2013 REPORT - -

- for Leu Medicines in Development 15 each for myeloproliferative neo- myeloproliferative for 15 each poly such as myelofibrosis, plasms, - and essential throm cythemia vera bocythemia; myelodysplastic and for affect diseases which are syndromes, ing the blood and bone marrow. • offer in development These medicines the thou- for survival greater hope for by affected of Americans who are sands of the blood.these in this listed for the cancers Definitions on report and other terms can be found web sponsor company to Links page 27. on the information more sites provide potential products. - of medi value on the information For an in-depth in- cines, look at current breakthroughs medical and key novation please patients, benefiting blood see . 2013—Overview and Lymphoma kemia

minutes minutes 4 of all cancers of all cancers

with , with leukemia, Every a person is diagnosed lymphoma or myeloma; for Accounting 9% diagnosed each year each diagnosed 98 for lymphoma, including Hodgkin 98 for and non-Hodgkin lymphoma, which Americans each 80,000 nearly affect year. including the four leukemia, for 97 nearly which affect major types, States people in the United 50,000 year. each of the a cancer myeloma, for 52 which impacts more plasma cells, in the year people each than 22,000 States. United hema- targeting are medicines 24 which affect malignancies, tological blood and lymph bone marrow, nodes.  Biopharmaceutical research companies companies research Biopharmaceutical blood for medicines 241 developing are lymphoma and cancers—leukemia, This report in lists medicines myeloma. by human clinical trials or under review Drug Administration and Food the U.S. (FDA). include: in development The medicines • • • • More Than 240 Medicines in Development for Development in Medicines Than 240 More Leukemia, Lymphoma and Other Blood Cancers Lymphoma Leukemia,

52 Myeloma

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ymphoma L

97

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Phase I Phase II Phase III Application Submitte Malignancies

Medicines in Development in Development Medicines Blood Leading Cancers For Hematological Hematological Medicines in Development for Leukemia & Lymphoma

Hematological Malignancies

Product Name Sponsor Indication Development Phase*

Adcetris® Millennium Pharmaceuticals treatment of CD30-positive Phase II Cambridge, MA hematological malignancies millennium.com (Orphan Drug) Seattle Genetics (see also lymphoma) seattlegenetics.com Bothell, WA

AMG 319 hematological malignancies Phase I (PI3K-delta inhibitor) Thousand Oaks, CA amgen.com

anti-CD22 antibody-drug hematological malignancies Phase II conjugate South San Francisco, CA (see also lymphoma) gene.com (DCDT 2980S)

anti-CD79b antibody-drug Genentech hematological malignancies Phase II conjugate South San Francisco, CA (see also lymphoma) gene.com (DCDS 4501A)

AR-42 Arno Therapeutics hematological malignancies Phase I/II (pan-DAC inhibitor) Flemington, NJ arnothera.com

AZD1208 AstraZeneca hematological malignancies Phase I (PIM kinase inhibitor) Wilmington, DE astrazeneca.com

AZD9150 AstraZeneca hematological malignancies Phase I (STAT3 inhibitor) Wilmington, DE astrazeneca.com

hematological malignancies Phase I (HDAC inhibitor) Henderson, NV (see also lymphoma) sppirx.com

CB3304 Cougar Biotechnology hematological malignancies Phase I (noscapine) Raritan, NJ cougarbiotechnology.com

darinaparsin ZIOPHARM Oncology hematological malignancies Phase II (ZIO-101) New York, NY (see also lymphoma, myeloma) ziopharm.com

fostamatinib AstraZeneca hematological malignancies Phase II (Syk inhibitor) Wilmington, DE astrazeneca.com Rigel Pharmaceuticals rigel.com South San Francisco, CA

GS-9973 B-cell hematological malignancies Phase I (Syk inhibitor) Foster City, CA gilead.com

*For more information about a specific medicine or company in the report, please click on the provided link.

2 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Hematological Malignancies

Product Name Sponsor Indication Development Phase

Jakafi® Incyte hematological malignancies Phase II ruxolitinib Wilmington, DE incyte.com

MEDI-551 AstraZeneca hematological malignancies Phase II (anti-CD19 mAb) Wilmington, DE astrazeneca.com MedImmune medimmune.com Gaithersburg, MD

MLN4924 Millennium Pharmaceuticals hematological malignancies Phase I (pevonedistat) Cambridge, MA millennium.com

MLN8237 Millennium Pharmaceuticals hematological malignancies Phase II (alisertib) Cambridge, MA (see also lymphoma) millennium.com

MLN9708 Millennium Pharmaceuticals hematological malignancies Phase I () Cambridge, MA (see also myeloma) millennium.com (second-generation )

AstraZeneca hematological malignancies Phase I (anti-CD22 recombinant Wilmington, DE astrazeneca.com immunotoxin) MedImmune medimmune.com Gaithersburg, MD

Bristol-Myers Squibb hematological malignancies Phase I (anti-PD-1) Princeton, NJ bms.com

Onyx Pharmaceuticals hematological malignancies Phase I South San Francisco, CA onyx.com

RG7112 Roche hematological malignancies Phase I (MDM2 antagonist) Nutley, NJ roche.com

RG7388 Roche hematological malignancies Phase I (proto oncogene protein-c mdm2 Nutley, NJ roche.com inhibitor)

SAR405838 Ascenta Therapeutics hematological malignancies Phase I (HDM2/p53 antagonist) Malvern, PA ascenta.com Sanofi US sanofi.com Bridgewater, NJ

SAR650984 ImmunoGen hematological malignancies Phase I (anti-CD38 naked mAb) Waltham, MA immunogen.com Sanofi US sanofi.com Bridgewater, NJ

Medicines in Development Leukemia & Lymphoma 2013 3 Medicines in Development for Leukemia & Lymphoma

Leukemia

Product Name Sponsor Indication Development Phase

ABT-199/GDC-0199/RG7601 AbbVie relapsed/refractory chronic Phase I (Bcl-2 inhibitor) North Chicago, IL lymphocytic leukemia (CLL) .com Genentech (see also lymphoma, myeloma) gene.com South San Francisco, CA roche.com Roche Nutley, NJ

Actimab-A™ Actinium Pharmaceuticals (AML) Phase I/II lintuzumab Ac-225 New York, NY actiniumpharmaceuticals.com

Syntrix Biosystems pediatric acute lymphoblastic Phase II Auburn, WA leukemia (ALL) syntrixbio.com

Arzerra® GlaxoSmithKline first-line CLL, relapsed CLL Phase III Rsch. Triangle Park, NC (see also lymphoma) gsk.com (Orphan Drug)

AT-101 Ascenta Therapeutics CLL Phase II completed (pan Bcl-2 inhibitor) Malvern, PA (see also lymphoma) ascenta.com

AT-406 Ascenta Therapeutics AML Phase I (multi-IAP inhibitor) Malvern, PA ascenta.com Debiopharm debiopharm.com Lausanne, Switzerland

bafetinib CytRx CLL Phase II completed Los Angeles, CA .com

BI-811283 Boehringer Ingelheim Pharmaceuticals AML Phase I/II (aurora B kinase inhibitor) Ridgefield, CT boehringer-ingelheim.com

BI-836826 Boehringer Ingelheim Pharmaceuticals CLL Phase I Ridgefield, CT boehringer-ingelheim.com

BI-836858 Boehringer Ingelheim Pharmaceuticals AML Phase I Ridgefield, CT boehringer-ingelheim.com

birinapant TetraLogic Pharmaceuticals AML Phase I/II Malvern, PA (see also lymphoma) tetralogicpharma.com

Bismab-A™ Actinium Pharmaceuticals AML Phase I/II lintuzumab Bi-213 New York, NY actiniumpharmaceuticals.com

4 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Leukemia

Product Name Sponsor Indication Development Phase

Amgen ALL Phase II (AMG 103) Thousand Oaks, CA (see also lymphoma) amgen.com

BMS-906024 Bristol-Myers Squibb T-cell ALL Phase I (notch inhibitor) Princeton, NJ (see also lymphoma) bms.com

BMS-936564 Bristol-Myers Squibb AML, CLL, diffuse large Phase I (anti-CXCR4) Princeton, NJ B-cell leukemia bms.com (see also lymphoma, myeloma)

Bosulif® first-line Ph+ chronic myeloid Phase III bosutinib New York, NY leukemia (CML) pfizer.com

BP-100-1.01 Bio-Path Holdings ALL, AML, CML Phase I (liposomal Grb-2) Houston, TX (see also myelodysplastic) biopathholdings.com (Orphan Drug)

calaspargase pegol Sigma-Tau Pharmaceuticals ALL in adolescents and children Phase III (Orphan Drug) Gaithersburg, MD sigmatau.com

CC-292 Celgene CLL Phase I (Btk inhiitor) Summit, NJ (see also lymphoma) celgene.com

CC-486 Celgene post-induction AML maintenance Phase II () Summit, NJ (see also myelodysplastic) celgene.com

Ceplene® EpiCept AML Phase III histamine Tarrytown, NY epicept.com

CNDO-109 Coronado Biosciences AML Phase II (tumor-activated natural Burlington, MA coronadobiosciences.com killer cells) (Orphan Drug)

CPX-351 Celator Pharmaceuticals AML Phase III (/) Princeton, NJ celatorpharma.com (Orphan Drug)

crenolanib AROG Pharmaceuticals AML Phase II (CP-868-596) Dallas, TX arogpharma.com

CTL019 Novartis Pharmaceuticals CLL Phase II (CAR T-cell therapy) East Hanover, NJ novartis.com University of Pennsylvania Philadelphia, PA

CWP232291 JW Pharmaceutical AML Phase I Seoul, South Korea

Medicines in Development Leukemia & Lymphoma 2013 5 Medicines in Development for Leukemia & Lymphoma

Leukemia

Product Name Sponsor Indication Development Phase

Dacogen® Eisai AML application submitted Woodcliff Lake, NJ eisai.com (Orphan Drug) ------pediatric AML Phase II eisai.com

DFP-10917 Delta-Fly Pharma ALL, AML Phase I/II ( inhibitor) Tokushima, Japan

dinaciclib Merck CLL Phase III (SOK inhibitor) Whitehouse Station, NJ merck.com (Orphan Drug)

Synta Pharmaceuticals AML Phase I Lexington, MA syntapharma.com

ENMD-2076 EntreMed AML Phase I completed (Orphan Drug) Rockville, MD (see also myeloma) entremed.com

Syndax Pharmaceuticals leukemia Phase II Waltham, MA (see also lymphoma) syndax.com

EPZ-5676 Epizyme leukemia Phase I (DOT1L inhibitor) Cambridge, MA epizyme.com

Erwinaze™ ALL Phase I Erwinia Palo Alto, CA jazzpharma.com chrysanthemi (IV formulation)

forodesine BioCryst Pharmaceuticals CLL Phase II (PNP inhibitor) Durham, NC (see also lymphoma) biocryst.com (Orphan Drug)

GNKG-168 SBI Biotech CLL Phase I (TLR9 agonist) Tokyo, Japan sbibiotech.jp

GS-9820 Gilead Sciences CLL Phase I (PI3K delta inhibitor) Foster City, CA (see also lymphoma) gilead.com

hTERT RNA vaccine BioTime AML Phase II Alameda, CA biotimeinc.com

HuM195/rGel Targa Therapeutics AML, CML Phase I (lintuzumab-gelonin conjugate) San Diego, CA (see also myelodysplastic) targatherapeutics.com

ibrutinib CLL (Fast Track) Phase III (Orphan Drug) Horsham, PA (see also lymphoma, myeloma) janssenbiotech.com Pharmacyclics pharmacyclics.com Sunnyvale, CA

6 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Leukemia

Product Name Sponsor Indication Development Phase

ibrutinib companion diagnostic CLL (diagnosis) in clinical trials Abbott Park, IL abbott.com Janssen Biotech janssenbiotech.com Horsham, PA pharmacyclics.com Pharmacyclics Sunnyvale, CA

Iclusig® ARIAD Pharmaceuticals newly-diagnosed CML Phase III ponatinib Cambridge, MA ariad.com (Orphan Drug) ------AML Phase II ariad.com

Gilead Sciences CLL Phase III (PI3K delta inhibitor) Foster City, CA (see also lymphoma) gilead.com

Imprime PGG® Biothera first-line CLL Phase I/II immunotherapeutic Eagan, MN (see also lymphoma) biothera.com

Pfizer ALL Phase III New York, NY (see also lymphoma) pfizer.com

Iomab™-B Actinium Pharmaceuticals AML Phase II anti-CD45 mAb New York, NY actiniumpharmaceuticals.com

ISF35 Memgen CLL Phase II (recombinant CD40 ligand San Diego, CA (see also lymphoma) memgenbio.com immunotherapy)

JVRS-100 Colby Pharmaceutical leukemia Phase I (DNA vaccine) San Jose, CA colbypharma.com

KX01 Kinex Pharmaceuticals AML, CML Phase I (non-ATP competitive Src kinase Buffalo, NY kinexpharma.com inhibitor)

LDE225 Novartis Pharmaceuticals CML Phase I (erismodegib) East Hanover, NJ novartis.com

lestaurtinib (Teva) AML Phase II (CEP-701) Horsham, PA (see also myeloproliferative) tevapharm.com

lirilumab Bristol-Myers Squibb AML Phase II (anti-Kir) Princeton, NJ bms.com

Medicines in Development Leukemia & Lymphoma 2013 7 Medicines in Development for Leukemia & Lymphoma

Leukemia

Product Name Sponsor Indication Development Phase

LOR-2040 Lorus Therapeutics AML Phase II (ribonucleotide reductase Toronto, Canada lorusthera.com inhibitor)

LY2090314 Eli Lilly AML, acute promyelocytic leukemia Phase II (GSK3-beta inhibitor) Indianapolis, IN (APL) lilly.com

Marqibo® Talon Therapeutics ALL in the elderly Phase III liposomal South San Francisco, CA (Fast Track) talontx.com (Orphan Drug)

Immunomedics CLL Phase I/II (anti-CD74 mAb) Morris Plains, NJ immunomedics.com (Orphan Drug)

MK-8242 Merck AML Phase I (MDM2 inhibitor) Whitehouse Station, NJ merck.com

mogamulizumab Kyowa Hakko Kirin adult T-cell leukemia Phase II (anti-CCR4 mAb) Tokyo, Japan (see also lymphoma) kyowa-kirin.com (Orphan Drug)

navitoclax AbbVie CLL Phase II (bcl-2 inhibitor) North Chicago, IL abbvie.com

Idec first-line CLL Phase III (anti-CD20 mAb) Weston, MA (see also lymphoma) biogenidec.com Genentech gene.com South San Francisco, CA roche.com Roche Nutley, NJ

OXi4503 OXiGENE refractory AML Phase I (Orphan Drug) South San Francisco, CA oxigene.com

perifosine AEterna Zentaris CLL Phase II Basking Ridge, NJ aezsinc.com

PF-04449913 Pfizer AML Phase I New York, NY pfizer.com

PKC412 Novartis Pharmaceuticals AML Phase III (midostaurin) East Hanover, NJ (see also myeloproliferative) novartis.com

8 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Leukemia

Product Name Sponsor Indication Development Phase

PKC412 (midostaurin) Invivoscribe Technologies AML (diagnosis) in clinical trials companion diagnostic San Diego, CA invivoscribe.com Novartis Pharmaceuticals novartis.com East Hanover, NJ

PLX3397 Plexxikon AML Phase II Berkeley, CA (see also lymphoma) plexxikon.com

PM01183 PharmaMar leukemia Phase I (cell-cycle inhibitor) Madrid, Spain pharmamar.com

PR104 Proacta AML Phase I/II La Jolla, CA proacta.com

PRI-724 Prism Pharma AML, CML Phase I/II (CBP/β-catenin inhibitor) Tokyo, Japan prismbiolab.com

Promacta® GlaxoSmithKline AML Phase II eltrombopag Rsch. Triangle Park, NC (see also myelodysplastic) gsk.com

quizartinib Ambit Biosciences relapsed/refractory AML Phase II (FLT3 inhibitor) San Diego, CA ambitbio.com ------first-line AML (combination therapy), Phase I post-HSCT maintenance in AML ambitbio.com

Revlimid® Celgene CLL (initial treatment and Phase III lenalidomide Summit, NJ maintenance) celgene.com (Orphan Drug) (see also lymphoma, myelodysplastic)

Revlimid® Celgene AML Phase II lenalidomide and Summit, NJ celgene.com Vidaza® injection (Orphan Drug)

RG7356 Roche AML Phase I (anti-CD44 mAb) Nutley, NJ roche.com

sapacitabine Cyclacel Pharmaceuticals AML Phase III (Orphan Drug) Berkeley Heights, NJ (see also myelodysplastic) cyclacel.com ------CLL Phase II cyclacel.com

SAR3419 ImmunoGen ALL Phase II (maytansin-loaded anti-CD19 Waltham, MA (see also lymphoma) immunogen.com mAb) Sanofi US sanofi.com Bridgewater, MA

Medicines in Development Leukemia & Lymphoma 2013 9 Medicines in Development for Leukemia & Lymphoma

Leukemia

Product Name Sponsor Indication Development Phase

SGI110 Astex Pharmaceuticals AML Phase II (DNMT1 inhibitor) Dublin, CA (see also myelodysplastic) astx.com

SGN-CD19A Seattle Genetics ALL Phase I (CD19 antibody-drug conjugate) Bothell, WA (see also lymphoma) seattlegenetics.com

SL-401 Stemline Therapeutics relapsed/refractory AML, relapsed/ Phase I/II (recombinant fusion protein) New York, NY refractory blastic plasmacytoid stemline.com (Orphan Drug) dendritic cell neoplasm (see also myelodysplastic)

Sprycel Bristol-Myers Squibb leukemia in children and Phase II dasatinib Princeton, NJ adolescents bms.com

tamibarotene CytRx acute promyelocytic leukemia Phase II (Orphan Drug) Los Angeles, CA (Fast Track) cytrx.com

Tasigna® Novartis Pharmaceuticals ALL (adolescents and children), Phase II nilotinib East Hanover, NJ CML (adolescents and children) novartis.com

TCN-P Cahaba Pharmaceuticals AML Phase I (AKT inhibitor) Princeton, NJ cahabapharma.com

Temodar® Merck AML Phase II completed Whitehouse Station, NJ merck.com

tetradecanoylphorbol acetate Biosuccess Biotech AML Phase I/II (TPA) (PD-616) Beverly Hills, CA biosuccessbiotech.com

TG02 Tragara Pharmaceuticals acute leukemia, CLL Phase I (multi-kinase inhibitor) Carlsbad, CA (see also myeloma) tragarapharma.com

TH-302 EMD Serono advanced leukemia Phase I (hypoxia-targeted drug) Rockland, MA (see also myeloma) emdserono.com Threshold Pharmaceuticals thresholdpharm.com South San Francisco, CA

tosedostat Cell Therapeutics AML Phase II Seattle, WA celltherapeutics.com Chroma Therapeutics Oxon, United Kingdom

Treanda® Cephalon (Teva) ALL, AML Phase I/II Frazer, PA (see also lymphoma, myeloma) tevapharm.com

TRU-016 Emergent BioSolutions CLL Phase II (anti-CD37 mAb) Rockville, MD emergentbiosolutions.com (Orphan Drug)

10 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Leukemia

Product Name Sponsor Indication Development Phase

TG Therapeutics CLL Phase I/II (TG-1101) New York, NY (see also lymphoma) tgtherapeutics.com (Orphan Drug)

VAY736 MorphoSys CLL Phase I (anti-BAFFR mAb) Martinsried, Germany morphosys.com Novartis Pharmaceuticals novartis.com East Hanover, NJ

Immunomedics CLL Phase II (Orphan Drug) Morris Plains, NJ (see also lymphoma) immunomedics.com

volasertib Boehringer Ingelheim Pharmaceuticals AML Phase III Ridgefield, CT boehringer-ingelheim.com

vosaroxin Sunesis Pharmaceuticals AML Phase III South San Francisco, CA sunesis.com

WT1 immunotherapeutic GlaxoSmithKline AML Phase II (antigen-specific cancer Rsch. Triangle Park, NC gsk.com immunotherapeutic/ASCI)

XmAb® 5574/MOR208 MorphoSys CLL Phase I (anti-CD19 mAb) Martinsried, Germany morphosys.com Xenvor xencor.com Monrovia, CA

Lymphoma

Product Name Sponsor Indication Development Phase

abexinostat Pharmacyclics follicular lymphoma, Phase II (HDAC inhibitor) Sunnyvale, CA mantle cell lymphoma pharmacyclics.com

ABT-199/GDC-0199/RG7601 AbbVie non-Hodgkin lymphoma Phase I (Bcl-2 inhibitor) North Chicago, IL (see also leukemia, myeloma) abbvie.com Genentech gene.com South San Francisco, CA roche.com Roche Nutley, NJ

Medicines in Development Leukemia & Lymphoma 2013 11 Medicines in Development for Leukemia & Lymphoma

Lymphoma

Product Name Sponsor Indication Development Phase

Adcetris® Millennium Pharmaceuticals Hodgkin lymphoma Phase III brentuximab vedotin Cambridge, MA (post-transplant relapse millennium.com (Orphan Drug) Seattle Genetics prevention), relapsed seattlegenetics.com Bothell, WA CD30-positive cutaneous T-cell lymphoma, first-line Hodgkin lymphoma, first-line CD30-positive mature T-cell lymphoma (see also hematological) ------relapsed/refractory CD30-positive Phase II non-Hodgkin lymphoma, CD30- millennium.com positive lymphoma malignancies, seattlegenetics.com first-line Hodgkin lymphoma in patients 60 years and older ------second-line Hodgkin lymphoma Phase I millennium.com seattlegenetics.com

AEB071 Novartis Pharmaceuticals diffuse large B-cell lymphoma Phase I (PKC inhibitor) East Hanover, NJ novartis.com

AEZS-112 AEterna Zentaris lymphoma Phase I completed (tubulin polymerization/ Basking Ridge, NJ aezsinc.com topoisomerase II inhibitor)

Afinitor® Novartis Pharmaceuticals diffuse large B-cell lymphoma Phase III everolimus East Hanover, NJ novartis.com

AFM13 Affimed Therapeutics Hodgkin lymphoma Phase I (bispecific tetravalent antibody) Heidelberg, Germany affimed.com (Orphan Drug)

anti-CD22 antibody-drug Genentech diffuse large B-cell lymphoma, Phase II conjugate South San Francisco, CA non-Hodgkin lymphoma gene.com (DCDT 2980S) (see also hematological)

anti-CD79b antibody-drug Genentech diffuse large B-cell lymphoma, Phase II conjugate South San Francisco, CA non-Hodgkin lymphoma gene.com (DCDS 4501A) (see also hematological)

AR-12 Arno Therapeutics lymphoma Phase I (PI3-K/Akt inhibitor) Flemington, NJ arnothera.com

12 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Lymphoma

Product Name Sponsor Indication Development Phase

Arzerra® GlaxoSmithKline diffuse large B-cell lymphoma, Phase III ofatumumab Rsch. Triangle Park, NC relapsed/refractory follicular gsk.com lymphoma (see also leukemia)

ASP3026 Astellas Pharma US late-stage B-cell lymphoma Phase I (ALK inhibitor) Deerfield, IL astellas.com

AT-101 Ascenta Therapeutics non-Hodgkin lymphoma Phase II completed (pan Bcl-2 inhibitor) Malvern, PA (see also leukemia) ascenta.com

autologous idiotypic cancer vaccine Bayer HealthCare Pharmaceuticals follicular lymphoma Phase I Wayne, NJ bayerpharma.com

BAY 80-6946 Bayer HealthCare Pharmaceuticals non-Hodgkin lymphoma Phase II (PI3K inhibitor) Wayne, NJ bayerpharma.com

belinostat Spectrum Pharmaceuticals peripheral B-cell lymphoma Phase II (HDAC inhibitor) Henderson, NV (Fast Track) sppirx.com (see also hematological)

Bexxar® GlaxoSmithKline mantle cell lymphoma Phase II and iodine Rsch Triangle Park, NC gsk.com I-131 tositumomab

BI-695500 Boehringer Ingelheim Pharmaceuticals non-Hodgkin lymphoma Phase III ( biosimilar) Ridgefield, CT boehringer-ingelheim.com

BiovaxID® International indolent follicular lymphoma Phase III B-cell lymphoma vaccine Tampa, FL (Fast Track) biovest.com (Orphan Drug) ------mantle cell lymphoma Phase II biovest.com

birinapant TetraLogic Pharmaceuticals lymphoma Phase I Malvern, PA (see also leukemia) tetralogicpharma.com

BKM120 Novartis Pharmaceuticals relapsed/refractory non-Hodgkin Phase II (PI3K inhibitor) East Hanover, NJ lymphoma novartis.com

blinatumomab Amgen non-Hodgkin lymphoma Phase II (AMG 103) Thousand Oaks, CA (see also leukemia) amgen.com

BMS-906024 Bristol-Myers Squibb T-cell lymphoblastic lymphoma Phase I (notch inhibitor) Princeton, NJ (see also leukemia) bms.com

BMS-936564 Bristol-Myers Squibb follicular lymphoma Phase I (anti-CXCR4) Princeton, NJ (see also leukemia, myeloma) bms.com

Medicines in Development Leukemia & Lymphoma 2013 13 Medicines in Development for Leukemia & Lymphoma

Lymphoma

Product Name Sponsor Indication Development Phase

brentuximab vedotin companion Millennium Pharmaceuticals cutaneous T-cell lymphoma in clinical trials diagnostic Cambridge, MA (diagnosis), T-cell lymphoma ventana.com Seattle Genetics (diagnosis) Bothell, WA Ventana Medical Systems Tucson, AZ

CC-292 Celgene lymphoma Phase I (BtK inhibitor) Summit, NJ (see also leukemia) celgene.com

CD-5789 Galderma USA cutaneous T-cell lymphoma Phase I Fort Worth, TX galdermausa.com M.D. Anderson Cancer Center Houston, TX

CEP-9722 Cephalon (Teva) mantle cell lymphoma Phase I (PARP inhibitor) Frazer, PA tevapharm.com

CGC-11047 Progen Pharmaceuticals lymphoma Phase I completed Queensland, Australia progen-pharma.com

CUDC-427 Curis lymphoma Phase I (IAP inhibitor) Lexington, MA curis.com

CUDC-907 Curis diffuse large B-cell lymphoma Phase I (HDAC/PI3K inhibitor) Lexington, MA (see also myeloma) curis.com

darinaparsin ZIOPHARM Oncology non-Hodgkin lymphoma Phase I (ZIO-101) New York, NY (see also hematological, myeloma) ziopharm.com

delanzomib Cephalon (Teva) non-Hodgkin lymphoma Phase I Frazer, PA (see also myeloma) tevapharm.com

DI-Leu16-IL2 alopexx Oncology non-Hodgkin lymphoma Phase I (CD20-antigen inhibitor) Cambridge, MA alopexx.com

DS-3078 Daiichi Sankyo lymphoma Phase I Parsippany, NJ dsi.com

entinostat Syndax Pharmaceuticals relapsed/refractory Hodgkin Phase II Waltham, MA lymphoma syndax.com (see also leukemia)

enzastaurin Eli Lilly diffuse large B-cell lymphoma Phase III Indianapolis, IN lilly.com

epratuzumab Immunomedics non-Hodgkin lymphoma Phase II (Orphan Drug) Morris Plains, NJ immunomedics.com

14 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Lymphoma

Product Name Sponsor Indication Development Phase

epratuzumab Y-90 Immunomedics non-Hodgkin lymphoma Phase I/II Morris Plains, NJ immunomedics.com

forodesine BioCryst Pharmaceuticals cutaneous T-cell lymphoma Phase II (PNP inhibitor) Durham, NC (see also leukemia) biocryst.com (Orphan Drug)

GDC-0425 Genentech lymphoma Phase I (ChK1 inhibitor) South San Francisco, CA gene.com

GDC-0575 Genentech lymphoma Phase I (ChK1 inhibitor) South San Francisco, CA gene.com

GDC-0980/RG7422 Genentech non-Hodgkin lymphoma Phase II (PI3 kinase/mTOR dual inhibitor) South San Francisco, CA gene.com Roche roche.com Nutley, NJ

GS-9820 Gilead Sciences lymphoma Phase I (PI3K delta inhibitor) Foster City, CA (see also leukemia) gilead.com

HBI-8000 HUYA Bioscience International lymphoma Phase I (HDAC inhibitor) San Diego, CA huyabio.com Quintiles Durham, NC

ibrutinib Janssen Biotech mantle cell lymphoma Phase III (Orphan Drug) Horsham, PA (see also leukemia, myeloma) janssenbiotech.com ------diffuse large B-cell lymphoma Phase II janssenbiotech.com ------follicular lymphoma Phase I janssenbiotech.com

idelalisib Gilead Sciences indolent non-Hodgkin lymphoma Phase III (PI3K delta inhibitor) Foster City, CA (see also leukemia) gilead.com

IMGN529 ImmunoGen non-Hodgkin lymphoma Phase I (CD37-targeting mAb) Waltham, MA immunogen.com

Imprime PGG® Biothera first-line advanced indolent Phase II/III immunotherapeutic Eagan, MN non-Hodgkin lymphoma biothera.com (see also leukemia)

inotuzumab ozogamicin Pfizer aggressive non-Hodgkin Phase III New York, NY lymphoma pfizer.com (see also leukemia)

Medicines in Development Leukemia & Lymphoma 2013 15 Medicines in Development for Leukemia & Lymphoma

Lymphoma

Product Name Sponsor Indication Development Phase

interleukin-12 gene therapy OncoSec Medical cutaneous T-cell lymphoma Phase II San Diego, CA oncosec.com

ISF35 Memgen non-Hodgkin lymphoma Phase II (recombinant CD40 ligand San Diego, CA (see also leukemia) memgenbio.com immunotherapy)

Istodax® Celgene newly-diagnosed peripheral Phase III Summit, NJ T-cell lymphoma celgene.com

JNJ-26481585 Janssen Research & Development cutaneous T-cell lymphoma Phase II (HDAC inhibitor) Raritan, NJ janssenrnd.com

JNJ-40346527 Janssen Research & Development Hodgkin lymphoma Phase I/II (FMS inhibitor) Raritan, NJ janssenrnd.com

JNJ-42756493 Janssen Research & Development lymphoma Phase I (FGFR inhibitor) Raritan, NJ janssenrnd.com

LEE011 Novartis Pharmaceuticals lymphoma Phase I (CDK-4/6 inhibitor) East Hanover, NJ novartis.com

LY3039478 Eli Lilly lymphoma Phase I Indianapolis, IN lilly.com

marizomib Nereus Pharmaceuticals lymphoma Phase I San Diego, CA (see also myeloma)

mechlorethamine gel Ceptaris Therapeutics mycosis fungoides application submitted (Orphan Drug) Malvern, PA (cutaneous T-cell lymphoma) ceptaris.com

MK-8808 Merck follicular lymphoma Phase I Whitehouse Station, NJ merck.com

MLN8237 Millennium Pharmaceuticals relapsed/refractory peripheral Phase III (alisertib) Cambridge, MA T-cell lymphoma millennium.com (see also hematological)

mocetinostat (MGCD0103) MethylGene diffuse large B-cell lymphoma, Phase II (HDAC inhibitor) Montreal, Canada follicular lymphoma methylgene.com (Orphan Drug)

mogamulizumab Kyowa Hakko Kirin cutaneous T-cell lymphoma Phase III (anti-CCR4 mAb) Tokyo, Japan (see also leukemia) kyowa-kirin.com (Orphan Drug) ------adult T-cell lymphoma, peripheral Phase II T-cell lymphoma kyowa-kirin.com

16 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Lymphoma

Product Name Sponsor Indication Development Phase

obinutuzumab Biogen Idec diffuse large B-cell lymphoma, Phase III (anti-CD20 mAb) Weston, MA first-line indolent non-Hodgkin biogenidec.com Genentech lymphoma, refractory indolent gene.com South San Francisco, CA non-Hodgkin lymphoma roche.com Roche (see also leukemia) Nutley, NJ

MENTRIK Biotech non-Hodgkin lymphoma Phase II (AME-133v) Dallas, TX mentrik.com

ON 013105 Onconova Therapeutics refractory lymphoma Phase I (cyclin D1 modulator) Newtown, PA onconova.com

ONO 4059 Ono Pharma USA B-cell lymphoma Phase I (Btk inhibitor) Trenton, NJ ono.co.jp

pacritinib Cell Therapeutics relapsed lymphoma Phase II completed Seattle, WA (see also myeloproliferative) celltherapeutics.com

(PD-0332991) Pfizer mantle cell lymphoma Phase I completed (CDK-4/6 kinase inhibitor) New York, NY (see also myeloma) pfizer.com

PF-05082566 Pfizer non-Hodgkin lymphoma Phase I (CD137 antigen agonist) New York, NY pfizer.com

pidilizumab CureTech diffuse large B-cell lymphoma Phase II (CT-011) Yavne, Israel curetechbio.com

Pixuvri® Cell Therapeutics diffuse large B-cell lymphoma, Phase III Seattle, WA follicular lymphoma celltherapeutics.com

PLX3397 Plexxikon Hodgkin lymphoma Phase II Berkeley, CA (see also leukemia) plexxikon.com

PNT2258 ProNAi Therapeutics B-cell lymphoma Phase II (bcl-2 oncogene inhibitor) Plymouth, MI pronai.com

Revlimid® Celgene relapsed/refractory mantle-cell application submitted lenalidomide Summit, NJ lymphoma celgene.com (see also leukemia, myelodysplastic) ------diffuse large B-cell lymphoma Phase III (maintenance), celgene.com follicular lymphoma ------relapsed/refractory diffuse large Phase II B-cell lymphoma celgene.com

Medicines in Development Leukemia & Lymphoma 2013 17 Medicines in Development for Leukemia & Lymphoma

Lymphoma

Product Name Sponsor Indication Development Phase

RG7602 Genentech lymphoma Phase I South San Francisco, CA gene.com Roche roche.com Nutley, NJ

SAR3419 ImmunoGen non-Hodgkin lymphoma Phase II (maytansin-loaded anti-CD19 Waltham, MA (see also leukemia) immunogen.com mAb) Sanofi US sanofi.com Bridgewater, NJ

SAR245409 (XL765) Exelixis non-Hodgkin lymphoma Phase II (PI3K/mTOR inhibitor) South San Francisco, CA exelixis.com Sanofi US sanofi.com Bridgewater, NJ

sepantronium bromide Astellas Pharma US non-Hodgkin lymphoma Phase II (YM155) Northbrook, IL astellas.com

SGN-75 Seattle Genetics non-Hodgkin lymphoma Phase I completed Bothell, WA seattlegenetics.com

SGN-CD19A Seattle Genetics non-Hodgkin lymphoma Phase I (CD19 antibody-drug conjugate) Bothell, WA (see also leukemia) seattlegenetics.com

SHP-141 Leukemia & Lymphoma Society cutaneous T-cell lymphoma Phase I (topical HDAC inhibitor) White Plains, NY shapepharma.com Shape Pharmaceuticals Cambridge, MA

SNS01-T Senesco Technologies diffuse large B-cell lymphoma, Phase I/II (nano-encapsulated gene therapy) Bridgewater, NJ mantle cell lymphoma senesco.com (Orphan Drug) (see also myeloma)

SNX-5422 Esanex non-Hodgkin lymphoma Phase I (Hsp90 inhibitor) Indianapolis, IN

TKM-PLK1 Tekmira Pharmaceuticals lymphoma Phase I (RNAi therapeutic) Burnaby, Canada tekmirapharm.com

trametinib GlaxoSmithKline lymphoma Phase II (GSK1120212) Rsch. Triangle Park, NC gsk.com

Treanda® Cephalon (Teva) first-line indolent B-cell application submitted bendamustine Frazer, PA non-Hodgkin lymphoma tevapharm.com (Orphan Drug) (see also leukemia, myeloma) ------mantle cell lymphoma Phase II tevapharm.com

18 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Lymphoma

Product Name Sponsor Indication Development Phase

ublituximab TG Therapeutics non-Hodgkin lymphoma Phase I/II (TG-1101) New York, NY (see also leukemia) tgtherapeutics.com

UNBS 5162 Drais Pharmaceuticals lymphoma Phase I Bridgewater, NJ draispharma.com

urelumab Bristol-Myers Squibb relapsed/refractory B-cell Phase I (anti-CD137 mAb) Princeton, NJ non-Hodgkin lymphoma bms.com

Velcade® Millennium Pharmaceuticals first-line mantle cell lymphoma Phase III Cambridge, MA millennium.com ------diffuse large B-cell lymphoma Phase II millennium.com

veltuzumab Immunomedics non-Hodgkin lymphoma Phase II Morris Plains, NJ (see also leukemia) immunomedics.com

veltuzumab/epratuzumab Y-90 Immunomedics diffuse large B-cell lymphoma Phase I Morris Plains, NJ immunomedics.com

liposomal Talon Therapeutics non-Hodgkin lymphoma Phase I South San Francisco, CA talontx.com

XmAb®2513 Xencor Hodgkin lymphoma Phase I anti-CD30 mAb Monrovia, CA xencor.com

zanolimumab Emergent BioSolutions peripheral T-cell lymphoma Phase II Rockville, MD emergentbiosolutions.com

Zevalin® Spectrum Pharmaceuticals diffuse large B-cell lymphoma Phase III Henderson, NV sppirx.com ------mantle cell lymphoma Phase II sppirx.com Myelodysplastic Syndromes

Product Name Sponsor Indication Development Phase

ACE-536 Acceleron Pharma anemia in myelodysplastic Phase I (TGF-beta superfamily Cambridge, MA syndromes acceleronpharma.com protein inhibitor) Celgene celgene.com (Orphan Drug) Summit, NJ

Aranesp® Amgen myelodysplastic syndromes Phase III darbepoetin alfa Thousand Oaks, CA amgen.com

Medicines in Development Leukemia & Lymphoma 2013 19 Medicines in Development for Leukemia & Lymphoma

Myelodysplastic Syndromes

Product Name Sponsor Indication Development Phase

ARRY-614 Array BioPharma myelodysplastic syndromes Phase I (p38/TIE2 inhibitor) Boulder, CO arraybiopharma.com

BP-100-1.01 Bio-Path Holdings myelodysplastic syndromes Phase I (liposomal Grb-2) Houston, TX (see also leukemia) biopathholdings.com

CC-486 Celgene lower-risk myelodysplastic Phase II (nucleoside analogue) Summit, NJ syndromes celgene.com (see also leukemia)

HuM195/rGel Targa Therapeutics myelodysplastic syndromes Phase I (lintuzumab-gelonin conjugate) San Diego, CA (see also leukemia) targatherapeutics.com

pracinostat MEI Pharma myelodysplastic syndromes Phase II (HDAC inhibitor) San Diego, CA (see also myeloproliferative) meipharma.com

Promacta® GlaxoSmithKline myelodysplastic syndromes Phase II eltrombopag Rsch. Triangle Park, NC (see also leukemia) gsk.com

Revlimid® Celgene myelodysplastic syndromes Phase III lenalidomide Summit, NJ (non-deletion 5q) celgene.com (Orphan Drug) (see also leukemia, lymphoma, myeloma)

rigosertib Onconova Therapeutics myelodysplastic syndromes Phase III (Plk1 inhibitor/c-akt inhibitor) Newtown, PA onconova.com (Orphan Drug)

sapacitabine Cyclacel Pharmaceuticals myelodysplastic syndromes Phase II (Orphan Drug) Berkeley Heights, NJ (see also leukemia) cyclacel.com

SGI110 Astex Pharmaceuticals myelodysplastic syndromes Phase II (DNMT1 inhibitor) Dublin, CA (see also leukemia) astx.com

SL-401 Stemline Therapeutics myelodysplastic syndromes Phase I/II (recombinant fusion protein) New York, NY (see also leukemia) stemline.com (Orphan Drug)

sotatercept Acceleron Pharma anemia in myelodysplastic Phase II (ACE-011) Cambridge, MA syndromes acceleronpharma.com Celgene celgene.com Summit, NJ

Telintra® Telik myelodysplastic syndromes Phase II ezatiostat Palo Alto, CA telik.com (Orphan Drug)

20 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Myeloma

Product Name Sponsor Indication Development Phase

ABT-199/GDC-0199/RG7601 AbbVie myeloma Phase I (Bcl-2 inhibitor) North Chicago, IL (see also leukemia, lymphoma) abbvie.com Genentech gene.com South San Francisco, CA roche.com Roche Nutley, NJ

ACY-1215 Acetylon Pharmaceuticals myeloma Phase I/II (HDAC inhibitor) Boston, MA acetylon.com

ALT-801 Altor BioScience myeloma Phase I/II (TCR/IL-2 fusion protein) Miramar, FL altorbioscience.com

antibody-drug conjugate Genentech myeloma Phase I (RG7598) South San Francisco, CA gene.com

Aplidin® PharmaMar myeloma Phase III plitidepsin Madrid, Spain pharmamar.com

ARRY-520 Array BioPharma myeloma Phase II (KSP inhibitor) Boulder, CO arraybiopharma.com

AT7519 Astex Pharmaceuticals myeloma Phase II (CDK inhibitor) Dublin, CA astx.com

AT9283 Astex Pharmaceuticals myeloma Phase II (aurora/JAK 2 inhibitor) Dublin, CA astx.com

AUY922 Novartis Pharmaceuticals myeloma Phase I/II (Hsp90 inhibitor) East Hanover, NJ novartis.com

BHQ880 Morphosys myeloma Phase II Martinsried, Germany morphosys.com Novartis Pharmaceuticals novartis.com East Hanover, NJ

BI-505 BioInvent International myeloma Phase I (ICAM-1-targeting mAb) Lund, Sweden bioinvent.com (Orphan Drug)

BIW-8962 BioWa myeloma Phase I/II (anti-GM2 mAb) La Jolla, CA biowa.com Kyowa Hakko Kirin kyowa-kirin.com Tokyo, Japan

Medicines in Development Leukemia & Lymphoma 2013 21 Medicines in Development for Leukemia & Lymphoma

Myeloma

Product Name Sponsor Indication Development Phase

BMS-936564 Bristol-Myers Squibb relapsed/refractory myeloma Phase I (CXCR4 ) Princeton, NJ (see also leukemia, lymphoma) bms.com

BT-062 Biotest Pharmaceuticals myeloma Phase I/II (anti-CD138 mAb) Boca Raton, FL biotest.com ImmunoGen immunogen.com Waltham, MA

CUDC-907 Curis myeloma Phase I (HDAC/PI3K inhibitor) Lexington, MA (see also lymphoma) curis.com

CX-4945 Cylene Pharmaceuticals myeloma Phase I (casein kinase II inhibitor) San Diego, CA

Janssen Biotech myeloma Phase I/II Horsham, PA (Fast Track) janssenbiotech.com

darinaparsin ZIOPHARM Oncology myeloma Phase II (ZIO-101) New York, NY (see also hematological, ziopharm.com lymphoma)

delanzomib Cephalon (Teva) myeloma Phase II Frazer, PA (see also lymphoma) tevapharm.com

DKN-01 Dekkun myeloma Phase I (DKK2 protein inhibitor) Cambridge, MA

AbbVie myeloma Phase III North Chicago, IL abbvie.com Bristol-Myers Squibb bms.com Princeton, NJ

ENMD-2076 EntreMed myeloma Phase I completed (Orphan Drug) Rockville, MD (see also leukemia) entremed.com

GL-0817 Gliknik myeloma Phase II (immune modulator) Baltimore, MD gliknik.com

GSK2110183 GlaxoSmithKline myeloma Phase I (AKT ) Rsch. Triangle Park, NC gsk.com

ibrutinib Janssen Biotech myeloma Phase II (Orphan Drug) Horsham, PA (see also leukemia, lymphoma) janssenbiotech.com

imetelstat Geron myeloma Phase II (telomerase inhibitor) Menlo Park, CA (see also myeloproliferative) geron.com

22 Medicines in Development Leukemia & Lymphoma 2013 Medicines in Development for Leukemia & Lymphoma

Myeloma

Product Name Sponsor Indication Development Phase

IMGN901 ImmunoGen myeloma Phase I () Waltham, MA immunogen.com

KW-2478 Kyowa Hakko Kirin myeloma Phase I/II (HSP90 inhibitor) Tokyo, Japan kyowa-kirin.com

Kyprolis® Onyx Pharmaceuticals relapsed/refractory myeloma Phase III South San Francisco, CA (monotherapy), relapsed myeloma onyx.com (Orphan Drug) (combination therapy)

LBH589 Novartis Pharmaceuticals myeloma Phase III () East Hanover, NJ novartis.com

LGH447 Novartis Pharmaceuticals myeloma Phase I (proto-oncogene pim-1 inhibitor) East Hanover, NJ novartis.com

GlaxoSmithKline myeloma Phase II Rsch. Triangle Park, NC gsk.com

marizomib Nereus Pharmaceuticals myeloma Phase I San Diego, CA (see also lymphoma)

intravenous Ligand Pharmaceuticals myeloma Phase II/III (captisol-enabled) La Jolla, CA ligand.com (Orphan Drug) Spectrum Pharmaceuticals sppirx.com Henderson, NV

MFGR-1877S Genentech myeloma Phase I completed (FGF-3 receptor antagonist) South San Francisco, CA gene.com

milatuzumab-doxorubicin Immunomedics myeloma Phase I/II conjugate Morris Plains, NJ immunomedics.com (anti-CD74 mAb)

MLN0128 Millennium Pharmaceuticals myeloma Phase I (TORC1/TORC2 inhibitor) Cambridge, MA millennium.com

MLN9708 Millennium Pharmaceuticals relapsed/refractory myeloma Phase III (ixazomib) Cambridge, MA (see also hematological) millennium.com (second-generation proteasome inhibitor)

Medicines in Development Leukemia & Lymphoma 2013 23 Medicines in Development for Leukemia & Lymphoma

Myeloma

Product Name Sponsor Indication Development Phase

Genentech myeloma Phase I (DFRF4539A) South San Francisco, CA gene.com

palbociclib (PD-0332991) Pfizer myeloma Phase I/II (CDK-4/6 kinase inhibitor) New York, NY (see also lymphoma) pfizer.com

PRLX-93936 Prolexsys Pharmaceuticals myeloma Phase I/II Salt Lake City, UT

PVX-410 OncoPep smoldering myeloma Phase I/II (therapeutic cancer vaccine) North Andover, MA oncopep.com

Revlimid® Celgene myeloma (newly-diagnosed and Phase III lenalidomide Summit, NJ maintenance) celgene.com (see also leukemia, lymphoma, myelodysplastic)

Janssen Biotech myeloma Phase II (anti-IL6 mAb) Horsham, PA janssenbiotech.com

SNS01-T Senesco Technologies myeloma Phase I/II (nano-encapsulated gene therapy) Bridgewater, NJ (see also lymphoma) senesco.com (Orphan Drug)

tabalumab Eli Lilly myeloma Phase II/III (BAFF antibody) Indianapolis, IN lilly.com

TG02 Tragara Pharmaceuticals myeloma Phase I (multi-kinase inhibitor) Carlsbad, CA (see also leukemia) tragarapharma.com

TH-302 EMD Serono myeloma Phase I/II (hypoxia-targeted drug) Rockland, MA (see also leukemia) emdserono.com Threshold Pharmaceuticals thresholdpharm.com South San Francisco, CA

TKI258 Novartis Pharmaceuticals myeloma Phase II (FGFR3 inhibitor) East Hanover, NJ novartis.com

Treanda® Cephalon (Teva) myeloma Phase I/II bendamustine Frazer, PA (see also leukemia, lymphoma) tevapharm.com

Zelboraf® Roche myeloma Phase II vemurafenib Nutley, NJ (BRAF V600 mutation-positive) roche.com

Zolinza® Merck myeloma Phase III Whitehouse Station, NJ merck.com

24 Medicines in Development Leukemia & Lymphoma 2013 Myeloproliferative Neoplasms

Product Name Sponsor Indication Development Phase

BMS-911543 Bristol-Myers Squibb myelofibrosis Phase I/II (JAK2 inhibitor) Princeton, NJ bms.com

imetelstat Geron essential thrombocythemia Phase II (telomerase inhibitor) Menlo Park, CA (see also myeloma) geron.com

INCB39110 InCyte myelofibrosis Phase II (JAK1 inhibitor) Wilmington, DE incyte.com

Jakafi® Incyte polycythemia vera Phase III ruxolitinib Wilmington, DE (see also hematological) incyte.com ------essential thrombocythemia Phase II incyte.com

lestaurtinib Cephalon (Teva) essential thrombocytosis, Phase II (CEP-701) Horsham, PA polycythemia vera tevapharm.com (see also leukemia)

LY2784544 Eli Lilly myeloproliferative disorders Phase II (JAK2 inhibitor) Indianapolis, IN lilly.com

momelotinib Gilead Sciences myelofibrosis Phase II (JAK inhibitor) Foster City, CA gilead.com (Orphan Drug)

NS-018 Nippon Shinyaku myelofibrosis Phase I/II (JAK2 inhibitor) Tokyo, Japan nippon-shinyaku.co.jp

pacritinib Cell Therapeutics myelofibrosis Phase III (JAK2/FLT3 inhibitor) Seattle, WA (see also lymphoma) celltherapeutics.com (Orphan Drug)

PKC412 Novartis Pharmaceuticals aggressive systemic mastocytosis Phase II (midostaurin) East Hanover, NJ (see also leukemia) novartis.com

Pomalyst® Celgene myelofibrosis Phase III pomalidomide Summit, NJ celgene.com

pracinostat MEI Pharma myelofibrosis Phase II (HDAC inhibitor) San Diego, CA (see also leukemia) meipharma.com

Medicines in Development Leukemia & Lymphoma 2013 25 Myeloproliferative Neoplasms

Product Name Sponsor Indication Development Phase

PRM-151 Promedior myelofibrosis Phase I (rhPTX-2 for injection) Lexington, MA promedior.com

SAR302503 Sanofi US myelofibrosis Phase III (JAK2 inhibitor) Bridgewater, NJ sanofi.com ------polycythemia vera, myelofibrosis Phase II (combination therapy) sanofi.com

Gilead Sciences myelofibrosis Phase II (mAb) Foster City, CA gilead.com

The content of this report has been obtained through public, government and industry sources, and the Adis “R&D Insight” data- base based on the latest information. Report current as of April 17, 2013. The medicines in this report include medicines being developed by U.S. based companies conducting trials in the United States and abroad, PhRMA-member companies conducting trials in the United States and abroad and foreign companies conducting clinical trials in the United States. The information in this report may not be comprehensive. For more specific information about a particular product, contact the individual company directly or go to www.clinicaltrials.gov. The entire series of Medicines in Development is available on PhRMA’s web site. A publication of PhRMA’s Communications & Public Affairs Department. (202) 835-3460 www.phrma.org | www.innovation.org | www.pparx.org | www.buysafedrugs.info Provided as a Public Service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association. Copyright © 2013 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper credit is given.

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26 Medicines in Development Leukemia & Lymphoma 2013 Glossary

adjunctive treatment—An auxiliary leukemia—A form of cancer in which Patients usually succumb to infections treatment that is secondary to the main abnormally growing white blood cells are or bleeding. The term “preleukemia” has treatment. scattered throughout the body and bone been used to describe these disorders. marrow. They can take over the marrow adjuvant—A substance or drug that aids and prevent it from making enough nor- myeloma—A malignant condition of another substance in its action. mal blood cells (white, red and platelets), middle to old age, characterized by the leaving the patient highly susceptible to uncontrolled proliferation and disordered allogeneic—Refers to having cell types serious infections, anemia and bleeding function of plasma cells in the bone that are distinct and cause reactions in episodes. The cells can also spill into the marrow. The condition, which makes the the immune system. blood, infiltrating and interfering with the patient particularly prone to infection, is rare, with about three new cases annu- application submitted—An application function of other organs. The four main ally per 100,000 population. Relapsed for marketing has been submitted by the types of leukemia are: acute lympho- myeloma, also called recurrent myeloma, company to the Food and Drug Admin- blastic leukemia (ALL), acute myeloid is multiple myeloma that returns after a istration (FDA). leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid successful course of treatment. Refrac- B-cell—A class of white blood cells im- leukemia (CML). The acute types have tory myeloma is multiple myeloma that portant to the body’s immune system. a rapid onset, and overwhelming infec- does not respond to treatment—whether tion or blood loss can cause death. The initial therapy or therapy for recurrent Fast Track—A process designed to chronic forms progress much more slowly. disease. Smoldering multiple myeloma facilitate the development and expedite refers to early disease without any symp- the review of drugs to treat serious lymphoma—Cancers in which the cells toms. For example, there is no bone diseases and fill an unmet medical need. of lymphoid tissue, found mainly in damage. The status is assigned by the U.S. Food the lymph nodes and spleen, multiply and Drug Administration. The purpose unchecked. Lymphomas fall into two myeloproliferative neoplasms (MPN)— is to get important new drugs to the categories: Hodgkin disease, character- Types of blood cancer that begin with patient earlier. Fast Track addresses a ized by a particular kind of abnormal cell, an abnormal mutation (change) in a broad range of serious diseases. Gener- and non-Hodgkin lymphomas, which stem cell in the bone marrow. That ally, determining factors include whether vary in their malignancy according to the change leads to an overproduction of the drug will have an impact on such nature and activity of the abnormal cells. any combination of white cells, red cells factors as survival, day-to-day function- Mantle cell lymphoma is a type of non- and platelets. Such blood cancers include ing, or the likelihood that the disease, if Hodgkin lymphoma. myelofibrosis, polycythemia vera, and left untreated, will progress from a less essential thrombocythemia. severe condition to a more serious one. mAb (monoclonal antibodies)—Large Orphan Drug—A drug to treat a dis- Filling an unmet medical need is defined protein molecules produced by white ease that has a patient population of as providing a therapy where none exists blood cells that seek out and destroy 200,000 or less in the United States, or or providing a therapy which may be harmful foreign substances. a disease that has a patient population potentially superior to existing therapy. macroglobulinemia—A disorder in which of more than 200,000 and a develop- Once a drug receives Fast Track designa- plasma cells produce an excessive quan- ment cost that will not be recovered tion, early and frequent communication tity of macroglobulins (large antibodies) from sales in the United States. between the FDA and a drug company is that accumulate in the blood. It results encouraged throughout the entire drug from a group of abnormal, cancerous Phase 0—First-in-human trials conduct- development and review process. The lymphocytes and plasma cells. Men are ed in accordance with FDA’s 2006 guid- frequency of communication assures that affected more often than women, and ance on exploratory Investigational New questions and issues are resolved quickly, the average age at onset is 65. Drug (IND) studies designed to speed often leading to earlier drug approval up development of promising drugs by and access by patients. myeloablation—A severe form of establishing very early on whether the myelosuppression, activity is decreased, agent behaves in human subjects as was hematological malignancies— resulting in fewer red blood cells, white anticipated from preclinical studies. Cancers of the blood or blood-forming blood cells, and platelets. It is a side ef- tissues, such as leukemia, Hodgkin and fect of some cancer treatments. Phase I—Researchers test the drug in a non-Hodgkin lymphomas, AIDS-related small group of people, usually between malignancies, myeloma, myelodysplasia myelodysplastic syndromes (MDS)— 20 and 80 healthy adult volunteers, to and myeloproliferative disorders. Blood disorders that ultimately are fatal. evaluate its initial safety and tolerability

Medicines in Development Leukemia & Lymphoma 2013 27 Glossary

profile, determine a safe dosage range, and effectiveness. They are the longest when patients still have some cancer cells and identify potential side effects. studies, and usually take place in multiple in their bone marrow after treatment. sites around the world. Phase II—The drug is given to volun- Smoldering—See preleukemia. teer patients, usually between 100 and preleukemia—A condition in which the 300, to see if it is effective, identify an bone marrow does not produce enough T-cell—One of two main classes of white optimal dose, and to further evaluate its blood cells. This condition may progress blood cells called lymphocytes, which are short-term safety. to become acute leukemia. Preleukemia important to the body’s disease-fighting also is called myelodysplastic syn- immune system. Phase III—The drug is given to a larger, dromes or smoldering leukemia. more diverse patient population, often thrombocytopenia—A reduction in the involving between 1,000 and 3,000 Relapsed/Refractory—Relapsed is a number of platelet cells in the blood, patients (but sometime many more condition when cancer cells return to a which causes a tendency to bleed, espe- thousands), to generate statistically patient’s bone marrow following treat- cially from the smaller blood vessels. significant evidence to confirm its safety ment, while refractory is a condition

28 Medicines in Development Leukemia & Lymphoma 2013 The Drug Discovery, Development and Approval Process

Developing a new medicine takes an average of 10-15 years; For every 5,000-10,000 compounds in the pipeline, only 1 is approved.

Drug Discovery and Development: A LONG, RISKY ROAD

DRUG DISCOVERY PRECLINICAL CLINICAL TRIALS FDA REVIEW LG-SCALE MFG Y

5,000–10,000 250 5 VEILLANCE ONE FDA-

VER COMPOUNDS APPROVED O DRUG

PHASE PHASE PHASE ARKETING SUR 1 2 3 -M ST NUMBER OF VOLUNTEERS PRE-DISC 20–80 100–300 1,000–3,000 A SUBMITTED 0.5–2 IND SUBMITTE D 3–6 YEARS6–7 YEARS ND

YEARS PHASE 4: PO The Drug Development and Approval Process The U.S. system of new drug approvals is in people. The IND shows results of previous ate statistically significant evidence to confirm perhaps the most rigorous in the world. experiments; how, where and by whom the new its safety and effectiveness. They are the lon- studies will be conducted; the chemical structure gest studies, and usually take place in multiple It takes 10-15 years, on average, for an experi- of the compound; how it is thought to work in sites around the world. mental drug to travel from lab to U.S. patients, the body; any toxic effects found in the animal according to the Tufts Center for the Study of New Drug Application (NDA)/Biologic License studies; and how the compound is manufac- Drug Development. Only five in 5,000 com- Application (BLA). Following the completion tured. All clinical trials must be reviewed and ap- pounds that enter preclinical testing make it to of all three phases of clinical trials, a company proved by the Institutional Review Board (IRB) human testing. And only one of those five is analyzes all of the data and files an NDA or BLA where the trials will be conducted. Progress approved for sale. with FDA if the data successfully demonstrate reports on clinical trials must be submitted at both safety and effectiveness. The applications On average, it costs a company $1.2 billion, least annually to FDA and the IRB. contain all of the scientific information that the including the cost of failures, to get one new Clinical Trials, Phase I—Researchers test the company has gathered. Applications typically medicine from the laboratory to U.S. patients, drug in a small group of people, usually between run 100,000 pages or more. according to a recent study by the Tufts Center 20 and 80 healthy adult volunteers, to evaluate for the Study of Drug Development. Approval. Once FDA approves an NDA or BLA, its initial safety and tolerability profile, deter- the new medicine becomes available for physi- Once a new compound has been identified in mine a safe dosage range, and identify potential cians to prescribe. A company must continue the laboratory, medicines are usually developed side effects. to submit periodic reports to FDA, including as follows: Clinical Trials, Phase II—The drug is given any cases of adverse reactions and appropriate Preclinical Testing. A pharmaceutical company to volunteer patients, usually between 100 and quality-control records. For some medicines, conducts laboratory and animal studies to show 300, to see if it is effective, identify an optimal FDA requires additional trials (Phase IV) to biological activity of the compound against the dose, and to further evaluate its short-term evaluate long-term effects. targeted disease, and the compound is evalu- safety. Discovering and developing safe and effective ated for safety. Clinical Trials, Phase III—The drug is given to a new medicines is a long, difficult, and expensive Investigational New Drug Application (IND). larger, more diverse patient population, often process. PhRMA member companies invested an After completing preclinical testing, a com- involving between 1,000 and 3,000 patients estimated $48.5 billion in research and develop- pany files an IND with the U.S. Food and Drug (but sometime many more thousands), to gener- ment in 2012. Administration (FDA) to begin to test the drug