The GEL4P Project has two major components and related objectives.

The first component of this proposal relates to Research activities focused on the use of Gelesis hydrogels for the treatment of three common and important clinical conditions that have a significant unmet need with respect to therapies that are effective, safe, and well tolerated:

• NASH/NAFLD disease,
• Glycemic control and weight loss pivotal,
• other GI health indications (Chronic Idiopathic Constipation).

The NASH study aims to develop and execute a large clinical study to determine the ability of a specific version of a Gelesis hydrogel (GS300) to positively impact non-alcoholic fatty liver disease (NAFLD), the precursor to non-alcoholic steatohepatitis and its sequelae of cardiovascular disease, cirrhosis, liver failure, liver cancer and the need for liver transplantation. By 2020, NAFLD/NASH is expected to become the most common cause of liver transplantation in the world and it is considered the next large epidemic threat to the health of the world being highly correlated with the dramatic worldwide increase in obesity and diabetes.

The potential for a Gelesis hydrogel to enhance glycemic control and weight loss (particularly in prediabetes and type 2 diabetes) will be assessed using Gelesis200 (GS200) versus placebo in the LIGHT-UP study and the MATCH sub-study. This population of patients typically has great difficulty losing weight and their obesity contributes to important co-moprbidities of diabetes including cardiovascular disease, hypertension, hypercholesterolnemia and stroke. Since approximately one-third of adults in the US and most western countries have pre-diabetes, if GS200 produces significance weight loss in prediabetics, there is a tremendous opportunity to improve the health of this population with a very large total addressable market.

Chronic idiopathic constipation (CIC) is a very common chronic GI disorder that can be quite debilitating and effects at least 14% of the adult population. It is therefore estimated that approximately 35 million adults in the US suffer from CIC. CIC is a functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation. Patients with CIC do not have an underlying anatomic or structural abnormality as the cause of their symptoms. It is recommended that patients with CIC be differentiated from patients with irritable bowel syndrome (IBS).

The second component relates to the Development of a pilot manufacturing plant in Calimera (Le), Italy that will enable Gelesis to take the next step to ultimately commercialize a highly innovative new therapy (Plenity™) for weight management in people with overweight and obesity.

Plenity and related versions of the hydrogels are highly unique as they are the only non-systemic superabsorbent hydrogels in the world made exclusively from natural food grade products. The first major objective of this grant is to build a larger pre-commercial pilot plant to learn how to produce Gelesis’ hydrogels at a larger scale to support further research of our current hydrogels, and to provide new hydrogels for research into treatment of other GI conditions.

Plenity has the potential to positively impact excessive weight and obesity and its related negative impacts on health (e.g., diabetes, cardiovascular disease, hypertension, sleep apnea, cancer, and depression.) The Pilot Plant will increase Gelesis’ capacity to produce Plenity from 3 kilograms per day to 500 kilograms per day until the scale-up process is validated and further manufacturing lines can be installed for commercial purposes. The size of the addressable market in the US is approximately 150 million adults who are overweight or have obesity with a BMI between 25kg/m2 and 40kg/m2. Similarly in Europe, World Health Organization estimates that 62% of adults are overweight comparable to the prevalence in the Americas of 63% (13). Based on 2016 WHO data, one in four (25.3%) European has obesity compared to 29% in the Americas.