AVEO ONCOLOGY, Inc. (AVEO)
Company website: http://www.aveooncology.com/ AVEO Pharmaceuticals, Inc., a biopharmaceutical company, develops targeted therapies for cancer and related diseases. The company's pipeline of product candidates include Tivozanib, a vascular endothelial growth factor (VEGF) to optimize VEGF blockade; Ficlatuzumab, a hepatocyte growth factor (HGF) inhibitory antibody, which has completed Phase II trial that inhibits the activity of the HGF/c-Met pathway; and AV-203, an anti-ErbB3 specific monoclonal antibody that has completed a Phase I dose escalation study. Its development programs also comprise AV-380, a humanized IgG1 inhibitory monoclonal antibody for the treatment or prevention of cachexia; and the AV-353 platform for the potential treatment of pulmonary arterial hypertension. The company has strategic partnerships with CANbridge Life Sciences Ltd.; EUSA Pharma (UK) Limited; Novartis International Pharmaceutical Ltd.; Biodesix, Inc.; St. Vincent's Hospital Sydney Limited; Biogen Idec International GmbH; and Kyowa Hakko Kirin Co., Ltd. The company was formerly known as GenPath Pharmaceuticals, Inc. and changed its name to AVEO Pharmaceuticals, Inc. in March 2005. AVEO Pharmaceuticals, Inc. was incorporated in 2001 and is based in Cambridge, Massachusetts. Product pipeline candidates include Tivozanib, Ficlatuzumab, AV-203, AV-353 and AV-380.
AV-380 (GDF-15 Program)
In August 2015, AVEO announced an exclusive, worldwide license agreement with Novartis for the development and commercialization of AVEO’s first-in-class, potent, humanized inhibitory antibody targeting growth differentiation factor 15 (GDF15), AV-380, and related antibodies, including modified or derivative forms of any such antibody.
GDF15 is a pro-inflammatory cytokine whose elevated circulating levels have been correlated with cachexia in cachectic cancer patients and several animal models of cancer cachexia. Current evidence suggests that a pro- inflammatory state may be responsible for many of the symptoms associated with cachexia, a complex metabolic syndrome characterized by malnutrition and severe involuntary weight loss due to the loss of muscle and fat tissue, as well as the clinical manifestation of anemia, inflammation and suppression of immune functions.
Preclinical data show that inhibition of GDF15 results in a switch from catabolism to anabolism, suggesting that GDF15 inhibition with AV-380 may reverse the effects of cachexia.
Cachexia is a serious and common complication in patients with advanced cancer and other chronic diseases. It affects some five million individuals in the United States.
Tivozanib, is a potent, selective, long half-life inhibitor of all three vascular endothelial growth factor (VEGF) receptors that is designed to optimize VEGF blockade while minimizing off-target toxicities.
AVEO remains encouraged by the clinical outcomes from its Phase 2 and Phase 3 studies in renal cell carcinoma and the efficacy and tolerability profile that tivozanib may offer to patients suffering from this challenging disease. In addition, promising biomarker results were observed in a Phase 2 study of tivozanib in colorectal cancer.
In August of 2014, AVEO regained all rights to tivozanib. In November 2014, AVEO entered into an option agreement with Ophthotech to investigate tivozanib for the potential treatment of non-oncologic diseases of the eye. In August 2015, AVEO entered into an exclusive license agreement with Pharmstandard OJSC for the development, manufacturing and commercialization of tivozanib in the territories of Russia, Ukraine and the Commonwealth of Independent States (CIS), for all indications excluding ocular conditions. The Company is actively pursuing partnerships in Europe to advance the development and commercialization of tivozanib in solid tumors.
AVEO is interested in collaborating with potential partners who share our vision for cancer drug development and positively impacting patients’ lives. Please contact AVEO firstname.lastname@example.org to discuss partnership opportunities with AVEO’s development pipeline.
European Medicines Agency (EMA), has recommended FOTIVDA™ (tivozanib) for approval as a treatment (Solid Dose) for patients with advanced renal cell carcinoma (RCC)
Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) inhibitory antibody that binds to the HGF ligand with high affinity and specificity to inhibit HGF/c-Met biological activities.
AVEO and Biodesix, Inc. have a worldwide agreement to develop and commercialize ficlatuzumab, with VeriStrat®, a serum protein test that is commercially available to help physicians guide treatment decisions for patients with advanced non-small cell lung cancer (NSCLC). Under the terms of the agreement, AVEO and Biodesix are conducting a proof-of-concept study of ficlatuzumab in combination with erlotinib in advanced NSCLC patients selected using BDX001, a serum protein test similar to the VeriStrat test.
An exploratory analysis from AVEO’s Phase 2 study in first-line NSCLC suggested that VeriStrat was prognostic for outcome in the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI)-treated patients and predicted differential treatment benefit for the combination of ficlatuzumab plus TKI over TKI alone. The predictive effect was observed in both progression-free survival and overall survival endpoints
AVEO scientists have demonstrated through the use of our Human Response Platform™ the importance of ErbB3 in promoting tumor growth. An increasing body of evidence also implicates the activation of ErbB3 in tumorigenesis and the development of resistance to anti-cancer agents. AV-203 is a clinical-stage ErbB3 (HER3) inhibitory antibody candidate designed to inhibit both ligand-dependent and ligand-independent ErbB3 signaling. ErbB3 is a receptor that is typically expressed in many human cancers, and AV-203 has demonstrated preclinical activity in a number of different tumor models including breast, head and neck, lung, ovarian and pancreatic cancers.
AVEO has successfully completed a Phase 1 safety study showing no dose limiting toxicities at maximum dose of 20mg/kg and CLIA (Clinical Laboratory Improvements Amendment) validation has been completed for a biomarker for potential patient selection.
AV-353 is the Company’s potent, selective, high affinity inhibitory antibody specific to Notch 3. The Notch 3 signaling pathway is important in cell-to-cell communication involving gene regulation mechanisms that control multiple cell differentiation processes during the entire life cycle. Scientific literature has implicated the Notch 3 receptor pathway in multiple diseases, including cancer, cardiovascular diseases and neurodegenerative conditions. Publications, including Nature Medicine (2009), have implicated the Notch 3 pathway in Pulmonary Arterial Hypertension (PAH). PAH is a rare and life-threatening disorder that affects approximately 250,000 people worldwide and is caused by enlargement of the arterial walls in small arteries between the heart and the lungs, resulting in restricted blood flow.
Current treatments in PAH focus only on controlling symptoms by avoiding vasoconstriction and increasing vasodilation of vessels and do not reverse the underlying cause of the disease. In contrast, with the results of a recently concluded preclinical animal studies supported by AVEO, AV-353 has generated a growing body of preclinical data that supports AV-353’s ability to potentially reverse the disease phenotype, which would represent a potential disease-modifying approach to treatment. AVEO is currently seeking a partner to develop and commercialize AV-353 worldwide in PAH.
For additional information, or to inquire about potential partnering opportunities, please contact Nikhil Mutyal (email@example.com). www.aveopharma.com One Broadway 14th Floor
Cambridge, MA 02142