A selective SYK inhibitor for
immune-mediated cytopenias.
Lanraplenib is an oral, once-daily, highly selective SYK inhibitor advancing toward registration in refractory Immune Thrombocytopenia and warm Autoimmune Haemolytic Anaemia, with platform potential across SYK-driven disease.
ITP remains poorly controlled.
Immune Thrombocytopenia is a chronic autoimmune disease marked by relapsing thrombocytopenia and bleeding risk. Corticosteroids remain first line, but many patients become steroid-dependent, and chronic exposure is toxic. Second-line options are largely non-durable and fail to modify the underlying disease biology. There is a clear, persistent need for durable, steroid-sparing, disease-modifying therapies.
Each class leaves residual disease or unacceptable toxicity.
Steroids
Broad immunosuppression with transient benefit. Cumulative toxicity limits long-term use; patients become steroid-dependent.
TPO-RAs
Nplate, Promacta. Increase platelet production without addressing the immune-mediated destruction driving disease.
Anti-CD20
B-cell depletion with delayed onset, variable durability and infection risk. Does not resolve underlying pathology.
FcRn antagonists
Lower circulating IgG but do not suppress ongoing autoantibody production at source. Infusion burden.
BTK inhibitors
Wayrilz / rilzabrutinib, hampered by FDA DILI warnings and unsustainable AEs in chronic non-oncology settings.
First-gen SYK inhibitors
Tavalisse/fostamatinib, poor kinase selectivity drives GI toxicity; sovleplenib relies on accumulation for efficacy.
One target.
Two arms of disease.
SYK is the central pathogenic node integrating B-cell autoantibody production with Fcγ-mediated destruction of IgG-opsonised platelets and red cells. Inhibiting SYK directly addresses the disease-driving mechanisms rather than compensatory pathways.
Reprograms autoantibody production
SYK inhibition disrupts BCR signalling in B cells, dampening activation and reducing anti-platelet / anti-RBC IgG output over time. Durable, disease-modifying control.
Blocks Fcγ-mediated phagocytosis
At the macrophage, SYK inhibition halts Fcγ-receptor signalling, preventing phagocytosis of opsonised platelets and red cells. Immediate protection, within days.
Purpose-built for chronic autoimmune use.
Lanraplenib was selected from a selectivity-driven medicinal chemistry campaign that retained the anilino-imidazopyrazine core while resolving the pH-dependent solubility, PPI drug–drug interactions, and BID dosing limitations of the earlier Gilead lead, entospletinib.
SYK inhibition
Designed to minimise off-target kinase activity that has bottlenecked earlier SYK inhibitors. >100× selectivity vs most off-targets.
once-daily
PK profile supports convenient chronic administration. 24-hour EC₅₀ coverage at 30 mg QD, suitable for long-term autoimmune care.
validated exposure
Human data show consistent, dose-proportional exposure aligned with preclinical SYK pathway inhibition. Phase 1 MAD: well tolerated at 15, 30, 50 mg.
safety
Eight completed Phase 1/2 studies; >250 patients. All AEs in healthy subjects Grade 1 and reversible. No dose-AE relationship observed.
Best-in-class, by selectivity.
In chronic ITP, medicines only work when patients actually take them, and GI toxicity is the quiet reason they don't. Roughly one in three patients on fostamatinib experience diarrhea, and discontinuation rates track directly with it. Lanraplenib's selectivity window is orders of magnitude wider at clinical exposures, removing the off-target GI burden that erodes adherence and long-term efficacy.
Higher fold = safer. Each bar shows fold-selectivity vs SYK at ATP Km, a larger gap means the drug must reach higher exposures to meaningfully engage the off-target kinase, producing adverse events.
Lanraplenib Cmax is well below off-target engagement thresholds. Fostamatinib's fatigue, diarrhea, hypertension trace to FLT3/KDR/EGFR co-engagement at its clinical dose.
A SYK-driven
platform.
The SYK-centric mechanism supports expansion beyond ITP into adjacent immune cytopenias and B-cell–driven diseases, with early preclinical evidence generated in CLL.
wAIHA
Warm autoimmune haemolytic anaemia. SYK-mediated macrophage phagocytosis of autoantibody-coated RBCs. ~1 in 8,000 prevalence; >50% refractory or relapse within 1 year.
CLL
SYK remains the central BCR signalling node upstream of BTK, preserving pathway control across BTK resistance mutations including A428D. Synergy with venetoclax.
Platform breadth
Evans syndrome, Graves' disease, IgG4-related disease, DLBCL, sickle cell. SYK biology is present in each. Lanraplenib offers a shared mechanism across a family of immune dysregulation.
A modular path to registration.
A Phase 2/3 modular design in relapsed/refractory ITP, with wAIHA registrational cohort. Clear, binary readouts on platelet and haemoglobin response.
20 mg & 30 mg vs placebo in R/R + steroid-sparing ITP. 20 pts per arm/dose.
Selected dose vs placebo, 2:1 randomisation (total: 108 pts). Endpoint: durable platelet response. Launch target: 2032.
Selected dose vs placebo, 2:1 randomisation (total: 96 pts). Endpoint: Hb response. Launch target: 2034.
Operators who've
done this before.
Drug discovery leaders with multiple assets in clinical development, supported by haematology, clinical, regulatory, and pharmacology advisors from Amgen, Rigel, BMS, and AstraZeneca.
Drug discovery leader with proven track record of assets reaching clinical development.
An experienced drug discovery programme leader focussed on translation to the clinic.
Medicinal chemist with 20 years in small molecule design and synthesis.
Pharmacologist with a decade of experience spanning hit discovery through IND.
A decade of drug discovery and development experience with two previous assets currently in the clinic.
Clinical strategy, study design and trial execution. >20 yrs experience in Hematology Clinical Operations at Amgen.
Strategic medical and clinical guidance across development programmes. Previous role supporting Rigel Therapeutics.
>15yrs regulatory affairs experience supporting biotech and Pharma, including experience gained at BMS.
Clinical Pharmacology specialist; >15 yrs at AZ including as Global Head of Bioanalysis.
Let's
transform
ITP care.
Sphinx Tx is actively exploring partnerships for Lanraplenib across ITP, wAIHA and platform indications. Licensing, co-development, and acquisition inquiries welcome.