DARA Completes Phase 1 Trial

Written by Jason Napodano, CFA

This morning (November 4, 2010), Dara Biosciences (DARA - Analyst Report) announced that it has successfully completed a phase 1 clinical study for DB959, its  peroxisome proliferator activated receptor (“PPAR”) delta/gamma agonist.  Dara is developing DB959 as an oral drug candidate for the treatment of Type 2 Diabetes.

The phase 1 single ascending doses study demonstrated DB959 to be safety and well tolerated, with no reports of moderate, severe, or serious adverse events in any subjects in the study.  Pharmacokinetic analysis of the trial indicated the compound is likely to meet the target dosing regimen of once a day.  The study was a randomized, placebo-controlled, double-blind, escalating single dose study and enrolled 76 healthy male and female volunteers.  Dose escalation covered a 100-fold range in dose.

We expect Dara to present detailed results at an upcoming scientific meeting in the first half of 2011.  Given the positive results seen in this clinical trial, the company plans to initiate a multiple ascending dose trial in the first half of 2011.  After that, a larger-scale phase II study in which DARA plans to study DB959 as both monotherapy and in combination with other standard glucose lowering agents such as metformin, dipeptidyl-peptidase IV (DPP-4) inhibitors, and sulphonylureas (SU).  We note that earlier in the month, Dara announced it had received $488K in Federal Grants qualifying under the Therapeutics Discovery Tax Credit program.  Dara plans to use this grant money to push forward DB959 in 2011.
                                       
Big Potential For DB959

Preclinical data on DB959 demonstrates our enthusiasm for the candidate.  Results show that DB959 controlled glucose while raising HDL and the HDL:LDL ratio and lowering triglycerides.  The data suggests a strong potential for cardiovascular benefits along with hemoglobin (Hb) A1c lowering.  At the June 2009 meeting of the American Diabetes Association (ADA), management presented two abstracts from preclinical data demonstrating safety and efficacy with DB959.  We highlight some of the animal model data below:

These beneficial effects on glucose and lipids were observed without causing the weight gain which is seen with other PPAR or thiazolidinediones (TZD) agonists.  TZDs are used by roughly two-thirds of all Type 2 patients, and include Takeda’s Actos (pioglitazone) and Glaxo’s Avandia (rosiglitazone), the latter of which has come under heavy scrutiny the past few years for a potential increased risk of myocardial ischemia, including heart attack.  TZDs have also been associated with greater incidence of hand and feet fractures and macular edema.  Not to mention, the high profile market withdrawal of Rezulin (troglitazone) in the late 90’s for increased incidence of drug-induced hepatitis that has kept a cloud over the class for the past ten years.  Despite this, sales of the two leading TZD’s, Actos and Avandia, posted sales of $6 billion worldwide prior to the meta-analysis calling into question the cardiovascular safety of Avandia.  Since that time, market share has dramatically shifted from Avandia to Actos, although peak sales of the class are still down over 30% since 2007. 

DARA is also conducting a 2-year carcinogenicity program on DB959, as well as a 29-day toxicology study so that all the preclinical data can be analyzed and in hand by the time the company is ready to seek a development or out-license partner on DB959 in 201 or 2012.  We think this presents shareholders with meaningful upside over the next several quarters.

Read the full analyst report on DARA