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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.
Sixty percent of patients receiving doses of 200 mg twice daily and higher had prolonged stable disease.
In a Phase 1 expansion cohort in patients with 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. Twenty-one
metastatic breast cancer patients were evaluated: of the 12 with available biopsies, eight 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.
Development Status: During fiscal 2012, ASLAN initiated a Phase 2 clinical trial with ASLAN001 in Asia
in patients with gastric cancer.
5.
Eli Lilly -- LY2603618 -- CHK-1 Inhibitor Program
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 and
Company acquired ICOS in 2007. Array received a $250 thousand 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 Eli Lilly's achievement of clinical and regulatory milestones with
LY2603618.
Development Status: LY2603618 is currently in multiple Phase 1b/2 clinical trials, including four that
began in 2011, in cancers such as non-small cell lung and pancreatic.
6.
Amgen -- AMG 151 -- Glucokinase Activator Program for Type 2 Diabetes
In December 2009, Array granted Amgen the exclusive worldwide rights to our small molecule
glucokinase activator (GKA) program, including AMG 151. Under the Collaboration and License
Agreement with Amgen, we were responsible for completing certain Phase 1 clinical trials of AMG 151,
which we 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.
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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. We will also receive royalties on sales of any approved drugs developed under
the agreement.
The agreement with Amgen will remain in effect on a product-by-product and country-by-country basis
until no further payments are due under the agreement unless terminated earlier. Either party may
terminate the agreement in the event of a material breach of a material obligation under the agreement by
the other party that remains uncured after 90 days prior notice. Amgen may terminate the agreement at
any time upon notice of 60 or 90 days depending on the development activities going on at the time of
such notice. The parties have also agreed to indemnify each other for certain liabilities arising under the
agreement.
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 via a dual
mechanism of action -- 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
well-established preclinical models of Type 2 diabetes, AMG 151 was highly 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, Januvia
(sitagliptin)
or 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.
Development Status: 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.
7.
Genentech -- GDC-0068 (RG7440), GDC-0425 (RG7602) and GDC-0575 (RG7741)
We 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. We initiated this collaboration to advance two of our proprietary oncology programs into clinical
development. These programs included small molecule leads we had developed along with additional,
related intellectual property. Under the agreement, Genentech made an up-front payment, provides
research funding and has so far paid us 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, we expanded our collaboration with Genentech to develop clinical candidates directed
against an additional third, fourth and fifth targets. Under the agreement, we receive 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, we and Genentech extended the agreement
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