Acusphere Issues Year-End Review to Shareholders.

Outlines Milestones for 2007

WATERTOWN, Mass. -- Acusphere, Inc. (NASDAQ:ACUS) today issued a letter to shareholders. The text of this letter is as follows:

Dear Fellow Shareholders:

As I have done in the past, I like to provide Acusphere shareholders with a review of the Company's achievements in 2006 and our plans for building upon those accomplishments as we move forward in 2007. Before I discuss past and future achievement, I thought it might be helpful to provide some background on our lead product, Imagify[TM], the first ultrasound contrast agent designed to detect myocardial perfusion, or blood flow to the heart muscle. I hope that this letter serves as a useful, single-source overview of the Acusphere value proposition.

Imagify Background

Ultrasound is one of the least expensive and convenient ways to image the body, but ultrasound alone is not capable of assessing myocardial perfusion (blood flow to the heart muscle). The ability to evaluate perfusion in the heart muscle allows for early detection of coronary artery disease--the leading cause of death in the U.S. and many other parts of the world. We believe that Imagify has the potential to improve the ability of heart ultrasound tests to compete with the nuclear stress test, an inconvenient and expensive standard for assessing perfusion today. Almost 12 million nuclear stress tests and heart ultrasound stress tests are performed each year in the U.S., providing Acusphere with an addressable market potential of more than $2 billion per year for Imagify in the U.S. alone. Our Imagify Phase 3 clinical program is designed to demonstrate that the efficacy of Imagify-enhanced heart ultrasound stress testing is statistically non-inferior or, in practical terms, equivalent to nuclear stress. Our two pivotal Phase 3 clinical trials are called RAMP-1 and RAMP-2 (Real-time Assessment of Myocardial Perfusion). We have evaluated Imagify in more than 1,000 patients thus far and believe that it is well tolerated.

2006 Accomplishments

In 2006, Acusphere took many steps forward towards its goal of commercializing Imagify by completing the RAMP-1 trial, completing enrollment and training of ultrasound blinded readers of the RAMP-2 trial, manufacturing commercial-scale development batches, strengthening our intellectual property position through two important license agreements, and expanding our senior management team.

Completed the RAMP-1 Trial

In June 2006, we announced the RAMP-1 trial results during the American Society of Echocardiography (ASE) Annual Conference. Our goal from this 320 patient trial was for two-out-of-three "blinded readers" of Imagify-enhanced ultrasound images to be non-inferior to a single blinded reader of the nuclear stress test images from the same patients. We evaluated non-inferiority in three different patient groups, using endpoints called accuracy, specificity and sensitivity. When we looked at all of the patients in the trial (accuracy), all three ultrasound blinded readers were non-inferior to nuclear stress; and when we looked at the subset of patients without disease (specificity), two ultrasound blinded readers were superior to the nuclear blinded reader. These results for both accuracy and specificity exceeded the trial design's criteria for success. When we looked at the subset of patients with disease (sensitivity), one ultrasound blinded reader was non-inferior to the nuclear reader while the other two ultrasound blinded readers did not meet this statistical test.

Based on feedback from our clinical investigators, who are key opinion leaders in the field, we were encouraged by the consistently high accuracy across all of the ultrasound blinded readers in RAMP-1, which gives us confidence in the performance of Imagify. Accuracy is the most objective of all the diagnostic endpoints. Sensitivity and specificity are more subjective and influenced by the preferences of the ultrasound blinded readers. We believe that our nuclear blinded reader and one of the ultrasound blinded readers had a preference to be "aggressive" readers, while the other two ultrasound blinded readers were "conservative" readers. In our view, aggressive readers make the judgment that images showing relatively small perfusion defects are abnormal (e.g. diseased), resulting in higher sensitivity than specificity; whereas conservative readers make the judgment that such ambiguous images are normal, resulting in higher specificity than sensitivity. Since all three of our ultrasound blinded readers met the statistical test for accuracy, we believe Imagify is performing well and we believe we can train our readers to be more aggressive, which we believe should increase their sensitivity while maintaining accuracy. We believe the RAMP-1 results represent an encouraging step forward toward our goal of submitting the NDA for Imagify in 2007.

When we announced the trial results at the American Society of Echocardiography Annual Conference, it was apparent to me that the prospect of an ultrasound contrast agent that can assess perfusion in an accurate, immediate and radiation-free way was very exciting to the physicians in attendance. Our confidence in Imagify remains high and it is now our belief that Imagify is positioned to be the first-to-market contrast agent for perfusion imaging using ultrasound.

Completed RAMP-2 Enrollment and Training of Ultrasound Blinded Readers

Enrollment in this 457 patient trial was completed in Q2 2006. In Q3 and Q4 2006 we trained all of our ultrasound blinded readers to read more aggressively. Using images from the completed RAMP-1 trial, all six of the RAMP-1 and RAMP-2 ultrasound blinded readers improved their sensitivity, and thus we believe all six are "aggressive" readers. This training was made possible with the availability of the images from the completed RAMP-1 trial. Prior to RAMP-1, only a limited database of ultrasound perfusion images existed. After completing this improved training program, the RAMP-2 ultrasound blinded readers are now in the process of reading all evaluable RAMP-2 images to take advantage of this training.

Manufactured Commercial-Scale Development Batches of Imagify

On the manufacturing front, we moved considerably closer to qualifying our commercial manufacturing facility for Imagify production. In Q1 2006, we completed commissioning of the equipment in the new facility and, in Q2 2006, we produced commercial-scale development batches of Imagify. This was achieved in part as a result of the support of our European partner, Nycomed, which accelerated a potential future milestone payment, helping us fund these efforts. The progress that we made in 2006 toward this goal reflects incredible teamwork and dedication from employees throughout our Company.

Strengthened Imagify Intellectual Property Position in Primary Markets

Acusphere took significant steps to secure intellectual property rights in the U.S. and Europe for Imagify by completing two transactions in Q2, one with General Electric Healthcare and the other with Bracco. We took these steps after seeing the RAMP-1 results and concluding that the results were strong enough to warrant paying now to remove these potential obstacles to our freedom to operate rather than incurring greater costs and risks as we move closer to commercialization. We are not aware of any other patents which we believe would cause intellectual property-related issues for Imagify in our primary markets of the U.S. and Europe.

Added Experienced Senior Management

In 2006, the Company added two key senior executives who are supporting the many preparations necessary to take full advantage of the potentially large Imagify commercial market opportunity. Mona Haynes joined Acusphere in Q1 2006 as our Vice President of Marketing and Sales with 25 years of pharmaceutical marketing and sales experience. At Biogen, she had overall marketing responsibility for Avonex[R], which grew from $75 million to $750 million under her leadership. Most recently, at Alkermes, she was responsible for building the marketing function for Vivitrol[TM], a drug that was recently licensed to Cephalon in a transaction valued at approximately $500 million. Jonathan Jaffe, M.D. joined Acusphere in Q3 2006 as Vice President of Medical Affairs with over 30 years of experience focused on cardiology and cardiovascular disorders. Dr. Jaffe is a board certified cardiologist and prior to joining Acusphere directed the Merck National Science Cardiovascular/ Endocrine/ Metabolic and Obesity team. At Merck he had responsibility for Zocor[R], Cozaar[R]/Hyzaar[R], Zetia[R], Vytorin[R] and Januvia[R]. His private sector medical experience was focused on practicing preventive cardiology and includes extensive background in echocardiography and vascular imaging. Both of these individuals bring a wealth of practical experience and a thorough grounding in the process involved in driving the adoption of new pharmaceutical products and both add to an already broad management team of which I am very proud.

Met Criteria for Success in Partnered HDDS Feasibility Program

In 2006, we conducted a feasibility study with a large pharmaceutical company using our HDDS technology in which we successfully met the criteria for success in reformulating one of the partner's pipeline products to overcome potential issues with getting the drug to effectively dissolve. That company is now evaluating whether or not to proceed with further development of this product candidate.

2007 Goals

We have many important goals for 2007, including completing the blinded reads of the RAMP-2 images and releasing the results, completing the qualification of our commercial manufacturing facility, submitting the NDA, completing additional clinical trials that will strengthen our market position at launch, and beginning development of a new HDDS product that will fit the commercial infrastructure we plan to build for Imagify.

Complete RAMP-2 Blinded Reads and Release Results

Completing the RAMP-2 blinded reads is a top priority this year. While Acusphere will have no access to the efficacy data of the RAMP-2 trial until all of the blinded reads are completed and our independent clinical research organization completes its quality checks, based on our training results using RAMP-1 images, we are very optimistic about the success of RAMP-2. Indeed, all of our activities relating to IP licensing, manufacturing qualification, and marketing preparations for commercialization are based upon an assumption of this success. All three ultrasound blinded readers have read more than 150 images, and we expect that the results will be made public in Q2 2007.

Qualification of the Imagify Commercial Manufacturing Facility

In January 2007, we completed all installation and operational qualification of the manufacturing equipment and utilities for our commercial manufacturing facility, which are the technical assessments related to verifying successful operation of the entire facility. As Imagify is an injectable product that must be manufactured under sterile, or aseptic, conditions, we are now focused on completing the necessary procedures and operator training to ensure that we can meet the required standards of sterility. We will then begin aseptic validation by running multiple batches filled with media designed to detect any biological contaminants in Q3. In the fourth quarter, after completing aseptic validation we will begin making process qualification batches, running the complete process from end-to-end under aseptic conditions.

Imagify NDA Submission

Once the RAMP-2 trial is complete and results announced, there are clinical documentation requirements that need to be completed prior to submitting the NDA. While our clinical team has already been working diligently on sections of the application that can be addressed ahead of time, the Acusphere team will be highly focused on completing the remaining clinical documentation and manufacturing qualification to complete the NDA submission in Q4 2007.

Complete Additional Clinical Trials to Strengthen Imagify's Market Position

As a part of our ongoing clinical program for Imagify, in 2007 we will continue investigating the performance of Imagify-enhanced heart ultrasound in a range circumstances that may be encountered beyond of the original scope of the Phase 3 pivotal study. One such trial, named ACCESS (Acquiring Consensus for Contrast Echocardiography System Settings), is designed to test Imagify in the current clinical environment and on a variety of ultrasound platforms, defining the settings that are optimum for Imagify on those platforms that may not have been available when the Phase 3 trial commenced in 2003. ACCESS is a small trial which will enroll approximately 50 patients. We expect to complete enrollment in Q2. While RAMP-1 and RAMP-2 focused on Imagify's "diagnostic" value, which is the ability to detect the presence or absence of disease at a fixed point in time, we anticipate evaluating Imagify's "prognostic" value, which is the ability to predict future cardiovascular events. No new enrollment will be required for this study, since over 700 images have already been collected from the appropriate patient population through the RAMP-1 and RAMP-2 trials. We believe that both studies can be completed with modest financial commitment and within our previously stated financial guidance.

Begin Development of New HDDS Product Candidate

Now that Imagify is moving closer to commercialization, it is important that we begin to re-capitalize on our product pipeline. We believe Acusphere's proprietary microparticle technology platform can provide many potential product candidates to fuel this pipeline development. We are focusing on products that fit into the hospital-based commercial infrastructure that we plan to build for Imagify. We anticipate announcing plans for an exciting new HDDS[TM] development program in Q3 2007.

Financial Guidance for 2007

Our cash position at the end of 2006 was $59.7 million (unaudited). This funding level provides Acusphere with the ability to stay focused on delivering the RAMP-2 results and continue with the manufacturing qualification progress in anticipation of the NDA submission. We begin 2007 expecting that our operating activities will require some $10-$12 million in cash per quarter, with additional quarterly expenditures of approximately $2 million for payments against asset-backed installment debt and dividends on preferred stock. In addition, we are scheduled to make payments totaling $8 million in the second quarter of 2007 as the final remaining non-contingent payments against previously announced intellectual property agreements. We anticipate that our spending on internal development of pipeline product opportunities will be relatively modest in 2007, reflecting their early stage of development. Our spending on the additional clinical programs will also be modest because together they involve only about 50 new patients. Based on this guidance, our current cash can meet our projected needs through 2007.

Overall, we are pleased with the progress that we have made in 2006 and are confident in our ability to successfully complete our important 2007 objectives:

* Release RAMP-2 results (Q2)

* Complete enrollment in the ACCESS trial (Q2)

* Announce a new HDDS development program (Q3)

* Begin aseptic validation of our commercial manufacturing facility (Q3)

* Complete process qualification batches (Q4)

* Submit the NDA for Imagify (Q4)

In closing, I want to welcome our new investors that have joined Acusphere in 2006 and thank our existing investors for your continued support and commitment as we move Imagify closer to commercial launch. We will continue to make Acusphere management available to our investors by participating in various investor conferences throughout the year. In the first quarter, we will participate at the BIO CEO conference (February in New York City), the SIG Healthcare Conference (March in New York City) and the Cowen & Co. Healthcare Conference (March in Boston). I look forward to the upcoming year and accomplishing our mission together.

Sincerely,

Sherri C. Oberg

President and CEO

About Imagify[TM] (perflubutane polymer microspheres) injectable suspension

Imagify (pronounced i-maj'-i-fo), formerly known as AI-700, is an investigational ultrasound contrast agent in Phase 3 clinical development, designed to provide physicians with valuable information on myocardial perfusion. Acusphere is developing Imagify to enable stress echo to assess myocardial perfusion and compete more effectively with nuclear stress testing, the leading procedure for detecting coronary heart disease. The Company believes that Imagify enhanced ultrasound has the potential to be a cost effective and convenient method to screen for coronary heart disease. An estimated 11.9 million procedures are done each year in the U.S. to detect coronary heart disease, the leading cause of death in the United States and the Company estimates that the U.S. commercial opportunity for Imagify approaches $2.4 billion. Imagify was designed to be used with commercially available ultrasound equipment and established imaging techniques and has been studied in more than 1000 patients to date.

Glossary of Terms Used Above

Accuracy: the ability to correctly diagnose all the patients in the study.

Aggressive Readers: Physicians who that make the judgment that images (nuclear or ultrasound) showing relatively small perfusion defects are diseased.

Blinded Readers: physicians with expertise in reading stress ultrasound images (ultrasound blinded reader) or nuclear stress images (nuclear blinded reader). The physicians have access to no clinical information about the patient, and so blinded reading is much more difficult than reading in the normal clinical setting, where physicians have access to patient history, symptoms and other test results.

Conservative Readers: Physicians who make the judgment that images (nuclear or ultrasound) showing relatively small perfusion defects are without disease.

Non-inferiority: a statistical type of trial analysis, which is designed to show that one test is comparable to another test, within a certain statistical margin of error.

RAMP-1 and RAMP-2: The two pivotal Phase 3 trials conducted by Acusphere to assess the safety and efficacy of Imagify. The purpose of these trials is to demonstrate that stress ultrasound with Imagify[TM] is non-inferior to nuclear stress testing. RAMP is an abbreviation of Real-time Assessment of Myocardial Perfusion with ultrasound.

Sensitivity: The ability to correctly diagnose patients with confirmed disease.

Specificity: The ability to correctly diagnose patients confirmed to be without disease.

About Acusphere, Inc.

Acusphere (NASDAQ: ACUS) is a specialty pharmaceutical company that develops new drugs and improved formulations of existing drugs using its proprietary microparticle technology. Acusphere's three initial product candidates are designed to address large unmet clinical needs within cardiology, oncology and asthma. These product candidates were created using proprietary technology that enables Acusphere to control the porosity and size of nanoparticles and microparticles in a versatile manner that allows particles to be customized to address the delivery needs of a variety of drugs. Acusphere's lead product candidate, Imagify, is a cardiovascular drug in Phase 3 clinical development. For more information about Acusphere visit the Company's web site at www.acusphere.com. "Acusphere" and "Imagify" are trademarks of Acusphere, Inc.

Forward-looking Statements 

The above press release contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 21E of the Securities Exchange Act of 1934, including statements regarding the successful completion of clinical trials, in particular, successful results for our RAMP-2 trial, and statements regarding the timing and likelihood of regulatory approval of an NDA submission for Imagify, the timing and success of the ACCESS trial for Imagify, the timing of announcement of a new HDDS development program, the timing and success of qualification of a commercial manufacturing facility, including process qualification and aseptic validation, capital requirements, the strength of our intellectual property position, the ability to establish and develop a sales team for Imagify and, commercial prospects for the Company's current and future product candidates. The Company's actual results may differ materially from those anticipated in these forward-looking statements based upon a number of factors, including anticipated operating losses and existing capital obligations, uncertainties associated with research, development, testing and related regulatory approvals, including uncertainties regarding the ultimate outcome of Acusphere's Phase 3 clinical trials for Imagify and uncertainties regarding the number of patients required to complete the Phase 3 clinical trials, future capital needs and uncertainty of additional financing, uncertainties regarding the cost, timing and ultimate success of the qualification of the Company's commercial manufacturing facility in accordance with applicable regulatory requirements, complex manufacturing, high quality requirements, lack of commercial manufacturing experience, dependence on third-party manufacturers, suppliers and collaborators, uncertainties associated with

intellectual property, competition, loss of key personnel, uncertainties associated with market acceptance and adequacy of reimbursement, technological change and government regulation, and other risks and challenges detailed in the Company's filings with the U.S. Securities and Exchange Commission, including the Company's Annual Report on Form 10-K and most recent Quarterly Report on Form 10-Q for the quarter ended September 30, 2006. Readers are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect events or circumstances that occur after the date of this press release or to reflect the occurrence of unanticipated events.