MOSAIC · 2020-03-05 · 2016 Choueiri TK, Fishman MN, Escudier B, McDermott DF, Drake CG, Kluger H, et al. Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma

© Mosaic Laboratories

MOSAICLABORATORIES

Overview of Mosaic Laboratories


General Company Overview

• Privately Owned; Founded in 2005

• Laboratory Testing Services to >160 Pharma and Biotech Clients

• Testing Focused on Anatomic Pathology Services

– Clinical Trials

– Medical Device

– Preclinical Studies

– Assay Validation

• Domestic and International Clients

• California License, New York Permit, CLIA Accreditation and CAP Accreditation

• Seven (7) Pathologists, including 2 Hematopathologists

• Sixty-Five (65) Employees

• New Larger Facility (moved December, 2019)


Services

• Histology and Histologic Stains

• Single Stain and Multiplex Immunohistochemistry• We develop 5+ new stains per month

• Standard and Digital Pathology

• FISH

• RNAScope

• Tissue Resources and Chemosensitivity Testing

• Collection Kits, Instruction Manuals, Requisition Forms

• Logistics and Sample Storage

• Prospective Clinical Trials with Rapid TAT• Single Stain IHC

• Multiplex IHC

• FISH

• RT-PCR


2019 Ott PA, Pavlick AC, Johnson DB, Hart LL, Infante JR, Luke JJ, Lutzky J, Rothschild NE, Spitler LE, Cowey CL, Alizadeh AR, Salama AK, He Y, Hawthorne TR, Bagley RG, Zhang J, Turner CD, Hamid O. A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma. Cancer. 2019. CellDex

2019 Ihling C, Naughton B, Zhang Y, Rolfe PA, Frick-Krieger E, Terracciano LM, Dussault I. Observational Study of PD-L1, TGF-beta, and Immune Cell Infiltrates in Hepatocellular Carcinoma. Front Med (Lausanne). 2019;8(6):15. 2019. Merck KGaA

2019 Mak G, Soria JC, Blagden SP, Plummer R, Fleming RA, Nebot N, Zhang J, Mazumdar J, Rogan D, Gazzah A, Rizzuto I, Greystoke A, Yan L, Tolson J, Auger KR, Arkenau HT. A phase Ib dose-finding, pharmacokinetic study of the focal adhesion kinase inhibitor GSK2256098 and trametinib in patients with advanced solid tumours. Br J Cancer. 120(10): 975-981. 2019. GSK

2019 Faiena I1, Astrow SH2, Elashoff DA3, Jain R2, Bot A2, Chamie K4, Belldegrun AS4, Pantuck AJ4, Drakaki A. Melanoma-associated antigen-A and programmed death-ligand 1 expression are associated with advanced urothelial carcinoma. Cancer Immunol Immunother. 68(5):743-751. 2019. Kite

2018 George DJ, Martini JF, Staehler M, Motzer RJ, Magheli A, Escudier B, Gerletti P, Li S, Casey M, Laguerre B, Pandha HS, Pantuck AJ, Patel A, Lechuga M, Ravaud A. Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study. Clin Cancer Res. 2018 Apr 1;24(7):1554-1561. Pfizer

2018 Krähenbühl L, Goldinger SM, Mangana J1, Kerl K, Chevolet I, Brochez L1, Horak C, Levesque M, Dummer R, Cheng PF. A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted Therapy in Advanced Melanoma. Neoplasia. 2018 Feb;20(2):218-225. BMS

2018 Aghajanian C, Bell-McGuinn KM, Burris HA, Siu LL, Stayner LA, Wheler JJ, Hong DS, Kurkjian C, Pant S, Santiago-Walker A, Gauvin JL, Antal JM, Opalinska JB1, Morris SR, Infante JR. A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors. Invest New Drugs. 2018 Dec;36(6):1016-1025. GlaxoSmithKline

2018 Carducci M, Shaheen M, Markman B, Hurvitz S, Mahadevan D, Kotasek D, Goodman OB Jr, Rasmussen E, Chow V, Juan G, Friberg GR, Gamelin E, Vogl FD, Desai J. A phase 1, first-in-human study of AMG 900, an orally administered pan-Aurora kinase inhibitor, in adult patients with advanced solid tumors. Invest New Drugs. 2018 Dec;36(6):1060-1071. Amgen

2018 Maitland ML, Piha-Paul S, Falchook G, Kurzrock R, Nguyen L, Janisch L, Karovic S, McKee M, Hoening E, Wong S, Munasinghe W, Palma J, Donawho C, Lian GK, Ansell P, Ratain MJ, Hong D. Clinical pharmacodynamic/exposure characterisation of the multikinase inhibitor ilorasertib (ABT-348) in a phase 1 dose-escalation trial. Br J Cancer. 2018 Apr;118(8):1042-1050. AbbVie

2018 Hodi FS, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Cowey CL, Lao CD, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Hill A, Hogg D, Marquez-Rodas I, Jiang J, Rizzo J, Larkin J, Wolchok JD. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Nov;19(11):1480-1492. BMS

2018 Wang L, Saci A, Szabo PM, Chasalow SD, Castillo-Martin M, Domingo-Domenech J, Siefker-Radtke A, Sharma P, Sfakianos JP, Gong Y, Dominguez-Andres A, Oh WK, Mulholland D, Azrilevich A, Hu L, Cordon-Cardo C, Salmon H, Bhardwaj N, Zhu J, Galsky MD. EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer. Nat Commun. 2018 Aug 29;9(1):3503. BMS

2018 Krahenbuhl L, Goldinger SM, Mangana J, Kerl K, Chevolet I, Brochez L, et al. A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted Therapy in Advanced Melanoma. Neoplasia. 2018 20(2):218-225. BMS

2018 George DJ, Martini JF, Staehler M, Motzer RJ, Magheli A, Escudier B, et al. Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study. Clin Cancer Res. 2018. Pfizer

References


2018 Hellmann MD, Nathanson T, Rizvi H, Creelan BC, Sanchez-Vega F, Ahuja A, Ni A, Novik JB, Mangarin LMB, Abu-Akeel M, Liu C, Sauter JL, Rekhtman N, Chang E, Callahan MK, Chaft JE, Voss MH, Tenet M, Li XM, Covello K, Renninger A, Vitazka P, Geese WJ, Borghaei H, Rudin CM, Antonia SJ, Swanton C, Hammerbacher J, Merghoub T, McGranahan N, Snyder A, Wolchok JD. Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer. Cancer Cell. 2018 May 14;33(5):843-852.e4. BMS

2017 Huck BR, Goodstal SM, Gimmi-Mckim C. Methods for Treating Cancer Using Pyrimidine and Pyridine Compounds with BTK Inhibitory Activity. US Patent Application. 2017 Merck KGaA

2017 Majzner RG, Simon JS, Grosso JF, Martinez D, Pawel BR, Santi M, et al. Assessment of programmed death-ligand 1 expression and tumor-associated immune cells in pediatric cancer tissues. Cancer. 2017 123(19):3807-3815. BMS

2017 Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, et al. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Annals of Onc. 2017 0:1-10 Bayer

2017 El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. The Lancet. 2017 389(10088):2492-2502. BMS

2017 Kim DJ, George C, Lee YB, Ahn CH, Frank J, Mazhari R, Dauffenbach LM, Olsen EP. Evaluation of UCK2 Protein Expression as a Potential Predictive Biomarker of RX-3117. AACR Meeting. Rexahn

2017 Yu H, Batenchuk C, Badzio A, Boyle TA, Czapiewski P, Chan DC, et al. PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2017;12(1):110-120. BMS

2017 Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017 Mar;18(3):312-322. (referenced in methods) BMS

2017 Yu H, Batenchuk C, Badzio A, Boyle TA, Czapiewski P, Chan DC, Lu X, et al. PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer. Thorac Oncol. 2017 Jan;12(1):110-120. (referenced in methods) BMS

2016 Mukai H, Saeki T, Aogi K, Naito Y, Matsubara N, Shigekawa T, et al. Patritumab plus trastuzumab and paclitaxel in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. Cancer Sci. 2016 Oct;107(10):1465-1470. (referenced in methods) Daiichi Sankyo

2016 Juan G, Paweletz K, Anderson A, Gamelin E, Friberg G, Loberg R, et al. Abstract 439: Detection of aurora kinase A (AURKA) focal amplification in plasma samples of patients with recurrent ovarian cancer. AACR Meeting (referenced in methods) Amgen.

2016 O’Farrell M, Heuer T, Grimmer K, Crowley R, Waszczuk J, Fridlib M, Ventura R, Rubio C, Lai J, Panda A, Buckley D, McCulloch W, Kemble G. FASN inhibitor TVB-2640 shows pharmacodynamic effect and evidence of clinical activity in KRAS mutant NSCLC patients in a Phase 1 study. AACR Meeting. 3-V Biosciences

2016 Hussein M, Wilks S, Monte M, Richards DA, Goldschmidt JH, Waterhouse D, Wang L, Yusko E, Emerson R, Taverna DM, Desai K, Mousses S, Qi Z, Hipp JD, Robins H, Kulig K, Batenchuk C. Characterization of the T-Cell Receptor Repertoire in Extensive-Disease Small Cell Lung Cancer. AACR Meeting. (referenced in acknowledgements) BMS

2016 Simonelli M, Zucali P, Santoro A, Thomas MB, de Braud FG, Borghaei H, et al. Phase I study of PF-03446962, a fully human monoclonal antibody against activin receptor-like kinase-1, in patients with hepatocellular carcinoma. Ann Oncol. 2016 Sep;27(9):1782-7. (referenced in methods) Pfizer

2016 Yu H, Batenchuk C, Badzio A, Boyle TA, Czapiewski P, et al. PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer. J Thorac Oncol. 2017 Jan;12(1):110-120. (referenced in methods) BMS

2016 Choueiri TK, Fishman MN, Escudier B, McDermott DF, Drake CG, Kluger H, et al. Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. Clin Cancer Res. November 15 2016 (22) (22) 5461-5471. (referenced in methods) BMS

References


2016 Weber JS, Gibney G, Sullivan RJ, Sosman JA, Slingluff CL Jr, Lawrence DP, et al. Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial. Lancet Oncol. 2016 Jul;17(7):943-55. (referenced in methods) BMS

2016 Lockhart AC, Liu Y, Dehdashti F, Laforest R, Picus J, Frye J, et al. Phase 1 Evaluation of [(64)Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors. Mol Imaging Biol. 2016 Jun;18(3):446-53. (referenced in methods) Daiichi Sankyo

2016 O’Farrell M, Heuer T, Grimmer K, Crowley R, Waszczuk J, Fridlib M, et al. FASN inhibitor TVB-2640 shows pharmacodynamic effect and evidence of clinical activity in KRAS mutant NSCLC patients in a Phase 1 study. AACR Meeting (referenced in methods). 3-V Bioscience

2016 Halim A, Bagley RG, Dauffenbach LM, Olsen EP, Keler T. IHC and RT-PCR Assays for Detection of Cancer Antigen NY-ESO-1 in Human Tissues. AACR Meeting. Celldex

2016 Halim A, Bagley RG, Keler T. Glycoprotein NMB (gpNMB) Overexpression is Prevalent in Human Cancers: Pancreatic Cancer, Non-Small Cell Lung Cancer, Head and Neck Cancer, and Osteosarcoma. AACR Meeting (referenced in methods). Celldex

2015 Mendell J, Freeman DJ, Feng W, Hettmann T, Schneider M, Blum S, et al. Clinical Translation and Validation of a Predictive Biomarker for Patritumab, an Anti-human Epidermal Growth Factor Receptor 3 (HER3) Monoclonal Antibody, in Patients With Advanced Non-small Cell Lung Cancer. EBioMedicine. 2015 Feb 12;2(3):264-71. Daiichi Sankyo

2015 Middleton MR, Friedlander P, Hamid O, Daud A, Plummer R, Falotico N, et al. Randomized phase II study evaluating veliparib (ABT-888) with temozolomide in patients with metastatic melanoma. Ann Oncol. 2015 Oct;26(10):2173-9. AbbVie

2015 Ciprotti M, Tebbutt NC, Lee FT, Lee ST, Gan HK, McKee DC, et al. Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2015 Aug 20;33(24):2609-16. Daiichi Sankyo

2015 Lockhart AC, Liu Y, Dehdashti F, Laforest R, Picus J, Frye J, et al. Phase 1 Evaluation of [64Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors. Mol Imaging Biol. 2015 Nov 13. Daiichi Sankyo

2015 Wong AL, Lim JS, Sinha A, Gopinathan A, Lim R, Tan CS, et al. Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib. J Transl Med. 2015 Feb 12;13:57. Bayer

2015 Gungor H, Saleem A, Babar S, Dina R, El-Bahrawy MA, Curry E, et al. Dose-Finding Quantitative 18F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies. J Nucl Med. 2015 Dec;56(12):1828-35. GlaxoSmithKline

2014 Wakui H, Yamamoto N, Nakamichi S, Tamura Y, Nokihara H, Yamada Y, et al. Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):511-6. Daiichi Sankyo

2014 Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau HT, Brown MP, et al. Dose selection, pharmacokinetics, and pharmacodynamics of BRAF inhibitor dabrafenib (GSK2118436). ClinCancer Res. 2014 Sep 1;20(17):4449-58. GlaxoSmithKline

2014 Friedberg JW, Mahadevan D, Cebula E, Persky D, Lossos I, Agarwal AB, et al. Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B-and T-cell non-Hodgkin lymphomas. J Clin Oncol. 2014 Jan 1;32(1):44-50. Millennium

2014 Ott PA, Hamid O, Pavlick AC, Kluger H, Kim KB, Boasberg PD, et al. Phase I/II study of the antibody-drug conjugate glembatumumab vedotin in patients with advanced melanoma. J Clin Oncol. 2014 Nov 10;32(32):3659-66. Celldex

2014 Sun A, Lam RL, Harman A, Pavlick AC, Herman GA, Dauffenbach LM, Kerfoot CA, et al. Induction of CDC2 Phosphorylation in Skin Biopsies from Patients with Solid Tumors Undergoing DNA-Damaging Chemotherapy. Global Journal of Medical Research. 2014 14(1): 11-21. Merck

References

Confidential Material© Mosaic Laboratories

2014 D'Angelo SP, Shoushtari AN, Agaram NP, Kuk D, Qin LX, Carvajal RD, et al. Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment. Hum Pathol. 2015 Mar;46(3):357-65. Memorial Sloan Kettering

2013 Aracil M, Dauffenbach LM, Diez MM, Richeh R, Moneo V, Leal JF, et al. Expression of XPG protein in human normal and tumor tissues. Int J Clin Exp Pathol. 2013 6(2):199-211. PharmaMar

2013 King AJ, Arnone MR, Bleam MR, Moss KG, Yang J, Fedorowicz KE, et al. Dabrafenib; Preclinical Characterization, Increased Efficacy when Combined with Trametinib, while BRAF/MEK Tool Combination Reduced Skin Lesions. PLoS ONE. 2013 8(7): e67583. GlaxoSmithKline

2013 Chao DT, Su M, Tanlimco S, Sho M, Choi D, Fox M, et al. Expression of TweakR in breast cancer and preclinical activity of enavatuzumab, a humanized anti-TweakR mAb. J Cancer Res Clin Oncol. 2013 Feb;139(2):315-25.2012 Abbott

2012 Sun A, Zhou W, Lunceford J, Strack P, Dauffenbach LM, Kerfoot CA. Level of phosphohistone H3 among various types of human cancers. BMJ Open. 2012 Oct 12;2(5). Merck

2012 Erickson-Miller CL, Pillarisetti K, Kirchner J, Figueroa DJ, Ottesen L, Martin AM, et al. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors. BMC Cancer. 2012;12:405. GlaxoSmithKline

2012 Jeffers M, Dauffenbach LM, Peña C, Lathia C, Bhargava A, Kerfoot CA. Comparison of Commercially Available Phosphorylated ERK Antibodies for Immunohistochemical BiomarkerAnalysis. AACR meeting. Bayer

2012 Arentsen HC, Hulsbergen-Van de Kaa CA, Jansen CFJ, Maj R, Leoni LM, et al. Pharmacokinetics and toxicity of intravesical TMX-101: a preclinical study in pigs. BJU International. 2011 Oct;108 (7): 1210–14. Telormedix

2012 O’Farrell M, Ventura R, Tai A, Matthews DJ. The PI3K/mTOR Inhibitor PWT33597 Regresses 786-0 Renal Xenografts. AACR meeting. Pathway Therapeutics

2011 Halim A, Dauffenbach LM, Kerfoot CA, Stull WR, Zwick-Wallasch E, Scheyer R, Senaldi G. Immunohistochemical Analysis of HB-EGF Expression in Breast, Colon, Gastric, Hepatocellular, Lung, Ovarian, Pancreatic and Prostate Cancer. American Association of Cancer Research Meeting. Daiichi Sankyo

2010 Rabbani SA, Ateeq B, Arakelian A, Valentino ML, Shaw DE, Dauffenbach LM, Kerfoot CA, Mazar AP. An Anti–Urokinase Plasminogen Activator Receptor Antibody (ATN-658) Blocks Prostate Cancer Invasion, Migration, Growth, and Experimental Skeletal Metastasis In Vitro and In Vivo. Neoplasia. 2010 12:778-288. Attenuon

2010 Jeffers M, Dauffenbach LM, Bhargava A, Lathia C, Kerfoot CA. Comparison of Commercially Available Phospho-AKT [Ser473] Antibodies for Immunohistochemical Biomarker Analysis. AACR meeting. Bayer

2010 Sun A, Lam RL, Pavlick AC, Harman A, Iannone R, Herman G, Dauffenbach LM, Kerfoot CA, Huang P, Bergstrom DA. A phase 1B study to evaluate induction of pCDC2 in skin biopsies from patients with solid tumors treated with DNA-damaging chemotherapy. AACR meeting. Merck

2010 Kim K, Kong SY, Fulciniti M, Li X, Song W, Nahar S, et al. Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo. Curr Pharm Des. Br J Haematol. 2010 May;149(4):537-49. EMD Serono

2010 Guise CP, Abbattista MR, Singleton RS, Holford SD, Connolly J, Dachs GU, et al. The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Res. 2010 Feb 15;70(4):1573-84. Proacta

2009 Reeves J, McNulty W, Thomas G, MacVicar G, Maleski J, Leopold L. Preliminary Report of an Open-Label, Multicenter, Phase I/II Study of AT-101 in Combination with Docetaxel and Prednisone in Men with Docetaxel Refractory Prostate Cancer. ASCO Genitourinary Cancers Symposium. Ascenta

References


2014 Wang T, Duffy JP, Wang J, Halas S, Salituro FG, Pierce AC, Zuccola HJ, Black JR, Hogan JK, Jepson S, Shlyakter D, Mahajan S, Gu Y, Hoock T, Wood M, Furey BF, Frantz JD, Dauffenbach LM, Germann UA, Fan B, Namchuk M, Bennani YL, Ledeboer MW. Janus kinase 2 inhibitors. Synthesis and characterization of a novel polycyclic azaindole. J Med Chem. 2009 Dec 24;52(24):7938-41. Vertex

2009 Drygin D, Bliesath J, Ho C, Siddiqui-Jain A, Streiner N, Chua P, et al. CX-4945, a small molecule inhibitor of CK2, inhibits angiogenesis by affecting the vascular endothelium and suppressing hypoxia-activated Hif-1α transcription. AACR Meeting. Cylene

2009 Kanekal S, Lei S, Redkar S. MP-470, a Rad51 Suppressor and Multiple TK Inhibitor, Retards Growth of Primary Human Glioblastoma Multiforma (GBM) Cells and Synergizes Eect of Temozolomide. AACR Meeting. SuperGen

ReferencesSelect References. Full list can be found at: http://www.mosaiclabs.com/news_publications and

http://www.mosaiclabs.com/news_posters.


EquipmentDiverse Autostainer Platform Availability

Leica Bond RX

Dako Link 48

Biocare IntelliPATH

Ventana BenchMark Ultra


Aperio AT Turbo

EquipmentImaging

Aperio ScanScope CS

Nuance Multispectral Imaging Camera


MOSAICLABORATORIES

Histology and Histologic Stains


Histology Services

– Three (3) histotechnologists

– Processing and Embedding of Fixed Tissues

– Processing, Fixation, and Embedding of Cellular Material• Cell lines

• Bone Marrow

• Blood

• Fluids

– FFPE Tissue Sectioning• Regular sectioning

• Genomic sectioning (aseptic technique, for downstream RNA/DNA testing)

• Tissues, fine needle aspirates, core needle biopsies, skin tissues, cellular material, cell lines

– Frozen Tissue OCT-Embedding

– Frozen Tissue Sectioning

– Histologic Stains• H&E

• Wright Giemsa

• Picro Sirius Red

• Trichrome

• Herovici


MOSAICLABORATORIES

Single Stain IHC Assays



15PGDH

20S Proteasome Subunit Alpha 5

4E-BP1

5T4

8-OHdG

Actin gamma 2

AdipoR1

AdipoR2

AE1/AE3

AKR1C3

AKT

AKT

AKT-1

AKT1 (S129)

ALK-1

Amphiregulin (AREG)

Androgen Receptor

Angiopoietin 1

Angiopoietin-2

ASGPR1

Aurora A

Aurora B

Aurora C

AXL

B2-Microglobulin

B7-H3

BAD

Bad (pSer136)

Bax

BCL-2

BCL-6

Bcl-xL

CD137L

CD138

CD141

CD178

CD15

CD16

CD163

CD16a

CD19

CD20

CD200

CD22

CD23

CD27

CD274 (PD-L1)

CD3

CD30

CD31

CD33

CD34

CD37

CD38

CD4

CD40

CD40L

CD45 LCA

CD45R0

CD54 (ICAM-1)

CD55

CD56

BCMA

Beclin-1 (BECN1)

Beta Heregulin

Beta-catenin

betacellulin

Bim

Blimp-1

BMI-1

BRAF V600E

BRG1

CAIX

CA9

Caldesmon

Calnexin

Calponin

Calponin-B

Calreticulin

CAM5.2

CCR2

CCR5 (RNAScope)

CCR6

CCR8

CD10

CD110

CD11b

CD11c

CD117

CD133

CD134 (OX40)

CD137

CD57

CD68

CD70

CD72

CD73

CD73 Enzyme

CD8

CD80

CD83

CD86

CD96

CDC2

CEA

CEACAM5

CEACAM6

CH24H (CYP46)

CHK1

Chromogranin A

cIAP pan

cIAP-1

cIAP-2

cKIT (CD117)

Cleaved Caspase 3

CLDN2

CLEC9A

c-MET

c-Myc

Cox2

CSF-1R/CD115

CTLA-4

CXCR3

CXCR4

Cyclin D1

Cyclin E1

Cytokeratin 18

Cytokeratin 7

Cytokeratin 8

DDR1

DDR2

DHODH

DNAM

DNMT1

DR5

E-Cadherin

Eg5

EGFR

elF4E

elF4E

Endocan

ENT1

Epcam Clone Ber-EP4

Epiregulin

ER

ERCC1

ERCC5

ERK

ERK1

ERK2

Ezrin

Fascin

– Mosaic has single stain IHC assays to over 370 targets



Factor VII

FAK

FAK2

FASN (Fatty Acid Synthase)

FGFR1

FGFR-4

FGL1

Folate Receptor 1

FOX03a

FoxM1

FOXO T24/32

FoxP3

FSP-1

Fucosyl-GM1

GALNT14

GD2

GFAP

GITR

Gli-1

Gli-2 GM-CSFRA (CSF2RA/CD116)

Glypican-3

GPNMB

Granzyme B

GSK3b

GSK-3b

GUCY2C

HB-EGF

hENT1

Hep Par1

HER-2

HER-3

HER-4

LDLR

Light Chain 3 (LC3B)

LYVE-1

MAC-2

MAGE-A

MCL-1

MDM2

MDR-1

MEK 1/2 (Total MEK)

Mesothelin

MLH1

MMA

MMP-19

MPM-2

MSH2

MSH6

MTAP

MUC1

MUC13

MUC16

MUM1

Murine CD11b

Murine CD11c

Murine CD25

Murine CD31

Murine CD4

Murine CD54 (ICAM1)

Murine CD8a

Murine F4/80

Murine FoxP3

Herceptest

Heregulin

HGF

HIF-1 alpha

HIF-2 alpha

HLA-A2

HLA Class 1 ABC (MHCI)

HLA-DP, DQ, DR Antigen (MHCII)

HPV

HPV16 E2

HPV16 (RNAScope)

HSP47

HSP70

HuC/D

ICOS

ICOSL

IDO

IGF1R alpha

IGF1R beta

IGFBP-2

IL8

IL12 p35

InsR

Integrin beta 1

Integrin beta 3

Integrin beta 6

Kappa Light Chains

Keratin 19

Ki-67 Lag3

LAGE1

Lambda Light Chains

Murine PD-L1

Murine TCR alpha + beta

Myeloperoxidase (MPO)

NCR1/NKP46

Nectin-2 / PVRL2

Neuropilin-1

Neutrophil NF2

NK1.1

NLRP3

Nucleophosmin

NY-ESO-1

OX40L

p16

p21 Waf1/Cip1

p27

p44/42 MAPK

p53

p68

p70 S6 Kinase

PAR2

PAX5

P-Cadherin

PCNA

PCP-2

PD-1

PD-L1

PD-L2

Perforin

pHH3 (Ser 28)

pHH3 (Ser10)

Phosphorylated (T389) p70 S6 Kinase



Phosphorylated JUN

Phosphorylated KAP1 Ser824

Phosphorylated Keratin

Phosphorylated Kit

Phosphorylated MAPK

Phosphorylated MEK

Phosphorylated MET

Phosphorylated Met (triple tyrosine)

Phosphorylated Met (Tyr1003)

Phosphorylated Met (Tyr1234/1235)

Phosphorylated Met (Tyr1349)

Phosphorylated NDRG1 (Thr346)

Phosphorylated p21

Phosphorylated p27

Phosphorylated p53

Phosphorylated p68

Phosphorylated PRAS40

Phosphorylated Rb (Ser807/811)

Phosphorylated RET

Phosphorylated SRC

Phosphorylated STAT3 (pY705)

Phosphorylated STAT5 (pY694)

Phosphorylated-S6 Ribosomal Protein (Ser235/236)

Phosphorylated-S6 Ribosomal Protein (Ser240/244)

Phosphorylated VEGFR2 Tyr1175



Phosphorylated VEGFR2 Tyr1054/1059

Phosphorylated Vimentin S56

Phosphorylated Vimentin S82

Phosphorylated YB1

PI(3,5)P2

PI3K p110alpha

PI3K p110beta

PI3K p110delta

PI3K p110gamma

PIK3CD

PIM-1

PIM-2

PIM-3

PLK

PMS2

Podoplanin (PDPN)

PPARγ

PR

PRAS40

PSMA

PTEN

PVR

RAD51

Raf1

RET

ROR1

RXRα

S100

S6 Ribosomal Protein

Phosphorylated (T421/S424) p70 S6 Kinase

Phosphorylated p90RSK

Phosphorylated 4EBP1 (Thr37/46)

Phosphorylated ACC Ser79

Phosphorylated AKT Ser129

Phosphorylated AKT Ser473

Phosphorylated AKT Thr308

Phosphorylated Aurora A

Phosphorylated BAD

Phosphorylated CAD

Phosphorylated CDC2 (Tyr15)

Phosphorylated CHK1 (Ser345)

Phosphorylated DDR1

Phosphorylated EGFR (Tyr1068)



Phosphorylated eIF4B

Phosphorylated elF4E

Phosphorylated ERK

Phosphorylated FAK

Phosphorylated FLT3 (Tyr589/591)

Phosphorylated FLT3 (TYR591)

Phosphorylated FLT3 (Tyr955)

Phosphorylated FLT3 (Tyr969)

Phosphorylated GSK3b S9/21

Phosphorylated H2AX

Phosphorylated HER2

Phosphorylated HER3

Phosphorylated IGF1R

Phosphorylated JNK

SDMA

Shh

SMA (smooth muscle actin)

Src

STAT3

STING

Survivin

Synaptophysin

TACC3

TCF7

TCR

TDO2

TGF alpha

TGF beta

Tie-2

TIGIT

TIM 1

TIM 3

TIP47 (Perilipin 3)

TLR-4

TLR-7

TMHH3 (Lys27)

TUNEL

uPA (Urokinase)

VEGFA (A-20)

VEGFR2

Vimentin

VWF

WT1

XIAP

α5β1 Integrin

Single Stain IHC Images

PD-L1 CD8

PD-1 FoxP3



CD73 P16 (CINtec)

CD40 GITR



CD163 LAG3

MHCI MHCII



CXCR4 DNAM

TIM-3 CTLA-4


MOSAICLABORATORIES

Multiplex IHC Assays



Mosaic has developed over 100 multiplex IHC assays


AKR1C3 + CD34 + CD117

Aurora A + pAurora A

Aurora A + pAurora A + pHH3

Aurora A + pHH3

B7-H3 + CD23

B7-H3 + DR5 + CD138

B7-H3 + DR5 + CD34 / CD117

CCR2 + CD8

CCR8+FoxP3

CD117 + IGFBP-2

CD137 + PD-1

CD138 + CD38

CD138 + cMYC

CD138 + pHH3

CD138 + pERK 20G11

CD28 + CD8

CD3 + CD4

CD3 + CD8

CD3 + CD3 + Granzyme B

CD3 + FoxP3

CD3 + LAG3

CD3 + MHCI

CD3 + PD-1

CD3 + Ki67 + CD4

CD3 + CD4 + FoxP3

CD3 + H3K27me3

CD31 + OX40

CD31 + Cleaved Caspase-3 + Ki-67

CD31 + OX40

CD33 + CD34 + H3K27me3

CD34 + CD117 (cKIT) + AURKA (20q13)/20q11

CD34 + CD31

CD34 + Cleaved Caspase-3

CD34 + pFLT3

CD34 + pHH3

CD37 + CD20

CD37 + CD38

CD38 + CD138 + Total FOXO 3a

CD38 + CD138 + Cleaved Caspase-3

CD38 + CD138 + Ki-67

CD38 + CD138 + pAKT

CD38 + CD138 + pAKT T308

CD38 + CD138 + pFOXO

CD38 + CD138 + pGSK3β

CD38 + CD138 + pPRAS40

CD38 + CD138 + Total AKT

CD38 + CD138 + Total FOXO 3a

CD38 + CD138 + Total GSK3β

CD38 + CD138 + Total PRAS40

CD39 + CD8

CD39 + TCF + CD8

CD4 + Ki-67

CD4 + CD3 + FoxP3

CD4 + CD8 + FoxP3

CD4 + CD8 + ICOS

CD4 + CD8 + IDO

CD4 + FoxP3

CD4 + FoxP3 + Ki-67


Mosaic has developed over 100 multiplex IHC assays


Ki-67 + Cleaved caspase-3

Ki-67 + CD11c

Lag3 + FoxP3 + CD8

Lag3 + MHCII + CD68

MHCI + MHCII

NKp46+Granzyme B

p70S6K T389 + Total p70SK

p70S6K T421/S424 + Total p70S6K

pAKT + Total AKT

PD-1 + CD45RO + CD8

pERK 20G11 + pAKT (MOS140)

pERK 20G11 + Total ERK

pERK MAPKYT + Total ERK

pERK MAPKYT + pERK 20G11

pHH3 + Ki-67

pHH3 + Cleaved Caspase-3 + Ki-67

PLK + Ki-67

pPRAS40 + Total PRAS40

SMA + NG2

Total BAD + pBAD

Total p27 + pp27

CD45R0 + CD31

CD68 + CD163

CD68 + PD-L1

CD8 + Ki-67

CD8 + PD-L1 FoxP3

CD8 + FoxP3 + PD-1

CD8 + LAG3

CD8 + NKp46 + Granzyme B

CD8 + pSTAT3

CD8 + PD-1 + Ki-67

CD68 + PD-L1 +

CD8 + CD3

CDC2 + pCDC2

CIAP1 + XIAP + CD34 + CD117

cIAP2 + CD117 + CD34

CSF1R + Tie-2

E-Cadherin + FSP-1 + NG2

E-Cadherin + NG2

ERK1 + ERK2

FSP-1 + NG2

GFAP + CH24H

Granzyme B + CD16a + CD3

Granzyme B + CD16a + CD163

IGF1R + InsR

Ki-67 + CD8MOS727

• Ki-67: DAB• CD8: RED• Whole slide scanning• Annotation of tumor, stroma, and

interface• Cytonuclear algorithm from Indica• Percent Positive and Positive cells/mm2


CD68 + CD163MOS665

• CD68: DAB• CD163: RED• Whole slide scanning• Annotation of tumor, stroma, and

interface• Cytonuclear algorithm from Indica• Percent Positive and Positive cells/mm2


CD68 + PD-L1 + CD3MOS738

• CD68: RED• PD-L1: DAB• CD3: GREEN• Nuance Multispectral Imaging• Center of Tumor and Invasive Margin


FoxP3 + PD-1 + CD8MOS739

• FoxP3: RED• PD-1: DAB• CD8: GREEN• Nuance Multispectral Imaging• Center of Tumor and Invasive Margin


FoxP3 + LAG3 + CD8MOS741

• FoxP3: RED• LAG3: DAB• CD8: GREEN• Nuance Multispectral Imaging• Center of Tumor and Invasive Margin


LAG3 + MHCII + CD68MOS744

• LAG3: RED• MHCII: DAB• CD68: GREEN• Nuance Multispectral Imaging• Center of Tumor and Invasive Margin


MOSAICLABORATORIES

Standard and Digital Pathology



Standard Pathology Review

• PD-L1 – Clone 28-8, Dako, SK005 IVD

– Clone 22C3, Dako SK006 IVD

– Clone SP263, Roche 790-4905 IVD

– Clone SP142, Roche, 740-4859 IVD

– Clone 73-10, Abcam, ab228415

– Clone 28-8, Abcam, ab205921

– Clone E1L3N, Cell Signaling, 13684

– Clone SP142, Abcam (Spring Bio), M4424

• CPS Scoring– CPS (0-100)

– Tumor Proportion Score (TPS) (1-100)

– Tumor Fractional Intensities (0, 1+, 2+, 3+). H-Score will be calculated.

– Are tumor associated immune cells present in the specimen (Yes, No, Not Evaluable, Not Applicable)

– Immune cell percent positive (over all cells) (0-100)

– Mononuclear Inflammatory Density Score (MIDS) (category 0-4)

• Estimate the number of mononuclear inflammatory cells (MIC) which express PD-L1 (staining at any

intensity) and associated with tumor cells. These include small and large lymphocytes, monocytes, and

macrophages within the tumor nests and the adjacent supporting stroma.

– Mononuclear Inflammatory Median Intensity (MIMI) (category 0-3)

• Estimate the mean intensity of mononuclear inflammatory cells which express PD-L1.


Standard Pathology Review

• Customized Tumor Cell Scoring

• Tumor Subcellular Localization Review– Membrane

– Cytoplasmic

– Nuclear

• Customized Immune Cell Scoring

• Heme Tumor Scoring

• Collaboration and Preparation of Interpretation Guidelines


Image Analysis Review

• Aperio (Leica)

• Halo (Indica)

– Cytonuclear Algorithm

– Halo Multiplex Algorithm

– Halo Area Quant Algorithm

– Halo Multiplex Algorithm


RGB Annotated

FFPE NSCLC Tissues

CD8 (mouse clone C8/144B), Aperio Nuclear v9 AlgorithmNote: Can be used for some cytoplasmic/membrane lymphocyte markers due to “fill holes”

Whole Slide Scan Image AnalysisSingle-stain w/ Aperio Nuclear Algorithm


RGB Annotated

FFPE CRCTissues

PD-1 (mouse clone NAT105), Indica Cytonuclear AlgorithmBest for cytoplasmic staining in tumor or lymphocytes if nuclei are still visible.

Whole Slide Scan Image AnalysisSingle-stain w/ Indica Cytonuclear Algorithm


Whole Slide Scan Image AnalysisMultiplex Whole Slide Scan

CD163 (Red, “tumor promoting” M2 subset of macrophages)CD68 (DAB, pan-macrophage marker)

FFPE Pancreatic

Cancer

FFPE HNSCC

CD163 (Masked Green), CD68 (Masked Red), Dual+ (Masked Light Blue)Negative (Masked Dark Blue)


Whole Slide Scan Image AnalysisMultiplex Whole Slide Scan; Halo Multiplex

CD3 was visualized with Vulcan Red chromogen (Biocare Medical, Concord, CA), CD16a was visualized with Stay Yellow chromogen (Abcam), and Granzyme B was visualized with Vina Green chromogen (Biocare Medical).

FFPE Gastric Cancer


Immuno-oncology ResearchRegion Selection

Annotating the Margin Region


Region of Interest

Examples of Annotating Tumor


Region of Interest

Annotating Tumor Annotating Stroma

Annotating Tumor/Stroma Interface

Confidential Material


MOSAICLABORATORIES

Imaging


Whole Slide Scanning

Whole slide scanning allows quantification of immune cells across the entire tissue.


Whole Slide Scanning

Negative control

pERK

Necrotic/Hypoxic Regions

Mouse Lymphocytes

5X

20X

Whole slide scanning allows evaluation of variances across tissue, provides documentation of results and allows quick meta-analyses using free viewer software



MOSAICLABORATORIES

FISH


FISH

Assays Available:

ALK, 2p23

AURKA, 20q13

CDKN2A, 9p21

BCL2, 18q21

BCL6, 3q27

EGFR, 7p12

FGFR1, 8p11

FGFR2, 10q26

Her2, 17q21.1 & IQFISH

Her3, 12q13

c-Met, 7q31

MDM2, 12q15

PTEN, 10q23.3

PIK3CA, 3q26.32

ZNF217, 20q13.2 (Aurora A adj)

Development Upon Request



MOSAICLABORATORIES

RNAscope


RNAscope

Assays Available:

ADORA2A

CCR5

CCR8

CD228

HPV16

LIV-1

PRLR

TIGIT

GITR

Development Upon Request

PRLR (Target RNA)

PPIB (Positive Control)

DapB (Negative Control)



MOSAICLABORATORIES

Tissue Resources and Chemosensitivity Testing


Tissue Resources

Paraffin-Embedded Tissues

• >10,000 Paraffin Blocks

• Tissue Arrays

Viably-Frozen Cancer Cells

• Brain, Breast, Colorectal, Head and Neck, Gastric, Lung, Ovarian, Renal Cell, Melanoma and Hematologic Malignancies and Other Cancers

• ~0.5 to 1 Million Cancer Cells Frozen per Vial

• Each Has a Matching Paraffin Block

• Used for Chemosensitivity Testing, Animal Models, and Molecular Profiling


Unique Explant SamplesViably-frozen Cells / Matched FFPE

Type Total

Brain Cancer 34

Breast Cancer 624

Colorectal Cancer 256

Esophageal Cancer 86

Gastric Cancer 148

Head and Neck Cancer 152

Kidney Cancer 61

Liver Cancer 64

Lung, Non Small cell Cancer 316

Lung, Small Cell Lung Cancer 3

Lymphomas and leukemias - ALL 11

Lymphomas and leukemias - AML 120

Lymphomas and leukemias - CLL 52

Lymphomas and leukemias - CML 51

Lymphomas and leukemias - NHL 23

Melanoma 81

Mesothelioma 1

Multiple Myeloma 24

Ovarian Cancer 324

Pancreatic Cancer 72

Prostate Cancer 78

Sarcoma 25


Chemosensitivity Testing

• Cancers show great heterogeneity in gene expression and mutations

• The best average drug for ovarian cancer may not be the best drug for Mrs. Smith’s ovarian cancer

• There is a need for individualized patient care

• Chemosensitivity testing has demonstrated excellent predictive accuracy for drug resistance


Chemosensitivity TestingMosaic Blue Soft Agar Assay


Chemosensitivity TestingMosaic Blue Soft Agar Assay

• Soft Agar: tumor cells grow, normal cells do not

• Requires fewer cells than many other methods

• Increased accuracy – assays run in triplicate

• Reaction is progressive giving greater evaluability

• Dye is non-toxic, allowing for post-treatment harvesting of cells – protein, RNA and DNA analysis of cells (resistant

& sensitive)


Chemosensitivity TestingMosaic Spot Assay for Hematologic Malignancies

• Compatible with ALL, CLL, NHL, Myeloma and blast crisis CML

• Cells are cultured in the presence or absence of drug

• Cells are stained to evaluate membrane integrity and then spun onto slides

• Slides are then fixed and stained to evaluate cell morphology

• Drug inhibition is calculated by comparison of living malignant cells in the treated vs. untreated wells



MOSAICLABORATORIES

Collection Kits, Instruction Manuals, Requisition Forms


Clinical Trial Support

– Mosaic Laboratories is currently supporting >200 clinical trial studies

– Mosaic provides shipper kits, customized instruction manuals and forms

– Instruction manuals contain details and images to facilitate proper sample collection, processing and shipping

– Samples for third party testing can be processed and stored until shipping



MOSAICLABORATORIES

Logistics and Sample Storage


Logistics and Sample Storage

– Customized manifests for shipping based on sponsor request

– Logistics• We help you create a customized request form for sample processing and shipping

– Example: Please section 5 slides at 10 micron with genomic technique. Send the 5 unstained slides along with the matching H&E stained slide (with pathology scribing) to Vendor #1. The manifest should include H&E results in the scribed region.

– Expedited (rush) shipping of samples to various laboratories

– Short-term or Long-term storage of samples• Unstained slides

• Stained slides

• FFPE blocks

• Frozen material – tumor tissue, plasma, PAXgene, Streck, etc…



MOSAICLABORATORIES

Prospective Clinical Trials with Rapid TAT


Prospective Inclusion Testing

– Accredited by CLIA and CAP, Clinical Laboratory License/Permit in CA and NY(Other states do not require a license for clinical trials)

– Expedited H&E and IHC testing with same-day to 3-day turnaround

– Image analysis IHC and FISH testing with a 5-day turnaround

– Customized reporting forms sent to sites and sponsor

– Report indicates whether patient is positive or negative for inclusion criteria

Documents

MOSAIC · 2020-03-05 · 2016 Choueiri TK, Fishman MN, Escudier B, McDermott DF, Drake CG, Kluger H, et al. Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma