Results from Phase I program completed in 112 healthy volunteers, obese subjects and type 2 diabetes patients support further development of AZP-531 in type 2 diabetes with a differentiated clinical profile, combining insulin sensitization and body weight reduction
European Phase II study of AZP-531 in Prader-Willi Syndrome on track for results in 2016 H1

LYON, France I October 29, 2015 I Alizé Pharma SAS, an Alizé Pharma group company specialized in the development of biopharmaceuticals to treat metabolic disorders and rare diseases, announces today the completion of a Phase Ib trial for AZP-531 in 36 Type 2 Diabetes (T2D) patients. This trial was the last stage in an overall Phase I program performed in 112 healthy volunteers, obese subjects and T2D patients.

Results from the T2D Phase Ib trial

The T2D trial was a double-blind 14-day multiple ascending dose Phase Ib study. The aim of the trial was to assess the effect of three doses of AZP-531 versus placebo in a total of 36 uncontrolled T2D patients treated with metformin as a single agent. The study was conducted in a single London-based Phase I center where patients stayed for the full duration of the treatment period.

The results showed an improvement in the metabolic status of patients in all groups, including placebo, suggesting a study effect in an uncontrolled T2D patient population. Notwithstanding this study effect, there was a better metabolic improvement with AZP-531. In particular, at the highest doses being studied (60 mcg/kg QD and 30 mcg/kg BID), HbA1c was significantly decreased with a mean decrease of -0.4% in 14 days (p<0.01 versus baseline). Body weight also significantly decreased at the highest dose (60 mcg/kg QD) with a mean decrease of -2.1 kg in 14 days (p<0.001 vs. baseline).

Administration of AZP-531 for 14 days was well tolerated across all doses. The single and multiple-dose PK parameters were comparable to those observed in healthy and obese study populations from previous AZP-531 trials.

Summary of results from the Phase I program

The Phase I program for AZP-531 was conducted in a total of 112 healthy volunteers, obese subjects and T2D patients. The results strongly support the development of AZP-531 in T2D as a once-daily injectable product with a differentiated clinical profile when compared to existing products and product candidates in advanced stages of development:

   Safety: Administration of AZP-531 for 14 days was well tolerated across all doses tested. The number of subjects with treatment emergent adverse events was similar in both placebo and AZP-531-treated groups. No clinically significant findings were noted with respect to safety labs, vital signs and cardiac assessments

   Pharmacokinetics: Subcutaneous administration resulted in 24-hour exposure to AZP-531, supporting a once-daily treatment regimen

   Pharmacodynamics: Data yielded highly promising and convergent signals of metabolic improvement in AZP-531 treated groups:

       Decreased glucose levels in obese subjects, especially in those with impaired glucose tolerance

       Decreased HbA1c in T2D patients

       No change in insulin levels, consistent with the insulin-sensitizing mechanism of action

       Decreased body weight in obese subjects and T2D patients

Update on Phase II trial in Prader-Willi Syndrome

The multi-center, randomized, double-blind trial aims to enroll up to 40 patients with Prader-Willi Syndrome (PWS) and assess the safety and efficacy of a two-week daily administration of AZP-531 vs. placebo. Recruitment is well advanced and as of today approximately two-thirds of patients have completed the treatment and follow-up periods. The drug has been well tolerated so far. An independent Data Monitoring Committee has reviewed the data collected from the first 20 completed patients and has not raised any safety concerns. Results from this Phase II trial are due to be available in the first half of 2016.

“Our strategy was to design and conduct a broad and ambitious Phase I program for AZP-531 in order to better characterize its profile in metabolic indications. The results on safety, pharmacokinetics and preliminary efficacy from this Phase I program exceeded our expectations and clearly warrant further development of AZP-531 in T2D,” said Soraya Allas, Medical Director at Alizé Pharma. “Our next step will be to deliver results from our ongoing Phase II trial in PWS; another potential and essentially distinct indication for AZP-531.”

“When considering the therapeutic options for T2D available today; despite the significant activity in the field, there is still a clear unmet need for insulin sensitizing drugs with a clean safety profile that also induce weight loss, a key objective in the management of these patients,” said Thierry Abribat, from TAB Consulting, President of Alizé Pharma. “We are delighted to note that so far our clinical data strongly support this clinical profile, with no notable adverse effects, thus underscoring AZP-531’s significant clinical and commercial potential as an add-on therapy, especially in combination with leading insulin secretagogues (GLP-1 agonists and DPP4 inhibitors).”

About the UAG/AZP-531 program

The launch of this clinical program follows five years of collaborative research between Alizé Pharma and its academic partners at the Erasmus Medical Center in Rotterdam, the Netherlands, and the University of Turin, Italy. This research has led to the identification of unacylated ghrelin (UAG) as a new therapeutic class and to the design of AZP-531, a stabilized peptide analog. The unique pharmacological profile of AZP-531 differentiates it from ghrelin antagonists and all existing therapeutic classes. Preclinical and clinical data suggest that UAG and its analogs have the therapeutic potential to address unmet medical needs in the treatment of T2D, PWS and some ischemia-related conditions, via a novel mechanism of action. Alizé Pharma owns a portfolio of 37 granted or pending patents protecting UAG analogs, including AZP-531 and their therapeutic applications. The clinical development program started in 2013. Three Phase I trials in 112 healthy volunteers, obese subjects and T2D patients have been completed. In parallel, a multi-center European Phase II trial in PWS is ongoing.

About type 2 diabetes (T2D)

T2D is a disease characterized by hyperglycemia; an excessively high level of glucose in the blood associated with inadequate amount or activity of endogenous insulin. This disease generally occurs in adults of an advanced age and tends to affect especially obese or overweight people. The number of patients suffering from T2D is constantly rising as a result of the obesity pandemics and an aging population. The International Diabetes Federation expects the number of diabetic patients worldwide to rise from 387 million in 2014 to 592 million by 2035. Managing diabetes and its cardiovascular complications is a major public health challenge. Currently, all available drugs can only delay the progress of the disease; there is no treatment that can cure diabetes and its complications. In this context, there is a major medical need to develop innovative drugs that are based on new mechanisms to be used in combination with existing drugs for the improved management of diabetes.

About Prader Willi Syndrome (PWS)

PWS is a rare genetic disease and the most common form of genetic obesity with an estimated prevalence of 1 to 9 per 100,000. It is a complex clinical syndrome, characterized by life-threatening obesity, short stature, hypogonadism as well as cognitive, behavioral and psychiatric disturbances. As a consequence of obesity, up to 25% of adult patients with PWS also develop T2D. Hyperphagia is the most salient and constant feature of the syndrome. It begins in early childhood and is associated with a lack of satiety. Patients typically display abnormal eating behaviors including obsessive food seeking, food storage, foraging and hoarding that represent a lifelong source of distress for them and their families. Patients live a dependent life requiring continuous care and supervision. In addition, hyperphagia is associated with significant morbidity and mortality. Obesity-related complications are the leading cause of death in this patient population. PWS is a unique clinical condition specifically associated with increased levels of acylated ghrelin, a potent orexigenic hormone. There is currently no effective pharmacological treatment for hyperphagia and its associated abnormal eating behaviors.

About Alizé Pharma

Alizé Pharma is a group of companies specialized in the development of innovative biopharmaceutical drugs, proteins and peptides for the treatment of metabolic diseases and rare diseases. The group is managed by a team of drug development experts and a board of directors with a breadth of international experience. Its business strategy is to advance programs based on medical innovation to the clinical stage and establish partnerships with pharmaceutical companies to secure both short and long-term revenue streams. Since its creation the group has raised over €15M from private and institutional investors and has acquired and implemented three programs:

   AZP-531, a stabilized analog of UAG, a physiological gastrointestinal peptide. This program is in Phase II clinical development for the treatment of PWS and has completed Phase I for T2D.

   Pegcrisantaspase (ASPAREC® / JZP416), a new pegylated recombinant L-asparaginase for the treatment of acute lymphoblastic leukemia (ALL). It is partnered with Jazz Pharmaceuticals (Nasdaq: JAZZ), and is currently in Phase II/III clinical development.

   I-HBD1, a peptide with bone anabolic properties, to be developed in osteoporosis and other bone diseases. This I-HBD1 program is at the lead optimization stage.

SOURCE: Alizé Pharma