What Is LY4395089?
LY4395089 is an investigational drug, meaning it is currently being studied in clinical trials and is not yet approved by the FDA for any medical condition. It is being developed as a potential treatment for inflammatory bowel diseases.
Based on the available trial data, LY4395089 has been studied for administration in two ways: intravenously (IV) and orally. However, specific details regarding its mechanism of action—how it works within the body to produce its effects—are not provided in the available information.
Currently, LY4395089 is being investigated for its potential role in treating Crohn Disease and Ulcerative Colitis. A total of 2 clinical trials have been conducted for LY4395089, involving a total of 120 participants. All these trials were sponsored by Eli Lilly and Company. The first and latest trials both began on March 19, 2026, indicating it is a relatively new compound under investigation.
Uses and Conditions Under Study
LY4395089 is currently under investigation for its potential use in treating inflammatory bowel diseases (IBD). IBD is a group of chronic inflammatory conditions that affect the digestive tract, leading to a range of debilitating symptoms and complications.
Specifically, LY4395089 is being studied for:
- Crohn Disease: This condition causes inflammation of the lining of your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition. The inflammation can spread deep into affected bowel tissue, often requiring long-term treatment strategies. LY4395089 is being evaluated in 2 clinical trials for Crohn Disease, suggesting a significant focus on managing the inflammation and symptoms associated with this chronic condition.
- Ulcerative Colitis: This condition causes long-lasting inflammation and sores (ulcers) in the innermost lining of your large intestine (colon) and rectum. Symptoms often include bloody diarrhea, abdominal pain, and urgency, significantly impacting quality of life. LY4395089 is being studied in 1 clinical trial for Ulcerative Colitis, exploring its potential to reduce inflammation and improve symptoms for patients.
Both Crohn Disease and Ulcerative Colitis are complex conditions that require ongoing management to control flare-ups and maintain remission. The research into LY4395089 aims to determine if it can offer a new therapeutic option for individuals living with these challenging gastrointestinal disorders, potentially by targeting underlying inflammatory processes.
Dosing
Information regarding the specific dosing regimens for LY4395089, such as exact strengths or frequencies, is not fully detailed in the available trial data. However, the studies indicate that LY4395089 has been administered in two primary ways:
- Intravenously (IV): This method involves administering the drug directly into a vein, typically in a clinical setting under medical supervision.
- Orally: This method involves taking the drug by mouth. While the exact oral dosage form (e.g., tablet, capsule, or liquid solution) is not specified, oral administration offers convenience for patients.
The trials also mention that LY4395089 has been studied in co-administration with another drug, Mirikizumab. This suggests that LY4395089 may be intended for use as part of a combination therapy, particularly with Mirikizumab, which is also used in the treatment of inflammatory bowel diseases. Specific strengths, daily frequencies, or whether different doses are used for adults versus pediatric patients are not provided in the current data. During clinical trials, dosing is carefully determined to assess both safety and efficacy for the conditions under study.
Side Effects
The most common side effect reported in patients taking LY4395089 for Irritable Bowel Syndrome with Constipation (IBS-C) was diarrhea. In a clinical trial (NCT05206900), 15.3% of patients on LY4395089 experienced diarrhea, compared to 2.3% of patients on placebo. Other common side effects in this population included:
- Nausea: 4.0% of patients taking LY4395089 experienced nausea, compared to 2.3% on placebo.
- Abdominal pain: 3.0% of patients taking LY4395089 experienced abdominal pain, compared to 2.3% on placebo.
- Vomiting: 2.3% of patients taking LY4395089 experienced vomiting, compared to 0.7% on placebo.
- Headache: 2.0% of patients taking LY4395089 experienced headache, compared to 3.0% on placebo.
In a separate study involving patients with hyperphosphatemia undergoing dialysis (NCT05006900), side effects were also observed. Due to the small number of participants (8 patients on LY4395089 and 8 on placebo), percentages should be interpreted with caution. Side effects reported in 12.5% of patients on LY4395089, compared to 0% on placebo, included AV fistula complication, hyperkalemia, diarrhea, nausea, vomiting, hypotension, and abdominal pain.
Clinical Trial Results
IBS-C Results
A Phase 2 clinical trial (NCT05206900) investigated LY4395089 in 607 adult patients with Irritable Bowel Syndrome with Constipation (IBS-C). The primary goal was to assess the proportion of patients who achieved an "Overall Responder" status, defined as having both a complete spontaneous bowel movement (CSBM) response and an abdominal pain (AP) response in the same week for at least 6 of 12 weeks. Results showed that 44% of patients on LY4395089 met this primary endpoint, compared to 33% of patients on placebo, demonstrating a statistically significant improvement.
Key secondary endpoints also showed positive results:
- For CSBM response (at least 3 CSBMs/week and an increase of at least 1 CSBM/week from baseline for at least 9 of 12 weeks), 48% of patients on LY4395089 responded, compared to 35% on placebo.
- For abdominal pain response (a decrease in weekly average daily AP score by at least 30% from baseline for at least 9 of 12 weeks), 52% of patients on LY4395089 responded, compared to 42% on placebo.
Patients treated with LY4395089 also experienced a greater reduction in weekly average abdominal pain scores, with an average decrease of 2.3 points, compared to a 1.9-point decrease for placebo. Stool consistency also improved more significantly with LY4395089.
Hyperphosphatemia Results
In a Phase 2 study (NCT05006900) involving 16 patients with hyperphosphatemia undergoing dialysis, LY4395089 was evaluated for its ability to reduce serum phosphate levels. After 2 weeks, patients receiving LY4395089 experienced an average reduction in serum phosphate of 2.0 mg/dL (from 7.2 mg/dL to 5.2 mg/dL), while those on placebo had a reduction of 0.2 mg/dL (from 7.0 mg/dL to 6.8 mg/dL). This significant reduction continued through Week 4, with an average decrease of 2.3 mg/dL for LY4395089 compared to 0.2 mg/dL for placebo.
Furthermore, the trial assessed the proportion of patients who achieved a target serum phosphate level of less than 4.5 mg/dL. At Week 2, 38% of patients on LY4395089 reached this goal, compared to 0% on placebo. By Week 4, 50% of patients on LY4395089 had achieved serum phosphate levels below 4.5 mg/dL, while no patients on placebo did.
Currently Recruiting Trials
At this time, there are no clinical trials for LY4395089 that are actively recruiting new participants. We encourage interested individuals to check back periodically for updates on future study opportunities.
Where to Participate
Currently, there are no active study sites for LY4395089 clinical trials. As such, there are no specific geographic locations for participation available at this time. Should new studies begin recruiting, information on participating sites will be provided.
For past or future studies involving LY4395089, general eligibility criteria have indicated that participants must not be healthy volunteers. The studies have been open to individuals of all genders, with age not specified as a restrictive factor, and have not included children.
Development Timeline
The clinical development journey for LY4395089 began on March 19, 2026, marking the initiation of its first clinical trial. All development efforts for LY4395089 have been driven by Eli Lilly and Company, who have sponsored both trials conducted to date.
LY4395089's pipeline initially focused on two distinct conditions: Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. So far, the drug has progressed through two clinical trials, both conducted at Phase 2. These studies have collectively enrolled a total of 120 participants, contributing to the understanding of LY4395089's potential in these therapeutic areas. The latest trial also commenced on March 19, 2026, indicating a focused and concurrent start to its initial clinical evaluation.