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Organ-i World Transplant Congress Soild Organ Rejection Test (k-SORT)
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Organ-i World Transplant Congress Soild Organ Rejection Test (k-SORT)

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SORT …

SORT

Solid Organ Rejection Test is a gene based biomarker panel that evaluates the gene expression profile of RNA isolated from peripheral blood leukocytes. SORT is intended for diagnosis and subsequent monitoring of renal transplant recipients who have a high probability of early cellular or humoral acute rejection at the time of testing. SORT should be utilized in conjunction with standard clinical assessment.

The renal transplant community is heavily reliant on serum creatinine levels as a trigger to diagnose acute rejection. However, serum creatinine is a late indicator of renal injury and exhibits high variability and high false positivity. These inadequacies lead to delayed diagnosis and irreversible renal damage.

As such, we developed the World’s first predictive test of acute rejection. This solid organ rejection test (SORT) accurately detects acute rejection 4 months prior to biopsy or other signs of clinical graft dysfunction.

SORT is intended to be utilized in conjunction with standard clinical assessment.

In the US for 0.5 Million patients with Renal Failure, transplant is the treatment of choice, but due to a critical shortage of organs, there are 85,000 patients on the waitlist of 2.5 years. Only 21,000 receive kidney transplants annually. This costs Medicare $6.3 Billion. The absence of accurate, non-invasive monitoring tests is an unmet need reflected in the high attrition rates. Organ-I is commercializing, ‘SORT’ (Solid Organ Rejection Test) first predictive, accurate, non-invasive test available to patients, averting the need for unnecessary biopsies and saving upwards of $750M.

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  • 1. Organ-I Company Overview
  • 2. 2 Overview Organ-i is a transplant franchise developing and commercializing next generation genomic and proteomic–based diagnostic tools to advance the standard of care for patients with solid organ transplants. • Operational since 2011, Stanford University Founder • >15 years of research and $ 20M NIH funding • Product focused peer reviewed journal publications • Exclusive license from Stanford University • World class SAB • Large renal transplant database • >20K tissue, blood and urine samples in bio-repository
  • 3. 3 Organ-i: Personalizing Treatment in Organ Transplantation Current challenge is the absence of a highly sensitive, early and accurate molecular test that indicates the risk and prevalence of AR in a peripheral blood sample independent of the invasive biopsy procedure.
  • 4. 4 kidney Solid Organ Rejection Test: k-SORT A 17 gene QPCR based assay: • Easy collection; no local processing • Not impacted by post-transplant time • High specifications for sensitivity, specificity of Acute Rejection • Predicts Histological Acute Rejection months before bx trigger • Applicable to pediatric and adult recipients
  • 5. 5 Kidney Solid Organ Rejection Test (k-SORT) Intended Use Statement k-SORT testing is intended to aid in the identification of renal transplant recipients with stable allograft function who have a low probability of acute rejection at the time of testing, in conjunction with standard clinical assessment.
  • 6. 6 Suggested Utilization Frequency of k-SORT for Post-transplant Monitoring • Risk of AR highest in 1st 12 months post transplantation • k-SORT reflects immune activity 3-4 months prior to histological diagnosis of AR Recommended testing schedule: Year 1: 5x 1) 1-2 weeks 2) 1 months 3) 3 months 4) 6 months 5) 12 months Year 2 onwards: 2-3x / year; specially in high-risk patients
  • 7. SCIENCE Performance and Clinical Utility of k-SORT
  • 8. 8 k-SORT Product Development Stringent sample selection; all blood samples biopsy matched
  • 9. 9 kSAS Customized Proprietary Algorithm Developed • kSAS allows for evaluation of gene- subsets among the 17 genes • Classify samples accurately across any external biases • Based on Pearson Correlation (individual sample to a reference profile of AR and No-AR) • Avoids any need for data normalization • Provides for automated technical QPCR quality control (QPCR data normalization, calculation of dCt, and ddCt) • Immediate output of numerical and categorical AR assessments for each sample.
  • 10. 10 k-SORT Assay in Pediatric & Young Adults • >-10 genes product; 5 genes sufficient by penalized Logistic regression • >-Validated by a Multi center NIH Trial: • >-130 pts; 12 US centers; 3 years f/u; 5 protocol bx/ pt; central histology • >-Blinded Analysis at NIH SORT specifications in pediatrics; ages 1-22 years • 91% sensitivity • 94% specificity, • 83% PPV, • 97% NPV • 92% accuracy • AUC 0.955Li et al, AJT, 2012 Sarwal et al, AJT, 2012 Naesens et al, AJT, 2012
  • 11. 11 Randomized multi-center SNSO1 NIH trial results SORT is Sensitive, Specific, Accurate & Non-invasive
  • 12. 12 Randomized multi-center SNSO1 NIH trial results SORT not confounded by other causes of graft dysfunction All pts with graft dysfunction SORT tested Phenotypes included >-BK nephritis, >-Calcineurin Induced Toxicity, >-Chronic allograft nephropathy, >-Recurrent GN >-Borderline AR >-SORT scores for other phenotypes well <50 SORT scores Unaffected by Noise from other causes of graft injury SORT picks up most Borderline (Early) AR Li et al, AJT, 2012 Sarwal et al, AJT, 2012 Naesens et al, AJT, 2012
  • 13. 13 k-SORT: 17 Gene Panel Assessment of Acute Rejection in renal Transplants patients n=558 AART Study Results 188 AR and 370 No AR 533/558 Biopsy Matched Samples 1. Accurate diagnosis of non-AR and AR in all ages of transplant patients Accuracy 92%, Sensitivity 86% and Specificity 94% 2. k-SORT not confounded by other causes of graft dysfunction Including BK nephritis, CNIT, CAN and recurrent GNs 3. k-SORT predicts AR 1-4 months prior to current diagnostic tools 4. k-SORT detects both types of rejection; cellular and antibody mediated 5. k-SORT is not confounded by time post-transplantation 6. k-SORT maybe used to monitor resolution of AR 7. Genes are directly or indirectly related through biologically common pathways
  • 14. 14 Anatomy of the AART Study
  • 15. 15 k-SORT : 143 AART patients; 4 Centers Predicted AR Probabilities by pls-DA 143; 47 AR vs. 96 No-AR
  • 16. 16 k-SORT Validation #1 : 124 AART; 5 centers Independent adult and pediatric patients (23 AR, 101 No-AR)
  • 17. 17 Prediction Capability of k-SORT; Validation #2 AART 191; UPMC, CPMC,UCLA, Stanford Total 191 samples w biopsy confirmed AR n= 65 before Bx n-=74 at biopsy n= 52 after biopsy 65% pts had high AR scores 0-3 months prior to Bx w apparently stable graft fx AR scores of 96% vs 19% in no AR pts Post Rx, 52% (16/31) had persistent elevated SORT scores (86%) Could this info be crucial in identifying a subset of non responders??
  • 18. 18 kSAS Validation #3: 100 AART; 4 centers 44 AR and 56 No-AR; on ABI Statistical analysis of the ABI data demonstrate a highly accurate test: • 17 target genes (18 S Housekeeping) • 36/39 correctly classified AR • Sensitivity: 92%(81) • 43/46 correctly classified No AR • Specificity: 93.5% • n=100, four different centers (Barcelona, Mexico, UCSF, Pitt) - 83 shown • 10-15% classified as Indeterminate
  • 19. 19 k-SORT detects both types of rejection Roedder et al., in submission k-SORT detects both types of AR Antibody Mediated Rejection v/s Acute Cellular Rejection • Similar prediction scores • Clustered at scores >80%k-S
  • 20. 20 k-SORT: >90%NPV; identification of low AR risk Roedder et al., in submission
  • 21. 21 k-SORT is not confounded by time post-transplantation k-SORT accurately predicts AR in patients several years post transplantation. This fact is valuable to detect late onset AR due to non compliance with meds.
  • 22. 22 k-SORT: Prospective Clinical Utility Study Pharma collaborators plan to use k-SORT in clinical trials SAILOR: A Prospective, Randomized Clinical Utility Study A controlled randomized, open-label, multi-centre study evaluating if a steroid-free immunosuppressive protocol, based on ATG- induction, low dose CNI & MMF, reduces the incidence of new onset diabetes after transplantation, in comparison with a standard steroid-based protocol with low-dose CNI • 4 EU Centers, 222 patient study. • Pt enrollment started in Feb 2013 • 24 month trial with option to do 5 year f/u • k-SORT blinded analysis ongoing in 2 Organ-i partnered CLIA Labs
  • 23. 23 Pharma Collaborations Pharma collaboration will be the largest independent validation of a kidney transplant genomic test in a prospectively collected cohort. These studies will greatly facilitate discussions with third party payers/reimbursement entities, as well as regulators. Importance of Pharma Collaborations with Organ-i • Cover US and EU: 1st Pharma trial in EU & 2nd Pharma Trial in US • Collaborations are being led by KOLs • Leverages a largely funded prospective clinical trial to further validate SORT • Tolerance test (SPOT) will also be validated at no incremental cost • Organ-i’s CLIA ab partners will conduct the testing without charge to Organ-i
  • 24. 24 Future Claims The following will be studied with the data collected from the trials: 1. Demonstrate prognostic/predictive capability through timed collections of Creatinine, k-SORT and protocol biopsies 2. Ability to reclassify patients with sub-acute rejection who are currently diagnosed through protocol biopsies and completely missed by Creatinine could be identified by k-SORT and managed through timely therapeutic intervention 3. Potential to validate a companion diagnostic for low dose Tacrolimus 4. Cell-mediated and antibody mediated rejection: Next generation of the test could fine tune the algorithm to discriminate between the two types of rejection, which is important as it would dictate the specific type of therapeutic intervention 5. SPOT test for tolerance/immunoquiescence claims confirmed, completing the personalization of transplant patient management