Jaguar Health, Inc. provided updates regarding the company's focus on rare and orphan disease indications: short bowel syndrome (SBS), microvillus inclusion disease (MVID), and cholera. Rare disease indications are the sole focus of Napo Therapeutics, the corporation established by Jaguar in Italy in 2021, with an initial focus on SBS. Jaguar is the majority shareholder of Napo Therapeutics.

The Company intends to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in the first half of 2023 for crofelemer, the Company's oral botanical drug, for the indication of MVID, an ultra-rare congenital diarrheal disorder (CDD) condition. MVID is a life-threatening autosomal recessive disease that affects newborns and children and leads to significant morbidity and even death from severe secretory diarrhea. MVID is a subset of various CDDs, which are a group of inherited chronic enteropathies characterized by heterogeneous etiology, and each type of CDD is thus a different disease with a different pathogenetic mechanism.

CDDs share a primary common symptom of severe chronic diarrhea, which may produce secondary symptoms, including significant dehydration, metabolic acidosis or alkalosis and malnutrition, which may become life-threatening. As previously announced, the Company has submitted an Orphan Drug Designation (ODD) application to the FDA for MVID and is awaiting a response on the application. The Orphan Drug Act of 1983, a law passed in the U.S. to facilitate development of drugs for rare diseases, provides for granting special status to a drug or biological product to treat a rare disease or condition upon request of a sponsor.

ODD qualifies the sponsor of the drug for various development incentives, including tax credits for qualified clinical testing and relief of filing fees. The European Medicines Agency (EMA) granted ODD for crofelemer in October 2022 for MVID in the European Union. Short Bowel Syndrome: Crofelemer has received ODD from both the FDA and the EMA for SBS, which is a complex condition characterized by diarrhea and/or severe malabsorption of fluids and nutrients due to surgical resection of bowel segments, congenital anomalies, or disease-associated loss of absorption; any or all of which may require parenteral support (PS) in the form of parenteral nutrition (PN) and/or intravenous (IV) fluids.

Investigator-initiated proof-of-concept clinical studies of the safety and effectiveness of crofelemer for reduction of PS in SBS patients with intestinal failure (SBS-IF) are expected to be conducted throughout 2023. For SBS-IF patients who endure the significant loss of their bowel, the resulting excessive intestinal fluid and electrolyte output may cause lifelong restriction and adjustment of oral intake of food and liquids, leading to the requirement of PN and/or IV fluids to maintain nutrient, electrolyte and fluid balance. The constant need for PS challenges the ability of patients to carry out activities of daily living (ADL), such as attending school or work, and has a significant impact on their daily quality of life (QOL).

Furthermore, lifelong PN may lead to potentially life-threatening complications like sepsis and/or organ failures. SBS affects approximately 10,000 to 20,000 people in the United States, according to the Crohn's & Colitis Foundation, and it is estimated that the population of SBS patients in Europe is approximately the same size. Cholera, an acute diarrheal illness caused by infection of the intestine with the bacterium Vibrio cholerae, is an orphan indication in the United States.

As announced in September 2022, the FDA has activated the Company's Investigational New Drug (IND) application for NP-300, a novel botanical drug product candidate for the symptomatic relief and treatment of moderate-to-severe diarrhea, with or without concomitant antimicrobial therapy, from bacterial, viral and parasitic infections including Vibrio cholerae. Due to the very low incidence and prevalence of cholera in the United States, the Company plans to request orphan drug designation (ODD) for NP-300 in the U.S. Upon completion of the requisite development activities to support the New Drug Application (NDA) and subsequent approval of NP-300 by the FDA for the symptomatic relief and treatment of diarrhea from cholera, the Company intends to pursue a Tropical Disease Priority Review Voucher ("TDPRV") under the FDA's financial incentive program to develop NP-300 for this indication. Priority review vouchers are transferable, and in past transactions by other companies have sold for values ranging from $67 million to $350 million, which provides for a potential immediate return on investment upon approval of NP-300 for the cholera-related diarrhea indication.

Crofelemer is an oral botanical (plant-based) drug extracted and purified from the red bark sap, also referred to as "dragon's blood," of the Croton lechleri tree in the Amazon Rainforest. The Company has established a sustainable harvesting program, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for Indigenous communities. NP-300 is a novel oral botanical drug product that is purified and sustainably derived from the red bark sap of the Croton lechleri tree, the same source as that for crofelemer, and is planned to be developed under the FDA's Botanical Guidance.