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Expert Financial Analysis and Reporting

Phase II Data for ADL 5945 in Opiod Induced Constipation is Excellent (ADLR, $2.23)

On a first quick review of the data from the phase II trial of ADL 5945 in chronic non-cancer pain patients with opioid-induced constipation, it looks like the efficacy and safety profile are excellent. The drug should enter a phase III trial and Adolor should be able to find a partner to fund much of the development. This adds a very important new component to the valuation. Biotechnology investors have come to dread the release of important binary trial data and with good reason as the failure rates are high and the stocks can be penalized severely if trials fail. I was willing to take the risk with Adolor on its phase II trial of ADL 5945 because it is my feeling that the value of the company based on Entereg alone could be $4.50 in 2013 without taking into account the potential for ADL 5945.


I am in the process of going through the data in detail, but I thought that I would just put out a quick take. The dose for phase III is likely to be a 0.25 mg dose taken twice per day. In the trial, this dose achieved statistical significance at p=0.0003 on the primary endpoint of change in spontaneous bowel movements (SBM) as compared to baseline. For this 0.25 mg dose, the change was 3.4 SBMs. The patient population in this study was chronic opioid users who had chronic constipation as a result of their opioid usage. This is defined as less than 3 SBMs per week. ADL 5945 was able to produce 4 or more SBMs in each week of the four week trial while placebo was never above 3. There is a major benefit is in quality of life for patients if they can achieve 3+ SBMs per week.

The safety profile seems excellent with the drug having placebo like side effects. The drug seems to be particularly safe in gastrointestinal side effects, which is the most troubling side effect concern for drugs used in this condition. It appears that the favorable GI side effect profile may meaningfully differentiate ADL 5945 from other drugs under development for this condition.

The company is planning for an end of phase II meeting with the FDA and is preparing for a phase III trial, which should begin in early 2012. The cost of the trial could be on the order of $60 million and Adolor will seek a partner. Obtaining a partner will be the next significant event to watch for. A meaningful front end payment of $20 million or so could obviate the need for any additional financing to complete the takeover of Entereg and the funding of the phase III trial.

I will be taking a closer look at the data in the near future. While I am impressed by the data, I am like most biotechnology analysts conditioned to look for problems. It is sometimes the case that topline data becomes less favorable as additional data is released. While I do not expect that will be the case, I will still be looking for it.

I have learned from past experience that topline data may not

Adolor Corporation (NasdaqGM:ADLR) today announced positive, statistically significant top line results from its two Phase 2 studies of ADL5945 in chronic non-cancer pain patients with opioid-induced constipation (OIC). ADL5945, a peripherally-acting mu opioid receptor antagonist, is an investigational drug being evaluated for the treatment of OIC as well as other associated gastrointestinal (GI) complications. Both randomized, double-blind, placebo-controlled studies were identical in design; Study 242 evaluated 0.25 mg and 0.10 mg of ADL5945 administered twice daily (BID) and Study

Study Results

Twice-daily Dosing (Study 242)

Statistical significance (p = 0.0003) was achieved for the primary endpoint in the 0.25 mg BID dose group. The primary endpoint of both studies was the change from baseline in the weekly average number of spontaneous bowel movements (SBMs). Response to treatment was dose dependent in Study 242, with an average change from baseline in SBM frequency over the 4-week treatment period of 1.4 SBMs for the placebo group, and 2.0 and 3.4 SBMs for the 0.10 mg and 0.25 mg doses of ADL5945, respectively. Statistical significance was not achieved for the 0.10 mg dose.

Statistical significance (p = 0.005) also was achieved in the 0.25 mg BID dose group for a key secondary endpoint, a responders analysis, with a 56% response rate for the active arm and a 26% response rate for the placebo arm of the study. This translates into a clinically relevant number needed to treat (NNT) of 3.3. For this analysis, responders were defined as those patients who achieved an average weekly frequency of at least three SBMs and an increase of at least one SBM above baseline.

Other exploratory endpoints (patients' global impression of change, BM comfort and satisfaction scores) demonstrated greater improvement as compared to baseline in the ADL5945 0.25 mg treatment group as compared to placebo.

Once-daily Dosing (Study 243)

In Study 243, statistical significance (p= 0.01) also was achieved for the primary endpoint. The average change from baseline in SBM frequency over the 4-week treatment period was 1.4 SBMs for the placebo group and 2.6 SBMs for the 0.25 mg ADL5945 treatment group.

Although the proportion of responders was higher in the 0.25 mg treatment group (42.5% vs. 29.3% in placebo), statistical significance was not achieved.

Other exploratory endpoints evaluating changes in bowel function trended in favor of ADL5945 as compared to placebo.

Safety and Tolerability

ADL5945 was well tolerated in both studies. The overall number of patients reporting at least one treatment-emergent adverse event was comparable across both studies (ADL5945: 29%; placebo: 26%). There was no evidence of drug-related central opioid withdrawal or reversal of analgesia in any of the ADL5945 treatment groups across both studies.

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