Holte, Denmark, March 8, 2010
Action Pharma A/S has completed a proof of concept clinical phase IB study with AP1030
currently being developed for treatment of type II diabetes associated with obesity. In a phase
IB study the effect of AP1030 on glucose metabolism in obese human volunteers was
investigated. AP1030 administered orally once-daily for two weeks in obese human volunteers
significantly improved glucose metabolism.
AP1030 is the first in a new drug class developed for oral once-daily treatment based on a new
mode of action (a positive allosteric modulator through new pharmacological targets, the
melanocortin receptors) and is part of Action Pharma’s small molecule program. The mode of
action of AP1030 involves a hypothalamic melanocortin type 4 receptor mediated effect, thereby
modulating appetite and central regulation of glucose metabolism. In addition, AP1030 exerts
anti-inflammatory effects mediated through melanocortin type 1 receptors aimed at reverting
low grade inflammation in fatty tissues and thereby reducing peripheral insulin resistance.
“The positive results obtained for AP1030 in the phase IB study is a major milestone for Action
Pharma”, says Ingelise Saunders, CEO of Action Pharma, and continues: “In contrast to other
weight reducing anti-diabetics, including GLP-1 analogues, AP1030 has the major advantage of
being administered once-daily orally potentially making it very attractive for the anti-diabetes
market.”
The clinical phase IB trial investigating the effect of AP1030 in obese human volunteers was
conducted in Paris, France, at SGS Aster’s phase I unit. The study was a randomized, doubleblind
placebo-controlled dose escalation study. A total of 50 obese volunteers with a body mass
index larger than 30, were enrolled in 5 cohorts.
Søren Nielsen, COO of Action Pharma, says: “The results show that oral once-daily administered
AP1030 for two weeks exerts a positive effect on glucose metabolism in obese individuals. This
is a group of volunteers where many display dysregulation of glucose metabolism in a prediabetic
stage. The positive clinical results with AP1030 as an orally available first-in-class antidiabetic
drug candidate are very encouraging. It is also important to add that AP1030 is well
tolerated and, due to the novel mode of action, does not increase blood pressure which has
been a challenge with earlier drug candidates targeting MCR4 receptors.”
The lead program in Action Pharma’s portfolio, AP214, is currently finalizing recruiting in a phase
II clinical trial and key results are expected Q3 2010. The initial target indication for AP214 is
the prevention of post-surgical kidney injury after major cardiac surgery. These patients are at
increased risk of kidney injury which again is associated with a marked increase in mortality, comorbidity
and, prolonged hospitalization. Action Pharma is in the process of partnering the
AP214 program to pharmaceutical companies with a focus in critical care medicine.
About Action Pharma A/S
Action Pharma is a privately owned Danish biotech company. Action Pharma develops novel drug
candidates targeting melanocortin receptors and bring these to the stage of clinical proof of
concept for subsequent partnering. The drug candidates are first in new drug classes and exploit
novel mode of action profiles with an efficacy that is superior compared to compounds currently
on the market. Action Pharma has a pipeline of several patent protected, in-house developed,
drug candidates. Two drug candidates are currently in clinical development, AP1030 (completed
phase IB) and AP214 (in phase II), and two drug candidates in late preclinical development. The
Action Pharma team has significant scientific expertise and has published more than 400
scientific papers.
AP214 is developed to prevent post-surgical kidney injury after major thoracic surgery. AP214 is
currently being tested in a phase II clinical trial investigating the effect of AP214 on organ
protection in patients undergoing cardiac surgery, who are at increased risk of kidney injury.
Every year, more than 150,000 patients in the USA and in the EU undergo major thoracic
surgery. Approximately 10-20% of these patients experience various degrees of kidney injury
which again is associated with marked increase in mortality, co-morbidity and prolonged
hospitalization. Currently, there is no treatment to prevent or treat kidney injury associated with
major surgery. Thus there is a major unmet medical need. AP214 mediates its potent effect via
the type 1 and type 3 melanocortin receptors. Initial results from an earlier phase II US clinical
trial and from a phase IB trial in human volunteers subjected to LPS-induced inflammation,
revealed positive effects of AP214.
AP1030, the lead compound within the Company’s small molecule program, has potent preclinically
documented anti-diabetic and anti-obesity effects. AP1030 is currently in clinical
development in obese individuals and has completed a two-week phase IB clinical trial with
positive effects on glucose metabolism. AP1030 has the potential to be superior to other antidiabetics,
including GLP-1 analogues, DPP-4 inhibitors and glitazones. Importantly, AP1030 can
be administered orally (once daily) in contrast to GLP-1 analogues. Moreover, the marked
weight reducing effects of AP1030 observed in non-clinical pharmacodynamic models contrast
the absence of weight reduction by other orally available anti-diabetics, including DPP-4
inhibitors. Thus, this makes AP1030 highly attractive in the market for type II diabetes
associated with obesity. The mode of action of AP1030, first in its drug class, involves a central
melanocortin type 4 receptor mediated effect, thereby modulating appetite and central
regulation of glucose metabolism plus a systemic anti-inflammatory melanocortin type 1
receptor mediated anti-diabetic effect aimed at reverting low grade inflammation in fatty tissue,
and thereby reducing peripheral insulin resistance.
In addition, Action Pharma develops AP1189, an oral treatment of systemic inflammatory
diseases such as rheumatoid arthritis and inflammatory bowel diseases. Similarly, AP405 is
developed for topical treatment of inflammatory skin diseases, such as atopic dermatitis.
Action Pharma has a strong investor base of leading European investors, including Sunstone
Capital, Global Life Science Ventures, InnovationsKapital, SLS Venture, Inventure Capital, and
Oestjysk Innovation. For more information, please visit www.actionpharma.com.
