Novel drugs for the treatment of aging-related diseases like colorectal cancer and glaucoma.

Colorectal cancer (CRC) is the third most prevalent cancer worldwide (10.2% of all cancer cases) and the second leading cause of cancer mortality. Several risk factors may increase the chance of developing CRC, such as age, familial CRC, lifestyle factors, colorectal polyps and inflammatory bowel diseases. It has been shown that CRC develops from adenomatous polyps that grow slowly before becoming malignant. By early detection and early removal of polyps and cancerous tissue, colorectal cancer is curable in most cases. It has been shown that the use of phosphodiesterase 5 (PDE5) inhibitors is associated with a lower risk of colorectal cancer in men with benign colorectal neoplasia due to the elimination of cancer stem cells via the protein kinas A (PKA) pathway. Additionally, low cyclic guanosine monophosphate (cGMP) levels due to either high PDE5 activity and/or low guanylate cyclase (GC) activity lead to altered intestinal barrier and impaired crypt-villus axis which ultimately results in CRC, inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). Based on in-vivo preclinical proof of concept studies the low molecular weight clinical candidate of the Swiss biotech company conferred protection from body weight loss and suppressed polyps’ formation in the Azoxymethane / Dextran Sodium Sulfate (AOM-DSS) colorectal cancer mouse model. Additionally, it inhibits markers of intestinal inflammation. This drug candidate with its unique dual mechanism of action is a very powerful and effective cGMP modulator that works locally with a very large therapeutic window. It is expected to be an ideal drug candidate for the prevention of polyps, adenoma formation and colon cancer but also for the treatment of IBD and IBS. In addition, it should act on the inhibition of tumour growth and the elimination of cancer stem cells, thus increasing the sensitivity to chemo- and radiotherapy of CRC cells. Furthermore, other applications include ocular diseases such as glaucoma. Glaucoma is a heterogeneous group of diseases with a common denominator: damage of optic nerve which leads to irreversible blindness. Worldwide, people affected by glaucoma are 64 million and they are expected to rise to 76 million in 2020 and 111 million in 2040. Current treatments aim to reduce intraocular pressure (IOP). However, only 30-50% of patients have elevated IOP at the initial stages; therefore, there is an urgent medical need to study more effective therapies. The approach of the Swiss company is to target neuroprotection by addressing two established risk factors, ocular blood flow and IOP, in parallel. The Swiss biotech company is seeking financial, license or research cooperation agreements. The partner sought could be a big pharma company interested in: - A licence agreement to commercialise the technology - A research cooperation agreement to launch clinical trials - A financial agreement to move to the next clinical phases The company is as well evaluating additional academic research cooperations to strengthen the scientific understanding of the unique mode of action compounds in the different indications mentioned above.