Biotechnology Awards 2021

12 GHP / Biotechnology Awards 2021 , Jan21443 Noonan syndrome is a rare genetic condition causing a wide range of distinctive developmental anomalies and associated health problems. Those that affect heart construction and growth, cause most of the disease’s morbidity andmortality. The average survivability of infants born with this disease often only live for 18 to 24months. Thanks to research undertaken by the teamat Igia Pharmaceuticals, many of these challenges will soon be overcome. We take a closer look at how Igia is developing drugs for this extraordinary condition. Best Noonan Syndrome Cardiac Dysfunction Drug Development Company 2021 When Igia began in March 2017, the aim of the company was to develop small molecule therapeutics for underserved patient populations. Its first program, a drug designed to remediate hypertrophic cardiomyopathy (HCM) in pediatric patients with Noonan Syndrome (NS) or Noonan Syndrome with Multiple Lentigines (NSML), is representative of that aim. The science underpinning this program builds upon discoveries made by Anton Bennett, PhD, a tenured professor of Pharmacology at the Yale Medical School. His work revolves around the examination of cellular signaling pathways related to early heart development. While looking for ways to modify and regulate these pathways, Prof. Bennett’s laboratory discovered a novel mechanism that appeared to control previously studied systems involved in early heart construction and heart muscle development. The Bennett team observed that when this pathway was dysregulated by genetic mutation, the resulting abnormal development in heart construction and cardiac muscle development could be rectified by using very low dose inhibitors of this new mechanism. Using mouse models of NS and NSML, the Bennett team showed that dosed mice could regain heart function originally lost to these mutations. After licensing Bennett’s discovery from Yale Medical School, the company begin its IG-100 Program to explore the potential human health benefit of these findings. Currently, Igia is setting up a Phase 2A clinical study to see if the observations and benefits seen in the mouse models translate to young and infant children with Noonan Syndrome. Note that currently, there is no known therapy for this disease, and many children with this etiology only live between 18-24 months of age. The field of both Pediatrics and Rare Diseases are fraught with immense challenges. Working on a program which involves both areas is doubly so, as it effectively triples the overall regulatory burden. Hence it makes sense to minimize that burden as much as possible, in order to expedite what otherwise could be a very long and arduous development process. To this end, the company made a strategic decision to leverage the FDA 505(b)2 regulatory pathway, which is typically reserved for the development of additional indications for currently marketed drugs. Because these molecules previously have undergone trials for approval of their original indications, subsequent studies can utilize the safety and toxicology data derived from these original trials. In this way, Igia can bypass Phase 1 and enter directly into an abbreviated Phase 2 clinical trial – referred to as a Phase 2A or “P2A” – with a small number of subjects. Igia is leveraging the P2A process as a core strategy in the development of its drug pipeline. The company is using the P2A with existing molecules to rapidly prove that the new drug mechanism (or “MOA” as it is referred to within drug development circles) successfully observed in animal models, also works in humans. Doing this through the 505(b) 2 process eliminates years of regulatory burden and the need for large, extensive trials. Further, this permits the company to move readily from IND to NDA, providing tremendous first-mover market advantage. If successful, and the MOA is proven, this will “open the door” to an entire class of related new and novel molecules available for study. Hence, the 505(b)2 process in Igia’s case, is used not as a repurposing tool per se, but as a way to quickly and inexpensively prove MOA, to in turn release additional IP for new drug development. Throughout the development of Igia’s IG-100 Program the Pediatric and Cardiovascular Divisions of the FDA have proven to be invaluable resources. The company recently was awarded both Orphan Drug status and Rare Disease designation. In addition, Igia was one of four companies to be indoctrinated into the FDA’s freshman class working with their newly established Model-Informed Drug Development program or “MIDD.” Igia’s IG-100 expects its IG-100 program to meet requirements for both Fast Track and Breakthrough status. Obtaining Fast Track designation will open the door to more frequent communications with the FDA, as well as eligibility for Accelerated Approval and Priority Review. Obtaining Breakthrough Therapy status would provide for expedited commercial development. Achieving either one of these designations alone would expedite program development, decrease risk and eliminate a great deal of cost. While the life sciences sector has been buoyed by the interest perpetuated by the pandemic, finding funding for programs that are not related to COVID has proven to be moderately difficult. While there is understandable priority, the company remains hopeful that as the pandemic dust settles and the world returns to some sense of normalcy, funding opportunities to those working in other areas will become more widely available. Company: Igia Pharmaceuticals Name: Jeff R Livingstone, PhD, CEO Email: [email protected]