADEPT or ADC tumor therapy

Antibody tumor therapies have provided therapeutic benefit to patients with cancer, autoimmune diseases and other serious medical conditions. However, many antibodies lack sufficient intrinsic anti-tumor activity to be used as therapeutics. Scientists at the University of Göttingen developed new highly potent drugs (with an IC50 in the pico-molar range) as well as selective antibody tumor therapeutical approaches through their prodrugs.

Challenge

While a prodrug needs to have low cytotoxicity, the activated drug must on the other hand show a very high cytotoxicity in the pico-molar range. Thus, there is a high medical unmet need to have prodrugs/drugs with a big therapeutic window and extremely high and selective cytotoxicity.

Our Solution

Scientists at the University of Göttingen developed new highly potent drugs (with an IC50 in the pico-molar range) as well as a selective tumor therapy through their prodrugs.

Advantages

• New highly soluble prodrugs with low cytotoxicity.
• Prodrug has low cytotoxicity (IC50 = 146.000 pmol/l), whereas drug is highly cytotoxic in low pico-molar range (IC50 = 0,11 pmol/l).
• Higher cytotoxicity than actually used Doxorubicin.
• Even less side-effects expected due to QIC50 Prodrug/Drug = 1.000.000
• Expected improvement in safety through bigger therapeutical dosage range.
• Specific tumor targeting through available antibodies.
• Activation of the prodrug into cytotoxic drug occurs through the enzyme at the tumor site only (ADEPT or ADC).
• NEW: Now including innovative linker technology to directly couple to antibody!

CBI moiety of Duocarmycin. Our prodrug technology is based on Duocarmycin analoga.

Applications

Tumor Therapy:

• Use of Prodrugs for an Antibody Directed Enzyme Prodrug Therapy (ADEPT) or Antibody Drug Conjugate (ADC).
• Use of Drugs for a direct cancer therapy possible.

Developmental Status

Preclinical:- in vitro PoC for second generation Prodrugs/Drugs.- in vivo PoC for ADEPT concept in mouse tumor models for first generation  Prodrugs/Drugs.

Patent Status

German patent application for first generation of bifunctional prodrugs.
A new German priority patent application has been filed for the second generation with innovative linker technology. Applicant: University of Göttingen public law foundation, Germany.

References

• Tietze, von Hof, Müller, Krewer, Schuberth, Angew. Chem. Int. Ed. 2010, 49(40), 7336-7339 - Second Generation.
• Schuster, Krewer, von Hof, Schmuck, Schuberth, Alves, Tietze, Org. Biomol. Chem. 2010, 8, 1833-1842.
• DE102009051799.

Contact

Dr. Stefan Uhle
Patent Manager Life Science
E-Mail: suhle(at)sciencebridge.de
Tel.: +49 551 30724 154
Reference: BioT-1248-SUG+BioC-1848-SUG

Tags: Therapy