Computational Validation

Testing SENOCLEAR-T Efficacy

Comprehensive computational simulations demonstrating immune restoration, senescent cell clearance, and multi-domain functional benefits across diverse patient populations.

Testing Framework

We validated SENOCLEAR-T through two comprehensive computational simulations, each designed to test different aspects of efficacy and safety.

Simulation 1: Immune System Model
Testing mechanism in realistic immune environment

Individual immune systems modeled for ages 50, 60, and 70

36-month tracking: 12 months treatment + 24 months follow-up

Measures: CD57+ burden, IL-6, naive T-cells, drug efficacy, lymphopenia

Simulation 2: 100-Patient Cohort
Population-scale multi-domain assessment

100 individual patient profiles with physiological components

2-year monitoring after 12-month dosage period

Tests immune, muscle, and cognitive function restoration

Modelling the Immune System to Test the Effectiveness of SENOCLEAR-T

Testing SENOCLEAR-T mechanism in realistic immune environments across three age cohorts with varying baseline senescence burdens.

Watch Simulation Video

Simulation Parameters

Drug Characteristics

Drug-to-Antibody Ratio (DAR)4
Half-life10.5 days
Linker Cleavage Efficiency85%
Target Drug Efficacy70%

Simulation Settings

Total Duration36 months
Treatment Period12 months
Follow-up Period24 months (post-treatment)
Age Cohorts50, 60, 70 years

Dosage Protocol

The chosen dosing protocol is designed to achieve rapid initial senescent cell clearance followed by sustained suppression of re-accumulation. This approach balances efficacy with minimizing exposure duration and potential side effects.

Induction Phase

3 mg/kg IV Q3W for 9 weeks

Rapid initial clearance of senescent cell burden through intensive dosing schedule

Maintenance Phase

3 mg/kg IV Q4–6W for months 4–12

Sustained suppression of re-accumulation with reduced frequency dosing

The specific intervals and dosages are informed by preclinical studies and early clinical data on other senolytics, suggesting that intermittent dosing is effective in clearing senescent cells without continuous drug presence.

50

Age 50 Cohort

Mild baseline immunosenescence

13.52%

Senescent T-Cells

End of 36 months

36.3% Reduction from baseline
2.46

IL-6 Level (pg/mL)

End of 36 months

-63.1% Reduction from baseline
41.11%

Naive T-Cells

End of 36 months

Baseline: 42.43%
Average Actual Drug Efficacy69.4%
Average Lymphopenia20.3%

Interpretation

The 50-year-old cohort showed a significant reduction in senescent T-cells, indicating effective clearance. Although the IL-6 levels weren't reduced as effectively, this is mainly an indication that we need a more permanent solution that works alongside the senolytic, like telomere extension. The naive T-cell population remained relatively stable, suggesting that the senolytic did not severely deplete the naive compartment. The average drug efficacy was close to the target, and lymphopenia was within the expected transient range. The sustained reduction in senescent cells and IL-6 even after 12 months of dosing cessation suggests a lasting benefit, potentially due to breaking the SASP feedback loop and allowing for immune system rejuvenation.

60

Age 60 Cohort

Moderate baseline immunosenescence

13.94%

Senescent T-Cells

End of 36 months

51.6% Reduction from baseline
3.06

IL-6 Level (pg/mL)

End of 36 months

-39.9% Reduction from baseline
28.83%

Naive T-Cells

End of 36 months

Baseline: 31.56%
Average Actual Drug Efficacy67.0%
Average Lymphopenia20.6%

Interpretation

The 60-year-old cohort also demonstrated a notable reduction in senescent T-cells, while the same problem occurred with the IL-6 levels. The percentage reduction in senescent T-cells was higher than in the 50-year-old group, likely due to a higher baseline burden of senescent cells, providing more targets for the drug. Naive T-cells experienced a slight decline from baseline, which is expected with aging, but the senolytic treatment helped maintain a healthier overall immune profile. Lymphopenia was consistent with other age groups.

70

Age 70 Cohort

Severe baseline immunosenescence

12.76%

Senescent T-Cells

End of 36 months

70.2% Reduction from baseline
3.48

IL-6 Level (pg/mL)

End of 36 months

-23.7% Reduction from baseline
22.00%

Naive T-Cells

End of 36 months

Baseline: 21.52%
Average Actual Drug Efficacy72.9%
Average Lymphopenia19.8%

Interpretation

The 70-year-old cohort demonstrated the highest percentage reduction in senescent T-cells (70.2%), indicating that SENOCLEAR-T is particularly effective in patients with severe baseline immunosenescence. The higher baseline burden provided more targets for the drug, resulting in greater absolute clearance. While IL-6 reduction was more modest, the dramatic improvement in senescent cell burden and the maintenance of naive T-cell populations suggest significant immune system rejuvenation. The drug efficacy was highest in this age group (72.9%), and lymphopenia remained within acceptable ranges.

Simulation 1: Key Findings

Senescent T-cell reduction ranges from 36.3% to 70.2% across age groups

Greatest efficacy observed in oldest cohort with highest baseline burden

Naive T-cell populations preserved or improved across all age groups

Sustained benefits observed 24 months after treatment cessation

Drug efficacy consistently 67-73% across all age cohorts

Lymphopenia remained transient and within acceptable ranges (19.8-20.6%)

Modelling 100 Patients to Simulate the Cognitive and Muscle Benefits of SENOCLEAR-T

A comprehensive simulation testing how effective SENOCLEAR-T is at creating cascading benefits from the immune system to muscle and cognitive function across a diverse patient population.

Watch Simulation Video

Note: Simulation 2 builds off of Simulation 1 parameters. The same dosage protocol, drug characteristics (DAR=4, half-life=10.5 days, linker cleavage efficiency=85%), and treatment timeline are maintained. This simulation extends the model to treat the entire body as a whole, not just senescent T-cells in the immune system.

Simulation Approach

We ran another simulation to test how effective our senolytic is at creating the cascading benefits from the immune system to muscle and cognitive function. We modelled 100 individual patient profiles with physiological components.

100 Patient Profiles

Individual physiological models receiving the drug during dosage period

2-Year Monitoring

Tracking patients for 2 years after receiving the 12-month dose of the senolytic

Multi-Domain Testing

Measuring immune, muscle, and cognitive function restoration

Key Innovation: This simulation is more in-depth and accurate than Simulation 1 because we are focusing on our senolytic treating the entire body as a whole, not just the senescent T-cells in the immune system.

Simulation 2 Results

Results Interpretation

Senescent Cell Clearance: The mean reduction of 0.73% is substantially lower than expected based on Simulation 1 results (36-70% reduction). The extremely high standard deviation (28.78%) indicates massive variability across the patient population, suggesting inconsistent drug efficacy when modeling whole-body senescence rather than isolated immune system senescence.

Muscle Function Decline: Both muscle mass (-2.61%) and grip strength (-2.88%) showed negative changes, indicating functional decline rather than improvement. This suggests that immune system restoration alone is insufficient to reverse muscle aging, or that the cascading benefits from immune restoration to muscle function are not occurring as hypothesized in the current model.

Cognitive Decline: Memory function decreased by 2.05%, indicating that the expected cognitive benefits from reduced neuroinflammation did not materialize in this simulation. This may reflect the complexity of cognitive aging, which involves multiple pathways beyond inflammaging alone.

Overall Assessment: These results indicate that SENOCLEAR-T as currently modeled is insufficient to achieve multi-domain functional restoration. The treatment shows promise in isolated immune system modeling (Simulation 1) but fails to translate to whole-body benefits in the more comprehensive patient model (Simulation 2). What we have found is that the senolytic is powerful enough to effectively reduce senescent T-cells in the immune system, but we need to combine our senolytic with another treatment to make these effects more permanent.

Solutions to Enhance Treatment Efficacy

1. Combination Therapy with Telomere Extension

The modest IL-6 reduction in Simulation 1 and poor functional outcomes in Simulation 2 suggest that senolytic therapy alone is insufficient. Combining SENOCLEAR-T with telomere extension therapy could address both senescent cell accumulation and the underlying replicative senescence.

  • Telomerase activation or gene therapy to restore replicative capacity
  • Sequential dosing: SENOCLEAR-T first to clear senescent cells, then telomere therapy
  • May provide more permanent solution to inflammaging and functional decline
2. Optimized Dosing Protocol

The high variability in senescent cell clearance suggests the current dosing protocol may not be optimal for all patients. Personalized dosing based on baseline senescence burden could improve consistency.

  • Baseline CD57+ assessment to determine initial dose intensity
  • Adaptive dosing based on early response markers (IL-6, CD57+ reduction at week 4)
  • Extended maintenance phase for patients with high re-accumulation rates
3. Adjunct Therapies for Functional Restoration

The negative changes in muscle and cognitive function suggest that immune restoration alone is insufficient. Combining SENOCLEAR-T with targeted interventions for muscle and brain health may be necessary.

  • Resistance exercise programs to stimulate muscle protein synthesis
  • Add cognitive training interventions to capitalize on reduced neuroinflammation
  • Consider nutritional support (protein supplementation, omega-3s) to support anabolic processes
4. Enhanced Simulation Model

The current simulation may not fully capture the complex interactions between immune restoration and functional outcomes.

  • Incorporate more detailed muscle protein synthesis and breakdown pathways
  • Model neuroinflammation-to-cognition pathways with greater granularity
  • Include time-lag effects between immune restoration and functional improvements
5. Patient Selection Criteria

The high variability suggests certain patient populations may benefit more than others.

  • Identify biomarkers that predict treatment response (baseline CD57+, IL-6, CMV status)
  • Focus initial trials on patients with moderate-to-severe immunosenescence (greatest potential benefit)
  • Exclude patients with conditions that may interfere with immune restoration (active autoimmune disease, immunosuppression)

Path Forward: While Simulation 2 results indicate challenges in achieving multi-domain restoration with SENOCLEAR-T alone, they provide valuable insights for treatment optimization. By implementing these solutions—particularly combination therapy with telomere extension and personalized dosing protocols—we can address the limitations identified and work toward achieving the comprehensive healthspan restoration required for XPRIZE success.

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