07.19.17 - PRESS RELEASE: Regenacy Pharmaceuticals Presents Data Demonstrating that HDAC1,2 Inhibition Improved Cognitive Function in Mouse Models of Alzheimer's Disease at the Alzheimer’s Association International Conference
Regenacy Pharmaceuticals is a pioneer in developing novel treatments through regeneration of normal protein function using oral, isoform selective histone deacetylase enzyme ("HDAC") inhibitors.
We were founded in December 2016 following the acquisition of Acetylon Pharmaceuticals by Celgene. Regenacy received exclusive rights to the clinical stage, orally bioavailable, HDAC6 selective inhibitor, ricolinostat (ACY-1215), for a range of non-cancer disease indications including peripheral neuropathy, polycystic kidney disease and cholangiocarcinoma. Regenacy also has a unique and proprietary portfolio of selective HDAC1,2 inhibitors with significant potential for treating hemoglobinopathies, cognitive dysfunction and leukemia.
Histone deacetylases (HDACs) are a family of 18 related enzymes found in all human cells that remove acetyl groups from intracellular proteins. This activity is critical in maintaining normal gene expression and protein function throughout the cell, tissues and body. Disruption of protein acetylation contributes to a wide range of major medical conditions. Currently marketed HDAC inhibitors lead to significant side-effects by indiscriminate targeting of multiple HDACs. Regenacy’s selective HDAC inhibitors have a greatly improved safety profile, reduce abnormal function of specific HDAC enzymes and can regenerate normal biological function.
Regenacy’s focus is the development of oral, selective HDAC inhibitor compounds to address major areas of unmet clinical need including diabetic and chemotherapy-induced peripheral neuropathy, polycystic kidney disease, cholangiocarcinoma, sickle cell disease, beta thalassemia, cognitive dysfunction and leukemia.
For more information on our discovery activities, please view our publications and presentations.
Diabetic Peripheral Neuropathy (DPN)
Diabetic Peripheral Neuropathy (DPN) is one of the most common and serious complications of Type 1 and Type 2 diabetes. DPN causes burning pain, numbness, and tingling in the hands and feet, all of which have a major impact on quality of life. Current treatments address only the pain and are minimally effective, addictive, and/or poorly tolerated and do not restore normal function.
Chemotherapy Induced Peripheral Neuropathy (CIPN)
An estimated 500,000 patients suffer from chemotherapy induced peripheral neuropathy (CIPN). CIPN is a common adverse effect of several cancer therapies including taxanes and platinum drugs. Symptoms include decreased sensation and tingling of the hands and feet, severe pain, numbness and muscle weakness, all of which can occur during cancer treatment, and frequently persist after chemotherapy has ended. There are no approved therapies to combat the debilitating symptoms of CIPN.
Charcot-Marie-Tooth Disease (CMT)
Charcot-Marie-Tooth disease (CMT) is a progressive and degenerative nerve disease that usually appears in adolescence or early adulthood. Symptoms include muscle weakness, decreased muscle size and loss of feeling in the hands and feet resulting in loss of coordination in the limbs. There are no FDA approved treatments to stop or reverse the loss of nerve function in CMT.
Sickle Cell Disease (SCD) and Beta Thalassemia (bT)
Hemoglobinopathies, including sickle cell disease (SCD) and beta thalassemia (bT), make up the largest group of severe genetic diseases worldwide. Many SCD patients are at risk for painful and life-threatening vaso-occlusive (blocked blood vessels) crises, and iron overload and other adverse consequences of repeated blood transfusion (bT), resulting in frequent hospitalization, organ failure and shortened life expectancy. There are few therapeutic options for these patients, who typically receive treatment only during crises (pain, hemorrhage, stroke), and no treatments fully restore normal red blood cell function.
Our team is poised to start Phase 2 trials in peripheral neuropathy with our selective HDAC6 inhibitor ricolinostat. We are also rapidly working to advance promising lead HDAC1,2 inhibitors through drug candidate selection, preclinical development and into human clinical trials for the treatment of sickle cell disease and beta-thalassemia.
Opportunities for ricolinostat: Peripheral neuropathy, polycystic kidney disease and cholangiocarcinoma.
Our lead program ricolinostat (ACY-1215) is currently positioned to enter Phase 2 clinical trials in peripheral neuropathy with first-in-class potential based on compelling proof-of-concept preclinical studies demonstrating restoration of normal nerve function. Ricolinostat has demonstrated an excellent safety and tolerability profile in prior Phase 1 and 2 clinical trials, particularly when contrasted with the high toxicity of currently marketed pan-HDAC inhibitors (e.g. vorinostat, panobinostat).
Ricolinostat selectively inhibits the intracellular enzyme HDAC6. HDAC6 regulates multiple intracellular processes such as protein degradation, cell motility, and cell-cell interactions. Selective inhibition of HDAC6 as a therapeutic target has the potential to ameliorate several severe chronic diseases and restore normal biological function.
Opportunities: Sickle cell disease, beta-thalassemia, cognitive dysfunction and leukemia (AML/MDS).
Regenacy’s HDAC1,2 inhibitors have demonstrated preclinical proof-of-concept for the treatment of sickle cell disease, beta-thalassemia and cognitive dysfunction. HDAC1,2 inhibition can increase the production of fetal hemoglobin (HbF) protein in primates. Elevated levels of normal HbF can reduce disease severity and restore normal function in patients with sickle cell disease or beta-thalassemia by replacing missing or defective adult hemoglobin. Recent studies in mouse models of Alzheimer’s Disease have shown that HDAC1,2 inhibition improved performance in spatial learning.
Regenacy’s proprietary, isoform selective HDAC1,2 inhibitors are differentiated from pan-Class I inhibitors by superior preclinical safety and tolerability profiles, and they include both blood-brain barrier penetrant and non-penetrant preclinical candidates formulated for oral administration as tablets, with excellent pharmacokinetic properties.