Massimo Radaelli, PhD, is a European pharmaceutical industry leader and entrepreneur who has devoted more than 35 years to the innovation of therapies to treat rare diseases. He is the CEO of Napo Therapeutics, a pharmaceutical company established in Milan, Italy, in 2021 by California-based Jaguar Health to develop and commercialise the plant-based drug crofelemer in Europe, with a particular focus on rare gastroenterological diseases. Radaelli explained to World Finance why a drug sustainably derived from an Amazon rainforest tree may provide a novel therapeutic option for patients with intestinal failure due to microvillus inclusion disease (MVID) and short bowel syndrome (SBS-IF).

Congratulations on your recent awards. What pleases you most about the recognition?
I am extremely honoured to have been recognised by World Finance’s sister brand, European CEO, as the winner of the ‘Global CEO Excellence Award 2025–26.’ I believe this new award recognises once more, at an international level, my lifelong commitment to the research and development of orphan medicines for the treatment of patients with rare diseases. I am grateful for the recognition and to have been able to spend decades focused on helping patients suffering from rare diseases around the world.

What makes intestinal failure such a devastating condition?
Intestinal failure often requires patients to receive life-sustaining fluids, electrolytes and nutrients through intravenous administration, which consists of total parenteral nutrition (TPN) with supplemental intravenous fluids, which together constitute parenteral support. Many intestinal failure patients require parenteral support up to seven days a week, and sometimes for 20 or more hours per day.

While crucial for intestinal failure patients, many of whom are infants or young children, parenteral support is associated with significant toxicities, similar to some toxicities associated with chemotherapy, often causing serious health problems including infections, metabolic complications, and liver and kidney function problems.

Intestinal failure in MVID and SBS-IF patients remains a serious unmet medical need. No therapies have been approved for MVID, and there are limited options, such as teduglutide and GLP-2 analogs, for a subset of SBS-IF patients. In conjunction with Jaguar Health and our sister company Napo Pharmaceuticals, we are developing crofelemer powder for oral solution – a paradigm-shifting first-in-class drug with clinical proof-of-concept data in these orphan intestinal failure indications. Given the lethal natural history of parenteral support treatment, crofelemer can potentially extend the lives of MVID and SBS-IF patients by reducing their required volume of parenteral support.

What updates can you provide about clinical and business development efforts for crofelemer for these rare diseases?
An independent proof-of-concept study of crofelemer in pediatric intestinal failure patients is ongoing in the UAE, with participating patients having now received crofelemer treatment for more than a year. The initial results from the study, presented in November 2025 at the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Annual Meeting, demonstrate disease progression modification with crofelemer through reduction of parenteral support that ranged from 12 to 37 percent.

With continued demonstration of clinical benefit in Jaguar Health’s ongoing placebo-controlled pivotal trial of crofelemer in pediatric MVID patients, which is expected to complete in the second quarter of 2026, and because MVID is an ultra-rare disease for which no approved treatments currently exist, we hope to achieve Breakthrough Therapy designation from the FDA for crofelemer to accelerate the US regulatory path to market and qualify crofelemer for the European Medicines Agency’s PRIME (priority medicines) programme for MVID to accelerate approval in the EU.

We are seeking a global or regional partner for development and/or commercialisation of crofelemer for MVID and SBS-IF, and will consider potential licensing, co-promotion, or strategic product acquisition opportunities. The near-term value driver is MVID, given the possibility of accelerated regulatory paths to market.

With an estimated worldwide prevalence of about 200 MVID patients, a trial of crofelemer in just a small number of patients is expected to be statistically meaningful and support registration. SBS-IF, the subject of our ongoing Phase two trial of crofelemer, represents the larger follow-on franchise opportunity, with an estimated population of about 12,000 patients in the US alone.

What are the advantages of the botanical drug development pathway?
Crofelemer is sustainably derived from the red bark sap of the Croton lechleri tree – a rapidly growing tree species common in the tropical forests of Colombia, Ecuador, Peru and Bolivia. The sap has a long history of medicinal use by indigenous peoples. Crofelemer is the active ingredient in Mytesi, Jaguar Health’s FDA-approved prescription drug tablet for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy.

Mytesi is the only oral product approved under FDA Botanical Guidance. The botanical drug development framework functions as a de facto IP shield: it does not protect a molecule, but rather the entire integrated manufacturing and quality system that delivers the approved botanical drug product to patients, meaning there’s really no practical pathway to bring a generic version of the drug to market.

Additionally, because data related to prior human exposure provides a pre-existing safety profile, Investigational New Drug applications for botanical drugs have an inherently lower probability of the late-stage safety failures that often terminate conventional New Chemical Entity programmes, effectively de-risking clinical development.