News Release Details

Crofelemer is a novel, oral plant-based non-opioid antidiarrheal medication

SAN FRANCISCO, CA / ACCESSWIRE / November 19, 2021 / Jaguar Health, Inc. (NASDAQ:JAGX) today announced topline results of the third-party, investigator-initiated Phase 2 HALT-D trial evaluating crofelemer for the prevention of chemotherapy-induced diarrhea (CID) in HER2-positive breast cancer patients being treated with trastuzumab, pertuzumab and a taxane.¹ These therapies are known to cause CID in up to 80% of breast cancer patients, reaching grade 3 (requiring hospitalization) in 8-12% of patients.^2-5 CID can have a negative impact on quality of life, particularly when it persists through much of the course of chemotherapy, and may result in stopping cancer treatment. There are no medications currently approved for CID. Jaguar Health believes crofelemer is the only antidiarrheal medication under clinical investigation that specifically targets the underlying mechanism of CID.

As reported in the abstract (Publication Number: P5-18-09) posted by the San Antonio Breast Cancer Symposium (SABCS), the study included 51 breast cancer patients randomly assigned to either crofelemer or control standard of care with no prophylactic antidiarrheal medications. Findings showed that the primary endpoint - the incidence of having diarrhea for two or more days - was not statistically different for the two groups since about 70% of patients had this outcome regardless of cycle or CID treatment group, which is consistent with the experience of CID in patients receiving these chemotherapy regimens. The crofelemer group demonstrated better outcomes compared to the control group for a number of key secondary endpoints:¹

• Lower incidence of grade 2 or higher-grade diarrhea for the crofelemer group compared to the control group during cycle 2, based on patient-reported outcomes: 9.0% vs. 33.3%.
• Lower incidence of grade 2 or higher-grade diarrhea for the crofelemer group compared to the control group during cycle 2, based on investigator assessments: 9.5% vs. 41.1%.
• No patients in the crofelemer group experienced grade 3 or grade 4 diarrhea during cycle 2 compared to 17.6% of patients in the control group, based on patient-reported outcomes.

"A number of findings of secondary endpoints were significantly in favor of crofelemer," said lead study investigator Paula Pohlmann, MD, PhD, formerly from Georgetown University and now Associate Professor, MD Anderson Cancer Center. "These positive HALT-D data not only support further testing of crofelemer in CID, they also provide evidence for the selection of more appropriate endpoints to assess improvements in CID, which take into account both the frequency and severity of diarrhea."

"These are important findings for patients with CID and the physicians who treat them," said Sandra M. Swain, MD, Associate Dean for Research Development at the Georgetown University Medical Center and the senior investigator of the study. "The data from this HALT-D trial gives us hope that the side effect of diarrhea seen with very effective chemotherapy for HER2-positive breast cancer can be diminished and make the treatment more tolerable for patients."

Jaguar Health President and CEO Lisa Conte said, "We are pleased by the findings of the HALT-D study. A major challenge in studying CID is the lack of consensus on how to measure it. Not only did the HALT-D study show the potential benefit of crofelemer for this indication, we believe it supports the endpoints we selected for our ongoing pivotal Phase 3 OnTarget trial. We want to thank the investigators for their important work on this study and we look forward to continuing to advance the development of crofelemer to potentially address the serious consequences of CID on both a cancer patient's dignity and their ability to continue their cancer treatment."

The HALT-D study is separate from the OnTarget study, the pivotal Phase 3 clinical trial of crofelemer for prophylaxis of diarrhea in adult cancer patients receiving targeted therapy. OnTarget was initiated in October 2020 by Napo Pharmaceuticals, Jaguar Health's wholly owned subsidiary.

More About HALT-D¹

The patients in the HALT-D trial were scheduled for at least three consecutive 21-day cycles of chemotherapy with THP (trastuzumab and pertuzumab with paclitaxel or docetaxel) or TCHP (docetaxel, carboplatin, trastuzumab and pertuzumab). Patients were randomized 1:1 to receive crofelemer during chemotherapy cycles 1 and 2, or standard-of-care with no prophylactic antidiarrheal therapy. All patients received breakthrough antidiarrheal medications as needed.

The primary endpoint was the incidence of any diarrhea (grades 1-4) for two or more consecutive days. Secondary endpoints included the incidence of any diarrhea and of severe diarrhea (grades 3 or 4), time to onset and duration of diarrhea, stool consistency, frequency of breakthrough antidiarrheal medication use, and quality-of-life measures. Data included physician assessments and patient-reported outcomes.

Full results for the secondary endpoints will be presented in the virtual and narrated poster available on the SABCS website and presented in person at the SABCS poster session from 7:00 am to 8:30 am CT on December 10. The full study results are expected to be submitted for publication in a medical journal. Jaguar Health plans to sponsor a closed satellite in-person/virtual event at SABCS on CID in breast cancer patients. The date and timing for the event will be provided in an upcoming announcement.

The HALT-D study was sponsored and conducted by Georgetown Lombardi Comprehensive Cancer Center and MedStar Health, and funded by Genentech, a member of the Roche Group. The crofelemer used in the study was provided by Jaguar Health.

About Chemotherapy-Induced Diarrhea

A significant proportion of patients undergoing cancer therapy experience diarrhea, and diarrhea has the potential to cause dehydration, potential infections, and non-adherence to treatment in this population. Novel "targeted cancer therapy" agents, such as epidermal growth factor receptor (EGFR) antibodies and tyrosine kinase inhibitors (TKIs), with or without cycle chemotherapy agents, may cause increased electrolyte and fluid content in the gut lumen, which results in passage of loose/watery stools (i.e., diarrhea). Diarrhea has been reported as one of the most common side effects of TKIs and may result in cancer therapy drug holidays or reductions from therapeutic dose, potentially impacting patient outcome. Diarrhea is also a common side effect of some approved CDK 4/6 inhibitors.

About Crofelemer

Crofelemer is a novel, oral plant-based medicine purified from the red bark sap, also referred to as "dragon's blood," of the medicinal Croton lechleri tree in the Amazon Rainforest. Napo 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. Crofelemer is the active ingredient in Mytesi®, Jaguar Health's FDA-approved drug to treat noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy (ART). It is the only oral plant-based prescription medicine approved under FDA Botanical Guidance.

About Jaguar Health, Inc., Napo Pharmaceuticals, Inc. & Napo EU S.p.A.

Jaguar Health, Inc. is a commercial stage pharmaceuticals company focused on developing novel, plant-based, non-opioid, and sustainably derived prescription medicines for people and animals with GI distress, specifically chronic, debilitating diarrhea. Our wholly owned subsidiary, Napo Pharmaceuticals, Inc., focuses on developing and commercializing proprietary plant-based human gastrointestinal pharmaceuticals from plants harvested responsibly from rainforest areas. Our Mytesi® (crofelemer) product is approved by the U.S. FDA for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy and the only oral plant-based prescription medicine approved under FDA Botanical Guidance. Napo Pharmaceuticals' wholly owned Italian subsidiary, Napo EU S.p.A., focuses on expanding crofelemer access in Europe.

For more information about Jaguar Health, please visit https://jaguar.health. For more information about Napo Pharmaceuticals, visit www.napopharma.com. For more information about Napo EU, visit www.napoeu.com.

About Mytesi®

Mytesi® (crofelemer delayed release tablets) is an antidiarrheal indicated for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy (ART). Mytesi® is not indicated for the treatment of infectious diarrhea. Infectious etiologies of diarrhea should be ruled out by a physician before starting Mytesi®. If infectious etiologies are not considered, there is a risk that patients with infectious etiologies will not receive the appropriate therapy and their disease may worsen. In clinical studies, the most common adverse reactions occurring at a rate greater than placebo were upper respiratory tract infection (5.7%), bronchitis (3.9%), cough (3.5%), flatulence (3.1%), and increased bilirubin (3.1%).

More information and complete Prescribing Information are available at Mytesi.com.

Forward-Looking Statements

Certain statements in this press release constitute "forward-looking statements." These include statements regarding Jaguar Health's belief that crofelemer is the only antidiarrheal medication under clinical investigation that specifically targets the underlying mechanism of CID, Jaguar Health's belief that the HALT-D study supports the endpoints Jaguar Health selected for its ongoing pivotal Phase 3 OnTarget trial, the expectation that the study results will be submitted for publication in a medical journal, and Jaguar Health's expectation that it will sponsor a closed satellite in-person/virtual event at SABCS on CID in breast cancer patients. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intend," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. The forward-looking statements in this release are only predictions. Jaguar Health has based these forward-looking statements largely on its current expectations and projections about future events. These forward-looking statements speak only as of the date of this release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar Health's control. Except as required by applicable law, Jaguar Health does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

CONTACT:

Peter Hodge
Jaguar Health, Inc.
phodge@jaguar.health
Jaguar-JAGX

References

1. Pohlmann PR, Graham D, Wu T, et al. HALT-D: A randomized open label phase 2 study of crofelemer for the prevention of chemotherapy induced diarrhea (cid) in patients with breast cancer receiving trastuzumab, pertuzumab, and a taxane. Abstract 2142 of poster presentation P5-18-09. Available sabcs.org (San Antonio Breast Cancer Symposium). Accessed November 19, 2021.
2. Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109-119. doi:10.1056/NEJMoa1113216
3. Dang C, Iyengar N, Datko F, et al. Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer [published correction appears in J Clin Oncol. 2019 Feb 1;37(4):354]. J Clin Oncol. 2015;33(5):442-447. doi:10.1200/JCO.2014.57.1745
4. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. doi:10.1016/S1470-2045(11)70336-9
5. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-2284. doi:10.1093/annonc/mdt182

SOURCE: Jaguar Health, Inc.