Autoimmunity Drug Development
Selectively block pathogenic plasma cells without B-cell depletion
The Challenge
B-Cell Depletion Is Too Broad
Current B-cell depletion approaches eliminate all B-cells, causing immunodeficiency and infection risk. Patients need targeted therapies that block pathogenic plasma cell formation while preserving protective immunity.
Long-Lived Plasma Cells Escape Treatment
In lupus/RA, pathogenic plasma cells in bone marrow niches are resistant to current therapies. They survive for years, continuously producing autoantibodies despite B-cell depletion.
Unknown Differentiation Stage to Target
Should you block MBC→plasmablast transition? Or plasmablast→plasma cell? Or target mature plasma cells? Without understanding normal differentiation, rational drug design is impossible.
Massive Unmet Need
Significant proportions of patients with lupus nephritis progress to kidney failure despite current therapy. RA and MS have substantial inadequate-response populations. The unmet need across antibody-mediated autoimmune diseases is substantial.
"We need a drug that stops autoantibody production in lupus WITHOUT causing pan-B-cell depletion. But we don't know which differentiation stage to target or how to test selectivity before clinical trials."
The Helomnix Solution
Helomnix in-vitro B-cell→plasma cell differentiation model enables screening of drugs that selectively inhibit specific differentiation stages. Test whether your compound blocks: (1) MBC activation, (2) plasmablast formation, (3) plasma cell maturation, or (4) mature plasma cell survival.
By profiling drug effects at each stage with flow cytometry and scRNA-seq, we identify therapeutic windows: doses that block pathogenic plasma cell formation while sparing memory B-cells (preserving vaccine responses and protective immunity).
This approach applies across autoimmune diseases: lupus (target autoreactive plasma cells), RA (synovial plasma cells), MS (CNS-infiltrating plasma cells), and others. The differentiation model is disease-agnostic—it tests mechanism, not disease context.
Unique Differentiator
Our in-vitro model is the ONLY commercial platform to test selective plasma cell differentiation inhibition. Used by autoimmunity researchers worldwide. Enables rational drug development vs. empirical screening.
How It Works
Drug Screening Setup
Test your drug candidate on our 10-day B→PC differentiation model at multiple doses. Monitor effects on each differentiation stage (MBC/Pre-PB/PB/PC).
Stage-Specific Inhibition Analysis
Flow cytometry at days 0, 3, 7, 10 quantifies which stage is blocked. ScRNA-seq reveals transcriptional mechanisms: which differentiation-stage master regulators are disrupted by the compound?
Selectivity Assessment
Test whether memory B-cells survive drug treatment and can still respond to antigens (vaccine mimic). Quantify therapeutic window: plasma cell blockade WITHOUT memory B-cell depletion.
Mechanistic Report & Strategy
Receive stage-specific IC50 values, selectivity index, scRNA-seq mechanism analysis, and structured evidence summary for autoimmunity indication assessment.
Real-World Application
A biotech developing a compound for hematological malignancies wanted to expand to autoimmunity indications. Question: Does the compound block pathogenic plasma cell formation selectively?
Before
Traditional approach: Test compound in mouse lupus models (significant investment over many months). Unclear which differentiation stage is affected and whether protective immunity is preserved.
After
Helomnix screening: The compound blocked the plasmablast-to-plasma cell transition at lower concentrations while sparing memory B-cells at higher doses. Single-cell profiling revealed disruption of a key transcriptional program driving terminal differentiation.
Outcome
Identified a meaningful therapeutic window with selective plasma cell inhibition. Prioritized lupus nephritis indication (plasma cell-driven). Designed Phase I with memory B-cell and vaccine response monitoring. Avoided expensive mouse studies.
Value to Your Organization
Market Opportunity
Selective plasma cell inhibitors address large unmet need across multiple major autoimmune indications including lupus, RA, and MS.
Selectivity De-Risking
Identify therapeutic window where pathogenic plasma cells are blocked but memory B-cells preserved. De-risk immunodeficiency concerns before Phase I.
Preclinical Efficiency
In-vitro screening is substantially more cost-effective and faster than mouse lupus/RA/MS models, with more mechanistic insight.
Our Methodology
Data Inputs
- Drug compound with known mechanism of action
- Desired dose range for testing
- Target autoimmune indication (lupus, RA, MS, etc.)
- Known effects on B-cell malignancies (if repurposing)
AI/ML Techniques
- Primary human memory B-cell isolation from healthy donors
- 10-day in-vitro differentiation protocol (MBC→Pre-PB→PB→PC)
- Drug treatment at multiple doses (0.1x-10x IC50)
- Flow cytometry for viability and differentiation markers
- Single-cell RNA-seq (10X Genomics) at days 3, 7, 10
- Memory B-cell functional assay (antigen response)
- Plasma cell antibody production quantification (ELISA)
Deliverables
- Stage-specific IC50 values (MBC, Pre-PB, PB, PC)
- Selectivity index: PC inhibition vs. MBC preservation
- Flow cytometry differentiation marker analysis
- ScRNA-seq mechanistic analysis: Which transcription factors and pathways are disrupted
- Memory B-cell functional preservation assessment
- Antibody production dose-response curves
- Structured evidence report: indication-specific mechanistic context
- Preclinical characterization summary to support program advancement
Discuss a Translational Application
We welcome discussions about how this approach can support your translational research.