Research & Development

There is a particular need for new therapies to treat bacteria-mediated and bacteria-related diseases of the GI tract. These include radiation enteritis, inflammatory bowel disease, irritable bowel syndrome, neonatal necrotizing enterocolitis (NEC), febrile neutropenia, traveler’s diarrhea, and other infectious diarrhea (including those in the developing world). Many of these diseases have no known preventative or cure, and existing treatments leave ample room for improved

treatment or prevention of recurrences. While they affect diverse patient populations and have different underlying causes, all of the above diseases share certain common features: pathologic interaction with gut bacteria, loss of normal barrier function of the gut wall and acute or chronic damage to mucosal tissues. Current approaches to the prevention and treatment of these diseases include antibiotics and vaccines against certain bacteria, anti-inflammatory and immunosuppressive drugs to blunt host responses, and supportive care. None of these approaches represents a comprehensive solution to these important diseases.

Midway’s products, including MDY-1001, represent unique derivatives of high molecular weight polyethylene glycol polymers (PEG), which are administered orally but not systemically absorbed. They act through a novel mechanism involving lipid rafts, found on the gastrointestinal surface (epithelial) cell to perform three functions: 1) they inactivate the bacteria’s response to signals that incite them to become virulent, 2) they enhance the activity of GI mucinous and cytoskeletal barriers that prevent pathogenic gut bacteria from interacting with or invading the gut wall at points of weakness and 3) they accelerate mucosal repair. With the incorporation of appropriate functional groups during synthesis, these polymeric compounds anchor into specific microdomains of the intestinal epithelium, appear to be non-toxic and can be administered orally. While lacking the unique activity of the larger molecules, existing products based on low molecular weight PEG are already widely used to cleanse the GI tract prior to endoscopic and radiological examinations and have a well established safety record.

Our leading internally developed product candidate is MDY-1001, a proprietary functional derivative of high molecular weight PEG 15-20. We intend to develop MDY-1001 initially for the prevention of radiation enteritis. MDY-1001 and other similar high molecular weight polymers also offer enormous promise in the prevention or treatment of diseases such as NEC, febrile neutropenia, IBD, IBS, and infectious diarrheas.

Acute radiation enteritis or proctitis, (i.e. radiation-induced inflammation and injury of the intestine or rectum, respectively), occurs during external pelvic or abdominal radiation therapy for malignant disease such as genitourinary tumors (e.g. prostate cancer, bladder cancer), gynecological tumors (e.g. cervical, uterine, ovarian, vaginal cancer) and rectal cancer. Most patients experience symptoms including diarrhea, abdominal cramps, and bleeding that alter their quality of life during and for some time after the radiotherapy. In some patients, the symptoms are severe enough to interfere with ongoing treatment and completion of an optimal course of therapy. Some patients develop symptoms of chronic injury after several months or years that remains poorly treatable and may require surgery.

Up to 50% of all cancer patients receive radiotherapy; but, the effectiveness of the radiation treatment is largely a function of how much radiation can be given. The amount of radiation is limited by the potential for injury to normal tissues. The incidence of radiation injury depends on the total radiation dose, treatment time and the fractionation of the total dose. Up to 75% of patients receiving pelvic radiation with the typical total dosages of 50 to 70 Gray will experience symptoms of acute radiation enteritis or proctitis during the treatment period. Therapy will be altered in 15 – 20% of patients receiving radiation due to acute radiation enteritis/proctitis. Acute radiation injury to the GI tract plays a significant role in the subsequent development of even more debilitating chronic radiation injury. Based on the incidence of cancer patients receiving radiation, there are approximately 550,000 patients worldwide are at risk of developing radiation enteritis/proctitis annually, including 205,000 in the United States. There are currently an estimated 1.5 – 2 million cancer survivors suffering from post-radiation intestinal dysfunction. Owing to the aging population in developed countries, the number of individuals at risk for developing radiation enteritis/proctitis will continue to increase.