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PRESENTED BY AMERICA’S BIOPHARMACEUTICAL RESEARCH COMPANIES BIOPHARMACEUTICALRESEARCH AMERICA’S BY PRESENTED Cancer MEDICINES IN DEVELOPMENT MEDICINES Some medicines are listed in more than one in more listed are Some medicines category. Medicines in Development for for in Development Medicines Cancer Br Key Issues

• A monoclonal antibody for non-small-cell lung cancer that blocks a signaling pathway allowing for immune responses that can recognize and destroy cancer cells;

• A medicine that targets and disrupts a signaling pathway associated with tumor growth in stomach cancer.

The development of new therapies would not be possible without the patients who volunteer to participate in clinical trials. Currently, there are 3,137 active clinical trials for cancer in the United States. Of those, 1,824 are now seeking volunteers to participate or have not yet started recruiting patients; the other 1,313 are ongoing but are not currently recruiting new patients.*

The progress made against cancer has resulted in better treatments that help extend lives, improve patients’ quality of life, and increase productivity contributing to economic growth. The hundreds of medicines being developed are our best hope for continuing that progress and lessening the burden of cancer. However, researching and developing new medicines remains a risky investment and a lengthy process. On average, it costs $1.2 billion and takes between 10–15 Medicines and Vaccines in years to bring a new, effective medicine to patients. Despite Development to Treat Cancer those risks, America’s biopharmaceutical research companies are continuing their efforts to develop effective new therapies Many of the medicines in the pipeline today are using for the prevention and treatment of cancer. novel approaches to attack cancer at the molecular level. Approximately 80 percent of cancer pipeline drugs are potentially fi rst-in-class treatments, according to the Tufts Center for the Study of Drug Development. Among the 771 medicines and vaccines in development are potential treatments for:

Colorectal Cancer—A humanized monoclonal antibody in development for metastatic colorectal cancer targets the cell surface protein “endosialin,” which is expressed on cells that are part of the tumor blood vessel structure. In preclinical studies, blocking the function of endosialin inhibited tumor growth and metastases.

Liver Cancer—A medicine in development for hepatocellular carcinoma (liver cancer) is a small molecule kinase inhibitor designed to selectively block transforming growth factor-beta (TGF-beta) signaling. The overexpression of TGF-beta in cells may enhance tumor growth and intensify metastases.

*Source: www.clinicaltrials.gov, search performed 9/25/2014. Search criteria: cancer, United States, Phase 0, 1, 2, 3; industry only; excluding unknown status.

2 Medicines in Development Cancer 2014 Key Issues

Lung Cancer—A fully human monoclonal antibody in thought to play a role in tumor growth and metastases in development for non-small-cell lung cancer targets the many cancers, including stomach cancer. An exploratory PD-1 (programmed death-1) checkpoint receptor which is biomarker analysis found that the addition of the medicine to expressed on activated T-cells. Cancer cells may exploit chemotherapy improved median overall survival in patients the checkpoint pathway to hide from the immune system with tumors that expressed high levels of MET protein. and protect the tumor. Blocking this pathway may allow for immune responses that recognize and destroy cancer cells. Another medicine which blocks the PD-1 receptor was “ ere is no question that when we talk recently approved by FDA for the treatment of malignant melanoma. about turning the tide against cancer, the most exciting opportunities, Pancreatic Cancer—In malignant solid tumors, oxygen levels are often low (called tumor hypoxia) relative to oxygen levels the new opportunities in fact, are in healthy tissue. Tumor hypoxia is associated with tumor understanding the biology and progression, metastases, and resistance to chemotherapy applying that biology to new treatments. and radiation treatment. A medicine in development is We are certainly at a turning point.” activated when it reaches the hypoxic region of the tumor environment where it eventually kills tumor cells in its vicinity. —J. Leonard Lichtenfeld, M.D., American Cancer Society The medicine is also being tested in patients with soft tissue sarcoma.

Stomach Cancer—A monoclonal antibody in testing for Advances in Cancer Treatment stomach cancer with high MET (mesenchymal-epithelial As we continue to advance cancer treatment, progress can transition factor) expression is designed to inhibit hepatocyte be seen in declining death rates from cancer and increases in growth factor (HGF)/scatter factor from binding to the cancer survivors. According to the ACS, the death rate from c-MET receptor. The HGF/c-Met signaling pathway is cancer has been steadily declining since the 1970s—declining more than 15 percent in the period from 2000-2011 alone. Five-year survival rates have increased 39 percent across all cancer types since 1975, with 2 out of 3 people diagnosed with cancer surviving at least fi ve years.

To sustain this progress in an environment of increasing pressure to contain health care costs, it is important to understand the valuable role new medicines play in improving patient outcomes. According to the ACS, 83 percent of survival gains are attributable to new treatments, including medicines. Some key advances in treatment include:

Personalized Medicines—Personalized medicines are therapeutics that are tailored to individual patients based on certain biologic and physiologic characteristics, such as genetic makeup. Patients can be identifi ed by their susceptibility to a certain disease or how they will likely respond to a specifi c therapy. By targeting therapies to patients most likely to benefi t, personalized medicines represent an important tool, as they may reduce the use of

Medicines in Development Cancer 2014 3 Key Issues

Targeted Therapies—Targeted therapies are designed to HOW CANCER COULD ECHO interfere with specifi c molecular targets involved in cancer cell growth or progression, whereas traditional chemotherapy HIV SUCCESS acts against all rapidly dividing cells, including healthy ones. Innovations in cancer treatment could echo the Several targeted therapies have been approved for use by success we have seen in HIV/AIDS treatment. the FDA. According to IMS Health, the role of targeted therapies in oncology treatment has grown from 11 percent in Advances in medicines for HIV/AIDS have 2003 to 46 percent in 2013. helped lower the death rate by 83 percent since the disease was fi rst recognized in 1981. Prior to Therapeutic Cancer Vaccines—In the late 1990s, scientists began experimenting with new vaccines that could harness 1995, when the fi rst antiretroviral medicine was the power of the immune system to fi ght cancer rather approved by the FDA, an HIV diagnosis was than to prevent it. One type of therapeutic vaccine, called a death sentence. Now, thanks to medicines autologous cellular immunotherapy, takes a patient’s own developed by biopharmaceutical scientists and immune cells and reprograms them to attack the cancer. The their research partners, it is a chronic condition fi rst and only therapeutic cancer vaccine was approved by the FDA in 2010 to treat metastatic prostate cancer. with manageable costs, and patients are able to reach nearly full life expectancy. Preventive Vaccines—Preventive vaccines target viruses or other infectious agents that can cause or contribute to the development of cancer. They are intended to prevent people from being infected with those viruses and agents so that unnecessary and often costly treatments or procedures in they do not develop cancer. For example, nearly all cases of patients who are unlikely to benefi t from them. Innovative cervical cancer can be attributed to human papillomavirus personalized medicines make up 12 to 50 percent of the (HPV), with two HPV subtypes (types 16 and 18) alone pipeline for all diseases, according to the Tufts Center for the causing 70 percent of cervical cancer cases. The FDA has Study of Drug Development.

4 Medicines in Development Cancer 2014 “ We used to think HIV costs would overwhelm us…but we  gured it out and let drug development progress… similarly, cancer care will evolve.” —Ira Klein, M.D., M.B.A., FACP, Aetna

approved vaccines to prevent infection by HPV types 16 and 18 and vaccines to prevent hepatitis B virus, which can cause liver cancer. Value in Cancer Care in the United States

New cancer medicines bring tremendous value to cancer patients and the U.S. health care system. Medicines are an important part of cancer treatment but represent just a small portion of all cancer costs. When compared to total

Medicines in Development By Disease and Phase Some medicines are listed in more than one category.

Bladder Cancer 18 Application Brain Cancer 47 Submitted Breast Cancer 73 Phase III Colorectal Cancer 46 Phase II Head/Neck Cancer 19 Phase I Hematological Malignancies 63 Kidney Cancer 24 Leukemia 87 Liver Cancer 37 Lung Cancer 98 Lymphoma 78 Myeloma 33 Ovarian Cancer 48 Pancreatic Cancer 39 Prostate Cancer 45 Sarcoma 11 Skin Cancer 56 Solid Tumors 213 Stomach Cancer 24 Other Cancers 36 Unspecified Cancer 53

Medicines in Development Cancer 2014 5

health care spending, cancer care represents an even smaller portion of costs.

• Spending on cancer medicines represents less than 1 percent of all health care spending for all diseases —$25.9 billion out of $2,800 billion.1

• Cancer medicines represent 20 percent of total spending on cancer care.2

• Between 1988 and 2000, 23 million years of life were saved due to cancer treatment advances. During that time, the United States realized $1.9 trillion in value due to improved productivity, extended life, and other factors resulting from improved cancer treatment.3

• On average, privately insured cancer patients pay out-of-pocket more than 20 percent of their total prescription drug costs, compared to 4 percent of inpatient hospital care and 7 percent of outpatient care.4

Sources: 1. IMS Institute for Healthcare Informatics, “Declining Medicine Use and Costs: For Better or Worse? A Review of the Use of Medicines in the United States in 2012.” 2. K. Fitch et al, “Benefi t Designs for High Cost Research Collaboration: Medical Conditions,” Milliman Research Report. 3. Lakdawalla et al, “An Economic Evaluation of the War on Cancer,” Journal of Health Economics. Public-Private Partnerships 4. PhRMA analysis based on Medical Expenditure Panel Survey (MEPS). As scientists probe deeper into the causes and signs of cancer, the amount of information has increased exponentially, and making sense of all the data is a colossal undertaking that no single individual or institution can handle alone.

As a result, biopharmaceutical research companies are working together and with academic medical centers, government, and non-profi t organizations to share, organize and make sense of huge volumes of information. Below are examples of collaboration to advance progress against cancer.

The Cancer Genome Atlas (TCGA) is a project to create a catalog (or atlas) of genomic changes associated with specifi c types of tumors to improve the prevention, diagnosis, and treatment of cancer through the collection and analysis of tissue samples. Sponsored by the National Cancer Institute and the National Human Genome Research Institute, the TCGA network includes scientists, bioinformaticians, bioethicists, doctors, nurses, advocates, and others. TCGA is currently focused on 32 tumor types, including nine rare cancers.

6 Medicines in Development Cancer 2014 Lung-MAP (Lung Cancer Master Protocol) is a effective in which patients and at a reduced cost. I-SPY 2 is multi-drug, multi-arm, biomarker-driven clinical trial focused focused on women with newly diagnosed, locally-advanced on developing new treatments for lung cancer. The trial breast cancer and will test whether adding investigational will recruit patients with advanced squamous cell lung drugs to standard chemotherapy is better than standard cancer, which represents approximately 25 percent of all chemotherapy alone prior to having surgery. lung cancers, from more than 500 medical centers in the is committed to improving United States. Unlike traditional clinical trials, Lung-MAP The CEO Roundtable on Cancer the health of employees and making progress against uses advanced molecular screening to match patients cancer. The Roundtable is comprised of executives from to an investigational treatment targeted to the genetic diverse American corporations, nonprofi t organizations alterations driving their cancer. Lung-MAP is a joint effort by fi ghting cancer, and National Cancer Institute-designated government, biopharmaceutical companies, patient advocacy cancer centers. Programs initiated by the Roundtable groups, and research institutions designed to improve clinical include the CEO Cancer Gold Standard, a workplace-based trial effi ciency and make new targeted therapies in lung wellness accreditation program that provides a framework cancer available as quickly and safely as possible. for employers to lower the risk of cancer, detect it early, I-SPY 2 is a research collaboration among the Biomarkers and ensure access to high-quality care. The Life Sciences Consortium, the FDA, the U.S. National Institutes of Health, Consortium brings together leading biopharmaceutical and biopharmaceutical companies. I-SPY 2 uses genetic research companies focused on cancer in collaboration to and biological markers from individual patient tumors and effectively deliver new medicines to prevent and treat cancer adaptive clinical trial design to develop new breast cancer and continue the emerging understanding of cancer biology. medicines quicker by identifying which ones are most

RESEARCHING CANCER MEDICINES: SETBACKS AND STEPPING STONES With the many advances made in cancer research, there are also setbacks. Researchers are discovering that cancer is actually a set of more than 200 extremely complex diseases. Finding medicines that effectively treat each one is an immense challenge. The path to new oncology drugs is littered with so-called failures that do not make it through human clinical trials to approval. Although it is very disappointing to see a promising drug candidate cut from the pipeline, researchers learn from every setback and build upon each one of them to achieve success with future research and get effective therapies to patients. A new PhRMA report looks at setbacks and approvals in melanoma, brain cancer and lung cancer between 1998 and 2014: • Researchers have had recent successes in treating melanoma with the approval of seven new medicines, building on 96 medicines that didn’t make it through clinical trials. • There has been progress against some subsets of lung cancer, but the disease remains deadly. Ten lung cancer medicines were approved, while another 167 potential medicines failed in clinical testing. • Brain cancer continues to be a diffi cult cancer to treat despite concentrated research. There were three approvals and 75 unsuccessful candidate medicines. Although these setbacks are valuable to researchers, they are also an indication of the diffi culty in developing medicines to treat cancer. These setbacks serve as a reminder that to make progress, we need a public policy framework that supports the drug development process as well as the promising science so that important innovations can reach patients.

Medicines in Development Cancer 2014 7 Facts

Facts About Cancer in the United States

Overview

• Cancer is the second leading cause of death by disease— • Pancreatic cancer is the fourth leading cause of cancer nearly 1 of every 4 deaths—in the United States, death. The average survival rate from pancreatic cancer exceeded only by heart disease.1 is low, in part because it is diffi cult to detect early. It is most frequently diagnosed among people aged 75-84.2 • Men have slightly less than a 1 in 2 lifetime risk of developing cancer; for women, the risk is a little more • Stomach cancer accounts for 1.3 percent of all new than 1 in 3. Approximately 77 percent of all cancers are cancer cases and mostly affects older people with an diagnosed in people ages 55 and older.1 average age of diagnosis at 69. Approximately 60 percent of people diagnosed with stomach cancer each • This year alone, more than 1.6 million new cancer cases year are age 65 or older.2 are expected to be diagnosed, and an estimated 585,720 people are expected to die of cancer.1 • Liver cancer and intrahepatic bile duct cancer is the seventh leading cause of cancer death. It is also more • Approximately 13.7 million Americans with a history of common among Asian/Pacifi c Islander and American cancer were alive in January 2012.1 The 5-year survival Indian/Alaska Native populations.2 rate for all cancers diagnosed between 2004 and 2010 is 66 percent, up from 49 percent in the mid-70s.2 • In 2014, an estimated 10,450 new cases of cancer will be diagnosed and 1,350 cancer deaths will occur in children • Lung cancer is the leading cause of cancer death in ages 0-14. Among adolescents ages 15-19, 5,330 new both men and women. An estimated 159,260 deaths, cases will be diagnosed and 610 deaths will occur.1 accounting for about 27 percent of all cancer deaths, are expected to occur in 2014. From 2006 to 2010, rates • The most common cancers among children are decreased 2.9 percent per year in men and 1.4 percent acute lymphoblastic leukemia (26 percent), brain and per year in women.1 central nervous system (CNS) cancers (21 percent), neuroblastoma (7 percent), and non-Hodgkin lymphoma • Colorectal cancer is the second leading cause of cancer (6 percent).1 death and accounts for 8.2 percent of all new cancer cases. It is more common in men than in women, and • Among adolescents the most common cancers are more common in African Americans.2 Hodgkin lymphoma (15 percent), thyroid carcinoma (11 percent), brain and CNS cancers (10 percent), and • Prostate cancer is the second leading cancer cause of testicular germ cell tumors (8 percent).1 death in men with nearly 30,000 deaths estimated this year. Prostate cancer death rates have been decreasing since the early 1990s in men of all races/ethnicities, Costs though they remain more than twice as high in African Americans as in any other ethnicity.1 • Although extraordinary advances are being made against cancer, the disease remains a major health care • An estimated 40,430 breast cancer deaths are expected in 2014, with men accounting for 430 of those. Breast challenge and a huge fi nancial burden, both nationally 3 cancer is the second cause of cancer death in women. and internationally. From 2006 to 2010, rates decreased 3.0 percent per • The National Institutes of Health (NIH) estimates the year in women under age 50 and 1.8 percent per year overall costs for cancer in 2009 at $216.6 billion: in women 50 and older. The decrease in breast cancer $86.6 billion for direct medical costs (total of all health death rates represents improvements in early detection and treatment, and possibly decreased incidence.1 expenditures) and $130 billion for indirect mortality costs (cost of lost productivity due to premature death).3 • This year nearly 300,000 new cases of gastrointestinal cancer will be diagnosed and nearly 150,000 deaths will • Globally, 12.9 million new cancer cases cost $286 billion occur in the United States.2 in 2009. In 2030, the 21.5 million projected new cancer cases will cost the world economy $458 billion.3

8 Medicines in Development Cancer 2014 Facts

New Cancer Cases/Deaths 1

Cancer Type Estimated 2014 New Cases Estimated 2014 Deaths

All Sites ...... 1,665,540 ...... 585,720 Male ...... 855,220 ...... 310,010 Female ...... 810,320 ...... 275,710

Acute Lymphocytic Leukemia ...... 6,020 ...... 1,440 Male ...... 3,140 ...... 810 Female ...... 2,880 ...... 630

Acute Myeloid Leukemia ...... 18,860 ...... 10,460 Male ...... 11,530 ...... 6,010 Female ...... 7,330 ...... 4,450

Bladder Cancer ...... 74,690 ...... 15,580 Male ...... 56,390 ...... 11,170 Female ...... 18,300 ...... 4,410

Brain Cancer (and other nervous system) ...... 23,380 ...... 14,320 Male ...... 12,820 ...... 8,090 Female ...... 10,560 ...... 6,230

Breast Cancer ...... 235,030 ...... 40,430 Male ...... 2,360 ...... 430 Female ...... 232,670 ...... 40,000

Cervical and Uterine Cancers ...... 64,990 ...... 12,610 Male ...... — ...... — Female ...... 64,990 ...... 12,610

Chronic Lymphocytic Leukemia ...... 15,720 ...... 4,600 Male ...... 9,100 ...... 2,800 Female ...... 6,620 ...... 1,800

Chronic Myeloid Leukemia ...... 5,980 ...... 810 Male ...... 3,130 ...... 550 Female ...... 2,850 ...... 260

table continued on next page

Medicines in Development Cancer 2014 9 Facts

New Cancer Cases/Deaths 1 (continued)

Cancer Type Estimated 2014 New Cases Estimated 2014 Deaths

Colorectal Cancer ...... 136,830 ...... 50,310 Male ...... 71,830 ...... 26,270 Female ...... 65,000 ...... 24,040

Esophageal Cancer ...... 18,170 ...... 15,450 Male ...... 14,660 ...... 12,450 Female ...... 3,510 ...... 3,000

Kidney Cancer ...... 63,920 ...... 13,860 Male ...... 39,140 ...... 8,900 Female ...... 24,780 ...... 4,960

Leukemia (all types) ...... 52,380 ...... 24,090 Male ...... 30,100 ...... 14,040 Female ...... 22,280 ...... 10,050

Liver Cancer (and bile duct) ...... 33,190 ...... 23,000 Male ...... 24,600 ...... 15,870 Female ...... 8,590 ...... 7,130

Lung Cancer (and bronchus) ...... 224,210 ...... 159,260 Male ...... 116,000 ...... 86,930 Female ...... 108,210 ...... 72,330

Lymphoma (all types) ...... 79,990 ...... 20,170 Male ...... 43,340 ...... 11,140 Female ...... 36,650 ...... 9,030

Melanoma-Skin Cancer ...... 76,100 ...... 9,710 Male ...... 43,890 ...... 6,470 Female ...... 32,210 ...... 3,240

Myeloma ...... 24,050 ...... 11,090 Male ...... 13,500 ...... 6,110 Female ...... 10,550 ...... 4,980

Non-Hodgkin Lymphoma ...... 70,800 ...... 18,990 Male ...... 38,270 ...... 10,470 Female ...... 32,530 ...... 8,520

table continued on next page

10 Medicines in Development Cancer 2014 Facts

New Cancer Cases/Deaths 1 (continued)

Cancer Type Estimated 2014 New Cases Estimated 2014 Deaths

Ovarian Cancer ...... 21,980 ...... 14,270 Male ...... — ...... — Female ...... 21,980 ...... 14,270

Pancreatic Cancer ...... 46,420 ...... 39,590 Male ...... 23,530 ...... 20,170 Female ...... 22,890 ...... 19,420

Prostate Cancer ...... 233,000 ...... 29,480 Male ...... 233,000 ...... 29,480 Female ...... — ...... —

Stomach Cancer ...... 22,220 ...... 10,990 Male ...... 13,730 ...... 6,720 Female ...... 8,490 ...... 4,270

Thyroid Cancer ...... 62,980 ...... 1,890 Male ...... 15,190 ...... 830 Female ...... 47,790 ...... 1,060

Sources:

1. Cancer Facts & Figures 2014, American Cancer Society, www.cancer.org

2. National Cancer Institute, www.cancer.gov

3. AACR Cancer Progress Report 2014, American Association for Cancer Research, www.cancerprogressreport.org

Medicines in Development Cancer 2014 11 Medicines and Vaccines in Development for Cancer

Bladder Cancer

Product Name Sponsor Indication Development Phase*

ABI-009 Aadi non-muscle invasive bladder cancer Phase I/II (nanoparticle albumin-bound Paci c Palisades, CA mTOR inhibitor)

ALT-801 Altor BioScience advanced bladder cancer, non-muscle Phase II (immunotherapy-fusion protein) Miramar, FL invasive bladder cancer www.altorbioscience.com

ALT-803 Altor BioScience non-muscle invasive bladder cancer Phase I/II (IL-15 superagonist complex) Miramar, FL (see also hematological, myeloma, www.altorbioscience.com skin)

apatorsen OncoGenex Pharmaceuticals metastatic bladder cancer Phase II (Hsp27 inhibitor) Bothell, WA (see also lung, pancreatic, prostate) www.oncogenex.com

apaziquone Spectrum Pharmaceuticals non-muscle invasive bladder cancer Phase III (DNA synthesis inhibitor) Henderson, NV (Fast Track) www.sppirx.com

ASG-15ME Agensys bladder cancer Phase I (antibody drug conjugate) Santa Monica, CA www.agensys.com Seattle Genetics www.seattlegenetics.com Bothell, WA

CG0070 Cold Genesys non-muscle invasive bladder cancer Phase II/III (oncolytic virus therapy) Newport Beach, CA www.coldgenesys.net

CV-301 Bavarian Nordic bladder cancer Phase II completed (targeted immunotherapy) Mountain View, CA (see also breast, colorectal) www.bavarian-nordic.com

Cynviloq™ Sorrento Therapeutics bladder cancer Phase II paclitaxel polymeric micelle San Diego, CA (see also breast, lung, ovarian, www.sorrentotherapeutics.com for injection pancreatic)

Cyramza® Lilly bladder cancer Phase II ramucirumab Indianapolis, IN (see also breast, colorectal, liver, lung, www.lilly.com ovarian, solid tumors, stomach)

instiladrin FKD Therapies super cial bladder cancer Phase II (gene therapy) Kuopio, Finland

Keytruda® Merck bladder cancer Phase I pembrolizumab Whitehouse Station, NJ (see also breast, head/neck, www.merck.com hematological, kidney, lung, myeloma, stomach)

*For more information about a specifi c medicine or company in this report, please use the website provided.

12 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancer

Bladder Cancer

Product Name Sponsor Indication Development Phase*

MAGE-A3 immunotherapeutic GlaxoSmithKline bladder cancer Phase II (recombinant antigen-speci c Research Triangle Park, NC www.gsk.com cancer immunotherapeutic)

mocetinostat Mirati Therapeutics bladder cancer Phase II (HDAC inhibitor) San Diego, CA (see also hematological, lymphoma) www.mirati.com

mycobacterium cell wall-DNA Bioniche Life Sciences refractory non-muscle invasive Phase II complex (MCNA) Belleville, Canada bladder cancer www.bioniche.com

RG7446 Genentech metastatic urothelial bladder cancer Phase II (anti-PD-L1 mAb) South San Francisco, CA (Breakthrough Therapy) www.gene.com (see also kidney, lung, skin)

TMX-101 Telormedix bladder cancer Phase II (TLR7 agonist) Bioggio, Switzerland www.telormedix.com

vesigenurtacel-L Heat Biologics bladder cancer Phae I/II (cancer immunotherapy) Durham, NC www.heatbio.com

Brain Cancer

Product Name Sponsor Indication Development Phase

2B3-101 to-BBB technologies brain metastases, recurrent malignant Phase II (doxorubicin liposomal) Leiden, Netherlands glioma www.tobbb.com ORPHAN DRUG

ABT-414 AbbVie glioblastoma multiforme Phase I (antibody drug conjugate) North Chicago, IL (see also solid tumors) www.abbvie.com ORPHAN DRUG

ADU-623 Aduro Biotech glioblastoma Phase I (bivalent Listeria-based Berkeley, CA www.adurobiotech.com immunotherapy)

aldoxorubicin CytRx glioblastoma multiforme Phase II (delivery-enhanced doxorubicin) Los Angeles, CA (see also lung, sarcoma) www.cytrx.com

AMG 595 Amgen advanced malignant glioma, Phase I (tubulin inhibitor) Thousand Oaks, CA anaplastic astrocytomas, www.amgen.com glioblastoma multiforme

ANG1005 Angiochem brain metastases, malignant glioma Phase II (targeted taxane derivative) Montreal, Canada (Fast Track) www.angiochem.com ORPHAN DRUG

Medicines in Development Cancer 2014 13 Medicines and Vaccines in Development for Cancer

Brain Cancer

Product Name Sponsor Indication Development Phase

antineoplaston Burzynski Research Institute glioma (combination therapy) Phase II ORPHAN DRUG Houston, TX www.burzynskiresearch.com

Avastin® Genentech glioblastoma multiforme (1st-line) Phase III completed bevacizumab South San Francisco, CA (see also lung, ovarian, other) www.gene.com

Azedra® Progenics Pharmaceuticals paraganglioma, malignant Phase II iobenguane I-131 Tarrytown, NY pheochromocytoma www.progenics.com ORPHAN DRUG (Fast Track)

BGJ398 Novartis Pharmaceuticals glioblastoma Phase II (FGF-R kinase inhibitor) East Hanover, NJ (see also hematological, liver, solid www.novartis.com tumors)

cancer gene therapy Advantagene anaplastic astrocytoma, Phase I/II (AdV-tK) Auburndale, MA glioblastoma, malignant glioma, www.advantagene.com recurrent ependymoma (see also pancreatic, prostate)

CPP-1X Cancer Prevention Pharmaceuticals neuroblastoma Phase II (e ornithine) Tucson, AZ (see also colorectal) www.canprevent.com

crenolanib AROG Pharmaceuticals glioma (pediatric) Phase I (PDGFR inhibitor) Dallas, TX (see also stomach) www.arogpharma.com ORPHAN DRUG

CTO Tactical Therapeutics glioma (combination therapy) Phase II (multiple oncokinase inhibitor) New York, NY (Fast Track) www.tacticaltherapeutics.com

DCVax®-L Northwest Biotherapeutics glioblastoma multiforme Phase III dendritic cell vaccine Bethesda, MD www.nwbio.com

DM-CHOC-PEN DEKK-TEC brain tumors Phase II New Orleans, LA www.dekk-tec.com

DNX-2401 DNAtrix recurrent glioblastoma Phase I (cell death stimulant) Houston, TX (Fast Track) www.dnatrix.com

E7080 Eisai glioma Phase II (multi-targeted kinase inhibitor) Woodcli Lake, NJ (see also liver, lung, skin, other) www.eisai.com

EGFRvIII CAR Kite Pharma glioblastoma Phase I/II (chimeric antigen receptor) Santa Monica, CA www.kitepharma.com National Cancer Institute Bethesda, MD

ERC-1671 Epitopoietic Research glioblastoma, gliosarcoma Phase II (cancer vaccine) Les Isnes, Belgium www.ercbelgium.com ORPHAN DRUG

14 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancer

Brain Cancer

Product Name Sponsor Indication Development Phase

G-202 GenSpera glioblastoma multiforme Phase II (calcium-transporting ATPase San Antonio, TX (see also liver, prostate) www.genspera.com inhibitor)

galunisertib Lilly glioblastoma, glioma Phase II (TGF-beta1 inhibitor) Indianapolis, IN (see also liver, pancreatic) www.lilly.com

heat shock protein vaccine Agenus recurrent glioblastoma multiforme, Phase II ORPHAN DRUG Lexington, MA newly diagnosed glioma www.agenusbio.com (see also skin)

ICT-107 ImmunoCellular Therapeutics glioblastoma (1st-line) Phase II (dendritic cell-based vaccine) Calabasas, CA www.imuc.com ORPHAN DRUG

ICT-121 ImmunoCellular Therapeutics recurrent glioblastoma Phase I (dendritic cell vaccine) Calabasas, CA www.imuc.com

KPT-330 Karyopharm Therapeutics glioblastoma multiforme Phase II (XPO1 inhibitor) Newton, MA (see also leukemia, prostate, solid www.karyopharm.com tumors, other)

KX02 Kinex Pharmaceuticals glioma Phase I Bu alo, NY www.kinexpharma.com

LDE225 Novartis Pharmaceuticals medulloblastoma Phase II (SMO protein inhibitor) East Hanover, NJ (see also skin, solid tumors) www.novartis.com

macitentan Actelion Pharmaceuticals glioblastoma Phase I South San Francisco, CA www.actelion.com

mibefradil Cavion recurrent high-grade glioma Phase I (t-type calcium channel Charlottesville, VA www.cavion.com antagonist) ORPHAN DRUG

mipsagargin GenSpera glioblastoma multiforme Phase II (ATPase inhibitor) San Antonio, TX (see also liver, prostate) www.genspera.com

MM-398 Merrimack Pharmaceuticals glioma Phase III (irinotecan nanotherapeutic) Cambridge, MA (see also colorectal, pancreatic) www.merrimackpharma.com

nivolumab Bristol-Myers Squibb glioblastoma Phase II (PD-1 inhibitor) Princeton, NJ (see also colorectal, head/neck, www.bms.com hematological, kidney, liver, lung, lymphoma, skin, solid tumors)

Medicines in Development Cancer 2014 15 Medicines and Vaccines in Development for Cancer

Brain Cancer

Product Name Sponsor Indication Development Phase

nivolumab + Yervoy® Bristol-Myers Squibb glioblastoma Phase II ipilimumab Princeton, NJ (see also colorectal, head/neck, www.bms.com hematological, kidney, lung, skin)

PEG-SN38 Belrose Pharma pediatric neuroblastoma Phase I (angiogenesis inhibitor) Princeton, NJ (see also breast, solid tumors) www.belrosepharma.com ORPHAN DRUG

PLX3397 Daiichi Sankyo glioblastoma Phase II (Fms/Kit/Flt3-ITD inhibitor) Parsippany, NJ (see also leukemia, skin) www.dsi.com Plexxikon www.plexxicon.com Berkeley, CA

RG7666 Genentech glioblastoma (2nd-line) Phase I (PI3K inhibitor) South San Francisco, CA www.gene.com

rindopepimut Celldex Therapeutics glioblastoma (1st-line) Phase III (EGFRvIII antagonist) Hampton, NJ (Fast Track) www.celldex.com ORPHAN DRUG ------recurrent glioblastoma Phase II (combination therapy) www.celldex.com (Fast Track)

SL-701 Stemline Therapeutics glioblastoma multiforme Phase I/II (cancer immunotherapy) New York, NY www.stemline.com

Toca 511 & Toca FC Tocagen high-grade gliomas Phase I/II ( ucytosine gene therapy) San Diego, CA www.tocagen.com

TPI 287 Cortice Biosciences recurrent glioblastoma, Phase II (microtubule stabilizing taxoid) New York, NY neuroblastoma www.corticebio.com ------breast cancer brain metastases, Phase I secondary brain metastases www.corticebio.com

TRC105 TRACON Pharmaceuticals glioblastoma multiforme Phase II (ENG protein inhibitor) San Diego, CA (see also kidney, sarcoma) www.traconpharma.com

TSC Di usion Pharmaceuticals glioblastoma Phase I/II (trans sodium crocetinate) Charlottesville, VA www.di usionpharma.com ORPHAN DRUG

TVI-Brain-1 TVAX Biomedical late-stage glioma Phase II completed (personalized cancer Lenexa, KS www.tvaxbiomedical.com immunotherapy)

VAL-083 DelMar Pharmaceuticals glioblastoma Phase I/II ORPHAN DRUG Vancouver, Canada www.delmarpharma.com

16 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancer

Brain Cancer

Product Name Sponsor Indication Development Phase

VB-111 VBL Therapeutics recurrent glioblastoma multiforme Phase I/II (vascular targeting system) Or Yehuda, Israel (Fast Track) www.vblrx.com ORPHAN DRUG (see also ovarian, other)

veliparib AbbVie brain metastases Phase I/II North Chicago, IL (see also breast, lung) www.abbvie.com

Breast Cancer

Product Name Sponsor Indication Development Phase

abemaciclib Lilly hormone receptor positive, Phase III (CDK 4/6 inhibitor) Indianapolis, IN HER2-negative breast cancer www.lilly.com (see also lung, lymphoma) ------metastatic breast cancer Phase II www.lilly.com

Abraxane® Celgene triple-negative breast cancer Phase III paclitaxel protein-bound particles Summit, NJ (1st-line) www.celgene.com for injectable suspension, (see also pancreatic) albumin-bound

ADI-PEG 20 Polaris Pharmaceuticals HER2 negative breast cancer Phase I (PEG arginine deiminase) San Diego, CA (see also leukemia, liver, lung, www.polarispharma.com lymphoma, skin)

Ad-RTS-IL-12 ZIOPHARM Oncology breast cancer Phase II (interleukin-12 gene therapy) Boston, MA (see also skin) www.ziopharm.com

AE37 Antigen Express HER2/neu positive breast cancer Phase II (immunotherapeutic) Worcester, MA (see also prostate) www.antigenexpress.com

A nitor® Novartis Pharmaceuticals HER2-positive breast cancer Phase III everolimus East Hanover, NJ (1st-line), HER2-positive breast cancer www.novartis.com (2nd/3rd-line) (see also lung, lymphoma, stomach)

ARN-810 Seragon Pharmaceuticals breast cancer Phase I (selective estrogen receptor San Diego, CA www.seragonpharm.com degrader)

ARRY-380/ONT-380 Array BioPharma breast cancer Phase I (HER2 inhibitor) Boulder, CO www.arraybiopharma.com Oncothyreon www.oncothyreon.com Seattle, WA

Medicines in Development Cancer 2014 17 Medicines and Vaccines in Development for Cancer

Breast Cancer

Product Name Sponsor Indication Development Phase

AV-203 AVEO Oncology early breast cancer Phase I completed (ERBB-3 receptor antagonist) Cambridge, MA www.aveooncology.com

AZD5363 AstraZeneca breast cancer Phase II (AKT kinase inhibitor) Wilmington, DE www.astrazeneca.com

bavituximab Peregrine Pharmaceuticals HER2-negative breast cancer Phase I Tustin, CA (see also liver, lung, skin, other) www.peregrineinc.com

BBI608 Boston Biomedical breast cancer Phase I/II (cancer stemness kinase inhibitor) Cambridge, MA (see also colorectal, lung, ovarian, www.bostonbiomedical.com skin, stomach)

BKM120 Novartis Pharmaceuticals metastatic breast cancer Phase III (PI3K inhibitor) East Hanover, NJ (ER-positive AI resistant/mTOR naïve) www.novartis.com (see also solid tumors) ------metastatic breast cancer Phase II (ER-positive post AI and mTOR inhibitor) www.novartis.com

BMN 673 BioMarin Pharmaceutical metastatic breast cancer Phase III (PARP inhibitor) Novato, CA www.bmrn.com

BZL-101 Bionovo breast cancer Phase I (glycolysis inhibitor) Emeryville, CA www.bionovo.com

CV-301 Bavarian Nordic breast cancer Phase II completed (targeted immunotherapy) Mountain View, CA (see also bladder, colorectal) www.bavarian-nordic.com

Cynviloq™ Sorrento Therapeutics metastatic breast cancer Phase III paclitaxel polymeric micelle San Diego, CA (see also bladder, lung, ovarian, www.sorrentotherapeutics.com for injection pancreatic)

Cyramza® Lilly breast cancer (combination therapy) Phase II ramucirumab Indianapolis, IN (see also bladder, colorectal, liver, www.lilly.com lung, ovarian, solid tumors, stomach)

eniluracil Adherex Technologies breast cancer Phase II completed Research Triangle Park, NC www.adherex.com

ENMD-2076 CASI Pharmaceuticals triple-negative breast cancer Phase II (aurora A/angiogenic kinase Rockville, MD (see also ovarian, sarcoma) www.casipharmaceuticals.com inhibitor)

entinostat Syndax Pharmaceuticals HR-positive breast cancer Phase III (HDAC inhibitor) Waltham, MA (Breakthrough Therapy) www.syndax.com

18 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancer

Breast Cancer

Product Name Sponsor Indication Development Phase

etirinotecan pegol Nektar Therapeutics metastatic breast cancer Phase III (PEGylated irinotecan) San Francisco, CA (Fast Track) www.nektar.com (see also colorectal, ovarian)

ganetespib Synta Pharmaceuticals breast cancer Phase II (Hsp90 inhibitor) Lexington, MA (see also leukemia, lung, ovarian) www.syntapharma.com

GDC-0980 Genentech breast cancer (combination therapy) Phase II (mTOR/PI3K inhibitor) South San Francisco, CA www.gene.com

glembatumumab vedotin CellDex Therapeutics triple negative breast cancer Phase II (antibody drug conjugate) Hampton, NJ (Fast Track) www.celldex.com (see also skin)

GTx-024/GTx-027 GTx androgen receptor-positive breast Phase II (SARM) Memphis, TN cancer www.gtxinc.com

Halaven® Eisai HER2-negative breast cancer Phase III eribulin Woodcli Lake, NJ (1st-line, 2nd-line) www.eisai.com (see also lung, sarcoma)

HER2 cancer immunotherapy AlphaVax late-stage breast cancer Phase I/II (AVX901) Research Triangle Park, NC www.alphavax.com Duke University Durham, NC

indoximod NewLink Genetics metastatic HER2-negative breast Phase II (IDO pathway inhibitor) Ames, IA cancer www.newlinkgenetics.com (see also prostate)

ipatasertib Array BioPharma (see also prostate, stomach) Phase II (GDC-0068) Boulder, CO www.arraybiopharma.com (Akt inhibitor) Genentech www.gene.com South San Francisco, CA

Jaka ® Incyte breast cancer Phase I ruxolitinib Wilmington, DE (see also colorectal, lung, pancreatic, www.incyte.com other)

Kadcyla® Genentech HER2-positive breast cancer Phase III ado-trastuzumab emtansine South San Francisco, CA (1st-line), HER2-positive breast www.gene.com cancer (adjuvant), HER2-positive breast cancer (adjuvant combination therapy), HER2-positive breast cancer (neoadjuvant combination therapy) (see also stomach)

KD019 Kadmon Pharmaceuticals breast cancer Phase I/II (TKI inhibitor) Warrendale, PA (see also lung) www.kadmon.com

Medicines in Development Cancer 2014 19 Medicines and Vaccines in Development for Cancer

Breast Cancer

Product Name Sponsor Indication Development Phase

Keytruda® Merck breast cancer Phase I pembrolizumab Whitehouse Station, NJ (see also bladder, head/neck, www.merck.com hematological, kidney, lung, myeloma, stomach)

LCL161 Novartis Pharmaceuticals breast cancer Phase II (IAP inhibitor) East Hanover, NJ www.novartis.com

LEE011 Novartis Pharmaceuticals breast cancer (1st-line) Phase III (CDK4/6 inhibitor) East Hanover, NJ (see also solid tumors) www.novartis.com

LFA102 Novartis Pharmaceuticals prolactin receptor-positive metastatic Phase I (anti-prolactin receptor mAb) East Hanover, NJ breast cancer www.novartis.com XOMA (see also prostate) www.xoma.com Berkeley, CA

lucitanib Clovis Oncology breast cancer Phase II (FGFR/VEGFR/PDGFR inhibitor) Boulder, CO (see also lung) www.clovisoncology.com

LY2606368 Lilly BRCA 1/2 mutation breast cancer, Phase II (Chk1 inhibitor) Indianapolis, IN triple-negative breast cancer www.lilly.com (see also ovarian, solid tumors)

margetuximab MacroGenics metastatic breast cancer Phase II (anti-HER2 mAb) Rockville, MD (see also solid tumors, other) www.macrogenics.com

MEDI-573 MedImmune metastatic breast cancer Phase II (anti-IGF mAb) Gaithersburg, MD www.medimmune.com

mifepristone Corcept Therapeutics triple-negative breast cancer Phase I Menlo Park, CA (combination therapy) www.corcept.com

MLN0128 Millennium Pharmaceuticals metastatic breast cancer Phase II (TORC1/TORC2 inhibitor) Cambridge, MA (see also hematological, solid tumors) www.millennium.com

MM-121 Merrimack Pharmaceuticals breast cancer Phase II (ErbB-3 receptor antagonist) Cambridge, MA (see also lung, ovarian) www.merrimackpharma.com

MM-302 Merrimack Pharmaceuticals advanced HER2-positive breast cancer Phase I (HER2-targeted nanotherapeutic) Cambridge, MA www.merrimackpharma.com

MVA-BN-HER2 Bavarian Nordic breast cancer Phase I/II (immunotherapy vaccine) Mountain View, CA www.bavarian-nordic.com

Myocet™ Sopherion Therapeutics metastatic breast cancer (1st-line) Phase III doxorubicin liposomal East Brunswick, NJ (Fast Track) www.sopherion.com

20 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancer

Breast Cancer

Product Name Sponsor Indication Development Phase

NeuVax™ Galena Biopharma node positive, HER2-positive breast Phase III nelipepimut-S Portland, OR cancer www.galenabiopharma.com (see also stomach) ------node-positive & negative Phase II HER2-positive breast cancer www.galenabiopharma.com (combination therapy) ------node-positive & negative Phase I completed HER2-positive breast cancer, www.galenabiopharma.com breast cancer (neoadjuvant)

Nexavar® Bayer HealthCare Pharmaceuticals breast cancer Phase III sorafenib Whippany, NJ (see also kidney) www.bayerpharma.com

niraparib TESARO BRCA-positive breast cancer Phase III (PARP inhibitor) Waltham, MA (see also ovarian, sarcoma) www.tesarobio.com

olaparib AstraZeneca breast cancer (adjuvant), metastatic Phase III (PARP inhibitor) Wilmington, DE breast cancer www.astrazeneca.com (see also ovarian, stomach)

palbociclib P zer advanced breast cancer (1st-line) application submitted (CDK4/6 inhibitor) New York, NY (Breakthrough Therapy) www.pfizer.com (see also colorectal) ------high risk early breast cancer, Phase III recurrent advanced breast cancer www.pfizer.com

patritumab Daiichi Sankyo breast cancer Phase II (anti-HER3 antibody) Parsippany, NJ (see also lung) www.dsi.com

PB272 Puma Biotechnology metastatic breast cancer Phase III (neratinib) Los Angeles, CA (see also solid tumors) www.pumabiotechnology.com ------metastatic breast cancer with Phase II brain metastases, breast cancer www.pumabiotechnology.com (neoadjuvant)

PEG-SN38 Belrose Pharma metastatic breast cancer Phase II (angiogenesis inhibitor) Princeton, NJ (see also brain, solid tumors) www.belrosepharma.com

Perjeta® Genentech HER2-positive metastatic breast Phase III pertuzumab South San Francisco, CA cancer (2nd-line), HER2-positive www.gene.com breast cancer (adjuvant) (see also stomach)

PF-05280014 P zer metastatic breast cancer Phase III (trastuzumab biosimilar) New York, NY www.pfizer.com

Medicines in Development Cancer 2014 21 Medicines and Vaccines in Development for Cancer

Breast Cancer

Product Name Sponsor Indication Development Phase

pictrelisib Genentech estrogen receptor-positive metastatic Phase II (PI3K inhibitor) South San Francisco, CA breast cancer, metastatic www.gene.com HER2-negative/hormone receptor-positive breast cancer (see also lung)

PM01183 Pharma Mar metastatic breast cancer Phase II (marine-derived alkylating agent) Madrid, Spain (see also leukemia) www.pharmamar.com

RAD1901 Radius Health brain metastases from breast cancer Phase I (SERM modulator) Waltham, MA www.radiuspharm.com

reparixin Dompe early-stage breast cancer Phase II (IL-8A/B receptor antagonist) Milan, Italy www.dompe.com ------meatastatic breast cancer Phase I www.dompe.com

SGN LIV1A Seattle Genetics metastatic breast cancer (2nd-line) Phase I (anti-LIV-1 mAb) Bothell, WA www.seattlegenetics.com

taselisib Genentech HER2-negative metastatic breast Phase I (PI3K inhibitor) South San Francisco, CA cancer, hormone receptor-positive www.gene.com breast cancer (see also solid tumors)

ThermoDox® Celsion breast cancer Phase II doxorubicin liposomal Lawrenceville, NJ (see also colorectal, liver) www.celsion.com

topotecan liposomal Spectrum Pharmaceuticals breast cancer Phase I Henderson, NV (see also lung) www.sppirx.com

TPIV100 TapImmune breast cancer Phase I (cancer immunotherapy) Seattle, WA www.tapimmune.com

trastuzumab biosimilar Actavis breast cancer Phase III Dublin, Ireland www.actavis.com Amgen www.amgen.com Thousand Oaks, CA

Tykerb® GlaxoSmithKline breast cancer (neoadjuvant, adjuvant) Phase III lapatinib Research Triangle Park, NC www.gsk.com

veliparib AbbVie BRCA-de cient breast cancer, Phase III North Chicago, IL triple negative breast cancer www.abbvie.com (neoadjuvant) (see also brain, lung)

22 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Breast Cancer

Product Name Sponsor Indication Development Phase

WT1 immunotherapeutic GlaxoSmithKline breast cancer Phase II (antigen-speci c cancer Research Triangle Park, NC www.gsk.com immunotherapeutic)

Xgeva® Amgen delay or prevention of bone Phase III denosumab Thousand Oaks, CA metastases in breast cancer www.amgen.com (see also lung)

Xtandi® Astellas Pharma US breast cancer Phase II enzalutamide Northbrook, IL (see also prostate) www.astellas.com (androgen receptor inhibitor) Medivation www.medivation.com San Francisco, CA

Zytiga® Janssen Research & Development metastatic estrogen receptor-positive Phase II abiraterone acetate Raritan, NJ HER2-negative breast cancer in www.janssenrnd.com postmenopausal patients Colorectal Cancer

Product Name Sponsor Indication Development Phase

abituzumab EMD Serono colorectal cancer Phase II (anti-integrin mAb) Rockland, MA (see also prostate) www.emdserono.com

AD-p53 gene therapy MultiVir colorectal cancer Phase I completed San Diego, CA www.multivir.com

BBI608 Boston Biomedical colorectal cancer Phase III (cancer stemness kinase inhibitor) Cambridge, MA (see also breast, lung, ovarian, skin, www.bostonbiomedical.com stomach) ------colorectal cancer Phase II (combination therapy) www.bostonbiomedical.com

birinapant TetraLogic Pharmaceuticals colorectal cancer Phase I/II completed (apoptosis stimulator) Malvern, PA (combination therapy) www.tetralogicpharm.com (see also hematological, ovarian)

CEA cancer immunotherapy AlphaVax late-stage colorectal cancer Phase I/II (AVX701) Research Triangle Park, NC www.alphavax.com Duke University Durham, NC

CEP-32496 Teva Pharmaceutical metastatic colorectal cancer Phase II (BRAF kinase inhibitor) Frazier, PA (see also skin, solid tumors) www.tevapharm.com

Medicines in Development Cancer 2014 23 Medicines and Vaccines in Development for Cancers

Colorectal Cancer

Product Name Sponsor Indication Development Phase

CPP-1X/sulindac Cancer Prevention Pharmaceuticals colorectal cancer Phase III (e ornithine/sulindac) Tucson, AZ (risk reduction) www.canprevent.com (see also brain)

CPX-1 Celator Pharmaceuticals colorectal cancer Phase II (irinotecan/ oxuridine liposomal) Ewing, NJ www.celatorpharma.com

CRLX101 Cerulean Pharma late-stage rectal cancer Phase I/II (camptothecin Cambridge, MA www.ceruleanrx.com nanopharmaceutical)

CV-301 BN ImmunoTherapeutics colorectal cancer Phase II (cancer immunotherapy) Mountain View, CA (see also bladder, breast) www.bavarian-nordic.com

Cyramza™ Lilly colorectal cancer Phase III ramucirumab Indianapolis, IN (see also bladder, breast, liver, lung, www.lilly.com ovarian, solid tumors, stomach)

E7820 Eisai colorectal cancer Phase II (integrin alpha2 inhibitor) Woodcli Lake, NJ www.eisai.com

encapsulated cell therapy Rogosin Institute colorectal cancer Phase II New York, NY www.rogosin.org

ensituximab Precision Biologics advanced colorectal cancer Phase II (neoplasm antigen inhibitor) Dallas, TX (see also pancreatic) www.precision-biologics.com

ETBX-011 Etubics colorectal cancer Phase II (vector cancer vaccine) Seattle, WA www.etubics.com

etirinotecan pegol Nektar Therapeutics colorectal cancer (2nd-line) Phase II/III (PEGylated irinotecan) San Francisco, CA (see also breast, ovarian) www.nektar.com

FANG™ Vaccine Gradalis colorectal cancer Phase II genetically modi ed autologous Dallas, TX (see also ovarian, skin, solid tumors) www.gradalisinc.com tumor cell vaccine

IMMU-130 Immunomedics metastatic colorectal cancer Phase II (antibody drug conjugate) Morris Plains, NJ www.immunomedics.com

Imprime PGG® Biothera metastatic colorectal cancer (3rd-line) Phase III intravenous immunostimulant Eagan, MN (see also leukemia, lung, lymphoma, www.biothera.com pancreatic)

Jaka ® Incyte colorectal cancer Phase I ruxolitinib Wilmington, DE (see also breast, lung, pancreatic, www.incyte.com other)

24 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Colorectal Cancer

Product Name Sponsor Indication Development Phase

KD018 Kadmon Pharmaceuticals colorectal cancer Phase I/II (Chinese botanical formulation) Warrendale, PA (see also liver) www.kadmon.com

KD032 Kadmon Pharmaceuticals colorectal cancer Phase I (Ras antagonist) Warrendale, PA (see also lung, pancreatic) www.kadmon.com

labetuzumab-SN-38 Immunomedics metastatic colorectal cancer Phase II (IMMU-130) Morris Plains, NJ www.immunomedics.com

LGX818 Novartis Pharmaceuticals BRAF-mutant metastatic colorectal Phase I/II (BRAF inhibitor) East Hanover, NJ cancer (combination therapy) www.novartis.com (see also skin, solid tumors)

linaclotide Actavis colon cancer prevention Phase I Dublin, Ireland www.ironwoodpharma.com Ironwood Pharmaceuticals Cambridge, MA

Mekinist® trametinib + GlaxoSmithKline colorectal cancer Phase II Ta nlar® dabrafenib + Research Triangle Park, NC www.gsk.com panitumumab combination

MM-398 Merrimack Pharmaceuticals colorectal cancer Phase III (irinotecan nanotherapeutic) Cambridge, MA (see also brain, pancreatic) www.merrimackpharma.com

MORAb-004 Eisai colorectal cancer Phase II (CD248 antigen inhibitor) Woodcli Lake, CA (see also lung, sarcoma, skin) www.eisai.com

nivolumab Bristol-Myers Squibb microsatellite instability Phase II (PD-1 inhibitor) Princeton, NJ (MSI)-positive colon cancer www.bms.com (see also brain, head/neck, hematological, kidney, liver, lung, lymphoma, skin, solid tumors)

nivolumab + Yervoy® Bristol-Myers Squibb MSI-positive colon cancer Phase II ipilimumab Princeton, NJ (see also brain, head/neck, www.bms.com hematological, kidney, lung, skin)

OncoVAX® Vaccinogen stage II colon cancer Phase III cancer immunotherapy Frederick, MD www.vaccinogeninc.com

palbociclib P zer colorectal cancer Phase I (CDK4/6 inhibitor) New York, NY (see also breast) www.pfizer.com

pelareorep Oncolytics Biotech KRAS mutant-positive metastatic Phase I Calgary, Canada colorectal cancer www.oncolyticsbiotech.com (see also head/neck, lung, myeloma, ovarian, pancreatic, skin, solid tumors, other)

Medicines in Development Cancer 2014 25 Medicines and Vaccines in Development for Cancers

Colorectal Cancer

Product Name Sponsor Indication Development Phase

pexastimogene devacirepvec StillaJen Biotherapeutics treatment refractory colorectal cancer Phase II (genetically-engineered oncolytic San Francisco, CA (see also kidney, liver) www.sillajen.com vaccinia virus)

PF-05212384 P zer colorectal cancer (3rd-line) Phase II (PI3K-mTOR inhibitor) New York, NY www.pfizer.com

RG7221 Genentech colorectal cancer Phase II (Ang2-VEGF Mab) South San Francisco, CA www.gene.com

RG7597 Genentech colorectal cancer Phase II (anti-HER3/EGFR DAF mAb) South San Francisco, CA (see also head/neck) www.gene.com

RRx-001 RadioRx metastatic colorectal cancer Phase II (free radical stimulant) Mountain View, CA (see also lymphoma, solid tumors) www.radiorx.com

simtuzumab Gilead Sciences colorectal cancer Phase II Foster City, CA (see also hematological) www.gilead.com

SM04755 Samumed advanced colorectal cancer Phase I (Wnt inhibitor) San Diego, CA (see also liver, pancreatic, stomach) www.samumed.com

Stivarga® Bayer HealthCare Pharmaceuticals colorectal cancer with resected Phase III regorafenib Whippany, NJ liver metastases www.bayerpharma.com (see also kidney, liver, solid tumors)

Sym004 EMD Serono colorectal cancer Phase II (anti-EGFR mAb) Rockland, MA (see also head/neck, solid tumors) www.emdserono.com

TAS-102 Taiho Oncology colorectal cancer Phase III (tipiracil/tri uridine) Princeton, NJ www. taihooncology.com

ThermoDox® Celsion colorectal metastases Phase II doxorubicin liposomal Lawrenceville, NJ (see also breast, liver) www.celsion.com

vemurafenib Daiichi Sankyo colorectal cancer Phase II (BRAF inhibitor) Parsippany, NJ www.dsi.com

Xilonix™ XBiotech colorectal cancer in patients with Phase III monoclonal (IgG1k) antibody Austin, TX cachexia, colorectal cancer www.xbiotech.com (Fast Track)

26 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Head/Neck Cancer

Product Name Sponsor Indication Development Phase

Ad-IL-24 MultiVir head and neck cancer Phase II (interleukin-24 gene therapy) San Diego, CA www.multivir.com

ADXS-HPV Advaxis head and neck cancer Phase I/II (live, attenuated Listeria Princeton, NJ (see also other) www.advaxis.com monocytogenes (Lm)-based immunotherapy vaccine) ORPHAN DRUG

AZD6738 AstraZeneca head and neck cancer Phase I (ATR serine/threonine kinase Wilmington, DE (see also leukemia) www.astrazeneca.com inhibitor)

GC4419 Galera Therapeutics squamous cell carcinoma of the Phase I (superoxide dismutase modulator) Malvern, PA head and neck www.galeratx.com

Gilotrif® Boehringer Ingelheim Pharmaceuticals squamous cell carcinoma of the Phase III afatinib Ridge eld, CT head and neck www.boehringer-ingelheim.com

GL-0817 Gliknik squamous cell cancer of the oral Phase II (cancer immunotherapy) Baltimore, MD cavity www.gliknik.com ORPHAN DRUG

GL-ONC1 Genelux head and neck cancer Phase I (oncolytic virus immunomodulator) San Diego, CA (see also lung, solid tumors, other) www.genelux.com

HF10 Takara Bio head and neck cancer Phase I (oncolytic virus immunomodulator) Shiga, Japan www.takara-bio.com

INO-3112 Inovio Pharmaceuticals head and neck cancer caused by Phase I (cancer therapeutic vaccine) Plymouth Meeting, PA HPV types 16/18 www.inovio.com (see also other)

IRX-2 IRX Therapeutics head and neck cancer Phase II completed (immunostimulant) New York, NY (Fast Track) www.irxtherapeutics.com

Keytruda® Merck advanced head and neck cancer Phase I pembrolizumab Whitehouse Station, NJ (see also bladder, breast, www.merck.com hematological, kidney, lung, myeloma, stomach)

MGCD265 Mirati Therapeutics squamous cell carcinoma of the Phase I (MET/Axl/VEGFR kinase inhibitor) San Diego, CA head and neck www.mirati.com (see also lung)

Medicines in Development Cancer 2014 27 Medicines and Vaccines in Development for Cancers

Head/Neck Cancer

Product Name Sponsor Indication Development Phase

Multikine® CEL-SCI head and neck cancer (1st-line) Phase III leukocyte interleukin, injection Vienna, VA www.cel-sci.com

nivolumab Bristol-Myers Squibb head and neck cancer (2nd-line) Phase III (PD-1 inhibitor) Princeton, NJ (see also brain, colorectal, www.bms.com hematological, kidney, liver, lung, lymphoma, skin, solid tumors)

nivolumab + Yervoy® Bristol-Myers Squibb head and neck cancer (2nd-line) Phase III ipilimumab Princeton, NJ (see also brain, colorectal, www.bms.com hematological, kidney, lung, skin)

pelareorep Oncolytics Biotech advanced head and neck cancer Phase III completed Calgary, Canada (see also colorectal, lung, myeloma, www.oncolyticsbiotech.com ovarian, pancreatic, skin, solid tumors, other)

RG7597 Genentech head and neck cancer Phase II (HER3/EGFR DAF mAb) South San Francisco, CA (see also colorectal) www.gene.com

Sym004 EMD Serono squamous cell carcinoma of the Phase II (anti-EGFR mAb) Rockland, MA head and neck www.emdserono.com (see also colorectal, solid tumors)

VTX-2337 VentiRx Pharmaceuticals head and neck cancer Phase II (TLR8 agonist immunotherapy) Seattle, WA (see also ovarian) www.ventirx.com

Hematological Malignancies

Product Name Sponsor Indication Development Phase

ABT-199/RG7601 AbbVie hematological malignancies Phase I (Bcl-2 inhibitor) North Chicago, IL (see also leukemia) www.abbvie.com Genentech www.gene.com South San Francisco, CA

ACE-536 Acceleron Pharma myelodysplastic syndromes Phase II (TGF-ß protein super family Cambridge, MA www.acceleronpharma.com inhibitor) Celgene www.celgene.com ORPHAN DRUG Summit, NJ

28 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Hematological Malignancies

Product Name Sponsor Indication Development Phase

AG-120 Agios Pharmaceuticals hematological malignancies Phase I (IDH1 inhibitor) Cambridge, MA (see also solid tumors) www.agios.com Celgene www.celgene.com Summit, NJ

AG-221 Agios Pharmaceuticals hematological malignancies Phase I (IDH2 inhibitor) Cambridge, MA www.agios.com ORPHAN DRUG Celgene www.celgene.com Summit, NJ

ALT-803 Altor BioScience hematological malignancies Phase I/II (IL-15 superagonist complex) Miramar, FL (see also bladder, myeloma, skin) www.altorbioscience.com

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

AMG 900 Amgen hematological malignancies Phase I (aurora kinase inhibitor) Thousand Oaks, CA (see also solid tumors) www.amgen.com

anti-LAG3 antibody Bristol-Myers Squibb hematological malignancies Phase I Princeton, NJ www.bms.com

AR-42 Arno Therapeutics hematological malignancies Phase I (pan-DAC inhibitor) Flemington, NJ (see also solid tumors) www.arnothera.com

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

AZD9150 AstraZeneca hematological malignancies Phase I (STAT3 inhibitor) Wilmington, DE www.astrazeneca.com Isis Pharmaceuticals www.isispharm.com Carlsbad, CA

BGJ398 Novartis Pharmaceuticals hematological malignancies Phase II (FGF-R kinase inhibitor) East Hanover, NJ (see also brain, liver, solid tumors) www.novartis.com

birinapant TetraLogic Pharmaceuticals myelodysplastic syndromes Phase II (apoptosis stimulator) Malvern, PA (see also colorectal, ovarian) www.tetralogicpharm.com

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

BPX-501 Bellicum Pharmaceuticals bone marrow transplantation in Phase I/II (T cell replacement therapy) Houston, TX hematological malignancies www.bellicum.com

CB-839 Calithera Biosciences hematological malignancies Phase I (glutaminase inhibitor) South San Francisco, CA (see also solid tumors) www.calithera.com

Medicines in Development Cancer 2014 29 Medicines and Vaccines in Development for Cancers

Hematological Malignancies

Product Name Sponsor Indication Development Phase

CC-486 Celgene myelodysplastic syndromes Phase III Summit, NJ (see also leukemia, solid tumors) www.celgene.com

CPI-0610 Constellation Pharmaceuticals myelodysplastic syndromes Phase I (BET inhibitor) Cambridge, MA (see also leukemia, lymphoma, www.constellationpharma.com myeloma)

CPX-351 Celator Pharmaceuticals myelodysplastic syndromes Phase II (cytarabine/daunorubicin) Ewing, NJ (see also leukemia) www.celatorpharma.com

EP-100 Esperance Pharmaceuticals hematological malignancies Phase II (membrane disrupting peptide) San Francisco, CA (see also solid tumors) www.esperancepharma.com

FF-10501 Boston Strategics hematological malignancies Phase I/II (cell di erentiation stimulant) Boston, MA www.bostonstrategics.com FUJIFILM Pharmaceuticals USA Boston, MA

GDC-0853 Genentech hematological malignancies Phase I South San Francisco, CA www.gene.com

GS-9973 Gilead Sciences hematological malignancies Phase II (Syk inhibitor) Foster City, CA www.gilead.com

HDM201 Novartis Pharmaceuticals hematological malignancies Phase I (tumor suppressor protein East Hanover, NJ (see also solid tumors) www.novartis.com p53 modulator)

HSC835 Novartis Pharmaceuticals hematological malignancies Phase I/II (stem cell therapy) East Hanover, NJ www.novartis.com

imetelstat Geron hematological malignancies Phase II Menlo Park, CA www.geron.com

ixazomib Millennium Pharmaceuticals hematological malignancies Phase I (proteasome inhibitor) Cambridge, MA (see also lymphoma, myeloma, solid www.millennium.com tumors)

KB004 KaloBios Pharmaceuticals hematological malignancies Phase II (EphA3 kinase inhibitor) South San Francisco, CA www.kalobios.com

Keytruda® Merck hematological malignancies Phase I pembrolizumab Whitehouse Station, NJ (see also bladder, breast, head/neck, www.merck.com kidney, lung, myeloma, stomach)

KPT-330 Karyopharm Therapeutics relapsed or refractory hematological Phase I (XPO1 inhibitor) Newton, MA malignancies www.karyopharm.com (see also brain, leukemia, prostate, solid tumors)

30 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Hematological Malignancies

Product Name Sponsor Indication Development Phase

LGH447 Novartis Pharmaceuticals myelodysplastic syndromes Phase I (proto oncogene protein c East Hanover, NJ (see also leukemia, myeloma) www.novartis.com pim-1 inhibitor)

MEDI-551 + rituximab MedImmune hematological malignancies Phase I (anti-CD19 mAb/anti-CD20 mAb) Gaithersburg, MD www.medimmune.com

MLN0128 Millennium Pharmaceuticals hematological malignancies Phase I (TORC1/TORC2 inhibitor) Cambridge, MA (see also breast, solid tumors) www.millennium.com

MLN4924 Millennium Pharmaceuticals hematological malignancies Phase I (Nedd8-activating enzyme Cambridge, MA (see also solid tumors) www.millennium.com inhibitor)

mocetinostat Mirati Therapeutics myelodysplastic syndromes Phase II (HDAC inhibitor) San Diego, CA (see also bladder, lymphoma) www.mirati.com ORPHAN DRUG

momelotinib Gilead Sciences myelo brosis Phase III (JAK inhibitor) Foster City, CA (see also pancreatic) www.gilead.com ORPHAN DRUG

MRX34 Mirna Therapeutics hematological malignancies Phase I (liposome-encapsulated Austin, TX (see also liver) www.mirnarx.com miR-34 mimic)

NiCord® Gamida Cell hematological malignancies Phase III cord blood stem cell therapy Jerusalem, Israel www.gamide-cell.com

nivolumab Bristol-Myers Squibb hematological malignancies Phase I (PD-1 inhibitor) Princeton, NJ (see also brain, colorectal, head/neck, www.bms.com kidney, liver, lung, lymphoma, skin, solid tumors)

nivolumab + Yervoy® Bristol-Myers Squibb hematological malignancies Phase I ipilimumab Princeton, NJ (see also brain, colorectal, head/neck, www.bms.com kidney, lung, skin)

OMP-52M51 OncoMed Pharmaceuticals hematological malignancies Phase I (NOTCH-1 inhibitor) Redwood City, CA (see also solid tumors) www.oncomed.com

oprozomib Onyx Pharmaceuticals hematological malignancies Phase II (proteasome inhibitor) South San Francisco, CA (monotherapy) www.onyx.com (see also solid tumors) ------hematological malignancies Phase I (combination therapy) www.onyx.com

Medicines in Development Cancer 2014 31 Medicines and Vaccines in Development for Cancers

Hematological Malignancies

Product Name Sponsor Indication Development Phase

OXi4503 OxiGENE myelodysplastic syndromes Phase I (vascular disrupting agent) South San Francisco, CA (see also leukemia) www.oxigene.com

pracinostat MEI Pharma myelodysplastic syndromes (1st-line), Phase II (HDAC inhibitor) San Diego, CA refractory myelodysplastic syndromes www.meipharma.com (see also leukemia)

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

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

RG7388 Genentech hematological malignancies Phase I (dual Raf/MEK inhibitor) South San Francisco, CA (see also solid tumors) www.gene.com

rigosertib Onconova Therapeutics high-risk and low-risk Phase III (PI3K/Plk1 inhibitor) Newtown, PA myelodysplastic syndromes www.onconova.com ORPHAN DRUG

sapacitabine Cyclacel Pharmaceuticals myelodysplastic syndromes Phase II ORPHAN DRUG Berkeley Heights, NJ (see also leukemia, lung) www.cyclacel.com

SGI110 Astex Pharmaceuticals myelodysplastic syndromes Phase II (DNMT inhibitor) Dublin, CA (see also leukemia, liver, ovarian) www.astx.com

simtuzumab Gilead Sciences myelo brosis Phase II Foster City, CA (see also colorectal) www.gilead.com

SL-401 Stemline Therapeutics blastic plasmacytoid dendritic cell Phase I/II (IL-3R inhibitor) New York, NY neoplasm www.stemline.com (see also leukemia)

sotatercept Acceleron Pharma myelodysplastic syndromes Phase II (activin inhibitor) Cambridge, MA www.acceleronpharma.com ORPHAN DRUG Celgene www.celgene.com Summit, NJ

SP-02 Solasia Pharma hematological malignancies Phase I (darinaparsin) Tokyo, Japan (see also solid tumors) www.solasia.co.jp

StemEx® Gamida Cell-Teva Joint Venture hematological malignancies Phase III carlecortemcel-L Jerusalem, Israel (Fast Track) www.gamida-cell.com ORPHAN DRUG

TAK-659 Millennium Pharmaceuticals hematological malignancies Phase I (SYK kinase inhibitor) Cambridge, MA (see also solid tumors) www.millennium.com

32 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Hematological Malignancies

Product Name Sponsor Indication Development Phase

TGR-1202 TG Therapeutics hematological malignancies Phase I (PI3-delta kinase inhibitor) New York, NY www.tgtherapeutics.com

TH-302 EMD Serono hematological malignancies Phase I (hypoxia-activated prodrug) Rockland, MA (see also lung, pancreatic, sarcoma, www.emdserono.com Threshold Pharmaceuticals skin, solid tumors) www.thresholdpharm.com South San Francisco, CA

TZ101 Targazyme cord blood stem cell transplantation Phase I (human recombinant enzyme) San Antonio, TX for hematological malignancies www.targazyme.com

ulocuplumab Bristol-Myers Squibb hematological malignancies Phase I Princeton, NJ www.bms.com

urelumab Bristol-Myers Squibb hematological malignancies Phase I Princeton, NJ (see also solid tumors) www.bms.com

varlilumab Celldex Therapeutics hematological malignancies Phase I (CD27 antigen inhibitor) Hampton, NJ (see also solid tumors) www.celldex.com

WT2725 Sunovion Pharmaceuticals hematological malignancies Phase I (cancer immunotherapy) Marlborough, MA (see also solid tumors) www.sunovion.com

Kidney Cancer

Product Name Sponsor Indication Development Phase

AGS-003 Argos Therapeutics metastatic renal cell carcinoma Phase III (personalized dendritic cell-based Durham, NC (combination therapy) (Fast Track) www.argostherapeutics.com vaccine) ------metastatic renal cell carcinoma Phase II (monotherapy) www.argostherapeutics.com

AGS-16M8F/AGS-16C3F Agensys kidney cancer Phase I (antibody drug conjugate) Santa Monica, CA www.agensys.com Astellas Pharma www.astellas.com Tokyo, Japan

AMG 172 Amgen kidney cancer Phase I (antibody drug conjugate) Thousand Oaks, CA www.amgen.com

Archexin® Rexahn metastatic kidney cancer Phase I/II AKT1 inhibitor Rockville, MD www.rexahn.com ORPHAN DRUG

Medicines in Development Cancer 2014 33 Medicines and Vaccines in Development for Cancers

Kidney Cancer

Product Name Sponsor Indication Development Phase

BNC105 Bionomics renal cell carcinoma Phase II (vascular disrupting agent) Thebarton, Australia (see also ovarian) www.bionomics.com.au

Cometriq® Exelixis metastatic renal cell carcinoma Phase III cabozantinib South San Francisco, CA (see also liver) www.exelixis.com

dalantercept Acceleron Pharma renal cell carcinoma Phase II (ALK1 antagonist) Cambridge, MA (see also liver) www.acceleronpharma.com

HyperAcute™ Renal NewLink Genetics metastatic renal cancer Phase I renal cancer immunotherapy Ames, IA www.newlinkgenetics.com vaccine

IMA901 immatics Biotechnologies renal cancer Phase III (multiple tumor-associated Tuebingen, Germany www.immatics.com peptides)

Inlyta® P zer renal cell carcinoma (adjuvant) Phase III axitinib New York, NY (see also liver) www.p zer.com

Keytruda® Merck kidney cancer Phase I/II pembrolizumab Whitehouse Station, NJ (see also bladder, breast, head/ www.merck.com neck, hematological, lung, myeloma, stomach)

LY2510924 Lilly metastatic clear-cell renal cell Phase II (CXCR4 peptide antagonist) Indianapolis, IN carcinoma www.lilly.com (see also lung)

Nexavar® Bayer HealthCare Pharmaceuticals renal cell carcinoma (adjuvant) Phase III sorafenib Whippany, NJ (see also breast) www.bayerpharma.com

nivolumab Bristol-Myers Squibb renal cell carcinoma (2nd/3rd-line) Phase II/III (PD-1 inhibitor) Princeton, NJ (see also brain, colorectal, head/neck, www.bms.com hematological, liver, lung, lymphoma, skin, solid tumors) ------renal cell carcinoma Phase I www.bms.com

nivolumab + Yervoy® Bristol-Myers Squibb renal cell carcinoma (1st-line) Phase III ipilimumab Princeton, NJ (see also brain, colorectal, head/neck, www.bms.com hematological, lung, skin) ------renal cell carcinoma Phase I www.bms.com

pexastimogene devacirepvec SillaJen Biotherapeutics treatment refractory kidney cancer Phase II (genetically-engineered oncolytic San Francisco, CA (see also colorectal, liver) www.sillajen.com vaccinia virus)

34 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Kidney Cancer

Product Name Sponsor Indication Development Phase

RG7446 Genentech renal cell carcinoma Phase II (anti-PD-L1 mAb) South San Francisco, CA (combination therapy) www.gene.com (see also bladder, lung, skin)

SGN-CD70A Seattle Genetics renal cell carcinoma Phase I Bothell, WA (see also leukemia) www.seattlegenetics.com

sonepcizumab Lpath renal cell carcinoma Phase II (anti-sphingosine-1-phosphate San Diego, CA www.lpath.com mAb)

Stivarga® Bayer HealthCare Pharmaceuticals renal cancer Phase II regorafenib Whippany, NJ (see also colorectal, liver, solid www.bayerpharma.com tumors)

Sutent® P zer renal cell carcinoma (adjuvant) Phase III sunitinib New York, NY www.pfizer.com

TRC105 TRACON Pharmaceuticals renal cell carcinoma Phase I/II (ENG protein inhibitor) San Diego, CA (see also brain, sarcoma) www.traconpharma.com

volitinib AstraZeneca papillary renal cell carcinoma Phase II (MET tyrosine kinase inhibitor) Wilmington, DE www.astrazeneca.com

Votrient® GlaxoSmithKline renal cell cancer (adjuvant) Phase III pazopanib Research Triangle Park, NC (see also ovarian) www.gsk.com ------renal cell cancer (combination with Phase I MK-3475) www.gsk.com Leukemia

Product Name Sponsor Indication Development Phase

Å6 peptide Angstrom Pharmaceuticals chronic lymphocytic leukemia (CLL), Phase II Solana Beach, CA small lymphocytic leukemia www.angstrominc.com

ABL 001 Novartis Pharmaceuticals leukemia Phase I (Bcr-abl tyrosine kinase inhibitor) East Hanover, NJ www.novartis.com

ABT-199/RG7601 AbbVie CLL Phase III (Bcl-2 inhibitor) North Chicago, IL (see also hematological) www.abbvie.com Genentech www.gene.com South San Francisco, CA ------acute myeloid leukemia (AML) Phase II www.abbvie.com www.gene.com

Medicines in Development Cancer 2014 35 Medicines and Vaccines in Development for Cancers

Leukemia

Product Name Sponsor Indication Development Phase

ACP-196 Acerta Pharma CLL (combination therapy) Phase I (Btk inhibitor) San Carlos, CA (see also lymphoma) www.acerta-pharma.com

ACP-319 Acerta Pharma CLL (combination therapy) Phase I (Btk inhibitor) San Carlos, CA www.acerta-pharma.com

ADI-PEG-20 Polaris Pharmaceuticals AML Phase II (PEG arginine deaminase) San Diego, CA (see also breast, liver, lung, www.polarispharma.com lymphoma, skin)

alvocidib Tolero Pharmaceuticals AML (1st-line) Phase III (angiogenesis inhibitor) Lehi, UT www.toleropharmaceuticals.com ------relapsed/refractory AML Phase II www.toleropharmaceuticals.com

AMG 232 Amgen AML Phase I Thousand Oaks, CA (see also solid tumors) www.amgen.com

Arzerra™ GlaxoSmithKline relapsed CLL Phase III ofatumumab Research Triangle Park, NC (see also lymphoma) www.gsk.com ORPHAN DRUG

ASP2215 Astellas Pharma US AML Phase I/II Northbrook, IL www.astellas.com

AZD6738 AstraZeneca CLL Phase I (ATR serine/threonine kinase Wilmington, DE (see also head/neck) www.astrazeneca.com inhibitor)

bendamustine ready-to-dilute Eagle Pharmaceuticals CLL application submitted liquid formulation Woodcli Lake, NJ (see also lymphoma, solid tumors) www.eagleus.com ORPHAN DRUG

BI 811283 Boehringer Ingelheim Pharmaceuticals AML Phase II completed (aurora kinase B inhibitor) Ridge eld, CT www.boehringer-ingelheim.com

BI 836858 Boehringer Ingelheim Pharmaceuticals AML Phase I Ridge eld, CT www.boehringer-ingelheim.com

BL-8040 BioLineRx AML (combination therapy) Phase II (CXCR4 receptor antagonist) Jerusalem, Israel www.biolinerx.com ORPHAN DRUG

blinatumomab Amgen Philadelphia-negative relapsed/ application submitted ORPHAN DRUG Thousand Oaks, CA refractory ß-precursor ALL www.amgen.com (Breakthrough Therapy) (see also lymphoma)

36 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Leukemia

Product Name Sponsor Indication Development Phase

Bosulif® Avillion Philadelphia-chromosome positive Phase III bosutinib London, United Kingdom chronic myeloid leukemia (CML) www.avillionllp.com P zer (1st-line) www.pfizer.com New York, NY

BP-100-1.01 Bio-Path Holdings ALL, AML, CML Phase I (liposomal Grb 2) Houston, TX (see also hematological) www.biopathholdings.com ORPHAN DRUG

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

CC-486 Celgene post-induction AML maintenance Phase III Summit, NJ (see also hematological, solid tumors) www.celgene.com

cerdulatinib Portola Pharmaceuticals CLL Phase I/II (dual Syk-JAK inhibitor) South San Francisco, CA (see also lymphoma) www.portola.com

CNDO-109 Coronado Biosciences AML Phase I/II (natural killer cell stimulant) Burlington, MA www.coronadobiosciences.com ORPHAN DRUG

CPI-0610 Constellation Pharmaceuticals acute leukemia Phase I (BET inhibitor) Cambridge, MA (see also hematological, lymphoma, www.constellationpharma.com myeloma)

CPX-351 Celator Pharmaceuticals ALL, AML Phase II (cytarabine/daunorubicin) Ewing, NJ (see also hematological) www.celatorpharma.com

CSL-362 CSL AML Phase I (anti-CD123 mAb) Victoria, Australia www.csl.com.au Janssen Research & Development www.janssenrnd.com Raritan, NJ

CTL019 Novartis Pharmaceuticals ALL Phase II (chimeric antigen receptor T-cell East Hanover, NJ (Breakthrough Therapy) www.novartis.com therapy)

CWP232291 JW Pharmaceutical AML Phase I Seoul, Korea

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

EPZ-5676 Celgene ALL and AML with altered MLL gene Phase I (DOT1L inhibitor) Summit, NJ www.celgene.com ORPHAN DRUG Epizyme www.epizyme.com Cambridge, MA

Medicines in Development Cancer 2014 37 Medicines and Vaccines in Development for Cancers

Leukemia

Product Name Sponsor Indication Development Phase

Erivedge® Genentech AML Phase II vismodegib South San Francisco, CA (see also skin) www.gene.com

Erwinaze® Jazz Pharmaceuticals ALL application submitted asparaginase erwinia Palo Alto, CA www.jazzpharma.com chrysanthemi intravenous ------ORPHAN DRUG ALL in patients who have developed a Phase II hypersensitivity to 1st-line www.jazzpharma.com asparaginase therapy

ERY-ASP ERYTECH Pharmaceuticals ALL (adults) Phase I (asparagine modulator) Lyon, France www.erytech.com ORPHAN DRUG

EZN-2285 Sigma-Tau Pharmaceuticals ALL Phase III completed (calaspargase pegol) Gaithersburg, MD www.sigmatau.com

FPI-01 Formula Pharmaceuticals ALL, AML Phase II (multi-peptide Berwyn, PA (see also myeloma) www.formulapharma.com immunotherapeutic)

ganetespib Synta Pharmaceuticals AML Phase II (Hsp90 inhibitor) Lexington, MA (see also breast, lung, ovarian) www.syntapharma.com

GMI-1271 GlycoMimetics AML Phase I (E-selectin antagonist) Gaithersburg, MD www.glycomimetics.com

HSV-Tk MolMed high risk acute leukemia Phase III (thymidine kinase cell therapy) Milan, Italy www.molmed.com ORPHAN DRUG

Iclusig® ARIAD Pharmaceuticals AML Phase II ponatinib Cambridge, MA (see also stomach) www.ariad.com

IGN523 Igenica AML Phase I (antibody drug conjugate) Burlingame, CA www.igenica.com

Imbruvica® Janssen Research & Development relapsed/refractory CLL application submitted ibrutinib Raritan, NJ (see also lymphoma) www.janssenrnd.com ------relapsed/refractory CLL (combination Phase III therapy), treatment naïve CLL www.janssenrnd.com

IMMU-114 Immunomedics CLL Phase I (humanized anti-HLA-DR) Morris Plains, NJ (see also lymphoma) www.immunomedics.com

Imprime PGG® Biothera high-risk CLL (1st-line) Phase II intravenous immunostimulant Eagan, MN (see also colorectal, lung, lymphoma, www.biothera.com pancreatic)

38 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Leukemia

Product Name Sponsor Indication Development Phase

inotuzumab ozogamicin P zer ALL Phase III (CD22-targeted cytotoxic agent) New York, NY www.pfizer.com ORPHAN DRUG

Iomab™ B Actinium Pharmaceuticals hematopoietic stem cell Phase II BC8-I-131 construct New York, NY transplantation in ALL www.actiniumpharma.com

IPI-145 In nity Pharmaceuticals CLL Phase III (PI3K inhibitor) Cambridge, MD (see also lymphoma) www.in .com ------high-risk CLL (treatment naïve) Phase I www.in .com

JCAR014 Juno Therapeutics acute ALL, refractory CLL Phase I/II (T lymphocyte immunotherapy) Seattle, WA (see also lymphoma) www.junotherapeutics.com

JCAR015 Juno Therapeutics B-cell ALL Phase I (T lymphocyte immunotherapy) Seattle, WA www.junotherapeutics.com

JCAR017 Juno Therapeutics leukemia Phase I/II (T lymphocyte immunotherapy) Seattle, WA www.junotherapeutics.com

KPT-330 Karyopharm Therapeutics elderly AML (2nd-line) Phase II (XPO1 inhibitor) Newton, MA (see also brain, hematological, www.karyopharm.com prostate, solid tumors)

KX01 Kinex Pharmaceuticals AML Phase I completed (non-ATP competitive Sre kinase Bu alo, NY www.kinexpharma.com inhibitor)

LGH447 Novartis Pharmaceuticals AML Phase I (proto oncogene protein c East Hanover, NJ (see also hematological, myeloma) www.novartis.com pim-1 inhibitor)

lintuzumab Ac-226 Actinium Pharmaceuticals AML (1st-line) Phase I/II New York, NY www.actiniumpharma.com

Marqibo® Spectrum Pharmaceuticals elderly Ph-negative ALL (1st-line) Phase III vinCRIStine sulfate LIPOSOME Henderson, NV (Fast Track) www.sppirx.com injection (see also lymphoma, other) ORPHAN DRUG

MEDI-551 MedImmune CLL Phase II (anti-CD19 mAb) Gaithersburg, MD (see also lymphoma) www.medimmune.com

MGD006 Macrogenics AML Phase I (CD123/CD3 bispeci c antibody) Rockville, MD www.macrogenics.com

milatuzumab-doxorubicin Immunomedics CLL Phase I/II (antibody drug conjugate) Morris Plains, NJ (see also lymphoma) www.immunomedics.com

Medicines in Development Cancer 2014 39 Medicines and Vaccines in Development for Cancers

Leukemia

Product Name Sponsor Indication Development Phase

mogamulizumab Kyowa Hakko Pharma adult T-cell leukemia Phase II (anti-CCR4 humanized antibody) Princeton, NJ (see also lymphoma) www.kyowa-kirin.com ORPHAN DRUG

MOR208 MorphoSys ALL, CLL Phase II (CD19 antigen inhibitor) Martinsried, Germany (see also lymphoma) www.morphosys.com ORPHAN DRUG

moxetumomab pasudotox MedImmune hairy cell leukemia Phase III (anti-CD22 recombinant Gaithersburg, MD www.medimmune.com immunotoxin) ------pediatric ALL Phase I www.medimmune.com

nivolumab + Sprycel® Bristol-Myers Squibb CML Phase I dasatinib Princeton, NJ www.bms.com

Oncoquest™-CLL XEME Biopharma CLL (1st-line) Phase I personalized cancer vaccine Monmouth Junction, NJ www.xemebiopharma.com

otlertuzumab Emergent BioSolutions CLL Phase II (CD37 protein inhibitor) Rockville, MD www.emergentbiosolutions.com ORPHAN DRUG

OXi4503 OxiGENE refractory AML Phase I (vascular disrupting agent) South San Francisco, CA (see also hematological) www.oxigene.com ORPHAN DRUG

PF-04449913 P zer AML Phase II (SMO [smoothened] antagonist) New York, NY www.pfizer.com

PKC412 Novartis Pharmaceuticals AML Phase III (signal transduction inhibitor) East Hanover, NJ www.novartis.com ORPHAN DRUG

PLX3397 Daiichi Sankyo AML Phase II (Fms/Kit/Flt3-ITD inhibitor) Parsippany, NJ (see also brain, skin) www.dsi.com Plexxikon www.plexxikon.com Berkeley, CA

PLX8394 Daiichi Sankyo hairy cell leukemia Phase I (BRAF inhibitor) Parsippany, NJ (see also solid tumors) www.dsi.com Plexxikon www.plexxikon.com Berkeley, CA

PM01183 Pharma Mar acute leukemia Phase II (marine-derived alkylating agent) Madrid, Spain (see also breast) www.pharmamar.com

pracinostat MEI Pharma AML (1st-line) Phase II (HDAC inhibitor) San Diego, CA (see also hematological) www.meipharma.com

40 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Leukemia

Product Name Sponsor Indication Development Phase

PRI-724 PRISM Pharma AML, CML Phase I/II (CBP/β-catenin inhibitor) Tokyo, Japan (see also pancreatic, solid tumors) www.prismbiolab.com

Promacta® GlaxoSmithKline AML Phase II eltrombopag Research Triangle Park, NC (see also hematological) www.gsk.com

Qinprezzo™ Sunesis Pharmaceuticals relapsed/refractory AML Phase III vosaroxin South San Francisco, CA (Fast Track) www.sunesis.com ORPHAN DRUG

quizartinib Ambit Biosciences relapsed refractory AML Phase III (FLT3 inhibitor) San Diego, CA (Fast Track) www.ambitbio.com

Revlimid® Celgene CLL maintenance (2nd-line) Phase III lenalidomide Summit, NJ (see also hematological, lymphoma, www.celgene.com ORPHAN DRUG myeloma)

RG7775 Genentech AML Phase I (MDM2 IN prodrug) South San Francisco, CA www.gene.com

sapacitabine Cyclacel Pharmaceuticals AML Phase III ORPHAN DRUG Berkeley Heights, NJ (see also hematological, lung) www.cyclacel.com

SG2000 Spirogen AML, CLL Phase I/II (DNA cross linking agent) London, United Kingdom

SGI110 Astex Pharmaceuticals AML Phase II (DNMT inhibitor) Dublin, CA (see also hematological, liver, ovarian) www.astx.com

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

SGN-CD33A Seattle Genetics AML Phase I (antibody drug conjugate) Bothell, WA www.seattlegenetics.com

SL-401 Stemline Therapeutics advanced AML Phase II (IL-3R inhibitor) New York, NY (see also hematological) www.stemline.com ORPHAN DRUG

Tasigna® Novartis Pharmaceuticals CML treatment free remission Phase III nilotinib East Hanover, NJ www.novartis.com

tetradecanoylphorbol acetate Rich Pharmaceuticals AML Phase II Beverly Hills, CA www.richpharmaceuticals.com

Medicines in Development Cancer 2014 41 Medicines and Vaccines in Development for Cancers

Leukemia

Product Name Sponsor Indication Development Phase

TG02 Tragara Pharmaceuticals refractory AML, relapsed CLL Phase I (CDK inhibitor) Carlsbad, CA (see also myeloma) www.tragarapharma.com

TG-1101 TG Therapeutics CLL Phase I (anti-CD20 mAb) New York, NY (see also lymphoma) www.tgtherapeutics.com

volasertib Boehringer Ingelheim Pharmaceuticals AML Phase III (PLK-1 antagonist) Ridge eld, CT (Breakthrough Therapy) www.boehringer-ingelheim.com ORPHAN DRUG

Zydelig® Gilead Sciences CLL (1st-line) Phase III idelalisib Foster City, CA (see also lymphoma) www.gilead.com

Liver Cancer

Product Name Sponsor Indication Development Phase

ADI-PEG 20 Polaris Pharmaceuticals hepatocellular carcinoma Phase III (PEG arginine deiminase) San Diego, CA (see also breast, leukemia, lung, www.polarispharma.com lymphoma, skin)

BA-003 Onexo hepatocellular carcinoma (2nd-line) Phase III (doxorubicin nanoparticles) Paris, France (Fast Track) www.onexo.com ORPHAN DRUG

bavituximab Peregrine Pharmaceuticals liver cancer Phase II Tustin, CA (see also breast, lung, skin, other) www.peregrineinc.com

BGJ398 Novartis Pharmaceuticals advanced cholangiocarcinoma Phase II (FGF-R kinase inhibitor) East Hanover, NJ (see also brain, hematological, solid www.novartis.com tumors)

CBL0102 Cleveland BioLabs hepatocellular carcinoma Phase I/II (SSRP1 protein inhibitor) Bu alo, NY www.cbiolabs.com ORPHAN DRUG Incuron www.incuron.ru Moscow, Russia

CF102 Can-Fite BioPharma hepatocellular carcinoma Phase II (A3 adenosine receptor agonist) Petach Tikva, Israel www.canfite.com

Cometriq® Exelixis late-stage hepatocellular carcinoma Phase III cabozantinib South San Francisco, CA (see also kidney) www.exelixis.com

42 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Liver Cancer

Product Name Sponsor Indication Development Phase

CX-4945 Senhwa Biosciences cholangiocarcinoma Phase II (casein kinase II inhibitor) San Diego, CA www.senhwabiosciences.com

Cyramza® Lilly hepatocellular carcinoma Phase III ramucirumab Indianapolis, IN (combination therapy) www.lilly.com ORPHAN DRUG (see also bladder, breast, colorectal, lung, ovarian, solid tumors, stomach)

dalantercept Acceleron Pharma hepatocellular carcinoma Phase II (ALK1 antagonist) Cambridge, MA (see also kidney) www.acceleronpharma.com

DCR-MYC Dicerna Pharmaceuticals hepatocellular carcinoma Phase I (c-myc inhibitor) Watertown, MA www.dicerna.com

doxorubicin nanoparticles BioAlliance Pharma liver cancer (2nd-line) Phase III ORPHAN DRUG Paris, France www.bioalliancepharma.com

E7080 Eisai hepatocellular carcinoma Phase III (multi-targeted kinase inhibitor) Woodcli Lake, NJ (see also brain, lung, skin, other) www.eisai.com

G-202 GenSpera liver cancer Phase II (calcium-transporting ATPase San Antonio, TX (see also brain) www.genspera.com inhibitor) ORPHAN DRUG

galunisertib Lilly liver cancer Phase II (TGF-beta1 inhibitor) Indianapolis, IN (see also brain, pancreatic) www.lilly.com

GC33/RG7686 Chugai Pharmaceutical metastatic liver cancer Phase II (anti-GPC3 antibody) Tokyo, Japan www.chugai.com Roche www.roche.com New York, NY

INC280 Incyte advanced liver cancer with c-Met Phase II (c-Met inhibitor) Wilmington, DE dysregulation www.incyte.com Novartis Pharmaceuticals www.novartis.com East Hanover, NJ

Inlyta® P zer liver cancer Phase II axitinib New York, NY (see also kidney) www.pfizer.com

ipafricept Bayer HealthCare Pharmaceuticals hepatocellular cancer Phase I (Wnt protein inhibitor) Whippany, NJ (see also ovarian, pancreatic) www.bayerpharma.com OncoMed Pharmaceuticals www.oncomed.com Redwood City, CA

KD018 Kadmon Pharmaceuticals liver cancer Phase I/II (Chinese botanical extract) Warrendale, PA (see also colorectal) www.kadmon.com

Medicines in Development Cancer 2014 43 Medicines and Vaccines in Development for Cancers

Liver Cancer

Product Name Sponsor Indication Development Phase

melphalan drug delivery system Delcath Systems secondary liver cancer arising from application submitted (drug-device combination) New York, NY metastatic ocular melanoma www.delcath.com ORPHAN DRUG (Fast Track)

mipsagargin GenSpera liver cancer Phase II (ATPase inhibitor) San Antonio, TX (see also brain, prostate) www.genspera.com ORPHAN DRUG

MRX34 Mirna Therapeutics unresectable primary liver cancer, Phase I (liposome-encapsulated miR-34 Austin, TX liver metastatases from other solid www.mirnarx.com mimic) tumors (see also hematological)

nivolumab Bristol-Myers Squibb hepatocellular carcinoma Phase I (PD-1 inhibitor) Princeton, NJ (see also brain, colorectal, head/ www.bms.com neck, hematological, kidney, lung, lymphoma, skin, solid tumors)

PDT with Photofrin® Pinnacle Biologics unresectable advanced perihilar Phase III por mer sodium Bannockburn, IL cholangiocarcinoma Bismuth type www.pinnaclebiologics.com ORPHAN DRUG III/IV (see also lung)

pexastimogene devacirepvec StillaJen Biotherapeutics advanced primary liver cancer Phase II (genetically-engineered oncolytic San Francisco, CA (see also colorectal, kidney) www.sillajen.com vaccinia virus) ORPHAN DRUG

PF-03446962 P zer hepatocellular carcinoma (2nd-line) Phase II (ALK1 inhibitor) New York, NY www.pfizer.com

PV-10 Provectus Biopharmaceuticals liver metastases Phase I (rose bengal disodium) Knoxville, TN (see also skin) www.pvct.com ORPHAN DRUG

refametinib Bayer HealthCare Pharmaceuticals RAS mutant hepatocellular carcinoma Phase II (MEK inihibitor) Whippany, NJ (see also solid tumors) www.bayerpharma.com

SGI110 Astex Pharmaceuticals liver cancer Phase II (DNMT inhibitor) Dublin, CA (see also hematological, leukemia, www.astx.com ovarian)

SM04755 Samumed advanced liver cancer Phase I (Wnt inhibitor) San Diego, CA (see also colorectal, pancreatic, www.samumed.com stomach)

SPI-1620 Spectrum Pharmaceuticals biliary cancer Phase II (endothelin B receptor agonist) Henderson, NV (see also lung) www.sppirx.com

44 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Liver Cancer

Product Name Sponsor Indication Development Phase

Stivarga® Bayer HealthCare Pharmaceuticals hepatocellular carcinoma (2nd-line) Phase III regorafenib Whippany, NJ (see also colorectal, kidney, solid www.bayerpharma.com tumors)

ThermoDox® Celsion primary liver cancer Phase III doxorubicin liposomal Lawrenceville, NJ (Fast Track) www.celsion.com ORPHAN DRUG (see also breast, colorectal) ------liver metastases Phase III www.celsion.com

tivantinib ArQule hepatocellular carcinoma Phase III (c-Met inhibitor) Woburn, MA www.arqule.com Daiichi Sankyo www.dsi.com Parsippany, NJ

TKM-PLK1 Tekmira Pharmaceuticals hepatocellular carcinoma Phase II (RNA interference) Burnaby, Canada (see also stomach, other) www.tekmira.com

VT-122 Vicus Therapeutics advanced liver cancer Phase II (cancer immunotherapy) Morristown, NJ (see also prostate) www.vicustherapeutics.com

Lung Cancer

Product Name Sponsor Indication Development Phase

abemaciclib Lilly non-small-cell lung cancer (NSCLC) Phase I (CDK 4/6 inhibitor) Indianapolis, IN (see also breast, lymphoma) www.lilly.com

ABT-RTA-408 AbbVie metastatic NSCLC Phase I North Chicago, IL (see also skin) www.abbvie.com Reata Pharmaceuticals www.reatapharma.com Irving, TX

ADI-PEG 20 Polaris Pharmaceuticals small-cell lung cancer (SCLC) Phase II (PEG arginine deiminase) San Diego, CA (see also breast, leukemia, liver, www.polarispharma.com lymphoma, skin) ------mesothelioma, NSCLC Phase I www.polarispharma.com

A nitor® Novartis Pharmaceuticals neuroendocrine lung tumors Phase III everolimus East Hanover, NJ (see also breast, lymphoma, stomach) www.novartis.com

Medicines in Development Cancer 2014 45 Medicines and Vaccines in Development for Cancers

Lung Cancer

Product Name Sponsor Indication Development Phase

aldoxorubicin CytRx SCLC Phase II (delivery-enhanced doxorubicin) Los Angeles, CA (see also brain, sarcoma) www.cytrx.com

alectinib Chugai Pharma USA NSCLC Phase II (ALK inhibitor) Berkeley Heights, NJ (Breakthrough Therapy) www.chugai-pharm.com Roche www.roche.com Basel, Swizterland

alisertib Millennium Pharmaceuticals SCLC Phase II (auroura A kinase inhibitor) Cambridge, MA (see also lymphoma, ovarian) www.millennium.com

antroquinonol Golden Biotechnology NSCLC Phase II New Taipei City, Taiwan www.goldenbiotech.com.tw

AP26113 ARIAD Pharmaceuticals NSCLC Phase II (ALK inhibitor) Cambridge, MA www.ariad.com

apatorsen OncoGenex Pharmaceuticals non-squamous NSCLC, squamous Phase II (Hsp27 inhibitor) Bothell, WA NSCLC www.oncogenex.com (see also bladder, pancreatic, prostate)

ASP8273 Astellas Pharma US NSCLC Phase I/II Northbrook, IL www.astellas.com

AT13387 Astex Pharmaceuticals NSCLC Phase II (HSP90 inhibitor) Dublin, CA (see also skin) www.astx.com

Avastin® Genentech NSCLC (adjuvant) Phase III bevacizumab South San Francisco, CA (see also brain, ovarian, other) www.gene.com

AZD9291 AstraZeneca advanced T790M mutation-positive Phase II/III (EGFR tyrosine kinase inhibitor) Wilmington, DE NSCLC www.astrazeneca.com (Breakthrough Therapy)

bavituximab Peregrine Pharmaceuticals NSCLC (2nd-line) Phase III Tustin, CA (see also breast, liver, skin, other) www.peregrineinc.com ------NSCLC (1st-line) Phase I www.peregrineinc.com

BBI608 Boston Biomedical NSCLC Phase I/II (cancer stemness kinase inhibitor) Cambridge, MA (see also breast, colorectal, ovarian, www.bostonbiomedical.com skin, stomach)

belinostat Spectrum Pharmaceuticals NSCLC Phase I/II Henderson, NV www.sppirx.com

46 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Lung Cancer

Product Name Sponsor Indication Development Phase

bevacizumab biosimilar Actavis NSCLC Phase III Parsippany, NJ www.actavis.com Amgen www.amgen.com Thousand Oaks, CA

BIND-014 BIND Therapeutics NSCLC Phase II (PSMA-targeted docetaxel) Cambridge, MA (see also prostate) www.bindtherapeutics.com

CRS-207 Aduro BioTech mesothelioma (combination therapy) Phase I (cancer immunotherapy) Berkeley, CA (see also pancreatic) ww.adurobiotech.com

custirsen (OGX-111) OncoGenex Pharmaceuticals NSCLC (Fast Track) Phase III (antisense oligonucleotide) Bothell, WA (see also prostate) www.oncogenex.com Teva Pharmaceutical www.tevapharm.com Frazier, PA

Cynviloq™ Sorrento Therapeutics NSCLC Phase III paclitaxel polymeric micelle for San Diego, CA (see also bladder, breast, ovarian, www.sorrentotherapeutics.com injection pancreatic)

Cyramza® Lilly NSCLC (combination therapy) Phase III ramucirumab Indianapolis, IN (see also bladder, breast, colorectal, www.lilly.com liver, ovarian, solid tumors, stomach)

CYT-6091 CytImmune Sciences NSCLC (2nd-line) Phase II (nanomedicine) Rockville, MD www.cytimmune.com

dacomitinib P zer EGFR-mutant NSCLC (1st-line) Phase III (pan-HER inhibitor) New York, NY (see also solid tumors) www.p zer.com

DKN-01 HealthCare Pharmaceuticals NSCLC Phase I (DKK1 protein inhibitor) Cambridge, MA (see also myeloma, other) www.healthcarepharmaceuticals.com

DPV-001 UbiVac NSCLC Phase II (toll-like receptor agonist) Portland, OR www.ubivac.com

E7080 Eisai NSCLC (3rd-line monotherapy), NSCLC Phase II (multi-targeted kinase inhibitor) Woodcli Lake, NJ (RET translocations) www.eisai.com (see also brain, liver, skin, other)

EGF816 Novartis Pharmaceuticals NSCLC Phase I/II (EGFR TK inhibitor) East Hanover, NJ www.novartis.com

clatuzumab AVEO Oncology NSCLC Phase II (HGF/c-MET inhibitor) Cambridge, MA www.aveooncology.com

foretinib GlaxoSmithKline NSCLC Phase II (c-MET kinase inhibitor) Research Triangle Park, NC www.gsk.com

Medicines in Development Cancer 2014 47 Medicines and Vaccines in Development for Cancers

Lung Cancer

Product Name Sponsor Indication Development Phase

ganetespib Synta Pharmaceuticals NSCLC Phase III (Hsp90 inhibitor) Lexington, MA (Fast Track) www.syntapharma.com (see also breast, leukemia, ovarian)

GI-4000 GlobeImmune NSCLC Phase II (natural killer cell stimulant) Louisville, CO (see also pancreatic) www.globeimmune.com

GL-ONC1 Genelux lung, malignant mesothelioma Phase I (oncolytic virus immunomodulator) San Diego, CA (see also head/neck, solid tumors, www.genelux.com other)

GSK2879552 GlaxoSmithKline relapsed/refractory SCLC Phase I (LSD1/CoREST inhibitor) Research Triangle Park, NC www.gsk.com

Halaven® Eisai NSCLC Phase III eribulin Woodcli Lake, NJ (see also breast, sarcoma) www.eisai.com

Imprime PGG® Biothera metastatic NSCLC (1st-line) Phase II intravenous immunostimulant Eagan, MN (see also colorectal, leukemia, www.biothera.com lymphoma, pancreatic)

INCB24360 Incyte NSCLC Phase I/II (IDO1 inhibitor) Wilmington, DE (see also ovarian, skin, other) www.incyte.com

INCB39110 Incyte NSCLC Phase I/II (JAK1 inhibitor) Wilmington, DE (see also solid tumors) www.incyte.com

ISIS-EIF4ERX Isis Pharmaceuticals NSCLC Phase II (antisense oligonucleotide) Carlsbad, CA (see also prostate) www.isispharm.com

Jaka ® Incyte NSCLC Phase I ruxolitinib Wilmington, DE (see also breast, colorectal, www.incyte.com pancreatic, other)

KD019 Kadmon Pharmaceuticals NSCLC Phase II (TKI inhibitor) Warrendale, PA (see also breast) www.kadmon.com ------Src-positive NSCLC Phase I www.kadmon.com

KD032 Kadmon Pharmaceuticals NSCLC Phase II (Ras antagonist) Warrendale, PA (see also colorectal, pancreatic) www.kadmon.com

Keytruda® Merck NSCLC Phase III pembrolizumab Whitehouse Station, NJ (see also bladder, breast, head/neck, www.merck.com hematological, kidney, myeloma, stomach)

Kyprolis® Onyx Pharmaceuticals SCLC Phase II car lzomab South San Francisco, CA (see also myeloma) www.onyx.com

48 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Lung Cancer

Product Name Sponsor Indication Development Phase

lifastuzumab vedotin Genentech NSCLC Phase I (anti-NaPi2b antibody drug South San Francisco, CA (see also ovarian) www.gene.com conjugate) (RG7599)

lucitanib Clovis Oncology squamous NSCLC Phase II (FGFR/VEGFR/PDGFR inhibitor) Boulder, CO (see also breast) www.clovisoncology.com

lung cancer DNA vaccine Immune Cell Therapy NSCLC Phase I (IC 1001) Chicago, IL www.immcellther.com

LY2510924 Lilly SCLC Phase II (CXCR4 peptide antagonist) Indianapolis, IN (see also kidney) www.lilly.com

LY2875358 Lilly NSCLC Phase II (c-Met mAb) Indianapolis, IN (see also stomach) www.lilly.com

LY2940680 Lilly SCLC Phase I/II (hedgehog/SMO antagonist) Indianapolis, IN www.lilly.com

MAGE-A3 immunotherapeutic GlaxoSmithKline NSCLC Phase III (recombinant antigen-speci c Research Triangle Park, NC www.gsk.com cancer immunotherapeutic)

ME-344 MEI Pharma SCLC Phase I (mitochondrial inhibitor) San Diego, CA (see also ovarian) www.meipharma.com

MEDI4736 MedImmune stage III NSCLC, NSCLC (3rd-line) Phase III (anti-PD-L1 mAb) Gaithersburg, MD www.medimmune.com

MEDI4736 + Iressa® ge tinib MedImmune NSCLC Phase I (anti-PD-L1 mAb/EGFR inhibitor) Gaithersburg, MD www.medimmune.com

MGCD265 Mirati Therapeutics NSCLC Phase I (MET/Axl/VEGFR kinase inhibitor) San Diego, CA (see also head/neck) www.mirati.com

MM-121 Merrimack Pharmaceuticals NSCLC Phase II (ErbB-3 receptor antagonist) Cambridge, MA (see also breast, ovarian) www.merrimackpharma.com

MORAb-003 Eisai NSCLC Phase II (IgG1 mAb) Woodcli Lake, NJ (see also ovarian) www.eisai.com Morphotek Exton, PA

MORAb-009 Eisai mesothelioma Phase II (megakaryocyte potentiating Woodcli Lake, NJ www.eisai.com factor inhibitor) Morphotek ------ORPHAN DRUG Exton, PA solid tumors Phase I www.eisai.com

Medicines in Development Cancer 2014 49 Medicines and Vaccines in Development for Cancers

Lung Cancer

Product Name Sponsor Indication Development Phase

NC-6004 NanoCarrier NSCLC Phase I/II (nanoparticle cisplatin) Tokyo, Japan www.nanocarrier.co.jp

necitumumab Lilly squamous NSCLC Phase III (EGFR inhibitor) Indianapolis, IN www.lilly.com

nivolumab Bristol-Myers Squibb NSCLC (1st-line), Phase III (PD-1 inhibitor) Princeton, NJ squamous NSCLC (2nd-line), www.bms.com non-squamous NSCLC (2nd-line) (see also brain, colorectal, head/neck, hematological, kidney, liver, lymphoma, skin, solid tumors) ------squamous NSCLC (3rd-line) Phase II www.bms.co ------NSCLC, SCLC Phase II www.bms.com

nivolumab + Yervoy® Bristol-Myers Squibb NSCLC, SCLC Phase I ipilimumab Princeton, NJ (see also brain, colorectal, head/neck, www.bms.com hematological, kidney, skin)

patritumab Daiichi Sankyo NSCLC Phase II (anti-HER3 antibody) Parsippany, NJ (see also breast) www.dsi.com

PDT with Photofrin® Pinnacle Biologics epithelioid malignant pleural Phase III por mer sodium Bannockburn, IL mesothelioma www.pinnaclebiologics.com ORPHAN DRUG (see also liver)

pelareorep Oncolytics Biotech NSCLC, squamous cell carcinoma of Phase II Calgary, Canada the lung www.oncolyticsbiotech.com (see also colorectal, head/neck, myeloma, ovarian, pancreatic, skin, solid tumors, other)

pictrelisib Genentech metastatic NSCLC Phase II (PI3K inhibitor) South San Francisco, CA (see also breast) www.gene.com

PRAME immunotherapeutic GlaxoSmithKline resectable NSCLC Phase II (recombinant antigen-speci c Research Triangle Park, NC www.gsk.com cancer immunotherapeutic)

PT 107 Pique Therapeutics NSCLC Phase II (allogeneic B7.1/HLA-A1 Durham, NC www.piquetherapeutics.com transfected tumor cell vaccine)

50 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Lung Cancer

Product Name Sponsor Indication Development Phase

RG7446 Genentech NSCLC (2nd-line) Phase III (anti-PD-L1 mAb) South San Francisco, CA (see also bladder, kidney, skin) www.gene.com

------NSCLC (3rd-line) Phase II www.gene.com ------EGFR-positive NSCLC Phase I www.gene.com

rociletinib (CO-1686) Clovis Oncology EGFR-mutated NSCLC Phase II (EGFR inhibitor) Boulder, CO (Breakthrough Therapy) www.clovisoncology.com

roniciclib Bayer HealthCare Pharmaceuticals SCLC Phase II (CDK inhibitor) Whippany, NJ www.bayerpharma.com

sapacitabine Cyclacel Pharmaceuticals NSCLC Phase II ORPHAN DRUG Berkeley Heights, NJ (see also hematological, leukemia) www.cyclacel.com

SC16LD6.5 Stem CentRx SCLC Phase I/II (antibody drug conjugate) South San Francisco, CA www.stemcentrx.com

seliciclib Cyclacel Pharmaceuticals NSCLC Phase II (CDK inhibitor) Berkeley Heights, NJ (see also other) www.cyclacel.com

selumetinib Array BioPharma KRAS-positive NSCLC (2nd-line) Phase III (MEK inhibitor) Boulder, CO (see also other) www.arraybiopharma.com AstraZeneca www.astrazeneca.com Wilmington, DE ------KRAS-negative NSCLC (2nd-line) Phase II www.arraybiopharma.com www.astrazeneca.com

SPI-1620 Spectrum Pharmaceuticals NSCLC Phase II (endothelin B receptor agonist) Henderson, NV (see also liver) www.sppirx.com

Ta nlar® GlaxoSmithKline NSCLC Phase II dabrafenib Research Triangle Park, NC (Breakthrough Therapy) www.gsk.com

tarextumab OncoMed Pharmaceuticals SCLC Phase I/II (anti-NOTCH 2/3) Redwood City, CA (see also pancreatic) www.oncomed.com

Tavocept™ BioNumerik Pharmaceuticals lung cancer Phase III San Antonio, TX www.bionumerik.com

tergenpumatucel-L NewLink Genetics advanced or metastatic NSCLC Phase II/III Ames, IA www.newlinkgenetics.com

Medicines in Development Cancer 2014 51 Medicines and Vaccines in Development for Cancers

Lung Cancer

Product Name Sponsor Indication Development Phase

TG4010 Transgene advanced NSCLC Phase II/III (MVA-MUC1-IL2 cancer vaccine) Cambridge, MA www.transgene.fr

TH-302 EMD Serono NSCLC Phase II (hypoxia-activated prodrug) Rockland, MA (see also hematological, pancreatic, www.emdserono.com Threshold Pharmaceuticals skin, sarcoma, solid tumors) www.thresholdpharm.com South San Francisco, CA

topotecan liposomal Spectrum Pharmaceuticals lung cancer Phase I Henderson, NV (see also breast) www.sppirx.com

tremelimumab MedImmune mesothelioma Phase III (anti-CTLA-4 mAb) Gaithersburg, MD www.medimmune.com

tremelimumab AstraZeneca NSCLC Phase I (anti-CTLA-4 mAb)/Iressa® Wilmington, DE www.astrazeneca.com ge tinib combination MedImmune www.medimmune.com Gaithersburg, MD

TSR-011 TESARO NSCLC Phase I/II (ALK/TRK inhibitor) Waltham, MA www.tesarobio.com

TUSC2 Genprex NSCLC Phase I/II (gene therapy) Austin, TX www.genprex.com

Vargatef™ Boehringer Ingelheim Pharmaceuticals NSCLC Phase III nintedanib Ridge eld, CT (see also ovarian) www.boehringer-ingelheim.com ------mesothelioma Phase II www.boehringer-ingelheim.com

veliparib AbbVie NSCLC Phase III North Chicago, IL (see also brain, breast) www.abbvie.com

viagenpumatucel-L Heat Biologics NSCLC Phase II (cancer immunotherapy) Durham, NC www.heatbio.com

vinorelbine liposomal Spectrum Pharmaceuticals SCLC Phase I Henderson, NV (see also ovarian) www.sppirx.com

vintafolide Endocyte NSCLC Phase II (folate-DAVLBH) West Lafayette, IN (see also solid tumors) www.endocyte.com

VS-6063 Verastem KRAS-mutant NSCLC, mesothelioma Phase II (FAK inhibitor) Cambridge, MA (see also ovarian) www.verastem.com ORPHAN DRUG

Xalkori® P zer ALK-positive NSCLC (1st-line) Phase III crizotinib New York, NY (see also solid tumors) www.pfizer.com ORPHAN DRUG

52 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Lung Cancer

Product Name Sponsor Indication Development Phase

Xgeva® Amgen metastatic NSCLC (1st-line) Phase II denosumab Thousand Oaks, CA (see also breast) www.amgen.com

Yervoy® Bristol-Myers Squibb SCLC (1st-line), squamous NSCLC Phase III ipilimumab Princeton, NJ (1st-line) www.bms.com (see also ovarian, prostate, skin, stomach)

Zykadia™ Novartis Pharmaceuticals ALK-positive advanced NSCLC Phase II ceritinib East Hanover, NJ (1st-line, treatment naïve) www.novartis.com

Lymphoma

Product Name Sponsor Indication Development Phase

abemaciclib Lilly mantle cell lymphoma Phase II (CDK 4/6 inhibitor) Indianapolis, IN (see also breast, lung) www.lilly.com

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

ACP-196 Acerta Pharma di use large B-cell lymphoma Phase I (Btk inhibitor) San Carlos, CA (DLBCL), www.acerta-pharma.com Waldenström’s macroglobulinemia (see also leukemia)

Adcetris® Seattle Genetics post-transplant Hodgkin lymphoma Phase III brentuximab vedotin Bothell, WA prevention, relapsed www.seattlegenetics.com ORPHAN DRUG CD30-positive cutaneous lymphoma, Hodgkin lymphoma (1st-line), CD30-positive mature T-cell lymphoma (1st-line) ------relapsed/refractory CD30-positive Phase II non-Hodgkin lymphoma (NHL), www.seattlegenetics.com Hodgkin lymphoma in the elderly (1st-line), DLBCL (1st-line) ------Hodgkin lymphoma (2nd-line) Phase I www.seattlegenetics.com

ADI-PEG 20 Polaris Pharmaceuticals NHL Phase II (PEG arginine deiminase) San Diego, CA (see also breast, leukemia, liver, lung, www.polarispharma.com skin)

Medicines in Development Cancer 2014 53 Medicines and Vaccines in Development for Cancers

Lymphoma

Product Name Sponsor Indication Development Phase

AEB071 Novartis Pharmaceuticals CD79-mutant or ABC-subtype DLBCL Phase I/II (PKC inhibitor) East Hanover, NJ (combination therapy) www.novartis.com (see also other)

A nitor® Novartis Pharmaceuticals DLBCL Phase III everolimus East Hanover, NJ (see also breast, lung, stomach) www.novartis.com

AFM 13 A med Therapeutics Hodgkin lymphoma Phase II (CD30 antigen modulator) Heidelberg, Germany www.a med.com ORPHAN DRUG

alisertib Millennium Pharmaceuticals relapsed or refractory peripheral Phase III (auroura A kinase inhibitor) Cambridge, MA T-cell lymphoma www.millennium.com (see also lung, ovarian)

AR-12 Arno Therapeutics lymphoma Phase I (PI3K/Akt inhibitor) Flemington, NJ (see also solid tumors) www.arnothera.com

Arzerra™ GlaxoSmithKline relapsed DLBCL, refractory and Phase III ofatumumab Research Triangle Park, NC relapsed follicular lymphoma www.gsk.com (see also leukemia)

bendamustine ready-to-dilute Eagle Pharmaceuticals NHL application submitted liquid formulation Woodcli Lake, NJ (see also leukemia, solid tumors) www.eagleus.com ORPHAN DRUG

BI 836826 Boehringer Ingelheim Pharmaceuticals NHL Phase I Ridge eld, CT www.boehringer-ingelheim.com

BiovaxID® Biovest International follicular NHL (Fast Track), Phase III dasiprotimut T Minneapolis, MN mantle cell lymphoma www.bioinvest.com (personalized cancer vaccine) ORPHAN DRUG

blinatumomab Amgen DLBCL Phase II ORPHAN DRUG Thousand Oaks, CA (see also leukemia) www.amgen.com

CC-122 Celgene DLBCL Phase I (pleiotropic pathway modulator) Summit, NJ (see also solid tumors) www.celgene.com

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

cerdulatinib Portola Pharmaceuticals NHL Phase I/II (dual Syk-JAK inhibitor) South San Francisco, CA (see also leukemia) www.portola.com

CMD-003 Cell Medica Epstein-Barr virus lymphoma Phase II (cell therapy) London, United Kingdom www.cellmedica.co.uk

54 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Lymphoma

Product Name Sponsor Indication Development Phase

copanlisib Bayer HealthCare Pharmaceuticals NHL Phase II (PI3K inhibitor) Whippany, NJ www.bayerpharma.com

CPI-0610 Constellation Pharmaceuticals lymphoma Phase I (BET inhibitor) Cambridge, MA (see also hematological, leukemia, www.constellationpharma.com myeloma)

CUDC-427 Curis late-stage lymphoma Phase I (IAP inhibitor) Lexington, MA (see also solid tumors) www.curis.com

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

Debio 1143 Debiopharma (see also solid tumors) Phase I (IAP inhibitor) Lausanne, Switzerland www.debiopharm.com

DI-Leu16-IL2 ALOPEXX Oncology NHL Phase I/II (CD20 antigen inhibitor) Concord, MA www.alopexx.com

DS-3032 Daiichi Sankyo (see also solid tumors) Phase I (MDM2 inhibitor) Parsippany, NJ www.dsi.com

DS-3078 Daiichi Sankyo (see also solid tumors) Phase I (mTOR inhibitor) Parsippany, NJ www.dsi.com

DS-8273 Daiichi Sankyo late-stage lymphoma Phase I (anti-DR5 antibody) Parsippany, NJ (see also solid tumors) www.dsi.com

EPZ-6438 Epizyme NHL Phase I/II (EZH2 inhibitor) Cambridge, MA (see also solid tumors) www.epizyme.com

fenretinide intravenous CerRx adult lymphoma Phase II Lubbock, TX (see also solid tumors) www.cerrx.com

Folotyn® Spectrum Pharmaceuticals peripheral T-cell lymphoma (1st-line) Phase III pralatrexate injection Henderson, NV www.sppirx.com

Gazyva® Genentech DLBCL, indolent NHL (1st-line), Phase III obinutuzumab South San Francisco, CA refractory indolent NHL www.gene.com

GDC-0575 Genentech lymphoma Phase I (ChK1 inhibitor) South San Francisco, CA (see also solid tumors) www.gene.com

Medicines in Development Cancer 2014 55 Medicines and Vaccines in Development for Cancers

Lymphoma

Product Name Sponsor Indication Development Phase

Imbruvica® Janssen Research & Development relapsed/refractory mantle cell Phase III ibrutinib Raritan, NJ lymphoma, treatment naïve mantle www.janssenrnd.com cell lymphoma (combination therapy), relapsed/refractory indolent NHL, non-germinal center B-cell subtype of DLBCL, Waldenström’s macroglobulinemia (Breakthrough Therapy)

IMGN529 ImmunoGen NHL Phase I (CD37 protein inhibitor) Waltham, MA www.immunogen.com

IMMU-114 Immunomedics NHL Phase I (humanized anti-HLA-DR) Morris Plains, NJ (see also leukemia) www.immunomedics.com

IMO-8400 Idera Pharmaceuticals DLBCL, Waldenström’s Phase I/II (TLR antagonist) Cambridge, MA macroglobulinemia www.iderapharma.com

Imprime PGG® Biothera advanced indolent NHL Phase II intravenous immunostimulant Eagan, MN (see also colorectal, leukemia, lung, www.biothera.com pancreatic)

INCB39110/INCB40093 Incyte B-lymphoid malignancies Phase I (JAK1 inhibitor/PI3K delta Wilmington, DE www.incyte.com inhibitor)

INCB40093 Incyte B-lymphoid malignancies Phase I (PI3K delta inhibitor) Wilmington, DE www.incyte.com

interleukin-12 gene therapy OncoSec Medical cutaneous T-cell lymphoma (CTCL), Phase II San Diego, CA Merkel cell carcinoma www.oncosec.com (see also skin)

IPI-145 In nity Pharmaceuticals indolent NHL Phase II (PI3K inhibitor) Cambridge, MD (see also leukemia) www.in .com ------mantle cell lymphoma Phase I www.in .com

Istodax® Celgene peripheral T-cell lymphoma (1st-line) Phase III romidepsin Summit, NJ www.celgene.com

ixazomib Millennium Pharmaceuticals relapsed/refractory follicular Phase II (proteasome inhibitor) Cambridge, MA lymphoma www.millennium.com (see also hematological, myeloma, solid tumors)

JCAR014 Juno Therapeutics NHL Phase I/II (T lymphocyte immunotherapy) Seattle, WA (see also leukemia) www.junotherapeutics.com

56 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Lymphoma

Product Name Sponsor Indication Development Phase

JNJ-26481585 Janssen Research & Development CTCL Phase II (HDAC inhibitor) Raritan, NJ www.janssenrnd.com

JNJ-40346527 Janssen Research & Development Hodgkin lymphoma Phase II completed (Fms inhibitor) Raritan, NJ www.janssenrnd.com

JNJ-42756493 Janssen Research & Development late-stage lymphoma Phase I (FGFR inhibitor) Raritan, NJ (see also solid tumors) www.janssenrnd.com

KTE-C19 CAR Kite Pharma DLBCL Phase I/II (chimeric antigen receptor) Santa Monica, CA www.kitepharma.com ORPHAN DRUG National Cancer Institute Bethesda, MD

Marqibo® Spectrum Pharmaceuticals aggressive NHL (1st-line) Phase III vinCRIStine sulfate LIPOSOME Henderson, NV (see also leukemia, other) www.sppirx.com injection

MEDI-551 MedImmune DLBCL Phase II (anti-CD19 mAb) Gaithersburg, MD (see also leukemia) www.medimmune.com

milatuzumab-doxorubicin Immunomedics NHL Phase I/II (antibody drug conjugate) Morris Plains, NJ (see also leukemia) www.immunomedics.com

mocetinostat Mirati Therapeutics DLBCL Phase II (HDAC inhibitor) San Diego, CA (see also bladder, hematological) www.mirati.com ORPHAN DRUG

mogamulizumab Kyowa Hakko Pharma CTCL Phase III (anti-CCR4 humanized antibody) Princeton, NJ (see also leukemia) www.kyowa-kirin.com ORPHAN DRUG ------adult T-cell lymphoma Phase II www.kyowa-kirin.com

MOR208 MorphoSys NHL Phase II (CD19 antigen inhibitor) Martinsried, Germany (see also leukemia) www.morphosys.com

nivolumab Bristol-Myers Squibb Hodgkin lymphoma (Breakthrough Phase II (PD-1 inhibitor) Princeton, NJ Therapy), NHL (1st-line), DLBCL www.bms.com (see also brain, colorectal, head/neck, hematological, kidney, liver, lung, skin, solid tumors)

non-Hodgkin’s lymphoma vaccine XEME Biopharma non-Hodgkin’s follicular lymphoma Phase II (personalized cancer vaccine) Monmouth Junction, NJ www.xemebiopharma.com

ocaratuzumab MENTRIK Biotech lymphoma Phase I compeleted (AME-133v) Dallas, TX www.mentrik.com

Medicines in Development Cancer 2014 57 Medicines and Vaccines in Development for Cancers

Lymphoma

Product Name Sponsor Indication Development Phase

ONO-4059 Ono Pharmaceuticals B cell lymphoma Phase I (Btk inhibitor) Osaka, Japan

pinatuzumab vedotin Genentech DLBCL, NHL Phase II (anti-CD22 antibody drug South San Francisco, CA www.gene.com conjugate)

Pixuvri® CTI BioPharma DLBCL Phase III pixantrone Seattle, WA www.ctibiopharma.com

PNT2258 ProNAi Therapeutics NHL Phase II (bcl-2 oncogene inhibitor) Plymouth, MI (see also solid tumors) www.pronai.com

polatuzumab vedotin Genentech DLBCL, NHL Phase II (anti-CD79b antibody drug South San Francisco, CA www.gene.com conjugate)

Resimmune™ Angimmune CTCL Phase I/II A-dmDT390-bisFv immunotoxin Rockville, MD (see also skin) www.angimmune.com

Revlimid® Celgene DLBCL (maintenance), follicular Phase III lenalidomide Summit, NJ lymphoma (1st-line), relapsed/ www.celgene.com refractory indolent lymphoma (see also hematological, leukemia, myeloma) ------DLBCL-ABC subtype (1st-line) Phase II www.celgene.com

RRx-001 RadioRx late-stage lymphoma Phase I (free radical stimulant) Mountain View, CA (see also colorectal, solid tumors) www.radiorx.com

SAR3419 Sano US B-cell refractory/relapsed Phase II (maytansin-loaded anti-CD19 Bridgewater, NJ malignancies www.sano .com mAb)

SGN-CD19A Seattle Genetics NHL Phase I (antibody drug conjugate) Bothell, WA (see also leukemia) www.seattlegenetics.com

SGN-CD70A Seattle Genetics NHL Phase I Bothell, WA (see also kidney) www.seattlegenetics.com

SHAPE TetraLogic Pharmaceuticals CTCL Phase I (HDAC inhibitor) Malvern, PA www.tetralogicpharma.com ORPHAN DRUG

SNS-01 Sevion Therapeutics DLBCL, mantle cell lymphoma Phase I/II (nano-encapsulated gene therapy) Bridgewater, NJ (see also myeloma) www.seviontherapeutics.com ORPHAN DRUG

58 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Lymphoma

Product Name Sponsor Indication Development Phase

TG-1101 TG Therapeutics mantle cell lymphoma Phase I (anti-CD20 mAb) New York, NY (see also leukemia) www.tgtherapeutics.com ORPHAN DRUG

Treanda® Teva Pharmaceutical advanced indolent NHL, mantle cell Phase III bendamustine liquid Frazier, PA lymphoma www.tevapharm.com ORPHAN DRUG ------relapsed or refractory mantle cell Phase II lymphoma www.tevapharm.com (combination therapy)

trifarotene Galderma CTCL Phase I Lausanne, Switzerland www.galderma.com

Velcade® Millennium Pharmaceuticals mantle cell lymphoma (1st-line) Phase III bortezomib Cambridge, MA www.millennium.com ------DLBCL Phase II www.millennium.com

veltuzumab Immunomedics NHL (combination therapy) Phase II (humanized anti-CD20 mAb) Morris Plains, NJ www.immunomedics.com

VS-5584 Verastem late-stage lymphoma Phase I (PI3K/mTOR inhibitor) Cambridge, MA (see also solid tumors) www.verastem.com

Zydelig® Gilead Sciences indolent NHL Phase III idelalisib Foster City, CA (see also leukemia) www.gilead.com

Myeloma

Product Name Sponsor Indication Development Phase

afuresertib GlaxoSmithKline multiple myeloma Phase I (AKT protein kinase inhibitor) Research Triangle Park, NC (see also ovarian) www.gsk.com

ALT-803 Altor BioScience multiple myeloma Phase I/II (IL-15 superagonist complex) Miramar, FL (see also bladder, hematological, skin) www.altorbioscience.com

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

Medicines in Development Cancer 2014 59 Medicines and Vaccines in Development for Cancers

Myeloma

Product Name Sponsor Indication Development Phase

BT062 Biotest Pharmaceuticals multiple myeloma Phase I/II (tubulin polymerisation inhibitor) Dreieich, Germany www.biotest.de

CB-5083 Cleave Biosciences multiple myeloma Phase I (P97 ATPase inhibitor) Burlingame, CA www.cleavebio.com

CPI-0610 Constellation Pharmaceuticals multiple myeloma Phase I (BET inhibitor) Cambridge, MA (see also hematological, leukemia, www.constellationpharma.com lymphoma)

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

daratumumab Janssen Research & Development relapsed/refractory multiple myeloma Phase III Raritan, NJ (Breakthrough Therapy) www.janssenrnd.com

DKN-01 HealthCare Pharmaceuticals multiple myeloma Phase I/II (DKK1 protein inhibitor) Cambridge, MA (see also lung, other) ww.healthcarepharmaceuticals.com

elotuzumab AbbVie multiple myeloma (1st-line) Phase III North Chicago, IL (combination therapy), relapsed/ www.abbvie.com Bristol-Myers Squibb refractory multiple myeloma www.bms.com Princeton, NJ (combination therapy) ------(Breakthrough Therapy) Phase II ------www.abbvie.com multiple myeloma (2nd-line) www.bms.com (combination therapy)

lanesib Array BioPharma multiple myeloma Phase II (KSP inhibitor) Boulder, CO www.arraybiopharma.com

FPI-01 Formula Pharmaceuticals multiple myeloma Phase I (multi-peptide Berwyn, PA (see also leukemia) www.formulapharma.com immunotherapeutic)

GSK2110183 GlaxoSmithKline multiple myeloma Phase I (AKT protein kinase inhibitor) Research Triangle Park, NC www.gsk.com

ixazomib Millennium Pharmaceuticals relapsed/refractory multiple myeloma Phase III (proteasome inhibitor) Cambridge, MA (see also hematological, lymphoma, www.millennium.com solid tumors)

Keytruda® Merck multiple myeloma Phase I pembrolizumab Whitehouse Station, NJ (see also bladder, breast, head/neck, www.merck.com hematological, kidney, lung, stomach)

Kyprolis® Onyx Pharmaceuticals multiple myeloma Phase III car lzomib South San Francisco, CA (combination therapy) www.onyx.com ORPHAN DRUG (see also lung)

60 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Myeloma

Product Name Sponsor Indication Development Phase

LGH447 Novartis Pharmaceuticals multiple myeloma Phase I/II (proto oncogene protein c East Hanover, NJ (see also hematological, leukemia) www.novartis.com pim-1 inhibitor)

marizomib intravenous Triphase Accelerator multiple myeloma Phase II ORPHAN DRUG San Diego, CA www.triphaseco.com

melphalan intravenous Spectrum Pharmaceuticals multiple myeloma Phase II (Captisol-Enabled® melphalan) Henderson, NV www.sppirx.com

MOR202 Celgene multiple myeloma Phase I (anti-CD38 antibody) Summit, NJ www.celgene.com MorphoSys www.morphosys.com Martinsried, Germany

NY-ESO-1/LAGE-1-speci c T-cells Adaptimmune advanced myeloma Phase I/II Oxon, United Kingdom (see also ovarian, sarcoma, skin) www.adaptimmune.com

panobinostat Novartis Pharmaceuticals multiple myeloma application submitted (HDAC inhibitor) East Hanover, NJ www.novartis.com

pelareorep Oncolytics Biotech relapsed multiple myeloma Phase I Calgary, Canada (see also colorectal, head/neck, www.oncolyticsbiotech.com lung, ovarian, pancreatic, skin, solid tumors, other)

plitidepsin Pharmamar relapsed refractory multiple myeloma Phase III ORPHAN DRUG Madrid, Spain www.pharmamar.com

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

Revlimid® Celgene multiple myeloma (1st-line) application submitted lenalidomide Summit, NJ (see also hematological, leukemia, www.celgene.com ORPHAN DRUG lymphoma) ------multiple myeloma (maintenance) Phase III www.celgene.com

rocilinostat Acetylon Pharmaceuticals multiple myeloma Phase I/II (HDAC inhibitor) Boston, MA www.acetylon.com

SAR650984 Sano US multiple myeloma Phase II (anti-CD38 naked mAb) Bridgewater, NJ www.sano .com

SNS-01 Sevion Therapeutics multiple myeloma Phase I/II (nano-encapsulated gene therapy) Bridgewater, NJ (see also lymphoma) www.seviontherapeutics.com ORPHAN DRUG

Medicines in Development Cancer 2014 61 Medicines and Vaccines in Development for Cancers

Myeloma

Product Name Sponsor Indication Development Phase

Sylvant® Janssen Research & Development smoldering multiple myeloma Phase II siltuximab Raritan, NJ www.janssenrnd.com

TAS-120 Taiho Oncology multiple myeloma Phase I (FGF/FGFR inhibitor) Princeton, NJ (see also solid tumors) www.taihooncology.com

TG02 Tragara Pharmaceuticals multiple myeloma Phase I (CDK inhibitor) Carlsbad, CA (see also leukemia) www.tragarapharma.com

Zolinza® Merck multiple myeloma (combination Phase III vorinostat Whitehouse Station, NJ therapy) www.merck.com

Ovarian Cancer

Product Name Sponsor Indication Development Phase

afuresertib GlaxoSmithKline ovarian cancer Phase II (Akt protein kinase inhibitor) Research Triangle Park, NC (see also myeloma) www.gsk.com

alisertib Millennium Pharmaceuticals ovarian cancer Phase II (auroura A kinase inhibitor) Cambridge, MA (see also lung, lymphoma) www.millennium.com

Avastin® Genentech platinum-resistant relapsed ovarian application submitted bevacizumab South San Francisco, CA cancer www.gene.com ORPHAN DRUG (see also brain, lung, other) ------metastatic ovarian cancer (1st-line), Phase III platinum-sensitive relapsed ovarian www.gene.com cancer

AZD1775 AstraZeneca ovarian cancer Phase II (WEE-1 inhibitor) Wilmington, DE www.astrazeneca.com

BBI608 Boston Biomedical ovarian cancer Phase I/II (cancer stemness kinase inhibitor) Cambridge, MA (see also breast, colorectal, lung, skin, www.bostonbiomedical.com stomach)

birinapant TetraLogic Pharmaceuticals ovarian cancer Phase I/II (apoptosis stimulator) Malvern, PA (combination therapy) www.tetralogicpharm.com (see also colorectal, hematological)

BNC105 Bionomics ovarian cancer Phase I (vascular disrupting agent) Thebarton, Australia (see also kidney) www.bionomics.com.au

CVac™ Prima BioMed ovarian cancer Phase II cancer vaccine MUC-1 Sydney, Australia (Fast Track) www.primabiomed.com.au ORPHAN DRUG

62 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Ovarian Cancer

Product Name Sponsor Indication Development Phase

Cynviloq™ Sorrento Therapeutics ovarian cancer Phase II paclitaxel polymeric micelle for San Diego, CA (see also bladder, breast, lung, www.sorrentotherapeutics.com injection pancreatic)

Cyramza® Lilly ovarian cancer Phase II ramucirumab Indianapolis, IN (see also bladder, breast, colorectal, www.lilly.com liver, lung, solid tumors, stomach)

demcizumab OncoMed Pharmaceuticals ovarian cancer Phase I/II (DLL4 inhibitor) Redwood City, CA www.oncomed.com

DPX-Survivac Immunovaccine ovarian cancer Phase I/II (peptide cancer vaccine) Halifax, Canada www.imvaccine.com

EGEN-001 EGEN ovarian cancer (monotherapy) Phase II (IL2-based immunotherapy) Huntsville, AL www.egeninc.com ORPHAN DRUG ------ovarian cancer (combination therapy) Phase I www.egeninc.com

elesclomol Synta Pharmaceuticals recurrent, persistent ovarian cancer Phase II (HSP70 heat shock protein) Lexington, MA www.syntapharma.com

ENMD-2076 CASI Pharmaceuticals ovarian clear cell carcinoma Phase II (aurora A/angiogenic kinase Rockville, MD (see also breast, sarcoma) www.casipharmaceuticals.com inhibitor) ORPHAN DRUG

etirinotecan pegol Nektar Therapeutics platinum-resistant ovarian cancer Phase II completed (PEGylated irinotecan) San Francisco, CA (see also breast, colorectal) www.nektar.com ORPHAN DRUG

FANG™ Vaccine Gradalis high-risk stage IIIc ovarian cancer Phase II genetically modi ed autologous Dallas, TX (see also colorectal, skin, solid www.gradalisinc.com tumor cell vaccine tumors)

GALE-301 Galena Biopharma ovarian cancer Phase II (folate binding protein Portland, OR (see also other) www.galenabiopharma.com immunotherapy)

ganetespib Synta Pharmaceuticals ovarian cancer Phase II (Hsp90 inhibitor) Lexington, MA (see also breast, leukemia, lung) www.syntapharma.com

INCB24360 Incyte ovarian cancer Phase II (IDO1 inhibitor) Wilmington, DE (see also lung, skin, other) www.incyte.com

Medicines in Development Cancer 2014 63 Medicines and Vaccines in Development for Cancers

Ovarian Cancer

Product Name Sponsor Indication Development Phase

ipafricept Bayer HealthCare Pharmaceuticals ovarian cancer Phase I (Wnt protein inhibitor) Whippany, NJ (see also liver, pancreatic) www.bayerpharma.com OncoMed Pharmaceuticals www.oncomed.com Redwood City, CA

Karenitecin® BioNumerik Pharmaceuticals advanced ovarian cancer Phase III cositecan San Antonio, TX www.bionumerik.com

lifastuzumab vedotin Genentech platinum-resistant ovarian cancer Phase II (anti-NaPi2b antibody drug South San Francisco, CA (see also lung) www.gene.com conjugate) ------(RG7599) platinum-sensitive ovarian cancer Phase I www.gene.com

LY2606368 Lilly BRCA 1/2 mutation ovarian cancer, Phase II (Chk1 inhibitor) Indianapolis, IN high grade ovarian cancer www.lilly.com (see also breast, solid tumors)

ME-344 MEI Pharma ovarian cancer Phase I (mitochondrial inhibitor) San Diego, CA (see also lung) www.meipharma.com

MEK162 Array BioPharma low-grade serious ovarian cancer Phase III (MEK inhibitor) Boulder, CO (see also skin, solid tumors) www.arraybiopharma.com Novartis Pharmaceuticals www.novartis.com East Hanover, NJ

MM-121 Merrimack Pharmaceuticals ovarian cancer Phase II (ErbB-3 receptor antagonist) Cambridge, MA (see also breast, lung) www.merrimackpharma.com

MORAb-003 Eisai platinum-sensitive ovarian cancer Phase III (IgG1 mAb) Woodcli Lake, NJ (see also lung) www.eisai.com ORPHAN DRUG Morphotek Exton, PA

niraparib TESARO ovarian cancer Phase III (PARP inhibitor) Waltham, MA (see also breast, sarcoma) www.tesarobio.com

NY-ESO-1/LAGE-1-speci c T-cells Adaptimmune ovarian cancer Phase I/II Oxon, United Kingdom (see also myeloma, sarcoma, skin) www.adaptimmune.com

olaparib AstraZeneca BRCA-mutated platinum-sensitive application submitted (PARP inhibitor) Wilmington, DE relapsed ovarian cancer www.astrazeneca.com (see also breast, stomach) ------BRCA-mutation ovarian cancer Phase III (1st-line) www.astrazeneca.com

64 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Ovarian Cancer

Product Name Sponsor Indication Development Phase

oregovomab Quest PharmaTech ovarian cancer (1st-line) Phase II ORPHAN DRUG Edmonton, Canada www.questpharmatech.com

OVax® AVAX Technologies relapsed ovarian cancer Phase I/II autologous tumor cell-based Philadelphia, PA www.avax-tech.com vaccine ORPHAN DRUG

pelareorep Oncolytics Biotech persistant or recurrent ovarian cancer Phase II Calgary, Canada (see also colorectal, head/neck, lung, www.oncolyticsbiotech.com myeloma, pancreatic, skin, solid tumors, other)

pimasertib/SAR245509 EMD Serono ovarian cancer Phase II (MEK inihibitor/dual PI3K, mTOR Rockland, MA (see also solid tumors) www.emdserono.com inhibitor) Sano US www.sano .com Bridgewater, NJ

RG7458 Genentech ovarian cancer Phase I (MUC16 antibody drug conjugate) South San Francisco, CA (see also pancreatic) www.gene.com

RG7882 Genentech ovarian cancer Phase I (antibody drug conjugate) South San Francisco, CA www.gene.com

rucaparib Clovis Oncology ovarian cancer Phase III (PARP inhibitor) Boulder, CO (see also pancreatic) www.clovisoncology.com ORPHAN DRUG

SGI110 Astex Pharmaceuticals ovarian cancer Phase II (DNMT inhibitor) Dublin, CA (see also leukemia, liver) www.astx.com

trebananib Amgen ovarian cancer Phase III (recombinant peptide-Fc fusion Thousand Oaks, CA www.amgen.com protein)

Vargatef™ Boehringer Ingelheim Pharmaceuticals ovarian cancer Phase III nintedanib Ridge eld, CT (see also lung) www.boehringer-ingelheim.com

VB-111 VBL Therapeutics ovarian cancer Phase I/II (vascular targeting system) Or Yehuda, Israel (see also brain, other) www.vblrx.com

vinorelbine liposomal Spectrum Pharmaceuticals ovarian cancer Phase I Henderson, NV (see also lung) www.sppirx.com

VS-6063 Verastem ovarian (combination therapy) Phase II (FAK inhibitor) Cambridge, MA (see also lung) www.verastem.com

Medicines in Development Cancer 2014 65 Medicines and Vaccines in Development for Cancers

Ovarian Cancer

Product Name Sponsor Indication Development Phase

VTX-2337 VentiRx Pharmaceuticals ovarian cancer Phase II (TLR8 agonist immunotherapy) Seattle, WA (see also head/neck) www.ventirx.com ORPHAN DRUG

Yervoy® Bristol-Myers Squibb ovarian cancer Phase II ipilimumab Princeton, NJ (see also lung, prostate, skin, www.bms.com stomach)

Yondelis® Janssen Research & Development relapsed ovarian cancer Phase III trabectedin Raritan, NJ (see also sarcoma) www.janssenrnd.com

Zybrestat® OXiGENE ovarian cancer Phase II fosbretabulin South San Francisco, CA www.oxigene.com ORPHAN DRUG Pancreatic Cancer

Product Name Sponsor Indication Development Phase

177Lu-DOTATATE Advanced Accelerator Applications metastatic gastro-entero-pancreatic Phase III (somatostatin receptor antagonist) New York, NY neuroendocrine tumors www.adacap.com ORPHAN DRUG

Abraxane® Celgene pancreatic cancer (adjuvant) Phase III paclitaxel protein-bound particles Summit, NJ (see also breast) www.celgene.com for injectable suspension (albumin-bound) ORPHAN DRUG

algenpantucel-L NewLink Genetics pancreatic cancer (resected) Phase III (cancer immunotherapy vaccine) Ames, IA (Fast Track) www.newlinkgenetics.com ORPHAN DRUG ------pancreatic cancer (borderline Phase III resectable of locally advanced www.newlinkgenetics.com unresectable)

anti-MUC1 AR20.5 mAb Quest PharmaTech pancreatic cancer Phase I/II (chemotherapy-enhanced Edmonton, Canada www.questpharmatech.com immunotherapy)

apatorsen OncoGenex Pharmaceuticals metastatic pancreatic cancer Phase II (Hsp27 inhibitor) Bothell, WA (see also bladder, lung, prostate) www.oncogenex.com

cancer gene therapy Advantagene pancreatic cancer Phase I (AdV-tK) Auburndale, MA (see also brain, prostate) www.advantagene.com

66 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Pancreatic Cancer

Product Name Sponsor Indication Development Phase

CPI-613 Cornerstone Pharmaceuticals pancreatic cancer Phase II ORPHAN DRUG Cranbury, NJ www.cornerstonepharma.com

CRS-207 Aduro BioTech pancreatic cancer in combination with Phase II (cancer immunotherapy) Berkeley, CA GVAX Pancreas www.adurobiotech.com ORPHAN DRUG (Breakthrough Therapy) (see also lung)

Cynviloq™ Sorrento Therapeutics pancreatic cancer Phase II paclitaxel polymeric micelle San Diego, CA (see also bladder, breast, lung, www.sorrentotherapeutics.com for injection ovarian)

ensituximab Precision Biologics advanced pancreatic cancer Phase II (neoplasm antigen inhibitor) Dallas, TX (see also colorectal) www.precision-biologics.com ORPHAN DRUG

FG-3019 Fibrogen advanced pancreatic cancer Phase II (connective tissue growth factor San Francisco, CA www. brogen.com inhibitor mAb)

galunisertib Lilly pancreatic cancer Phase I/II (TGF-beta1 inhibitor) Indianapolis, IN (see also brain, liver) www.lilly.com

GI-4000 GlobeImmune resected pancreatic cancer Phase II (mutated Ras cancer vaccine) Louisville, CO (see also lung) www.globeimmune.com

glufosfamide Eleison Pharmaceuticals metastatic pancreatic cancer Phase III ORPHAN DRUG St. Petersburg, FL (2nd-line) www.eleison-pharma.com (Fast Track)

Imprime PGG® Biothera advanced pancreatic ductal cancer Phase I intravenous immunostimulant Eagan, MN (see also colorectal, leukemia, lung, www.biothera.com lymphoma)

ipafricept Bayer HealthCare Pharmaceuticals pancreatic cancer Phase I (Wnt protein inhibitor) Whippany, NJ (see also liver, ovarian) www.bayerpharma.com OncoMed Pharmaceuticals www.oncomed.com Redwood City, CA

IRT-102 TNI Biotech pancreatic cancer Phase II (methionine enkephalin) Orlando, FL www.tnibiotech.com

Jaka ® Incyte pancreatic cancer Phase II ruxolitinib Wilmington, DE (see also breast, colorectal, lung, www.incyte.com other)

KD032 Kadmon Pharmaceuticals pancreatic cancer Phase II (Ras antagonist) Warrendale, PA (see also colorectal, lung) www.kadmon.com ORPHAN DRUG

Medicines in Development Cancer 2014 67 Medicines and Vaccines in Development for Cancers

Pancreatic Cancer

Product Name Sponsor Indication Development Phase

masitinib AB Science USA metastatic pancreatic cancer Phase III Short Hills, NJ (see also stomach) www.ab-science.com

MLN0264 Millennium Pharmaceuticals advanced pancreatic cancer Phase II (GCC antibody drug conjugate) Cambridge, MA (see also stomach) www.millennium.com

MM-398 Merrimack Pharmaceuticals pancreatic cancer (2nd-line) Phase III (irinotecan/nanotherapeutic) Cambridge, MA (see also brain, colorectal) www.merrimackpharma.com

momelotinib Gilead Sciences pancreatic cancer Phase II (JAK inhibitor) Foster City, CA (see also hematological) www.gilead.com

necuparanib Momenta Pharmaceuticals pancreatic cancer Phase I/II ORPHAN DRUG Cambridge, MA www.momentapharma.com

PCI-27483 Pharmacyclics pancreatic cancer Phase II (FVIIa inhibitor) Sunnyvale, CA www.pharmacyclics.com

PEGPH20 Halozyme Therapeutics metastatic pancreatic cancer Phase II (pegylated recombinant human San Diego, CA (Fast Track) www.halozyme.com hyaluronidase)

pelareorep Oncolytics Biotech advanced pancreatic cancer Phase II Calgary, Canada (see also colorectal, head/neck, lung, www.oncolyticsbiotech.com myeloma, ovarian, skin, solid tumors, other)

pimasertib EMD Serono pancreatic cancer Phase II (MEK inhibitor) Rockland, MA (see also skin) www.emdserono.com

PLX7486 Daiichi Sankyo pancreatic cancer Phase I (TRK inhibitor) Parsippany, NJ (combination therapy) www.dsi.com Plexxikon (see also solid tumors) www.plexxikon.com Berkeley, CA

PRI-724 Prism Pharma pancreatic cancer Phase I (CBP/ß-catenin inhibitor) Tokyo, Japan (see also leukemia, solid tumors) www.prismbiolab.com

RG7458 Genentech pancreatic cancer Phase I (MUC16 antibody drug conjugate) South San Francisco, CA (see also ovarian) www.gene.com

RG7600 Genentech unresectable pancreatic cancer Phase I (mesothelin antibody drug South San Francisco, CA www.gene.com conjugate)

rucaparib Clovis Oncology BRCA-mutated pancreatic cancer Phase II (PARP inhibitor) Boulder, CO (see also ovarian) www.clovisoncology.com

68 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Pancreatic Cancer

Product Name Sponsor Indication Development Phase

SM04755 Samumed advanced pancreatic cancer Phase I (Wnt inhibitor) San Diego, CA (see also colorectal, liver, stomach) www.samumed.com

Sprycel® Bristol-Myers Squibb pancreatic cancer Phase II dasatinib Princeton, NJ (see also other) www.bms.com Otsuka America Pharmaceutical www.otsuka.com Rockville, MD

tarextumab OncoMed Pharmaceuticals pancreatic cancer Phase I/II (anti-NOTCH 2/3) Redwood City, CA (see also lung) www.oncomed.com

TH-302 EMD Serono pancreatic cancer Phase III (hypoxia-activated prodrug) Rockland, MA (see also hematological, lung, www.emdserono.com ORPHAN DRUG Threshold Pharmaceuticals sarcoma, skin, solid tumors) www.thresholdpharm.com South San Francisco, CA

TL-118 Tiltan Pharma metastatic pancreatic cancer Phase II Jerusalem, Israel (1st-line) www.tiltanpharma.com

Y-90 clivatuzumab tetraxetan Immunomedics relapsed pancreatic cancer Phase III ORPHAN DRUG Morris Plains, NJ (Fast Track) www.immunomedics.com ------pancreatic cancer (1st-line) Phase I/II (Fast Track) www.immunomedics.com Prostate Cancer

Product Name Sponsor Indication Development Phase

abituzumab EMD Serono prostate cancer Phase II (anti-integrin mAb) Rockland, MA (see also colorectal) www.emdserono.com

AE37 Antigen Express prostate cancer Phase II (immunotherapeutic) Worcester, MA (see also breast) www.antigenexpress.com

APC100 Adamis Pharmaceuticals prostate cancer Phase I/II (androgen antagonist) San Diego, CA www.adamispharmaceuticals.com

apatorsen OncoGenex Pharmaceuticals prostate cancer Phase II (Hsp27 inhibitor) Bothell, WA (see also bladder, lung, pancreatic) www.oncogenex.com

ATL101 ATLAB Pharma metastatic prostate cancer Phase II (177 Lu-labeled anti-PSMA mAb) Nantes, France www.atlab-pharma.com Weill Medical College New York, NY

Medicines in Development Cancer 2014 69 Medicines and Vaccines in Development for Cancers

Prostate Cancer

Product Name Sponsor Indication Development Phase

AZD5312 AstraZeneca prostate cancer Phase I (androgen receptor inhibitor) Wilmington, DE www.astrazeneca.com Isis Pharmaceuticals www.isispharm.com Carlsbad, CA

BIND-014 BIND Therapeutics prostate cancer Phase II (PSMA-targeted docetaxel) Cambridge, MA (see also lung) www.bindtherapeutics.com

BPX-201 Bellicum Pharmaceuticals metastatic castration-resistant Phase I/II (dendritic cell vaccine) Houston, TX prostate cancer www.bellicum.com (combination therapy)

cancer gene therapy Advantagene newly diagnosed prostate cancer Phase III (AdV-tK) Auburndale, MA (Fast Track) www.advantagene.com (see also brain, pancreatic)

CFG920 Novartis Pharmaceuticals metastatic castration-resistant Phase I/II (steroid 17-alpha-hydroxylase East Hanover, NJ prostate cancer www.novartis.com inhibitor)

custirsen (OGX-111) OncoGenex Pharmaceuticals metastatic castration-resistant Phase III (antisense oligonucleotide) Bothell, WA prostate cancer (2nd-line) www.oncogenex.com Teva Pharmaceutical (Fast Track) www.tevapharm.com Frazier, PA (see also lung)

DCVax®-Prostate Northwest Biotherapeutics late-stage hormone independent Phase II completed dendritic cell vaccine Bethesda, MD prostate cancer www.nwbio.com

EC1169 Endocyte prostate cancer Phase I (PSMA-tubulysin) West Lafayette, IN www.endocyte.com

galeterone Tokai Pharmaceuticals metastatic castration-resistant Phase II (androgen receptor antagonist) Cambridge, MA prostate cancer www.tokaipharma.com (Fast Track)

GTx-758 GTx secondary hormone therapy for Phase II (ER alpha agonist) Memphis, TN castration-resistant prostate cancer www.gtxinc.com

indoximod NewLink Genetics metastatic castration-resistant Phase II (IDO pathway inhibitor) Ames, IA prostate cancer www.newlinkgenetics.com (see also breast)

ipatasertib Array BioPharma prostate cancer Phase II (GDC-0068) Boulder, CO (see also breast, stomach) www.arraybiopharma.com (Akt inhibitor) Genentech www.gene.com South San Francisco, CA

IRX4204 Io Therapeutics prostate cancer Phase II (retinoid X receptor agonist) Santa Ana, CA www.io-therapeutics.com

70 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Prostate Cancer

Product Name Sponsor Indication Development Phase

ISIS-EIF4ERX Isis Pharmaceuticals castration-resistant prostate cancer Phase II (antisense oligonucleotide) Carlsbad, CA (see also lung) www.isispharm.com

Jevtana® Sano US metastatic prostate cancer Phase III cabazitaxel Bridgewater, NJ www.sano .com

JNJ-56021927/ARN-509 Janssen Research & Development hormone refractory prostate cancer Phase III (androgen receptor antagonist) Raritan, NJ www.janssenrnd.com

KPT-330 Karyopharm Therapeutics metastatic prostate cancer Phase II (XPO1 inhibitor) Newton, MA (see also brain, hematological, www.karyopharm.com leukemia, solid tumors)

LFA102 Novartis Pharmaceuticals prolactin receptor-positive Phase I (anti-prolactin receptor mAb) East Hanover, NJ castration-resistant prostate cancer www.novartis.com XOMA (see also breast) www.xoma.com Berkeley, CA

MER-104 Merrion Pharmaceuticals prostate cancer Phase I (oral acyline) Dublin, Ireland www.merrionpharma.com

mipsagargin GenSpera prostate cancer Phase II (ATPase inhibitor) San Antonio, TX (see also brain, liver) www.genspera.com

MVA-BN-PRO Bavarian Nordic hormone refractory prostate cancer Phase I/II (immunotherapy vaccine) Mountain View, CA www.bavarian-nordic.com

MVI-816 Madison Vaccines prostate cancer Phase II (PAP plasmid DNA) Madison, WI www.madisonvaccinesinc.com

NX-1207 Nymox Pharmaceutical early-stage prostate cancer Phase II completed (apoptosis stimulant) Hasbrouck Heights, NJ www.nymox.com

ODM-201 Bayer HealthCare Pharmaceuticals prostate cancer Phase II (androgen receptor inhibitor) Whippany, NJ www.bayerpharma.com Orion www.orion. Espoo, Finland

ONC1-13B AllaChem metastatic prostate cancer Phase I/II (androgen receptor antagonist) Hallandale Beach, FL www.allachem.com

orteronel Millennium Pharmaceuticals metastatic castration-resistant Phase III (lyase inhibitor) Cambridge, MA prostate cancer www.millennium.com ------non-metastatic prostate cancer Phase II www.millennium.com

ozarelix Spectrum Pharmaceuticals hormone dependent prostate cancer Phase II (GnRH inhibitor) Henderson, NV www.sppirx.com

Medicines in Development Cancer 2014 71 Medicines and Vaccines in Development for Cancers

Prostate Cancer

Product Name Sponsor Indication Development Phase

prostate cancer vaccine OncBioMune prostate cancer Phase I (PSA/IL-2/GM-CSF vaccine) Baton Rouge, LA www.oncbiomune.com

Prostvac® Bavarian Nordic metastatic castration-resistant Phase III targeted immunotherapy Mountain View, CA prostate cancer www.bavarian-nordic.com National Cancer Institute Bethesda, MA

Provenge® Dendreon recurrent early stage prostate cancer Phase III sipuleucel-T Seattle, WA www.dendreon.com ------recurrent hormone refractory, Phase II metastatic prostate cancer www.dendreon.com

PSMA ADC therapeutic Progenics Pharmaceuticals prostate cancer Phase II (antibody drug conjugate) Tarrytown, NY www.progenics.com

RG7450 Genentech prostate cancer Phase I (anti-STEAP1 antibody drug South San Francisco, CA www.gene.com conjugate)

TAK-385 Millennium Pharmaceuticals prostate cancer Phase II (GnRH angonist) Cambridge, MA www.millennium.com

tasquinimod Active Biotech metastatic hormone refractory Phase III Lund, Sweden prostate cancer www.activebiotech.com

TeloB-VAX Adamis Pharmaceuticals prostate cancer Phase I (telomerase vaccine) San Diego, CA www.adamispharmaceuticals.com

VT-122 Vicus Therapeutics pre-chemotherapy prostate cancer Phase II (cancer immunotherapy) Morristown, NJ (see also liver) www.vicustherapeutics.com

Xo go® Bayer HealthCare Pharmaceuticals bone metastases in Phase III radium-223 dichloride Whippany, NJ castration-resistant prostate cancer www.bayerpharma.com (1st-line) (combination therapy) ------bone metastases in Phase II castration-resistent prostate cancer www.bayerpharma.com (combination therapy)

Xtandi® Astellas Pharma US metastatic castration-resistant application submitted enzalutamide Northbrook, IL prostate cancer (treatment naïve) www.astellas.com (androgen receptor inhibitor) Medivation (see also breast) www.medivation.com San Francisco, CA ------non-metastatic castration-resistant Phase III prostate cancer www.astellas.com www.medivation.com

72 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Prostate Cancer

Product Name Sponsor Indication Development Phase

Yervoy® Bristol-Myers Squibb prostate cancer (1st-line) Phase III ipilimumab Princeton, NJ (see also lung, ovarian, skin, stomach) www.bms.com

zoptarelin doxorubicin AEterna Zentaris castration-/taxane-resistant prostate Phase II (type II DNA topoisomerase Quebec, Canada cancer www.aezsinc.com inhibitor) (see also other) Sarcoma

Product Name Sponsor Indication Development Phase

aldoxorubicin CytRx soft tissue sarcoma (2nd-line) Phase III (delivery-enhanced doxorubicin) Los Angeles, CA (see also brain, lung) www.cytrx.com ORPHAN DRUG ------Kaposi’s sarcoma, Phase II soft tissue sarcoma (1st-line) www.cytrx.com

ENMD-2076 CASI Pharmaceuticals soft tissue sarcoma Phase II (aurora A/angiogenic Rockville, MD (see also breast, ovarian) www.casipharmaceuticals.com kinase inhibitor)

Halaven® Eisai soft tissue sarcoma Phase III eribulin Woodcli Lake, NJ (see also breast, lung) www.eisai.com ORPHAN DRUG

inhaled lipid cisplatin Eleison Pharmaceuticals prevention of pulmonary metastases Phase II St. Petersburg, FL from osteosarcoma (pediatric) www.eleison-pharma.com

MORAb-004 Eisai soft tissue sarcoma Phase II (CD248 antigen inhibitor) Woodcli Lake, NJ (see also colorectal, skin) www.eisai.com ORPHAN DRUG

niraparib TESARO Ewing’s sarcoma Phase I (PARP inhibitor) Waltham, MA (see also breast, ovarian) www.tesarobio.com

NY-ESO-1/LAGE-1-speci c T-cells Adaptimmune synovial sarcoma Phase I Oxon, United Kingdom (see also myeloma, ovarian, skin) www.adaptimmune.com

sarcoma vaccine MabVax Therapeutics metastatic sarcoma Phase II San Diego, CA www.mabvax.com

TH-302 EMD Serono soft tissue sarcoma Phase III (hypoxia-activated prodrug) Rockland, MA (see also hematological, lung, www.emdserono.com Threshold Pharmaceuticals pancreatic, skin, solid tumors) www.thresholdpharm.com South San Francisco, CA

Medicines in Development Cancer 2014 73 Medicines and Vaccines in Development for Cancers

Sarcoma

Product Name Sponsor Indication Development Phase

TRC105 TRACON Pharmaceuticals advanced soft tissue sarcoma Phase I/II (ENG protein inhibitor) San Diego, CA (see also brain, kidney) www.traconpharma.com

Yondelis® Janssen Research & Development soft tissue sarcoma Phase III trabectedin Raritan, NJ (see also ovarian) www.janssenrnd.com

Skin Cancer

Product Name Sponsor Indication Development Phase

ABT-RTA-408 AbbVie relapsed/refractory melanoma Phase I North Chicago, IL (see also lung) www.abbvie.com Reata Pharmaceuticals www.reatapharma.com Irving, TX

ADI-PEG 20 Polaris Pharmaceuticals metastatic melanoma Phase I (PEG arginine deiminase) San Diego, CA (see also breast, leukemia, liver, lung, www.polarispharma.com ORPHAN DRUG lymphoma)

Ad-RTS-IL-12 ZIOPHARM Oncology malignant melanoma Phase II (interleukin-12 gene therapy) Boston, MA (see also breast) www.ziopharm.com

AE-M Antigen Express melanoma Phase I (immunotherapeutic) Worcester, MA www.antigen-express.com

alpha-gal glycosphingolipid Agalimmune melanoma Phase I completed (immunotherapy) Irvine, CA www.agalimmune.com

ALT-803 Altor BioScience metastatic melanoma Phase I/II (IL-15 superagonist complex) Miramar, FL (see also bladder, hematological, www.altorbioscience.com myeloma)

AT13387 Astex Pharmaceuticals melanoma Phase II (HSP90 inhibitor) Dublin, CA (see also lung) www.astx.com

bavituximab Peregrine Pharmaceuticals advanced melanoma Phase I Tustin, CA (see also breast, liver, lung, other) www.peregrineinc.com

BBI608 Boston Biomedical melanoma Phase I/II (cancer stemness kinase inhibitor) Cambridge, MA (see also breast, colorectal, lung, www.bostonbiomedical.com ovarian, stomach)

Cavatak™ Viralytics malignant melanoma Phase II coxsackievirus A21 Sydney, Australia www.viralytics.com ORPHAN DRUG

74 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Skin Cancer

Product Name Sponsor Indication Development Phase

CEP-32496 Teva Pharmaceutical advanced melanoma Phase II (BRAF kinase inhibitor) Frazier, PA (see also colorectal, solid tumors) www.tevapharm.com

cobimetinib Genentech metastatic melanoma Phase III (MEK inhibitor) South San Francisco, CA (see also solid tumors) www.gene.com

dorgenmeltucel-L NewLink Genetics malignant melanoma Phase II Ames, IA www.newlinkgenetics.com

E7016 Eisai malignant melanoma Phase II (PARP inhibitor) Woodcli Lake, NJ www.eisai.com

E7080 Eisai melanoma Phase II (multi-targeted kinase inhibitor) Woodcli Lake, NJ (see also brain, liver, lung, other) www.eisai.com

Erivedge® Genentech operable basal cell carcinoma Phase II vismodegib South San Francisco, CA (see also leukemia) www.gene.com

FANG™ Vaccine Gradalis advanced melanoma Phase II genetically modi ed autologous Dallas, TX (see also colorectal, ovarian, www.gradalisinc.com tumor cell vaccine solid tumors)

G100 Immune Design Merkel cell carcinoma Phase I (TLR4 agonist) Seattle, WA www.immunedesign.com

glembatumumab vedotin CellDex Therapeutics stage III or IV melanoma Phase II (antibody drug conjugate) Hampton, NJ (see also skin) www.celldex.com

GM-CT-01 Galectin Therapeutics melanoma Phase I (galectin inhibitor) Norcross, GA www.galectintherapeutics.com

GR-MD-02 Galectin Therapeutics melanoma Phase I (galectin-3 inhibitor) Norcross, GA www.galectintherapeutics.com

heat shock protein vaccine Agenus melanoma Phase I ORPHAN DRUG Lexington, MA (see also brain) www.agenusbio.com

IMCgp100 Immunocore malignant melanoma Phase I (CD3 antigen inhibitor) Oxon, United Kingdom www.immunocore.com

INCB24360 Incyte metastatic melanoma Phase II (IDO1 inhibitor) Wilmington, DE (see also lung, ovarian, other) www.incyte.com

interleukin-12 gene therapy OncoSec Medical malignant melanoma Phase II San Diego, CA (see also lymphoma) www.oncosec.com

LDE225 Novartis Pharmaceuticals advanced basal cell carcinoma Phase II (SMO protein inhibitor) East Hanover, NJ (see also brain, solid tumors) www.novartis.com

Medicines in Development Cancer 2014 75 Medicines and Vaccines in Development for Cancers

Skin Cancer

Product Name Sponsor Indication Development Phase

LGX818 Novartis Pharmaceuticals BRAF-mutant melanoma Phase III (BRAF inhibitor) East Hanover, NJ (see also colorectal, solid tumors) www.novartis.com

MAGE-A3 immunotherapeutic GlaxoSmithKline melanoma Phase III (recombinant antigen-speci c Research Triangle Park, NC www.gsk.com cancer immunotherapeutic)

MEDI4736 + dabrafenib MedImmune melanoma Phase I + trametinib Gaithersburg, MD www.medimmune.com (anti-PD-L1 mAb/BRAF inhibitor/ MEK inhibitor)

MEK162 Array BioPharma NRAS-mutant melanoma Phase III (MEK inhibitor) Boulder, CO (see also ovarian, solid tumors) www.arraybiopharma.com Novartis Pharmaceuticals www.novartis.com East Hanover, NJ

MEK162 and LGX818 Novartis Pharmaceuticals BRAF-mutant melanoma Phase III (MEK inhibitor/BRAF inhibitor) East Hanover, NJ www.novartis.com

Mekinist® trametinib + GlaxoSmithKline metastatic melanoma (adjuvant) Phase III Ta nlar® dabrafenib combination Research Triangle Park, NC www.gsk.com ORPHAN DRUG

melapuldencel-T NeoStem Oncology malignant melanoma Phase II (dendritic cell immunotherapy) New York, NY (Fast Track) www.neostem.com ORPHAN DRUG

MORAb-004 Eisai melanoma Phase II (CD248 antigen inhibitor) Woodcli Lake, NJ (see also colorectal, sarcoma) www.eisai.com

MSB0010445 EMD Serono melanoma Phase II (NHS-IL2 cancer immunotherapy) Rockland, MA www.emdserono.com

MSB0010718C EMD Serono Merkel cell carcinoma Phase II (anti-PD-L1 mAb) Rockland, MA (see also solid tumors) www.emdserono.com

MVax® AVAX technologies melanoma Phase III autologous tumor cell-based Philadelphia, PA www.avax-tech.com vaccine

nivolumab Bristol-Myers Squibb melanoma (1st-line), Phase III (PD-1 inhibitor) Princeton, NJ melanoma, (2nd-3rd-line) www.bms.com (see also brain, colorectal, head/neck, hematological, kidney, liver, lung, lymphoma, solid tumors) ------melanoma Phase I/II www.bms.com

76 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Skin Cancer

Product Name Sponsor Indication Development Phase

nivolumab + Yervoy® Bristol-Myers Squibb melanoma (1st-line) Phase II/III ipilimumab Princeton, NJ (see also brain, colorectal, head/neck, www.bms.com hematological, kidney, lung) ------melanoma Phase I www.bms.com

NY-ESO-1/LAGE-1-speci c T-cells Adaptimmune melanoma Phase I/II Oxon, United Kingdom (see also myeloma, ovarian, sarcoma) www.adaptimmune.com

Ontak® Eisai melanoma Phase II denileukin diftitox Woodcli Lake, NJ www.eisai.com

pelareorep Oncolytics Biotech metastatic melanoma Phase II Calgary, Canada (see also colorectal, head/neck, lung, www.oncolyticsbiotech.com myeloma, ovarian, pancreatic, solid tumors, other)

Picato® LEO Pharma basal cell cancer Phase II ingenol mebutate Parsippany, NJ www.leo-pharma.us

pimasertib EMD Serono melanoma Phase II (MEK inhibitor) Rockland, MA (see also pancreatic) www.emdserono.com

PLX3397 Daiichi Sankyo melanoma Phase II (Fms/Kit/Flt3-ITD inhibitor) Parsippany, NJ (combination therapy) www.dsi.com Plexxikon (see also brain, leukemia) www.plexxikon.com Berkeley, CA ------melanoma Phase I www.dsi.com www.plexxikon.com

POL-103A Polynoma late-stage malignant melanoma Phase III (immunotherapy vaccine) San Diego, CA www.polynoma.com ORPHAN DRUG

PV-10 Provectus Biopharmaceuticals malignant melanoma Phase II (rose bengal sodium) Knoxville, TN (see also liver) www.pvct.com ORPHAN DRUG

Resimmune™ Angimmune metastatic melanoma Phase I/II A-dmDT390-bisFv immunotoxin Rockville, MD (see also lymphoma) www.angimmune.com

RG7446 Genentech malignant melanoma Phase I (anti-PD-L1 mAb) South San Francisco, CA (see also bladder, kidney, lung) www.gene.com

RG7636 Genentech metastatic melanoma Phase I (ETBR antibody drug conjugate) South San Francisco, CA www.gene.com

Medicines in Development Cancer 2014 77 Medicines and Vaccines in Development for Cancers

Skin Cancer

Product Name Sponsor Indication Development Phase

talimogene laherparepvec Amgen regionally and distantly metastatic application submitted (cancer immunotherapy) Thousand Oaks, CA melanoma www.amgen.com

TH-302 EMD Serono advanced melanoma Phase II (hypoxia-activated prodrug) Rockland, MA (see also hematological, lung, www.emdserono.com Threshold Pharmaceuticals pancreatic, sarcoma, solid tumors) www.thresholdpharm.com South San Francisco, CA

TRX518 GITR advanced melanoma Phase I (GITR receptor antagonist) Cambridge, MA (see also solid tumors) www.gitrrx.com

tumor in ltrating lymphocyte Lion Biotechnologies malignant melanoma (2nd-line) Phase II (autologous cell therapy) Woodland Hills, CA www.lbio.com National Cancer Institute ------Bethesda, MD malignant melanoma (1st-line Phase I combination therapy) www.lbio.com

Yervoy® Bristol-Myers Squibb melanoma (adjuvant), metastatic Phase III ipilimumab Princeton, NJ melanoma (dose optimization) www.bms.com (see also lung, ovarian, prostate, stomach) ------melanoma (adolescents) Phase II www.bms.com

Zelboraf® Genentech BRAF-mutation-positive metastatic Phase III vemurafenib South San Francisco, CA melanoma (adjuvant) www.gene.com (see also other) ------BRAF-mutation-positive metastatic Phase I melanoma www.gene.com Solid Tumors

Product Name Sponsor Indication Development Phase

ABBV-399 AbbVie Phase I (antibody drug conjugate) North Chicago, IL www.abbvie.com

ABC294640 Apogee Biotechnology advanced solid tumors Phase I (sphingosine kinase-2 inhibitor) Hummelstown, PA www.apogee-biotech.com

ABT-414 AbbVie squamous cell solid tumors Phase II (antibody drug conjugate) North Chicago, IL (see also brain) www.abbvie.com

ABT-700 AbbVie advanced solid tumors Phase I (c-Met inhibitor) North Chicago, IL www.abbvie.com

78 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

ABT-767 AbbVie Phase I (PARP inhibitor) North Chicago, IL www.abbvie.com

ABT-806 AbbVie advanced solid tumors Phase I (epidermal growth factor receptor North Chicago, IL www.abbvie.com [EGFR] mAB)

AG-120 Agios Pharmaceuticals (see also hematological) Phase I (IDH1 inhibitor) Cambridge, MA www.agios.com Celgene www.celgene.com Summit, NJ

AGS-22ME Agensys Phase I (antibody drug conjugate) Santa Monica, CA www.agensys.com Seattle Genetics www.seattlegenetics.com Bothell, WA

ALB-109564(a) Bessor-Brightwaters Pharma Phase I (tubulin inhibitor) Framingham, MA www.bessor-brightwaterspharma. com

ALT-836 Altor BioScience Phase I/II (recombinant chimeric Miramar, FL www.altorbioscience.com anti-tissue factor antibody)

altiratinib Deciphera Pharmaceuticals Phase I (MET/TIE2/VEGFR2 Cambridge, MA www.deciphera.com kinase inhibitor)

AM0010 ARMO BioSciences Phase I (PEGylated recombinant Redwood City, CA www.armobio.com human IL-10)

AMG 208 Amgen Phase I (c-Met inhibitor) Thousand Oaks, CA www.amgen.com

AMG 232 Amgen (see also leukemia) Phase I Thousand Oaks, CA www.amgen.com

AMG 337 Amgen advanced solid tumors Phase I (c-Met inhibitor) Thousand Oaks, CA (see also stomach, other) www.amgen.com

AMG 780 Amgen advanced solid tumors Phase I (angiogenesis inhibitor) Thousand Oaks, CA www.amgen.com

AMG 820 Amgen Phase I (c-fms antagonist) Thousand Oaks, CA www.amgen.com

Medicines in Development Cancer 2014 79 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

AMG 900 Amgen late-stage solid tumors Phase I (aurora kinase inhibitor) Thousand Oaks, CA (see also hematological) www.amgen.com

anti-LAG3 antibody Bristol-Myers Squibb (combination therapy) Phase I Princeton, NJ (see also other) www.bms.com

APS001F Anaeropharma Science Phase I (recombinant anaerobic bacteria) Tokyo, Japan www.anaeropharma.co.jp

APTO-253 Aptose Biosciences late-stage solid tumors Phase I (KLA4 activator) Toronto, Canada www.aptose.com

AR-12 Arno Therapeutics (see also lymphoma) Phase I (PI3K/Akt inhibitor) Flemington, NJ www.arnothera.com

AR-42 Arno Therapeutics (see also hematological) Phase I (pan-DAC inhibitor) Flemington, NJ www.arnothera.com

ARQ 087 ArQule Phase I (FGFR antagonist) Woburn, MA www.arqule.com

ARQ 092 ArQule Phase I (AKT inhibitor) Woburn, MA www.arqule.com

ARQ 761 ArQule Phase I (E2F1 transcription factor Woburn, MA www.arqule.com stimulant)

ATI-1123 Azaya Therapeutics Phase I (docetaxel liposomal) San Antonio, TX www.azayatherapeutics.com

AT13148 Astex Pharmaceuticals Phase I (ROCK inhibitor) Dublin, CA www.astx.com

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

AZD2014 AstraZeneca Phase II (mTOR serine/threonine Wilmington, DE www.astrazeneca.com kinase inhibitor)

AZD4547 AstraZeneca Phase II (FGFR tyrosine kinase inhibitor) Wilmington, DE www.astrazeneca.com

AZD8186 AstraZeneca Phase I (PI3K beta inhibitor) Wilmington, DE www.astrazeneca.com

BAX-69 Baxter Healthcare metastatic solid tumors Phase I (anti-MIF antibody) Deer eld, IL www.baxter.com

80 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

BAY949343 Bayer HealthCare Pharmaceuticals advanced solid tumors Phase I (mesothelin antibody drug Whippany, NJ www.bayerpharma.com conjugate)

BAY1129980 Bayer HealthCare Pharmaceuticals solid tumors with LYPD3 protein Phase I (C4.4a antibody drug conjugate) Whippany, NJ expression www.bayerpharma.com

BBI503 Boston Biomedical Phase I/II (cancer stemness kinase inhibitor) Cambridge, MA www.bostonbiomedical.com

bendamustine ready-to-dilute Eagle Pharmaceuticals (see also leukemia, lymphoma) Phase I liquid formulation Woodcli Lake, NJ www.eagleus.com

BGB-283 BeiGene Phase I (BRAF inhibitor) Beijing, China www.beigene.com EMD Serono www.emdserono.com Rockland, MA

BGB-290 BeiGene Phase I (tankyrase inhibitor) Beijing, China www.beigene.com EMD Serono www.emdserono.com Rockland, MA

BGJ398 Novartis Pharmaceuticals advanced solid tumors Phase I (FGF-R kinase inhibitor) East Hanover, NJ (see also brain, hematological, liver) www.novartis.com

BI 836845 Boehringer Ingelheim Pharmaceuticals Phase I (somatomedin inhibitor) Ridge eld, CT www.boehringer-ingelheim.com

BI 853520 Boehringer Ingelheim Pharmaceuticals Phase I (PTK2 protein inhibitor) Ridge eld, CT www.boehringer-ingelheim.com

BI 860585 Boehringer Ingelheim Pharmaceuticals Phase I Ridge eld, CT www.boehringer-ingelheim.com

BKM120 Novartis Pharmaceuticals (see also breast) Phase I (PI3K inhibitor) East Hanover, NJ www.novartis.com

BLY719 Novartis Pharmaceuticals Phase I (PI3K-alpha inhibitor) East Hanover, NJ www.novartis.com

BPM 31510 intravenous Berg Pharma Phase I (ubidecarenone IV) Framingham, MA www.berghealth.com

briciclib Onconova Therapeutics metastatic solid tumors Phase I (cyclin D1 modulator) Newtown, PA www.onconova.com

BVD-CNV BioMed Valley Discoveries Phase I (C. novyi-NT) Kansas City, MO www.biomed-valley.com

Medicines in Development Cancer 2014 81 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

CB-839 Calithera Biosciences advanced solid tumors Phase I (glutaminase inhibitor) South San Francisco, CA (see also hematological) www.calithera.com

CBL0137 Cleveland BioLabs advanced solid tumors Phase I (curaxin) Bu alo, NY www.cbiolabs.com

CC-115 Celgene Phase I (dual TORK/DNA PK inhibitor Summit, NJ www.celgene.com modulator)

CC-122 Celgene (see also lymphoma) Phase I (pleiotropic pathway modulator) Summit, NJ www.celgene.com

CC-223 Celgene Phase I (dual TORK inhibitor) Summit, NJ www.celgene.com

CC-486 Celgene (see also hematological) Phase I Summit, NJ www.celgene.com

CDX-1401 Celldex Therapeutics solid tumors expressing NY-ESO-1 Phase I (NY-ESO-1 cancer vaccine) Hampton, NJ protein www.celldex.com

CEP-32496 Teva Pharmaceutical advanced solid tumors Phase I (BRAF kinase inhibitor) Frazier, PA (see also colorectal, skin) www.tevapharm.com

CEP-37250/KHK2801 Kyowa Hakko Kirin Pharma advanced solid tumors Phase I Princeton, NJ www.kyowa-hakko-kirin.com Teva Pharmaceutical www.tevapharm.com Frazier, PA

CEP-37440 Teva Pharmaceutical late-stage solid tumors Phase I (dual anaplastic lymphoma kinase Frazier, PA www.tevapharm.com and PTK2 protein inhibitor)

CGM097 Novartis Pharmaceuticals late-stage solid tumors Phase I (p53/MDM2-interaction inhibitor) East Hanover, NJ www.novartis.com

CLR457 Novartis Pharmaceuticals advanced solid tumors Phase I/II (PI3K inhibitor) East Hanover, NJ www.novartis.com

cobimetinib Genentech (see also skin) Phase I (MEK inhibitor) South San Francisco, CA www.gene.com

crolibulin Immune Pharmaceuticals Phase II Cambridge, MA www.immunepharmaceuticals.com

CUDC-427 Curis late-stage solid tumors Phase I (IAP inhibitor) Lexington, MA (see also lymphoma) www.curis.com

82 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

Cyramza® Lilly combination therapy Phase II ramucirumab Indianapolis, IN (see also bladder, breast, colorectal, www.lilly.com liver, lung, ovarian, stomach)

dacomitinib P zer (see also lung) Phase I (pan-HER inhibitor) New York, NY www.pfizer.com

DCVax®-Direct Northwest Biotherapeutics inoperable solid tumors Phase I/II dendritic cell vaccine Bethesda, MD www.nwbio.com

Debio 1143 Debiopharma (see also lymphoma) Phase I (IAP inhibitor) Lausanne, Switzerland www.debiopharm.com

Debio 1347 Debiopharm late-stage solid tumors Phase I (FGFR inhibitor) Lausanne, Switzerland www.debiopharm.com

DFP-11207 Delta-Fly Pharma advanced solid tumors Phase I (thymidylate synthase expression Tokushima, Japan inhibitor)

DLYE-5953A Genentech refractory solid tumors Phase I South San Francisco, CA www.gene.com

DS-3032 Daiichi Sankyo (see also lymphoma) Phase I (MDM2 inhibitor) Parsippany, NJ www.dsi.com

DS-3078 Daiichi Sankyo (see also lymphoma) Phase I (mTOR inhibitor) Parsippany, NJ www.dsi.com

DS-7423 Daiichi Sankyo Phase I (PI3K/mTOR inhibitor) Parsippany, NJ www.dsi.com

DS-8273 Daiichi Sankyo late-stage solid tumors Phase I (anti-DR5 antibody) Parsippany, NJ (see also lymphoma) www.dsi.com

E6201 Eisai advanced solid tumors Phase I (MEK-1/MEKK-1 kinase inhibitor) Woodcli Lake, NJ www.eisai.com

E7389 Eisai Phase I (liposomal eribulin) Woodcli Lake, NJ www.eisai.com

EC1456 Endocyte Phase I (folate-tubulysin) West Lafayette, IN www.endocyte.com

enoticumab Regeneron Pharmaceuticals advanced solid malignancies Phase I Tarrytown, NY www.regeneron.com

Medicines in Development Cancer 2014 83 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

entolimod Cleveland BioLabs advanced solid tumors Phase I (cancer immunotherapy) Bu alo, NY www.cbiolabs.com

EP-100 Esperance Pharmaceuticals (see also hematological) Phase II (membrane disrupting peptide) San Francisco, CA www.esperancepharma.com

EPZ-6438 Epizyme INI1-de cient solid tumors Phase I (EZH2 inhibitor) Cambridge, MA (see also lymphoma) www.epizyme.com

FANG™ Vaccine Gradalis advanced solid tumors Phase I genetically modi ed autologous Dallas, TX (see also colorectal, ovarian, skin) www.gradalisinc.com tumor cell vaccine

fenretinide intravenous CerRx adult solid tumors, pediatric mixed Phase II Lubbock, TX tumors www.cerrx.com (see also lymphoma)

G305 Immune Design Phase I (GLA-SE+NY-ESO-1 protein) Seattle, WA www.immunedesign.com

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

GDC-0994 Genentech Phase I (ERK inhibitor) South San Francisco, CA www.gene.com

GI-6301 GlobeImmune Phase I completed (brachyury peptide vaccine) Lousiville, CO www.globeimmune.com

GL-ONC1 Genelux (see also head/neck, lung, other) Phase II (oncolytic virus immunomodulator) San Diego, CA www.genelux.com

GO-203-2c Genus Oncology Phase I (MUC1 inhibitor) Vernon Hills, IL www.genusoncology.com

GS-5745 Gilead Sciences Phase I (MMP9 mAb inhibitor) Foster City, CA www.gilead.com

HDM201 Novartis Pharmaceuticals (see also hematological) Phase I (tumor suppressor protein East Hanover, NJ www.novartis.com p53 modulator)

I-131-CLR1404 Cellectar Biosciences advanced solid tumors Phase I completed (molecular radiotherapeutic) Madison, WI www.cellectar.com

IMGN289 ImmunoGen EGFR-positive solid tumors Phase I (EGFR kinase inhibitor) Waltham, MA www.immunogen.com

84 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

IMGN853 ImmunoGen folate receptor alpha-positive solid Phase I (folate receptor 1 inhibitor) Waltham, MA tumors www.immunogen.com

IMMU-132 Immunomedics metastatic solid tumors Phase II (antibody drug conjugate) Morris Plains, NJ www.immunomedics.com

INC280 Novartis Pharmaceuticals late-stage solid tumors Phase II (c-Met inhibitor) East Hanover, NJ www.novartis.com

INCB39110 Incyte advanced solid tumors Phase I (JAK1 inhibitor) Wilmington, DE (see also lung) www.incyte.com

IT-139 Intezyne Phase I (GRP78 protein inhibitor) Tampa, FL www.intezyne.com

ixazomib Millennium Pharmaceuticals (see also hematological, lymphoma, Phase I (proteasome inhibitor) Cambridge, MA myeloma) www.millennium.com

JNJ-42756493 Janssen Research & Development late-stage solid tumors Phase I (FGFR inhibitor) Raritan, NJ (see also lymphoma) www.janssenrnd.com

KPT-330 Karyopharm Therapeutics advanced solid tumors Phase I (XPO1 inhibitor) Newton, MA (see also brain, leukemia, prostate, www.karyopharm.com other)

KTN3379 Kolltan Pharmaceuticals late-stage solid tumors Phase I (ErbB3 kinase inhibitor) New Haven, CT www.kolltan.com

LB-100 Lixte Biotechnology Phase I (protein phosphatase 2A inhibitor) East Setauket, NY www.lixte.com

LDE225 Novartis Pharmaceuticals (see also brain, skin) Phase II (SMO protein inhibitor) East Hanover, NJ www.novartis.com

LEE011 Novartis Pharmaceuticals (see also breast) Phase I (CDK4/6 inhibitor) East Hanover, NJ www.novartis.com

LGX818 Novartis Pharmaceuticals BRAF-mutant tumors Phase II (BRAF inhibitor) East Hanover, NJ (see also colorectal, skin) www.novartis.com

LJM716 Novartis Pharmaceuticals Phase I (ERBB-3 receptor antagonist) East Hanover, NJ www.novartis.com

lirilumab Bristol-Myers Squibb solid tumors (with nivolumab), Phase I (anti-KIR mAb) Princeton, NJ solid tumors (with Yervoy® ) www.bms.com

Medicines in Development Cancer 2014 85 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

LOXO-101 Array BioPharma Phase I (PanTrk inhibitor) Boulder, CO www.arraybiopharma.com Loxo Oncology www.loxooncology.com Stamford, CT

LV305 Immune Design Phase I (NY-ESO-1 Zvex) Seattle, WA www.immunedesign.com

LY2606368 Lilly advanced solid tumors Phase I (Chk1 inhibitor) Indianapolis, IN (see also breast, ovarian) www.lilly.com

margetuximab MacroGenics (see also breast, other) Phase I (anti-HER2 mAb) Rockville, MD www.macrogenics.com

ME-143 MEI Pharma refractory solid tumors Phase I (NADH oxidase inhibitor) San Diego, CA www.meipharma.com

MEDI-565 MedImmune Phase I (anti-CEA BITE mAb) Gaithersburg, MD www.medimmune.com

MEDI0639 MedImmune Phase I (anti-DLL-4 mAb) Gaithersburg, MD www.medimmune.com

MEDI0680 MedImmune Phase I (anti-PD-1 mAb) Gaithersburg, MD www.medimmune.com

MEDI3617 MedImmune Phase I (anti-ANG-2 mAb) Gaithersburg, MD www.medimmune.com

MEDI4736 + MEDI0680 MedImmune Phase I (anti-PD-L1 mAb/anti-PD-1 mAb) Gaithersburg, MD www.medimmune.com

MEDI4736 + tremelimumab MedImmune Phase I (anti-PD-L1 mAb/anti-CTLA-4 Gaithersburg, MD www.medimmune.com mAB)

MEDI6469 AgonOx Phase I (murine anti-OX40 mAb) Portland, OR www.agonox.com MedImmune www.medimmune.com Gaithersburg, MD

MEK162 Novartis Pharmaceuticals (see also ovarian, skin) Phase I/II (MEK inhibitor) East Hanover, NJ www.novartis.com

MGA271 Macogenics Phase I (CD276 protein inhibitor) Rockville, MD www.macrogenics.com

MGCD516 Mirati Therapeutics late-stage solid tumors Phase I (multi kinase inhibitor) San Diego, CA www.mirati.com

86 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

MGN 1703 Mologen Phase I completed (TLR9 agonist) Berlin, Germany www.mologen.com

MINT1526A Genentech Phase I (integrin-alpha-5/beta-1 inhibitor) South San Francisco, CA www.gene.com

MK-2206 Merck Phase II (AKT inhibitor) Whitehouse Station, NJ www.merck.com

MK-4166 Merck Phase I (TNFRSF18 protein stimulant) Whitehouse Station, NJ www.merck.com

MK-8033 Merck Phase I completed (c-Met/RON inhibitor) Whitehouse Station, NJ www.merck.com

MK-8242 Merck Phase I (MDM-2 inhibitor) Whitehouse Station, NJ www.merck.com

MLN0128 Millennium Pharmaceuticals (see also breast, hematological) Phase I (TORC1/TORC2 inhibitor) Cambridge, MA www.millennium.com

MLN1117 Millennium Pharmaceuticals Phase I (PI3K alpha inhibitor) Cambridge, MA www.millennium.com

MLN2480 Millennium Pharmaceuticals Phase I (Pan-Raf kinase inhibitor) Cambridge, MA www.millennium.com

MLN4924 Millennium Pharmaceuticals (see also hematological) Phase I (Nedd8-activating enzyme Cambridge, MA www.millennium.com inhibitor)

MLN7243 Millennium Pharmaceuticals Phase I (UAE inhibitor) Cambridge, MA www.millennium.com

MM-151 Merrimack Pharmaceuticals refractory advanced solid tumors Phase I (EGFR oligoclonal antibody) Cambridge, MA www.merrimackpharma.com

MNK-010 Mallinckrodt Pharmaceuticals Phase I St. Louis, MO www.mallinckrodt.com

MSB0010718C EMD Serono (see also skin) Phase I (anti-PD-L1 mAb) Rockland, MA www.emdserono.com

MSC2156119 EMD Serono Phase I (c-Met kinase inhibitor) Rockland, MA www.emdserono.com

MSC2363318A EMD Serono Phase I (p70S6K/Akt inhibitor) Rockland, MA www.emdserono.com

Medicines in Development Cancer 2014 87 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

MUC-1 dendritic cancer vaccine MicroVAX Phase I Manassas, VA

MVA-BN Brachyury Bavarian-Nordic Phase I (immunotherapy vaccine) Mountain View, CA www.bavarian-nordic.com

NC-4016 NanoCarrier Phase I (DACH platin micelle) Chiba, Japan www.nanocarrier.co.jp

NHS-IL12 EMD Serono Phase I (cancer immunotherapy) Rockland, MA www.emdserono.com

nivolumab Bristol-Myers Squibb solid tumors (signal detection) Phase I (PD-1 inhibitor) Princeton, NJ (see also brain, colorectal, head/neck, www.bms.com hematological, kidney, liver, lung, lymphoma, skin)

NLG919 NewLink Genetics Phase I (immune checkpoint inhibitor) Ames, IA www.newlinkgenetics.com

OMP-52M51 OncoMed Pharmaceuticals (see also hematological) Phase I (NOTCH-1 inhibitor) Redwood City, CA www.oncomed.com

ONT-10 Oncothyreon Phase I (cancer immunotherapy) Seattle, WA www.oncothyreon.com

OPB-111077 Otsuka Pharmaceutical Phase I Rockville, MD www.otsuka.com

oprozomib Onyx Pharmaceuticals (see also hematological) Phase I (proteasome inhibitor) South San Francisco, CA www.onyx.com

oraxol Kinex Pharmaceuticals Phase I (oral paclitaxel) Bu alo, NY www.kinexpharma.com

OTS167 OncoTherapy Science Phase I (MELK protein inhibitor) Kanagawa Prefecture, Japan www.oncotherapy.co.jp

PB272 Puma Biotechnology HER2-mutated solid tumors Phase II (neratinib) Los Angeles, CA (see also breast) www.pumabiotechnology.com

PEG-SN38 Belrose Pharma (see also brain, breast) Phase I (angiogenesis inhibitor) Princeton, NJ www.belrosepharma.com

pelareorep Oncolytics Biotech relapsed or refractory solid tumors Phase I Calgary, Canada (pediatric) www.oncolyticsbiotech.com (see also colorectal, head/neck, lung, myeloma, ovarian, pancreatic, skin, other)

88 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

PFK-158 Advanced Cancer Therapeutics Phase I (PFKFB3 inhibitor) Louisville, KY www.advancedcancertherapeutics. com

pimasertib/SAR405838 EMD Serono Phase I (MEK inhibitor/hDM2 inhibitor) Rockland, MA www.emdserono.com Sano US www.sano .com Bridgewater, NJ

pimasertib/SAR245409 EMD Serono (see also ovarian) Phase I (MEK inhibitor/dual PI3K, mTOR Rockland, MA www.emdserono.com inhibitor) Sano US www.sano .com Bridgewater, NJ

PLX7486 Daiichi Sankyo TRK-driven tumors Phase I (TRK inhibitor) Parsippany, NJ (see also pancreatic) www.dsi.com Plexxikon www.plexxikon.com Berkeley, CA

PLX8394 Daiichi Sankyo (see also leukemia) Phase I (BRAF inhibitor) Parsippany, NJ www.dsi.com Plexxikon www.plexxikon.com Berkeley, CA

PM060184 Pharmamar Phase I (tubulin polymerisation inhibitor) Madrid, Spain www.pharmamar.com

PNT2258 ProNAi Therapeutics (see also lymphoma) Phase II (bcl-2 oncogene inhibitor) Plymouth, MI www.pronai.com

PRI-724 PRISM Pharma (see also leukemia, pancreatic) Phase I (CBP/β-catenin inhibitor) Tokyo, Japan www.prismbiolab.com

PT-112 Phosplatin Therapeutics late-stage solid tumors Phase I (apoptosis stimulant) New York, NY www.phosplatin.com

purine nucleoside phosphorylase PNP Therapeutics Phase I gene therapy Birmingham, AL www.pnptherapeutics.com

QBI-139 Quintessence Biosciences Phase I (RNA inhibitor) Madison, WI www.quintbio.com

rebastinib Deciphera Pharmaceuticals Phase I/II (TRK, BCR-ABL, TIE2 inhibitor) Cambridge, MA www.deciphera.com

Medicines in Development Cancer 2014 89 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

refametinib Bayer HealthCare Pharmaceuticals advanced metastatic solid tumors Phase I/II (MEK inhibitor) Whippany, NJ www.bayerpharma.com

RG7304 Genentech Phase I (dual Raf/MEK inhibitor) South San Francisco, CA www.gene.com

RG7388 Genentech (see also hematological) Phase I (dual Raf/MEK inhibitor) South San Francisco, CA www.gene.com

RG7841 Genentech Phase I (antibody drug conjugate) South San Francisco, CA www.gene.com

RRx-001 RadioRx late-stage solid tumors Phase I (free radical stimulant) Mountain View, CA (see also colorectal, lymphoma) www.radiorx.com

RX-3117 Rexahn late-stage solid tumors Phase I (cancer speci c cytotoxic agent) Rockville, MD www.rexahn.com

RX-5902 Rexahn late-stage solid tumors Phase I (p68 RNA helicase) Rockville, MD www.rexahn.com

RXDX 101 Ignyta Phase I/II (selective tyrosine kinase inhibitor) San Diego, CA www.ignyta.com

SAR125844 Sano US Phase I (c-Met kinase inhibitor) Bridgewater, NJ www.sano .com

SAR245408 Sano US Phase I (PI3K inhibitor) Bridgewater, NJ www.sano .com

SAR260301 Sano US PTEN-de cient tumors Phase I (PI3K-beta inhibitor) Bridgewater, NJ www.sano .com

SAR307746 Regeneron Pharmaceuticals Phase I (anti-ANG2 mAb) Tarrytown, NY www.regeneron.com Sano US www.sano .com Bridgewater, NJ

SAR405838 Ascenta Therapeutics Phase I (HDM2/p53 antagonist) Malvern, PA www.ascenta.com Sano US www.sano .com Bridgewater, NJ

SAR566658 Sano US Phase I (maytansin-loaded anti-CA6 mAb) Bridgewater, NJ ww.sano .com

90 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

sEphB4-HSA VasGene Therapeutics Phase I (recombinant albumin fusion Los Angeles, CA protein)

SF1126 SignalRx Pharmaceuticals Phase I completed (pan-PI3K inhibitor) San Diego, CA www.signalrx.com

SP-02 Solasia Pharma (see also hematological) Phase I (darinaparsin) Tokyo, Japan www.solasia.co.jp

Stivarga® Bayer HealthCare Pharmaceuticals advanced solid tumors Phase I/II regorafenib Whippany, NJ (see also colorectal, kidney, liver) www.bayerpharma.com

Sym004 EMD Serono (see also colorectal, head/neck) Phase I (anti-EGFR mAb) Rockland, MA www.emdserono.com

TAK-659 Millennium Pharmaceuticals (see also hematological) Phase I (SYK kinase inhibitor) Cambridge, MA www.millennium.com

TAK-733 Millennium Pharmaceuticals Phase I (MEK inhibitor) Cambridge, MA www.millennium.com

TAS-114 Taiho Oncology Phase I (dUTPase/DPD inhibitor) Princeton, NJ www.taihooncology.com

TAS-119 Taiho Oncology late-stage solid tumors Phase I (aurora kinase A inhibitor) Princeton, NJ www.taihooncology.com

TAS-120 Taiho Oncology advanced solid tumors Phase I (FGF/FGFR inhibitor) Princeton, NJ (see also myeloma) www.taihooncology.com

taselisib Genentech (see also breast) Phase I (PI3K inhibitor) South San Francisco, CA www.gene.com

TCN-P Cahaba Pharmaceuticals Phase II (triciribine) Princeton, NJ www.cahabapharma.com

TEN-010 Tensha Therapeutics advanced solid tumors Phase I (BET inhibitor) Cambridge, MA www.tenshatherapeutics.com

TEW-7197 MedPacto Phase I (TGF-beta type I receptor Suwon, South Korea www.medpacto.com antagonist)

TH-302 EMD Serono (see also hematological, lung, Phase I (hypoxia-activated prodrug) Rockland, MA pancreatic, sarcoma, skin) www.emdserono.com Threshold Pharmaceuticals www.thresholdpharm.com South San Francisco, CA

Medicines in Development Cancer 2014 91 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

thioureidobutyronitrile Cellceutix Phase I (tumor suppressor protein p53 Beverly, MA www.cellceutix.com stimulant)

TKI258 Novartis Phamaceuticals Phase II (multi-targeted receptor tyrosine East Hanover, NJ www.novartis.com kinase inhibitor)

TRX518 GITR advanced solid tumors Phase I (GITR receptor antagonist) Cambridge, MA (see also skin) www.gitrrx.com

TVB-2640 3-V Biosciences advanced solid tumors Phase I (FASN inhibitor) Menlo Park, CA www.3vbio.com

U3-1565 Daiichi Sankyo Phase I (anti-HB-EGF antibody) Parsippany, NJ www.dsi.com

urelumab Bristol-Myers Squibb (see also hematological) Phase I Princeton, NJ www.bms.com

vanticitumab OncoMed Pharmaceuticals advanced solid tumors Phase I (anti-Fzd7 antibody) Redwood City, CA www.oncomed.com

varlilumab Celldex Therapeutics (see also hematological) Phase I (CD27 inhibitor) Hampton, NJ www.celldex.com

VGX 100 Ceres Oncology Phase I (VEGF-C antibody) Victoria, Australia www.ceresoncology.com

vintafolide Endocyte advanced solid tumors Phase I (folate-DAVLBH) West Lafayette, IN (combination therapy) www.endocyte.com (see also lung)

VS-4718 Verastem late-stage solid tumors Phase I (FAK inhibitor) Cambridge, MA www.verastem.com

VS-5584 Verastem late-stage solid tumors Phase I (PI3K/mTOR inhibitor) Cambridge, MA (see also lymphoma) www.verastem.com

VX15 Vaccinex Phase I (CD100 antigen inhibitor) Rochester, NY www.vaccinex.com

VX-970 Vertex Pharmaceuticals Phase I (ATR protein inhibitor) Boston, MA www.vrtx.com

WT2725 Sunovion Pharmaceuticals (see also hematological) Phase I (cancer immunotherapy) Marlborough, MA www.sunovion.com

92 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Solid Tumors

Product Name Sponsor Indication Development Phase

X396 Xcovery advanced solid tumors Phase I (ALK inhibitor) West Palm Beach, FL www.xcovery.com

X82 Tyrogenex Phase I (VEGFR/PDGFR antagonist) West Palm Beach, FL www.xcovery.com/tyrogenex-inc

Xalkori® P zer (see also lung) Phase I crizotinib New York, NY www.pfizer.com

Stomach Cancer

Product Name Sponsor Indication Development Phase

A nitor® Novartis Pharmaceuticals non-functioning gastrointestinal Phase III everolimus East Hanover, NJ neuroendocrine tumors www.novartis.com (see also breast, lymphoma, stomach)

AMG 337 Amgen gastric cancer Phase II (c-Met inhibitor) Thousand Oaks, CA (see also solid tumors, other) www.amgen.com

BBI608 Boston Biomedical gastric cancer Phase III (cancer stem cell inhibitor) Cambridge, MA (see also breast, colorectal, lung, www.bostonbiomedical.com ovarian, skin, other) ------gastrointestinal cancers Phase I (combination therapy) www.bostonbiomedical.com

crenolanib AROG Pharmaceuticals GIST Phase II (PDGFR inhibitor) Dallas, TX (see also brain) www.arogpharma.com

Cyramza® Lilly gastric cancer (2nd-line application submitted ramucirumab Indianapolis, IN combination therapy) www.lilly.com ORPHAN DRUG (see also bladder, breast, colorectal, liver, lung, ovarian, solid tumors)

Iclusig® ARIAD Pharmaceuticals GIST (2nd-line) Phase II ponatinib Cambridge, MA (see also leukemia) www.ariad.com

ipatasertib Array BioPharma gastric cancer Phase II (GDC-0068) Boulder, CO (see also breast, prostate) www.arraybiopharma.com (Akt inhibitor) Genentech www.gene.com South San Francisco, CA

Medicines in Development Cancer 2014 93 Medicines and Vaccines in Development for Cancers

Stomach Cancer

Product Name Sponsor Indication Development Phase

Kadcyla® Genentech advanced HER2-positive gastric cancer Phase III ado-trastuzumab emtansine South San Francisco, CA (see also breast) www.gene.com

Keytruda® Merck gastric cancer Phase I pembrolizumab Whitehouse Station, NJ (see also bladder, breast, www.merck.com head/neck, hematological, kidney, lung, myeloma)

LY2875358 Lilly advanced gastric cancer Phase II (c-Met mAb) Indianapolis, IN (see also lung) www.lilly.com

masitinib AB Science USA late-stage GIST (1st-line) Phase III ORPHAN DRUG Short Hills, NJ (see also pancreatic) www.ab-science.com

Minnelide™ 001 Minneamrita Therapeutics advanced gastrointestinal tumors Phase I HSP70 inhibitor Moline, IL

MLN0264 Millennium Pharmaceuticals advanced gastrointestinal cancer Phase II (GCC antibody drug conjugate) Cambridge, MA (see also pancreatic) www.millennium.com

MM-111 Merrimack Pharmaceuticals gastric cancer (2nd-line) Phase II (ErbB3/ErbB2 receptor antagonist) Cambridge, MA www.merrimackpharma.com ORPHAN DRUG

NeuVax® Galena Biopharma gastric cancer Phase I completed nelipepimut-S Portland, OR (see also breast, kidney, liver, lung, www.galenabiopharma.com lymphoma, skin, other)

olaparib AstraZeneca gastric cancer (2nd-line) Phase III (PARP inhibitor) Wilmington, DE (see also breast, stomach) www.astrazeneca.com

Perjeta® Roche advanced HER2-positive gastric cancer Phase III pertuzumab Nutley, NJ (see also breast) www.roche.com

rilotumumab Amgen MET-positive gastric cancer Phase III (hepatocyte growth factor/ Thousand Oaks, CA www.amgen.com scatter factor inhibitor)

S-1 Taiho Oncology gastric cancer Phase III (gimeracil/oteracil/tegafur Princeton, NJ www.taihooncology.com xed-dose combination)

SM04755 Samumed advanced gastric cancer Phase I (Wnt inhibitor) San Diego, CA (see also colorectal, liver, pancreatic) www.samumed.com

Somatuline® Depot Ipsen Biopharmaceuticals gastroenteropancreatic application submitted lanreotide auto-gel formulation Basking Ridge, NJ neuroendocrine tumors www.ipsenus.com

94 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Stomach Cancer

Product Name Sponsor Indication Development Phase

telatinib Eddingpharm gastric cancer Phase II completed (VEGFR inhibitor) Westlake Village, CA www.eddingpharm.com ORPHAN DRUG

TKM-PLK1 Tekmira Pharmaceuticals gastrointestinal neuroendocrine Phase II (RNA interference) Burnaby, Canada tumors www.tekmira.com (see also liver, other)

Yervoy® Bristol-Myers Squibb gastric cancer Phase II ipilimumab Princeton, NJ (see also lung, ovarian, prostate, skin) www.bms.com

Other Cancers

Product Name Sponsor Indication Development Phase

Adcetris® Seattle Genetics CD30-positive non-lymphoma Phase II brentuximab vedotin Bothell, WA malignancies www.seattlegenetics.com (see also lymphoma)

ADXS-HPV Advaxis cervical cancer Phase II (live, attenuated Listeria Princeton, NJ (see also head/neck, other) www.advaxis.com monocytogenes (Lm)-based ------immunotherapy vaccine) anal cancer Phase I/II ORPHAN DRUG www.advaxis.com

AEB701 Novartis Pharmaceuticals uveal melanoma (combination Phase I/II (PKC inhibitor) East Hanover, NJ therapy) www.novartis.com (see also lymphoma)

AMG 337 Amgen gastroesophageal junction cancer, Phase II (c-Met inhibitor) Thousand Oaks, CA esophageal cancer www.amgen.com (see also stomach, solid tumors)

ATR-101 Atterocor adrenocortical carcinoma Phase I (sterol O-acyltransferase inhibitor) Ann Arbor, MI www.atterocor.com ORPHAN DRUG

Avastin® Genentech recurrent cervical cancer application submitted bevacizumab South San Francisco, CA (see also brain, lung, ovarian) www.gene.com Roche www.roche.com Nutley, NJ ------metastatic or locally advanced Phase III high-risk neuroendocrine tumor www.gene.com www.roche.com

Medicines in Development Cancer 2014 95 Medicines and Vaccines in Development for Cancers

Other Cancers

Product Name Sponsor Indication Development Phase

bavituximab Peregrine Pharmaceuticals rectal cancer Phase I Tustin, CA (see also breast, liver, lung, skin) www.peregrineinc.com

BBI608 Boston Biomedical gastroesophageal junction cancer Phase III (cancer stem cell inhibitor) Cambridge, MA (see also breast, colorectal, lung, www.bostonbiomedical.com ovarian, skin, stomach)

DN24-02 Dendreon HER2-positive urothelial carcinoma Phase II (active cellular immunotherapy) Seattle, WA www.dendreon.com

DKN-01 HealthCare Pharmaceuticals esophageal cancer, gastroesophageal Phase I (DKK1 protein inhibitor) Cambridge, MA junction cancer, gastroesophageal www.healthcarepharmaceuticals.com cancer (see also lung, myeloma)

E7080 Eisai thyroid cancer Phase III completed (multi-targeted kinase inhibitor) Woodcli Lake, NJ (see also brain, liver, lung, skin) www.eisai.com ------endometrial cancer Phase II www.eisai.com

GALE-301 Galena Biopharma endometrial cancer Phase II (folate binding protein Portland, OR (see also ovarian) www.galenabiopharma.com immunotherapy)

GI-6207 GlobeImmune medullary thyroid cancer Phase II (natural killer cell stimulant) Louisville, CO www.globeimmune.com

GL-ONC1 Genelux peritoneal carcinomatosis Phase I/II (oncolytic virus immunomodulator) San Diego, CA (see also head/neck, lung, solid www.genelux.com tumors)

GSK525762 GlaxoSmithKline NUT gene midline carcinoma Phase I (bromodomain inhibitor) Research Triangle Park, NC www.gsk.com

INCB24360 Incyte fallopian tube cancer, Phase II (IDO1 inhibitor) Wilmington, DE peritoneal cancer www.incyte.com (see also lung, ovarian, skin)

INO-3106 Inovio HPV-6-associated aerodigestive Phase I (therapeutic vaccine) Plymouth Meeting, PA malignancies www.inovio.com

INO-3112 Inovio Pharmaceuticals cervical cancer caused by HPV Phase I (cancer therapeutic vaccine) Plymouth Meeting, PA types 16/18 www.inovio.com (see also head/neck)

96 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Other Cancers

Product Name Sponsor Indication Development Phase

Jaka ® Incyte polycythemia vera Phase III ruxolitinib Wilmington, DE (see also breast, colorectal, lung, www.incyte.com pancreatic) ------advanced malignancies Phase I www.incyte.com

margetuximab MacroGenics gastroesophageal cancer Phase II (anti-HER2 mAb) Rockville, MD (see also breast, solid tumors) www.macrogenics.com

Marqibo® Spectrum Pharmaceuticals pediatric cancers Phase I/II vinCRIStine sulfate LIPOSOME Henderson, NV (see also leukemia, lymphoma) www.sppirx.com injection

milciclib Nerviano Medical Sciences malignant thymoma Phase II (CDK inhibitor) Nerviano, Italy www.nervianoms.com

MORAb-066 Eisai advanced TF-expressing malignancies Phase I (tissue factor antigen inhibitor) Woodcli Lake, NJ www.eisai.com

NTO-1151 Nanotherapeutics cervical cancer, vaginal cancer Phase II (ribonuclease inhibitor) Alachua, FL www.nanotherapeutics.com National Cancer Institute Bethesda, MD

pelareorep Oncolytics Biotech fallopian tube cancer, primary Phase II Calgary, Canada peritoneal cancer www.oncolyticsbiotech.com (see also colorectal, head/neck, lung, myeloma, ovarian, pancreatic, skin, solid tumors)

seliciclib Cyclacel Pharmaceuticals nasopharyngeal cancer Phase II (CDK inhibitor) Berkeley Heights, NJ (see also lung) www.cyclacel.com

selumetinib Array BioPharma di erentiated thyroid cancer, Phase III (MEK inhibitor) Boulder, CO uveal melanoma www.arraybiopharma.com AstraZeneca (see also lung) www.astrazeneca.com Wilmington, DE

SOR-C13 Soricimed Biopharma cancers that overexpress the TRPV6 Phase I (TRPV6 protein inhibitor) Sackville, Canada calcium channel www.soricimed.com

Sprycel® Bristol-Myers Squibb pediatric cancer Phase II dasatinib Princeton, NJ (see also pancreatic) www.bms.com Otsuka America Pharmaceutical www.otsuka.com Rockville, MD

Medicines in Development Cancer 2014 97 Medicines and Vaccines in Development for Cancers

Other Cancers

Product Name Sponsor Indication Development Phase

telotristat etiprate Lexicon Pharmaceuticals malignant carcinoid syndrome Phase III (TPH1 inhibitor) The Woodlands, TX (Fast Track) www.lexicon-genetics.com ORPHAN DRUG

tirapazamine SRI International cervical cancer Phase III (type II DNA topoisomerase Menlo Park, CA www.sri.com inhibitor)

TKM-PLK1 Tekmira Pharmaceuticals adrenocortical carcinoma Phase II (RNA interference) Nurnaby, Canada (see also liver, stomach) www.tekmira.com

V503 Merck prevention of HPV-related cancers application submitted (human papillomavirus vaccine Whitehouse Station, NJ www.merck.com 9-valent)

VB-111 VBL Therapeutics thyroid cancer Phase II (vascular targeting system) Or Yehuda, Israel (see also brain, ovarian) www.vblrx.com

Zelboraf® Genentech BRAF-mutation-positive papillary Phase II vemurafenib South San Francisco, CA thyroid cancer www.gene.com (see also skin)

zoptarelin doxorubicin AEterna Zentaris endometrial cancer (2nd-line) Phase III (type II DNA topoisomerase Quebec, Canada (see also prostate) www.aezsinc.com inhibitor)

Unspecifi ed Cancer

Product Name Sponsor Indication Development Phase

AGS-67E Agensys Phase I (antibody drug conjugate) Santa Monica, CA www.agensys.com Astellas Pharma Tokyo, Japan

AMG 110 Amgen Phase I (recombinant bi-speci c antibody) Thousand Oaks, CA www.amgen.com

BAY1082439 Bayer HealthCare Pharmaceuticals Phase I (PI3K inhibitor) Whippany, NJ www.bayerpharma.com

BAY1125976 Bayer HealthCare Pharmaceuticals Phase I (allosteric AKT1/2 inhibitor) Whippany, NJ www.bayerpharma.com

98 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Unspecifi ed Cancer

Product Name Sponsor Indication Development Phase

BAY1143572 Bayer HealthCare Pharmaceuticals Phase I (PTEFb inhibitor) Whippany, NJ www.bayerpharma.com

BAY1161909 Bayer HealthCare Pharmaceuticals Phase I (MPS1 inhibitor) Whippany, NJ www.bayerpharma.com

BAY1163877 Bayer HealthCare Pharmaceuticals Phase I (Pan-FGFR inhibitor) Whippany, NJ www.bayerpharma.com

BAY1179470 Bayer HealthCare Pharmaceuticals Phase I (FGFR2 antibody) Whippany, NJ www.bayerpharma.com

BAY2010112 Bayer HealthCare Pharmaceuticals Phase I (PSMA BiTE antibody) Whippany, NJ www.bayerpharma.com

BVD-523 BioMed Valley Discoveries Phase I/II (ERK 1/2 kinase inhibitor) Kansas City, MO www.biomed-valley.com

CHML Glory Pharmaceuticals Phase I (cytotropic heterogeneous Vienna, VA www.anticancerdrug.com molecular lipids)

CSF-1R mAb Lilly Phase I Indianapolis, IN www.lilly.com

G1T28-1 (IV) G1 Therapeutics Phase I (CDK 4/6 inhibitor) Research Triangle Park, NC www.g1therapeutics.com

GCS-100 La Jolla Pharmaceutical Phase I completed (galectin-3 protein inhibitor) San Diego, CA www.lajollapharmaceutical.com

GPX-150 Gem Pharmaceuticals Phase I Birmingham, AL www.gempharmaceuticals.com

GSK2256098 GlaxoSmithKline Phase I (focal adhesion kinase inhibitor) Research Triangle Park, NC www.gsk.com

GSK2636771 GlaxoSmithKline Phase I (PI3K inhibitor) Research Triangle Park, NC www.gsk.com

GSK2816126 GlaxoSmithKline Phase I (EZH2 enzyme inhibitor) Research Triangle Park, NC www.gsk.com

GSK2849330 GlaxoSmithKline Phase I (ErbB3 mAb) Research Triangle Park, NC www.gsk.com

GSK3052230 GlaxoSmithKline Phase I (FGF ligand trap) Research Triangle Park, NC www.gsk.com

Medicines in Development Cancer 2014 99 Medicines and Vaccines in Development for Cancers

Unspecifi ed Cancer

Product Name Sponsor Indication Development Phase

HBI-8000 Huya Bioscience Phase I (HDAC inhibitor) San Diego, CA www.huyabio.com

high ADCC anticancer mAb Boehringer Ingelheim Pharmaceuticals Phase I Ridge eld, CT www.boehringer-ingelheim.com Xencor www.xencor.com Monrovia, CA

IGF-methotrexate conjugate IGF Oncology Phase I Birchwood, MN www.igfoncology.com

IP-112 InnoPharma application submitted Piscataway, NJ www.innopharmainc.com

LGK974 Novartis Pharmaceuticals Phase I (WNT signaling pathway inhibitor) East Hanover, NJ www.novartis.com

LY2228820 Lilly Phase II (p38 MAP kinase inhibitor) Indianapolis, IN www.lilly.com

LY2874455 Lilly Phase II (FGF receptor inhibitor) Indianapolis, IN www.lilly.com

LY2780301 Lilly Phase I (p70S6/AKT dual inhibitor) Indianapolis, IN www.lilly.com

LY2801653 Lilly Phase II (c-Met inhibitor) Indianapolis, IN www.lilly.com

LY3009120 Lilly Phase I (pan-Raf inhibitor) Indianapolis, IN www.lilly.com

LY3023414 Lilly Phase I (PI3K/mTOR dual inhibitor) Indianapolis, IN www.lilly.com

LY3039478 Lilly Phase I (NOTCH inhibitor) Indianapolis, In www.lilly.com

MM-141 Merrimack Pharmaceuticals Phase I (IGF-1R/ErbB3 bispeci c Cambridge, MA www.merrimackpharma.com tetravalent antibody)

notch inhibitor Bristol-Myers Squibb Phase I Princeton, NJ www.bms.com

olaratumab Lilly Phase II (PDGF-alpha receptor antagonist) Indianapolis, IN ww.lilly.com

100 Medicines in Development Cancer 2014 Medicines and Vaccines in Development for Cancers

Unspecifi ed Cancer

Product Name Sponsor Indication Development Phase

OMN54 Omnitura Therapeutics Phase I (signal transduction pathway Redwood Shores, CA www.omnitura.com inhibitor)

OPB-51602 Otsuka Pharmaceutical Phase I (molecular targeting drug) Rockville, MD www.otsuka.com

PBI-05204 Phoenix Biotechnology Phase I (triple kinase inhibitor) San Antonio, TX www.phoenixbiotechnology.com

PD-0325901 P zer Phase I (MEK1/2 inhibitor) New York, NY www.pfizer.com

PF-03084014 P zer Phase I (gamma secretase inhibitor) New York, NY www.pfizer.com

PF-05082566 P zer Phase I (CD137 antigen agonist) New York, NY www.pfizer.com

PF-06263507 P zer Phase I (auristatin-based antibody drug New York, NY www.pfizer.com conjugate)

PF-06439535 P zer Phase I (bevacizumab biosimilar) New York, NY www.pfizer.com

PF-06463922 P zer Phase I (dual ALK/ROS1 inhibitor) New York, NY www.pfizer.com

PF-06664178 P zer Phase I New York, NY www.pfizer.com

PF-06647263 P zer Phase I (immunoconjugate) New York, NY www.pfizer.com

PF-06650808 P zer Phase I New York, NY www.pfizer.com

REGN1400 Regeneron Pharmaceuticals Phase I (ERBB-3 receptor modulator) Tarrytown, NY www.regeneron.com

rintatolimod Hemispherx Pharma adjuvant therapy Phase I/II Philadelphia, PA www.hemispherx.net

SNX-5422 Esanex Phase I (HSP90 heat-shock protein Indianapolis, IN inhibitor)

TGF-BR2 mAb Lilly Phase I Indianapolis, IN www.lilly.com

Medicines in Development Cancer 2014 101 Medicines and Vaccines in Development for Cancers

Unspecifi ed Cancer

Product Name Sponsor Indication Development Phase

trametinib + GSK2141795 GlaxoSmithKline Phase I (MEK1/2 inhibitor + AKT protein Research Triangle Park, NC www.gsk.com kinase inhibitor)

VEGFR-3 mAb Lilly Phase I Indianapolis, IN www.lilly.com

Defi nitions Application Submitted—An application for marketing has been submitted by the company to the U.S. Food and Drug Administration (FDA).

Breakthrough Therapy—Upon request by a sponsor, the FDA can grant this designation to expedite the development and review of a drug or biologic intended, alone or in combination with one or more other drugs, to treat a serious or life threatening disease or condition and preliminary clinical evidence indicates that it may demonstrate substan- tial improvement over existing therapies on one or more clinically-signi cant endpoints, such as substantial treatment e ects observed early in clinical development. If a drug or biologic is designated as a breakthrough therapy, the FDA will expedite the development and review. With this designation, all Fast Track features convey to the medicine.

Fast Track—Upon request by a sponsor, the FDA can grant this designation to facilitate the development and expedite the review of a drug or biologic to treat a serious condition and ll an unmet medical need. When considering a biopharmaceutical company’s request for Fast Track designation for an investigational drug or biologic, the FDA evaluates whether it will a ect factors such as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one, and whether a condition can be adequately addressed by available therapy. With Fast Track designation, early and frequent communication between the FDA and the biopharmaceutical company is encouraged throughout the entire drug development and review process to help to quickly resolve any questions or issues that arise, potentially leading to an earlier approval and access by patients.

Orphan Designation—Upon request by a sponsor, the FDA can grant special status (“orphan status”) to a drug or biologic to treat a rare disease or condition. In order to receive an orphan designation, a qualifying drug or biologic must be intended for the treatment, diagnosis, or prevention of a rare disease or condition that affects fewer than 200,000 people in the United States, or that affects more than 200,000 persons but is not expected to recover the costs of its development and marketing.

Phase I—Researchers test the investigational drug or biologic in a small group of people, usually between 20 and 100 healthy adult volunteers, to evaluate its initial safety and tolerability profile, determine a safe dosage range, and identify potential side effects.

Phase II—The investigational drug or biologic is given to volunteer patients, usually between 100 and 500, to determine whether it is e ective, identify an optimal dose, and to further evaluate its short-term safety.

Phase III—The investigational drug or biologic is given to a larger, more diverse patient population, often involving between 1,000 and 5,000 patients (but sometimes many more), to generate statistically signi cant evidence to con rm its safety and e ectiveness. Phase III studies are the longest studies and usually take place in multiple sites around the world.

The content of this report has been obtained through public, government and industry sources, and the Adis “R&D Insight” database based on the latest information. Report current as of September 26, 2014. 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 specifi c 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 website. A publication of PhRMA’s Communications & Public Affairs Department (202) 835-3460 www.phrma.org | www.innovation.org | www.pparx.org Provided as a public service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association. Copyright © 2014 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper credit is given. Pharmaceutical Research and Manufacturers of America • 950 F Street, NW, Suite 300, Washington, DC 20004

102 Medicines in Development Cancer 2014 The Drug Discovery, Development and Approval Process

Developing a new medicine takes an average of 10-15 years. Of the tens of thousands of compounds screened, only one is approved.

The Drug Development and Approval Process The U.S. system of new drug approvals is fi les an IND with the U.S. Food and Drug (but sometimes many more), to generate perhaps the most rigorous in the world. Administration (FDA) to begin to test the drug statistically signifi cant evidence to confi rm its It takes 10-15 years, on average, for an in people. The IND shows results of previous safety and effectiveness. They are the longest investigational drug to travel from the lab to U.S. experiments; how, where and by whom the new studies, and usually take place in multiple sites patients, according to the Tufts Center for the studies will be conducted; the chemical structure around the world. Study of Drug Development. Tens of thousands of the compound; how it is thought to work in New Drug Application (NDA)/Biologic License of compounds may be screened early in the body; any toxic effects found in the animal Application (BLA)—Following the completion development, but only one ultimately receives studies; and how the compound is manufactured. of all three phases of clinical trials, a company approval. Even medicines that reach clinical trials All clinical trials must be reviewed and approved analyzes all of the data and fi les an NDA or BLA have only a 16 percent chance of being approved. by the Institutional Review Board (IRB) where with FDA if the data successfully demonstrate the trials will be conducted. Progress reports on On average, it costs a company $1.2 billion, both safety and effectiveness. The applications clinical trials must be submitted at least annually including the cost of failures, to get one new contain all of the scientifi c information that the to FDA and the IRB. medicine from the laboratory to U.S. patients, company has gathered. Applications typically according to a 2007 study by the Tufts Center Clinical Trials, Phase I—Researchers test the run 100,000 pages or more. for the Study of Drug Development. More recent drug in a small group of people, usually between Approval—Once FDA approves an NDA or studies estimate the cost to be even higher. 20 and 100 healthy adult volunteers, to evaluate BLA, the new medicine becomes available its initial safety and tolerability profi le, determine Once a new compound has been identifi ed in for physicians to prescribe. A company must a safe dosage range, and identify potential side the laboratory, medicines are usually developed continue to submit periodic reports to FDA, effects. as follows: including any cases of adverse reactions and Clinical Trials, Phase II—The drug is given appropriate quality-control records. For some Preclinical Testing—A pharmaceutical company to volunteer patients, usually between 100 and medicines, FDA requires additional trials conducts laboratory and animal studies to show 500, to see if it is effective, identify an optimal (Phase IV) to evaluate long-term effects. biological activity of the compound against the dose, and to further evaluate its short-term targeted disease, and the compound is evaluated Discovering and developing safe and effective safety. for safety. new medicines is a long, diffi cult, and expensive Clinical Trials, Phase III—The drug is given to a process. PhRMA member companies invested Investigational New Drug Application (IND)— larger, more diverse patient population, often an estimated $51.1 billion in research and After completing preclinical testing, a company involving between 1,000 and 5,000 patients development in 2013.

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