Liminatus Pharma (NASDAQ: LIMN) has completed pivotal preclinical safety studies for IBA101, a second-generation CD47 inhibitor designed to overcome the severe blood-related toxicities that derailed earlier CD47 programs. The company plans to initiate Phase 1 clinical trials in early 2027 following regulatory submissions to both U.S. and Korean authorities in the second half of 2026.
Enhanced Safety Profile Addresses Historical Challenges
In a 4-week GLP toxicology study conducted at Charles River Laboratories using cynomolgus monkeys, IBA101 demonstrated a favorable safety profile at all tested dose levels, including the highest dose of 100 mg/kg/week. Critically, no clinical or laboratory evidence of hemolysis, anemia, or thrombocytopenia were observed, with the No Observed Adverse Effect Level (NOAEL) established at 100 mg/kg/week.
"The primate study results support our safety assumptions and inform our clinical dosing strategy," said Chris Kim, CEO of Liminatus Pharma.
This safety profile represents a significant advancement over first-generation CD47 inhibitors. Both Gilead's acquisition of Forty Seven Inc. and Pfizer's licensing deal for CD47 blockade technology were ultimately paused due to severe anemia and thrombocytopenia caused by off-target binding to red blood cells and platelets.
Strategic Engineering Approach
IBA101 employs targeted epitope selection and Fc engineering to selectively bind CD47 epitopes on tumor and immune cells while sparing healthy red blood cells and platelets. Additional glycosylation on RBC and platelet CD47 proteins prevents IBA101 engagement, minimizing off-target interactions and reducing cytopenia risk.
The antibody blocks the CD47 "don't-eat-me" signal to promote macrophage-mediated clearance and reshapes the tumor environment to boost antigen presentation and T-cell activation. This dual-axis mechanism reactivates macrophage-mediated clearance while remodeling the tumor microenvironment by enhancing macrophage turnover and antigen presentation.
Korean Clinical Collaboration
Liminatus has established a strategic partnership with Professor Se-Hoon Lee, a renowned lung cancer specialist at Samsung Medical Center in Seoul. Professor Lee's team will play a central role in the Phase 1 dose-escalation and combination trial, which will incorporate advanced translational endpoints including immune profiling, serial tumor biopsies, and multi-omics analysis.
"Partnering with Professor Lee is not merely about ensuring smooth trial operations; as both a lung cancer specialist and a clinician with deep expertise in pulmonary oncology and cancer immunotherapies, he is the ideal collaborator to uncover the translational data essential for designing Phase 2 during the Phase 1 study," said Kim.
The Phase 1 protocol features a 3+3 dose-escalation design followed by expansion cohorts and adaptive combination arms with approved PD-1/PD-L1 agents. During the initial monotherapy dose-escalation phase, the company plans to characterize IBA101's safety profile at each dose level. In subsequent combination cohorts with PD-1/PD-L1 blockade, in-depth studies will focus on patients demonstrating meaningful anti-tumor responses.
Preclinical Efficacy Data
In mouse models, combining IBA101 with PD-1 blockade drove complete tumor regression without systemic toxicity. Preclinical combination studies pairing IBA101 with PD-1/PD-L1 inhibitors resulted in significant increases in complete response rates versus monotherapy, supporting expectations for superior clinical efficacy.
Market Positioning and Commercial Potential
Global PD-1/PD-L1 sales exceeded $30 billion in 2024, but looming patent expirations will invite biosimilar competition. Combining CD47 blockade technology with PD-1/PD-L1 therapies offers enhanced response rates in combination regimens and a fresh patent lifecycle to extend commercial value. Liminatus projects that a successful IBA101 launch could secure a significant share of the post-patent market.
Regulatory Timeline and Next Steps
With its preclinical safety profile established, Liminatus is preparing IND-enabling packages for simultaneous submissions to the FDA and Korea's Ministry of Food and Drug Safety (MFDS) in the second half of 2026. The company anticipates site activations and patient screening to begin in early 2027.
IBA101 is licensed from Innobation Bio (Seoul) and represents Liminatus's lead asset as the company advances toward best-in-human trials. Beyond oncology, the company is exploring IBA101's potential in chronic inflammatory diseases through early mechanistic studies in humanized mouse models to evaluate macrophage activation for clearing senescent cells and pro-inflammatory debris.
