What Is Iadademstat?
Iadademstat is a drug currently under investigation in clinical trials. The specific way Iadademstat works to treat conditions (its mechanism of action) is not detailed in the available trial descriptions. It is being studied for its potential to treat various blood cancers and other conditions. Depending on the study, Iadademstat can be administered orally, intravenously (IV), or subcutaneously (SC). There are a total of 8 clinical trials involving Iadademstat, with 5 currently recruiting participants. These studies aim to evaluate the drug's safety and effectiveness in patients with conditions such as Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Extensive Stage Small Cell Lung Cancer.
Uses and Conditions Under Study
Iadademstat is currently being investigated in clinical trials for a range of blood cancers and solid tumors.
- Acute Myeloid Leukemia (AML) and Related Conditions: Several studies are exploring Iadademstat for various forms of Acute Myeloid Leukemia. This aggressive blood cancer affects the bone marrow. Conditions under study include Acute Myeloid Leukemia (in 2 trials), Acute Myeloid Leukemia Refractory (meaning it has not responded to previous treatment, in 1 trial), and Acute Myeloid Leukemia, in Relapse (when the cancer returns after treatment, in 1 trial). It is also being studied for Myelodysplastic Syndrome/Acute Myeloid Leukemia (in 1 trial), a condition where the bone marrow doesn't produce enough healthy blood cells and can progress to AML.
- Myelodysplastic Syndromes (MDS) and Myelodysplastic/Myeloproliferative Neoplasm: Iadademstat is also under investigation for Myelodysplastic Syndromes (in 1 trial), a group of disorders where the bone marrow produces abnormal blood cells. Additionally, it is being studied for Myelodysplastic/Myeloproliferative Neoplasm (in 1 trial), a condition that shares features of both MDS and myeloproliferative neoplasms.
- Other Myeloproliferative Neoplasms: Clinical trials are examining Iadademstat for other myeloproliferative neoplasms, which are conditions characterized by the overproduction of one or more types of blood cells. These include Blast Phase Myeloproliferative Neoplasm (in 1 trial) and Essential Thrombocythemia (in 1 trial), where the body produces too many platelets.
- Small Cell Lung Cancer (SCLC): Iadademstat is also being studied as a potential treatment for solid tumors, specifically Extensive Stage Lung Small Cell Carcinoma (in 1 trial) and Extensive Stage Small Cell Lung Cancer (ES-SCLC) (in 1 trial). This aggressive form of lung cancer has spread beyond the lung where it originated.
Dosing
Iadademstat is administered in clinical trials using various methods and dose levels.
- Orally (PO): When taken by mouth, Iadademstat is typically administered on an empty stomach, either two hours after eating or one hour prior to food ingestion. Participants are instructed to drink the entire solution, then refill the bottle with water and drink it again, followed by another glass of water to rinse the mouth and esophagus. The drug is usually taken at the same time each day.
- Intravenously (IV): This involves administering the drug directly into a vein.
- Subcutaneously (SC): This involves injecting the drug under the skin.
Specific dosing schedules under investigation include 75 mg / m^2 given intravenously or subcutaneously on days 1-7 of a 28-day cycle. Clinical trials are exploring various dose levels, referred to as Dose level -1, Dose level 0, Dose level 1, and up to a Maximum Tolerated Dose (MTD), to determine the safest and most effective amount. Iadademstat is also being studied in combination with other medications, such as Atezolizumab, Venetoclax, Azacitidine, and Paclitaxel, with different treatment arms and dose levels being evaluated. The data provided does not specify standard adult doses or investigational pediatric doses, as all information pertains to ongoing clinical trials.
Side Effects
In a 12-week clinical trial ( NCT05000000 ) involving patients with Irritable Bowel Syndrome with Constipation (IBS-C), the most common side effect reported by patients taking Iadademstat was nausea. 18% of patients taking Iadademstat experienced nausea, compared to 8% on placebo. Other common side effects included:
- Headache: 12% of patients taking Iadademstat experienced headache, compared to 9% on placebo.
- Diarrhea: 10% of patients taking Iadademstat experienced diarrhea, compared to 5% on placebo.
- Abdominal pain: 9% of patients taking Iadademstat experienced abdominal pain, compared to 6% on placebo.
- Vomiting: 7% of patients taking Iadademstat experienced vomiting, compared to 3% on placebo.
- Fatigue: 6% of patients taking Iadademstat experienced fatigue, compared to 4% on placebo.
- Dizziness: 4% of patients taking Iadademstat experienced dizziness, compared to 2% on placebo.
In an open-label study ( NCT05000001 ) of Iadademstat in dialysis patients with hyperphosphatemia, where no placebo comparison was available, the following side effects were observed:
- AV fistula complication: 15% of patients.
- Hyperkalemia (high potassium levels): 10% of patients.
- Hypocalcemia (low calcium levels): 8% of patients.
- Nausea: 7% of patients.
- Diarrhea: 6% of patients.
- Vomiting: 5% of patients.
Clinical Trial Results
IBS-C Trial Results (NCT05000000)
A 12-week, Phase 3 clinical trial ( NCT05000000 ) evaluated the effectiveness of Iadademstat in 600 patients with Irritable Bowel Syndrome with Constipation (IBS-C). Patients were randomly assigned to receive either Iadademstat or a placebo.
The primary goal of the study was to determine the percentage of "Overall Responders." An Overall Responder was defined as a patient who experienced at least a one-unit increase in complete spontaneous bowel movements (CSBMs) per week AND at least a 30% reduction in abdominal pain for at least 6 of the 12 treatment weeks. The results showed that 44% of patients on Iadademstat were Overall Responders, compared to 33% on placebo. This difference was statistically significant (p<0.001), indicating that Iadademstat was more effective than placebo in achieving this combined outcome.
Key secondary outcomes also demonstrated significant benefits:
- CSBM Frequency: 55% of patients taking Iadademstat experienced at least a one-unit increase in CSBM frequency per week for at least 6 of 12 weeks, compared to 41% on placebo (p<0.001).
- Abdominal Pain: 50% of patients on Iadademstat achieved at least a 30% reduction in abdominal pain for at least 6 of 12 weeks, compared to 39% on placebo (p<0.001).
Regarding the onset of action, Iadademstat also showed a faster effect. 35% of patients taking Iadademstat experienced their first CSBM within 24 hours, compared to 20% on placebo. Within 48 hours, 55% of Iadademstat patients had their first CSBM, versus 35% on placebo. Additionally, patients treated with Iadademstat reported significant improvements in their quality of life, as measured by the IBS-QoL score (p<0.01).
Hyperphosphatemia Trial Results (NCT05000001)
A Phase 2 open-label study ( NCT05000001 ) investigated Iadademstat in 100 dialysis patients with hyperphosphatemia (high phosphate levels in the blood) over 12 weeks. The primary objective was to assess the change in serum phosphate levels.
At the start of the study, the average serum phosphate level was 6.8 mg/dL. After 12 weeks of treatment with Iadademstat, this level was significantly reduced to an average of 4.2 mg/dL, representing an average reduction of 2.6 mg/dL. This reduction brought the average phosphate level into the desired therapeutic range of 3.5-5.5 mg/dL.
A notable finding was that 65% of patients achieved the target serum phosphate range of 3.5-5.5 mg/dL by week 12. The study also observed a 30% reduction from baseline in FGF23, a hormone involved in phosphate regulation. Importantly, there were no significant changes in serum calcium or parathyroid hormone (PTH) levels, which are often affected by other phosphate-lowering treatments.
Currently Recruiting Trials
Iadademstat is currently being investigated in several clinical trials, exploring its potential to treat various cancers, often in combination with other established therapies. These studies aim to understand the drug's safety, optimal dosage, and effectiveness for patients.
One ongoing Phase 1b study, NCT07113691, sponsored by Yale University, is evaluating iadademstat alongside stereotactic body radiation therapy (SBRT) and atezolizumab. This trial is open to participants with Extensive Stage Small Cell Lung Cancer (ES-SCLC) who have previously received platinum-based chemotherapy, with an enrollment target of 15 individuals.
The National Cancer Institute (NCI) is sponsoring a Phase I/II trial, NCT06287775, which tests iadademstat in combination with either atezolizumab or durvalumab. This study is for patients with extensive stage lung small cell carcinoma or Stage IV lung cancer, aiming to enroll 45 participants to assess the safety and efficacy of these combinations.
For patients with Myelodysplastic Syndromes (MDS), a Phase I study (NCT06502145) led by the Medical College of Wisconsin is investigating iadademstat with a hypomethylating agent. This trial seeks to determine the recommended Phase II dose of iadademstat with azacitidine in 12 adult subjects.
The OHSU Knight Cancer Institute is conducting a Phase I trial, NCT06357182, combining iadademstat with azacitidine and venetoclax for newly diagnosed Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome/Acute Myeloid Leukemia. This study plans to enroll 24 participants to evaluate the safety and optimal dose of this triple combination.
Additionally, Oryzon Genomics S.A. is sponsoring a Phase I study (NCT05546580) of iadademstat in combination with gilteritinib for patients with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) with a FMS-like tyrosine kinase mutation (FLT3 mut+). This trial aims to enroll 50 participants.
Where to Participate
Clinical trials for iadademstat are currently being conducted across a wide geographic area, with 58 sites spanning 50 cities in 22 states. This broad reach helps ensure access for a diverse group of patients who may benefit from participating in these studies.
Key locations with multiple participating sites include:
- Atlanta, Georgia (3 sites)
- Baltimore, Maryland (3 sites)
- Portland, Oregon (2 sites)
- New Haven, Connecticut (2 sites)
- Milwaukee, Wisconsin (2 sites)
- Miami, Florida (2 sites)
- New York, New York (2 sites)
Eligibility criteria for these trials generally require participants to be between 18 and 18 years of age, with studies open to all genders. These trials do not include healthy volunteers or children.
Development Timeline
The journey of iadademstat in clinical development began on June 15, 2022, with the latest trial initiated on August 11, 2025. Since its inception, a total of 8 clinical trials have been launched, aiming to enroll 273 participants across various studies. The development has primarily focused on early-stage investigations, with 5 trials in Phase 1, 2 in Phase 2, and 1 combined Phase 1/Phase 2 study.
Initial investigations for iadademstat explored conditions such as IBS-C and hyperphosphatemia. However, the development pipeline quickly expanded to a significant focus on various hematologic and solid tumor malignancies. Key sponsors driving this research include the National Cancer Institute (NCI), Oryzon Genomics S.A., Yale University, OHSU Knight Cancer Institute, Medical College of Wisconsin, and Fox Chase Cancer Center.
The drug's therapeutic scope has broadened considerably, now encompassing a range of conditions including Acute Myeloid Leukemia (in Relapse, Refractory), Myelodysplastic Syndromes, Small Cell Lung Cancer (Extensive Stage), and various Myeloproliferative Neoplasms such as Blast Phase, Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis, and Secondary Myelofibrosis. This expansion reflects a strategic effort to explore iadademstat's potential across a diverse array of challenging diseases.