PA-18-574
Project Summary/Abstract
SER-227 is a long-acting polymer pro-drug of buprenorphine that is being developed to treat post-
operative pain following major surgeries such as bunionectomy, abdominoplasty, thoracotomy and
knee and hip surgery. SER-227 has no biological activity by itself, but when administered in vivo
by subcutaneous injection it enters the vascular compartment where a plasma esterase
(butyrylcholinesterase, BChE) enzymatically releases the active pharmaceutical ingredient,
buprenorphine. The polymer confers prolonged circulatory half-life, allowing buprenorphine to be
released continuously over ~ 3-4 days. Buprenorphine is a mixed mu-agonist/antagonist at the mu
opioid receptor (MOR), and an antagonist at the kappa opioid receptor. A single administration
of SER-227 has been shown to provide both immediate and prolonged analgesia in the Brennan
model. Prompt analgesia, which subsequently lasts ~ 3-4 days, should obviate the need to initiate
therapy by a potentially addictive opioid in the hospital and allow patients to be discharged on
non-additive drugs such as acetaminophen or NSAIDs.
SER-227 is to be administered as a subcutaneous injection in the immediate post-operative period
(e.g. recovery room). This product is intended to be a one-time injection (by a
surgeon/anesthesiologist) that will provide both immediate and > 3 days of analgesia. SER-227 is
predicted to demonstrate very low abuse liability (indeed, long-acting implants of buprenorphine
are used to treat opioid use disorder) and is likely to be used largely in surgical centers; it is not
intended for self-administration.
A Research Strategy is presented that will focus on the early development and preclinical
objectives of this program, where the ultimate goal is to demonstrate that SER-227 can be
manufactured and tested preclinically to show that it is safe for use in a Phase I clinical study.
1. SER-227 chemistry and process optimization to generate a technical package, and
2. SER-227 manufactured under current Good Manufacturing Practices, and
3. Evaluated in formal toxicology studies in rodent and non-rodent animals so that justifications
can be made to support a ‘first-in-man’ study,
4. Submission of an Investigational New Drug application (IND) along with a Phase I clinical
protocol in normal volunteers to measure the safety, tolerability and pharmacokinetics of
buprenorphine that is released from SER-227.
This ‘Direct to Phase II’ submission is made under the ‘HEAL Initiative, Notice of Interest in
Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR)
Applications Directed at Enhanced Pain Management and Improved Treatments for Opioid Misuse
and Addiction’. Based upon prior experience in studies of similar design, we anticipate this Phase
of the program would take 18 to 24 months to complete.
