LifeMine Therapeutics has dosed the first participant in a Phase 1 clinical trial evaluating LIFE-001, a novel calcineurin inhibitor (CNi) designed to treat immune-mediated disorders and prevent organ transplant rejection. The Cambridge, Massachusetts-based biopharmaceutical company announced this milestone as it transitions to a clinical-stage organization.
LIFE-001 represents a significant advancement in immunosuppressive therapy, engineered specifically to avoid the immunophilin-dependent organ damage associated with traditional calcineurin inhibitors. The drug was developed using LifeMine's proprietary Top-Down Drug Discovery™ platform, which leverages digital genomic search technology from fungi to identify next-generation precision medicines.
Novel Mechanism and Improved Safety Profile
Unlike conventional calcineurin inhibitors, LIFE-001 employs an immunophilin-independent mechanism designed to maintain efficacy while eliminating the off-target toxicity that has limited the utility of existing therapies.
"CNis have been a primary treatment for organ and tissue transplantation, as well as multiple immune-mediated disorders, for many years," explained Simon Cooper, MBBS, Chief Medical Officer at LifeMine. "Despite their broad utility, off-tissue toxicity and narrow therapeutic index have limited the use of legacy CNis and represent a key unmet need for both physicians and patients."
Preclinical studies have demonstrated that LIFE-001 offers a radically improved safety profile compared to existing calcineurin inhibitors. The drug has shown compelling efficacy in validated animal models of ulcerative colitis and Crohn's disease, suggesting potential applications across a range of inflammatory conditions.
Clinical Trial Design and Objectives
The first-in-human Phase 1 clinical trial is structured to comprehensively evaluate LIFE-001's clinical profile:
- Phase 1a will include single ascending dose (SAD) and multiple ascending dose (MAD) components, enrolling approximately 100 adult participants
- The study will assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD)
- Phase 1b will evaluate preliminary efficacy across multiple immune-mediated disease cohorts, including ulcerative colitis
The controlled-release formulation of LIFE-001 offers potential advantages in terms of convenience and adherence. The long-acting injectable formulation may provide predictable drug exposure while eliminating the need for frequent blood monitoring and concomitant therapies often required with traditional calcineurin inhibitors.
Potential for Broad Clinical Applications
Gregory Verdine, Ph.D., Co-founder, President and Chief Executive Officer of LifeMine, highlighted the drug's potential impact: "Owing to the unrivalled breadth and depth of efficacy in calcineurin inhibition as a proven mode of immune suppression across over 30 distinct indications, and with LIFE-001 now having overcome the deficiencies of legacy CNis, this fundamentally reinvented, immunophilin-independent drug has the potential to become the go-to universal immunosuppressant."
The company believes LIFE-001 could eventually replace all legacy calcineurin inhibitors with a best-in-class alternative offering improved safety, tolerability, and convenience. The drug's mechanism may provide advantages over both traditional immunosuppressants and newer biologic therapies.
Funding and Future Development
LifeMine has secured funding for the entire Phase 1a study and is currently raising additional capital to support efficacy studies planned for 2026 and beyond. The company has raised more than $320 million to date from leading life science investors.
"LifeMine's transition into a clinical-stage company marks a significant achievement for our team and underscores the power of our genomic discovery engine to bring sophisticated medicines to patients in urgent need of breakthrough disease intervention," said Verdine.
The company's platform integrates human genetics and genomics, bioinformatics, machine learning, and synthetic biology to identify novel therapeutic candidates. This approach has enabled the development of LIFE-001's previously unprecedented structure and mechanism of action.
As the clinical trial progresses, LifeMine will evaluate LIFE-001's potential across multiple immune-mediated disorders, potentially establishing a new standard for immunosuppressive therapy in conditions ranging from inflammatory bowel disease to organ transplantation.
