Researchers at Avidin have synthesized analogues of novel Immune Modulatory Drugs (IMIDs) which may have benefits over the current treatments for multiple myeloma (MM), leukemias and other cancers.

The IP held by Avidin on the novel IMIDs, the trifluorinated-alkylamino-imids is valuable, offering the possibility of widening the application of the currently used thalidomide or Lenalidomid (Revlimid™, Celgene Inc.).

New Analogues

Our chemists at Avidin have synthesized more than 120 trifluorinated-alkylamino-imid derivatives and our and biologists tested them on various cancer cell lines (>20; including leukemias, hepatocellular carcinomas, melanomas, breast, lung and prostate cancer cell lines). The most effective analogues have been tested to find compounds that have better pharmacokinetic and pharmacodinamic profiles, and are more potent in xenograft models. The isomer-selective synthesis of the lead molecule, Avinomid is straightforward and can be easily upscaled to kilograms under GMP conditions.

Pre-clinical Results

Avinomid showed impressive effectiveness against the CML xenograft model in mouse. The survival increased dramatically by only 3x5 daily oral administration of 100 mg/kg Avinomid. Now we are repeating the experiment with different doses and with xenograft model for AML, as well.
Avinomid showed no toxic side effects in mouse and in rat even as high as 1 g/kg in an acute experiment and had no sign of toxicity in a sub-acute experiment at a 300 mg/kg dose. Avidin is currently organizing the GLP-toxicology for Avinomid in a sub-acute (30-60 days) oral administration.

Human melanoma cells were double-stained with (a) the blue fluorescent Ac-1041 (3 μM); (b) lipid droplet-specific Oil Red’O. (c) Purple color derives from co-localization of both dyes

Applications

The main indication for which thalidomide and Lenalidomid are currently used is multiple myeloma. Our new analogues showed impressive effectiveness against other types of haematological malignancies (including AML and CML in xenograft model), therefore the application of Avinomid would be wider than the currently used thalidomide or Revlimid. The market in the US for pharmaceutical treatments of MM by Revlimid is large and growing. The overall response rate of Revlimid in combination with dexamethasone was app. 60 %, but with increased risk for thrombotic events.

IP position

Avidin has a patent application for the therapeutic application (cancer, inflammation, infectious diseases) of trifluorinated-alkylamino-imids, as new compounds.
The patent is new (submitted in 2007 and entered to PTC in June, 2008) that enables long-term exploitation of the IP.

Financing

The preclinial development of Avinomid is currently financed by Avidin. In 2007 Avidin won a grant (2 M US$) to lead a consortium (including National Institute of Oncology, University of Szeged, Department of Pathology, Department of Pharmacodynamics and Biopharmacy in Hungary) to test Avinomid in pre-clinical studies.
Avidin is now seeking partners for licensing and development of Avinomid to finish preclinical phase and enter Phase I/II clinical trial in 2010.