Document:

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                                                                   Exhibit 10.27

THIS CONVERTIBLE PROMISSORY NOTE AND THE SHARES OF COMMON STOCK ISSUABLE UPON
CONVERSION HEREOF HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED, AND MAY NOT UNDER ANY CIRCUMSTANCES BE SOLD, TRANSFERRED OR OTHERWISE
DISPOSED OF WITHOUT AN EFFECTIVE REGISTRATION STATEMENT FOR SUCH SECURITIES
UNDER THE SECURITIES ACT OF 1933, AS AMENDED, AND ANY APPLICABLE STATE
SECURITIES LAWS, OR AN OPINION OF COUNSEL SATISFACTORY TO THE COMPANY THAT
REGISTRATION IS NOT REQUIRED UNDER SUCH ACT OR APPLICABLE STATE SECURITIES LAWS.

THE TRANSFER OF THE SECURITIES REPRESENTED BY THIS CERTIFICATE IS ALSO SUBJECT
TO THE RESTRICTIONS CONTAINED IN THAT CERTAIN SECURITIES PURCHASE AGREEMENT,
DATED JUNE 30, 2000 BY AND BETWEEN ACUSPHERE, INC. AND ELAN INTERNATIONAL
SERVICES, LTD.

                                 ACUSPHERE, INC.
                    CONVERTIBLE SUBORDINATED PROMISSORY NOTE

U.S.$8,010,000                                                     JUNE 30, 2000

                  The undersigned, ACUSPHERE, INC., a Delaware corporation with
offices at University Park at M.I.T., 38 Sidney Street, Cambridge, MA 02139 (the
"Company"), unconditionally promises to pay to ELAN INTERNATIONAL SERVICES,
LTD., a Bermuda exempted limited liability company ("EIS"), or its permitted
assigns, transferees and successors as provided herein (collectively with EIS,
the "Holder"), on June 30, 2006, (the "Maturity Date"), at such place as may be
designated by the Holder to the Company, the principal amount outstanding
hereunder (not to exceed U.S.$8,010,000 (excluding capitalized interest), or
such lesser amount as shall then be payable pursuant to the terms of Section 3
hereof, together with interest thereon accrued at a rate per annum equal to 6%,
from and after the date of the initial disbursement of funds hereunder (the
"Original Issue Date"), compounded on an annual basis, the initial such
compounding to commence on the date that is 360 days from and after the Original
Issue Date and thereafter on each 360-day anniversary (each such date, a
"Compounding").

         SECTION 1. SECURITIES PURCHASE AGREEMENT.

                  This Note is issued pursuant to a Securities Purchase
Agreement dated as of the date hereof, by and between the Company and EIS (as
amended at any time, the "Securities Purchase Agreement"), and the Holder hereof
is intended to be afforded the benefits thereof, including the representations
and warranties set forth therein. The Company shall use the proceeds of the
issuance and sale of this Note solely in accordance with the provisions set
forth therein and as required therein. Capitalized terms used but not otherwise
defined herein shall, unless otherwise indicated, have the meanings given such
terms in the Securities Purchase Agreement.
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                                      -2-

         SECTION 2. PAYMENTS OF PRINCIPAL AND INTEREST.

                  Unless earlier converted in accordance with the terms of
Section 4 below, or repaid in accordance with the terms hereof or reduced
pursuant to Section 3 below, the entire outstanding principal amount of this
Note, together with any accrued interest thereon, shall be due and payable on
the Maturity Date. Accrued interest hereon shall not be paid in cash, but shall
be capitalized and added to the principal amount outstanding hereunder on each
Compounding Date.

         SECTION 3. REDUCTION OF AMOUNTS PAYABLE HEREUNDER.

                  If EIS shall have exercised the EIS Exchange Right (as such
term is defined in the Securities Purchase Agreement) then, unless, pursuant to
Section 5(c) of the Securities Purchase Agreement, EIS shall have caused to be
paid to the Company within 30 days of such exercise the Make-Whole Amount, then
the Company shall be entitled to have such amounts as shall then be outstanding
hereunder reduced by the Make-Whole Amount or such portion of the Make-Whole
Amount as has not been repaid by EIS at such time. Such reduction shall be
evidenced in writing by an appropriate notation hereon or such other
documentation as shall be agreed to in writing by the Company and the holder
hereof, which agreement shall not be unreasonably withheld or delayed.

         SECTION 4. CONVERSION.

         (a) Conversion Right.

                  (i) Until this Note is repaid in full, the Holder shall have
the right from time to time, in its sole discretion, to convert all or any
portion of the outstanding principal amount and accrued and unpaid interest
then-outstanding hereunder, (the "Conversion Right"), into such number of shares
of common stock of the Company (the "Common Stock") that shall be obtained by
(A) dividing (1) the initial $6 million of the aggregate outstanding principal
amount of this Note and all accrued and unpaid interest thereon by (2) $8.00 and
(B) dividing (1) the remainder of the sum of the aggregate outstanding principal
amount of this Note and all accrued and unpaid interest thereon by (2) the
dollar amount equal to the greater of $8.00 or 75% of the then Fair Market Value
(as defined below) of one share of the Common Stock, subject to adjustment as
provided below in this Section (the "Conversion Price").

                  (ii) The Holder shall be entitled to exercise the Conversion
Right from time to time as to the unconverted portion of this Note upon at least
10 days' prior written notice to the Company, such notice to be in the form
attached hereto as Annex I. Within 10 days of the conversion date specified in
such notice, the Company shall issue appropriate stock certificates to EIS
representing the aggregate number of shares of Common Stock due to EIS as a
result of such conversion.
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                                      -3-

         (b) Reclassification. Etc. In case of (i) any reclassification,
reorganization, change or conversion of securities of the class issuable upon
conversion of the outstanding principal amount and accrued and unpaid interest
then-outstanding hereunder (other than a change in par value, or from par value
to no par value), or (ii) any consolidation of the Company with or into another
entity (other than a merger or consolidation with another entity in which the
Company is the surviving entity and that does not result in any reclassification
or change of the class of securities issuable upon the conversion of the
outstanding principal amount and accrued and unpaid interest then-outstanding
hereunder), or (iii) any sale of all or substantially all the assets of the
Company, then the Company, or such successor or purchasing entity, as the case
may be, shall duly execute and deliver to the Holder a new Note or a supplement
hereto (in form and substance reasonably satisfactory to the Holder of this
Note), so that the Holder shall have the right to receive, in lieu of the shares
of Common Stock otherwise issuable upon the conversion of such outstanding
principal amount and accrued and unpaid interest then-outstanding hereunder, the
kind and amount of shares of stock and other securities, money and property
receivable upon such reclassification, reorganization, change, merger,
consolidation or conversion by a holder of the number of shares of Common Stock
then issuable under this Note. Such new Note shall provide for adjustments that
shall be as nearly equivalent as may be practicable to the adjustments provided
for in this Section 4. The provisions of this Section 4(b) shall similarly
attach to successive reclassifications, reorganizations, changes, mergers,
consolidations, transfers or conversions.

         (c) Below Market Issuance: Stock Dividends; Etc. If at any time while
there is any outstanding principal amount and accrued interest then-outstanding
hereunder the Company shall:

                  (i) issue or sell any shares of Common Stock at a price below
both the lesser of the then-current Fair Market Value per share (as defined
below) and the Applicable Adjustment Price (as set forth in Section 4(i) below)
in effect immediately prior to such issuance, then each of such Applicable
Adjustment Price and such Conversion Price shall forthwith (except as otherwise
provided in this Section 4(d)) be adjusted to a price equal to a price
determined by multiplying such Applicable Adjustment Price or Conversion Price,
as the case may be, by a fraction, the numerator of which shall be the sum of
(w) the number of shares of Common Stock outstanding immediately prior to such
issuance, and (x) the number of shares of Common Stock that the aggregate
consideration received by the Company for such issuance would purchase at the
Applicable Adjustment Price; and the denominator of which shall be the sum of
(y) the number of shares of Common Stock outstanding immediately prior to such
issuance and (z) the number of additional shares of such Common Stock so issued
or sold; for purposes hereof, "Fair Market Value" shall mean (x) the closing
price on the business day prior to such determination on the principal national
securities exchange on which the Common Stock is traded, if any, (y) the last
quoted price on the business day prior to such determination if the Common Stock
is traded on the Nasdaq National Market or Nasdaq SmallCap Market, or (z) if the
Common Stock is not
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                                      -4-

listed on a national securities exchange or traded on the Nasdaq National Market
or the Nasdaq SmallCap Market, then as determined in good faith by the Company's
board of directors, such determination to be delivered in writing to EIS by the
Company; or

                  (ii) fix a record date for the effectuation of a split or
subdivision of the outstanding shares of Common Stock or the determination of
holders of Common Stock entitled to receive a dividend or other distribution
payable in additional shares of Common Stock or other securities or property or
rights convertible into, or entitling the holder thereof to receive directly or
indirectly, any of the foregoing (hereinafter referred to as "Common Stock
Equivalents") without payment of any consideration by such holder for the
additional shares of Common Stock or the Common Stock Equivalents (including the
additional shares of Common Stock or other securities or property issuable upon
conversion or exercise thereof) or with payment (determined, in the case of
Common Stock Equivalents, on an as-converted basis) that is less than the lower
of (x) the then-Fair Market Value of the Common Stock and (y) the Applicable
Adjustment Price then in effect, then and in each case, the Conversion Right
shall be for, in addition to the number of shares of the Common Stock otherwise
deliverable upon exercise of the Conversion Right, and without adjustment to the
Conversion Price, the amount of such additional shares of Common Stock and any
Common Stock Equivalents that the holder hereof would have received or become
entitled to receive on the same terms and conditions as if such holder had been
a holder of record of such Common Stock as shall have been deliverable
immediately prior to such record date pursuant to the terms of this Section 4;
or

                  (iii) If the number of shares of Common Stock outstanding at
any time is decreased by a combination of the outstanding shares of Common
Stock, then, following the record date of such combination, each of the
Applicable Adjustment Price and the Conversion Price shall be appropriately
increased so that the number of shares of Common Stock issuable on conversion
hereof shall be decreased in proportion to such decrease in outstanding shares.

                  (iv) The following provisions shall apply for purposes of this
Section 4(c):

                  (A) the aggregate maximum number of shares of Common Stock or
         other amount of securities or property issuable or deliverable as the
         case may be, or delivered upon conversion or exercise of Common Stock
         Equivalents (assuming the satisfaction of any conditions to
         convertibility or exercisability, including, without limitation, the
         passage of time, but without taking into account potential antidilution
         adjustments) shall be deemed to have been issued or delivered at the
         time such Common Stock Equivalents were issued;

                  (B) in the event of any change in the number of shares of
         Common Stock deliverable or in the consideration payable to the Company
         upon conversion or exercise of such Common Stock Equivalents including,
         but not limited to, a change resulting from the antidilution provisions
         thereof, the Conversion Price, to the extent in any way affected
<PAGE>
                                      -5-

         by or computed using such Common Stock Equivalents, shall be recomputed
         to reflect such change, but no further adjustment shall be made for the
         actual issuance of Common Stock or any payment of such consideration
         upon the exercise of any such options or rights or the conversion or
         exchange of such securities;

                  (C) upon the termination or expiration of the convertibility
         or exercisability of any such Common Stock Equivalents, the Conversion
         Price, to the extent in any way affected by or computed using such
         Common Stock Equivalents, shall be recomputed to reflect the issuance
         of only the number of shares of Common Stock (and Common Stock
         Equivalents which remain convertible or exercisable) actually issued
         upon the conversion or exercise of such Common Stock Equivalents; and

                  (D) if EIS objects to the fair market value determination made
         by the Company's board of directors pursuant to Section 4(c)(i), then
         such holders may provide the Company with a written notice no later
         than ten (10) days after the date of the notice delivered to EIS
         pursuant to Section 4(c)(i) (the "EIS Objection Notice"), which EIS
         Objection Notice shall notify the Company of such objection and shall
         propose an independent appraisal firm or investment banking firm (an
         "Independent Appraiser") to determine such fair market value in such
         manner as such Independent Appraiser shall reasonably determine. Such
         Independent Appraiser shall be subject to the unanimous approval of the
         Company's board of directors acting in its sole discretion. In the
         event EIS and the Company's board of directors (acting by unanimous
         vote) are unable to mutually appoint in writing an Independent
         Appraiser within ten (10) days after the date of the EIS Objection
         Notice, an arbitrator will be appointed by the American Arbitration
         Association in Boston, Massachusetts to determine such fair market
         value in such manner as such arbitrator shall reasonably determine. The
         cost of any such appraisal or arbitration, as the case may be, shall be
         borne (a) by EIS if the fair market value as determined by such
         appraisal or arbitration, as the case may be, does not exceed the
         determination of fair market value by the Company's board of directors
         by more than ten percent (10%), or (b) by the Company if the fair
         market value as determined by such appraisal or arbitration, as the
         case may be, exceeds the determination of fair market value by the
         Company's board of directors by more than ten percent (10%).

         (d) Other Distributions. In the event the Corporation shall declare a
distribution payable in securities of other persons, evidences of indebtedness
issued by the Corporation or other persons, assets, cash (excluding cash
dividends declared out of retained earnings) or options or rights not referred
to in the previous section (c), then, in each such case for the purpose of this
section (d), the Holder shall be entitled to a proportionate share of any such
distribution as though such Holder was a holder of the number of shares of
Common Stock of the Corporation into .which this Note would be convertible as of
the record date fixed for the determination of the holders of Common Stock of
the Corporation entitled to receive such distribution.
<PAGE>
                                      -6-

         (e) No Impairment. The Company will not, by amendment of its
Certificate of Incorporation or bylaws or through any reorganization,
recapitalization, transfer of assets, consolidation, merger, dissolution, issue
or sale of securities or any other voluntary action, avoid or seek to avoid the
observance or performance of any of the terms to be observed or performed
hereunder by the Company, but will at all times in good faith assist in the
carrying out of all the provisions of this Section 4 and in the taking of all
such action as may be necessary or appropriate in order to protect the rights of
EIS against impairment.

         (f) Notice of Adjustments. Whenever the consideration issuable upon a
conversion hereunder shall be changed pursuant to this Section 4, the Company
shall prepare a certificate setting forth, in reasonable detail, the event
requiring the change and the kind and amount of shares of stock and other
securities, money and property subsequently issuable upon a conversion hereof.
Such certificate shall be signed by its chief financial officer and shall be
delivered to EIS.

         (g) Fractional Shares: Rounding. No fractional shares of Common Stock
will be issued in connection with any exercise hereunder, but in lieu of such
fractional shares the Company shall make a cash payment therefor based on the
applicable Conversion Price. All calculations under this Section 4 shall be made
to the nearest cent or to the nearest one-hundredth of a share, as the case may
be.

         (h) Certain Issues of Common Stock Excepted. Anything herein to the
contrary notwithstanding, the Company shall not be required to make any
adjustment of the Conversion Price (i) in the case of the issuance of an
aggregate of up to 1,985,458 shares of Common Stock (or stock options to
purchase such shares of Common Stock) to employees, officers or directors of or
consultants to the Company pursuant to plans or arrangements approved by the
Company's board of directors, (ii) in the case of issuance of shares of Common
Stock upon the conversion of any issued and outstanding series of the Company's
preferred stock, (iii) in the case of the issuance of Common Stock or Common
Stock Equivalents to Comdisco, Inc. or Transamerica Business Credit Corporation,
or any of their respective transferees, pursuant to financing arrangements
approved by the Company's board of directors, (iv) in the case of the issuance
of shares of Common Stock pursuant to the redemption by the Company of its
Series G Convertible Preferred Stock pursuant to Section 3 of Part A of Article
Fourth of the Company's Certificate of Incorporation, or (v) in the case of the
issuance of Series G Paid-in-Kind Dividends pursuant to Section 1 of Part A of
Article Fourth of the Company's Certificate of Incorporation; provided, however,
that if Section 4.7(i) of Part A of Article Fourth of the Company's Certificate
of Incorporation has been amended by a vote of 66 2/3% of the voting power of
all then outstanding shares of Preferred Stock (on an as converted to Common
Stock basis and, also assuming for such purposes, the conversion of the then
aggregate outstanding principal amount of this Note and all accrued and unpaid
interest thereon into shares of Common Stock pursuant to Section 4(a) of this
Note), then Section 4(h)(i) hereto shall be deemed to be amended to provide for
such issuance of Common Stock to employees, officers or directors of or
consultants to the Company pursuant to plans
<PAGE>
                                      -7-

or arrangements approved by the Company's board of directors as have been
approved by such holders.

         (i) The Applicable Adjustment Price shall initially be $4.75, subject
to adjustment as provided in 4(c) hereto.

         SECTION 5. EVENTS OF DEFAULT.

                  The occurrence of any of the following events shall constitute
an event of default (an "Event of Default"):

         (a) a default in the payment of the principal amount of this Note, when
and as the same shall become due and payable;

         (b) a default in the payment of any accrued and unpaid interest on this
Note, when and as the same shall become due and payable;

         (c) a breach by the Company of its obligations under any of the
Transaction Documents, which breach remains uncured at the conclusion of the
cure period specified within the relevant Transaction Documents, after written
notice thereof by EIS;

         (d) a distress, execution, sequestration or other process is levied or
enforced upon the Company or sued out against a material part of its property
which is not discharged or challenged within 60 days;

         (e) the Company is unable to pay its debts in the normal course of
business;

         (f) the Company ceases wholly or substantially to carry on its
business, otherwise than for the purpose of a reconstruction or amalgamation,
without the prior written consent of the EIS (such consent not to be
unreasonably withheld); or

         (g) the appointment of a liquidator, receiver, administrator, examiner,
trustee or similar officer of the Company or over all or substantially all of
its assets under the law.

         SECTION 6. REMEDIES IN THE EVENT OF DEFAULT.

         (a) In the case of any Event of Default by the Company, the Holder may
in its sole discretion demand that the aggregate amount of funds advanced to the
Company under this Note and outstanding hereunder and accrued and unpaid
interest thereon shall, in addition to all other rights and remedies of the
Holder hereunder and under applicable law, be and become immediately due and
payable upon written notice delivered by the Holder to the Company.
Notwithstanding
<PAGE>
                                      -8-

the preceding sentence, the rights of the Holder as set forth in Sections 4 and
5 hereunder shall survive any such acceleration and payment.

         (b) The Company hereby waives demand and presentment for payment,
notice of nonpayment, protest and notice of protest, diligence, filing suit, and
all other notice and promises to pay the Holder its costs of collection of all
amounts due hereunder, including reasonable attorneys' fees.

         (c) In the case of any Event of Default under this Note by the Company,
this Note shall continue to bear interest after such default at the interest
rate otherwise in effect hereunder plus 2% per annum (but in any event not in
excess of the maximum rate of interest permitted by applicable law).

         SECTION 7. SUBORDINATION.

         (a) The Company, for itself, its successors and assigns, covenants and
agrees, and the holder of this Note and each successor Holder of this Note by
such holder's acceptance hereof, likewise covenants and agrees, that
notwithstanding any other provision of this Note, the payment of the principal
of and interest on this Note shall be subordinated in right of payment, to the
extent and in the manner hereinafter set forth, to the prior payment in full of
all Senior Debt (as hereinafter defined) at any time outstanding. The provisions
of this Section 7 shall constitute a continuing representation to all persons
who, in reliance upon such provisions, become the holders of or continue to hold
Senior Debt, and such provisions are made for the benefit of the holders of
Senior Debt, and such holders are hereby made obligees hereunder the same as if
their names were written herein as such, and they or any of them may proceed to
enforce such provisions against the Company or against the holder of this Note
without the necessity of joining the Company as a party.

         (b) Payment of Senior Debt. In the event of any insolvency or
bankruptcy proceedings, or any receivership, liquidation, reorganization or
other similar proceedings in connection therewith, relative to the Company or to
its property, or, in the event of any proceedings for voluntary liquidation,
dissolution or other winding up of the Company or distribution or marshaling of
its assets or any composition with creditors of the Company, whether or not
involving insolvency or bankruptcy, then and in any such event all Senior Debt
shall be paid in full before any payment or distribution of any character,
whether in cash, securities or other property, shall be made on account of this
Note; and any such payment or distribution, except securities (other than Junior
Securities, as defined below) which are subordinated and junior in right of
payment to the payment of all Senior Debt then outstanding in terms of
substantially the same tenor as this Section 7 ("Junior Securities"), which
would, but for the provisions hereof, be payable or deliverable in respect of
this Note shall be paid or delivered directly to the holders of Senior Debt (or
their duly authorized representatives), in the proportions in which they hold
the same, until all Senior Debt shall have been paid in full, and every Holder
of this Note by becoming a Holder hereof
<PAGE>
                                      -9-

shall have designated and appointed the holder or holders of Senior Debt (and
their duly authorized representatives) as his or its agents and attorney-in-fact
to demand, sue for, collect and receive such Senior Debt holder's ratable share
of such payments and distributions and to file any necessary proof of claim
therefor and to take all such other action (including the right to vote such
Senior Debt holder's share of this Note), in the name of the Holder of this Note
or otherwise, as such Senior Debt holders (or their authorized representatives)
may determine to be necessary or appropriate for the enforcement of this Section
7. The Holder and each successor Holder of this Note by its or his acceptance
thereof agrees to execute, at the request of the Company, a separate agreement
with any holder of Senior Debt on the terms set forth in this Section 7, and to
take all such other action as such holder or such holder's representative may
request in order to enable such holder to enforce all claims upon or in respect
of such holder's ratable share of this Note.

         (c) No Payment on Note Under Certain Conditions. In the event that any
default occurs in the payment of the principal of or interest on any Senior Debt
(whether as a result of acceleration thereof by the holders of such Senior Debt
otherwise) and during the continuance of such default for a period up to sixty
(60) days and thereafter if judicial proceedings shall have been instituted with
respect to such defaulted payment, or (if a shorter period) until such payment
has been made or such default has been cured or waived in writing by such holder
of Senior Debt, then and during the continuance of such event no payment of
principal or interest (other than payment in Junior Securities) on this Note
shall be made by the Company or accepted by any Holder of this Note who has
received notice from the Company or from a holder of Senior Debt of such event.

         (d) Payment Held in Trust. In case any payment or distribution shall be
paid or delivered to any Holder of this Note before all Senior Debt shall have
been paid in full, despite or in violation or contravention of the terms of this
subordination, such payment or distribution shall be held in trust for and paid
and delivered ratably to the holders of Senior Debt (or their duly authorized
representatives), until all Senior Debt shall have been paid in full.

         (e) Subrogation. Subject to the payment in full of all Senior Debt and
until this Note shall be paid in full, the Holder of this Note shall be
subrogated to the rights of the holders of Senior Debt (to the extent of
payments or distributions previously made to such holders of Senior Debt
pursuant to the provisions of subsections (a) and (c) of this Section 7) to
receive payments or distributions of assets of the Company applicable to the
Senior Debt. No such payments or distributions applicable to the Senior Debt
shall, as between the Company and its creditors, other than the holders of
Senior Debt and the Holder of this Note, be deemed to be a payment by the
Company to or on account of this Note; and for the purposes of such subrogation,
no payments or distributions to the holders of Senior Debt to which the Holder
of this Note would be entitled except for the provisions of this Section 7
shall, as between the Company and its creditors, other
<PAGE>
                                      -10-

than the holders of Senior Debt and the Holder of this Note, be deemed to be a
payment by the Company to or on account of the Senior Debt.

         (f) Scope of Section. The provisions of this Section 7 are intended
solely for the purpose of defining the relative rights of the Holder of this
Note, on the one hand, and the holders of the Senior Debt, on the other hand.
Nothing contained in this Section 7 or elsewhere in this Note is intended to or
shall impair, as between the Company, its creditors other than the holders of
Senior Debt, and the Holder of this Note, the obligation of the Company, which
is unconditional and absolute, to pay to the Holder of this Note the principal
of and interest on the Note as and when the same shall become due and payable in
accordance with the terms thereof, or to affect the relative rights of the
Holder of this Note and creditors of the Company other than the holders of
Senior Debt, or to benefit any creditors of the Company other than the holders
of the Senior Debt, nor shall anything herein or therein prevent the Holder of
this Note from accepting any payment with respect to this Note or exercising all
remedies otherwise permitted by applicable law upon default under this Note,
subject to the rights, if any, under this Section 7 of the holders of Senior
debt in respect of cash, property or securities of the Company received by the
Holder of this Note.

         (g) Survival of Rights. The right of any present or further holder of
Senior Debt to enforce subordination of this Note pursuant to the provisions of
this Section 7 shall not at any time be prejudiced or impaired by any act or
failure to act on the part of the Company or any such holder of Senior Debt,
including, without limitation, any forbearance, waiver, consent, compromise,
amendment, extension, renewal or taking or release of security of or in respect
of any Senior Debt or by noncompliance by the Company with the terms of such
subordination regardless of any knowledge thereof the holder may have or
otherwise be charged with.

         (h) Amendment or Waiver. The provisions of this Section 7 may not be
amended or waived in any manner which is detrimental to any Senior Debt without
the consent of the holders of a majority of the then existing Senior Debt.

         (i) Senior Debt Defined. The term "Senior Debt" shall mean indebtedness
of the Company for (i) up to $5 million dollars at any one time outstanding
borrowed from a bank or other institutional lender under a working capital
facility, including any renewal thereof, whether outstanding on the date hereof
or thereafter created or incurred and (ii) capital lease obligations incurred in
the ordinary course of business which are secured by the assets therein leased.

         SECTION 8. MISCELLANEOUS.

         (a) This Note and all of the provisions hereof shall be binding upon
and inure to the benefit of the parties hereto and their respective successors
and permitted assigns. All or any part of this Note may be assigned or
transferred by the Holder and its permitted assigns and transferees
<PAGE>
                                      -11-

to their respective affiliates and subsidiaries, as well as any special
purpose financing or similar vehicle established by the Holder. Other than as
set forth above, no party shall assign or transfer all or any part of this Note,
or any interest therein, without the prior written consent of the other party.

         (b) All notices, demands and requests of any kind to be delivered to
any party in connection with this Note shall be in writing and shall be deemed
to have been duly given if personally or hand delivered or if sent by an
internationally-recognized overnight delivery courier or by registered or
certified mail, return receipt requested and postage prepaid, or by facsimile
transmission addressed as follows:

                  (i)      if to the Company, to:

                           Acusphere, Inc.
                           University Park at M.I.T.
                           38 Sidney Street
                           Cambridge, MA 02139

                           Attention:       Steven D. Delaney
                                            Vice President, Finance &
                                            Administration
                           Facsimile:       617-577-0233

                  with a copy to:

                           Testa, Hurwitz & Thibeault, LLP
                           High Street Tower
                           125 High Street
                           Boston, MA 02110

                           Attention: Lawrence Wittenberg
                           Facsimile: 617-248-7100

                  (ii) if to EIS, to:

                           Elan International Services, Ltd.
                           102 St. James Court
                           Flatts, Smiths Parish

                           Bermuda FL 04
                           Attention: Chief Executive Officer
                           Facsimile: (441) 292-2224
<PAGE>
                                      -12-

                  with a copy to:

                           Cahill Gordon & Reindel
                           80 Pine Street
                           New York, NY 10005

                           Attention: William M. Hartnett
                           Facsimile: 212-269-5420

or to such other address as the party to whom notice is to be given may have
furnished to the other party hereto in writing in accordance with provisions of
this Section 7. Any such notice or communication shall be deemed to have been
effectively given (i) in the case of personal or hand delivery, on the date of
such delivery, (ii) in the case of an internationally-recognized overnight
delivery courier, on the second business day after the date when sent, (iii) in
the case of mailing, on the fifth business day following that day on which the
piece of mail containing such communication is posted and (iv) in the case of
facsimile transmission, the date of telephone confirmation of receipt.

         (c) This Note may not be modified or amended, or any of the provisions
hereof waived, except by written agreement of the Company and the Holder dated
after the date hereof.

         (d) This Note shall be governed by and construed in accordance with the
internal laws of the State of New York, without giving effect to principles of
conflicts of laws. Any dispute under this Note that is not settled by mutual
consent shall be finally adjudicated by any federal or state court sitting in
the City, County and State of New York, and the Company consents to the
exclusive jurisdiction of such courts (or any appellate court therefrom) over
any such dispute.

         (e) This Note may be executed and delivered to the Holder by a
facsimile transmission; such transmission shall be deemed a valid signature.

                            [Signature page follows]
<PAGE>
         IN WITNESS WHEREOF, the Company has executed and delivered this Note
on, the date first above written.

                                                 ACUSPHERE, INC.

                                                 By: /s/ Sherri C. Oberg
                                                     -------------------
                                                     Name:  Sherri C. Oberg
                                                     Title: President and C.E.O.
<PAGE>
                                     ANNEX I

            FORM OF NOTICE OF ELECTION TO EXERCISE A CONVERSION RIGHT

Date:

To:      Acusphere, Inc.

From:

Re:      Exercise of a Conversion Right

         Pursuant to the terms of the Convertible Promissory Note (the "Note")
issued by Acusphere, Inc. (the "Company") to ___________ ("Holder") dated
_______, __, specifically Section 4 thereof, Holder hereby notifies the Company
of its intention to exercise a right of conversion.

         Pursuant to Section 4 of the Note, Holder hereby elects to convert U.S$
__________ in aggregate principal amount and all accrued and unpaid interest
thereon for shares of the Company's Common Stock, par value $[ ] per share,
effective , ___________, __.

         We have instructed our attorneys to contact the Company to discuss the
timing and documentation of the conversion.

                                         Sincerely,

                                         [HOLDER]

                                         By: ___________________________________
                                             Name:
                                             Title:<PAGE>
                                                                   Exhibit 10.28

                          SECURITIES PURCHASE AGREEMENT

         SECURITIES PURCHASE AGREEMENT (this "Agreement"), dated as of June 30,
2000, between ACUSPHERE, INC., a Delaware corporation (the "Company"), and ELAN
INTERNATIONAL SERVICES, LTD., a Bermuda exempted limited liability company
("EIS"), and a wholly owned subsidiary of ELAN CORPORATION, PLC, an Irish public
limited company ("Elan").

                                    RECITALS:

         A. The Company desires to issue and sell to EIS, and EIS desires to
purchase from the Company, on the date hereof, (i) 1,232,308 shares of a
newly-created series of the Company's convertible exchangeable preferred stock,
par value U.S.$.01 per share, captioned "Series G Non-Voting Convertible
Preferred Stock" (the "Series G Preferred Stock"), and (ii) 1,127,819 shares of
a newly-created series of the Company's convertible preferred stock, par value
U.S. $.01 per share, captioned "Series H Convertible Preferred" (the "Series H
Preferred Stock"). The Company further desires to issue and sell to EIS, and EIS
desires to purchase from the Company, from time to time, up to U.S. $8,010,000
aggregate principal amount of convertible debt of the Company in the form
attached hereto as Exhibit A-1 (the "Note"), amounts in respect of which shall
be disbursed from time to time in accordance with its terms and subject to the
conditions contained herein and therein. The Series G Preferred Stock and the
Series H Preferred Stock collectively are referred to herein as the "Shares".
The Shares and the Note collectively are referred to herein as the "Securities".
The rights, preferences and privileges of the Series G Preferred Stock and the
Series H Preferred Stock are as set forth in the Company's Amended and Restated
Certificate of Incorporation, the form of which is attached hereto as Exhibit B
(the "Charter").

         B. The Company and EIS have formed ACUSPHERE NEWCO, LTD., an exempted
limited liability company incorporated under the laws of Bermuda ("Newco"), and
pursuant to the terms of a Subscription, Joint Development and Operating
Agreement, dated as of the date hereof (as amended at any time, the "JDOA"),
simultaneously with the transactions contemplated by this Agreement, (i) the
Company shall acquire 6,000 voting common shares of Newco, par value U.S. $1.00
per share (the "Newco Common Stock"), representing 100% of the issued and
outstanding shares of such class of stock, and 3,612 non-voting convertible
preference shares of Newco. par value of U.S. $1.00 per share (the "Newco
Preferred Stock"; together with the Newco Common Stock, the "Newco Stock"),
representing 60.2% of the aggregate outstanding shares of Newco Preferred Stock
and, on a fully diluted basis, 30.1% of the aggregate outstanding shares of
Newco Stock and (ii) EIS shall acquire 2,388 shares of Newco Preferred Stock,
representing 39.8% of the aggregate outstanding shares of Newco Preferred Stock
and, on a fully diluted basis. 19.9% of the Newco Stock. Additionally, as of the
date hereof, Newco has entered into license agreements with (i) Elan and its
subsidiary Elan Pharma International Limited (such agreements, as amended at any
time, collectively the "Elan License Agreement") and (ii) the
<PAGE>
                                      -2-

Company (such agreement, as amended at any time, the "Company License
Agreement"; together with the Elan License Agreement, the "License Agreements").

         C. The Company and EIS are executing and delivering on the date hereof
a Fifth Amended and Restated Investors' Rights Agreement and a Fourth Amended
and Restated Co-Sale Agreement in the forms attached hereto as Exhibit C-l and
Exhibit C-2 (as amended at any time, the "Company Registration Rights
Agreements") in respect of (i) the Company's common stock, par value U.S. $1.00
per share (the "Acusphere Common Stock") issued or issuable upon conversion of
the Shares or exercise of all or any portion of the Note and (ii) any other
Acusphere Common Stock owned by EIS or any of its affiliates or their respective
permitted transferees. The Company, EIS and Newco are also executing and
delivering on the date hereof a Registration Rights Agreement in the form
attached hereto as Exhibit D (as amended at any time, the "Newco Registration
Rights Agreement"). The Company and EIS are also executing and delivering on the
date hereof the Exchange Agreement in connection with the EIS Exchange Right (as
such term is defined in Section 5(c) below) in the form attached hereto as
Exhibit E (as amended at any time, the "Exchange Agreement"). This Agreement,
the Charter, the Note, the JDOA, the Company Registration Rights Agreements, the
Newco Registration Rights Agreement, the License Agreements, the Exchange
Agreement and each other document or instrument executed and delivered in
connection with the transactions contemplated hereby and by the JDOA
collectively are referred to herein as the "Transaction Documents".

                                   AGREEMENT:

         In consideration of the foregoing premises and the mutual covenants
contained herein, the sufficiency of which is hereby acknowledged, the parties
hereby agree as follows:

         SECTION 1. Closing.

         (a) Time and Place. The closing of the Initial Purchase (as defined
below) (the "Initial Closing") shall occur on the date hereof (the "Initial
Closing Date"). The funding of each advance under the Note (each, a "Note
Closing") shall occur on such dates as set forth in Section 1(e) (each, a "Note
Closing Date"). The Initial Closing and each Note Closing individually are
referred to herein as a "Closing", and the Initial Closing Date and each Note
Closing Date individually are referred to herein as a "Closing Date". The
Initial Closing shall be held at the offices of Cahill Gordon & Reindel, 80 Pine
Street, New York, New York 10005 (by means of facsimile or overnight mail) and
each Note Closing shall be a paper closing by means of facsimile or as otherwise
agreed by the parties.

         (b) Sale and Purchase. At the Initial Closing, subject to the terms and
conditions hereof, the Company shall issue and sell to EIS, and EIS shall
purchase from the Company, (i) 1,232,308 shares of Series G Preferred Stock and
(ii) 1,127,819 shares of Series H Preferred
<PAGE>
                                      -3-

Stock (the "Initial Purchase"). In addition, subject to the terms and conditions
hereof and as set forth in the Note, the Company shall issue to EIS the Note as
set forth in Section 1(e).

         (c) Purchase Price. The aggregate purchase price for the Initial
Purchase shall be U.S.$19,514,999.35 (the "Initial Purchase Price"),
U.S.$12,015,003 of which represents the purchase price for the 1,232,308 shares
of Series G Preferred Stock, and U.S.$7,499,996.35 of which represents the
purchase price for the 1,127,819 shares of Series H Preferred Stock.

         (d) Initial Closing Delivery. On the Initial Closing Date, subject to
the terms and conditions hereof: (i) EIS shall pay the Initial Purchase Price by
wire transfer of U.S.$19,514,999.35 to an account designated in writing by the
Company ; (ii) the parties hereto shall execute and deliver to each other, as
applicable, (A) certificates representing 1,232,308 shares of Series G Preferred
Stock, (B) certificates representing 1,127,819 shares of Series H Preferred
Stock, (C) the Company Registration Rights Agreements, (D) the Newco
Registration Rights Agreement, (E) the JDOA, (F) the Charter as filed with the
Secretary of State of the State of Delaware, (G) the License Agreements, (H) a
customary secretary's certificate from the secretary of the Company, including a
certificates as to the incumbency of the officers of the Company executing any,
of the Transaction Documents, (I) certificates as to the incumbency of the
officers of EIS executing an), of the Transaction Documents and (J) any other
documents or instruments reasonably requested by a party hereto; (iii) the
Company shall cause to be delivered to EIS an opinion of counsel in the form
attached hereto as Exhibit F; and (iv) Newco shall cause to be delivered to each
of the Company, EIS and Newco the opinion of their special Bermuda counsel,
Comers Dill & Pearman.

         (e) Note Purchases. It is estimated that Newco will require additional
funds to commence development of Newco's products. Within the period commencing
on the Initial Closing Date and ending on the third year anniversary of the
Initial Closing Date, (the "Development Period"). EIS and the Company may
provide to Newco up to an aggregate maximum amount of U.S.$10,000,000, such
funding to be provided by EIS and the Company on a pro rata basis based on their
respective equity interests, on a fully-diluted basis, in Newco (the
"Development Funding"). In order to ensure the Company has funds available for
its share of the Development Funding, EIS has agreed to advance to the Company
up to U.S.$8,010,000 subject to the terms and conditions set forth below and in
the Note.

         (A) The Company shall issue to EIS the Note in the form attached hereto
as Exhibit A-1, and from time to time at the request of the Company, EIS shall
make advances thereunder to the Company (each an "Advance") in an aggregate
principal amount of up to U.S.$8,010,000 (the "Total Commitment"); provided that
the Total Commitment shall be reduced in an amount equal to amounts funded by
the Company to Newco as Development Funding (each a "Development Funding
Contribution") for which an Advance was not concurrently requested in respect of
the Note. The aggregate amount of the Advances made to the Company shall not in
any event exceed the amount of Development Funding funded by the Company to
<PAGE>
                                      -4-

Newco (after giving effect to any concurrent Advance made under the Note and
Development Funding Contribution made by the Company)(the "Maximum Amount").

         (B) Each Advance shall be subject to the following terms and
conditions:

                  (i) Each Advance shall be made at such time that (x) each
         Participant (as defined in the JDOA) shall have determined, pursuant to
         Clause 6.3 of the JDOA that Development Funding shall be provided, (y)
         Newco shall have provided written notice thereof to EIS and to the
         Company and (z) the Company shall have delivered a written request to
         EIS in the form attached hereto as Exhibit A-2 (the "Disbursement
         Notice") not less than 10 business days prior to the requested Note
         Closing Date;

                  (ii) The minimum amount of each Advance shall be not less than
         $250,000, (or such lesser amount up to the Maximum Amount or the Total
         Commitment, as the case may be, if the amount that remains available is
         less than $250,000). The Company shall be entitled to receive up to 4
         Advances in any calendar year;

                  (iii) Each Advance under the Note shall (x) occur only during
         the Development Period, (y) shall not exceed the Total Commitment and
         (z) shall not exceed the Maximum Amount;

                  (iv) At the time of each Advance, no material breach or
         default by the Company under any Transactions Document shall have
         occurred and be continuing;

                  (v) At the time of each Advance, the representations and
         warranties of the Company contained in Section 2(a), (b)(ii)(iv), (c),
         (d), (g), (i), (j), (k), (1) and (m) herein shall be true and correct
         in all material respects as of the date made and as of the Note Closing
         Date, except for changes to Section 2(b)(iii), (k)(i) and (iii), and
         (m) since the date hereof to the extent such changes have not caused a
         Company Material Adverse Effect (as defined below); and

                  (vi) At the time of any such Advance, EIS shall have received
         any required approvals under the Mergers and Takeovers (Control) Acts
         1978-1996, the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as
         amended, and any other similar law and regulation; provided that in the
         event that EIS has not obtained approval under the Mergers and
         Takeovers (Control) Acts 1978-1996, the Hart-Scott-Rodino Antitrust
         Improvements Act of 1976, as amended, or any other similar law or
         regulation at the time a determination of the necessity of such funding
         by the Newco Directors and such approval would be required, the Company
         shall issue to EIS a nonconvertible note substantially in the form of
         the Note (other than provisions relating to conversion), and the
         parties hereto shall work together in good faith to agree on an
         alternative funding mechanism for future borrowings.
<PAGE>
                                      -5-

         (C) On each such Note Closing Date, (x) EIS shall fund the requested
amount by wire transfer in immediately available funds and (y) the Company shall
cause to be delivered to EIS an officers' certificate confirming that the
conditions described in clauses (B)(i)(v) above have been satisfied and the
Company shall furnish such documents and instruments that EIS shall reasonably
request, including updates of the Company documents referred to in Section
1(d)(ii)(I).

         (f) Exemption from Registration. The Securities and any underlying
shares of Acusphere Common Stock will be issued under an exemption or exemptions
from registration under the U.S. Securities Act of 1933, as amended (the
"Securities Act"). Accordingly, the certificates evidencing the Series G
Preferred Stock, the Series H Preferred Stock, the Note and any shares of
Acusphere Common Stock or other securities issuable upon the exercise,
conversion or exchange of any of the Securities shall, upon issuance, contain a
legend, substantially in the form as follows:

         THE SECURITIES REPRESENTED HEREBY HAVE NOT BEEN REGISTERED UNDER THE
         U.S. SECURITIES ACT OF 1933, AS AMENDED (THE "ACT"), OR APPLICABLE
         STATE SECURITIES LAWS AND NO INTEREST THEREIN MAY BE SOLD, TRANSFERRED
         OR OTHERWISE DISPOSED OF UNLESS THERE IS AN EFFECTIVE REGISTRATION
         STATEMENT FOR SUCH SECURITIES UNDER THE ACT AND ANY APPLICABLE STATE
         SECURITIES LAWS OR THE ISSUER OF THESE SECURITIES RECEIVES AN OPINION
         OF COUNSEL FOR THE HOLDER OF THESE SECURITIES SATISFACTORY TO THE
         ISSUER THAT REGISTRATION IS NOT REQUIRED UNDER THE ACT OR ANY
         APPLICABLE STATE SECURITIES LAWS.

         THE TRANSFER OF THE SECURITIES REPRESENTED BY THIS CERTIFICATE IS ALSO
         SUBJECT TO THE RESTRICTIONS CONTAINED IN THAT CERTAIN SECURITIES
         PURCHASE AGREEMENT, DATED AS OF JUNE 30, 2000, BY AND BETWEEN
         ACUSPHERE, INC. AND ELAN INTERNATIONAL SERVICES, LTD.

         (g) Additional Legend. The certificates evidencing the Series G
Preferred Stock. the Note and any shares of Acusphere Common Stock or other
securities issuable upon the exercise, conversion or exchange of any of such
securities shall, upon issuance, contain a legend, substantially in the form as
follows:

         THE SECURITIES REPRESENTED BY THIS CERTIFICATE ARE ALSO SUBJECT TO THE
         EXCHANGE PROVISIONS CONTAINED IN THAT CERTAIN EXCHANGE AGREEMENT, DATED
         AS OF JUNE 30, 2000, BY
<PAGE>
                                      -6-

         AND BETWEEN ACUSPHERE, INC. AND ELAN INTERNATIONAL SERVICES, LTD.

         SECTION 2. Representations and Warranties of the Company. The Company
hereby represents and warrants to EIS, as of each Closing Date, as follows:

         (a) Organization and Qualification. The Company is duly organized,
validly existing and in good standing under the laws of the State of Delaware
and has all requisite corporate power and authority to own and lease its
properties, to carry on its business as presently conducted and as proposed to
be conducted and to consummate the transactions contemplated hereby. The Company
is duly qualified as a foreign corporation and in good standing to do business
in each jurisdiction in which the nature of the business conducted or the
property owned by it requires such qualification, except where the failure to be
so qualified would not, individually or in the aggregate, have a material
adverse effect on the business, assets, liabilities (contingent or otherwise),
operations, condition (financial or otherwise), or prospects of the Company (a
"Company Material Adverse Effect").

         (b) Capitalization. (i) Immediately prior to the Closing, the
capitalization of the Company was as follows:
<TABLE>
<CAPTION>
                                                                                  Number of Shares
                                                                   ------------------------------------------------

                                                                                    Issued and      Issued and Held
Capital Stock                                                      Authorized       Outstanding       in Treasury
-------------                                                      ----------       -----------     ---------------
<S>                                                                <C>              <C>             <C>
Acusphere Common Stock                                             40,000,000         2,565,561           36,161
Series A Preferred Stock, par value $.01 per share                    816,169           816,169                0
Series B Preferred Stock, par value $.01 per share                  2,315,625         2,265,625                0
Series C Preferred Stock, par value $.01 per share                  3,980,140         3,913,551                0
Series D Preferred Stock, par value $.01 per share                  3,498,882         3,405,624                0
Series E Preferred Stock, par value $.01 per share                  1,211,774           757,577                0
</TABLE>
<PAGE>
                                      -7-

<TABLE>
<CAPTION>
<S>                                                                <C>              <C>             <C>
Series F Preferred Stock, par value $.01 per share                 13,177,410         2,252,330                0
Series G Preferred Stock, par value $.01 per share                  2,000,000                 0                0
Series H Preferred Stock, par value $.01 per share                  1,127,819                 0                0
Undesignated                                                                0                 0                0
</TABLE>

         (ii) As of the Initial Closing Date, the Company has reserved a
sufficient number of shares of Acusphere Common Stock for issuance upon
conversion of the Shares and conversion of the Note and a sufficient number of
shares of Series G Preferred Stock for issuance as dividends on the Series G
Preferred Stock.

         (iii) There are no preemptive rights, voting agreements, rights of
first offer or refusal, options, warrants or other conversion privileges or
rights presently outstanding to purchase, subscribe for or otherwise acquire, or
any securities convertible into or exercisable for or into, any, of the
Company's capital stock (collectively, "Preemptive Rights"), except as described
on Schedule 2(b). There are no agreements to register any of the Company's
outstanding securities under U.S. federal securities laws, other than the
Company Registration Rights Agreements and except as described on Schedule 2(b).

         (iv) All of the outstanding shares of capital stock of the Company have
been issued in accordance with applicable state and federal laws and regulations
(or exemptions therefrom) governing the sale and purchase of securities, all of
such shares have been duly and validly issued and are full), paid and
non-assessable. The Shares, when issued against payment therefor in accordance
with this Agreement or, in the case of the Series G Preferred Stock, as
dividends in respect of previously issued shares of Series G Preferred Stock,
will be duly and validly issued, full paid and non-assessable, and the Note
(including additional amounts issued as accrued interest), when issued in
accordance with this Agreement, will be duly and validly issued, and in each
case will not be issued in violation of any Preemptive Rights. The shares of
Acusphere Common Stock issuable upon conversion, redemption or exercise, as
applicable, of the Shares and the Note (the "Underlying Shares"), when issued
upon conversion, redemption or exercise in accordance with the terms thereof,
will be duly and validly issued, fully paid and non-assessable, and will not be
issued in violation of any Preemptive Rights.

         (c) Authorization of Transaction Documents. The Company has full
corporate power and authority to execute and deliver this Agreement and each of
the other Transaction Documents to which it is a party, and to perform its
obligations hereunder and thereunder. The
<PAGE>
                                      -8-

execution, delivery and performance by the Company of this Agreement and each of
the other Transaction Documents to which it is a party (including the issuance
and sale of the Securities and the Underlying Shares) have been duly authorized
by all requisite corporate action by the Company and, when executed and
delivered by the Company, this Agreement and each of the other Transaction
Documents to which it is a party will be the valid and binding obligations of
the Company, enforceable against the Company in accordance with their respective
terms, subject to applicable bankruptcy, insolvency, fraudulent conveyance,
reorganization or similar laws affecting the rights of creditors generally and
subject to general principles of equity.

         (d) No Violations. The execution, delivery and performance by the
Company of this Agreement and each of the other Transaction Documents to which
it is a party (including the issuance and sale of the Securities) and the
compliance with the provisions hereof and thereof by the Company do not violate,
conflict with or constitute or result in a breach of or default under (or an
event which with notice or passage of time or both would constitute a default)
or give rise to any right of termination, cancellation or acceleration under, or
result in the creation of any Encumbrance (as defined below) upon any properties
or assets of the Company under (i) the Certificate of Incorporation or bylaws of
the Company, (ii) applicable law, statute, rule or regulation, or any ruling,
Writ, injunction, order, judgment or decree of any court, arbitrator,
administrative agency or other governmental body applicable to the Company or
any of its properties or assets or (iii) any contract or agreement affecting the
Company, except, in each case, where such violation, conflict, breach, default,
termination, cancellation, acceleration or Encumbrance would not, individually
or in the aggregate, have a Company Material Adverse Effect. As used herein, the
term "Encumbrance" shall mean an), lien, charge, encumbrance, claim, option,
proxy, pledge, security interest, or other similar right of an), nature other
than statutory liens securing payments not yet due and payable or due but not
yet delinquent.

         (e) Approvals. Except as set forth on Schedule 2(e), no permit,
authorization, consent, approval, or order of or by, or an), notification of or
filing with, any person or entity (governmental or otherwise) is required in
connection with the execution, delivery or performance of this Agreement or the
other Transaction Documents (including the issuance and sale of the Securities)
by the Company.

         (f) Financial Statements. Schedule 2(f) contains (i) the audited
balance sheets of the Company at December 31, 1999 and 1998 and the related
statements of operations, stockholders' equity (deficit) and cash flows for the
years then ended, together with the reports and opinions thereon of Arthur
Andersen LLP (the "Audited Financial Statements") and (ii) the unaudited balance
sheet of the Company at May 31, 2000 and the related statements of operations
and cash flows for the five months then ended (the "Unaudited Financial
Statements"; collectively with the Audited Financial Statements, the "Financial
Statements"). The Financial Statements are accurate and complete and fairly
present, in all material respects, the financial position of the Company and the
results of its operations and its cash flows at such dates and for the periods
<PAGE>
                                      -9-

indicated and were prepared in conformity in all material respects with United
States generally accepted accounting principles applied on a consistent basis
throughout the periods indicated (except as may be otherwise indicated therein),
subject, in the case of the Unaudited Financial Statements, to normal yearend
audit adjustments (which shall not be material in the aggregate) and the absence
of footnote disclosures. As of the Initial Closing Date, the Company has not
incurred and is not liable for any material liabilities or obligations except as
set forth on the face of the May 31, 2000 balance sheet or Schedule 2(f).

         (g) Taxes. The Company has filed in a timely manner any federal, state,
local and foreign tax returns, reports and filings (collectively, "Returns"),
including income, franchise, property and other taxes, and has paid or accrued
the appropriate amounts reflected on such Returns heretofore required to be
filed. Except as set forth on Schedule 2(g), none of the Returns have been
audited or challenged, nor has the Company received any notice of challenge nor
have any of the amounts or other data included in the Returns been challenged or
reviewed by any governmental authority.

         (h) Plans. Except as set forth on Schedule 2(h), which sets forth an
accurate and complete list and description of all employee benefit plans
maintained or sponsored by the Company or to which the Company is required to
make contributions (the "Benefit Plans"), the Company does not maintain,
sponsor, is not required to make contributions to or otherwise have any
liability with respect to any pension, profit sharing, thrift or other
retirement plan, employee stock ownership plan, deferred compensation, stock
ownership, stock purchase, performance share, bonus or other incentive plan,
severance plan, health or group insurance plan, welfare plan, or other similar
plan, agreement, policy or understanding (whether written or oral), whether or
not such plan is intended to be qualified under Section 401 (a) of the U.S.
Internal Revenue Code of 1986, as amended, or within the meaning of Section 3(3)
of the U.S. Employee Retirement Income Security Act of 1974, as amended, which
plan covers any employee or former employee of the Company. The Benefit Plans
have been and are administered in substantial compliance with their terms and
the requirements of applicable law.

         (i) Absence of Certain Events. Since December 31, 1999, except as
contemplated by the Transaction Documents or as set forth on Schedule 2(i), (A)
the Company has not (i) made, paid or declared any dividend or distribution to
any equity holder (in such capacity) or redeemed any of its capital stock, (ii)
varied its business plan or practices, in any material respect, from past
practices, (iii) entered into any financing, joint venture, license or similar
arrangement that would limit or restrict its ability to perform its obligations
hereunder and under each of the other Transaction Documents or (iv) suffered or
permitted to be incurred any liability or obligation or any Encumbrance against
any of its properties or assets that would limit or restrict its ability to
perform its obligations hereunder and under each of the other Transaction
Documents; and (B) there has not been any change or development which has had,
or could reasonably be expected to have, a Company Material Adverse Effect.
<PAGE>
                                      -10-

         Without limiting the generality of the foregoing, since December 31,
1999, except as set forth on Schedule 2(i), there has not been (1) any lapse of
any of the Company's trade secrets, inventions, patents, patent applications or
continuations (in whole or in part), trademarks, trademark registrations,
service marks, service mark registrations, copyrights, copyright registrations,
or any application therefor or filing in respect thereof (collectively, and
together with any and all know-how, trade secrets and proprietary business or
technology information, the "Intellectual Property") that could reasonably be
expected to result in a Company Material Adverse Effect; (2) loss of the
services of any of the key officers or key employees of the Company; (3) any
incurrence of or entry into any liability, mortgage, Encumbrance, commitment or
transaction, including without limitation, any borrowing (or assumption or
guarantee thereof) or guarantee of a third party's obligations, or capital
expenditure (or lease in the nature of a conditional purchase of capital
equipment) in excess of U.S.$50,000 other than in the ordinary course of
business; (4) any material change by the Company in accounting methods or
principles; or (5) any change in the assets, liabilities, condition (financial
or otherwise), results or operations or prospects of the Company from those
reflected on the Financial Statements, except changes in the ordinary course of
business and changes that have not had or could not reasonably be expected to
have, individually or in the aggregate, a Company Material Adverse Effect.

         (j) No Liabilities. Since December 31, 1999, the Company has not
incurred or suffered an), liability or obligation, matured or unmatured,
contingent or otherwise, except in the ordinary course of business and except
any such liability or obligation that have not had and could not reasonably be
expected to have, individually or in the aggregate, a Company Material Adverse
Effect.

         (k) Properties and Assets: Etc.

            (i) Except as set forth on Schedule 2(k), the Company has good and
marketable title to its properties and assets shown in the Financial Statements
to be owned by the Company, and has valid leasehold interests to the properties
and assets shown in the Financial Statements to be leased by the Company, in
each case subject to no Encumbrances.

           (ii) The Company owns or possesses sufficient legal rights to use
pursuant to license, sublicense, agreement or permission all Intellectual
Property used in the operation of its business as presently conducted, in each
case subject to no Encumbrances required to be disclosed in the Financial
Statements except as set forth therein, other than any failure to own or possess
sufficient legal rights which, individually or in the aggregate, would not have
a Company Material Adverse Effect. All of the Intellectual Property which is
owned by the Company is owned free and clear of all Encumbrances; none of the
Company's rights in or use of the Intellectual Property has been or, to the
Company's knowledge, is currently threatened to be challenged; other than as
described in Schedule 2(k), to the Company's knowledge, without making any
inquiry other than those, if any, routinely conducted by the Company in the
ordinary course of business. no current or currently planned product based upon
the Company's Intellectual
<PAGE>
                                      -11-

Property would infringe any patent, trademark, service mark, trade name or
copyright of any other person or entity issued or pending on the Closing Date if
the Company were to distribute, sell, market or manufacture such products, and
the Company is not aware of any actual or threatened claim by any person or
entity alleging any infringement by the Company of a patent, trademark, service
mark, trade name or copyright possessed by such person or entity. None of such
Intellectual Property, whether foreign or domestic, has been canceled,
abandoned, or otherwise terminated, other than such cancellations, abandonments
or terminations which, individually or in the aggregate, would not have a
Company Material Adverse Effect.

         (iii) Schedule 2(k) lists the material contracts of the Company, and
each is a legal and valid agreement binding upon the Company and, to the
Company's knowledge, is in full force and effect. To the Company's knowledge,
there is no material breach or default by any party thereunder.

         (iv) The Company has and maintains adequate and sufficient insurance,
including liability, casualty and products liability insurance, covering risks
associated with its business, properties and assets, including insurance that is
customary for companies similarly situated.

         (v) The Company, its business and properties and assets are in
compliance in all material respects with all applicable laws and regulations,
including without limitation, those relating to (i) health, safety and employee
relations, (ii) environmental matters, including the discharge of any hazardous
or potentially hazardous materials into the environment and (iii) the
development, commercialization and sale of pharmaceutical and biotechnology
products, including all applicable regulations of the U.S. Food and Drug
Administration and comparable applicable foreign regulatory authorities.

         (l) Legal Proceedings. etc. There is no legal, administrative,
arbitration or other action or proceeding or governmental or investigation
pending, or to the Company's knowledge, threatened against the Company, or any
director, officer or employee of the Company in their capacities as such that
(i) challenges the validity or performance of this Agreement or the other
Transaction Documents or (ii) could reasonably be expected to have a Company
Material Adverse Effect. The Company is not in violation of or default under,
any material laws, judgments, injunctions, orders or decrees of any court,
governmental department, commission, agency. instrumentality or arbitrator
applicable to its business, other than any violation or default which.
individually or in the aggregate, would not have a Company Material Adverse
Effect.

         (m) Disclosure. The representations and warranties set forth herein and
in the other Transaction Documents, when viewed collectively, do not contain any
untrue statement of a material fact or omit to state any, material fact
necessary to make the statements contained herein not misleading in light of the
circumstances in which they were made.
<PAGE>
                                      -12-

         (n) Brokers or Finders. There have been no investment bankers, brokers
or finders used by the Company in connection with the transactions contemplated
by the Transaction Documents and no persons or entities are entitled to a fee or
compensation in respect thereof.

         SECTION 3. Representation and Warranties of EIS. EIS hereby represents
and warrants to the Company, as of the date hereof, as follows:

         (a) Organization. EIS is an exempted company duly organized, validly
existing and in good standing under the laws of Bermuda and has all requisite
corporate power and authority to own and lease its properties, to carry on its
business as presently conducted and as proposed to be conducted and to
consummate the transactions contemplated hereby. EIS is duly qualified as a
foreign corporation and in good standing to do business in each jurisdiction in
which the nature of the business conducted or the property owned by it requires
such qualification, except where the failure to be so qualified would not,
individually or in the aggregate, have a material adverse effect on the
business, assets, liabilities (contingent or otherwise), operations, condition
(financial or otherwise), or prospects of EIS (an "EIS Material Adverse
Effect").

         (b) Authorization of Transaction Documents. EIS has full corporate
power and authority to execute and deliver this Agreement and each of the other
Transaction Documents to which it is a party, and to perform its obligations
hereunder and thereunder. The execution, deliver), and performance by EIS of
this Agreement and each other Transaction Document to which it is a party
(including the purchase and acceptance of the Securities) have been duly
authorized by all requisite corporate action by EIS and, when executed and
delivered by EIS, this Agreement and each of the other Transaction Documents to
which it is a party will be the valid and binding obligations of EIS,
enforceable against it in accordance with their respective terms, subject to
applicable bankruptcy, insolvency, fraudulent conveyance, reorganization or
similar laws affecting the rights of creditors generally and subject to general
principles of equity.

         (c) No Violation. The execution, delivery and performance by EIS of
this Agreement and each other Transaction Document to which it is a party
(including the purchase and acceptance of the Securities) and compliance with
provisions hereof and thereof by EIS will not violate conflict with or
constitute or result in a breach of or default under (or an event which with
notice or passage, of time or both would constitute a default) or give rise to
any right of termination, cancellation or acceleration under (i) the charter or
bylaws of EIS, (ii) applicable law, statute, rule or regulation, or any ruling,
writ, injunction, order, judgment or decree of any court, arbitrator,
administrative agency or other governmental body applicable to EIS or any of its
properties or assets or (iii) any material contract to which EIS is a party,
except, in each case, where such violation, breach, default, termination,
cancellation or acceleration would not, individually or in the aggregate, have
an EIS Material Adverse Effect.
<PAGE>
                                      -13-

         (d) Approvals. Except for consent required under the Mergers and
Takeovers (Control) Acts 1978-1996 (Ireland), the Hart-Scott-Rodino Antitrust
Improvements Act of 1976, as amended, and any other similar law and regulation,
no material permit, authorization, consent, approval or order of or by, or any
notification of or filing with, any person or entity (governmental or otherwise)
is required in connection with the execution, delivery or performance of this
Agreement or the other Transaction Documents by EIS.

         (e) Investment Representations.

         (i) EIS is sophisticated in transactions of this type and capable of
evaluating the merits and risks of the transactions described herein and in the
other Transaction Documents to which it is a party, and has the capacity to
protect its own interests. EIS has not been formed solely for the purpose of
entering into the transactions described herein and therein and is acquiring the
Securities (and the Underlying Shares) for investment for its own account, not
as a nominee or agent, and not with the view to, or for resale, distribution or
fractionalization thereof, in whole or in part, and no other person (other than
Elan) has a direct or indirect interest, beneficial or otherwise in the
Securities (or the Underlying Shares); provided, however, that EIS shall be
permitted to convert or exchange such Securities in accordance with their terms.

         (ii) EIS has not and does not intend to enter into any contract,
undertaking, agreement or arrangement with any person or entity to sell,
transfer or pledge the Securities (or the Underlying Shares).

         (iii) EIS acknowledges its understanding that the private placement and
sale of the Securities (and the Underlying Shares) is exempt from registration
under the Securities Act. In furtherance thereof, EIS represents and warrants
that it is an "accredited investor" as that term is defined in the regulations
under the Securities Act, has the financial ability to bear the economic risk of
its investment, has adequate means for providing for its current needs and
personal contingencies and has no need for liquidity with respect to its
investment in the Company.

         (iv) EIS agrees that it shall not sell or otherwise transfer any of the
Securities (or the Underlying Shares) without registration under the Securities
Act or pursuant to an opinion of counsel reasonably satisfactory to the Company
that an exemption from registration is available, and fully understands and
agrees that it must bear the total economic risk of its purchase for an
indefinite period of time because, among other reasons, none of the Securities
(or the Underlying Shares) have been registered under the Securities Act or
under the securities laws of any applicable state or other jurisdiction and,
therefore, cannot be resold, pledged, assigned or otherwise disposed of unless
subsequently registered under the Securities Act and under the applicable
securities laws of such states or jurisdictions or an exemption from such
registration is available. EIS understands that the Company is under no
obligation to register the Securities (or the Underlying Shares) on its behalf
with the exception of certain registration rights with respect to certain of the
Securities (and the Underlying Shares), as provided in the Company Registration
<PAGE>
                                      -14-

Rights Agreements. EIS understands the lack of liquidity and restrictions on
transfer of the Securities (and the Underlying Shares) and that this investment
is suitable only for a person or entity of adequate financial means that has no
need for liquidity of this investment and that can afford a total loss of its
investment.

         (f) Legal Proceedings, etc. There is no legal, administrative,
arbitration or other action or proceeding or governmental investigation pending,
or to EIS's knowledge threatened, against EIS that challenges the validity or
performance of this Agreement or the other Transaction Documents to which EIS is
a party.

         (g) Brokers or Finders. There have been no investment bankers, brokers
or finders used by EIS in connection with the transactions contemplated by the
Transaction Documents and no persons or entities are entitled to a fee or
compensation in respect thereof.

         SECTION 4. Covenants of the Parties.

         (a) Certain Covenants. From and after the Initial Closing Date and
until the earlier to occur of the exercise or expiration of the EIS Exchange
Right (as such term is defined in Section 5(c) hereof), the Company shall not
without the prior written consent of EIS: (i) sell, transfer, encumber, pledge
or otherwise affect, in any respect, the shares of Newco Preferred Stock
transferable to EIS upon exercise by EIS of the EIS Exchange Right and (ii)
affect, in any respect, the Company's ability to permit EIS to exercise the EIS
Exchange Right in full, as provided herein.

         (b) Fully-diluted Stock Ownership. Notwithstanding any other provision
of this Agreement, in the event that EIS shall have determined that at any time
it (together with its affiliates, if applicable) holds or has the right to
receive Acusphere Common Stock (or securities or rights, options or warrants
exercisable, exchangeable or convertible for or into Acusphere Common Stock)
representing in the aggregate in excess of 9.9% of the Company's outstanding
Acusphere Common Stock on a fully diluted basis, EIS shall have the right to
elect to convert all or an), part of the Securities into other preferred,
nonvoting securities of the Company (to be specified by EIS, but having terms no
more favorable than the Securities being so converted by EIS) such that EIS and
its affiliates will not directly or indirectly own more than 9.9% of the
Acusphere Common Stock for a period of at least two years from the date such
election is made. In the event that EIS shall elect such conversion, EIS and its
affiliates shall retain the right to transfer all or a portion of such
securities (including the Acusphere Common Stock issuable upon conversion
thereof) to their respective affiliates. Each of the Company and EIS shall use
commercially reasonable efforts to effect such transactions and any required
subsequent conversions or adjustments to EIS's securities position, on a
quarterly basis, within 15 business days of the end of each of EIS's fiscal
quarters.
<PAGE>
                                      -15-

         (c) Use of Proceeds. The Company shall use the proceeds of (i) the
issuance and sale of the Series G Preferred Stock solely to meet its initial
capitalization obligations to Newco as described in the JDOA and (ii) the
Advances made in respect of the Note solely to make a substantially concurrent
Developmental Funding Contribution to Newco, as described in Section 1(e), and,
in each case, for no other purpose.

         (d) Confidentiality; Non-Disclosure.

         (i) Subject to clause (ii) below, from and after the date hereof,
neither the Company nor EIS (nor their respective affiliates) shall disclose to
any person or entity this Agreement or the other Transaction Documents or the
contents thereof or the parties thereto, except that such parties may make such
disclosure (x) to their directors, officers, employees and advisors, and
potential bank creditors and investors, so long as they shall have advised such
persons of the obligation of confidentiality herein and for whose breach or
default the disclosing party shall be responsible or (y) as required by
applicable law, rule, regulation or judicial or administrative process, provided
that the disclosing party uses commercially reasonable efforts to obtain an
order or ruling protecting the confidentiality of confidential information of
the other party contained herein or therein and notifies the other party prior
to such disclosure so that such other party may, if it chooses, seek such
relief. The parties shall be entitled to seek injunctive or other equitable
relief in respect of any breach or threatened breach of the foregoing covenant
without the requirement of posting a bond or other collateral.

         (ii) Prior to issuing any press release or public disclosure in respect
of this Agreement or the transactions contemplated hereby, the party proposing
such issuance shall obtain the consent of the other party to the contents
thereof, which consent shall not be unreasonably withheld or delayed; it being
understood that if such second party shall not have responded to such consent
request within three business days, such consent shall be deemed given.

         (e) Further Assurances. From and after the date hereof, each of the
parties hereto agree to do or cause to be done such further acts and things and
deliver or cause to be delivered to each other such additional assignments,
agreements, powers and instruments, as each may reasonably require or deem
advisable to carry into effect the purposes of this Agreement and the other
Transaction Documents.

         SECTION 5. Certain Rights of EIS.

         (a) Company Board of Directors. For so long as EIS or its affiliates,
directly or indirectly, collectively own at least 10.0% (5% after the initial
public offering of Acusphere Common Stock) of the Acusphere Common Stock (or
securities convertible, exchangeable or exercisable for or into the Acusphere
Common Stock which, with such owned Acusphere Common Stock represents at least
10.0% (5% after the initial public offering of Acusphere Common Stock)
ownership, assuming the exercise, conversion or exchange thereof by EIS and its
affiliates
<PAGE>
                                      -16-

but not of any other Acusphere Common Stock equivalents) on a fully diluted
basis, EIS shall be entitled to nominate one director who shall be reasonably
acceptable to Acusphere (the "EIS Director") for election to the Company's board
of directors; provided that the EIS Director enters into an appropriate board
membership agreement with the Company regarding confidentiality and; provided,
further, however, that EIS shall only be entitled to nominate the EIS Director
under this Section 5(a) if, within two years from the date hereof, the Company
elects one or more additional directors to the board in connection with any
joint venture, joint development arrangement, licensing arrangement or any
similar strategic transaction. In connection with the foregoing, the Company
will take all necessary and/or appropriate steps to effect such appointment,
including the inclusion of the designated EIS Director as part of the management
recommended slate of directors presented at any regular or special meeting of
the stockholders of the Company at which directors of the Company are to be
elected. Prior to such election, the designated EIS Director shall be entitled
to be an observer at the meetings of the Company's board of directors.

         (b) Conversion and Exchange Rights. The Company acknowledges that the
Charter sets forth certain rights of the holders of the Shares to convert the
Shares into newly issued shares of Acusphere Common Stock and that the Exchange
Agreement sets forth certain rights of the holders of the Series G Preferred
Stock to exchange such shares of Series G Preferred Stock (or shares of
Acusphere Common Stock into which such shares of Series G Preferred Stock were
converted under certain specified circumstances) for certain shares of Newco
Stock (the "EIS Exchange Right"), and agrees that it will not take any action
which would impair such rights other than as otherwise permitted by the
provisions thereof.

         In the event that EIS shall exercise the EIS Exchange Right, EIS shall
cause to be paid to Acusphere, within 30 days of such exercise, an amount equal
to the incremental percentage of the outstanding share capital of Newco obtained
by EIS pursuant to the exercise of the EIS Exchange Right of the aggregate
amount of the Development Funding through the date of such exercise provided by
each of the parties to Newco in accordance with the terms hereof (plus accrued
and unpaid interest on the applicable portion of the Note), from and after the
date hereof and until the date of such exercise (the "Make-Whole Amount"). EIS
may pay such amount, at its option, either (i) in cash or (ii) by offset against
the amount payable under the Note or a combination of (i) and (ii).

         SECTION 6. Pledge of Newco Stock. In order to secure the Company's
obligations pursuant to the EIS Exchange Right, the Company hereby pledges,
assigns and sets over to EIS, all of the Company's right, title and interest in
and to all shares of Newco Stock deliverable by the Company upon exercise of the
EIS Exchange Right (including stock distributions and dividends thereon) for
such period of time as the EIS Exchange Right shall be exercisable. The Company
shall cause to be delivered to EIS all of the certificates together with duly
executed stock power in favor of EIS evidencing such shares, and cause to be
filed with the
<PAGE>
                                      -17-

Secretary of State of Delaware an appropriate UCC-1 financing statement in
respect of such pledge, assignment or setting over, and take all other
necessary, appropriate and customary actions in connection therewith. Such
pledge shall be governed by the applicable provisions of the Delaware Uniform
Commercial Code. Upon exercise of the EIS Exchange Right, EIS shall be entitled
to keep and retain such share certificates, which shall then be owned by EIS in
accordance with the terms thereof. Until EIS exercises the EIS Exchange Right,
the Company shall retain all rights in and to the pledged Newco Stock (including
without limitation all voting, dividend, liquidation and other rights), subject
only to this pledge and the JDOA.

         SECTION 7. Survival and Indemnification.

         (a) Survival. For the purposes of this Section, the representations and
warranties of the Company and EIS contained herein shall survive for a period of
24 months from and after the date hereof.

         (b) Indemnification. In addition to all rights and remedies available
to the parties hereto at law or in equity, the Company (in such capacity,
"Indemnifying Party") shall indemnify EIS, its stockholders, officers, directors
and assigns, their affiliates, and its affiliates' stockholders, officers,
directors, employees, agents, representatives, successors and assigns
(collectively, the "Indemnified Person"), and save and hold each Indemnified
Person harmless from and against and pay on behalf of or reimburse each such
Indemnified Person, as and when incurred, for any and all loss, liability,
demand, claim, action, cause of action, cost, damage, deficiency, tax, penalty,
fine or expense, whether or not arising out of any claims by or on behalf of
such Indemnified Person or any third party, including interest, penalties,
reasonable attorneys' fees and expenses and all amounts paid in investigation,
defense or settlement of any of the foregoing up to, but not exceeding, $17.5
million in the aggregate (collectively, "Losses"), that any such Indemnified
Person may suffer, sustain incur or become subject to, as a result of, in
connection with, relating or incidental to or by virtue of:

                  (i) any misrepresentation or breach of warranty on the part of
         the Indemnifying Party in the case of the Company under Section 2 of
         this Agreement or in the case of EIS under Section 3 of this Agreement
         or any of the other Transaction Documents (as limited thereby) (it
         being understood that the Company shall not be responsible for any such
         misrepresentation or breach of warranty by Newco); or

                  (ii) any non-fulfillment, default or breach of any covenant or
         agreement on the part of the Indemnifying Party under Section 4 of this
         Agreement.

         (c) Maximum Recovery. Notwithstanding anything in this Agreement to the
contrary, in no event shall the Indemnifying Parties be liable for
indemnification under this Section 7 in an amount in excess of the aggregate of
the purchase price paid for the Shares and the amounts advanced and not repaid
under the Note. No Indemnified Person shall assert any such claim unless Losses
in respect thereof incurred by any Indemnified Person, when aggregated with
<PAGE>
                                      -18-

all previous Losses hereunder, equal or exceed U.S.$50,000, but at such time
that an Indemnified Person is entitled to assert a claim, such claim shall
include all Losses covered by this Section 7.

         (d) Exception. Notwithstanding the foregoing, upon judicial
determination that is final and no longer appealable, that the act or omission
giving rise to the indemnification set forth above resulted primarily out of or
was based primarily upon the Indemnified Person's negligence (unless such
Indemnified Person's negligence was based upon the Indemnified Person's reliance
in good faith upon any of the representations, warranties, covenants or promises
made by the Indemnifying Party herein) the Indemnifying Party shall not be
responsible for any Losses sought to be indemnified in connection therewith, and
the Indemnifying Party shall be entitled to recover from the Indemnified Person
all amounts previously paid in full or partial satisfaction of such indemnity,
together with all costs and expenses (including reasonable attorneys fees) of
the Indemnifying Party reasonably incurred in connection with the Indemnified
Persons claim for indemnity, together with interest at the rate per annum
publicly announced by Morgan Guaranty Trust Company as its prime rate from the
time of payment of such amounts to the Indemnified Person until repayment to the
Indemnifying Party.

         (e) Investigation. All indemnification rights hereunder shall survive
the execution and delivery of this Agreement and the consummation of the
transactions contemplated hereby, irrespective of any investigation, inquiry or
examination made for or on behalf of, or any knowledge of the Indemnified Person
or the acceptance of any certificate or opinion.

         (f) Contribution. If the indemnity provided for in this Section 7 shall
be, in whole or in part, unavailable to any Indemnified Person, due to Section
7(b) being declared unenforceable by a court of competent jurisdiction based
upon reasons of public policy, so that Section 7(b) shall be insufficient to
hold each such Indemnified Person harmless from Losses which Would otherwise be
indemnified hereunder, then the Indemnifying Party and the Indemnified Person
shall each contribute to the amount paid or payable for such Loss in such
proportion as is appropriate to reflect not only the relative benefits received
by the Indemnifying Party on the one hand and the Indemnified Person on the
other, but also the relative fault of the Indemnifying Part), and be in addition
to any liability that the Indemnifying Party may otherwise have. The indemnity,
contribution and expense reimbursement obligations that the Indemnifying Party
has under this Section 7 shall survive the expiration of the Transaction
Documents. The parties hereto further agree that the indemnification and
reimbursement commitments set forth in this Agreement shall apply whether or not
the Indemnified Person is a formal party to any such lawsuit, claims or other
proceedings.

         (g) Limitation. This Section 7 is not intended to limit the rights or
remedies otherwise available to any party hereto with respect to this Agreement
or the Transaction Documents.

<PAGE>

                                      -19-

      SECTION 8. Notices. All notices, demands and requests of any kind to be
delivered to any party in connection with this Agreement shall be in writing and
shall be deemed to have been duly given if personally or hand delivered or if
sent by an internationally-recognized overnight delivery courier or by
registered or certified mail, return receipt requested and postage prepaid, or
by facsimile transmission addressed as follows:

      (i)   if to the Company, to:

            Acusphere, Inc.
            University Park at M.I.T.
            38 Sidney Street
            Cambridge, MA 02139
            Attention: Steven W. Delaney
                       Vice President,
                       Finance & Administration
            Facsimile: 617-577-0233

            with a copy to:

            Testa, Hurwitz & Thibeault, LLP
            High Street Tower
            125 High Street
            Boston, MA 02110
            Attention: Lawrence Wittenberg
            Facsimile: 617-248-7100

      (ii)  If to EIS, to:

            Elan International Services, Ltd.
            102 St. James Court
            Flatts, Smiths Parish
            Bermuda FL 04
            Attention: Chief Executive Officer
            Facsimile: (441) 292-2224

            With a copy to:

            Cahill Gordon & Reindel
            80 Pine Street
            New York, NY 10005
            Attention: William M. Hartnett
            Facsimile: 212-269-5420
<PAGE>
                                      -20-

or to such other address as the party to whom notice is to be given may have
furnished to the other party hereto in writing in accordance with provisions of
this Section 8. Any such notice or communication shall be deemed to have been
effectively given (i) in the case of personal or hand delivery, on the date of
such delivery, (ii) in the case of an internationally-recognized overnight
delivery courier, on the second business day after the date when sent, (iii) in
the case of mailing, on the fifth business day following that day on which the
piece of mail containing such communication is posted and (iv) in the case of
facsimile transmission, the date of telephone confirmation of receipt.

      SECTION 9. Entire Agreement. This Agreement and the other Transaction
Documents contain the entire understanding of the parties with respect to the
subject matter hereof and thereof and supersede all prior agreements and
understandings among the parties with respect thereto.

      SECTION 10. Amendments and Waiver. This Agreement may not be modified or
amended, or any of the provisions hereof waived, except by written agreement of
the Company and EIS dated after the date hereof.

      SECTION 11. Counterparts and Facsimile. The Transaction Documents may be
executed in any number of counterparts, and each such counterpart hereof shall
be deemed to be an original instrument, but all such counterparts together shall
constitute one agreement. Each of the Transaction Documents may be signed and
delivered to the other party by facsimile transmission; such transmission shall
be deemed a valid signature.

      SECTION 12. Heading's. The section and paragraph headings contained in
this Agreement are for reference purposes only and shall not affect in any way
the meaning or interpretation of the Agreement.

      SECTION 13. Governing Law; Disputes. This Agreement shall be governed by
and construed in accordance with the internal laws of the State of New York,
without giving effect to principles of conflicts of laws. Any dispute under the
Transaction Documents that is not settled by mutual consent shall be finally
adjudicated by any federal or state court sitting in the City, Count), and State
of New York, and each party consents to the exclusive jurisdiction of such
courts (or any appellate court therefrom) over any such dispute.

      SECTION 14. Expenses. Each of the parties shall be responsible for its own
costs and expenses incurred in connection with the transactions contemplated
hereby and by the other Transaction Documents.

      SECTION 15. Exhibits and Schedules. The exhibits to and schedules
delivered by or on behalf of any, party in connection with this Agreement are an
integral part of this
<PAGE>
                                      -21-

Agreement, and any statements contained in such schedules shall be deemed to be
representations and warranties under this Agreement.

      SECTION 16. Assignments and Transfers. This Agreement and all of the
provisions hereof shall be binding upon and inure to the benefit of the parties
hereto and their respective successors and permitted assigns. All or any part of
this Agreement, the Securities and the Underlying Shares may be assigned or
transferred by EIS and its permitted assigns and transferees to their respective
affiliates and subsidiaries, as well as any special purpose financing or similar
vehicle established by EIS; provided, however, that EIS shall remain liable for
its obligations hereunder after any such assignment. Other than as set forth
above, no party shall assign or transfer all or any part of this Agreement, the
Securities and the Underlying Shares, or any interest therein, without the prior
written consent of the other party.

      SECTION 17. Severability. In case any provision of this Agreement shall be
invalid, illegal or unenforceable, the validity, legality and enforceability of
the remaining provisions shall not be in any, way affected or impaired thereby.

                            [Signature page follows]
<PAGE>
      IN WITNESS WHEREOF, each of the undersigned has duty executed this
Agreement as of the date first written above.

                                    ACUSPHERE, INC.

                                    By: /s/ Sherri C. Oberg
                                        -----------------------------
                                        Name: Sherri C. Oberg
                                        Title: President and C.E.O.

                                    ELAN INTERNATIONAL SERVICES, LTD.

                                    By: /s/ Kevin Insley
                                        -----------------------------
                                        Name:
                                        Title:
<PAGE>
                                   EXHIBIT A-1

                                  FORM OF NOTE
<PAGE>
                                   EXHIBIT A-2

                   FORM OF NOTICE OF REQUEST FOR DISBURSEMENT

Date:

To:         Elan International Services, Ltd.

From:       Acusphere, Inc.

Re:         Disbursement Request

      Pursuant to Section 1(e) of the Securities Purchase Agreement between
Acusphere, Inc. (the "Company") and Elan International Services, Ltd. ("EIS"),
dated [________________], 2000, the Company hereby notifies EIS of its request
for a disbursement thereunder in the amount of U.S.$____________ on
______________, ____ (the "Note Closing Date"). Please provide funding on the
Note Closing Date in the requested amount to the Company in accordance with the
following wire instructions:

                                    ACUSPHERE, INC.

                                    By: ______________________________
                                        Name:
                                        Title:
<PAGE>
                                    EXHIBIT B

            FORM OF AMENDED AND RESTATED CERTIFICATE OF INCORPORATION
<PAGE>
                                   EXHIBIT C-1

             SIXTH AMENDED AND RESTATED INVESTORS' RIGHTS AGREEMENT
<PAGE>
             SIXTH AMENDED AND RESTATED INVESTORS' RIGHTS AGREEMENT

                                 ACUSPHERE, INC.

                                  JUNE 30, 2000
<PAGE>
                                TABLE OF CONTENTS

<TABLE>
<S>                                                                           <C>
1.    Termination of 2000 Investors' Rights Agreement; Waiver and Consent ..   2
      1.1   Termination of 2000 Investors' Rights Agreement ................   2
      1.2   Waiver and Consent .............................................   2

2.    Registration Rights ..................................................   2
      2.1   Definitions ....................................................   2
      2.2   Demand Registration ............................................   3
      2.3   "Piggy-Back" Registration ......................................   5
      2.4   Form S-3 Registration ..........................................   6
      2.5   Obligations of Acusphere .......................................   7
      2.6   Furnish Information ............................................   8
      2.7   Expenses of Demand and S-3 Registrations .......................   8
      2.8   Expenses of "Piggy-Back" Registration ..........................   9
      2.9   Delay of Registration ..........................................   9
      2.10  Indemnification ................................................   9
      2.11  Reports Under Securities Exchange Act of 1934 ..................  11
      2.12  Assignment of Registration Rights ..............................  12
      2.13  Limitations on Subsequent Registration Rights ..................  12
      2.14  "Market Stand-Off" Agreement ...................................  12
      2.15  Termination of Registration Rights .............................  13

3.    Covenants of Acusphere ...............................................  13
      3.1   Delivery of Financial Statements ...............................  13
      3.2   Inspection and Observation .....................................  14
      3.3   Termination of Information, Inspection and Observation
            Covenants; Assignment ..........................................  14
      3.4   Right of First Refusal .........................................  15
      3.5   Preparation of Audited Financial Statements ....................  17
      3.6   Stock Purchase Agreements ......................................  17
      3.7   Termination of Certain Covenants ...............................  17
      3.8   Covenants Relating to SBA Matters ..............................  17
      3.9   Regulatory Compliance Cooperation ..............................  18
      3.10  Consideration of Section 1202(c) ...............................  19
      3.11  Registration Rights ............................................  19

4.    Miscellaneous ........................................................  19
      4.1   Successors and Assigns .........................................  19
      4.2   Governing Law ..................................................  19
      4.3   Counterparts ...................................................  19
      4.4   Titles and Subtitles ...........................................  20
      4.5   Notices ........................................................  20
      4.6   Expenses .......................................................  20
      4.7   Amendments and Waivers .........................................  20
</TABLE>

                                      - i -
<PAGE>
<TABLE>
<S>                                                                           <C>
      4.8   Severability ...................................................  20
      4.9   Aggregation of Stock ...........................................  20
      4.10  Entire Agreement; Amendment; Waiver ............................  20
</TABLE>

                                       ii
<PAGE>
             SIXTH AMENDED AND RESTATED INVESTORS' RIGHTS AGREEMENT

      THIS SIXTH AMENDED AND RESTATED INVESTORS' RIGHTS AGREEMENT (this
"Agreement") is made as of the 30th of June, 2000, by and among Acusphere, Inc.,
a Delaware corporation ("Acusphere"), and those investors listed on Schedule A
attached hereto (the "Investors"); and, solely for purposes of Sections 1, 3.4
and 4 of this Agreement, Sherri C. Oberg ("Oberg").

                                    RECITALS

      WHEREAS, certain of the Investors (the "Existing Investors") hold shares
of Acusphere's Series A Convertible Preferred Stock, $.01 par value per share
(the "Series A Stock"), Acusphere's Series B Convertible Preferred Stock, $.01
par value per share (the "Series B Stock"), Acusphere's Series C Convertible
Preferred Stock, $.01 par value per share (the "Series C Stock"), Acusphere's
Series D Convertible Preferred Stock, $.01 par value per share (the "Series D
Stock"), Acusphere's Series E Convertible Preferred Stock, $.01 par value per
share (the "Series E Stock"), and Acusphere's Series F Convertible Preferred
Stock, $.01 par value per share (the "Series F Stock," and, together with the
Series A Stock, Series B Stock, Series C Stock, Series D Stock and Series E
Stock, the "Preferred Stock"), respectively, and possess certain registration
and other rights in connection therewith pursuant to a Fifth Amended and
Restated Investors' Rights Agreement, dated as of April 25, 2000, by and among
Acusphere and such Existing Investors (the "2000 Investors' Rights Agreement");
and

      WHEREAS, Elan International Services, Ltd. ("Elan") is party to the
Securities Purchase Agreement, dated as of the date hereof (the "Securities
Purchase Agreement"), by and among Elan, Elan Corporation, plc, an Irish public
limited company, and Acusphere providing, inter alia, for the purchase by Elan
of shares of Acusphere's Series G Non-Voting Convertible Preferred Stock, $.0l
par value per share (the "Series G Stock") and shares of Acusphere's Series H
Convertible Preferred Stock, $.0l par value per share (the "Series H Stock"),
and for the purchase by Elan of a convertible promissory note in the aggregate
principal amount of up to $8,010,000 (the "Note"), which Note is convertible, at
the option of the holder, into shares of Common Stock (as defined below); and

      WHEREAS, among the conditions to the consummation of the transactions
contemplated by the Securities Purchase Agreement is the execution and delivery
of an Investors' Rights Agreement providing certain registration rights for
Elan; and

      WHEREAS, each of the parties hereto desires to set forth in a single
document such registration and certain other rights of the Investors.

      NOW, THEREFORE, in consideration of the mutual promises, covenants and
conditions hereinafter set forth and for other good and valuable consideration
Acusphere, each Investor and Oberg, severally and not jointly, hereby agree as
follows:

1.    Termination of 2000 Investors' Rights Agreement; Waiver and Consent.

                                      -1-
<PAGE>
      1.1 Termination of 2000 Investors' Rights Agreement. The parties hereto
hereby acknowledge and agree that the 2000 Investors' Rights Agreement is hereby
amended, restated and superseded in all respects by this Agreement.

      1.2 Waiver and Consent. The Existing Investors and all other parties to
the 2000 Investors' Rights Agreement hereby (i) consent to the issuance of the
Series G Stock and Series H Stock to Elan in accordance with the terms of the
Securities Purchase Agreement, (ii) consent to the issuance of Common Stock to
the holders of the Note, upon the conversion thereof, (iii) consent to the
issuance of the Series G Paid-in-Kind Dividends pursuant to the terms of
Acusphere's Amended and Restated Certificate of Incorporation and (iv) waive all
preemptive rights and rights of first refusal, and all related notice
provisions, under all existing agreements with respect to the issuance by
Acusphere of such Series G Stock, Series G Paid-in-Kind Dividends, Series H
Stock and Common Stock.

2.    Registration Rights. Acusphere covenants and agrees as follows:

      2.1 Definitions. For purposes of this Section 2:

            (a) The term "Act" means the Securities Act of 1933, as amended.

            (b) The term "Common Stock" means shares of Common Stock, $.0l par
value per share, of Acusphere.

            (c) The term "Elan Registrable Securities" means (i) the Common
Stock issuable or issued upon conversion of the Series G Stock and the Series H
Stock, (ii) the Common Stock issued upon conversion of the Note, and (iii) any
common stock of Acusphere issued as (or issuable upon the conversion of exercise
of any warrant, right or other security which is issued as) a dividend or other
distribution with respect to, or in exchange for or in replacement of the shares
referenced in (i) and (ii) above, excluding in all cases, however, any
Registrable Securities sold by a person in the transaction in which the rights
under this Section 2 are not assigned.

            (d) The term "Form S-1" means such form under the Act as in effect
on the date hereof, or any registration form under the Act subsequently adopted
by the SEC which permits the registration of securities under the Act for which
no other form is authorized or prescribed.

            (e) The term "Form S-3" means such form under the Act as in effect
on the date hereof or any registration form under the Act subsequently adopted
by the SEC which permits inclusion or incorporation of substantial information
by reference to other documents filed by Acusphere with the SEC.

            (f) The term "Holder" means any person owning or having the right to
acquire Registrable Securities or any assignee thereof in accordance with
Section 2.12 hereof.

            (g) The term "1934 Act" shall mean the Securities Exchange Act of
1934, as amended.

                                      -2-
<PAGE>
            (h) The terms "register," "registered," and "registration" refer to
a registration effected by preparing and filing a registration statement or
similar document in compliance with the Act, and the declaration or ordering of
effectiveness of such registration statement or document.

            (i) The term "Registrable Securities" means (A) (i) the Common Stock
issuable or issued upon conversion of the Series A Stock, the Series B Stock,
the Series C Stock, the Series D Stock, the Series E Stock and the Series F
Stock, and (ii) any Common Stock of Acusphere issued as (or issuable upon the
conversion or exercise of any warrant, right or other security which is issued
as) a dividend or other distribution with respect to, or in exchange for or in
replacement of the shares referenced in (i) above, excluding in all cases,
however, any Registrable Securities sold by a person in a transaction in which
the rights under this Section 2 are not assigned, and (B) the Elan Registrable
Securities.

            (j) The number of shares of "Registrable Securities then
outstanding" shall be determined by the number of shares of Common Stock
outstanding which are, and the number of shares of Common Stock issuable
pursuant to then exercisable or convertible securities which are, Registrable
Securities.

            (k) The term "SEC" means the Securities and Exchange Commission.

            (l) The term "SBIC Investor" means any Investor that is a Small
Business Investment Company, as defined in 13 C.F.R. Section 107.

      2.2 Demand Registration.

            (a) If Acusphere shall receive at any time after the earlier of (i)
December 31, 2002 or (ii) six months after the closing of an initial public
offering of securities of Acusphere (other than a registration statement
relating either to the sale of securities to employees of Acusphere pursuant to
a stock option, stock purchase or similar plan or a SEC Rule 145 transaction), a
written request from (i) the Holders of at least forty percent (40%) of the
Registrable Securities other than the Elan Registrable Securities then
outstanding, or (ii) the Holders of at least a majority of the Elan Registrable
Securities then outstanding, that Acusphere effect a registration statement
under the Act with respect to all or a part of the Registrable Securities, then
Acusphere shall:

                  (i) within ten (10) days of the receipt thereof, give written
      notice of such request to all Holders; and

                  (ii) effect as soon as practicable, and in any event within
      ninety (90) days of the receipt of such request, the registration under
      the Act of all Registrable Securities which the Holders request to be
      registered, subject to the limitations of subsection 2.2(b), within thirty
      (30) days of the mailing of such notice by Acusphere in accordance with
      Section 4.5.

            (b) If the Holders initiating the registration request hereunder
(the "Initiating Holders") intend to distribute the Registrable Securities
covered by their request by means of an

                                      -3-
<PAGE>
underwriting, they shall so advise Acusphere as a part of their request made
pursuant to subsection 2.2(a) and Acusphere shall include such information in
the written notice referred to in subsection 2.2(a). The underwriter will be
selected by Acusphere and shall be reasonably acceptable to a majority in
interest of the Initiating Holders. In such event, the right of any Holder to
include Registrable Securities in such registration shall be conditioned upon
such Holder's participation in such underwriting and the inclusion of such
Holder's Registrable Securities in the underwriting (unless otherwise mutually
agreed by a majority in interest of the Initiating Holders and such Holder) to
the extent provided herein. All Holders proposing to distribute their securities
through such underwriting shall (together with Acusphere as provided in
subsection 2.5(e)) enter into an underwriting agreement in customary form with
the underwriter or underwriters selected for such underwriting. Notwithstanding
any other provision of this Section 2.2, if the underwriter advises the
Initiating Holders in writing that marketing factors require a limitation of the
number of shares to be underwritten, then the Initiating Holders shall so advise
all Holders of Registrable Securities which would otherwise be underwritten
pursuant hereto, and the number of shares of Registrable Securities that may be
included in the underwriting shall be allocated among all Holders thereof,
including the Initiating Holders, in proportion (as nearly as practicable) to
the amount of Registrable Securities of Acusphere owned by each Holder;
provided, however, that the number of shares of Registrable Securities to be
included in such underwriting shall not be reduced unless all other securities
are first entirely excluded from the underwriting.

            (c) Notwithstanding the foregoing, if Acusphere shall furnish to the
Holders requesting registration pursuant to this Section 2.2, a certificate
signed by the Chief Executive Officer of Acusphere stating that in the good
faith judgment of the Board of Directors of Acusphere, it would be seriously
detrimental to Acusphere and its stockholders for a registration statement to be
filed and it is, therefore, essential to defer the filing of such registration
statement, Acusphere shall have the right to defer taking action with respect to
such filing for a period of not more than one hundred twenty (120) days after
receipt of the request of the Initiating Holders; provided, however, that
Acusphere may not utilize this right more than once.

            (d) Acusphere shall not be obligated to effect, or to take any
action to effect, any registration pursuant to this Section 2.2 after Acusphere
has effected four registrations on Form S-1 or its then equivalent pursuant to
this Section 2.2 and such registration statements have been declared or ordered
effective and the sales of Registrable Securities under such registration
statements have closed; provided, however, that in any event (i) the Holders of
at least forty percent (40%) of the Registrable Securities other than the Elan
Registrable Securities shall be entitled to at least one demand registration
pursuant to Section 2.2(a) hereto, and (ii) the Holders of at least a majority
of the Elan Registrable Securities shall be entitled to at least one demand
registration pursuant to Section 2.2(a) hereto.

            (e) No incidental right under this Section 2.2 shall be construed to
limit any registration required under Section 2.3 or Section 2.4 herein.

                                      -4-
<PAGE>
      2.3 "Piggy-Back" Registration.

            (a) If (but without any obligation to do so) Acusphere proposes to
register (including for this purpose a registration effected by Acusphere for
stockholders other than the Holders) any of its stock or other securities under
the Act in connection with the public offering of such securities solely for
cash (other than a registration relating solely to the sale of securities to
participants in a stock plan, a registration on any form which does not include
substantially the same information as would be required to be included in a
registration statement covering the sale of the Registrable Securities, a
registration in which the only Common Stock being registered is Common Stock
issuable upon conversion of debt securities which are also being registered, or
a registration relating to the sale of securities in connection with a
transaction covered by Rule 145 promulgated under the Act), Acusphere shall, at
such time, promptly give each Holder written notice of such registration. Upon
the written request of each Holder given within twenty (20) days after mailing
of such notice by Acusphere in accordance with Section 4.5, Acusphere shall,
subject to the provisions of subsection 2.3(b), cause to be registered under the
Act all of the Registrable Securities that each such Holder has requested to be
registered.

            (b) Underwriting Requirements. In connection with any offering
involving an underwriting of shares of Acusphere's capital stock, Acusphere
shall not be required under this Section 2.3 to include any of the Holders'
securities in such underwriting unless such Holders accept the terms of the
underwriting as agreed upon between Acusphere and the underwriters selected by
it (or by other persons entitled to select the underwriters), and then only in
such quantity as the underwriters determine in their sole discretion will not
jeopardize the success of the offering by Acusphere. If the total amount of
securities, including Registrable Securities, requested by stockholders to be
included in such offering exceeds the amount of securities to be sold (other
than by Acusphere) that the underwriters determine in their sole discretion is
compatible with the success of the offering, then Acusphere shall be required to
include in the offering only that number of such securities, including
Registrable Securities, which the underwriters determine in their sole
discretion will not jeopardize the success of the offering; provided, however,
there shall first be excluded from such registration statement all shares of
Common Stock sought to be included therein by (i) any director, consultant,
officer or employee of Acusphere or any subsidiary of Acusphere (except those
joining such registration pursuant to the Stock Repurchase and Registration
Agreement, dated April 30, 1996, among Acusphere, Robert S. Langer, Harry R.
Allcock and Sherri C. Oberg, the "Founders' Registration Agreement"), and (ii)
stockholders exercising any contractual or incidental registration rights
subordinate and junior to the rights of the Holders of Registrable Securities.
If after such shares are excluded, the underwriters shall determine in their
sole discretion that the number of securities which remain to be included in the
offering exceeds the amount of securities to be sold that the underwriters
determine is compatible with the success of the offering, then the Common Stock
to be included, if any, shall be apportioned pro rata among the holders of
Common Stock providing notice of their desire to participate in the offering
pursuant to this Agreement and the Founders' Registration Agreement (the
"Selling Stockholders") according to the total amount of securities entitled to
be included therein owned by each Selling Stockholder, or in such other
proportions as shall mutually be agreed to by such Selling Stockholders.
Notwithstanding the foregoing, in no event shall (i) the amount of securities of
the Selling Stockholders included in the offering be reduced below thirty
percent (30%) of the total amount of securities included in

                                      -5-
<PAGE>
such offering, unless such offering is the initial public offering of
Acusphere's securities in which case the Selling Stockholders may be excluded if
the underwriters make the determination described above and no other
stockholder's securities are included or (ii) notwithstanding (i) above, any
shares being sold by a Holder exercising a demand registration right similar to
that granted in Section 2.2 be excluded from such offering. For purposes of the
preceding sentence concerning apportionment, for any Selling Stockholder which
is a partnership or corporation, the partners, retired partners and stockholders
of such Selling Stockholder, or the estates and family members of any such
partners and retired partners and any trusts for the benefit of any of the
foregoing persons shall be deemed to be a single "Selling Stockholder", and any
pro-rata reduction with respect to such "selling holder" shall be based upon the
aggregate amount of shares carrying registration rights owned by all entities
and individuals included in such "Selling Stockholder", as defined in this
sentence.

            (c) No incidental right under this Section 2.3 shall be construed to
limit any registration required under Section 2.2 or Section 2.4 herein.

      2.4 Form S-3 Registration. In case Acusphere shall receive from any Holder
or Holders of Registrable Securities a written request or requests that
Acusphere effect a registration on Form S-3 and any related qualification or
compliance with respect to all or a part of the Registrable Securities owned by
such Holder or Holders, Acusphere will:

            (a) promptly give written notice of the proposed registration, and
any related qualification or compliance, to all other Holders; and

            (b) as soon as practicable, effect such registration and all such
qualifications and compliances as may be so requested and as would permit or
facilitate the sale and distribution of all or such portion of such Holder's or
Holders' Registrable Securities as are specified in such request, together with
all or such portion of the Registrable Securities of any other Holder or Holders
joining in such request as are specified in a written request given within
fifteen (15) days after receipt of such written notice from Acusphere; provided,
however, that Acusphere shall not be obligated to effect any such registration,
qualification or compliance, pursuant to this Section 2.4: (i) if Form S-3 is
not available for such offering by the Holders; (ii) if the Holders, together
with the holders of any other securities of Acusphere entitled to inclusion in
such registration, propose to sell Registrable Securities and such other
securities (if any) at an aggregate price to the public of less than $500,000;
or (iii) if Acusphere shall furnish to the Holders a certificate signed by the
Chief Executive Officer of Acusphere stating that in the good faith judgment of
the Board of Directors of Acusphere, it would be seriously detrimental to
Acusphere and its stockholders for such Form S-3 registration to be effected at
such time, in which event Acusphere shall have the right to defer the filing of
the Form S-3 registration statement for a period of not more than sixty (60)
days after receipt of the request of the Holder or Holders under this Section
2.4; provided, however, that Acusphere shall not utilize this right more than
once in any eighteen month period

            (c) Subject to the foregoing, Acusphere shall file a registration
statement covering the Registrable Securities and other securities so requested
to be registered as soon as practicable after receipt of the request or requests
of the Holders. Registrations effected pursuant

                                      -6-
<PAGE>
to this Section 2.4 shall not be counted as demands for registration or
registrations effected pursuant to Sections 2.2 or 2.3, respectively.

      2.5 Obligations of Acusphere. Whenever required under this Section 2 to
effect the registration of any Registrable Securities, Acusphere shall, as
expeditiously as reasonably possible:

            (a) Prepare and file with the SEC a registration statement with
respect to such Registrable Securities and use its best efforts to cause such
registration statement to become effective, and, upon the request of the Holders
of a majority of the Registrable Securities registered thereunder, keep such
registration statement effective for a period of up to one hundred twenty (120)
days or until the distribution contemplated in the Registration Statement has
been completed; provided, however, that (i) such 120-day period shall be
extended for a period of time equal to the period the Holder refrains from
selling any securities included in such registration at the request of an
underwriter of Common Stock (or other securities) of Acusphere; and (ii) in the
case of any registration of Registrable Securities on Form S-3 which are
intended to be offered on a continuous or delayed basis, such 120-day period
shall be extended, if necessary, to keep the registration statement effective
until all such Registrable Securities are sold, provided that Rule 415, or any
successor rule under the Act, permits an offering on a continuous or delayed
basis, and provided further that applicable rules under the Act governing the
obligation to file a post-effective amendment permit, in lieu of filing a
post-effective amendment which (A) includes any prospectus required by Section
10(a)(3) of the Act or (B) reflects facts or events representing a material or
fundamental change in the information set forth in the registration statement,
the incorporation by reference of information required to be included in (A) and
(B) above to be contained in periodic reports filed pursuant to Section 13 or
15(d) of the 1934 Act in the registration statement.

            (b) Prepare and file with the SEC such amendments and supplements to
such registration statement and the prospectus used in connection with such
registration statement as may be necessary to comply with the provisions of the
Act with respect to the disposition of all securities covered by such
registration statement.

            (c) Furnish to the Holders such numbers of copies of a prospectus,
including a preliminary prospectus, in conformity with the requirements of the
Act, and such other documents as they may reasonably request in order to
facilitate the disposition of Registrable Securities owned by them.

            (d) Use its best efforts to register and qualify the securities
covered by such registration statement under such other securities or Blue Sky
laws of such jurisdictions as shall be reasonably requested by the Holders;
provided that Acusphere shall not be required in connection therewith or as a
condition thereto to qualify to do business or to file a general consent to
service of process in any such states or jurisdictions, unless Acusphere is
already subject to service in such jurisdiction and except as may be required by
the Act.

            (e) In the event of any underwritten public offering, enter into and
perform its obligations under an underwriting agreement, in usual and customary
form, with the managing

                                      -7-
<PAGE>
underwriter of such offering. Each Holder participating in such underwriting
shall also enter into and perform its obligations under such an agreement.

            (f) Notify each Holder of Registrable Securities covered by such
registration statement at any time when a prospectus relating thereto is
required to be delivered under the Act as a result of the happening of any event
as a result of which the prospectus included in such registration statement, as
then in effect, includes an untrue statement of a material fact or omits to
state a material fact required to be stated therein or necessary to make the
statements therein not misleading in the light of the circumstances then
existing.

            (g) Cause all such Registrable Securities registered pursuant
hereunder to be listed on each securities exchange on which similar securities
issued by Acusphere are then listed.

            (h) Provide a transfer agent and registrar for all Registrable
Securities registered pursuant hereunder and a CUSIP number for all such
Registrable Securities, in each case not later than the effective date of such
registration.

            (i) Furnish, at the request of any Holder requesting registration of
Registrable Securities pursuant to this Section 2, on the date that such
Registrable Securities are delivered to the underwriters for sale in connection
with a registration pursuant to this Section 2, if such securities are being
sold through underwriters, or, if such securities are not being sold through
underwriters, on the date that the registration statement with respect to such
securities becomes effective, (i) an opinion, dated such date, of the counsel
representing Acusphere for the purposes of such registration, in form and
substance as is customarily given to underwriters in an underwritten public
offering, addressed to the underwriters, if any, and to the Holders requesting
registration of Registrable Securities and (ii) a letter dated such date, from
the independent certified public accountants of Acusphere, in form and substance
as is customarily given by independent certified public accountants to
underwriters in an underwritten public offering, addressed to the underwriters,
if any, and to the Holders requesting registration of Registrable Securities.

      2.6 Furnish Information. It shall be a condition precedent to the
obligations of Acusphere to take any action pursuant to this Section 2 with
respect to the Registrable Securities of any selling Holder that such Holder
shall furnish to Acusphere such information regarding itself, the Registrable
Securities held by it, and the intended method of disposition of such securities
as shall be required to effect the registration of such Holder's Registrable
Securities.

      2.7 Expenses of Demand and S-3 Registrations. All expenses other than
underwriting discounts and commissions incurred in connection with
registrations, filings or qualifications pursuant to Sections 2.2 and 2.4,
including (without limitation) all registration, filing and qualification fees,
printers' and accounting fees, fees and disbursements of counsel for Acusphere
and transfer taxes, if any, and the reasonable fees and disbursements of one
counsel for the selling Holders shall be borne by Acusphere; provided, however,
that Acusphere shall not be required to pay for any expenses of any registration
proceeding begun pursuant to Section 2.2 or 2.4 if the registration request is
subsequently withdrawn at the request of the Holders of a

                                      -8-
<PAGE>
majority of the Registrable Securities to be registered (in which case all
Holders participating in the registration shall bear such expenses), unless, in
the case of a registration pursuant to Section 2.2, the Holders of a majority of
the Registrable Securities agree to forfeit their right to one demand
registration pursuant to Section 2.2; provided further, however, that if at the
time of such withdrawal, the Holders have learned of a material adverse change
in the condition, business, or prospects of Acusphere from that known to the
Holders at the time of their request and have withdrawn the request with
reasonable promptness following disclosure by Acusphere of such material adverse
change, then the Holders shall not be required to pay any of such expenses and
shall retain their rights under Sections 2.2 and 2.4.

      2.8 Expenses of "Piggy-Back" Registration. Acusphere shall bear and pay
all expenses incurred in connection with any registration, filing or
qualification of Registrable Securities with respect to the registrations
pursuant to Section 2.3 for each Holder, including (without limitation) all
registration, filing, and qualification fees, printers' and accounting fees
relating or apportionable thereto and transfer taxes, if any, and the fees and
disbursements of one counsel for the selling Holders selected by them, but
excluding underwriting discounts and commissions relating to the Registrable
Securities.

      2.9 Delay of Registration. No Holder shall have any right to obtain or
seek an injunction restraining or otherwise delaying any such registration as
the result of any controversy that might arise with respect to the
interpretation or implementation of this Section 2.

      2.10 Indemnification. In the event any Registrable Securities are included
in a registration statement under this Section 2:

            (a) To the extent permitted by law, Acusphere will indemnify and
hold harmless each Holder, any underwriter (as defined in the Act) for such
Holder and each person, if any, who controls such Holder or underwriter within
the meaning of the Act or the 1934 Act, against any losses, claims, damages, or
liabilities (joint or several) to which they may become subject under the Act,
the 1934 Act or other federal or state law, insofar as such losses, claims,
damages, or liabilities (or actions in respect thereof) arise out of or are
based upon any of the following statements, omissions or violations
(collectively a "Violation"): (i) any untrue statement or alleged untrue
statement of a material fact contained in such registration statement, including
any preliminary prospectus or final prospectus contained therein or any
amendments or supplements thereto, (ii) the omission or alleged omission to
state therein a material fact required to be stated therein, or necessary to
make the statements therein not misleading, or (iii) any violation or alleged
violation by Acusphere of the Act, the 1934 Act, any state securities law or any
rule or regulation promulgated under the Act, the 1934 Act or any state
securities law; and Acusphere will pay to each such Holder, underwriter or
controlling person, as incurred, any legal or other expenses reasonably incurred
by them in connection with investigating or defending any such loss, claim,
damage, liability, or action; provided, however, that the indemnity agreement
contained in this subsection 2.10(a) shall not apply to amounts paid in
settlement of any such loss, claim, damage, liability, or action if such
settlement is effected without the consent of Acusphere (which consent shall not
be unreasonably withheld), nor shall Acusphere be liable in any such case for
any such loss, claim, damage, liability, or action to the extent that it arises
out of or is based upon a Violation which occurs in reliance upon and in
conformity with written

                                      -9-
<PAGE>
information furnished expressly for use in connection with such registration by
any such Holder, underwriter or controlling person.

            (b) To the extent permitted by law, each selling Holder will
indemnify and hold harmless Acusphere, each of its directors, each of its
officers who has signed the registration statement, each person, if any, who
controls Acusphere within the meaning of the Act, any underwriter, any other
Holder selling securities in such registration statement and any controlling
person of any such underwriter or other Holder, against any losses, claims,
damages, or liabilities (joint or several), to which any of the foregoing
persons may become subject, under the Act, the 1934 Act or other federal or
state law, insofar as such losses, claims, damages, or liabilities (or actions
in respect thereto) arise out of or are based upon any Violation, in each case
to the extent (and only to the extent) that such Violation occurs in reliance
upon and in conformity with written information furnished by such Holder
expressly for use in connection with such registration; and each such Holder
will pay, as incurred, any legal or other expenses reasonably incurred by any
person intended to be indemnified pursuant to this subsection 2.10(b), in
connection with investigating or defending any such loss, claim, damage,
liability, or action; provided, however, that the indemnity agreement contained
in this subsection 2.10(b) shall not apply to amounts paid in settlement of any
such loss, claim, damage, liability or action if such settlement is effected
without the consent of the Holder, which consent shall not be unreasonably
withheld; provided, that, in no event shall any indemnity under this subsection
2.10(b) exceed the net proceeds from the offering received by such Holder.

            (c) Promptly after receipt by an indemnified party under this
Section 2.10 of notice of the commencement of any action (including any
governmental action), such indemnified party will, if a claim in respect thereof
is to be made against any indemnifying party under this Section 2.10, deliver to
the indemnifying party a written notice of the commencement thereof and the
indemnifying party shall have the right to participate in, and, to the extent
the indemnifying party so desires, jointly with any other indemnifying party
similarly noticed, to assume the defense thereof with counsel mutually
satisfactory to the parties; provided, however, that an indemnified party
(together with all other indemnified parties which may be represented without
conflict by one counsel) shall have the right to retain one separate counsel,
with the fees and expenses to be paid by the indemnifying party, if
representation of such indemnified party by the counsel retained by the
indemnifying party would be inappropriate due to actual or potential differing
interests between such indemnified party and any other party represented by such
counsel in such proceeding. The failure to deliver written notice to the
indemnifying party within a reasonable time of the commencement of any such
action, if prejudicial to its ability to defend such action, shall relieve such
indemnifying party of any liability to the indemnified party under this Section
2.10, but the omission so to deliver written notice to the indemnifying party
will not relieve it of any liability that it may have to any indemnified party
otherwise than under this Section 2.10.

            (d) If the indemnification provided for in this Section 2.10 is held
by a court of competent jurisdiction to be unavailable to an indemnified party
with respect to any loss, liability, claim, damage, or expense referred to
therein, then the indemnifying party, in lieu of indemnifying such indemnified
party hereunder, shall contribute to the amount paid or payable by such
indemnified party as a result of such loss, liability, claim, damage, or expense
in such

                                      -10-
<PAGE>
proportion as is appropriate to reflect the relative fault of the indemnifying
party on the one hand and of the indemnified party on the other in connection
with the statements or omissions that resulted in such loss, liability, claim,
damage, or expense as well as any other relevant equitable considerations. The
relative fault of the indemnifying party and of the indemnified party shall be
determined by reference to, among other things, whether the untrue or alleged
untrue statement of a material fact or the omission to state a material fact
relates to information supplied by the indemnifying party or by the indemnified
party and the parties' relative intent, knowledge, access to information, and
opportunity to correct or prevent such statement or omission; provided, that, in
the case of contribution by a selling Holder, in no event shall any contribution
under this subsection 2.10(d) exceed the net proceeds from the offering received
by such contributing party.

            (e) Notwithstanding the foregoing, to the extent that the provisions
on indemnification and contribution contained in the underwriting agreement
entered into in connection with the underwritten public offering are in conflict
with the foregoing provisions, the provisions in the underwriting agreement
shall control.

            (f) The obligations of Acusphere and Holders under this Section 2.10
shall survive the completion of any offering of Registrable Securities in a
registration statement under this Section 2, and otherwise.

      2.11 Reports Under Securities Exchange Act of 1934. With a view to making
available to the Holders the benefits of Rule 144 promulgated under the Act and
any other rule or regulation of the SEC that may at any time permit a Holder to
sell securities of Acusphere to the public without registration or pursuant to a
registration on Form S-3, Acusphere agrees to use its best efforts to:

            (a) make and keep public information available, as those terms are
understood and defined in SEC Rule 144, at all times after ninety (90) days
after the effective date of the first registration statement filed by Acusphere
for the offering of its securities to the general public;

            (b) take such action, including the voluntary registration of its
Common Stock under Section 12 of the 1934 Act, as is necessary to enable the
Holders to utilize Form S-3 for the sale of their Registrable Securities, such
action to be taken as soon as practicable after the end of the fiscal year in
which the first registration statement filed by Acusphere for the offering of
its securities to the general public is declared effective;

            (c) file with the SEC in a timely manner all reports and other
documents required of Acusphere under the Act and the 1934 Act; and

            (d) furnish to any Holder, so long as the Holder owns any
Registrable Securities, forthwith upon request (i) a written statement by
Acusphere that it has complied with the reporting requirements of SEC Rule 144
(at any time after ninety (90) days after the effective date of the first
registration statement filed by Acusphere), the Act and the 1934 Act (at any
time after it has become subject to such reporting requirements), or that it
qualifies as a registrant whose securities may be resold pursuant to Form S-3
(at any time after it so qualifies), (ii) a copy of the most recent annual or
quarterly report of Acusphere and such other reports and documents

                                      -11-
<PAGE>
so filed by Acusphere, and (iii) such other information as may be reasonably
requested in availing any Holder of any rule or regulation of the SEC which
permits the selling of any such securities without registration or pursuant to
such form.

      2.12 Assignment of Registration Rights. The rights to cause Acusphere to
register Registrable Securities pursuant to this Section 2 may be assigned (but
only with all related obligations) by a Holder to a transferee or assignee of
such securities who, after such assignment or transfer, holds at least 75,000
shares of Registrable Securities (subject to appropriate adjustment for stock
splits, stock dividends, combinations and other recapitalizations), provided:
(a) Acusphere is, within a reasonable time after such transfer, furnished with
written notice of the name and address of such transferee or assignee and the
securities with respect to which such registration rights are being assigned;
(b) such transferee or assignee agrees in writing to be bound by and subject to
the terms and conditions of this Agreement, including without limitation the
provisions of Section 2.14 below; and (c) such assignment shall be effective
only if immediately following such transfer the further disposition of such
securities by the transferee or assignee is restricted under the Act.

      2.13 Limitations on Subsequent Registration Rights. From and after the
date of this Agreement, Acusphere shall not, without the prior written consent
of the Holders of a majority of the Registrable Securities then outstanding,
enter into any agreement with any holder or prospective holder of any securities
of Acusphere which would allow such holder or prospective holder (a) to include
such securities in any registration filed under Section 2.2 or described in
Section 2.3 hereof, unless under the terms of such agreement, such holder or
prospective holder may include such securities in any such registration only to
the extent that the inclusion of such securities will not reduce the amount of
the Registrable Securities of the Holders which are to be included or (b) to
make a demand registration which could result in such registration statement
being declared effective prior to the earlier of either of the dates set forth
in subsection 2.2(a) or within one hundred twenty (120) days of the effective
date of any registration effected pursuant to Section 2.2.

      2.14 "Market Stand-Off" Agreement. Each Investor hereby agrees that,
during the period of duration (not to exceed one hundred eighty (180) days)
specified by Acusphere and an underwriter of Common Stock or other securities of
Acusphere, following the effective date of a registration statement of Acusphere
filed under the Act, such Investor shall not, to the extent requested by
Acusphere and such underwriter, directly or indirectly sell, offer to sell,
contract to sell (including, without limitation, any short sale), grant any
option to purchase or otherwise transfer or dispose of (other than to donees who
agree to be similarly bound) any securities of Acusphere held by it at any time
during such period except Common Stock included in such registration; provided,
however, that:

            (a) such agreement shall be applicable only with respect to a
      registration statement covering Acusphere's initial public offering of
      securities; and

            (b) all officers and directors of Acusphere and all other persons
      with registration rights (whether or not pursuant to this Agreement) enter
      into similar agreements.

                                      -12-
<PAGE>
            In order to enforce the foregoing covenant, Acusphere may impose
stop-transfer instructions with respect to the Registrable Securities of an
Investor (and the shares or securities of every other person subject to the
foregoing restriction) until the end of such period.

            Notwithstanding the foregoing, the obligations described in this
Section 2.14 shall not apply to a registration relating solely to employee
benefit plans on Form S-1 or Form S-8 or similar forms which may be promulgated
in the future, or a registration relating solely to a SEC Rule 145 transaction
on Form S-4 or similar forms which may be promulgated in the future.

      2.15 Termination of Registration Rights. No Holder shall be entitled to
exercise any right provided for in this Section 2 if there is then an active
public trading market for the Common Stock and such Holder may sell all of such
Holder's Registrable Securities under Rule 144 promulgated under the Act in a
three-month period. No holder shall be entitled to exercise any right provided
for in Section 2.2 after five (5) years following the consummation of the sale
of securities pursuant to a registration statement filed by Acusphere under the
Act in connection with the initial firm commitment underwritten offering of its
securities to the general public.

3.    Covenants of Acusphere.

      3.1 Delivery of Financial Statements. Acusphere shall deliver to each
Significant Investor (as defined in Section 3.2(b) hereof), as long as such
Investor holds shares of Preferred Stock:

            (a) as soon as practicable, but in any event within ninety (90) days
after the end of each fiscal year of Acusphere, an income statement for such
fiscal year, a balance sheet of Acusphere and statement of stockholders' equity
as of the end of such year, and a schedule as to the sources and applications of
funds for such year, such year-end financial reports to be in reasonable detail,
prepared in accordance with generally accepted accounting principles ("GAAP"),
and audited and certified by independent public accountants of nationally
recognized standing selected by Acusphere;

            (b) as soon as practicable, but in any event within forty-five (45)
days after the end of each of the first three (3) quarters of each fiscal year
of Acusphere, an unaudited profit or loss statement and schedule as to the
sources and application of funds for such fiscal quarter and an unaudited
balance sheet as of the end of such fiscal quarter;

            (c) within thirty (30) days of the end of each month, an unaudited
income statement and schedule as to the sources and application of funds and
balance sheet for and as of the end of such month, in reasonable detail;

            (d) as soon as practicable, but in any event forty-five (45) days
prior to the end of each fiscal year, a budget and business plan for the next
fiscal year, prepared on a monthly basis, including balance sheets and sources
and applications of funds statements for such months and, as soon as prepared,
any other budgets or revised budgets prepared by Acusphere;

            (e) with respect to the financial statements called for in
subsections (a), (b) and (c) of this Section 3.1, an instrument executed by the
Chief Financial Officer or Chief

                                      -13-
<PAGE>
Executive Officer of Acusphere and certifying that such financials were prepared
in accordance with GAAP consistently applied with prior practice for earlier
periods (with the exception of footnotes that may be required by GAAP) and
fairly present the financial condition of Acusphere and its results of operation
for the period specified, subject to year-end audit adjustment; and

            (f) such other information relating to the financial condition,
business, prospects or corporate affairs of Acusphere as such Significant
Investor or any assignee of such Significant Investor may from time to time
request, provided, however, that Acusphere shall not be obligated under this
subsection (f) or any other subsection of Section 3.1 to provide information
which it deems in good faith to be a trade secret or similar confidential
information.

      3.2 Inspection and Observation.

            (a) Acusphere shall permit each Significant Investor (as defined in
Section 3.2(b) hereof), at such Significant Investor's expense, to visit and
inspect Acusphere's properties, to examine its books of account and records and
to discuss Acusphere's affairs, finances and accounts with its officers, all at
such reasonable times as may be requested by such Significant Investor;
provided, however, that Acusphere shall not be obligated pursuant to this
Section 3.2 to provide access to any information which its Board of Directors
reasonably considers to be a trade secret or similar confidential information.

            (b) Acusphere will permit any Significant Investor (as hereinafter
defined), any authorized representative thereof or any Series E Investor holding
at least five percent (5%) of the Common Stock on a fully-diluted basis (the
"Series E Five-Percent Holder"), to attend all meetings of the Board of
Directors of Acusphere in a nonvoting observer capacity and shall, upon the
written request of such Significant Investor or Series E Five-Percent Holder,
provide such Significant Investor or Series E Five-Percent Holder with such
notice and other information with respect to such meetings as are delivered to
the directors of Acusphere; provided, however, that it is hereby acknowledged
and agreed that only a single representative of each group consisting of a
Significant Investor and its affiliates will be entitled to attend any such
meeting pursuant to this Section 3.2(b). Upon the written request of any such
Significant Investor or Series E Five-Percent Holder, Acusphere shall notify
such Significant Investor or Series E Five-Percent Holder, within ten (10) days
thereof, of the taking of any action by the Board of Directors of Acusphere in
lieu of a meeting thereof. As used in this Section 3, the term "Significant
Investor" shall mean (i) Elan so long as it, together with its affiliates, holds
5% or more of Acusphere's issued and outstanding shares of Common Stock on a
fully diluted basis (assuming the conversion or exercise, as the case may be, of
all outstanding securities or rights to acquire shares of Acusphere's Common
Stock) and (ii) any other Investor who, together with its affiliates, holds at
least 200,000 shares of Preferred Stock, including Common Stock issuable upon
the conversion of Preferred Stock (as presently constituted and subject to
subsequent adjustment for stock splits, stock dividends, reverse stock splits,
recapitalizations and the like).

      3.3 Termination of Information, Inspection and Observation Covenants,
Assignment. The covenants set forth in Section 3.1 and Section 3.2 shall
terminate as to each Investor and be of no further force or effect when the sale
of securities pursuant to a registration statement filed by Acusphere under the
Act in connection with the firm commitment underwritten offering of its

                                      -14-
<PAGE>
securities to the general public is consummated or when Acusphere first becomes
subject to the periodic reporting requirements of Sections 12(g) or 15(d) of the
1934 Act, whichever event shall first occur; provided, however, that the
covenants set forth in Section 3.2 shall not terminate with respect to Elan so
long as it, together with its affiliates, holds 5% or more of Acusphere's issued
and outstanding shares of Common Stock on a fully diluted basis (assuming the
conversion or exercise, as the case may be, of all outstanding securities or
rights to acquire shares of Acusphere's Common Stock). The rights to receive and
access information relating to Acusphere pursuant to Sections 3.1 and 3.2 may be
assigned (but only with all related obligations) by an Investor to a transferee
or assignee of such securities who, after such assignment or transfer, holds at
least 75,000 shares of Registrable Securities (subject to appropriate adjustment
for stock splits, stock dividends, combinations and other recapitalizations),
provided: (a) Acusphere is, within a reasonable time after such transfer,
furnished with written notice of the name and address of such transferee or
assignee and the securities with respect to which such information rights are
being assigned; and (b) such transferee or assignee agrees in writing to be
bound by and subject to the terms and conditions of this Agreement.

      3.4 Right of First Refusal. Subject to the terms and conditions specified
in this Section 3.4, Acusphere hereby grants to each of the Investors a right of
first refusal with respect to future sales by Acusphere of its Shares (as
hereinafter defined). For purposes of this Section 3.4 and Section 4 only, the
term "Investor" shall include Oberg and any general partners and affiliates of
an Investor. For purposes of this Section 3.4 only, the term "Investor" shall
not include Elan or any of its affiliates after the fourth anniversary of this
Agreement. Each Investor shall be entitled to apportion the right of first
refusal hereby granted it among itself and its partners and affiliates in such
proportions as it deems appropriate. For purposes hereof, an "affiliate" of any
Investor is an entity or a person that directly or indirectly controls, is
controlled by, or is under common control with such Investor.

            Each time Acusphere proposes to offer any shares of, or securities
convertible into or exercisable for any shares of, any class of its capital
stock ("Shares"), Acusphere shall first make an offering of such Shares to the
Investors in accordance with the following provisions:

            (a) Acusphere shall deliver a notice by certified mail ("Notice") to
each Investor stating (i) its bona fide intention to offer such Shares, (ii) the
number of such Shares to be offered, and (iii) the price and terms, if any, upon
which it proposes to offer such Shares.

            (b) Within thirty (30) calendar days after receipt of the Notice,
each Investor may elect to purchase or obtain, at the price and on the terms
specified in the Notice, some or all of such Investor's pro rata portion of such
Shares. Each Investor's pro rata portion of such Shares shall be equal to a
fraction of such Shares, the numerator of which is the number of shares of
Registrable Securities or Common Stock as the case may be, then held by such
Investor and the denominator of which shall be equal to the sum of the total
number of shares of Registrable Securities and Common Stock then held by all
Investors; provided, however, that, solely for purposes of determining such pro
rata portion pursuant to this Section 3.4(b), "Registrable Securities" shall not
include any shares of Series G Stock or any share of Common Stock issued as (or
issuable upon the conversion or exercise of any warrant, right or other security
which is

                                      -15-
<PAGE>
issued as) a dividend or other distribution with respect to, or in exchange for
or in replacement of such shares. If any Investor does not elect to exercise its
or his right to purchase its or his total pro rata portion of the Shares,
Acusphere shall promptly give notice of such failure to the other Investors who
did elect to purchase (the "Participants"). Each Investor shall have a right of
over-allotment such that if any Investor fails to exercise its or his right to
purchase its or his total pro rata portion of the Shares, the Participants may
purchase such portion, by giving written notice to Acusphere with five (5) days
from the date that Acusphere provides written notice to the other Participants
of the number of Shares with respect to which such non-purchasing Investor has
failed to exercise its rights hereunder.

            (c) If the Investors do not elect to purchase all Shares referred to
in the Notice, Acusphere may, during the 90-day period following the expiration
of the period provided in subsection 3.4(b) hereof (including the additional
five day period provided for over-allotments), offer the remaining unsubscribed
portion of such Shares to any person or persons at a price not less than, and
upon terms no more favorable to the offeree than those specified in the Notice.
If Acusphere does not enter into an agreement for the sale of the unsubscribed
portion of such Shares within such period, or if such agreement is not
consummated within thirty (30) days of the execution thereof, the right provided
hereunder shall be deemed to be revived and such Shares shall not be offered
unless first reoffered to the Investors in accordance herewith; provided,
however, that if during such 90-day period, Acusphere offers such Shares to any
person or persons at a price and/or upon terms more favorable to the offeree
than those specified in the Notice, then Acusphere must first reoffer the Shares
to the Investors on such favorable terms and the procedure set forth above shall
be followed, with the exception that the 30-day period set forth in subsection
3.4(b) shall be a 15-day period.

            (d) The right of first refusal in this Section 3.4 shall not be
applicable (i) to the issuance or sale on or after March 30, 1994, of up to
1,985,458 shares of Common Stock (or options therefor) to Acusphere's employees,
consultants, or directors for the primary purpose of soliciting or retaining
their services, provided each such employee, consultant or director executes an
agreement providing for (A) vesting of shares (or the option to purchase shares)
over at least a four-year period, (B) market stand-off agreements similar to
that set forth in Section 2.14 of this Agreement, and (C) rights of first
refusal on transfers of such shares which shall first be a right of Acusphere,
then of Acusphere's assignees; provided, however, that any such requirements may
be waived by action of Acusphere's Board of Directors, provided that all
representatives of the Investors on the Board of Directors of Acusphere consent
to such waiver, (ii) to the issuance of securities in or after consummation of a
bona fide, firmly underwritten public offering of shares of Common Stock,
registered under the Act pursuant to a registration statement on Form S-1, at an
offering price per share of at least $9.90, as adjusted for splits, stock
dividends and similar adjustments, and with net proceeds to Acusphere (after
discounts and commission) of at least $15,000,000, (iii) to the issuance of
securities pursuant to the conversion of convertible securities, (iv) to the
issuance of 130,169 and 22,216 shares of Common Stock to the Massachusetts
Institute of Technology ("MIT") on or about March 30, 1995 and June 4, 1996,
respectively, (v) to the issuance of securities solely to prevent dilution as a
result of any stock splits, stock dividends, combinations, recapitalizations or
issuances of securities below the then applicable conversion price for the
Preferred Stock, (vi) to the issuance of securities (including convertible
securities and the securities issuable upon conversion or exercise of such

                                      -16-
<PAGE>
convertible securities) to Comdisco, Inc. or Transamerica Business Credit
Corporation, or any of their respective transferees, pursuant to financing
arrangements approved by the Board of Directors, including all of the directors
then serving on the Board of Directors which were designated by the holders of
the Company's Preferred Stock in accordance with the Fourth Amended and Restated
Voting Agreement of even date herewith, (vii) to the issuance of shares of
Common Stock pursuant to the redemption by the Company of the Series G Stock
pursuant to Acusphere's Amended and Restated Certificate of Incorporation, as in
effect from time to time after the date hereof, (viii) to the issuance of shares
of Common Stock pursuant to the conversion feature of the Note, or (ix) to the
issuance of Series G Paid-in-Kind Dividends pursuant to Acusphere's Amended and
Restated Certificate of Incorporation, as in effect from time to time after the
date hereof.

            (e) The right of first refusal set forth in this Section 3.4 may not
be assigned or transferred, except that (i) such right is assignable by each
Holder to any wholly owned subsidiary or parent of, or to any corporation or
entity that is, within the meaning of the Act, controlling, controlled by or
under common control with, any such Holder, or to any partner of a Holder that
is a partnership and (ii) such right is assignable between and among any of the
Holders.

      3.5 Preparation of Audited Financial Statements. Acusphere shall undertake
to prepare and shall deliver to each Investor, as soon as practicable, its
audited financial statements (balance sheet, profit and loss statement,
statement of stockholders' equity and statement of cash flows, including notes
thereon) as of December 31, 2000, and for each fiscal year thereafter.

      3.6 Stock Purchase Agreements. All officers and employees of and
consultants to Acusphere who purchase shares of Acusphere's capital stock shall
be required to execute a stockholder agreement providing for (i) vesting of
shares (or option to purchase shares) over a four-year period, (ii) market
stand-off agreements similar to that set forth in Section 2.14 of this
Agreement, and (iii) rights of first refusal on transfers of such shares which
shall first be a right of Acusphere, then of Acusphere's assignees; provided
however, that any such requirements may be waived by action of Acusphere's Board
of Directors, provided that any representative of the Investors on the Board of
Directors of Acusphere consents to such waiver.

      3.7 Termination of Certain Covenants. The provisions set forth in Section
3.6 shall terminate and be of no further force or effect upon the consummation
of the sale of securities pursuant to a registration statement filed by
Acusphere under the Act in connection with the firm commitment underwritten
offering of its securities to the general public.

      3.8 Covenants Relating to SBA Matters. At such times as any SBIC Investor
holds any securities of Acusphere, Acusphere shall comply with the covenants set
forth in this Section 3.8.

            (a) Use of Proceeds. The proceeds from the prior issuances and sales
of preferred stock which the Company still retains (the "Proceeds") shall be
used by Acusphere for its growth, modernization or expansion. Acusphere shall
provide each SBIC Investor and the

                                      -17-
<PAGE>
Small Business Administration (the "SBA") reasonable access to Acusphere's books
and records for the purpose of confirming the use of Proceeds.

            (b) Business Activity. During the period ending on April 25, 2001,
Acusphere shall not change the nature of its business activity if such change
would render Acusphere ineligible as provided in 13 C.F.R. Section 107.720.

            (c) Compliance. So long as any SBIC Investor holds any securities of
Acusphere, Acusphere will at all times comply with the non-discrimination
requirements of 13 C.F.R. Parts 112, 113 and 117.

            (d) Information. Within 45 days after the end of each fiscal year
and at such other times as an SBIC Investor may reasonably request, Acusphere
shall deliver to such SBIC Investor a written assessment, in form and substance
satisfactory to such SBIC Investor, of the economic impact of such SBIC
Investor's investment specifying the full-time equivalent jobs created or
retained in connection with such investment, and the impact of the investment on
Acusphere's business in terms of profits and on taxes paid by Acusphere and its
employees. Upon request, Acusphere promptly (and in any event within 20 days of
such request) will furnish to each SBIC Investor all information reasonably
requested by such SBIC Investor in order for such SBIC Investor to comply with
the requirements of 13 C.F.R. Section 107.620 or to prepare and file SBA Form
468 and any other information requested or required by any governmental agency
asserting jurisdiction over such SBIC Investor. Acusphere shall afford to
representatives of the SBA reasonable access to the books, records and
properties of Acusphere and its subsidiaries. Any submission of any financial
information under Section 3.1, above, or this Section 3.8(d) shall include a
certificate of Acusphere's president, chief executive officer, treasurer or
chief financial officer. If a SBIC Investor requests confidential information
from Acusphere for the purpose of providing such information to the SBA, then,
if requested in writing by Acusphere at the time Acusphere provides such
information to such SBIC Investor, the SBIC Investor shall, to the extent
permitted by law, request that such confidential information be treated
confidentially by the SBA.

            (e) Number of Holders of Voting Securities. Acusphere shall notify
each SBIC Investor (i) on or prior to the taking of any action which increases
the number of record holders of Acusphere's voting securities from fewer than 50
to 50 or more, and (ii) of any other action or occurrence which increases the
number of record holders of Acusphere's voting securities from fewer than 50 to
50 or more, as soon as practicable after Acusphere becomes aware that such other
action or occurrence has occurred or is proposed to occur.

      3.9 Regulatory Compliance Cooperation. In the event that Bank of America
Ventures determines that it has a Regulatory Problem (as defined below), it
shall have the right to transfer its Registrable Securities without regard to
any restrictions on transfer set forth in this Agreement, the Series F
Convertible Preferred Stock Purchase Agreement dated April 25, 2000, as in
effect from time to time (the "Series F Agreement"), the Fourth Amended and
Restated Voting Agreement, or the Fifth Amended and Restated Co-Sale Agreement
and Acusphere shall take all such actions as are reasonably requested by Bank of
America Ventures in order to (i) effectuate and facilitate any transfer by it of
any securities of Acusphere then held by it to any

                                      -18-
<PAGE>
person designated by Bank of America Ventures provided that such person is
reasonably acceptable to Acusphere and agrees in writing to be bound by this
Agreement, the Series F Agreement, the Fourth Amended and Restated Voting
Agreement, and the Fifth Amended and Restated Co-Sale Agreement, (ii) permit
Bank of America Ventures (or any of its affiliates) to exchange all or any
portion of any voting security of Acusphere then held by it on a share-for-share
basis for shares of a nonvoting security of Acusphere, which nonvoting security
shall be identical in all respects to the voting security exchanged for it,
except that it shall be nonvoting and shall be convertible into a voting
security on such terms as are requested by it in light of regulatory
considerations then prevailing and (iii) amend this Agreement, as amended from
time to time, to effectuate and reflect the foregoing. The parties to this
Agreement agree to vote all of Acusphere's securities held by them in favor of
such amendments and actions. For purposes of this Agreement, a "Regulatory
Problem" means any set of facts or circumstances wherein it has been asserted by
any governmental regulatory agency that Bank of America Ventures is not entitled
to hold, or exercise any significant right with respect to securities of
Acusphere.

      3.10 Consideration of Section 1202(c). At such time or times, if any, that
Acusphere considers repurchasing any shares of its Series F Stock, Series E
Stock, Series D Stock or Series C Stock, Acusphere agrees to consider the effect
that such repurchase would have on such stock's qualification as "Qualified
Small Business Stock," as defined in Section 1202(c) of the Internal Revenue
Code of 1986, as amended (the "Code"). Notwithstanding the foregoing, Acusphere
shall have no obligation to take, or refrain from taking any action that would
affect such stock's status as "Qualified Small Business Stock." Acusphere will
use reasonable efforts to comply with the reporting and recordkeeping
requirements of Section 1202 of the Code and the regulations promulgated
thereunder.

      3.11 Registration Rights. Acusphere shall not grant to any person or
entity registration rights which are on par with or senior to the registration
rights granted to the holders of the Registrable Securities, unless holders of a
majority of the then outstanding shares of Registrable Securities consent in
writing.

4.    Miscellaneous.

      4.1 Successors and Assigns. Except as otherwise provided herein, the terms
and conditions of this Agreement shall inure to the benefit of and be binding
upon the respective successors and assigns of the parties (including transferees
of any shares of Registrable Securities). Nothing in this Agreement, express or
implied, is intended to confer upon any party other than the parties hereto or
their respective successors and assigns any rights, remedies, obligations, or
liabilities under or by reason of this Agreement, except as expressly provided
in this Agreement.

      4.2 Governing Law. This Agreement shall be governed by and construed under
the laws of the Commonwealth of Massachusetts as applied to agreements among
Massachusetts residents entered into and to be performed entirely within
Massachusetts.

      4.3 Counterparts. This Agreement may be executed in two or more
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same

                                      -19-
<PAGE>
instrument. Any person who may, after the date hereof, purchase shares of Series
F Stock pursuant to the Series F Agreement, as amended from time to time, shall
become a party to this Agreement as an "Investor" and a holder of "Preferred
Stock" and "Registrable Securities" for all purposes hereunder, all upon
execution of a counterpart to this Agreement signed by such person and
Acusphere.

      4.4 Titles and Subtitles. The titles and subtitles used in this Agreement
are used for convenience only and are not to be considered in construing or
interpreting this Agreement.

      4.5 Notices. Unless otherwise provided, any notice required or permitted
under this Agreement shall be given in writing and shall be deemed effectively
given upon personal delivery to the party to be notified or upon deposit with
the United States Post Office, by registered or certified mail, postage prepaid
and addressed to the party to be notified at the address indicated for such
party on the signature page hereof, or at such other address as such party may
designate by ten (10) days' advance written notice to the other parties.

      4.6 Expenses. If any action at law or in equity is necessary to enforce or
interpret the terms of this Agreement, the prevailing party shall be entitled to
reasonable attorneys' fees, costs and necessary disbursements in addition to any
other relief to which such party may be entitled.

      4.7 Amendments and Waivers. Any term of this Agreement may be amended and
the observance of any term of this Agreement may be waived (either generally or
in a particular instance and either retroactively or prospectively), only with
the written consent of Acusphere and the holders of a majority of the
Registrable Securities then outstanding (provided that if an amendment or waiver
affects any Investor in a manner that is different from the effect of such
waiver or amendment on all other Investors, then the consent of such Investor
shall be required for such amendment or waiver, and further provided that no
such amendment or waiver will be effective to increase any obligations of Oberg
without her written consent). Any amendment or waiver effected in accordance
with this paragraph shall be binding upon each holder of any Registrable
Securities then outstanding, each future holder of all such Registrable
Securities, and Acusphere.

      4.8 Severability. If one or more provisions of this Agreement are held to
be unenforceable under applicable law, such provision shall be excluded from
this Agreement and the balance of the Agreement shall be interpreted as if such
provision were so excluded and shall be enforceable in accordance with its
terms.

      4.9 Aggregation of Stock. All shares of Registrable Securities held or
acquired by affiliated entities or persons shall be aggregated together for the
purpose of determining the availability of any rights under this Agreement.

      4.10 Entire Agreement. This Agreement (including the Exhibits and
Schedules hereto, if any) constitutes the full and entire understanding and
agreement between the parties with regard to the subjects hereof and thereof.

                  [REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

                                      -20-
<PAGE>
      IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date first above written.

                                ACUSPHERE, INC.
                                38 Sidney Street
                                Cambridge, MA 02139

                                By: /s/ Sherri C. Oberg
                                    ------------------------------------------
                                    Sherri C. Oberg
                                    President and Chief Executive Officer

                                MVI MEDICAL VENTURE
                                INVESTMENTS LIMITED
                                c/o New Medical Technologies
                                Elisabethenstrasse 23
                                CH - 4051 Basel
                                Switzerland

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:

                                BENEFIT CAPITAL MANAGEMENT
                                CORPORATION (as investment manager for the
                                Prudential Insurance Company of America separate
                                account # VCA-GA-5298)
                                39 Old Ridgebury Road E2-278
                                Danbury CT 06817
                                Attn:  Sue DeCarlo

                                By: /s/ Sue DeCarlo
                                    ------------------------------------------
                                    Name: Sue DeCarlo
                                    Title: Sr. VP and CFO
<PAGE>
                                PRISM VENTURE PARTNERS I, L.P.
                                100 Lowder Brook Drive
                                Suite 2500
                                Westwood, MA  02090

                                By: Prism Investment Partners, L.P.

                                By: Prism Venture Partners, L.L.C.

                                By: /s/ Laurie J. Thomsen
                                    ------------------------------------------
                                    Laurie J. Thomsen
                                    Managing Director

                                THE CIT GROUP/EQUITY INVESTMENTS, INC.
                                650 CIT Drive
                                Livingston, NJ 07039

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:

                                ABS EMPLOYEES' VENTURE FUND L.P.
                                1 South Street
                                Baltimore, MD 21202-3220

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:

                                BANK OF AMERICA VENTURES
                                950 Tower Lane, Suite 700
                                Foster City, CA 94404

                                By: /s/ Kate D. Mitchell
                                    ------------------------------------------
                                    Name: Kate D. Mitchell
                                    Title: Managing Director
<PAGE>
                                BA VENTURE PARTNERS II
                                c/o BankAmerica Ventures
                                950 Tower Lane, Suite 700
                                Foster City, CA 94404

                                By: /s/ Kate D. Mitchell
                                    ------------------------------------------
                                    Name: Kate D. Mitchell
                                    Title: Managing Director

                                ALTA V LIMITED PARTNERSHIP
                                One Post Office Square
                                Boston, MA 02109

                                By: Alta V Management Partners, L.P.

                                By: /s/ Terrance McGuire
                                    ------------------------------------------
                                    Name:
                                    Title:

                                CUSTOMS HOUSE PARTNERS
                                One Post Office Square
                                Boston, MA 02109

                                By: /s/ Terrance McGuire
                                    ------------------------------------------
                                    Name:
                                    Title:

                                POLARIS VENTURE PARTNERS, L.P.
                                1000 Winter Street
                                Suite 3350
                                Waltham, MA 02154

                                By: Polaris Venture Management Co., LLC,
                                    Its General Partner

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:
<PAGE>
                                POLARIS VENTURE PARTNERS FOUNDERS'
                                FUND, L.P.
                                1000 Winter Street
                                Suite 3350
                                Waltham, MA 02154

                                By: Polaris Venture Management Co., LLC
                                    Its General Partner

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:

                                THE VENTURE CAPITAL FUND OF NEW
                                ENGLAND III, L.P.
                                160 Federal Street, 23rd Floor
                                Boston, MA 02110

                                By: FH & Co. III, L.P., General Partner

                                By: /s/ William C. Mills, III
                                    ------------------------------------------
                                    Name:
                                    Title:

                                TRUSTEES OF BOSTON UNIVERSITY
                                Attn: Managing Director,
                                      Community Technology Fund
                                108 Bay State Road
                                Boston, MA 02215

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:
<PAGE>
                                BANCBOSTON VENTURES, INC.
                                175 Federal Street
                                Boston, MA 02110

                                By: /s/ Marcia T. Bates
                                    ------------------------------------------
                                    Name: Marcia T. Bates
                                    Title: Managing Director

                                AEGIS MANAGEMENT CORPORATION
                                PROFIT SHARING TRUST FBO TED R.
                                DINTERSMITH
                                c/o Charles River Ventures
                                Bay Colony Corporate Center
                                1000 Winter Street
                                Suite 3300
                                Waltham, MA 02154

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:

                                ROBERT S. LANGER
                                77 Lombard Street
                                Newton, MA 02158

                                ----------------------------------------------

                                DAVID NORMAN
                                26 Turtle Rock Court
                                Tiburon, CA 94920

                                ----------------------------------------------

                                FOR THE PURPOSES OF SECTIONS 1, 3.4 AND 4
                                ONLY

                                SHERRI C. OBERG
                                157 Bristol Road
                                Wellesley, MA 02181

                                /s/ Sherri C. Oberg
                                ----------------------------------------------
<PAGE>
                                TECHNOLOGY FUNDING PARTNERS III, L.P.,
                                A Delaware Limited Partnership
                                2000 Alameda de las Pulgas
                                San Mateo, CA 94403

                                By: Technology Funding, Inc.
                                    Managing General Partner

                                By:
                                    ------------------------------------------
                                    Vice President

                                ELAN INTERNATIONAL SERVICES, LTD.

                                102 St. James Court
                                Flatts, Smiths Parish
                                Bermuda FL 04

                                By: /s/ Kevin Insley
                                    ------------------------------------------
                                    Name:
                                    Title:
<PAGE>
                                                                      Schedule A

                                    Investors

      Elan International Services, Ltd.
      MVI Medical Venture Investments Limited
      Benefit Capital Management Corporation (as investment manager for the
            Prudential Insurance Company of America separate account #
      VCA-GA-5298)
      Prism Venture Partners I, L.P.
      The CIT Group/Equity Investments, Inc.
      ABS Employees' Venture Fund L.P.
      Bank of America Ventures
      BA Venture Partners II
      Alta V Limited Partnership
      Customs House Partners
      Polaris Venture Partners, L.P.
      Polaris Venture Partners Founders' Fund, L.P.
      The Venture Capital Fund of New England III, L.P.
      Trustees of Boston University
      BancBoston Ventures, Inc.
      Private Equity Portfolio Fund II, LLC Technology Funding Partners III,
      L.P.
      Aegis Management Corporation Profit Sharing FBO Ted R. Dintersmith
      Robert S. Langer
      David Norman
      Walter Levison Estate
<PAGE>
                                 EXHIBIT C-2

                  FIFTH AMENDED AND RESTATED CO-SALE AGREEMENT
<PAGE>
                  FIFTH AMENDED AND RESTATED CO-SALE AGREEMENT

      This Fifth Amended and Restated Co-Sale Agreement is made as of the 30th
of June, 2000 by and among Acusphere, Inc., a Delaware corporation
("Acusphere"), Harry R. Allcock, Robert S. Langer and Sherri C. Oberg
(individually, a "Founder" and collectively, the "Founders"), and each of the
investors listed on Schedule A attached hereto (individually, an "Investor" and
collectively, the "Investors").

      WHEREAS, the Founders hold certain outstanding shares of Common Stock,
$.0l par value per share (the "Common Stock"), of Acusphere; and

      WHEREAS, certain of the Investors (the "Series A Investors") hold shares
of Acusphere's Series A Convertible Preferred Stock, $.0l par value per share
(the "Series A Preferred Stock"), certain of the Investors (the "Series B
Investors") hold shares of Acusphere's Series B Convertible Preferred Stock,
$.0l par value per share (the "Series B Preferred Stock"), certain of the
Investors (the "Series C Investors") hold shares of Acusphere's Series C
Convertible Preferred Stock, $.01 par value per share (the "Series C Preferred
Stock"), certain of the Investors (the "Series D Investors") hold shares of
Acusphere's Series D Convertible Preferred Stock, $.01 par value per share ( the
"Series D Preferred Stock"), certain of the Investors (the "Series E Investors")
hold shares of Acusphere's Series E Convertible Preferred Stock, $.01 par value
per share (the "Series E Preferred Stock"), and certain of the Investors (the
"Series F Investors") hold shares of Acusphere's Series F Convertible Preferred
Stock, $.01 par value per share (the "Series F Preferred Stock"), and possess
certain co-sale rights in connection therewith, pursuant to a Fourth Amended and
Restated Co-Sale Agreement dated as of April 25, 2000 by and among Acusphere,
such Series A Investors, Series B Investors, Series C Investors, Series D
Investors, Series E Investors, Series F Investors and the Founders (the "2000
Co-Sale Agreement"); and

      WHEREAS, certain of the Investors (the "Elan Investors") are parties to
the Securities Purchase Agreement dated as of the date hereof (the "Securities
Purchase Agreement") by and among such Elan Investors and Acusphere providing,
inter alia, for the purchase by such Elan Investors of shares of Acusphere's
Series H Convertible Preferred Stock, $.0l par value per share (the "Series H
Preferred Stock"), and a convertible promissory note in the maximum aggregate
principal amount of $8,010,000 (the "Convertible Note"); and

      WHEREAS, among the conditions to the consummation of the transactions
contemplated by the Securities Purchase Agreement is the execution and delivery
of an agreement providing for certain rights of co-sale in connection with
certain transfers of Stock of Acusphere by the Founders; and

      WHEREAS, each of the parties hereto desires to set forth in a single
document the co-sale and other rights of the Investors.

      NOW, THEREFORE, in consideration of mutual promises and covenants set
forth herein, and for other good and valuable consideration the parties hereto
agree as follows:
<PAGE>
                                      -2-

1. Termination of 2000 Co-Sale Agreement. The parties hereto hereby acknowledge
and agree that the 2000 Co-Sale Agreement is hereby amended, restated and
superseded in all respects by this Agreement.

2. Definitions.

      2.1 "Stock" shall mean any and all shares of Acusphere's Common Stock now
owned or subsequently acquired by the Founders.

      2.2 "Preferred Stock" shall mean Acusphere's outstanding Series A
Preferred Stock, Series B Preferred Stock, Series C Preferred Stock, Series D
Preferred Stock, Series E Preferred Stock, Series F Preferred Stock and Series H
Preferred Stock.

      2.3 "Common Stock" shall mean (i) Acusphere's Common Stock, (ii) shares of
Common Stock issued or issuable upon conversion of Acusphere's outstanding
Series A Preferred Stock, Series B Preferred Stock, Series C Preferred Stock,
Series D Preferred Stock, Series E Preferred Stock, Series F Preferred Stock or
Series H Preferred Stock, (iii) shares of Common Stock issuable upon exercise of
outstanding options and (iv) shares of Common Stock issuable upon conversion of
any outstanding convertible securities, including the Convertible Note.

3. Sales by a Founder.

      3.1 If any Founder (the "Selling Founder") proposes to sell or transfer
any shares of Stock in one or more related transactions which will result in (i)
the transfer of 10,000 or more shares of Stock by such Founder or (ii) the
transferee of such shares holding more than fifty percent (50%) of the Common
Stock, then, subject to any right of first refusal or repurchase right in any
agreements which the Founders may have with Acusphere, such Founder shall
promptly give written notice (the "Notice") to Acusphere, the Investors and the
other Founders at least twenty (20) days prior to the closing of such sale or
transfer. The Notice shall describe in reasonable detail the proposed sale or
transfer including, without limitation, the number of shares of Stock to be sold
or transferred, the nature of such sale or transfer, the consideration to be
paid, and the name and address of each prospective purchaser or transferee. In
the event that the sale or transfer is being made pursuant to the provisions of
paragraph 4.1 or 4.2 hereof, the Notice shall state under which paragraph the
sale or transfer is being made.

      3.2 The Investors and the other Founders shall have the right, exercisable
upon written notice to the Selling Founder within fifteen (15) days after
receipt of the Notice, to participate in such sale of Stock on the same terms
and conditions set forth in the Notice.

      3.3 The Investors and the other Founders shall have the right to sell all
or any part of their pro rata portion of the number of shares of Common Stock
equal to the product obtained by multiplying (i) the aggregate number of shares
of Stock covered by the Notice by (ii) a fraction, the numerator of which is the
number of shares of Common Stock owned by the Investor or other
<PAGE>
                                      -3-

Founder, as the case may be, at the time of the sale or transfer and the
denominator of which is the total number of shares of Common Stock owned by the
Selling Founder, the Investors and the other Founders at the time of the sale or
transfer.

      3.4 If any Investor or other Founder does not elect to fully participate
in the Selling Founder's sale pursuant to this Section 3, the Selling Founder
shall promptly give notice of such failure to the Investors and/or other
Founders who did so elect (the "Participants"). Such notice may be made by
telephone if confirmed in writing within two (2) days. Each Participant shall
have five (5) days from the date such notice was given to agree to sell such
Participant's pro rata share of the unsold portion. For purposes of this
paragraph 3.4, a Participant's pro rata share shall be the ratio of (x) the
number of shares of Common Stock held by such Participant to (y) the total
number of shares of Common Stock held by all Participants.

      3.5 The Participants shall effect their participation in the sale by
promptly delivering to the Selling Founder for transfer to the prospective
purchaser one or more certificates, properly endorsed for transfer, which
represent:

            (a) the type and number of shares of Common Stock which the
Participant elects to sell; or

            (b) that number of shares of Preferred Stock which is at such time
convertible into the number of shares of Common Stock which the Participant
elects to sell; provided, however, that if the prospective purchaser objects to
the delivery of Preferred Stock in lieu of Common Stock, the Participant shall
convert such Preferred Stock into Common Stock and deliver Common Stock as
provided in this paragraph 3.5. Acusphere agrees to make any such conversion
concurrent with the actual transfer of such shares to the purchaser.

            (c) The stock certificate or certificates that the Participant
delivers to the Selling Founder pursuant to this paragraph 3.5 shall be
transferred to the prospective purchaser along with the stock certificate or
certificates representing the shares of Stock to be sold by the Selling Founder,
such number of shares of Stock to be correspondingly reduced by the
Participant's shares, in consummation of the sale of the Stock pursuant to the
terms and conditions specified in the Notice, and the Selling Founder shall
concurrently therewith remit to each Participant that portion of the sale
proceeds to which such Participant is entitled by reason of its participation in
such sale. To the extent that any prospective purchaser or purchasers prohibits
such assignment or otherwise refuses to purchase shares or other securities from
a Participant who is exercising its rights of co-sale hereunder, the Selling
Founder shall not sell to such prospective purchaser or purchasers any Stock
unless and until, simultaneously with such sale, the Selling Founder shall
purchase such shares or other securities from such Participant for the same
consideration and on the same terms and conditions as the proposed transfer
described in the Notice.

            (d) The exercise or non-exercise of the rights of the Investors or
other Founders hereunder to participate in one or more sales of Stock made by
the Selling Founder
<PAGE>
                                      -4-

shall not adversely affect their rights to participate in subsequent sales of
Stock subject to paragraph 3.1.

            (e) If all of the Investors or other Founders elect not to
participate in the sale of the Stock subject to the Notice, the Selling Founder
may, not later than sixty (60) days following delivery of the Notice, conclude a
transfer of not less than all of the Stock covered by the Notice on terms and
conditions not more favorable to the transferor than those described in the
Notice, and such transferred shares shall no longer be subject to the terms of
this Agreement. Any proposed transfer on terms and conditions more favorable
than those described in the Notice, as well as any subsequent proposed transfer
of any of the remaining Stock by the Selling Founder, shall again be subject to
the co-sale rights of Investor and shall require compliance by the Selling
Founder with the procedures described in this Section 3.

4. Exempt Transfers.

      4.1 Notwithstanding the foregoing, the co-sale rights of the Investors and
other Founders shall not apply to (i) any pledge of Stock made pursuant to a
bona fide loan transaction that creates a mere security interest, (ii) any
transfer to the ancestors, descendants or spouse or to trusts for the benefit of
such persons or a Founder; or (iii) any bona fide gift; provided that (A) the
transferring Founder shall inform the Investors and the other Founders of such
pledge, transfer or gift prior to effecting it and (B) the pledgee, transferee
or donee shall furnish the Investors and the other Founders with a written
agreement to be bound by and comply with all provisions of this agreement. Such
transferred Stock shall remain "Stock" hereunder, and such pledgee, transferee
or donee shall be treated as a "Founder" for purposes of this Agreement.

      4.2 Notwithstanding the foregoing, the provisions of Section 3 shall not
apply to the sale of any Stock (i) to the public pursuant to a registration
statement filed with, and declared effective by, the Securities and Exchange
Commission under the Securities Act of 1933, as amended (the "Securities Act")
or (ii) to Acusphere.

5. Prohibited Transfers.

      5.1 In the event a Selling Founder should sell any Stock in contravention
of the co-sale rights of the Investors and the other Founders under this
Agreement (a "Prohibited Transfer"), each Investor and other Founder, in
addition to such other remedies as may be available at law, in equity or
hereunder, shall have the put option provided below, and the Selling Founder
shall be bound by the applicable provisions of such option.

      5.2 In the event of a Prohibited Transfer, each Investor and other Founder
shall have the right to sell to the Selling Founder the type and number of
shares of Stock equal to the number of shares such Investor or other Founders,
as the case may be, would have been entitled to transfer to the purchaser under
paragraph 3.3 hereof had the Prohibited Transfer been effected pursuant to and
in compliance with the terms hereof. Such sale shall be made on the following
terms and conditions:
<PAGE>
                                      -5-

            (a) The price per share at which the shares are to be sold to the
Selling Founder shall be equal to the price per share paid by the purchaser to
the Selling Founder in the Prohibited Transfer. The Selling Founder shall also
reimburse each Investor and other Founder for any and all fees and expense,
including legal fees and expenses, incurred pursuant to the exercise or the
attempted exercise of co-sale rights under Section 3.

            (b) Within ninety (90) days after the earlier of the dates on which
the Investor or other Founder (A) received notice of the Prohibited Transfer or
(B) otherwise become aware of the Prohibited Transfer, each Investor and other
Founder shall, if exercising the option created hereby, deliver to the Selling
Founder the certificate or certificates representing shares to be sold, each
certificate to be properly endorsed for transfer.

            (c) The Selling Founder shall, upon receipt of the certificate or
certificates for the shares to be sold by any Investor or other Founder,
pursuant to this paragraph 5.2, pay the aggregate purchase price therefor and
the amount of reimbursable fees and expenses, as specified in subparagraph
5.2(a), in cash or by other means acceptable to the Investor or other Founder.

            (d) Notwithstanding the foregoing, any attempt by a Selling Founder
to transfer Stock in violation of Section 3 hereof shall be void and Acusphere
agrees it will not effect such a transfer nor will it treat any alleged
transferee as the holder of such shares without the written consent of each
Investor and other Founder; provided, however, that if an Investor or other
Founder elects to exercise the put option as discussed above, then such Investor
or other Founder shall be deemed to have provided its written consent permitting
Acusphere to transfer the Stock on its records.

6. Legend.

      6.1 Each certificate representing shares of Stock now or hereafter owned
by the Founders or issued to any person in connection with a transfer pursuant
to Section 4.1 hereof shall be endorsed with the following legend:

            "THE SALE, PLEDGE, HYPOTHECATION OR TRANSFER OF THE SECURITIES
            REPRESENTED BY THIS CERTIFICATE IS SUBJECT TO THE TERMS AND
            CONDITIONS OF A CERTAIN FIFTH AMENDED AND RESTATED CO-SALE AGREEMENT
            BY AND AMONG THE CORPORATION AND CERTAIN HOLDERS OF STOCK OF THE
            CORPORATION. COPIES OF SUCH AGREEMENT MAY BE OBTAINED UPON WRITTEN
            REQUEST TO THE SECRETARY OF THE CORPORATION."

      6.2 Each Founder agrees that Acusphere may instruct its transfer agent to
impose transfer restrictions on the shares represented by certificates bearing
the legend referred to in Section 6.1 above to enforce the provisions of this
Agreement and Acusphere agrees to promptly do so. The legend shall be removed
upon termination of this Agreement.
<PAGE>
                                      -6-

7. Miscellaneous.

      7.1 Governing Law. This Agreement shall be governed by and construed under
the laws of the Commonwealth of Massachusetts as applied to agreements among
Massachusetts residents, made and to be performed entirely within the
Commonwealth of Massachusetts.

      7.2 Amendment. Any provision may be amended and the observance thereof may
be waived (either generally or in a particular instance and either retroactively
or prospectively), only by the written consent of (i) Acusphere, (ii) the
Investors holding a majority of the aggregated Common Stock and Preferred Stock
held by the Investors (provided that if an amendment or waiver affects any
Investor in a manner that is different from the effect of such amendment or
waiver on all other Investors, then the consent of such Investor shall be
required for such waiver or amendment), and (iii) the Founders holding a
majority of the Stock held by the Founders; provided, however, that the consent
of each Founder shall be required for any amendment which results in all
Founders not being treated identically (except for differences resulting solely
from differences in the number of shares of Stock held by each of the Founders)
under this Agreement, as so amended.

      7.3 Assignment of Rights. This Agreement and the rights and obligations of
the parties hereunder shall inure to the benefit of, and be binding upon, their
respective successors, assigns and legal representatives.

      7.4 Term. This Agreement shall terminate upon the earlier of (i) the
closing of a firm commitment underwritten public offering pursuant to an
effective registration statement under the Securities Act covering the offer and
sale of Acusphere's Common Stock at a per share offering price of at least
$9.90, as adjusted for stock splits, stock dividends and other similar
adjustments, and an aggregate net offering price (less discounts and
commissions) of not less than $15,000,000 and (ii) the closing of Acusphere's
sale of all or substantially all of its assets or the acquisition of Acusphere
by another entity by means of merger or consolidation resulting in the exchange
of the outstanding shares of Acusphere's capital stock for securities or
consideration issued, or caused to be issued, by the acquiring entity or its
subsidiary.

      7.5 Ownership. Each Founder represents and warrants that he or she is the
sole legal and beneficial owner of the shares of Stock subject to this Agreement
and that no other person has any interest (other than a community property
interest) in such shares.

      7.6 Notices. All notices required or permitted hereunder shall be in
writing and shall be deemed effectively given upon personal delivery to the
party to be notified or five (5) days after deposit in the United States mail,
by registered or certified mail, postage prepaid and properly addressed to the
party to be notified as set forth on the signature page hereof or at such other
address as such party may designate by ten (10) days advance written notice to
the other parties hereto.
<PAGE>
                                      -7-

      7.7 Severability. In the event one or more of the provisions of this
Agreement should, for any reason, be held to be invalid, illegal or
unenforceable in any respect, such invalidity, illegality or unenforceability
shall not affect any other provisions of this Agreement, and this Agreement
shall be construed as if such invalid, illegal or unenforceable provision had
never been contained herein.

      7.8 Attorney Fees. In the event that any dispute among the parties to this
Agreement should result in litigation, the prevailing party in such dispute
shall be entitled to recover from the losing party all fees, costs and expenses
of enforcing any right of such prevailing party under or with respect to this
Agreement, including without limitation, such reasonable fees and expenses of
attorneys and accountants, which shall include, without limitation, all fees,
costs and expenses of appeals.

      7.9 Counterparts. This Agreement may be executed in two or more
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument. Any person who may, after
the date hereof, purchase shares of Series F Preferred Stock pursuant to the
Series F Convertible Preferred Stock Purchase Agreement dated April 25, 2000, as
amended from time to time, shall become a party to this Agreement as an
"Investor" and a holder of "Preferred Stock" and "Common Stock" for all purposes
hereunder, all upon execution of a counterpart to this Agreement signed by such
person and Acusphere.

      7.10 Stock Split. In the event of any stock split, stock dividend,
recapitalization, reorganization, or the like (i) any securities issued as a
result thereof with respect to shares of Stock shall become shares of Stock for
purposes of this Agreement and shall be endorsed with the legend set forth in
paragraph 6.1 hereof and (ii) all references to numbers of shares in this
Agreement shall be appropriately adjusted to reflect such stock dividend, stock
split, combination or other recapitalization of shares by Acusphere occurring
after the date of this Agreement.

      7.11 Aggregation of Stock. All shares of Common Stock held or acquired by
affiliated entities or persons shall be aggregated together for the purpose of
determining the availability of any rights under this Agreement.

                  [REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]
<PAGE>
      IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date first above written.

                                ACUSPHERE, INC.
                                38 Sidney Street
                                Cambridge, MA 02139

                                /s/ Sherri C. Oberg
                                ----------------------------------------------
                                Sherri C. Oberg
                                President and Chief Executive Officer

                                MVI MEDICAL VENTURE
                                INVESTMENTS LIMITED
                                c/o New Medical Technologies
                                Elisabethenstrasse 23
                                CH - 4051 Basel
                                Switzerland

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:

                                BENEFIT CAPITAL MANAGEMENT
                                CORPORATION
                                (as investment manager for the Prudential
                                Insurance Company of America separate
                                account # VCA-GA-5298)
                                39 Old Ridgebury Road E2-278
                                Danbury CT 06817
                                Attn:  Sue DeCarlo

                                By: /s/ Sue DeCarlo
                                    ------------------------------------------
                                    Name: Sue DeCarlo
                                    Title: Sr VP and CFO
<PAGE>
                                PRISM VENTURE PARTNERS I, L.P.
                                100 Lowder Brook Drive
                                Suite 2500
                                Westwood, MA  02090

                                By: Prism Investment Partners, L.P.

                                By: Prism Venture Partners, L.L.C.

                                By: /s/ Laurie J. Thomsen
                                    ------------------------------------------
                                    Laurie J. Thomsen
                                    Managing Director

                                THE CIT GROUP/EQUITY INVESTMENTS, INC.
                                650 CIT Drive
                                Livingston, NJ 07039

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:

                                ABS EMPLOYEES' VENTURE FUND L.P.
                                1 South Street
                                Baltimore, MD 21202-3220

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:

                                BANK OF AMERICA VENTURES
                                950 Tower Lane, Suite 700
                                Foster City, CA 94404

                                By: /s/ Kate D. Mitchell
                                    ------------------------------------------
                                    Name: Kate D. Mitchell
                                    Title: Managing Director
<PAGE>
                                BA VENTURE PARTNERS II
                                c/o BankAmerica Ventures
                                950 Tower Lane, Suite 700
                                Foster City, CA 94404

                                By: /s/ Kate D. Mitchell
                                    ------------------------------------------
                                    Name: Kate D. Mitchell
                                    Title: Managing Director

                                ALTA V LIMITED PARTNERSHIP
                                One Post Office Square
                                Boston, MA 02109

                                By: Alta V Management Partners, L.P.

                                By: /s/ Terrance McGuire
                                    ------------------------------------------
                                    Name:
                                    General Partner

                                CUSTOMS HOUSE PARTNERS
                                One Post Office Square
                                Boston, MA 02109

                                By: /s/ Terrance McGuire
                                    ------------------------------------------
                                    Name:
                                    General Partner

                                POLARIS VENTURE PARTNERS, L.P.
                                1000 Winter Street
                                Suite 3350
                                Waltham, MA 02154

                                By: Polaris Venture Management Co., LLC
                                    Its General Partner

                                By:
                                    ------------------------------------------
                                    Name:
                                    Member
<PAGE>
                                POLARIS VENTURE PARTNERS FOUNDERS'
                                FUND, L.P.
                                1000 Winter Street
                                Suite 3350
                                Waltham, MA 02154

                                By: Polaris Venture Management Co., LLC
                                    Its General Partner

                                By:
                                    ------------------------------------------
                                    Name:
                                    Member

                                THE VENTURE CAPITAL FUND OF NEW
                                ENGLAND III, L.P.
                                160 Federal Street, 23rd Floor
                                Boston, MA 02110

                                By: FH & Co., III, L.P., General Partner

                                By: /s/ William C. Mills III
                                    ------------------------------------------
                                    William C. Mills III
                                    General Partner

                                TRUSTEES OF BOSTON UNIVERSITY
                                108 Bay State Road
                                Boston, MA 02215
                                Attn:  B.U.N.P.

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:
<PAGE>
                                BANCBOSTON VENTURES, INC.
                                100 Federal Street
                                Boston, MA 02110

                                By: /s/ Marcia T. Bates
                                    ------------------------------------------
                                    Name: Marcia T. Bates
                                    Title: Managing Director

                                AEGIS MANAGEMENT CORPORATION PROFIT
                                SHARING TRUST FBO TED R. DINTERSMITH
                                c/o Charles River Ventures
                                Bay Colony Corporate Center
                                1000 Winter Street
                                Suite 3300
                                Waltham, MA 02154

                                By:
                                    ------------------------------------------
                                    Name:
                                    Title:

                                DAVID NORMAN
                                26 Turtle Rock Court
                                Tiburon, CA 94920

                                ----------------------------------------------

                                TECHNOLOGY FUNDING PARTNERS III, L.P.
                                2000 Alameda de las Pulgas
                                San Mateo, CA 94403

                                By: Technology Funding, Inc.
                                    Managing General Partner

                                By:
                                    ------------------------------------------
                                    Name:
                                    Vice President
<PAGE>
                                TECHNOLOGY FUNDING VENTURE
                                PARTNERS V, AN AGGRESSIVE GROWTH
                                FUND, L.P.
                                2000 Alameda de las Pulgas
                                San Mateo, CA 94403

                                By: Technology Funding, Inc.
                                    Managing General Partner

                                By:
                                    ------------------------------------------
                                    Name:
                                    Vice President

                                TECHNOLOGY FUNDING MEDICAL
                                PARTNERS I, L.P.
                                2000 Alameda de las Pulgas
                                San Mateo, CA 94403

                                By: Technology Funding Inc.
                                    Managing General Partner

                                By:
                                    ------------------------------------------
                                    Name:
                                    Vice President

                                ELAN INTERNATIONAL SERVICES, LTD.
                                102 St. James Court
                                Flatts, Smiths Parish
                                Bermuda FL 04

                                By: /s/ Kevin Insley
                                    ------------------------------------------
                                    Name:
                                    Title:
<PAGE>
                                FOUNDERS:

                                ROBERT S. LANGER
                                77 Lombard Street
                                Newton, MA 02158

                                ----------------------------------------------

                                SHERRI C. OBERG
                                157 Bristol Road
                                Wellesley, MA 02181

                                /s/ Sherri C. Oberg
                                ----------------------------------------------

                                HARRY R. ALLCOCK
                                494 Kemmerer Road
                                State College, PA 16801

                                ----------------------------------------------
<PAGE>
                                                                      SCHEDULE A

                                    Investors

Elan International Services, Ltd.
MVI Medical Venture Investments Limited
Benefit Capital Management Corporation (as investment manager for the
      Prudential Insurance Company of America separate account # VCA-GA-5298)
Prism Venture Partners I, L.P.
The CIT Group/Equity Investments, Inc.
ABS Employees' Venture Fund L.P.
Bank of America Ventures
BA Venture Partners II
Alta V Limited Partnership
Customs House Partners
Polaris Venture Partners, L.P.
Polaris Venture Partners Founders' Fund, L.P.
The Venture Capital Fund of New England III, L.P.
Trustees of Boston University
BancBoston Ventures, Inc.
Private Equity Portfolio Fund II, LLC
Technology Funding Partners III, L.P.
Technology Funding Venture Partners V, an Aggressive Growth Fund, L.P.
Technology Funding Medical Partners I, L.P.
Aegis Management Corporation Profit Sharing Trust FBO Ted R. Dintersmith
David Norman
Estate of Walter Levison
<PAGE>
                                    EXHIBIT D

                   FORM OF NEWCO REGISTRATION RIGHTS AGREEMENT
<PAGE>
                                    EXHIBIT E

                           FORM OF EXCHANGE AGREEMENT
<PAGE>
                                    EXHIBIT F

               FORM OF OPINION OF TESTA, HURWITZ & THIBEAULT, LLP

                                  June 30, 2000

Elan International Services, Ltd.
102 St. James Court
Flatts, Smith's Parish
Bermuda FL 04

      Re:   Acusphere. Inc. Financing

Ladies and Gentlemen:

      We have acted as counsel to Acusphere, Inc., a Delaware corporation (the
"Company"), in connection with the execution and delivery of the Securities
Purchase Agreement (including the exhibits thereto, the "Agreement") of even
date herewith between the Company and you relating to the issuance and sale by
the Company of (i) up to 1,232,308 shares of its Series G Convertible Preferred
Stock, $.01 par value per share (the "Series G Shares"), (ii) up to 1,127,819
shares of its Series F Convertible Preferred Stock, $.01 par value per share
(the " Series H Shares") and (iii) its Convertible Promissory Note in the
maximum face amount of $8,010,000 (the "Note"), and the related Sixth Amended
and Restated Investors' Rights Agreement (the "IRA") and Fifth Amended and
Restated Co-Sale Agreement (the "Co-Sale Agreement"). The Agreement, the Note,
the IRA and the Co-Sale Agreement are referred to collectively herein as the
"Financing Agreements." Capitalized terms used herein and not otherwise defined
herein shall have the meanings assigned to such terms in the Agreement.

      In connection with the opinion set forth below, we have examined
originals, or copies certified or otherwise identified to our satisfaction, of
such documents, certificates (copies of which have been furnished to you),
instruments and corporate records that we deemed appropriate for the purposes of
this opinion. We have relied upon certificates of public officials and officers
of the Company with respect to factual matters contained therein; however,
nothing has come to our attention which would lead us to believe that such facts
are inaccurate or incomplete. We have also relied on the representations and
warranties contained in the Agreement with respect to factual matters. In our
examination, we have assumed the genuineness of all signatures, the authenticity
of all documents submitted to us as originals, the conformity to original
documents of all documents submitted to us as certified or photostatic copies
and the authenticity of the originals of such latter documents.

      Where we render an opinion "to the best of our knowledge" or concerning an
item "known to us" or our opinion otherwise refers to our knowledge, our
opinion, with respect to matters of fact, is based solely upon inquiry of
attorneys within this firm who perform legal services for the Company, receipt
of a certificate executed by an officer of the Company (copies of which have
<PAGE>
                                       -2-

been furnished to you), an examination of documents in our files and documents
made available to us by the Company, or such other investigation, if any, as we
specifically set forth herein.

      The opinion hereinafter expressed is qualified to the extent that the
enforceability of any of the agreements, documents or obligations referred to
herein may be subject to or affected by applicable bankruptcy, insolvency,
fraudulent conveyance or transfer, reorganization, moratorium or other laws
relating to or affecting the rights of creditors generally. We do not express
any opinion herein as to the availability of any equitable or other specific
remedy upon breach of any of the agreements, documents or obligations referred
to herein. We are members of the Bar of the Commonwealth of Massachusetts and
are not expert in and express no opinion with respect to the laws of any
jurisdiction other than the laws of the Commonwealth of Massachusetts, the
United States of America and the General Corporation Law of the State of
Delaware. Accordingly, for purposes of this opinion we assume that the Financing
Agreements are governed by the laws of the Commonwealth of Massachusetts. We
assume that the Financing Agreements have been duly authorized, executed and
delivered by you and all other parties (other than the Company) thereto and that
you and all such other parties (other than the Company) have all requisite legal
capacity, power and authority and have taken all necessary action to effect the
transactions contemplated by each such agreement to which it is a party. We
assume that there has been full disclosure to you and the stockholders of the
Company of all material facts. We render or imply no opinion with respect to
compliance with applicable antifraud statutes, rules or regulations of
applicable state or federal law. We express no opinion as to the enforceability
of Section 2.10 of the IRA.

      Insofar as the opinion expressed herein relates to factual matters, we
have relied upon the representations and warranties in the Financing Agreements,
an examination of documents in our files and documents made available to us by
the Company and upon certificates of even date herewith of the Chief Executive
Officer of the Company, copies of which have been furnished to you, and nothing
has come to our attention leading us to question the accuracy thereof.

      For purposes of our opinion in paragraph 1 below as to the valid existence
and good standing of the Company, we have relied upon certificates of the
Secretaries of State of Delaware and Massachusetts, copies of which have been
furnished to you. For purposes of our opinion in paragraph 2 below, we have
reviewed the Company's minute book and stock transfer records and have relied
upon a certificate of even date herewith of the Company.

      Based on and subject to the foregoing, we are of the opinion that:

      1. The Company is a corporation duly organized and validly existing and in
good standing under the laws of the State of Delaware, with the requisite
corporate power and authority to own its property and to carry on its business
as presently conducted and to execute, deliver and perform its obligations under
the Financing Agreements and to consummate the transactions contemplated
thereby. The Company is qualified to do business and is in good standing as a
foreign corporation in the Commonwealth of Massachusetts.
<PAGE>
                                       -3-

      2. As of the Closing, the authorized capital stock of the Company consists
of 40,000,000 shares of Common Stock, $.01 par value, 2,565,561 shares of which
are issued and outstanding, and 28,110,127 shares of Preferred Stock, $.01 par
value (the "Preferred Stock"). Of the Preferred Stock, 816,169 shares have been
designated Series A Convertible Preferred Stock, all of which are issued and
outstanding, 2,315,625 shares have been designated Series B Convertible
Preferred Stock, 2,265,625 of which are issued and outstanding, 3,980,140 shares
have been designated Series C Convertible Preferred Stock, 3,913,551 of which
are issued and outstanding, 3,498,882 shares have been designated Series D
Convertible Preferred Stock, 3,405,624 of which are issued and outstanding,
1,211,774 shares have been designated Series E Convertible Preferred Stock,
757,577 of which are issued and outstanding, 13,177,410 shares have been
designated Series F Convertible Preferred Stock, of which 2,525,330 are issued
and outstanding, 1,982,308 shares have been designated Series G Convertible
Preferred, none of which is outstanding, and 1,127,819 shares have been
designated Series H Convertible Preferred Stock, none of which are outstanding.
All of such issued and outstanding shares have been duly authorized and validly
issued and are fully paid and nonassessable. All corporate and stockholder
action on the part of the Company necessary for the authorization and issuance
of the Series G Convertible Preferred Stock, the Series H Convertible Preferred
Stock and the shares of Common Stock issuable upon conversion thereof, has been
taken and all of the shares of Series G Convertible Preferred Stock and Series H
Convertible Preferred Stock, when issued in compliance with the provisions of
the Agreement, will be validly issued and fully paid and nonassessable. The
rights, restrictions, privileges and preferences in respect of each class or
series of authorized capital stock of the Company are as set forth in the
Charter, and such rights, restrictions, privileges and preferences are valid and
enforceable against the Company. Except for (A) the conversion privileges of the
Series A Convertible Preferred Stock, the Series B Convertible Preferred Stock,
the Series C Convertible Preferred Stock, the Series D Convertible Preferred
Stock, the Series E Convertible Preferred Stock, the Series F Convertible
Preferred Stock, the Series G Convertible Preferred Stock and the Series H
Convertible Preferred Stock, (B) those rights disclosed in the Sixth Amended and
Restated Investors' Rights Agreement, (C) the conversion privileges of Comdisco,
Inc. pursuant to that Subordinated Loan and Security Agreement dated as of
October 19, 1998, as amended, and (D) as otherwise set forth in disclosure
schedules to the Agreement, there are no preemptive rights., or to the best of
our knowledge, any options, warrants, conversion privileges or other rights (or
agreements for any such rights) outstanding to purchase or otherwise obtain an),
of the Company's securities. The offer and sale of all shares of capital stock
and other securities of the Company issued prior to the date hereof complied
with or were exempt from all registration requirements under all applicable
federal and state securities laws.

      3. The shares of Common Stock issuable upon conversion of the Series G
Shares, including shares of Series G Shares payable as in-kind dividends on the
Series G Shares, the Series 1i Shares and the Note (the "Conversion Shares")
have been duly and validly reserved for issuance, and are not subject to any
statutory preemptive rights or rights of first refusal, and, when issued upon
such conversion, will be validly issued, fully paid and nonassessable.

      4. Each of the Financing Agreements have been validly and duly authorized
by the Company, duly executed and delivered by an authorized officer of the
Company and constitute a legal, valid and binding obligation of the Company
enforceable in accordance with its terms.
<PAGE>
                                       -4-

      5. All consents, approvals, orders or authorizations of, and all
qualifications, registrations, designations, declarations or filings with, any
federal or state governmental authority on the part of the Company required in
connection with the consummation of the transactions contemplated by the
Financing Agreements, except such post-closing filings as may be required after
the date hereof under applicable federal and state securities laws, which
filings will be made within the requisite period, have been obtained, and are
effective, as of the Closing, and we are not aware of any proceedings, or
written threat of any proceedings, which question the validity thereof.

      6. Assuming the accuracy of your representations and warranties as set
forth in the Agreement, and based in part upon the same, the offer and sale of
the Securities being purchased by you pursuant to the terms of the Agreement are
exempt from (i) the registration requirements of Section 5 of the Securities Act
of 1933, as amended, by virtue of Section 4(2) thereof and (ii) the registration
requirements of Chapter 110A of the Massachusetts General Laws and, under such
securities laws as they presently exist, the issuance of Common Stock upon
conversion of the Series G Shares, the Series H Shares and the Note would also
be exempt from such registration and qualification requirements.

      7. The execution, delivery, performance of and compliance with the terms
of the Financing Agreements will not conflict with or violate any provision of
any applicable federal, state or local law, rule or regulation or any provision
of the Charter or the Company's Amended and Restated Bylaws and, to the best of
our knowledge, will not conflict with or constitute a default under the
provision of any judgment, writ, decree or order, known to us to which the
Company is a party or by which the Company is bound.

      8. Neither the Charter nor the Amended and Restated Bylaws of the Company
is in violation of any, provision of the General Corporation Law of the State of
Delaware.

      This opinion is solely for your benefit, and it may not be quoted or
relied on by any other person without our prior written consent.

                                    Very truly yours,

                                    TESTA, HURWITZ & THIBEAULT, LLP

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