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.
- 1. Organ-I Company Overview
2. 2 Overview Organ-i is a transplant franchise developing and
commercializing next generation genomic and proteomicbased
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 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-is 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
