Mytesi (crofelemer) / Jaguar Health, Knight Therap - LARVOL DELTA

Proof-of-Concept Data for Rare Disease Indications MVID and SBS-IF for Jaguar Health's Crofelemer to be Presented at April 2025 ELITE PED-GI Congress (ACCESSWIRE) - P2 | N=12 | NCT06721871 | Sponsor: Napo Pharmaceuticals, Inc. | "Jaguar Health...announced that preliminary results from the ongoing pediatric investigator-initiated trial (IIT) of a novel liquid formulation of crofelemer, Jaguar's novel plant-based anti-secretory prescription drug, for various congenital diarrheal disorders (CDD), including MVID and SBS with intestinal failure (SBS-IF), will be presented by Dr. Mohamad Miqdady at the April 24-26, 2025 Annual ELITE PED-GI Congress in Abu Dhabi in the United Arab Emirates...This ongoing proof-of-concept study is evaluating crofelemer's potential to be safely administered to patients with MVID, SBS-IF, and other CDDs in escalating doses, improve stool formation, improve the absorption of nutrients, and lower TPN needs - which have never been achieved in an MVID patient."

Clinical data • Gastrointestinal Disorder • Short Bowel Syndrome

CRO-SBS-IF: Safety and Efficacy of Crofelemer in Adult Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF) Without Colon-in-continuity (CIC) (clinicaltrials.gov) - P2 | N=18 | Not yet recruiting | Sponsor: Napo Therapeutics, S.p.A.

New P2 trial • Gastroenterology • Gastrointestinal Disorder • Short Bowel Syndrome

Metabolomic, Microbiome and Transcriptomic Study of Crofelemer or Loperamide in Rat Model of Afatinib-induced Intestine Epithelial Damage and Diarrhea (ATS 2025) - No abstract available

Preclinical • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: Lindsey Russell, MD | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Disorder • Short Bowel Syndrome

Yield of Diagnostic Tests and Effects of Crofelemer for Chronic Idiopathic Diarrhea in Non-HIV Patients (clinicaltrials.gov) - P4 | N=93 | Completed | Sponsor: The University of Texas Health Science Center, Houston | Recruiting ➔ Completed | Trial primary completion date: Oct 2024 ➔ Jan 2025

Trial completion • Trial primary completion date • Infectious Disease

Natural history including the incidence, severity and management of diarrhea in patients with breast cancer receiving abemaciclib and pertuzumab-based therapies with or without standard chemotherapy: Data from placebo arm of the OnTarget study (SABCS 2024) - P3 | "Key exclusions included immunotherapy, neratinib, irinotecan, colitis/ostomy/abdominal surgery ≤3 months, and antidiarrheal or antibiotic use ≤7 days...Patients were randomized 1:1 to placebo (n=142) or crofelemer (n=145) to prevent diarrhea...In contrast, those receiving pertuzumab/trastuzumab/docetaxel and carboplatin [n=17] had maximum median grade diarrhea during cycle 1 with 7.1 LWS/week (IQR: 4.6-12.3), and 75% of these patients reported rescue loperamide use... This PRO-based prophylactic study on the incidence of diarrhea in patients with breast cancer receiving abemaciclib or pertuzumab-based therapies with standard chemotherapy over a 12-week period showed that most patients with breast cancer required dose modifications due to diarrhea and/or used rescue medications to remain on their cancer therapy. The use of real-time PRO data on CTD in adult patients with breast cancer shows that diarrhea remains a neglected and under-reported comorbidity of cancer..."

Clinical • Breast Cancer • Oncology • Solid Tumor

OnTarget crofelemer diarrhea prophylaxis trial: responder analysis of patients with breast cancer receiving targeted therapy with or without chemotherapy (SABCS 2024) - P3 | "Key exclusions included immunotherapy, neratinib, irinotecan, colitis/ostomy/abdominal surgery ≤3 months, and any antidiarrheal or antibiotic use ≤7 days...A total of 184 (64.1%) patients with breast cancer participated; median age 57 yrs [IQR: 48-65 yrs], 16.5% non-White); 96 (54.6%) received abemaciclib, 67 (38.1%) pertuzumab/trastuzumab, and 13 (7.4%) kinase inhibitors... In this responder analysis of patients with breast cancer on targeted therapies, crofelemer CTD prophylaxis resulted in a greater proportion of monthly responders of diarrhea improvement compared to placebo, with better-sustained response in those with preserved functional status (ECOG 0-1)."

Clinical • Breast Cancer • Oncology • Solid Tumor • CFTR

Ascending Doses of Crofelemer Powder for Oral Solution in Pediatric Microvillus Inclusion Disease (MVID) (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Napo Pharmaceuticals, Inc.

New P2 trial • Pediatrics • Rare Diseases

Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for Preventive Treatment of Migraine (clinicaltrials.gov) - P=N/A | N=0 | Withdrawn | Sponsor: Neurolief Ltd. | N=57 ➔ 0 | Trial completion date: Jun 2025 ➔ Nov 2024 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jun 2025 ➔ Nov 2024

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • CNS Disorders • Migraine • Pain

Crofelemer Improves Symptoms of Chronic Idiopathic Diarrhea (ACG 2024) - "Outcomes were available for 19 patients with chronic idiopathic diarrhea who completed a 28-day course of crofelemer (74% female; mean age 57.2 years). Two patients (10.5%) described worsening diarrhea, 6 (31.6%) described a neutral effect, and 11 (57.9%) improved with crofelemer (Figure 1). Using a binary outcome, 58.8% (11/19) improved with crofelemer while 42.1% (8/19) did not improve."

Cystic Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases

Pilot Study of Crofelemer for Functional Diarrhea (ACG 2024) - "17 FDr patients completed the 4 week double blind period (crofelemer n=9, placebo=8). Average BSFS decreased from 5.88 +/- 0.35 (mean +/- SD) at baseline to 5.28 +/- 0.66 in the crofelemer group. Average BSFS decreased from 6.09 +/- 0.60 to 5.85 +/- 0.74 in the placebo group."

Clinical • Constipation • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease • Pain

Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for Preventive Treatment of Migraine (clinicaltrials.gov) - P=N/A | N=57 | Not yet recruiting | Sponsor: Neurolief Ltd. | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

OnTARGET: Prophylaxis of Diarrhea in Adult Cancer Patients Receiving Targeted Cancer Therapy (clinicaltrials.gov) - P3 | N=287 | Completed | Sponsor: Napo Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Oct 2023 | Trial primary completion date: Apr 2024 ➔ Aug 2023

Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Yield of Diagnostic Tests and Effects of Crofelemer for Chronic Idiopathic Diarrhea In Non-HIV Patients (clinicaltrials.gov) - P4 | N=100 | Recruiting | Sponsor: The University of Texas Health Science Center, Houston | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome (clinicaltrials.gov) - P1 | N=6 | Not yet recruiting | Sponsor: Lindsey Russell, MD

New P1 trial • Gastrointestinal Disorder • Short Bowel Syndrome

OnTARGET: Prophylaxis of Diarrhea in Adult Cancer Patients Receiving Targeted Cancer Therapy (clinicaltrials.gov) - P3 | N=256 | Active, not recruiting | Sponsor: Napo Pharmaceuticals, Inc. | Trial primary completion date: Nov 2023 ➔ Mar 2024

Trial primary completion date • Oncology • Solid Tumor

Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for Preventive Treatment of Migraine (clinicaltrials.gov) - P=N/A | N=57 | Not yet recruiting | Sponsor: Neurolief Ltd. | Trial completion date: Aug 2024 ➔ Dec 2024 | Initiation date: Jan 2024 ➔ Jul 2024 | Trial primary completion date: Aug 2024 ➔ Dec 2024

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Migraine • Pain

Effects of orally administered crofelemer on the incidence and severity of neratinib-induced diarrhea in female dogs. (PubMed, PLoS One) - "The average number of weekly loose/watery stools were not different between the crofelemer BID and QID treatment groups (p = 0.84). This study showed that crofelemer prophylaxis reduced the incidence/severity of neratinib-associated diarrhea in female beagle dogs without the need for any loperamide administration."

Journal • Breast Cancer • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • EGFR

Dog Study Published in PLOS ONE Shows Statistically Significant Results for Use of Jaguar Health’s Crofelemer for Preventive Treatment of Cancer Therapy-Related Diarrhea (CTD) (BioSpace) - "'Seven patients underwent treatment with crofelemer and loperamide in this study, 5 of whom were able to control diarrhea with crofelemer alone. Though this study involved a small number of patients, the results show activity of crofelemer for the management of neratinib-induced diarrhea, which warrants further investigation of crofelemer for treatment of cancer therapy-related diarrhea (CTD),' said study investigator Hope S. Rugo, MD..."

Media quote

Toward New AQP4 Inhibitors: ORI-TRN-002. (PubMed, Int J Mol Sci) - "Evaluating ORI-TRN-002 on AQP4-expressing Xenopus laevis oocytes using a high-resolution volume recording system revealed an IC of 2.9 ± 0.6 µM, establishing it as a novel AQP4 inhibitor. ORI-TRN-002 exhibits superior solubility and overcomes free fraction limitations compared to other reported AQP4 inhibitors, suggesting its potential as a promising anti-edema therapy for treating cerebral edema in the future."

Journal • CNS Disorders • Vascular Neurology • AQP4

ONTARGET: Phase 3 randomized, double-blind, placebo-controlled trial evaluating crofelemer for the prophylaxis of diarrhea in adult patients with solid tumors receiving targeted therapies with or without standard chemotherapy (SABCS 2023) - P2, P3 | "Key exclusions include immunotherapy, neratinib or irinotecan (due to required SOC antimotility prophylaxis), colitis/ostomy/abdominal surgery ≤3 months, or antidiarrheal/laxative/antibiotic use ≤7 days. Enrollment is complete with 287 patients from 46 sites in 5 countries from 8/2020 through 5/2023. Primary cancer diagnoses were breast (183; 64%), lung (37; 13%), renal (36; 12.5%), liver (12; 4%) and other (19; 6.5%). Most frequent TTx were CDK 4/6 and EGFR inhibitors."

Clinical • P3 data • Breast Cancer • Oncology • Solid Tumor • BRCA

Jaguar Health Reports Third Quarter 2023 Financial Results (Yahoo Finance) - "Jaguar is supporting investigator-initiated and investigator IND proof-of-concept studies of crofelemer for the rare disease indications of microvillus inclusion disease (MVID) and short bowel syndrome (SBS) with intestinal failure in the US, EU and Middle East/North Africa (MENA) regions, with results expected from the end of 2023 and into 2024."

Preclinical • Short Bowel Syndrome

Jaguar Health Enters Exclusive Crofelemer Revenue Sharing License and Commercialization Agreement with Quadri Pharmaceuticals Store for Rare Intestinal Failure Diseases in Middle East Markets (Yahoo Finance) - "Napo Pharmaceuticals (Napo), a Jaguar Health, Inc...announced that it has entered a revenue sharing license and commercialization agreement (the 'Agreement') with Quadri Pharmaceuticals Store LLC (Quadri Pharma) that grants Quadri Pharma exclusive promotional, commercialization, and distribution rights for the rare disease indications of microvillus inclusion disease (MVID), other congenital diarrheal disorders, and short bowel syndrome (SBS) with intestinal failure for a powder formulation of crofelemer for oral solution in multiple Middle East countries, following regulatory approval to market crofelemer for these indications."

Licensing / partnership • Short Bowel Syndrome

Issuance of New US Patent Bolsters IP Protection for Jaguar Health in the Treatment of Short Bowel Syndrome (SBS) (BioSpace) - "Napo Pharmaceuticals, Inc. (Napo), a Jaguar Health...announced that the United States Patent and Trademark Office on October 10, 2023 issued a new U.S. patent to Napo for methods for treating short bowel syndrome (SBS), bile acid diarrhea, and diarrhea associated with small intestine resection or gallbladder removal, in patients with an inhibitor of chloride-ion transport such as crofelemer, Napo's novel plant-based prescription drug....Jaguar is supporting investigator-initiated and investigator IND proof-of-concept studies of crofelemer for SBS and microvillus inclusion disease (MVID) with intestinal failure in the US, European Union, and Middle East/North Africa (MENA) regions, with results expected before the end of 2023 and in 2024."

Clinical data • Patent • Short Bowel Syndrome

Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for Preventive Treatment of Migraine (clinicaltrials.gov) - P=N/A | N=57 | Not yet recruiting | Sponsor: Neurolief Ltd. | Trial completion date: Dec 2023 ➔ Aug 2024 | Initiation date: Sep 2023 ➔ Jan 2024 | Trial primary completion date: Dec 2023 ➔ Aug 2024

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Migraine • Pain