The Medicines Company Release: Results Of First-In-Man Study With Investigational Anesthetic ABP-700 Presented At ANESTHESIOLOGY® 2015 And International Society Of Anesthetic Pharmacology Annual Meetings

• Study results showed promising safety and tolerability profile including for respiratory and cardiovascular effects
• Linear and dose-proportional pharmacokinetics
• Dose dependent and rapidly reversing pharmacodynamic effect
• Normal adrenocortical responsiveness
• Aqueous formulation with no reported injection site discomfort
• Research awarded “Best in Congress” by International Society of Anesthetic Pharmacology

SAN DIEGO--(BUSINESS WIRE)--Results of the first-in-man study, ANVN-01, with ABP-700, a positive allosteric GABA_A receptor modulator in development for general anesthesia and procedural sedation, were presented at the annual meetings of ANESTHESIOLOGY® 2015 and The International Society of Anesthetic Pharmacologists in San Diego. In addition to the pharmacokinetic and pharmacodynamic data presented at the meeting, data on the effects of ABP-700 on adrenal responsiveness from pre-clinical and two Phase I studies was also presented.

“The presented studies suggest rapid reversing of anesthetic effect, dose dependence of depth and duration of sedation effect, linear pharmacokinetics and dose proportionality, and no effect on adrenal responsiveness. Also, ABP-700 preserves respiratory status at clinically relevant anesthetic doses. The apparent lack of respiratory depression is very striking.”

The ANVN-01 abstract was also recognized as “Best in Congress” by the International Society of Anesthetic Pharmacology on October 23 just prior to the start of the ASA meeting.

In conjunction with the ASA meeting, The Medicines Company held an ABP-700 Scientific Advisory Board to discuss not only ANVN-01 but also three additional clinical studies that are part of the Phase 1 program for ABP-700. Jason Campagna, M.D., PhD, Senior Vice President, Surgery and Perioperative Care at The Medicines Company, noted that the data presented at ASA and discussed at the SAB “support our belief that ABP-700 may be a potentially significant advance in anesthesia and procedural sedation.”

Professor Michel Struys, Professor and Chairman, Department of Anesthesiology, University Medical Center Groningen, Netherlands, and principal investigator for the ABP-700 Phase I program, summarized the findings: “The presented studies suggest rapid reversing of anesthetic effect, dose dependence of depth and duration of sedation effect, linear pharmacokinetics and dose proportionality, and no effect on adrenal responsiveness. Also, ABP-700 preserves respiratory status at clinically relevant anesthetic doses. The apparent lack of respiratory depression is very striking.”

Dr. Talmage Egan, Chairman, Department of Anesthesiology, University of Utah Health Care, noted, “The currently available intravenous anesthetic agents fall short of the ideal. Novel drugs that reduce the risks associated with current anesthetics while offering rapid reversibility would be a welcome addition to the anesthesia formulary. While of course it is still early in the development program, these initial results for ABP-700 are promising.”

ANVN-01 Results

ANVN-01 was a double-blind, randomized, placebo-controlled trial that evaluated the agent’s safety, tolerability, pharmacokinetics and pharmacodynamics in 60 healthy adult volunteers. ABP-700 was given as a single bolus intravenous injection of 0.03 to 1.0mg/kg. Pharmacokinetics were linear and dose-proportional. Depth and duration of sedation were dose dependent as measured by both Modified Observer’s Assessment of Alertness/Sedation scale (MOAA/S) and bispectral index (BIS) and rapidly reversing at all doses. There was no observed blood pressure reduction associated with ABP-700. Nausea or vomiting, common side effects from anesthesia, were reported in less than 2 percent of ABP-700 subjects. Adverse events related to involuntary muscle movement, tachycardia and respiratory effects were dose dependent and consistent with the mechanism of action of ABP-700.

Impact on Adrenal Function Results

Also shown were data about ABP-700 effects on adrenal gland function. These data derive from two separate Phase I studies. In one study, subjects received placebo or a 0.03-1.0mg/kg bolus of APB-700; in the other, subjects received placebo or a 30-minute IV infusion of either ABP-700 (0.9 to 1.97 mg/kg) or propofol (2.25 mg/kg). Results showed that in adrenocortical responsiveness to synthetic ACTH stimulation one hour after bolus doses or 30-minute infusion doses was normal and indistinguishable from placebo or propofol. These results suggest that with ABP-700, any impact on adrenocortical steroid synthesis in humans after single bolus administration or short-term continuous infusion is likely to be brief, clinically unimportant, and equivalent to the current clinical standard of care, propofol.

Conference Call

ABP-700 results will be discussed on a telephone and WebEx conference call on October 27th at 5:30 am PST (8:30 am EST). The following leading anesthesiology experts will be participating on the call:

• J. Robert Sneyd, Dean and Professor of Anaesthesia, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK
• Michel Struys, Professor and Chairman, Department of Anesthesiology, University Medical Center Groningen, Netherlands
• Talmage Egan, MD, Professor and Chairman, Department of Anesthesiology, University of Utah Health Care
• Douglas Raines, MD, Professor of Anesthesia, Massachusetts General Hospital and Harvard Medical School, and inventor of ABP-700

Domestic Dial-in: +1 (877) 359-9508

Ex-US Dial-in: +1 (224) 357-2393

Passcode for both Dial-in numbers: 66920252

This call is being webcast and can be accessed via The Medicines Company website at www.themedicinescompany.com. In addition, the slides that will be used during the call can be found on the event page of the Investor Relations section of our website.

About ABP-700

ABP-700, an investigational product not approved for commercial use in any market, is a novel, positive allosteric modulator of the GABAA receptor currently being developed for general anesthesia and procedural sedation. ABP-700 is from a family of compounds invented by Dr. Douglas Raines at the Massachusetts General Hospital.

About The Medicines Company

The Medicines Company’s purpose is to save lives, alleviate suffering and contribute to the economics of healthcare by focusing on 3000 leading acute/intensive care hospitals worldwide. Its vision is to be a leading provider of solutions in three areas: serious infectious disease care, acute cardiovascular care and surgery and perioperative care. The company operates in the Americas, Europe and the Middle East, and Asia Pacific regions with global centers today in Parsippany, NJ, USA and Zurich, Switzerland.

Forward-Looking Statements

Statements contained in this press release about The Medicines Company that are not purely historical, and all other statements that are not purely historical, may be deemed to be forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words “hopes” and “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties that may cause the Company’s actual results, levels of activity, performance or achievements to be materially different from those expressed or implied by these forward-looking statements. Important factors that may cause or contribute to such differences include whether ABP-700 will advance in the clinical trials process on a timely basis or at all, whether physicians, patients and other key decision makers will accept clinical trial results, whether the Company will make regulatory submissions for ABP-700 on a timely basis or at all, whether its regulatory submissions will receive approvals from regulatory agencies on a timely basis or at all, the Company’s ability to successfully compete with potential competitors which may discover, develop or commercialize competing products more successfully than we do, and such other factors as are set forth in the risk factors detailed from time to time in the Company’s periodic reports and registration statements filed with the Securities and Exchange Commission including, without limitation, the risk factors detailed in the Company’s Quarterly Report on Form 10-Q filed with the SEC on August 7, 2015, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.