Boulder, Colorado-based Array BioPharma Inc. (NASDAQ:ARRY) is a $594M market cap biopharmaceutical company that discovers, develops and commercializes targeted small molecule drugs to treat cancers and inflammatory diseases. The company believes that there is significant synergy between these two research areas, and that developing drugs in one of the areas may lead to therapies in the other field.
Array believes that targeted cancer therapies have the potential to change the focus of treatment away from categorizing and treating diseases by organ type toward categorizing and treating by the level of gene expression in individual patients, These therapies are sometimes referred to as "personalized medicine."
Targeted therapies hold the promise of specifically targeting the underlying mechanisms of disease by regulating aspects of cellular function that affect cancer cells to a greater extent than normal cells. These therapies may prove to be more effective with fewer side effects than cytotoxic chemotherapy drugs. Array's research strategy in the cancer market is to build a pipeline of targeted therapies.
Array is not alone. Major pharmaceutical firms have increased research and development and in-licensing investment in this market, particularly the targeted cancer therapy market. Some of the targeted therapies currently on the market have become blockbuster drugs. These include Novartis' (NYSE:NVS) Gleevec (imatinib mesylate),Genentech's/Roche's (OTCQX:RHHBY) Avastin (bevacizumab), Herceptin (trastuzumab), Rituxan (rituximab), and Zelboraf (vemurafenib).
This article is the first of three articles about Array. This article looks at Array's promising collaborations with some of the biggest names in the industry including Roche, Amgen (NASDAQ:AMGN), Celgene (NASDAQ:CELG), Novartis and AstraZeneca (NYSE:AZN). Through these partnerships, the company has been able to raise substantial non-dilutive capital totaling over $175 million in recent years. If you were to calculate all the potential partnership milestones Array could earn, it totals more than $3 billion.
Array is evolving into a late-stage development company, with two wholly-owned programs, as well as three partnered programs, selumetinib with AstraZeneca, MEK162 with Novartis and danoprevir with InterMune/Roche that may begin Phase 3 trials by the end of 2013.
In late 2012, Array raised $70.9 million in a public offering by completing an underwritten public offering of 20.7 million shares of its common stock at a price of $3.65 per share. The net proceeds from the sale will be used to fund potential Phase 3 clinical trials or pivotal programs.
Many Array investors are most excited about Array's work with MEK inhibitors.
MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which signals cancer cell proliferation and survival. MEK has been shown to be activated in several tumor types such as non-small cell lung cancer, melanoma, thyroid, ovarian, and, in particular, tumors with BRAF and NRAS mutations.
MEK-162 is a small molecule MEK inhibitor that targets a key position in this pathway and is in Phase 2 development in a range of tumors.
MEK-162 has been administered to more than 430 patients in clinical trials for either safety assessment or the treatment of oncology or inflammatory disease. Array believes MEK162 has demonstrated an acceptable safety profile and has shown clinical activity in the ongoing cancer studies. MEK162 was identified by Novartis as reaching clinical proof of concept in November 2011.
Array invented MEK-162 and licensed worldwide rights to develop and commercialize the drug to Novartis in April 2010. Array entered into an agreement with Novartis for the worldwide development of small-molecule MEK inhibitors, including MEK162 (formerly ARRY-162) and its back-up, ARRY-300. Under the terms of the agreement, Array initially received $45 million comprising an upfront and milestone payment. Array is eligible to receive an additional $422 million if certain clinical, regulatory and commercial milestones are achieved. In addition, Array plans to co-develop ARRY-162 in one or more specific indications and fund a portion of development costs. The agreement provides Array with double-digit royalties on sales of approved drugs outside of the United States with a significantly higher royalty rate for U.S. sales provided that Array meets its co-funding obligations. Array also has a co-detailing right in the United States for approved drugs.
When melanoma is diagnosed early, it is at its most treatable stage. However, when it spreads to other parts of the body and becomes a metastatic disease, it is the deadliest and most aggressive form of skin cancer. This is the population being studied with MEK162.
The American Cancer Society estimates there will be more than 76,000 new cases of melanoma and over 9,000 melanoma deaths in the United States in 2013. BRAF and NRAS mutations occur in 40% to 60% and 15% to 20% of patients with melanoma, respectively. Because MEK inhibitors target the RAS/RAF/MEK/ERK pathway, which is activated with BRAF mutation, these drug candidates may also have the potential for activity not only in patients with BRAF-mutant melanoma, but also in patients with tumors that harbor mutations in the NRAS gene, who currently have no adequate treatment option and poor prognosis.
In 2012, researchers announced that MEK-162 had a disease control rate (partial response and stable disease) of 67% among patients with NRAS mutations. This is the first targeted therapy to show activity in patients with NRAS mutated melanoma. The disease control rate was 60% among patients with BRAF mutations.
In addition to the MILO (MEK Inhibitor in Low Grade Serous Ovarian Cancer) study in both NRAS- and BRAF-mutant melanoma, MEK-162 is being investigated in numerous clinical trials for several different indications:
- Phase 1 dose escalation study testing MEK162 and paclitaxel on patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer;
- Phase 2 trial testing the safety and efficacy of single-agent MEK162 in adult patients with locally advanced and unresectable or metastatic malignant cutaneous melanoma, harboring BRAFV600E or NRAS mutations;
- Phase 2 study assessing the anti-tumor activity of LGX818 in combination with MEK-162 and four other agents;
- Phase 3 study comparing the efficacy and safety of MEK=162 versus dacarbazine in patients with advanced (Stage IIIC) unresectable or metastatic (Stage IV) NRAS Q61 mutation-positive melanoma;
- Phase 1 study testing MEK162 with RAF265 in patients with advanced solid tumors harboring RAS or BRAFV600E;
- Phase 1/2b study testing LGX818 with MEK-162 in adult patients with BRAF dependent advanced solid tumors;
- Phase 2 trial assessing the safety, tolerability, pharmacokinetics and pharmacodynamics of MEK162 in Noonan Syndrome Hypertrophic Cardiomyopathy;
- Phase 1b clinical trial studying the combination of the orally administered phosphatidylinositol 3'-kinase ((PI3K)) inhibitor BKM120 in combination with MEK162 in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations;
- Phase Ib study to determine the maximum tolerated dose and/or RP2D of the orally administered PI3K/mTOR inhibitor BEZ235 in combination with MEK-162;
- Phase 1b/2 trial examining the combination of MEK162 and AMG 479 (ganitumab) in KRAS-mutant colorectal adenocarcinoma, metastatic pancreatic adenocarcinoma, and mutant BRAFV600 melanoma;
- Phase 1 study of MEK-162 in Japanese patients with advanced solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists;
- Phase 1b/2 study testing MEK-162 with LEE011 in patients with NRAS mutant melanoma;
- Phase 1b/2 trial testing MEK-162 with AEBo71 in adult patients with metastatic uveal melanoma;
- Phase 1b/2 trial investigating whether MEK162 is a helpful drug in patients with bile duct or gallbladder cancers when given with gemcitabine and cisplatin
- Phase 1b/2 dose finding trial exploring the combination of BYL719 and MEK162 in adult patients with advanced CRC, esophageal cancer, pancreatic cancer, NSCLC or other advanced solid tumors with documented RAS or BRAF mutations.
On May 6, 2013, Array announced that it would conduct its first company-led Phase 3 clinical trial to study MEK-162 as a treatment for patients with recurrent low-grade serous ovarian cancer. The study, called MILO, will evaluate the efficacy and safety of MEK162 compared to standard chemotherapy treatments.
Novartis has also recently accelerated its goal of regulatory submissions for MEK162 to 2015. In addition, Novartis announced plans to pursue additional clinical development in combination with a Raf inhibitor in BRAF mutant melanoma.
MEK162 and MEK300
MEK162, the first targeted therapy to show activity in patients with NRAS mutant melanoma, showed clinical activity and good tolerability in patients with BRAF and NRAS mutated advanced melanoma. Novartis is evaluating the development options of MEK162 in melanoma.
Promising data on MEK162 in an ongoing Phase 2 trial of patients with BRAF and NRAS mutated advanced melanoma were presented at the 2012 ASCO Annual Meeting. In this trial, MEK162 showed clinical activity and good tolerability in patients with BRAF or NRAS melanoma. This was the first targeted therapy to show activity in patients with NRAS mutated melanoma. The ongoing Phase 2 open-label trial is being conducted by Novartis and continues to enroll patients. As of February 2012, eight of the 35 patients with BRAF mutations evaluable for response had partial responses, including two confirmed partial responses, and 13 patients demonstrated stable disease. The disease control rate was 60% among these patients. Of the 28 patients with NRAS mutations who were evaluable for response, six had partial responses, including three confirmed partial responses, and 13 patients had stable disease. The disease control rate was 68% among these patients. The median progression-free survival was 3.55 months for patients with BRAF mutation and 3.65 months for patients with NRAS mutations.
MEK162 has been administered to more than 430 patients/volunteers in clinical trials for either safety assessment or the treatment of oncology or inflammatory disease. Array reports that the drug candidate has demonstrated an acceptable safety profile and has shown clinical activity in the ongoing cancer studies.
On November 8, 2012, Novartis provided an update on the clinical development strategy for MEK162. Novartis intends to initiate pivotal trials in patients with NRAS mutant melanoma during 2013, with the goal of regulatory submissions on or after 2016. In addition, Novartis announced plans to pursue clinical development in combination with a Raf inhibitor, in BRAF mutant melanoma, with regulatory submissions forecast for on or after 2016.
In December 2003, Array entered into an out-licensing and collaboration agreement with AstraZeneca to develop its MEK program. Under the agreement, AstraZeneca acquired exclusive worldwide rights to Array's clinical development candidate, selumetinib (previously known as AZD6244, or ARRY-142886), together with two other compounds for oncology indications, including AZD8330, which Array invented during the collaboration with AstraZeneca.
Array retained the rights to all therapeutic indications for MEK compounds not selected by AstraZeneca for development, subject to the parties' agreement to work exclusively together. In April 2009, the exclusivity of the parties' relationship ended. Both companies are now independently researching, developing and commercializing small molecule MEK inhibitors for oncology indications.
Array has earned $21.5 million in up-front and milestone payment from the AstraZeneca collaboration. The agreement also provided for research funding, which is now complete, as well as potential additional development milestone payments of approximately $75 million and royalties on product sales. Under this collaboration, Array was responsible for Phase 1 clinical testing, which it completed in 2004. AstraZeneca is responsible for all future development and commercialization of the compounds under the collaboration.
Selumetinib targets the mitogen-activated protein kinase kinases (MEK or MAPK/ERK kinases) that function downstream of RAS.
Selumetinib is also being investigated in clinical trials for various cancer types including NSCLC, thyroid cancer, melanoma, pancreatic cancer, lymphoma, colorectal cancer and other types of cancer.
Last year, AstraZeneca presented data from a Phase 2 study comparing the efficacy of selumetinib in combination with docetaxel versus docetaxel alone in second-line therapy in 87 patients with KRAS-mutation positive locally advanced or metastatic non-small cell lung cancer (NSCLC) (Stage IIIB - IV). In the study, researchers found that there was statistically significant improvement in progression-free survival, objective response rate, and alive and progression-free at six months. Researchers also noted that there was a trend for improvement in median overall survival in favor of selumetinib in combination with docetaxel versus docetaxel alone, but did not reach statistical significance. Hazards were non-proportional. ll secondary endpoints, including response rate and progression free survival were significantly improved for selumetinib in combination with docetaxel versus docetaxel alone. This study was the first completed randomized combination trial with a MEK inhibitor in KRAS mutant advanced NSCLC. Array believes it was the first prospective study to demonstrate clinical benefit as defined by response rate and progression free survival of a targeted therapy for patients with KRAS mutant cancer of any type.
Approximately 20% to 25% of the NSCLC patient population has the KRAS mutation, which equates to approximately 160,000 patients globally. Currently, patients with KRAS NSCLC have a poor prognosis with limited treatment options. Targeting MEK dependent tumors with selumetinib demonstrates the potential of a personalized approach to medicine in the treatment of cancer.
Selumetinib is also showing promise as a treatment for ovarian cancer. In April 2012, the Gynecologic Oncology Group presented results of a Phase 2 trial with selumetinib in women with recurrent low-grade serous ovarian or peritoneal cancer. In this trial, 52 women received 100-mg doses of selumetinib orally twice daily in four-week cycles until disease progression or toxicity. Prior to the trial, 58% of the patients in the trial had received three or more rounds of chemotherapy. The disease control rate, defined as either complete or partial response or progression-free survival or progression-free survival of greater than six months, was reached in 81% of patients. Eight patients had complete (1) or partial (7) responses, and 34 (63%) had progression-free survival of greater than 6 months. The median survival rate without cancer progression was 11 months. Only three patients experienced grade 4 adverse events.
There are over 30 on-going trials with selumetinib, including trials in NSCLC, thyroid cancer, melanoma, ocular melanoma, hepatocellular cancer, rectal cancer, colorectal cancer, pancreatic cancer and breast cancer.
In March 2013, AstraZeneca announced that it expects to initiate two pivotal trials with selumetinib this year. The first trial will investigate selumetinib in combination with docetaxel in KRAS-mutant non-small cell lung cancer. The second trial will be a pivotal trial with selumetinib in thyroid cancer.
AstraZeneca has projected selumetinib peak annual sales to exceed $1 billion and suggested selumetinib may have potential application in high unmet need indications such as uveal melanoma, neurofibromatosis and gastrointestinal cancers. In addition, AstraZeneca recently presented data that selumetinib has advantages of over GlaxoSmithKline's (NYSE:GSK) MEK inhibitor, trametinib, when combined with standard chemotherapy.
AstraZeneca recently announced that it expects to initiate a Phase 3 selumetinib trial in 2013 in patients with NSCLC.
In 2002, Array entered into a collaboration with InterMune for the discovery of novel small molecule inhibitors of the Hepatitis C Virus, or HCV, NS3/4A protease. As a result of drug discovery activities under this collaboration, scientists at Array and InterMune jointly discovered danoprevir.
In October 2010, Roche acquired danoprevir from InterMune for $175 million. InterMune ceased all further development efforts under the collaboration. Under the terms of Array's collaboration agreement with InterMune, InterMune has an obligation to make milestone payments to Array based on the selection and progress of danoprevir, as well as royalties on commercial sales of danoprevir. Array has received $1.8 million in milestone payments and have the potential to earn an additional $9 million if all clinical and commercialization milestones for danoprevir are achieved under the agreement.
In 2011, Roche expanded its portfolio of investigational medicines for hepatitis C through the purchase of danoprevir. The hepatitis market is evolving and, to meet the different needs of people infected with hepatitis C virus (HCV), future treatment options are likely to include interferon-free, as well as interferon-containing triple- and quadruple-combination therapy regimens. Roche has several oral, direct-acting antiviral agents in late-stage development for HCV, including danoprevir, which is currently in a Phase 2 clinical trial. Roche is conducting two Phase 2 trials, MATTERHORN and INFORM-SVR, of danoprevir in combination with mericitabine, a nucleoside polymerase inhibitor being developed by Roche, with and without interferon, or IFN, in two Phase 2 trials. Roche also conducted a Phase 2 trial, DAUPHINE, of danoprevir in IFN-containing regimens for HCV.
In April 2012, Roche announced data at the Annual Meeting of the European Association for the Study of the Liver Congress from the DAUPHINE and INFORM-SVR studies. The DAUPHINE trial showed high sustained viral response (SVR) rates, maintaining undetectable viral levels 12 weeks after stopping treatment, and good tolerability with danoprevir in IFN-containing regimens for HCV. In this trial, up to 93% of genotype 1 and 100% of genotype 4 patients achieved SVR12 with ritonavir-boosted danoprevir, IFN and ribavirin, considered a clinical cure. In the INFORM-SVR Phase 2 trial, 71% of genotype 1b patients achieved SVR12 with boosted danoprevir, mericitabine and ribavirin as part of an IFN-free regimen. Results from a third MATTERHORN Phase 2 trial evaluating danoprevir in combination with mericitabine are currently expected during the second half of 2012.
In April 2013, Roche and Ascletis announced that the two companies had entered into a collaboration to develop and commercialize Roche's investigational drug danoprevir in China for the treatment of HCV. It is estimated that over 10 million patients in China are chronically infected with HCV.
In July 2011, Array entered into a collaboration agreement with Aslan Pharmaceuticals to develop Array's HER2 / EGFR inhibitor, ASLAN001, formerly known as ARRY-543. This drug candidate is currently in Phase 2 development in patients with gastric cancer in Asia. Under the agreement, Aslan is funding and developing ASLAN001 through clinical proof of concept. Upon achievement of proof of concept, Aslan will identify a global partner for Phase 3 development and commercialization. Array will share a significant portion of the proceeds of this partnering transaction.
ASLAN001 is a novel, selective and oral HER2 / EGFR inhibitor, and has shown clinical activity in both HER2-positive and EGFR-positive tumors. Over 200 patients have received ASLAN001 either as monotherapy or in combination with chemotherapy.
Gastric cancer is a major public-health problem in East Asia. Patients with locally advanced, metastatic or recurrent disease have a poor prognosis, with an overall median survival of approximately 11 months. EGFR and HER2 receptors are commonly overexpressed together in gastric cancer.
Data from pivotal studies of Herceptin (trastuzumab), indicated that the activity of this drug is limited to the subset of patients whose disease has amplified copies of the HER2 gene. Array believes ASLAN001 has the potential to augment or supersede the activity of Herceptin in this population, and in the broader population of gastric cancers that co-express both EGFR and HER2 receptors.
In a Phase 1 trial, ASLAN001 produced prolonged stable disease in patients with solid tumors who had previously failed prior treatments. Tablets of ASLAN001 were well-tolerated up to 500 mg twice daily dosing. Systemic concentrations of ASLAN001 increased with escalating doses at all dose levels tested. Researchers found that 60% of patients receiving doses of 200 mg twice daily and higher had prolonged stable disease.
In a Phase 1 expansion cohort for HER2-positive metastatic breast cancer or other ErbB-family cancer, ASLAN001 was generally well-tolerated and demonstrated evidence of tumor regression and prolonged stable disease in EGFR- and HER2-expressing cancers. For the study, 21 metastatic breast cancer patients were evaluated. Of the 12 with available biopsies, 8 were confirmed HER2-positive. Of the confirmed patients with HER2-positive metastatic breast cancer in this study, 63% had stable disease. Clinical benefit (measured by tumor regression or stable disease) was demonstrated in five of the eight confirmed HER2 patients and patients with confirmed co-expression of HER2 and EGFR tended to have the best clinical benefit.
In a cohort of patients with other cancers shown to over-express HER2 and EGFR, a patient with cholangiocarcinoma experienced a tumor marker response that was accompanied by a 25% regression of target lesions.
ASLAN has initiated a Phase 2 clinical trial with ASLAN001 in Asia in patients with gastric cancer.
In 1999 and 2000, Array entered into collaboration agreements involving small molecule ChK-1 inhibitors with ICOS Corporation. IC83 resulted from the collaboration between Array and ICOS. Eli Lilly (NYSE:LLY) acquired ICOS in 2007. Array received a $250,000 milestone payment after the first patient was dosed with IC83, now LY2603618, in a Phase 1 clinical trial in early 2007. The agreements provided research funding, which has now ended. Array is entitled to receive additional milestone payments totaling $3.5 million based on Lilly's achievement of clinical and regulatory milestones with LY2603618.
LY2603618 is currently in multiple Phase 1b/2 clinical trial.
GKAs, such as AMG 151, represent a promising new class of drugs for the treatment of Type 2 diabetes. Glucokinase is the enzyme that senses glucose in the pancreas. Glucokinase also increases glucose utilization and decreases glucose production in the liver. GKAs regulate glucose levels by working in both the pancreas and the liver. The activation of glucokinase lowers glucose levels by enhancing the ability of the pancreas to sense glucose, which leads to increased insulin production. Simultaneously, GKAs increase the net uptake of blood glucose by the liver.
In multiple preclinical models of Type 2 diabetes, AMG 151 was found to be efficacious in controlling both fasting and non-fasting blood glucose, with rapid onset of effect and maximal efficacy within five to eight once daily doses. When combined with existing standard-of-care drugs (metformin, Merck's (NYSE:MRK) Januvia (sitagliptin) or Takeda's Actos (pioglitazone)), AMG 151 provided additional glucose control, which reached maximal efficacy after five to seven days of once-daily dosing. AMG 151 did not increase body weight, plasma triglycerides or total cholesterol, whether used as monotherapy or in combination with other diabetes drugs.
Under the collaboration and license agreement with Amgen, Array was responsible for completing certain Phase 1 clinical trials of AMG 151, which Array completed during fiscal 2011. Amgen also funded an agreed upon number of full-time Array employees as part of the research collaboration intended to identify and advance second-generation GKAs. Amgen is responsible for the further development and commercialization of AMG 151 and any resulting second-generation compounds. The agreement also provides Array with an option to co-promote any approved GKAs with Amgen in the U.S. with certain limitations.
In partial consideration for the rights granted to Amgen under the agreement, Amgen paid an up-front fee of $60 million. In June 2012, Array received an $8.5 million milestone payment following achievement of a pre-defined patient enrollment milestone in a Phase 2a trial. Array is entitled to receive up to approximately $658 million in additional aggregate milestone payments if all clinical and commercialization milestones specified in the agreement for AMG 151 and at least one backup compound are achieved. Array will also receive royalties on sales of any approved drugs developed under the agreement.
In October 2011, Amgen initiated a randomized and blinded 28-day Phase 2a trial of AMG 151 in combination with metformin in approximately 224 patients with Type 2 diabetes. The primary endpoint for this study is change in fasting plasma glucose levels from baseline to end of treatment.
GDC-0068, GDC-0425 and GDC-0575
Array entered into a licensing and collaboration agreement with Genentech, a member of the Roche Group, in December 2003 to develop small molecule drugs against multiple therapeutic targets in the field of oncology. Array initiated this collaboration to advance two of its proprietary oncology programs into clinical development. These programs included small molecule leads Array developed.
Under the agreement, Genentech made an up-front payment, provides research funding and has paid Array for milestones for nominating a clinical candidate and advancing it into regulated safety assessment testing and Phase 1. In addition, Genentech has agreed to make additional potential development milestone payments and pay us royalties on certain resulting product sales. Genentech is solely responsible for clinical development and commercialization of the resulting products.
In 2005 and 2009, Array expanded its collaboration with Genentech to develop clinical candidates directed against an additional third, fourth and fifth targets. Under the agreement, Array receives additional research funding, as well as potential research and development milestone payments and product royalties based on the success of each new program.
In September 2010, Array and Genentech extended the agreement for an additional two years of funded research through January 2013. Genentech has paid Array a total of $21.3 million in up-front and milestone payments. Array has the potential to earn an additional $26.3 million for all programs if Genentech continues development and achieves the remaining clinical milestones set forth in the agreement.
In June 2011, Genentech advanced one collaborative drug, GDC-0068, an AKT inhibitor, into a Phase 1b, open label, dose escalation trial evaluating the safety and pharmacology of GDC-0068 in combination with either Taxotere (docetaxel) or mFOLFOX6 (fluoropyrimine) plus oxaliplatin in patients with advanced solid tumors.
At the 2012 ASCO annual meeting, Genentech presented results from this trial showing that GDC-0068, when combined with Taxotere or mFOLFOX6, was safe and well-tolerated up to the single agent maximum tolerated dose (600 mg). There were no dose limiting toxicities observed during dose escalations; one out of 47 patients discontinued due to GDC-0068-related adverse events. There were no pharmacokinetic interactions observed between GDC-0068 and Taxotere or mFOLFOX6. Both combinations show evidence of clinical benefit, including patients with PI3K/Akt pathway alterations and with prior treatment with taxanes or platinum agents. This trial continues to enroll and evaluate patients in dose expansion cohorts.
During 2012, Genentech initiated a Phase 1b/2 trial with GDC-0068 or GDC-0980, a PI3 Kinase/mTor dual inhibitor, with abiraterone acetate versus abiraterone acetate in patients with locally advanced castration-resistant prostate cancer, as well as a Phase 1 trial with GDC-0068 in combination with GDC-0973, a MEK inhibitor being developed in collaboration with Exelixis (NASDAQ:EXEL), to evaluate the safety, tolerability and pharmacokinetics of GDC-0068 in patients with locally advanced or metastatic solid tumors.
In February 2007, Array entered into a licensing and collaboration agreement with the privately held biopharmaceutical company VentiRx, under which Array was granted VentiRx exclusive worldwide rights to certain molecules from our toll-like receptor, or TLR, program. The program contained a number of compounds targeting TLRs to activate innate immunity, including VTX-2337. Array received equity in VentiRx as well as an up-front payment and the right to receive potential milestone payments and royalties on product sales. Array has received $1.1 million in milestone payments and have the potential to earn $57.5 million if VentiRx achieves the remaining clinical and commercial milestones under the agreement.
Phase 1 results on VTX-2337 were reported at the ASCO annual meeting in 2011. Overall, VTX-2337 was well-tolerated, with the most common drug-related adverse events being mild to moderate in severity and including injection-site reactions and transient flu-like symptoms. The maximum tolerated dose of VTX-2337 was established to be 3.9 mg/m2. In addition, pharmacodynamic effects-as measured by a defined panel of biomarkers identified in preclinical studies-provide evidence of the biological activity of VTX-2337 in stimulating an innate immune response in cancer patients. Researchers found that 25% of patients treated with VTX-2337 experienced disease stabilization based on RECIST criteria at eight weeks. Patients with disease stabilization at eight weeks received additional doses of VTX-2337, ranging from one to six additional cycles (3 to 18 additional doses), until disease progression. One patient with metastatic melanoma demonstrated tumor regression after cessation of VTX-2337 remains disease free at 18 months post-treatment.
VentiRx has advanced VTX-2337 into clinical trials designed to evaluate the compound in multiple oncology indications in combination with a variety of anticancer agents, including chemotherapy and monoclonal antibody therapy. Clinical trials of VTX-2337 currently underway include a combination study with chemotherapy in late stage ovarian cancer and a combination trial with cetuximab in head and neck cancer patients.
During October 2012, VentiRx Pharmaceuticals announced the formation of an exclusive, world-wide collaboration with Celgene for the development of VTX-2337. Under terms of the agreement, Celgene will provide a $35 million upfront payment to fund further research and development of VTX-2337 through pre-defined clinical endpoints. During the option period, VentiRx will be eligible to receive additional funding, including a potential equity investment by Celgene.
In September 2007, Array entered into a worldwide strategic collaboration with Celgene focused on the discovery, development and commercialization of novel therapeutics in cancer and inflammation. Under the agreement, Celgene made an up-front payment of $40 million to Array in part to provide research funding for activities conducted by Array.
In November 2010, Array received a $10 million milestone payment upon filing an investigational new drug (IND) application for ARRY-382, a cFMS inhibitor, which is currently in a Phase 1 clinical trial in patients with solid tumors. Under this program, Array is entitled to receive potential milestone payments of $190 million if certain discovery, development and regulatory milestones are achieved and an additional $300 million if certain commercial milestones are achieved. Additionally, under the second program selected, Array is entitled to receive potential milestone payments of $200 million if certain discovery, development and regulatory milestones are achieved and an additional $300 million if certain commercial milestones are achieved. We will also receive royalties on net sales of any drugs.
During fiscal 2012, Array received $1.5 million in payments from Celgene to extend the research activities on one of the preclinical programs.
Array continued a dose escalation study of ARRY-382 in patients with cancer during fiscal 2012.
Array has a world class small molecule drug discovery and development platform that allows it to move rapidly from hit identification through clinical proof of concept. During the last 10 years, Array has brought 19 compounds into clinical development.
In Part 2, I take look at the drug candidates Array is developing on its own.
Disclosure: I am long AMGN, EXEL, MRK. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.