The Bristol-Myers Squibb Pipeline
Bristol-Myers Squibb (BMS) agreed to acquire Medarex for $16.00 per share in cash for an aggregate purchase price of approximately $2.4 billion. The acquisition will broaden BMS' current pipeline of anticancer drugs in clinical trials by the addition of several anticancer agents in clinical development in the Medarex pipeline, and bring the late stage anticancer agent ipilimumab in-house. In addition, Medarex has several agents in preclinical development and has over the years forged many collaborations based on its monoclonal antibody (MAb) technology platform that may result in milestones and royalties down the line.
The Novartis Pipeline
In addition to several approved oncology-related drugs, Novartis has one of the broadest pipelines of novel anticancer drugs in clinical development with the majority being targeted agents in early clinical development. Targets addressed include BRaf (B-Raf); CRaf (C-Raf, RAF1); vascular endothelial growth factor (VEGF) receptor 2 (VEGFr2, Flk1, KDR); CD40; colony stimulating factor 1 (macrophage), CSF1; Dickkopf-1 (DKK1); fms-like tyrosine kinase 3 (FLT3); c-Kit; platelet-derived growth factor receptor beta (PDGFrB, PDGFr); protein kinase C (PKC); heat-shock protein 90 (hsp90); histone deacetylase (HDAC); inhibitor of apoptosis (IAP); mammalian target of rapamycin (mTOR); phosphatidylinositol 3`kinase (PI3K); smoothened (SMO); somatotropin release inhibiting factor receptor (SRIFr); insulin-like growth factor 1 (IGF1); and fibroblast growth factor receptor 3 (FGFr3).
The Amgen Pipeline
Amgen is clinically evaluating 7 anticancer agents targeting a variety of markers including hepatocyte growth factor/scatter factor (HGF/SF),
hepatocyte growth factor receptor (HGFr)/c-Met, HEr3 (ErbB3), insulin-like growth factor 1 receptor (IGF1r), Tie-2, angiopoietin-1 and 2, tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAILr2), vascular endothelial growth factor (VEGF) receptor 1 (VEGFr1), VEGFr2, VEGFr3, platelet-derived growth factor receptor beta (PDGFrB), Kit, and RET. The company's strategy in the oncology sector is to pursue agents with broad anticancer activity, primarily angiogenesis inhibitors and apoptosis inducers/enhancers. In addition, Amgen submitted for FDA approval its drug denosumab, an investigational RANK Ligand inhibitor for the treatment and prevention of postmenopausal osteoporosis as well as bone loss in patients undergoing hormone ablation therapy for either prostate or breast cancer.
The Pfizer Pipeline
Pfizer has one of the most diverse pipelines of oncology drugs with 21 agents in clinical development for numerous indications including breast, pancreatic, prostate, and thyroid cancer, colorectal cancer (CRC), non-small cell lung cancer (NSCLC), renal cell cancer (CRC), soft-tissue sarcoma, malignant melanoma, leukemia/lymphoma, multiple myeloma, and myelodysplastic syndrome (MDS), among others. Agents in the pipeline include 4 immunotherapies; 6 monoclonal antibody (MAb)-based agents; and 12 small molecule drugs. A unique feature of the pipeline is its breath of targets, with 20 agents targeting various molecular markers including Activin A receptor type II-like 1 (ACVrL1), ALK1; Anaplastic lymphoma kinase (ALK); Angiopoietin-2 (Ang2); Aurora A (Aurora-2); Aurora B (STK12/Aurora-1); c-Kit; Cadherin 3, type 1 (CDH3), P-cadherin; CD40; Checkpoint 1 (Chk1); Cyclin-dependent kinase 4 (CDK4); CTLA4; EGFr, ErbB1; HEr2 (ErbB2); HEr3 (ErbB3); HEr4 (ErbB4); Focal adhesion kinase (FAK); Hsp90; Insulin-like growth factor 1 receptor (IGF1r)); Met [hepatocyte growth factor receptor (HGFr); Notch 1 (TAN1); Poly (ADP-ribose) polymerase (PARP); Toll-like receptor 9 (TLr9); Vascular endothelial growth factor (VEGF) receptor 2 (VEGFr2, KDR); Platelet-derived growth factor receptor alpha (PDGFrA); PDGFr; and Fms-like tyrosine kinase 3 (FLT3). Although the majority of agents (13/21) are in phase I clinical trials, 7 drugs are in phase II/III clinical trials. Sutent (sunitinib), Pfizer’s proprietary drug on the market, approved for the treatment of refractory gastrointestinal stromal tumors (GIST), and as first line treatment in metastatic renal carcinoma (RCC), generated global revenues of $847 million in 2008. Sutent is in phase II and phase III clinical trials in numerous indications including breast, colorectal, gastric, prostate, liver, and lung cancer. Upon its acquisition, Wyeth’s Torisel (temsirolimus) whose global sales were $122 million in 2008, will boost the group’s oncology related sales derived from novel agents.
The Medarex Pipeline
Medarex has one of the broadest pipelines of monoclonal antiboby (MAb)-based anticancer agents in the industry, with over 21 products in clinical development either by the company itself or its partners. The company recently highlighted the status of 6 of its own anticancer MAb in clinical development, addressing a diverse list of targets including CD19, CD30, CD70, CTLA4, and the PD-L1/PD-1 pathway, a unique novel approach to cancer treatment. Most advanced among these agents is ipilimumab, having been evaluated in over 45 clinical trials, and now in phase III clinical trials in malignant melanoma and slated for a phase III clinical trial in hormone-refractory prostate cancer.
The Human Genome Sciences Pipeline
Human Genome Sciences is evaluating 3 anticancer agents in phase I and II clinical trials.
The GPC Biotech/Agennix Pipeline
The pipeline of the proposed GPC Biotech and Agennix merger comprises 3 agents in clinical trials. One of these agents, talactoferrin, being evaluated in a phase III clinical trial in non-small cell lung cancer (nsclc), is available for partnering.
The Micromet Pipeline
Micromet is investigating 4 agents in clinical trials in solid tumors and hematologic malignancies, and has a broad preclinical pipeline.
The AVEO Pharmaceuticals Pipeline
AVEO Pharmaceuticals is evaluating in clinical trials 3 anticancer agents, AV-951, AV-299, and AV-412.
The Bavarian Nordic Cancer Vaccine Pipeline
Bavarian Nordic is investigating 3 therapeutic vaccines in clinical trials, MVA-BN-HER2 in HEr2-overexpressing breast cancer, and Prostvac and MVA-BN PRO in hormone-refractory prostate cancer (HRPC). The company is planning to initiate a phase I/II clinical trial with an improved version of MVA-BN-HER2 that induced an up to 20-fold higher T-cell immune response than its predecessor.
The Enzon Pharmaceuticals Pipeline
Enzon Pharmaceuticals is investigating in phase I clinical trials 4 anticancer agents with potentially broad application in the treatment of both solid tumors and hematologic malignancies.
The EntreMed Pipeline
EntreMed is emphasizing the clinical development of ENMD-2076 that is in phase I clinical trials in solid tumors and multiple myeloma and has shown promise in preclinical studies in triple-negative breast cancer, colorectal cancer (CRC), and leukemia; other agents in its clinical pipeline include MKC-1 and ENMD-1198.
The AVEO Pharmaceuticals Pipeline
AVEO Pharmaceuticals is evaluating in clinical trials 3 anticancer agents, AV-951, AV-299, and AV-412.
The Exelixis Pipeline
Exelixis has one of the broadest pipelines of small molecule targeted anticancer agents in clinical development, with several agents being developed in collaboration with partners including Bristol-Myers Squibb, GlaxoSmithKline and Genentech.
The Curis Pipeline
As of January 2009, Genentech is to initiate a pivotal, global, single arm, 2-cohort, phase II clinical trial with GDC-0449, an orally administered small molecule hedgehog pathway inhibitor, as monotherapy, in approximately 100 patients with locally advanced or metastatic basal cell carcinoma (BCC).
Under a collaboration agreement, Curis will receive a $6 million cash payment from Genentech which, when added to its existing capital, would provide sufficient funds for the company’s currently planned operations into mid-2010.
Curis continues to execute its strategy of seeking to enter into collaborations with CUDC-305, an Hsp90 inhibitor, and CUDC-101, a first-in-class HDAC/EGFr/HEr2 inhibitor. |
