Adipotide

Obesity is the number one health threat and one of the leading causes of preventable deaths in the United States.  Arrowhead’s anti-obesity drug candidate, Adipotide, selectively destroys the blood supply that supports the growth of unhealthy fat by the targeted induction of apoptosis (cell death) in the vasculature of adipose tissue. The peptide consists of two functional domains. The homing domain targets a membrane associated protein, Prohibitin, on adipose vascular endothelial cells. The membrane disrupting domain causes apotosis by disrupting mitochondrial membranes inside the cells.

Published data include reports that obese study animals lost nearly one-third of their body weight after one month of daily subcutaneous injections.

Adipotide's Advantages

  • Shown to promote weight loss in preclinical studies.
  • Shown to reduce symptoms of diabetes.
  • Novel mechanism compared to other therapeutics on the market or in trials.
  • No modulation of neurotransmitters, thus unlikely to have psychological side effects.
  • No amphetamine-like mechanism.
  • Mechanism not likely to yield GI side effects.

Discovery

Ablaris' angiogenesis inhibitors are based on a platform technology licensed from MD Anderson Cancer Center in Houston, TX. White adipose tissue (fat) is highly vascularized and both the expansion and maintenance of adipose tissue depend on a continued ability to build supporting vasculature. Ablaris' platform technology utilizes Arrowhead’s Homing Peptide™ library developed in the laboratory of Dr. Renata Pasqualini and Dr. Wadih Arap. This peptide targeting library provides a map of the unique cell receptors on the vasculature that varies in different tissues. Targeting vasculature based on this variation allows for specific delivery of drug payloads to specific target cells, while avoiding collateral injury to other healthy/non-targeted cells. Using this technique, peptide sequences that target receptors specific to white adipose tissue were identified.

Adipotide Phase 1 Clinical Trial

An Investigational New Drug Application (IND) for Adipotide was accepted by the FDA, and a Phase I clinical trial has been initiated to test the safety of the compound in human patients. MD Anderson Cancer Center in Houston will treat up to 39 obese prostate cancer patients in the Phase I study and will bear all direct costs of this trial. Up to 5 dose levels of the drug will be tested. Three participants will be enrolled at each dose level, with the first group of participants receiving the lowest dose level by injection under the skin once per day for 28 days and each new group receiving a higher dose than the group before it, if no intolerable side effects are seen. This will continue until the highest tolerable dose is found. For more information about these clinical trials, please visit http://www.clinicaltrials.gov.

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