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 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

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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.

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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

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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.

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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

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k-SORT Product Development
Stringent sample selection; all blood samples biopsy matched

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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.

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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

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Randomized multi-center SNSO1 NIH trial results
SORT is Sensitive, Specific, Accurate & Non-invasive

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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

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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

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Anatomy of the AART Study

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k-SORT : 143 AART patients; 4 Centers
Predicted AR Probabilities by pls-DA 143; 47 AR vs. 96 No-AR

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k-SORT Validation #1 : 124 AART; 5 centers
Independent adult and pediatric patients (23 AR, 101 No-AR)

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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??

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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

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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

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k-SORT: >90%NPV; identification of low AR risk
Roedder et al., in submission

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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.

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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

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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

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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