IMMUNOSCORE®

Scoring Immune Response in Colon Cancerfor unmatched clinical perfomance in routine settings

#immunoscore#immunoscore

� Patient survival fate is dependenton preexisting immunity �on preexisting immunity existing immuni �

Dr Jérôme Galon, Head of the Integrative Cancer Immunologyat the Cordeliers Research Center in Paris, France

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Pagès F, Mlecnik B, Marliot F et al. International validation of the consensus

cancer: a prognostic and accuracy study. Lancet. 2018; 391 (10135)

Sinicrope F, Shi Q, Hermitte F et al.Immunoscore to provide prognostic information in low- (T1-3N1) and high-risk (T4 or N2) subsets of stage III colon carcinoma patients treated with adjuvant FOLFOX in a phase III trial (NCCTG N0147; Alliance). J Clin Oncol. 2018; 36:4s (suppl; abstr 614)

Sinicrope F, Shi Q, Hermitte F et al. Association of immune markers and Immunoscore with survival of stage III colon carcinoma (CC) patients (pts) treated with adjuvant FOLFOX: NCCTG N047 (Alliance). J Clin Oncol. 2017; 35:15s (suppl; abstr 3579)

Mlecnik B, Bindea G, Angell HK et al. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability.Immunity.2016;15;44(3)

Kirilovsky A, Marliot F, El Sissy C et al. Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients. Int Immunol. 2016;28(8)

Mlecnik B, Tosolini M, Kirilovsky A et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011;29(6)

Pagès F, Kirilovsky A, Mlecnik B et al. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol. 2009;27(35)

Galon J, Costes A, Sanchez-Cabo F et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795)

REFERENCE PUBLICATIONS

Email: infos@haliodx.com

HalioDx - Luminy Biotech Entreprises163 Avenue de Luminy - 13288 Marseille Cedex 9 - FRANCE

Phone +33 (0) 4 91 29 30 90 - Fax +33 (0) 4 91 29 30 99

HalioDx Inc, Biotech Eight 737 N 5th St, 6th Floor,Richmond, VA 23219 - USA

www.immunoscore-colon.com

www.haliodx.com

Immunoscore®, IS2C402onc des patients atteintntss de cancer localisé du colonncer loca iDispositif médical de Diagnostic in Vitro pour aider au pronostic d

HalioDx SAS (France)chantillon disponible en liigngneent lldédié à la ppréparation de l’échaLire attentivement les instructions fournies dans le document déd

(www.immunoscore-colon.com)

Patient Tissue sample

Stain & Scan Slides

ComputeImmunoscore®

Report Immunoscore® results

HalioDx labPathology lab

� Immunoscore® results are reported within 10 working days after receipt of the specimen, giving a score which is the patient's own Immunoscore® �

*CE-IVD for European Community countries, performed in CLIA

WHY IMMUNOSCORE®*Immunoscore®* is an in vitro diagnostic test predicting the risk of relapse in localized colon cancer patients, by measuring the host immune response at the tumor site.

Immunoscore® is available as a full service solution (performed in HalioDx laboratories).

IMMUNOSCORE® WORKFLOW

IMMUNOSCORE® SITC VALIDATION STUDYPagès F et al. The Lancet 2018

CLINICAL UTILITY IN LOCALIZED COLON CANCER

IMMUNOSCORE® FOR STAGE II CC PATIENTS

In the large Immunoscore® SITC study (more than 2,500 Stage I-III patients), Immunoscore® was strongly predictive of the patient outcome and .

Among Stage II patients (n = 1,434), Immunoscore® (Immunoscore® Low) higher risk of recurrence at 5 years (23% vs 8% in patients with Immunoscore® High).

IMMUNOSCORE® FOR STAGE III CC

PATIENTS

In a retro-prospective study from the prospective NCCTG N0147 clinical trial, Immunoscore® has been tested on 600 resected tumors of Stage III CC patients from the FOLFOX arm.

- Overall, patients with High Immunoscore® have a

(HR=0.59, 95% CI, p=0.0013).

- Among the low-risk group (T1-3 N1), 1 out of 2

patients have high risk of relapse (Immunoscore Low,

n=153/287)

years DFS (DFS at 3 years=78% vs 92%).

These data demonstrate the ability of Immunoscore®

HR=0.68p<0.05

HR=0.6 p<0.01

(%)

Survival (Years)

0

400

60

80

100001

10 4 5 6 7 882

Immunoscore High/MSI events = 37/162

Immunoscore High/MSS events = 126/474

Immunoscore Low/MSI events = 11/27

Immunoscore Low/MSS events = 75/178

DFS in Stage II patients (n=841)

- Discrepancy between MSI/MSS status and Immunos-

1 out of 5 patients

regarding the DFS (n=156/841).

- Patients’ survival is driven by Immunoscore®

regardless of their microsatellite status.

Immunoscore® in addition of MSI/MSS status should

improve the management of Stage II CC patients.

- Untreated high-risk patients with Immunoscore® High

have good clinical outcome similar to low-risk patients

(5Y TTR of 87.4 vs 89.1).

- 7 out of 10 patients (n=438/630) with high-risk

features might be spared from chemotherapy.

clinico-pathological risk features.

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(%)

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ars)s)TimTimTi e tte to ro ro ecucucuuuecurrerrrrrence (Year

00

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60

800

100

111110000 4 55 66 77 8882

TTR in Stage II untreated patients according to

Low-Risk

High-Risk IS 0-1

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Time froom randomization (years)

0

0

200

404

60

8080

100101 0

51 2 4444

High risk patients

(DFS at 3 yr: 78% vs. 92%)

HRLOW-HIGH

p=0.0208

Immunoscore High events = 23/134

Immunoscore Low events = 43/153

Mucinous (colloid)

MSI

Sex

Clinical parameters plus Immunoscore

Immunoscore(high, intermediate, low)

VELIPI

Differentiation

AJCC/UICCTNM stage

LARGEST CONTRIBUTION OF IMMUNOSCORE®

HRHIGH-LOW

(95% CI 0.23 - 0.40)p<0.0001

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Years from surgery e, TTR)(Time To Recurrence, TT

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10 4 5 6 7 82

Immunoscore Low

Immunoscore Intermediate

Immunoscore High

TTR in Stage I-III patients (n=2681)

IMMUNE INFILTRATIONLOCALIZED COLON CANCER PATIENTS RISK OF RELAPSE

High in ltration of T lymphocytes

Low inltration of T lym

phocytes (in red)

LOW Immunoscore®

HIGH Immunoscore®

HIGHRISK

LOWRISK