First-in-Class ADAR1 Inhibitor Rebecsinib Enters Phase 1 Trial for AML and Myelofibrosis at UC San Diego
核心洞察
Rebecsinib, a first-in-class ADAR1 (搜索) inhibitor, has entered a Phase 1 clinical trial at UC San Diego with the first patient treated on July 6.
The trial is open to adults with relapsed/refractory secondary AML and higher-risk myelofibrosis (搜索), two rare blood cancers with few treatment options.
Discovered by Catriona Jamieson, MD, PhD, the drug was studied aboard the International Space Station, where microgravity accelerates disease modeling and drug testing.
A first-in-class investigational drug targeting the ADAR1 (搜索) gene has reached the clinic. Rebecsinib, an experimental anti-cancer agent discovered at UC San Diego, is now being evaluated in a Phase 1 clinical trial for patients with two rare and difficult-to-treat blood cancers. The first patient received the drug on July 6, marking a milestone that principal investigator James Mangan, MD, PhD, professor of medicine at UC San Diego School of Medicine and a hematologist and oncologist at UC San Diego Health, described as "promising."
"This trial has great science behind it," Mangan said. "It uses a totally novel mechanism and really is for patients who have a desperate, unmet need."
The trial, sponsored by Aspera Biomedicines (搜索), is enrolling adults 18 years of age and older who have secondary acute myeloid leukemia (搜索) (AML) that has either recurred or not responded to treatment, as well as patients with higher-risk myelofibrosis (搜索). Both are rare blood cancers for which few treatment options exist initially — and no good options if they return.
A Novel Mechanism Targeting ADAR1 (搜索)
Rebecsinib is the first and only ADAR1 (搜索) inhibitor to receive an investigational new drug application from the U.S. Food and Drug Administration, which green-lit the clinical trial in March of last year. The drug inhibits the ADAR1 gene, which is involved in the proliferation of more than 20 cancer types. When activated, ADAR1 produces the ADAR1p150 protein, which promotes tumor growth by hiding cancer from the immune system.
Catriona Jamieson, MD, PhD, director of the UC San Diego Sanford Stem Cell Institute, professor of medicine, and chief of the Division of Regenerative Medicine, discovered the drug and has led its development from the laboratory to the clinic. "Rebecsinib shows all the promise in the world not only to halt the progression of multiple cancers, but to shrink them, as well as prevent their spread to multiple sites in the body," Jamieson said.
For AML and myelofibrosis (搜索) patients, the rebecsinib clinical trial represents a new avenue of hope. "If this works, it's a good option for those who don't otherwise have targeted agents available to them," Mangan said.
Space-Based Research Accelerates Development
Rebecsinib is one of the very first drugs studied in the cosmos. Jamieson has sent multiple research payloads to the International Space Station (ISS), testing the drug on various highly lethal cancers with ADAR1 (搜索) involvement, including ovarian cancer, metastatic breast cancer (搜索), AML, and glioblastoma multiforme (搜索). These experiments were made possible by millions in grants from NASA's In-Space Production Applications program.
The unique conditions of space — including microgravity and galactic cosmic radiation — create a stressful environment that mimics accelerated aging and disease progression on Earth. Depending on the experiment, one month in microgravity can give researchers a preview of several years, if not more than a decade, of disease maturation. Jamieson's research found that space activates ADAR1 (搜索), which in turn produces ADAR1p150, the protein that shields cancer from immune detection.
"Space gives Dr. Jamieson a tremendous chance to see a lot of changes in stem cell DNA in a short period of time," Mangan said. He added that rebecsinib could potentially serve as "a therapeutic mechanism to restore stem cell function after space travel" for astronauts, with implications for the accumulated stresses and mutations that occur over decades of human aging.
In the summer of 2024, Jamieson received the ISS National Laboratory Compelling Results Award in Biology and Medicine for her discovery that the drug blocks ADAR1 (搜索) activation in cancer — in space. Donor Rebecca Moores, whose funding of Jamieson's lab enabled the drug's development, noted that Jamieson's cancer stem cell research launched on SpaceX CRS-34 "mere weeks before the first patient received rebecsinib in clinical trial."
Patient Perspectives and Unmet Need
The trial's launch carries deep significance for patients living with these rare blood cancers. Patient advocate Andrew Schorr, 75, who has lived with myelofibrosis (搜索) and chronic lymphocytic leukemia (搜索) for decades, expressed cautious optimism. "Every patient needs hope for what could be their next treatment, because these drugs peter out," Schorr said. "Cancer finds a way around them. They're not as effective over time, as your disease progresses. You're always left wondering what the next option is."
Sandra Dillon, 50, diagnosed with an aggressive form of myelofibrosis (搜索) in 2006, spent 13 years taking fedratinib — a drug Jamieson played a prominent role in reviving after the FDA placed it on clinical hold. Dillon described those years as "magical," with minimal side effects. More recently, however, her disease progressed, and she underwent a bone marrow transplant last fall before the rebecsinib trial opened. "If you could just take a pill, it would be a far better solution," Dillon said. "When I think about rebecsinib, I think of it as that next stage — if one medication stops working, there are other options that could be effective for this very rare blood disease."
A Rapid Bench-to-Bedside Trajectory
The path from discovery to first-in-human trial has been notably swift. "To take it from a basic science paper published in Cell Stem Cell in 2023 to first-in-human Phase I clinical trial in just three years is a tremendous effort," Mangan said. "Dr. Jamieson has a proven track record of bringing drugs successfully from bench to clinic, and ultimately to FDA approval, for patients."
The trial may eventually expand to other ADAR1 (搜索)-involved cancers, including lymphoma, glioblastoma multiforme (搜索), and metastatic breast cancer (搜索). Mangan noted that cancer centers "across the U.S. are very excited about opening this trial."
Schorr suggested that rebecsinib's development pathway — leveraging space-based research to accelerate data collection — could represent a new model for drug development. "Could this be an example of a new model for drug development?" he asked. "And could rebecsinib be helpful for other conditions?"