Document:

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                                                                     Exhibit 4.3

                                                                  EXECUTION COPY

                           ALTUS PHARMACEUTICALS INC.

                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

     This Amended and Restated Investor Rights Agreement (this "Agreement")
dated as of May 21, 2004 is entered into by and among Altus Pharmaceuticals
Inc., a Delaware corporation (the "Company") (f/k/a "Altus Biologics Inc."),
Vertex Pharmaceuticals Incorporated, a Massachusetts corporation ("Vertex"),
Cystic Fibrosis Foundation Therapeutics, Inc., a Maryland corporation ("CFF"),
Joshua S. Boger, Richard H. Aldrich, and Thomas G. Auchincloss, Jr.
(collectively, the "Vertex Officers") and the individuals and entities listed on
Exhibit A attached hereto (the "Purchasers"), and amends and restates that
certain Investor Rights Agreement dated September 26, 2001, among the Company
and the parties thereto as amended as of December 7, 2001 (the "Prior
Agreement"). Vertex, CFF and the Purchasers are sometimes referred to herein as
the "Holders."

                                    Recitals

     WHEREAS, the Company and certain of the Purchasers have entered into a
Series C Convertible Preferred Stock and Warrant Purchase Agreement of even date
herewith (the "Purchase Agreement");

     WHEREAS, the execution and delivery of this Agreement is a condition to the
consummation of the transactions contemplated by the Purchase Agreement;

     WHEREAS, the parties to the Prior Agreement desire to amend and restate the
Prior Agreement in its entirety so as to read in its entirety as set forth
herein;

     WHEREAS, the undersigned parties represent the necessary voting power
required to amend the Prior Agreement pursuant to Section 7(g) thereof; and

     WHEREAS, the Company, Vertex, CFF and the Purchasers desire to provide for
certain arrangements with respect to (i) the registration of shares of capital
stock of the Company under the Securities Act (as defined below), (ii)
percentage maintenance rights with respect to certain issuances of securities of
the Company, and (iii) certain covenants of the Company and other parties
hereto.

     NOW, THEREFORE, in consideration of the mutual promises and covenants
contained in this Agreement, the parties hereto agree as follows:

     1. Certain Definitions.

     As used in this Agreement, the following terms shall have the following
respective meanings:
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               "Board of Directors" means the Board of Directors of the Company.

               "Commission" means the Securities and Exchange Commission, or any
other federal agency at the time administering the Securities Act.

               "Common Stock" means the common stock, $.01 par value per share,
of the Company.

               "Exchange Act" means the Securities Exchange Act of 1934, as
amended, or any successor federal statute, and the rules and regulations of the
Commission issued under such Act, as they each may, from time to time, be in
effect.

               "Initiating Holders" means the Stockholders initiating a request
for registration pursuant to Section 2.1(a) or 2.1(b), as the case may be.

               "Initial Public Offering" means the initial underwritten public
offering of shares of Common Stock pursuant to an effective Registration
Statement.

               "Prospectus" means the prospectus included in any Registration
Statement, as amended or supplemented by an amendment or prospectus supplement,
including post-effective amendments, and all material incorporated by reference
or deemed to be incorporated by reference in such Prospectus.

               "Purchaser Warrants" means the warrants to purchase shares of the
Series C Convertible Preferred Stock issued to certain of the Purchasers
pursuant to the terms of the Purchase Agreement and warrants to purchase shares
of the Series B Convertible Preferred Stock held by certain of the Purchasers.

               "Registration Expenses" means the expenses described in Section
2.4.

               "Registrable Shares" means (i) the shares of Common Stock issued
or issuable upon conversion of the Shares, (ii) any shares of Common Stock, and
any shares of Common Stock issued or issuable upon the conversion or exercise of
any other securities of the Company, now owned or hereafter acquired by the
Purchasers, Vertex, the Vertex Officers or CFF and (iii) any other shares of
Common Stock issued in respect of such shares (because of stock splits, stock
dividends, reclassifications, recapitalizations, or similar events); provided,
however, that shares of Common Stock which are Registrable Shares shall cease to
be Registrable Shares upon the earlier of:

               (i) any sale pursuant to a Registration Statement or Rule 144
under the Securities Act,

               (ii) any sale in any manner to a person or entity which, by
virtue of Section 5 of this Agreement, is not entitled to the rights provided by
this Agreement; or

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               (iii) as to the beneficial owner of such Registrable Shares, at
such time after the Closing of the Company's Initial Public Offering when such
beneficial owner is able to sell all of his or its Registrable Shares in a
three-month period pursuant to Rule 144 under the Securities Act (without giving
effect to Rule 144(k) thereunder); provided that, notwithstanding this clause
(iii), such Registrable Shares shall continue to be Registrable Shares at any
time during the term hereof that such beneficial owner is subject to any "market
stand off" "lock up" or similar type of obligation with respect to any of the
Company's securities (and such shares have not been previously sold in a sale
under clause (i) or (ii) above).

               Wherever reference is made in this Agreement to a request or
consent of holders of a certain percentage of Registrable Shares, the
determination of such percentage shall include shares of Common Stock issuable
upon conversion or exercise of convertible securities and warrants convertible
into or exercisable for the Shares even if such conversion or exercise has not
been effected.

               "Registration Statement" means a registration statement filed by
the Company with the Commission for a public offering and sale of securities of
the Company (other than a registration statement on Form S-8 or Form S-4, or
their successors, or any other form for a similar limited purpose, or any
registration statement covering only securities proposed to be issued in
exchange for securities or assets of another corporation).

               "Securities Act" means the Securities Act of 1933, as amended, or
any successor federal statute, and the rules and regulations of the Commission
issued under such Act, as they each may, from time to time, be in effect.

               "Selling Stockholder" means any Stockholder owning Registrable
Shares included in a Registration Statement.

               "Series B Director" means a director of the Company elected by
the holders of the outstanding Series B Convertible Preferred Stock in
accordance with the terms of the Company's Certificate of Incorporation, as in
effect from time to time (the "Charter"), and subject to that certain Amended
and Restated Stockholders' Voting Agreement dated as of even date herewith by
and among the Company, the Purchasers and Vertex (each as defined therein) (the
"Voting Agreement").

               "Series C Director" means a director of the Company elected by
the holders of a majority of the outstanding shares of Series C Convertible
Preferred Stock in accordance with the terms of the Charter and subject to the
Voting Agreement.

               "Series B Convertible Preferred Stock" means the Company's Series
B Convertible Preferred Stock, $.01 par value per share.

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               "Series C Convertible Preferred Stock" means the Company's Series
C Convertible Preferred Stock, $.01 par value per share.

               "Shares" means shares of Series B Convertible Preferred Stock and
Series C Convertible Preferred Stock issued to the Purchasers and issuable upon
exercise of the Purchaser Warrants.

               "Stockholders" means the Purchasers, Vertex, the Vertex Officers,
CFF and any persons or entities to whom the rights granted under this Agreement
are transferred by any Purchasers, their successors or assigns pursuant to
Section 5 hereof.

               "Triggering Public Offering" means either (i) a public offering
of the Company's Common Stock which triggers mandatory conversion into Common
Stock of all of the Company's outstanding preferred stock, $.01 par value per
share, which is convertible into Common Stock (the "Convertible Preferred
Stock") pursuant to the terms of the Charter or in connection with which all of
the outstanding shares of Convertible Preferred Stock are otherwise converted
into shares of Common Stock, or (ii) an Initial Public Offering consented to by
the holders of a majority of the Registrable Shares.

     2. Registration Rights.

          2.1 Required Registrations.

               (a) At any time after the earlier of (x) two years from the date
hereof or (y) six months after the closing of the Initial Public Offering, a
Stockholder or Stockholders may request, in writing, that the Company effect the
registration on Form S-1 or Form S-2 (or any successor form) of Registrable
Shares owned by such Stockholder or Stockholders having an aggregate value of at
least $20,000,000 (based on the then current market price or fair value of the
Common Stock as determined in good faith by the Board of Directors).

               (b) At any time after the Company becomes eligible to file a
Registration Statement on Form S-3 (or any successor form relating to secondary
offerings), a Stockholder or Stockholders holding Registrable Shares may
request, in writing, that the Company effect the registration on Form S-3 (or
its successor form), of Registrable Shares having an aggregate value of at least
$10,000,000 (based on the then current public market price of the Common Stock).

               (c) Upon receipt of any request for registration pursuant to this
Section 2, the Company shall promptly give written notice of such proposed
registration to all other Stockholders. Such Stockholders shall have the right,
by giving written notice to the Company within 30 days after the Company
provides its notice, to elect to have included in such registration such of
their Registrable Shares as such Stockholders may request in such notice of
election, subject in the case of an underwritten offering to the approval of the
managing underwriter as provided in Section 2.1(d) below. Thereupon, the Company
shall, as expeditiously as possible, use its reasonable best efforts to effect

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the registration on an appropriate registration form of all Registrable Shares
which the Company has been requested to so register (provided, however, that in
the case of a registration requested under Section 2.1(b), the Company will only
be obligated to effect such registration on Form S-3 (or any successor form)).

               (d) If the Initiating Holders intend to distribute the
Registrable Shares covered by their request by means of an underwriting, they
shall so advise the Company as a part of their request made pursuant to Section
2.1(a) or (b), as the case may be, and the Company shall include such
information in its written notice referred to in Section 2.1(c). The right of
any other Stockholder to include its Registrable Shares in such registration
pursuant to Section 2.1(a) or (b), as the case may be, shall be conditioned upon
such other Stockholder's participation in such underwriting on the terms set
forth herein. If the Company desires that any officers or directors of the
Company holding securities of the Company be included in any registration for an
underwritten offering requested pursuant to this Section 2.1(d), the Company may
include the securities of such officers and directors in such registration and
underwriting on the terms set forth herein. The Company shall (together with all
Stockholders, officers and directors proposing to distribute their securities
through such underwriting) enter into an underwriting agreement in customary
form (including, without limitation, customary indemnification and contribution
provisions on the part of the Company) with the managing underwriter; provided
that such underwriting agreement shall not provide for indemnification or
contribution obligations on the part of Stockholders materially greater than the
obligations of the Stockholders pursuant to Section 2.5. Notwithstanding any
other provision of this Section 2.1(d), if the managing underwriter advises the
Company that the inclusion of all shares requested to be registered would
adversely affect the offering, the securities of the Company held by officers or
directors of the Company (other than Registrable Shares) shall be excluded from
such registration and underwriting to the extent deemed advisable by the
managing underwriter, and if a further limitation of the number of shares is
required, the number of shares that may be included in such registration and
underwriting shall be allocated among all holders of Registrable Shares
requesting registration in proportion, as nearly as practicable, to the
respective number of Registrable Shares held by them at the time of the request
for registration made by the Initiating Holders pursuant to Section 2.1(a) or
(b), as the case may be. If any holder of Registrable Shares, officer or
director who has requested inclusion in such registration as provided above
disapproves of the terms of the underwriting, such person may elect to withdraw
therefrom by written notice to the Company, and the securities so withdrawn
shall also be withdrawn from registration. If the managing underwriter has not
limited the number of Registrable Shares or other securities to be underwritten,
the Company may include securities for its own account in such registration if
the managing underwriter so agrees and if the number of Registrable Shares and
other securities which would otherwise have been included in such registration
and underwriting will not thereby be limited.

               (e) The Initiating Holders shall have the right to select the
managing underwriter(s) for any underwritten offering requested pursuant to
Section 2.1(a) or (b), subject to the approval of the Company, which approval
will not be unreasonably withheld, conditioned or delayed.

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               (f) The Company shall not be required to effect more than three
registrations pursuant to Section 2.1(a) in total, or in any 12-month period
more than two registrations pursuant to Section 2.1(b). In addition, the Company
shall not be required to effect any Registration Statement hereunder (other than
on Form S-3 or any successor form relating to secondary offerings) within six
months after the effective date of the Registration Statement relating to the
Initial Public Offering or within three months after the effective date of any
other Registration Statement relating to an underwritten public offering. For
purposes of this Section 2.1(f), a Registration Statement shall not be counted
until such time as such Registration Statement has been declared effective by
the Commission (unless the Initiating Holders withdraw their request for such
registration (other than as a result of information concerning the business or
financial condition of the Company which is made known to the Stockholders after
the date on which such registration was requested) and elect not to pay the
Registration Expenses therefor pursuant to Section 2.4). For purposes of this
Section 2.1(f), a Registration Statement shall not be counted if, as a result of
an exercise of the underwriter's cut-back provisions, less than seventy-five
percent (75%) of the total number of Registrable Shares that Stockholders have
requested to be included in such Registration Statement are so included.

               (g) If at the time of any request to register Registrable Shares
by Initiating Holders pursuant to this Section 2.1, the Company is engaged or
has plans to engage in a registered public offering or is engaged in any other
activity which, in the good faith determination of the Board of Directors, would
be adversely affected by the requested registration, then the Company may at its
option direct that such request be delayed for a period not in excess of 90 days
from the date of such request, such right to delay a request to be exercised by
the Company not more than once in any 12-month period.

          2.2 Incidental Registration.

               (a) During the period from 180 days following the Initial Public
Offering to five (5) years following the Triggering Public Offering, whenever
the Company proposes to file a Registration Statement (other than a Registration
Statement filed pursuant to Section 2.1), it will, prior to such filing, give
written notice to all Stockholders of its intention to do so. Upon the written
request of a Stockholder or Stockholders given within 20 days after the Company
provides such notice (which request shall state the intended method of
disposition of such Registrable Shares), the Company shall use its reasonable
best efforts to cause all Registrable Shares which the Company has been
requested by such Stockholder or Stockholders to register to be registered under
the Securities Act to the extent necessary to permit their sale or other
disposition in accordance with the intended methods of distribution specified in
the request of such Stockholder or Stockholders, subject to Section 2.2(b)
below; provided that the Company shall have the right to postpone or withdraw
any registration effected pursuant to this Section 2.2 without obligation to any
Stockholder.

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               (b) If the registration for which the Company gives notice
pursuant to Section 2.2(a) is a registered public offering involving an
underwriting, the Company shall so advise the Stockholders as a part of the
written notice given pursuant to Section 2.2(a). In such event, the right of any
Stockholder to include its Registrable Shares in such registration pursuant to
this Section 2.2 shall be conditioned upon such Stockholder's participation in
such underwriting on the terms set forth herein. All Stockholders proposing to
distribute their securities through such underwriting shall enter into an
underwriting agreement in customary form with the underwriter or underwriters
selected for the underwriting by the Company. Notwithstanding any other
provision of this Section 2.2, if the managing underwriter determines that the
inclusion of all shares requested to be registered would adversely affect the
offering, the Company may limit the number of Registrable Shares to be included
in the registration and underwriting. The Company shall so advise all holders of
Registrable Shares requesting registration, and the number of shares that are
entitled to be included in the registration and underwriting shall be allocated
in the following manner: the securities of the Company held by holders other
than Registrable Shares held by Stockholders shall be excluded from such
registration and underwriting to the extent deemed advisable by the managing
underwriter; and, if a further limitation on the number of shares is required,
the number of shares that may be included in such registration and underwriting
shall be allocated among all Stockholders requesting registration in proportion,
as nearly as practicable, to the respective number of Registrable Shares which
they held at the time the Company gives the notice specified in Section 2.2(a),
provided that the number of Registrable Shares permitted to be included therein
shall in any event be at least fifty percent (50%) of the securities included
therein (based on aggregate market values). If any Stockholder would thus be
entitled to include more securities than such holder requested to be registered,
the excess shall be allocated among other requesting Stockholders pro rata in
the manner described in the preceding sentence. If any holder of Registrable
Shares or any officer or director disapproves of the terms of any such
underwriting, such person may elect to withdraw therefrom by written notice to
the Company, and any Registrable Shares or other securities excluded or
withdrawn from such underwriting shall be withdrawn from such registration.

          2.3 Registration Procedures.

               (a) If and whenever the Company is required by the provisions of
this Agreement to use its reasonable best efforts to effect the registration of
any Registrable Shares under the Securities Act, the Company shall:

                    (i) file with the Commission a Registration Statement with
respect to such Registrable Shares and use its reasonable best efforts to cause
such Registration Statement to become effective as soon as possible;

                    (ii) as expeditiously as possible prepare and file with the
Commission any amendments and supplements to such Registration Statement and the
Prospectus included in such Registration Statement as may be necessary to comply
with the provisions of the Securities Act (including the anti-fraud provisions
thereof) and

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to keep such Registration Statement effective for 12 months from the effective
date or such lesser period until all such Registrable Shares are sold;

                    (iii) as expeditiously as possible furnish to each Selling
Stockholder such reasonable numbers of copies of the Prospectus, including any
preliminary Prospectus, in conformity with the requirements of the Securities
Act, and such other documents as such Selling Stockholder may reasonably request
in order to facilitate the public sale or other disposition of the Registrable
Shares owned by such Selling Stockholder;

                    (iv) as expeditiously as possible use its reasonable best
efforts to register or qualify such Registrable Shares covered by such
Registration Statement under the securities or Blue Sky laws of such states as
the Selling Stockholders shall reasonably request, and do any and all other acts
and things that may reasonably be necessary or desirable to enable the Selling
Stockholders to consummate the public sale or other disposition in such states
of such Registrable Shares owned by the Selling Stockholders; provided, however,
that the Company shall not be required in connection with this paragraph (iv) to
qualify as a foreign corporation or execute a general consent to service of
process in any jurisdiction unless the Company is already subject to such
jurisdiction;

                    (v) as expeditiously as possible, use its reasonable best
efforts to cause all such Registrable Shares to be listed on each securities
exchange or automated quotation system on which similar securities issued by the
Company are then listed;

                    (vi) promptly provide a transfer agent and registrar for all
such Registrable Shares not later than the effective date of such Registration
Statement;

                    (vii) promptly make available for inspection by the Selling
Stockholders, any managing underwriter participating in any disposition pursuant
to such Registration Statement, and any attorney or accountant or other agent
retained by any such underwriter or selected by the Selling Stockholders, all
financial and other records, pertinent corporate documents and properties of the
Company and cause the Company's officers, directors, employees and independent
accountants to supply all information reasonably requested by any such seller,
underwriter, attorney, accountant or agent in connection with such Registration
Statement;

                    (viii) as expeditiously as possible, notify each Selling
Stockholder, promptly after it shall receive notice thereof, of the time when
such Registration Statement has become effective or a supplement to any
Prospectus forming a part of such Registration Statement has been filed;

                    (ix) as expeditiously as possible following the
effectiveness of such Registration Statement, notify each seller of such
Registrable

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Shares of any request by the Commission for the amending or supplementing of
such Registration Statement or any Prospectus forming part of such Registration
Statement;

                    (x) use its reasonable best efforts to furnish, on the date
that such Registrable Shares are delivered to the underwriters for sale, if such
securities are being sold through underwriters, (1) an opinion, dated as of such
date, of the counsel representing the Company 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, and (2) a
letter, dated as of such date, from the independent certified public accountants
of the Company, in form and substance as is customarily given by independent
certified public accountants to underwriters in an underwritten public offering,
addressed to the underwriters; and

                    (xi) execute and deliver such instruments and take such
other actions as the Holders of the Registrable Shares covered by such
Registration Statement may reasonably request in order to facilitate the
effectiveness of such Registration Statement and qualification or compliance
under applicable Blue Sky laws, and the disposition of the shares covered by
such Registration Statement.

               (b) If the Company has delivered a Prospectus to the Selling
Stockholders and after having done so such Prospectus is amended to comply with
the requirements of the Securities Act, the Company shall promptly notify the
Selling Stockholders and, if requested, the Selling Stockholders shall
immediately cease making offers of Registrable Shares pursuant to such
Prospectus and return all such Prospectuses to the Company. The Company shall
promptly provide the Selling Stockholders with revised Prospectuses and,
following receipt of the revised Prospectuses, the Selling Stockholders shall be
free to resume making offers of the Registrable Shares pursuant to the revised
Prospectuses.

               (c) In the event that, in the judgment of the Company, it is
advisable to suspend use of a Prospectus included in a Registration Statement
due to pending material developments or other events that have not yet been
publicly disclosed and as to which the Company believes public disclosure would
be detrimental to the Company, the Company shall notify all Selling Stockholders
to such effect, and, upon receipt of such notice, each such Selling Stockholder
shall immediately discontinue any sales of Registrable Shares pursuant to such
Registration Statement until such Selling Stockholder has received copies of a
supplemented or amended Prospectus or until such Selling Stockholder is advised
in writing by the Company that the then current Prospectus may be used and has
received copies of any additional or supplemental filings that are incorporated
or deemed incorporated by reference in such Prospectus. Notwithstanding anything
to the contrary herein, the Company shall not exercise its rights under this
Section 2.3(c) to suspend sales of Registrable Shares for a period in excess of
60 consecutive days and not more than twice in any 365-day period.

          2.4 Allocation of Expenses. The Company will pay all Registration
Expenses for all registrations under this Agreement; provided, however, that if
a registration under Section 2.1 is withdrawn at the request of the Initiating
Holders (other

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than as a result of: (i) information concerning the business or financial
condition of the Company which is made known to the Stockholders after the date
on which such registration was requested or (ii) the exclusion, in accordance
with Sections 2.1(d) or 2.2(b), of a portion of the Registrable Shares sought to
be registered by such Initiating Holders that reduces the total number of
Registrable Shares being registered to less than seventy-five percent (75%) of
the number of Registrable Shares originally requested to be registered) and if
the Initiating Holders elect not to have such registration counted as a
registration requested under Section 2.1, the requesting Stockholders shall pay
the Registration Expenses of such registration pro rata in accordance with the
number of their Registrable Shares included in such registration. For purposes
of this Section, the term "Registration Expenses" shall mean all expenses
incurred by the Company in complying with this Agreement, including, without
limitation, all registration and filing fees, listing fees for an exchange or
automated quotation system, printing expenses, fees and expenses of counsel for
the Company and the fees and expenses of one legal counsel selected by the
Selling Stockholders to represent the Selling Stockholders, state Blue Sky fees
and expenses, and the expense of any special audits incident to or required by
any such registration, but excluding underwriting discounts, selling commissions
and the fees and expenses of Selling Stockholders' own counsel (other than the
counsel selected to represent all Selling Stockholders).

          2.5 Indemnification and Contribution.

               (a) In the event of any registration of any of the Registrable
Shares under the Securities Act pursuant to this Agreement, the Company will
indemnify and hold harmless each Selling Stockholder, each underwriter of such
Registrable Shares, and each other person, if any, who controls such Selling
Stockholder or underwriter within the meaning of the Securities Act or the
Exchange Act against any losses, claims, damages or liabilities, joint or
several, to which such Selling Stockholder, underwriter or controlling person
may become subject under the Securities Act, the Exchange Act, state securities
or Blue Sky laws or otherwise, insofar as such losses, claims, damages or
liabilities (or actions in respect thereof) arise out of or are based upon any
untrue statement or alleged untrue statement of any material fact contained in
any Registration Statement under which such Registrable Shares were registered
under the Securities Act, any Prospectus contained in such Registration
Statement, or any amendment or supplement to such Registration Statement or
Prospectus, or arise out of or are based upon the omission or alleged omission
to state a material fact required to be stated therein or necessary to make the
statements therein in light of the circumstances under which they were made, not
misleading, or any violation or alleged violation by the Company of the
Securities Act, the Exchange Act, any state securities or Blue Sky laws or any
rule or regulation promulgated under the Securities Act, the Exchange Act or any
state securities or Blue Sky laws in connection with the Registration Statement
or the offering contemplated thereby; and the Company will reimburse each such
Selling Stockholder, underwriter and controlling person for any legal or any
other expenses reasonably incurred by such Selling Stockholder, underwriter or
controlling person in connection with investigating or defending against any
such loss, claim, damage, liability or action; provided, however, that the
Company will not be liable in any such case to the extent that any such loss,
claim, damage or liability arises out of or is based upon any untrue

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statement or omission made in such Registration Statement, Prospectus, or any
such amendment or supplement, in reliance upon and in conformity with
information furnished to the Company, in writing, by or on behalf of such
Selling Stockholder, underwriter or controlling person specifically for use in
the preparation thereof.

               (b) In the event of any registration of any of the Registrable
Shares under the Securities Act pursuant to this Agreement, each Selling
Stockholder, severally and not jointly, will indemnify and hold harmless the
Company, each of its directors and officers, each underwriter (if any), each
other Selling Stockholder and each person, if any, who controls the Company, any
of the other Selling Stockholders or any such underwriter within the meaning of
the Securities Act or the Exchange Act, against any losses, claims, damages or
liabilities, joint or several, to which the Company, such directors and
officers, underwriter or controlling person may become subject under the
Securities Act, Exchange Act, state securities or Blue Sky laws or otherwise,
insofar as such losses, claims, damages or liabilities (or actions in respect
thereof) arise out of or are based upon any untrue statement or alleged untrue
statement of a material fact contained in any Registration Statement under which
such Registrable Shares were registered under the Securities Act, any Prospectus
contained in such Registration Statement, or any amendment or supplement to such
Registration Statement or Prospectus, or arise out of or are based upon any
omission or alleged omission to state a material fact required to be stated
therein or necessary to make the statements therein not misleading, if and to
the extent (and only to the extent) that the statement or omission was made in
reliance upon and in conformity with information relating to such Selling
Stockholder furnished in writing to the Company by such Selling Stockholder
specifically for use in connection with the preparation of such Registration
Statement, Prospectus, amendment or supplement; provided, however, that the
obligations of a Selling Stockholder hereunder shall be limited to an amount
equal to the net proceeds to such Selling Stockholder of Registrable Shares sold
in connection with such registration.

               (c) Each party entitled to indemnification under this Section 2.5
(the "Indemnified Party") shall give notice to the party required to provide
indemnification (the "Indemnifying Party") promptly after such Indemnified Party
has actual knowledge of any claim as to which indemnity may be sought, and shall
permit the Indemnifying Party to assume the defense of any such claim or any
litigation resulting therefrom; provided, that counsel for the Indemnifying
Party, who shall conduct the defense of such claim or litigation, shall be
approved by the Indemnified Party (whose approval shall not be unreasonably
withheld); and, provided, further, that the failure of any Indemnified Party to
give notice as provided herein shall not relieve the Indemnifying Party of its
obligations under this Section 2.5 except to the extent that the Indemnifying
Party is adversely affected by such failure. The Indemnified Party may
participate in such defense at such party's expense; provided, however, that the
Indemnifying Party shall pay such expense 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 the Indemnified Party and
any other party represented by such counsel in such proceeding; provided further
that in no event shall the Indemnifying Party be required to pay the expenses of
more than one law firm in any proceeding or series of related proceedings in the
same jurisdiction as counsel for all

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Indemnified Parties. The Indemnifying Party also shall be responsible for the
expenses of such defense if the Indemnifying Party does not elect to assume such
defense. No Indemnifying Party, in the defense of any such claim or litigation
shall, except with the consent of each Indemnified Party, consent to entry of
any judgment or enter into any settlement which does not include as an
unconditional term thereof the giving by the claimant or plaintiff to such
Indemnified Party of a release from all liability in respect of such claim or
litigation, and no Indemnified Party shall consent to entry of any judgment or
settle such claim or litigation without the prior written consent of the
Indemnifying Party, which consent shall not be unreasonably withheld.

               (d) In order to provide for just and equitable contribution in
circumstances in which the indemnification provided for in this Section 2.5 is
due in accordance with its terms but for any reason is held to be unavailable to
an Indemnified Party in respect to any losses, claims, damages and liabilities
referred to herein, then the Indemnifying Party shall, in lieu of indemnifying
such Indemnified Party, contribute to the amount paid or payable by such
Indemnified Party as a result of such losses, claims, damages or liabilities to
which such party may be subject in such proportion as is appropriate to reflect
the relative fault of the Company on the one hand and the Selling Stockholders
on the other in connection with the statements or omissions which resulted in
such losses, claims, damages or liabilities, as well as any other relevant
equitable considerations. The relative fault of the Company and the Selling
Stockholders shall be determined by reference to, among other things, whether
the untrue or alleged untrue statement of a material fact related to information
supplied by the Company or the Selling Stockholders and the parties' relative
intent, knowledge, access to information and opportunity to correct or prevent
such statement or omission. The Company and the Selling Stockholders agree that
it would not be just and equitable if contribution pursuant to this Section
2.5(d) were determined by pro rata allocation or by any other method of
allocation which does not take account of the equitable considerations referred
to above. Notwithstanding the provisions of this Section 2.5(d), (i) in no case
shall any one Selling Stockholder be liable or responsible for any amount in
excess of the net proceeds received by such Selling Stockholder from the
offering of Registrable Shares in connection with such registration and (ii) the
Company shall be liable and responsible for any amount in excess of such
proceeds received by it; provided, however, that no person guilty of fraudulent
misrepresentation (within the meaning of Section 11(f) of the Securities Act)
shall be entitled to contribution from any person who was not guilty of such
fraudulent misrepresentation. Any party entitled to contribution will, promptly
after receipt of notice of commencement of any action, suit or proceeding
against such party in respect of which a claim for contribution may be made
against another party or parties under this Section 2.5(d), notify such party or
parties from whom contribution may be sought, but the omission so to notify such
party or parties from whom contribution may be sought shall not relieve such
party from any other obligation it or they may have thereunder or otherwise
under this Section 2.5. No party shall be liable for contribution with respect
to any action, suit, proceeding or claim settled without its prior written
consent, which consent shall not be unreasonably withheld.

                                       12
<PAGE>
               (e) The obligations of the Company and the Selling Stockholders
under this Section 2.5 shall survive completion of any offering of Registrable
Shares in a Registration Statement and the termination of this Agreement.

          2.6 [RESERVED.]

          2.7 Information by Holder. Each holder of Registrable Shares included
in any registration shall furnish to the Company such information regarding such
holder and the distribution proposed by such holder as the Company may
reasonably request in writing and as shall be required in connection with any
registration, qualification or compliance referred to in this Agreement.

          2.8 "Stand-Off" Agreement. Each Stockholder, if requested by the
Company and the managing underwriter of an underwritten public offering by the
Company of Common Stock, shall not sell or otherwise transfer or dispose of any
Registrable Shares or other securities of the Company held by such Stockholder
for a period of 180 days following the effective date of a Registration
Statement; provided, that:

               (a) such agreement shall only apply to the Triggering Public
Offering;

               (b) all stockholders of the Company then holding at least one
percent (1%) of the outstanding Common Stock (on an as-converted basis) and all
officers and directors of the Company enter into similar agreements; and

               (c) in the event the managing underwriter waives any requirement
for any similar agreement with any person or entity specified in clause (b)
above, the waiver shall apply to such Stockholder.

     The Company may impose stop-transfer instructions with respect to the
Registrable Shares or other securities subject to the foregoing restriction
until the end of such 180-day period.

          2.9 Confidentiality of Notices. Any Stockholder receiving any written
notice from the Company regarding the Company's plans to file a Registration
Statement shall treat such notice as Confidential Information (as defined below)
and shall not disclose such information to any person other than as necessary to
exercise its rights under this Agreement.

          2.10 Limitations on Subsequent Registration Rights. The Company shall
not, without the prior written consent of Stockholders holding at least
fifty-five percent (55%) of the Registrable Shares then held by all
Stockholders, enter into any agreement (other than this Agreement) with any
holder or prospective holder of any securities of the Company which grants such
holder or prospective holder rights to include securities of the Company in any
Registration Statement; provided, however, the Company may grant to such holders
rights to initiate a registration on Form S-3 (or its

                                       13
<PAGE>
successor) without such consent so long as the Stockholders are entitled to
include Registrable Shares in such a registration on a pro rata basis with such
holders based on the number of shares of Common Stock (on an as-converted basis)
owned by Stockholders and such holders.

          2.11 Rule 144 Requirements. After the earliest of (i) the closing of
the sale of securities of the Company pursuant to a Registration Statement, (ii)
the registration by the Company of a class of securities under Section 12 of the
Exchange Act, or (iii) the issuance by the Company of an offering circular
pursuant to Regulation A under the Securities Act, the Company agrees to:

               (a) make and keep current public information about the Company
available, as those terms are understood and defined in Rule 144;

               (b) use its reasonable best efforts to file with the Commission
in a timely manner all reports and other documents required of the Company under
the Securities Act and the Exchange Act (at any time after it has become subject
to such reporting requirements); and

               (c) furnish to any holder of Registrable Shares upon request (i)
a written statement by the Company as to its compliance with the reporting
requirements of Rule 144, the Securities Act and the Exchange Act (at any time
after it has become subject to such reporting requirements), (ii) a copy of the
most recent annual or quarterly report of the Company, and (iii) such other
reports and documents of the Company as such holder may reasonably request to
avail itself of any similar rule or regulation of the Commission allowing it to
sell any such securities without registration.

          2.12 Termination. All of the Company's obligations to register
Registrable Shares under Sections 2.1 and 2.2 shall terminate five (5) years
after the closing of the Triggering Public Offering.

     3. Percentage Maintenance Right.

          3.1 Rights of Purchasers and Vertex.

               (a) The Company shall not issue, sell or exchange, agree to
issue, sell or exchange, or reserve or set aside for issuance, sale or exchange,
(i) any shares of its Common Stock, (ii) any other equity securities of the
Company, including, without limitation, shares of preferred stock, (iii) any
option, warrant or other right to subscribe for, purchase or otherwise acquire
any equity securities of the Company, or (iv) any debt securities convertible
into capital stock of the Company (collectively, the "Offered Securities"),
unless in each such case the Company shall have first complied with this Section
3.1. The Company shall deliver to each Purchaser and Vertex (an "Offeree" or the
"Offerees") a written notice of any proposed or intended issuance, sale or
exchange of Offered Securities (the "Offer"), which Offer shall (i) identify and
describe the Offered Securities, (ii) describe the price and other terms upon
which they are to be issued, sold or exchanged, and the number or amount of the
Offered Securities to be issued, sold or exchanged, (iii) identify the persons
or entities to which or with

                                       14
<PAGE>
which the Offered Securities are to be offered, issued, sold or exchanged, and
(iv) offer to issue and sell to or exchange with such Offeree (A) a pro rata
portion of the Offered Securities determined by dividing the aggregate number of
shares of Common Stock then held by such Offeree (giving effect to the
conversion of all securities of the Company convertible into capital stock of
the Company then held, including, but not limited to, shares of Convertible
Preferred Stock, Purchaser Warrants, warrants to purchase Common Stock held by
Vertex as of the date of this Agreement (the "Vertex Warrants") and all accrued
but unpaid dividends (whether or not declared) on the Series B Convertible
Preferred Stock and Series C Convertible Preferred Stock, as converted into
shares of Common Stock based on the fair market value of the Common Stock at the
time of delivery of the Offer (as determined in good faith by the Board of
Directors), which are then outstanding as if they had been exercised) by the
total number of shares of Common Stock then outstanding (giving effect to the
conversion of all securities of the Company convertible into capital stock of
the Company then held, including, but not limited to, outstanding shares of
Convertible Preferred Stock, Purchaser Warrants, Vertex Warrants, all options to
purchase Common Stock granted pursuant to the Company's stock option plans and
all accrued but unpaid dividends (whether or not declared) on the Series B
Convertible Preferred Stock and Series C Convertible Preferred Stock, as
converted into shares of Common Stock based on the fair market value of the
Common Stock at the time of delivery of the Offer (as determined in good faith
by the Board of Directors), which are then outstanding as if they had been
exercised) and multiplying such fraction by 1.4 (such resulting sum to be
referred to herein as the "Basic Amount"); provided, however, that if the
aggregate Basic Amount subscribed for by all Offerees exceeds the number of
Offered Securities, then each Offeree's Basic Amount shall be reduced to equal
that proportion of the Offered Securities which such initial Basic Amount
subscribed for by such Offeree bears to all of the initial Basic Amounts
subscribed for by all Offerees, and (B) any additional portion of the Offered
Securities attributable to the Basic Amounts of other Offerees as such Offeree
shall indicate it will purchase or acquire should the other Offerees subscribe
for less than their Basic Amounts (the "Undersubscription Amount").

               (b) To the extent the consideration the Company is to receive in
exchange for the Offered Securities (the "Consideration") is something other
than cash, the Offer shall indicate the fair market value of the Consideration,
as determined by the Board of Directors in good faith (the "Consideration Cash
Equivalent"), and shall offer to issue and sell to or exchange with the Offeree
the Basic Amount and the Undersubscription Amount for either (i) the
Consideration or (ii) the Consideration Cash Equivalent at the Offeree's option.

               (c) To accept an Offer, in whole or in part, an Offeree must
deliver a written notice to the Company prior to fifteen (15) days after the
date of delivery of the Offer, setting forth the portion of the Offeree's Basic
Amount that such Offeree elects to purchase and, if such Offeree shall elect to
purchase all of its Basic Amount, the Undersubscription Amount (if any) that
such Offeree elects to purchase (the "Notice of Acceptance"). If the Basic
Amounts subscribed for by all Offerees are less than the total of all of the
Basic Amounts available for purchase, then each Offeree who has set forth an
Undersubscription Amount in its Notice of Acceptance shall be entitled to

                                       15
<PAGE>
purchase, in addition to the Basic Amounts subscribed for, the Undersubscription
Amount it has subscribed for; provided, however, that if the aggregate
Undersubscription Amounts subscribed for exceed the difference between the total
of all of the Basic Amounts available for purchase and the Basic Amounts
subscribed for (the "Available Undersubscription Amount"), each Offeree who has
subscribed for any Undersubscription Amount shall be entitled to purchase only
that portion of the Available Undersubscription Amount as the Undersubscription
Amount subscribed for by such Offeree bears to the total Undersubscription
Amounts subscribed for by all Offerees, subject to rounding by the Board of
Directors to the extent it deems reasonably necessary.

               (d) The Company shall have sixty (60) days from the expiration of
the period set forth in Section 3.1(c) above to issue, sell or exchange all or
any part of such Offered Securities as to which a Notice of Acceptance has not
been given by the Offerees (the "Refused Securities"), but only to the
purchasers described in the Offer and only upon terms and conditions (including,
without limitation, unit prices and interest rates) which are not more
favorable, in the aggregate, to such acquiring person or persons or less
favorable to the Company than those set forth in the Offer.

               (e) In the event the Company shall propose to sell less than all
the Refused Securities (any such sale to be in the manner and on the terms
specified in Section 3.1(d) above), then each Offeree may, at its sole option
and in its sole discretion, reduce the number or amount of the Offered
Securities specified in its Notice of Acceptance to an amount that shall be not
less than the number or amount of the Offered Securities that the Offeree
elected to purchase pursuant to Section 3.1(a) above multiplied by a fraction,
(i) the numerator of which shall be the number or amount of Offered Securities
the Company actually proposes to issue, sell or exchange (including Offered
Securities to be issued or sold to Offerees pursuant to Section 3.1(a) above
prior to such reduction) and (ii) the denominator of which shall be the original
amount of the Offered Securities. In the event that any Offeree so elects to
reduce the number or amount of Offered Securities specified in its Notice of
Acceptance, the Company may not issue, sell or exchange more than such reduced
number or amount of the Offered Securities unless and until such securities have
again been offered to the Offerees in accordance with Section 3.1(a) above.

               (f) Upon the closing of the issuance, sale or exchange of all or
less than all of the Refused Securities, the Offerees shall acquire from the
Company or the underwriters, as the case may be, and the Company shall issue to
the Offerees, the number or amount of Offered Securities specified in the
Notices of Acceptance, as reduced pursuant to Section 3.1(e) above if the
Offerees have so elected, upon the terms and conditions specified in the Offer.

               (g) The purchase by the Offerees of any Offered Securities is
subject in all cases to the preparation, execution and delivery by the Company
and the Offerees of a purchase agreement relating to such Offered Securities
reasonably satisfactory in form and substance to the Offerees and their
respective counsel.

                                       16
<PAGE>
               (h) Any Offered Securities not acquired by the Offerees or other
persons in accordance with Section 3.1(d) and (f) above may not be issued, sold
or exchanged until they are again offered to the Offerees under the procedures
specified in this Agreement.

               (i) The rights of the Offerees under this Section 3 shall not
apply to:

                    (1) the issuance of any shares of Common Stock as a stock
dividend to holders of Common Stock or upon any subdivision or combination of
shares of Common Stock;

                    (2) the issuance of any shares of Common Stock upon
conversion of the Shares or other shares of Convertible Preferred Stock or
exercise of any warrants or options to acquire capital stock of the Company
outstanding on the date of this Agreement;

                    (3) the issuance of shares of Common Stock or options with
respect thereto (subject in either case to appropriate adjustment in the event
of any stock dividend, stock split, combination or other similar
recapitalization affecting such shares on or after the date of this Agreement),
issued or issuable to employees, directors or officers of, or consultants to,
the Company or any of its subsidiaries pursuant to any plan, agreement or
arrangement approved by the Board or Directors, including at least one Series B
Director and at least one Series C Director so long as the holders of the Series
B Convertible Preferred Stock and the Series C Convertible Preferred Stock have
the right to appoint a Series B Director and Series C Director, respectively
("Company Plans");

                    (4) the issuance of securities solely in consideration for
the acquisition (whether by merger or otherwise) by the Company or any of its
subsidiaries of all or substantially all of the stock or assets of any other
entity that has been approved by the Board of Directors;

                    (5) the issuance of securities in connection with any
strategic alliance, collaboration or license agreement or agreement approved by
the Board of Directors, including at least one Series B Director and at least
one Series C Director so long as the holders of the Series B Convertible
Preferred Stock and the Series C Convertible Preferred Stock have the right to
appoint a Series B Director and Series C Director, respectively; or

                    (6) the issuance of shares of Common Stock by the Company in
a firm commitment underwritten public offering pursuant to an effective
registration statement under the Securities Act.

          3.2 Termination. This Section 3 shall terminate upon the earlier of
the following events:

                                       17
<PAGE>
               (a) the sale of all or substantially all of the assets or
business of the Company, by merger, sale of assets or otherwise; or

               (b) the closing of a Triggering Public Offering.

     4. Covenants.

          4.1 Affirmative Covenants.

               (a) Inspection and Observation. The Company shall permit each
Purchaser and Vertex, or any authorized representative thereof, to visit and
inspect the properties of the Company, including its corporate and financial
records, and to discuss its business and finances with officers of the Company,
during normal business hours following reasonable notice and as often as may be
reasonably requested, provided that such Purchaser, or authorized representative
thereof, is not employed by or associated with a competitor of the Company.

               (b) Financial Statements and Other Information. The Company shall
deliver to each Purchaser that holds not less than five percent (5%) of the
total number of then outstanding Shares (including shares of Common Stock issued
upon conversion of the Shares) outstanding on any given date, and to Vertex, so
long as it owns at least five percent (5%) of the then outstanding Registrable
Shares:

                    (i) within 120 days after the end of each fiscal year of the
Company, an audited balance sheet of the Company as at the end of such year and
audited statements of income and of cash flows of the Company for such year,
certified by certified public accountants of established national reputation
selected by the Company, and prepared in accordance with U.S. generally accepted
accounting principles ("GAAP");

                    (ii) within 45 days after the end of each fiscal quarter of
the Company (other than the fourth quarter), an unaudited balance sheet of the
Company as at the end of such quarter, and unaudited statements of income and of
cash flows of the Company for such fiscal quarter and for the current fiscal
year to the end of such fiscal quarter, together with a brief executive summary
prepared by the officers of the Company and covering any material business
issues within the Company's business;

                    (iii) as soon as available, but in any event not later than
30 days prior to the commencement of each new fiscal year, a business plan and
projected financial statements for such fiscal year;

                    (iv) such other notices, information and data with respect
to the Company as the Company delivers to the holders of its capital stock at
the same time it delivers such items to such holders; and

                    (v) with reasonable promptness, such other information and
data as such Purchaser may from time to time reasonably request, provided that
such Purchaser is not employed by or associated with a competitor of the
Company.

                                       18
<PAGE>
The foregoing financial statements shall be prepared on a consolidated basis if
the Company then has any subsidiaries. The financial statements delivered
pursuant to clauses (ii) and (iii) of paragraph (b) shall be accompanied by a
certificate of the chief financial officer of the Company stating that such
statements have been prepared in accordance with GAAP consistently applied
(except as noted) and fairly present the financial condition and results of
operations of the Company at the date thereof and for the periods covered
thereby.

               (c) Reserved.

               (d) Material Changes and Litigation. The Company shall promptly
notify each Purchaser and Vertex of any material adverse change in the business,
prospects, assets or condition, financial or otherwise, of the Company and of
any litigation or governmental proceeding or investigation brought or, to the
best of the Company's knowledge, threatened against the Company, or against any
officer, director, key employee or principal stockholder of the Company which,
if adversely determined, would have a Company Material Adverse Effect, as such
term is defined in the Purchase Agreement.

               (e) Key-Person Insurance. The Company shall maintain term life
insurance upon the lives of Peter Lanciano and Alexey Margolin in the amount of
$2 million each, with the proceeds payable to the Company for so long as they
remain employees of the Company or for five years from the date of this
Agreement, whichever is shorter.

               (f) Agreements with Employees.

                    (i) The Company shall require (x) all persons now or
hereafter employed by the Company and (y) all independent contractors utilized
by the Company who have access to confidential or proprietary information of the
Company to enter into nondisclosure and assignment of inventions agreements
substantially in the form of Exhibit E-1 to the Purchase Agreement.

                    (ii) The Company agrees that it will not, without the prior
approval of a majority of the Board of Directors, including at least one Series
B Director and one Series C Director so long as the holders of the Series B
Convertible Preferred Stock and the Series C Convertible Preferred Stock have
the right to appoint a Series B Director and Series C Director, respectively,
terminate, amend or waive any rights under any inventions, confidentiality,
non-competition or restricted stock agreement between the Company and those
individuals set forth on Exhibit B attached hereto from time to time.

               (g) Board of Directors.

                    (i) The Company shall promptly reimburse in full each
director of the Company who is not an employee of the Company for all of his or
her reasonable out-of-pocket expenses incurred in attending each meeting of the
Board of

                                       19
<PAGE>
Directors or any committee thereof and shall pay each such director such
compensation as determined for service on the Board of Directors.

                    (ii) Upon the appointment of each member of the Board of
Directors who is not an employee of the Company, the Company shall also grant to
such director options to purchase shares of Common Stock, as further described
in the stock option agreement to be entered into between such director and the
Company.

                    (iii) The Company shall cause the Board of Directors to meet
at least six (6) times per year, unless otherwise agreed by a majority of the
members of the Board of Directors, including at least one Series B Director and
Series C Director so long as the holders of the Series B Convertible Preferred
Stock and the Series C Convertible Preferred Stock have the right to appoint a
Series B Director and Series C Director, respectively.

                    (iv) From the date hereof, the By-laws of the Company shall
contain a provision defining a quorum of the Board of Directors as a majority of
directors, including at least one Series B Director and Series C Director so
long as the holders of the Series B Convertible Preferred Stock and the Series C
Convertible Preferred Stock have the right to appoint a Series B Director and
Series C Director, respectively; provided, however, that in connection with any
action to be taken by the Board of Directors, including any action explicitly
requiring the approval of at least one Series B Director and Series C Director,
respectively, in the event that a quorum was not present at any duly noticed
meeting because no Series B Director or Series C Director, respectively, was
present, a deferred meeting may be held four (4) to six (6) business days
thereafter at which a quorum shall consist solely of a majority of directors,
and the matter may be approved by majority vote of the directors present at such
deferred meeting regardless of the vote or attendance of either of the Series B
Directors or Series C Directors, respectively.

                    (v) The Company shall not enter into any agreement with any
stockholder, officer or director of the Company, or any "affiliate" or
"associate" of such persons (as such terms are defined in the rules and
regulations promulgated under the Securities Act), including without limitation
any agreement or other arrangement providing for the furnishing of services by
rental of real or personal property from, or otherwise requiring payments to,
any such person or entity, but excluding any arrangement providing for
compensation for services as a director that is paid to all directors, without
the consent of at least a majority of the members of the Board of Directors
having no interest in such agreement or arrangement.

                    (vi) The affirmative vote of a majority of the members of
the Board of Directors, including at least one Series B Director and one Series
C Director so long as the holders of the Series B Convertible Preferred Stock
and the Series C Convertible Preferred Stock have the right to appoint a Series
B Director and Series C Director, respectively, shall be required to (i)
establish or increase the compensation of executive officers of the Company or
(ii) grant stock options to any officer of the Company.

                                       20
<PAGE>
               (h) Reservation of Common Stock. The Company shall reserve and
maintain a sufficient number of shares of Common Stock for issuance upon
conversion of all of the outstanding Shares and exercise of the Purchaser
Warrants.

               (i) International Investment and Trade in Services Survey Act.
The Company shall use its best efforts to file on a timely basis all reports
required to be filed by it under 22 U.S.C. Section 3104, or any similar statute,
relating to a foreign person's direct or indirect investment in the Company.

               (j) Subsequent Purchasers Becoming Parties to Co-Sale Agreement.
The Company shall require each acquiror of shares of its capital stock who, as a
result of such acquisition, becomes a holder of at least one percent (1%) of the
Company's outstanding voting capital stock, as a condition of such purchase, to
become a party to the Co-Sale Agreement (as that term is defined in the Purchase
Agreement).

               (k) Officers to Become Parties to Co-Sale Agreement. The Company
shall require any employee who may become an officer of the Company to become a
party to the Co-Sale Agreement (as that term is defined in the Purchase
Agreement) as an Executive (as that term is defined in the Co-Sale Agreement).

               (l) Statutory Rights. The provisions of Sections 4.1(a) and (b)
above shall not be in limitation of any rights which any Purchaser may have
under any applicable law with respect to the books and records of the Company or
to inspect its properties or to discuss its affairs, finances and accounts.

               (m) Director's Insurance. The Company will obtain and maintain
directors' and officers' liability insurance with appropriate coverage as may be
determined by a majority of the non-employee directors of the Company when those
same directors determine it is appropriate, but in any case prior to the first
public offering of the Company securities.

               (n) Observer Rights.

                    (i) CMEA Ventures Life Sciences 2000, L.P. and CMEA Ventures
Life Sciences 2000, Civil Law Partnership (together, the "CMEA Group" shall be
permitted to select one representative, reasonably acceptable to the Company
(the Observer"), who shall initially be David J. Collier, M.D. to attend all
meetings of the Board of Directors in a non-voting, observer capacity. In
connection therewith, the Company shall give such Observer copies of all
notices, minutes, consents and other materials, financial or otherwise, which
the Company provides to the Board of Directors; provided, however, that the
Company reserves the right to exclude the Observer from access to any material
or meeting or portion thereof if the Chief Executive Officer or the Board of
Directors believes that such exclusion is advisable (a) to enable the Company or
the Board of Directors to comply with any laws, regulations or court orders, (b)
to meet any legal obligations of the Company or the Board of Directors, (c) to
preserve the attorney-client privilege, (d) to protect the Company's or any
third party's

                                       21
<PAGE>
confidential proprietary information or (e) to protect the competitive or other
business interests of the Company.

                    (ii) CMEA Group's rights set forth in this Section 4(n)
shall expire upon the earliest to occur of (x) the closing of the Company's
initial firm-commitment underwritten public offering of shares of Common Stock
pursuant to an effective registration statement under the Securities Act of
1933, as amended (the "Act"), resulting in at least $50 million of net proceeds
to the Company at a minimum price to the public of $6.4721037 per share (subject
to appropriate adjustment for stock splits, stock dividends, recapitalizations
and other similar events), (y) the sale of all or substantially all of the
assets or business of the Company, by merger, sale of assets or otherwise, or
(z) at such time when CMEA Group no longer holds at least thirty percent (30%)
of the shares of the Series B Convertible Preferred Stock initially purchased by
CMEA Group (subject to appropriate adjustment for stock splits, stock dividends,
recapitalizations and other similar events).

                    (iii) CMEA Group's rights under Section 4.1(n) are
conditioned upon the prior execution of a Confidentiality and Non-Disclosure
Agreement reasonably acceptable to the Company between CMEA (and its
representatives, as applicable) and the Company.

               (o) Committees. For so long as the holders of the Series B
Convertible Preferred Stock and Series C Convertible Preferred Stock have the
right to elect a member to the Board of Directors, at least one of each such
member shall be appointed to any significant committee created by the Board of
Directors, including, but not limited to, the compensation committee and audit
committee of the Board of Directors; provided, however, that in no event shall a
member of the Board of Directors designated by the holders of the outstanding
shares of Series B Convertible Preferred Stock or Series C Convertible Preferred
Stock be appointed to a committee formed for the purpose of evaluating any
proposed transaction between the Company and, (i) in the case of the Series B
Director, any entity of which such director may be an officer or director, or an
"affiliate" or "associate" (as such terms are defined in the rules and
regulations promulgated under the Securities Act), or (ii) in the case of the
Series C Director, Warburg Pincus Private Equity VIII, L.P. ("Warburg Pincus").

               (p) Confidentiality. Each Stockholder agrees that he, she or it
will keep confidential and will not disclose, divulge or use for any purpose
other than to monitor his, her or its investment in the Company any information
that is labeled as confidential, proprietary or secret which such Stockholder
may obtain from the Company pursuant to financial statements, reports and other
materials submitted by the Company to such Stockholder pursuant to this
Agreement or the Ancillary Agreements (as that term is defined in the Purchase
Agreement), or pursuant to visitation or inspection rights granted to the
Purchasers and Vertex hereunder ("Confidential Information"), unless such
Confidential Information (i)

                                       22
<PAGE>
is known, or until such Confidential Information becomes known, to the public
(other than as a result of a breach of this Section 4.1(p) by such Stockholder),
(ii) is or has been independently developed or conceived by such Stockholder
without use of the Company's Confidential Information or (iii) is or has been
made known or disclosed to such Stockholder by a third party without a breach of
any obligation of confidentiality such third party may have to the Company;
provided, however, that a Stockholder may disclose Confidential Information (a)
to such Stockholder's attorneys, accountants, consultants, and other
professionals to the extent necessary to obtain their services in connection
with monitoring its investment in the Company, (b) to any prospective purchaser
of any Shares from such Stockholder as long as such prospective purchaser agrees
in writing to be bound by the provisions of this Section 4.1(p), (c) to any
affiliate of such Stockholder or to a partner, stockholder or subsidiary of such
Stockholder, provided that such person is obligated not to disclose, divulge or
use any Conditional Information to the same extent as such Stockholder, or (d)
if required to do so by law or applicable regulation or by any order of a court
of competent jurisdiction or any judicial, regulatory or governmental body or
stock exchange, provided that such Stockholder will, prior to disclosing any
Confidential Information, to the extent reasonably practicable, inform the
Company of the obligation to disclose and identify the Confidential Information
that will be disclosed and further provided that such Stockholder limits such
disclosure to only that which is necessary to comply with such law, regulation
or order.

          4.2 Termination of Covenants. All covenants of the Company contained
in Section 4.1 other than Sections 4.1(o) and (p) shall terminate, and be of no
further force or effect, upon the closing of a Triggering Public Offering.

          4.3 Post Triggering Public Offering Board Rights. From the date on
which the Company completes a Triggering Public Offering for shares of Common
Stock pursuant to a registration under the Act, and for as long as Warburg
Pincus (and its affiliates) owns at least seventy-five percent (75%) of the
Common Stock issuable upon conversion of the Series C Convertible Preferred
Stock issued to Warburg Pincus pursuant to the Purchase Agreement on the date
thereof, the Company will nominate and use its reasonable efforts to have two
individuals designated by Warburg Pincus elected to the Board of Directors. From
the date on which the Company completes its Triggering Public Offering, and for
as long as Warburg Pincus (and its affiliates) owns at least fifty percent (50%)
of the Common Stock issuable upon conversion of the Series C Convertible
Preferred Stock issued to Warburg Pincus pursuant to the Purchase Agreement on
the date thereof, the Company will nominate and use its reasonable efforts to
have one individual designated by Warburg Pincus elected to the Board of
Directors.

     5. Transfers of Rights. This Agreement, and the rights and obligations of
each Holder hereunder, may be assigned by such Holder to a person or entity to
whom Registrable Shares are transferred by such Holder as follows: (i) to any
person or entity to which at least the lesser of (x) 250,000 Registrable Shares
or (y) all of the Registrable Shares owned by such Holder (including shares of
Common Stock into which Registrable Shares have been converted and as adjusted
for stock splits, stock dividends,

                                       23
<PAGE>
recapitalizations and similar events occurring on or after the date of this
Agreement) are transferred by such Holder, (ii) to an affiliate (as such term is
defined in the Securities Act) of such Holder, (iii) in the case of a Holder
that is a partnership, to a partner of such partnership or a retired partner of
such partnership who retires after the date hereof, or to the estate of any such
partner or retired partner, or (iv) in the case of a Holder that is a limited
liability company, to a member of such limited liability company or a retired
member who resigns after the date hereof or to the estate of any such member or
retired member, and, in each case, such transferee shall be deemed to succeed to
the interest of his, her or its respective transferor for purposes of this
Agreement; provided, that, the transferee provides written notice of such
assignment to the Company and agrees in writing to be bound hereby.

     6. Termination of Prior Agreements. Each of the parties hereto acknowledges
that this Agreement and the agreements referenced herein represent the entire
agreement between the parties with respect to the subject matter herein. All
previous agreements relating to registration rights and/or preemptive or
percentage maintenance rights for the Company's capital stock have been
terminated and supplanted by this Agreement and those agreements referenced
herein.

     7. General.

               (a) Mergers, Etc. The Company shall not, directly or indirectly,
enter into any merger, consolidation or reorganization in which the Company
shall not be the surviving company unless the proposed surviving company shall,
prior to such merger, consolidation or reorganization, agree in writing to
assume the obligations of the Company under Section 2 of this Agreement, and for
that purpose references hereunder to "Registrable Shares" shall be deemed to be
references to the securities which the holders of Registrable Shares would be
entitled to receive in exchange for Registrable Shares under any such merger,
consolidation or reorganization; provided, however, that the provisions of this
Section 7(a) shall not apply in the event of any merger, consolidation or
reorganization in which the Company is not the surviving company if the holders
of Registrable Shares are entitled to receive in exchange therefor (i) cash or
(ii) securities of the acquiring company which may be immediately sold to the
public without registration under the Securities Act.

               (b) Severability. The invalidity or unenforceability of any
provision of this Agreement shall not affect the validity or enforceability of
any other provision of this Agreement.

               (c) Specific Performance. In addition to any and all other
remedies that may be available at law in the event of any breach of this
Agreement, each Purchaser shall be entitled to specific performance of the
agreements and obligations of the Company hereunder and to such other injunctive
or other equitable relief as may be granted by a court of competent
jurisdiction.

                                       24
<PAGE>
               (d) Governing Law. This Agreement shall be governed by and
construed in accordance with the internal laws of the State of Delaware (without
reference to the conflicts of law provisions thereof).

               (e) Notices. All notices, requests, consents, and other
communications under this Agreement shall be in writing and shall be deemed
delivered (i) two business days after being sent by registered or certified
mail, return receipt requested, postage prepaid or (ii) one business day after
being sent via a reputable nationwide overnight courier service guaranteeing
next business day delivery, in each case to the intended recipient as set forth
below:

     If to the Company, at 125 Sidney Street, Cambridge, Massachusetts 02139,
Attention: President, or at such other address or addresses as may have been
furnished in writing by the Company to the Purchasers, with a copy to Mintz,
Levin, Cohn, Ferris, Glovsky and Popeo, P.C., One Financial Center, Boston,
Massachusetts 02111, Attention: Jonathan L. Kravetz, Esq.; or

     If to a Purchaser, at his or its address set forth on Exhibit A, or at such
other address or addresses as may have been furnished to the Company in writing
by such Purchaser. If the Purchaser is holder of Series B Convertible Preferred
Stock, a copy of such notice shall be delivered to Tomlinson Zisko LLP, 200 Page
Mill Road, Second Floor, Palo Alto, California 94306, Attention: Jill E.
Fishbein, Esq., and if the Purchaser is a holder Series C Convertible Preferred
Stock, a copy of such notice shall be delivered to Willkie Farr & Gallagher LLP,
787 Seventh Avenue, New York, New York 10019 Attention: Steven J. Gartner, Esq.

     Any party may give any notice, request, consent or other communication
under this Agreement using any other means (including, without limitation,
personal delivery, messenger service, telecopy, first class mail or electronic
mail), but no such notice, request, consent or other communication shall be
deemed to have been duly given unless and until it is actually received by the
party for whom it is intended. Any party may change the address to which
notices, requests, consents or other communications hereunder are to be
delivered by giving the other parties notice in the manner set forth in this
Section 7(c).

               (f) Complete Agreement. This Agreement constitutes the entire
agreement and understanding of the parties hereto with respect to the subject
matter hereof and supersedes all prior agreements and understandings relating to
such subject matter.

               (g) Amendments and Waivers. Any term of this Agreement, excluding
any terms set forth in Section 3, may be amended or terminated and the
observance of any term of this Agreement, excluding any terms set forth in
Section 3, may be waived with respect to all parties to this Agreement (either
generally or in a particular instance and either retroactively or
prospectively), with the written consent of the Company and the holders of at
least fifty-five percent (55%) of the Registrable Shares (as adjusted for stock
splits, stock dividends, recapitalizations and similar events

                                       25
<PAGE>
occurring on or after the date of this Agreement) held by all Stockholders;
provided, however, that Sections 2.1(a) and (b) may not be amended without the
consent of Vertex; and provided further, however, in addition to the
aforementioned consent described above, any amendment or termination or waiver
of the observance of (i) Sections 4.1(g)(iv), 4.1(o), or 4.2 (to the extent it
applies to Sections 4.1(g)(iv) or 4.1(o)) shall require the written consent of
the Stockholders holding a majority of the shares of the series of capital stock
entitled to designate the director whose rights, privileges or authority are
affected by such amendment, termination or waiver and (ii) Section 4.3 shall
require the consent of Warburg Pincus. Notwithstanding the foregoing, any term
of Section 3 may be amended or terminated and the observance of any such term
may be waived with respect to all parties to this Agreement (either generally or
in a particular instance and prospectively) with the written consent of the
Company and the holders of at least eighty percent (80%) of the Registrable
Shares (as adjusted for stock splits, stock dividends, recapitalizations and
similar events occurring on or after the date of this Agreements) held by Vertex
and the Purchasers. Solely for the purposes of this Section 7(g), Registrable
Shares shall not include Common Stock issuable pursuant to either Article
FOURTH, Section E.1.(c) or Section F.1.(c) of the Company's Certificate of
Incorporation, as amended from time to time. Notwithstanding the foregoing, this
Agreement may be amended or terminated, and any right hereunder may be waived
with respect to all parties to this Agreement with the consent of less than all
parties to this Agreement, and shall be binding upon each party, even if they do
not execute such consent, only in a manner which applies to all parties to this
Agreement, whose rights are being terminated, amended or waived, in the same
fashion. The Company shall give prompt written notice of any amendment or
termination hereof or waiver hereunder to any Stockholder that did not consent
in writing to such amendment, termination or waiver. Any amendment, termination
or waiver effected in accordance with this Section 7(g) shall be binding on all
parties hereto, even if they do not execute such consent. No waivers of or
exceptions to any term, condition or provision of this Agreement, in any one or
more instances, shall be deemed to be, or construed as, a further or continuing
waiver of any such term, condition or provision, unless explicitly so provided
in such waiver or extension.

               (h) Pronouns. Whenever the context may require, any pronouns used
in this Agreement shall include the corresponding masculine, feminine or neuter
forms, and the singular form of nouns and pronouns shall include the plural, and
vice versa.

               (i) Counterparts; Facsimile Signatures. This Agreement may be
executed in any number of counterparts (including, in the case of the
Purchasers, Financing Signature Pages (as defined in the Purchase Agreement)),
each of which shall be deemed to be an original, and all of which together shall
constitute one and the same document. This Agreement and the Financing Signature
Pages may be executed by facsimile signatures.

               (j) Section Headings. The Section headings are for the
convenience of the parties and in no way alter, modify, amend, limit or restrict
the contractual obligations of the parties.

                                       26
<PAGE>
               (k) Aggregation of Stock. All Shares held by affiliated entities
or persons shall be aggregated together for purposes of determining the
availability of any rights under this Agreement (provided that no shares shall
be attributed to more than one entity or person within any such group of
affiliated entities or persons).

               (l) Further Assurances. Each of the parties hereto shall execute
and deliver such instruments and take such other actions as the other parties
may reasonably request in order to carry out the intent of this Agreement.

               (m) Rights of Purchasers. Each Purchaser shall have the absolute
right to exercise or refrain from exercising any right or rights that such
Purchaser may have by reason of this Agreement including without limitation, the
right to consent to the waiver of any obligation of the Company and to enter
into an agreement with the Company for the purpose of modifying this Agreement.
Each such Purchaser shall not incur any liability to any other Purchaser with
respect to exercising or refraining from exercising any such right or rights
that such Purchaser may have by reason of this Agreement.

               (n) Delays or Omissions. No delay or omission to exercise any
right, power or remedy accruing to any party under this Agreement, upon any
breach or default of any other party under this Agreement, shall impair any such
right, power or remedy of such non-breaching or non-defaulting party nor shall
it be construed to be a waiver of any such breach or default, or an acquiescence
therein, or of or in any similar breach or default thereafter occurring; nor
shall any waiver of any single breach or default be deemed a waiver of any other
breach or default theretofore or thereafter occurring. Any waiver, permit,
consent or approval of any kind or character on the part of any party of any
breach or default under this Agreement, or any waiver on the part of any party
of any provisions or conditions of this Agreement, must be in writing and shall
be effective only to the extent specifically set forth in such writing. All
remedies, either under this Agreement or by law or otherwise afforded to any
party, shall be cumulative and not alternative.

               (o) Successors and Assigns. 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, except as expressly limited in this
Agreement. 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.

               (p) Construction and Titles. This Agreement has been negotiated
between the parties hereto, and the language hereof shall not be construed for
or against any party. 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. A reference herein to any Section shall be deemed to include a
reference to every subsection thereof.

                                       27
<PAGE>
               (q) Attorney's Fees. If any action at law or in equity (including
arbitration) is instituted to enforce or interpret the terms of this Agreement,
the prevailing party shall be entitled to reasonable attorney's fees, costs and
necessary disbursements in addition to any other relief to which such party may
be entitled.

               (r) Waiver of Prior Rights. The Company and undersigned parties
constituting two-thirds of the Registrable Shares (as defined in the Prior
Agreement), hereby waive any and all rights pursuant to the Percentage
Maintenance Right set forth in Section 3 thereof with respect to the Company's
issuance and sale of the shares of Series C Convertible Preferred Stock and
Purchaser Warrants exercisable for shares of Series C Convertible Preferred
Stock pursuant to the Purchase Agreement.

                  [Remainder of Page Intentionally Left Blank]

                                       28
<PAGE>
     Executed as of the date first written above.

                                        COMPANY:

                                        ALTUS PHARMACEUTICALS INC.

                                        By: /s/ Peter L. Lanciano
                                            ------------------------------------
                                        Name: Peter L. Lanciano
                                        Title: President and CEO

                                        VERTEX PHARMACEUTICALS INCORPORATED

                                        By: /s/ Kenneth S. Boger
                                            ------------------------------------
                                        Name: Kenneth S. Boger
                                        Title: Sr. Vice President and General
                                               Counsel

                                        NOMURA INTERNATIONAL PLC

                                        By: /s/ Denise Pollard-Knight
                                            ------------------------------------
                                        Name: Denise Pollard-Knight
                                        Title: Head of Nomura Phase 4 Ventures

                                        U.S. VENTURE PARTNERS VIII, L.P.
                                        USVP VIII AFFILIATES FUND, L.P.
                                        USVP ENTREPRENEUR PARTNERS VIII-A, L.P.
                                        USVP ENTREPRENEUR PARTNERS VIII-B, L.P.

                                        By Presidio Management Group VIII,
                                        L.L.C.

                                        The General Partner of Each

                                        By: /s/ Michael P. Maher
                                            ------------------------------------
                                        Name: Michael P. Maher
                                        Title: Attorney In-Fact

                                        CMEA VENTURES LIFE SCIENCES 2000, L.P

                                        By: /s/ Thomas R. Baruch
                                            ------------------------------------
                                        Name: Thomas R. Baruch
                                        Title: General Partner

                [Amended and Restated Investor Rights Agreement]
<PAGE>
                                        CMEA VENTURES LIFE SCIENCES 2000,
                                        CIVIL LAW PARTNERSHIP

                                        By: /s/ Thomas R. Baruch
                                            ------------------------------------
                                        Name: Thomas R. Baruch
                                        Title: General Partner

                [Amended and Restated Investor Rights Agreement]
<PAGE>
                                        P/S BI BIOMEDICINSK VENTURE III

                                        By: /s/ Jesper Zeuthen
                                            ------------------------------------
                                        Name: Jesper Zeuthen
                                              ----------------------------------
                                        Title: Managing Director

                                        CLARIDEN BANK

                                        By: /s/ Eric Bernhardt
                                            ------------------------------------
                                        Name: Eric Bernhardt
                                        Title: Senior Vice President

                [Amended and Restated Investor Rights Agreement]
<PAGE>
                                    EXHIBIT A

                               List of Purchasers

WARBURG PINCUS PRIVATE EQUITY VIII, L.P.
466 Lexington Avenue
New York, NY 10017
Attention: Stewart Hen

U.S. VENTURE PARTNERS VIII, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

USVP VIII AFFILIATES FUND, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

USVP ENTREPRENEUR PARTNERS VIII-A, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

USVP ENTREPRENEUR PARTNERS VIII-B, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

NOMURA PHASE4 VENTURES LP
c/o Nomura International plc
Nomura House
1 St. Martin's-le-Grand
London EC1A 4NP
United Kingdom
Attention: Charles Sermon

P/S BI BIOMEDICINSK VENTURE III
Sundkrogsgade 7
P.O. Box 2672
DK-2100 Copenhagen
Denmark
Attention: Jens W. Kindtler
<PAGE>
CLARIDEN BANK
Claridenstrasse 26
CH-8022 Zurich
Switzerland
Attention: Eric Bernhardt

CMEA VENTURES LIFE SCIENCES 2000, L.P.
One Embarcadero Center, Suite 3250
San Francisco, CA 94111
415.352.1520 ext. 200 (voice)
415.352.1524 (fax)
Attention: David Collier and Meryl Schreibstein

CMEA VENTURES LIFE SCIENCES 2000, CIVIL LAW PARTNERSHIP
One Embarcadero Center, Suite 3250
San Francisco, CA 94111
415.352.1520 ext. 200 (voice)
415.352.1524 (fax)
Attention: David Collier and Meryl Schreibstein

KIM FENNEBRESQUE
c/o SG Cowen & Co.
1221 Avenue of the Americas, 10th Floor
New York, NY 10020
(212) 278-4000 (office)
(212) 278-1641 (fax)

DAVID M. MALCOLM
460 Long Ridge
Bedford, NY 10530
(212) 278-4000 (office)
(212) 278-5599 (fax)

STELIOS PAPADOPOULOS
3 Summerset Drive South
Great Neck, NY 11020
(516) 487-5654 (home)
(516) 487-0245 (fax)

PETER REIKES
200 East 64th Street, #23A
New York, NY 10021
(212) 278-4000 (office)
(212) 278-4289 (fax)
<PAGE>
SENGAL M. SELASSIE
187 Gates Avenue
Montclair, NJ 01042
(973) 744-7525 (home)
(973) 744-7569 (fax)
(212) 278-4000 (office)
(212) 278-5454 (fax)

CHRISTOPHER A. WHITE
247 West 87th Street, #18F
New York, NY 10024
(212) 278-4000 (office)
(212) 278-5454 (fax)

NOMURA INTERNATIONAL PLC
Nomura House
1 St. Martin's-le-Grand
London EC1A 4NP
United Kingdom
Attention: Charles Sermon

SG COWEN VENTURES I, L.P.
1221 Avenue of the Americas
New York, NY 10020

PAUL J. LEACH
1134 Federal Avenue East
Seattle, WA 98102

ML INVESTMENTS LLC
One Financial Center
Boston, MA 02111

CHINA DEVELOPMENT INDUSTRIAL BANK INCORPORATED
125, Nanking East Road, Section 5
Taipei 105
Taiwan, R.O.C.
Attn: James Yen

PALLADIN OPPORTUNITY FUND LLC
195 Maplewood Avenue
Maplewood, NJ 07040
Attn: Ira Leiderman
<PAGE>
CDIB BIOTECH USA INVESTMENT, CO.
21 North Skokie Highway, Suite 104
Lake Bluff, IL 60044
Attn:Geoffrey Bonn

BAOTUNG VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.

WANTUNG VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.

CHUNG-SHAN VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.

CHUNG-SHAN II VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.
<PAGE>
                                    EXHIBIT B

                                 List of Parties

1.   Peter L. Lanciano, Chairman, President, and CEO

2.   Anton Hoos, M.D., Vice President, Pharmaceutical Development

3.   Alexey L. Margolin, Ph.D., Vice President of Science

4.   Robert Gallotto, Vice President of Commercial Development, Branded Products

5.   Jonathan Lieber, Vice President of Finance

6.   Richard Forrest, Corporate Counsel<PAGE>
                                                                     Exhibit 4.4

                                                                  EXECUTION COPY

                           ALTUS PHARMACEUTICALS INC.

        AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

     This Amended and Restated Right of First Refusal and Co-Sale Agreement
(this "Agreement") dated as of May 21, 2004 is entered into by and among Vertex
Pharmaceuticals Incorporated, a Massachusetts corporation ("Vertex"), the
persons and entities listed on Exhibit A attached hereto (individually, a
"Purchaser" and collectively, the "Purchasers"), Altus Pharmaceuticals Inc., a
Delaware corporation (the "Company") (f/k/a "Altus Biologics Inc."), each of the
executives of the Company listed on Exhibit B hereto (individually, an
"Executive" and collectively, the "Executives") who is now, or after the date
hereof becomes, an executive of the Company and joins in and becomes a party to
this Agreement by executing and delivering to the Company an Instrument of
Accession in the form of Annex 1 hereto, and each other holder of 1% or more of
the outstanding voting stock of the Company listed on Exhibit C hereto
(individually, an "Other Holder" and collectively, the "Other Holders"), who
owns, or shall after the date hereof acquire, 1% or more of the outstanding
voting stock of the Company and joins in and becomes a party to this Agreement
by executing and delivering to the Company an Instrument of Accession in the
form of Annex 2 hereto, and amends and restates that certain Right of First
Refusal and Co-Sale Agreement among the Company and the parties thereto dated
September 26, 2001, as amended as of December 7, 2001 (the "Prior Agreement").
Vertex, the Purchasers and the Other Holders are sometimes referred to in this
agreement as the "Stockholders." Executives and Former Employees (as defined
below) are expressly excluded from the definition of Stockholders,
notwithstanding the fact that an Executive may hold 1% or more of the
outstanding voting stock of the Company. For the purposes of this Agreement a
"Former Employee" shall be any Executive who ceases to be employed by or serve
as a consultant to the Company. A Former Employee ceases to be an Executive for
all purposes under this Agreement.

                                    Recitals

     WHEREAS, the Company, Vertex, certain of the Purchasers, the Executives and
the Other Holders have previously entered into the Prior Agreement;

     WHEREAS, the Company and certain of the Purchasers are parties to that
certain Series C Convertible Preferred Stock and Warrant Purchase Agreement of
even date herewith (the "Purchase Agreement");

     WHEREAS, the execution and delivery of this Agreement is a condition to the
consummation of the transactions contemplated by the Purchase Agreement;

     WHEREAS, the parties to the Prior Agreement desire to amend and restate the
Prior Agreement in its entirety so as to read in its entirety as set forth
herein;

     WHEREAS, the undersigned parties represent the necessary voting power in
order to amend the Prior Agreement as set forth in Section 11.5 thereof; and
<PAGE>
     WHEREAS, the purpose of this Agreement is to protect the management and
control of the Company from influence by any person not acceptable to the
Stockholders, and to assist the Stockholders in selling their Shares if they so
desire.

     NOW, THEREFORE, for valuable consideration, it is agreed as follows.

     1. Certain Definitions.

     As used in this Agreement, the term "Shares" shall include all shares of
capital stock of the Company held by Stockholders, Executives and/or Former
Employees, whether now owned or hereafter acquired. For purposes of calculating
any person's "pro rata" ownership of Shares, all shares of capital stock that
are convertible into common stock, $.01 par value per share, of the Company (the
"Common Stock") shall be deemed to have been converted into Common Stock of the
Company, and for purposes of Sections 5 and 6 only, the warrants held by Vertex
as of the date hereof, warrants (the "Series B Warrants") held by certain
Purchasers as of the date hereof to purchase shares of Series B Convertible
Preferred Stock, $.01 par value per share, (the "Series B Preferred") and the
warrants (the "Series C Warrants") issued on the date hereof to the Purchasers
of Series C Convertible Preferred Stock, $.01 par value per share, (the "Series
C Preferred") to purchase shares of Series C Preferred (the Series C Warrants
together with the Series B Warrants, the "Purchaser Warrants"), so long as they
remain outstanding, shall be deemed to have been exercised.

     2. Restrictions on Transfer.

          2.1 Any sale, transfer or other disposition, whether voluntarily or by
operation of law ("Transfer") of any of the Shares by a Stockholder, Executive
or Former Employee, other than according to the terms of this Agreement, shall
be void and shall not transfer any right, title, or interest in or to any of
such Shares to the purported transferee.

          2.2 An Executive may not Transfer Shares except in accordance with
Section 3 or Section 8.

          2.3 An original copy of this Agreement, duly executed by each of the
parties hereto, shall be delivered to the Secretary of the Company and
maintained at the principal executive office of the Company and made available
for inspection by any person requesting it.

          2.4 Each Stockholder, Executive and Former Employee agrees to present
the certificates representing the Shares presently owned or hereafter acquired
by him, her or it to the Secretary of the Company and cause the Secretary to
stamp on such certificates in a prominent manner the following legend in
substantially the following form:

          "The sale or other disposition of any of the shares represented by
          this certificate is restricted by an Amended and Restated Right of
          First Refusal and Co-Sale Agreement, dated as of May 21, 2004, as
          amended from time to time, among certain of the shareholders of this
          corporation and this corporation (the "Agreement"). A copy of the
          Agreement is available for

                                       2
<PAGE>
          inspection during normal business hours at the principal executive
          office of this corporation."

     3. Transfers Not Subject to Restrictions. Any Stockholder, Executive or
Former Employee may Transfer Shares (i) to his or her parents, spouse, children,
siblings, in-laws, grandchildren, or children or grandchildren of siblings or
in-laws, or to a trust established for the benefit of himself or herself or any
such family member, or dispose of them under his or her will (in the case of a
Stockholder, Executive or Former Employee who is a natural person), (ii) to an
affiliate (as such term is defined under the Securities Act of 1933, as amended
(the "Securities Act")) of such Stockholder (in the case of a Stockholder that
is an entity) or (iii) to a partner, a retired partner, member or retired member
of such Stockholder, or to the estate of any such partner or member (in the case
of a Stockholder that is a partnership or limited liability company), without
compliance with Sections 4 through 6, provided that any transferee pursuant to
clause (i), (ii) or (iii) above delivers to the Company and the Stockholders a
written instrument agreeing to be bound by the terms of this Agreement as if it
were the transferor.

     4. Offer of Sale; Notice of Proposed Sale.

     If any Stockholder or Former Employee desires to Transfer any of his, her
or its Shares, or any interest in such Shares, in any transaction other than
pursuant to Section 3 of this Agreement, such Stockholder or Former Employee
(the "Selling Stockholder") shall first deliver written notice of his, her or
its desire to do so (the "Notice") to the Company and each of the Stockholders
in the manner prescribed in Section 12.4 of this Agreement. The Notice must
specify: (i) the name and address of the party to which the Selling Stockholder
proposes to sell or otherwise dispose of the Shares or an interest in the Shares
(the "Offeror"), (ii) the number, class and series of Shares the Selling
Stockholder proposes to sell or otherwise dispose of (the "Offered Shares"),
(iii) the consideration per Share to be delivered to the Selling Stockholder for
the proposed sale, transfer or disposition, and (iv) all other material terms
and conditions of the proposed transaction.

     5. Stockholders' Option to Purchase.

          5.1 Subject to Section 6, each Stockholder other than the Selling
Stockholder (the "Non-Selling Stockholders") shall have an option, exercisable
for a period of fifteen (15) business days from the date of delivery of the
Notice, to purchase, on a pro rata basis according to the number of Shares owned
by such Non-Selling Stockholder, the Offered Shares for the consideration per
share and on the terms and conditions set forth in the Notice. Such option shall
be exercised by delivery by such Non-Selling Stockholder of written notice to
the Secretary of the Company. Notwithstanding the foregoing, in no event shall
Vertex be entitled to exercise any rights under this Section 5 to the extent
that any purchase hereunder by Vertex would result in Vertex holding more than
ten percent (10%) of the Company's issued and outstanding shares of Series B
Preferred or Series C Preferred.

          5.2 Subject to the terms of Section 6, each Non-Selling Stockholder
who does not elect to purchase Shares pursuant to Section 5.1 may, within the
same 15-day period referred to in Section 5.1, notify the Secretary of the
Company of its desire to participate in the sale of the

                                       3
<PAGE>
Shares on the terms set forth in the Notice, and the number, class and series of
Shares it wishes to sell.

          5.3 In the event options to purchase have been exercised by the
Non-Selling Stockholders with respect to some but not all of the Offered Shares,
those Non-Selling Stockholders who have exercised their options within the
15-day period specified in Section 5.1 shall have an additional option, for a
period of ten (10) days next succeeding the expiration of such 15-day period, to
purchase all or any part of the balance of such Offered Shares on the terms and
conditions set forth in the Notice, which option shall be exercised by the
delivery of written notice to the Secretary of the Company. In the event there
are two or more such Non-Selling Stockholders that choose to exercise the
last-mentioned option for a total number of Offered Shares in excess of the
number available, the Offered Shares available for each such Non-Selling
Stockholders option shall be allocated to such Non-Selling Stockholder pro rata
based on the number of Shares owned by the Non-Selling Stockholder so electing.

          5.4 If the options to purchase the Offered Shares are exercised in
full by the Non-Selling Stockholders, the Company shall immediately notify all
of the Non-Selling Stockholders of that fact. The closing of the purchase of the
Offered Shares shall take place at the offices of the Company no later than five
(5) days after the date of such notice to the Non-Selling Stockholders.

          5.5 The option to purchase provided for in this Section 5 shall not
apply to any Approved Sale as that term is defined in Section 7.

          5.6 The option provided for in this Section 5 shall have priority over
any first refusal rights held by the Company or by any other parties to this
Agreement.

     6. Failure to Fully Exercise Options; Co-Sale.

          6.1 If the Non-Selling Stockholders do not exercise their options to
purchase all of the Offered Shares within the periods described in this
Agreement (the "Option Period"), then all options of the Non-Selling
Stockholders to purchase the Offered Shares, whether exercised or not, shall
terminate, and each Non-Selling Stockholder which has, pursuant to Section 5,
expressed a desire to sell Shares in the transaction (a "Participating
Stockholder"), shall be entitled to do so pursuant to this Section; provided,
however, that with respect to Offered Shares consisting of Series C Preferred,
the Participating Stockholders may only elect to sell Shares consisting of
Series C Preferred. The Company shall promptly, on expiration of the Option
Period, notify the Selling Stockholder of the number of Shares the Participating
Stockholders wish to sell, specifying the class and series of such Shares and
the number of Shares within each class and series. The Selling Stockholder shall
use his, her or its best efforts to interest the Offeror in purchasing, in
addition to the Offered Shares, the Shares that any Participating Stockholder
wishes to sell. If the Offeror does not wish to purchase all of the Shares made
available by the Selling Stockholder and the Participating Stockholders, then
each Participating Stockholder and the Selling Stockholder shall be entitled to
sell, at the price and on the terms and conditions set forth in the Notice
(provided that the price set forth in the Offer with respect to shares of Common
Stock shall be appropriately adjusted, if necessary, based on the

                                       4
<PAGE>
conversion ratio of any Convertible Preferred Stock to be sold), a portion of
the Shares being sold to the Offeror as follows:

               (i) With respect to the Offered Shares consisting of shares of
Series C Preferred, that number of shares of Series C Preferred in the same
proportion as such Selling Stockholder's or Participating Stockholder's
ownership of Series C Preferred bears to the aggregate number of shares of
Series C Preferred owned by the Selling Stockholder and the Participating
Stockholders; and

               (ii) With respect to the Offered Shares that do not consist of
shares of Series C Preferred, that number of Shares in the same proportion as
such Selling Stockholder's or Participating Stockholder's ownership of Shares
bears to the aggregate number of Shares owned by the Selling Stockholder and the
Participating Stockholders.

The transaction contemplated by the Notice shall be consummated not later than
sixty (60) days after the expiration of the Option Period.

          6.2 If the Participating Stockholders do not elect to sell the full
number of Shares which they are entitled to sell pursuant to Section 6.1, the
Selling Stockholder shall be entitled to sell to the Offeror, according to the
terms set forth in the Notice, that number of his, her, or its own Shares which
equals the difference between the number of Shares desired to be purchased by
the Offeror and the number of Shares the Participating Stockholders desire to
sell pursuant to Section 6.1. If the Selling Stockholder wishes to Transfer any
such Shares at a price per Share which differs from that set forth in the
Notice, upon terms different from those previously offered to the Stockholders,
or more than sixty (60) days after the expiration of the Option Period, then, as
a condition precedent to such transaction, such Shares must first be offered to
the Stockholders on the same terms and conditions as given the Offeror, and in
accordance with the procedures and time periods set forth above.

          6.3 The proceeds of any sale made by the Selling Stockholder without
compliance with the provisions of this Section 6 shall be deemed to be held in
constructive trust in such amount as would have been due to the Participating
Stockholders if the Selling Stockholder had complied with this Agreement.

     7. Voting and Required Sale. If any person or entity offers to acquire all
or substantially all of the assets or business of the Company, by merger, sale
of assets, stock purchase or otherwise, and

               (i) the aggregate consideration payable in respect thereof is
equal to or greater than the Threshold Price (as defined below) and the
Purchasers holding 55% in interest of the voting power of the then outstanding
shares of Series B Preferred and Series C Preferred voting together as a single
class on an as converted basis have voted in favor of such transaction (whether
at an annual or special meeting of stockholders or by written consent in lieu
thereof); or

               (ii) the aggregate consideration payable in respect thereof is
less than the Threshold Price and at least 55% of the voting power of all issued
and outstanding shares of capital stock of the Company (other than issued and
outstanding shares of voting capital stock

                                       5
<PAGE>
held by Vertex or any holder of capital stock of the Company for which the
transaction is an Interested Transaction (as defined below)) have voted in favor
of such transaction (whether at an annual or special meeting of stockholders or
by written consent in lieu thereof) (any of (i) or (ii) above shall be referred
to herein as an "Approved Sale")); then

     Vertex, the Executives and the Former Employees (the "Obligees") shall be
     obligated to (a) vote all of their Shares in favor of the transaction, (b)
     sell, transfer or exchange all of their Shares in connection with such
     transaction on the same terms as those consented to by such consenting
     stockholders of the Company's voting capital stock (with appropriate
     adjustment to reflect the conversion of convertible securities and the
     preferences and priorities of the Company's preferred stock, $.01 par value
     per share (the "Preferred Stock")), and (c) execute and deliver such
     instruments of conveyance and transfer and take such other action,
     including executing any purchase agreement, merger agreement, indemnity
     agreement, escrow agreement or related documents, as may be reasonably
     required by the Company in order to carry out the terms and provisions of
     this Section 7. If the Approved Sale is structured as a merger or
     consolidation, the Obligees shall waive any dissenters' rights, appraisal
     rights or similar rights in connection with the Approved Sale. If an
     Obligee fails or refuses to vote or sell his, her or its Shares as required
     by, or votes his, her or its Shares in contravention of, this Section 7,
     then each such Obligee hereby grants to the Secretary of the Company an
     irrevocable proxy, coupled with an interest, to vote such Shares in
     accordance with this Section 7, and hereby appoints the Secretary of the
     Company its attorney in fact, to sell such Shares in accordance with the
     terms of this Section 7. At the closing of the Approved Sale, each Obligee
     shall deliver, against receipt of the consideration payable in such
     transaction, certificates representing the Shares which such Obligee holds
     of record or beneficially, with all endorsements necessary for transfer. In
     the event that an Obligee fails or refuses to comply with the provisions of
     this Section 7, the Company, the Stockholders and the purchaser in such
     transaction, at their option, may elect to proceed with such transaction
     notwithstanding such failure or refusal and, in such event and upon tender
     of the specified consideration to any such Obligee, the rights of any such
     party with respect to the Shares shall cease.

          The "Threshold Price" shall mean $8.549420 times the number of shares
     of Common Stock then outstanding (and assuming the conversion of all
     outstanding convertible preferred stock, the exercise of all outstanding
     options and the exercise of all outstanding warrants (options and warrants
     that are outstanding at any point in time are hereinafter referred to as
     "Common Stock Equivalents")).

          An "Interested Transaction" with respect to any "Person" (which for
     purposes of this Agreement shall include persons and entities) shall mean a
     transaction between the Company and any other corporation, limited
     liability company, partnership, association, organization or other entity
     (the "Transaction Party") if such Person either (i) is an officer,
     director, member, partner or affiliate of the Transaction Party or (ii) has
     a "Financial Interest" (as defined below) in the Transaction Party or with
     respect to the transaction (other than a financial interest resulting
     solely from such Person's proportionate interest as a stockholder of the
     Company)).

                                       6
<PAGE>
          A Person has a "Financial Interest" in a Transaction Party or a
     transaction if such Person, directly or indirectly, has (i) an ownership or
     investment interest in the Transaction Party; (ii) a compensation
     arrangement with the Transaction Party or with respect to the transaction;
     or (iii) a right to acquire an ownership or investment interest in, or
     compensation arrangement with the Transaction Party; provided, however,
     that the ownership of 3% or less of the total outstanding equity of a
     Transaction Party by any Person shall not constitute a Financial Interest.
     Notwithstanding the foregoing, a transaction shall not constitute an
     Interested Transaction as to any Person who a majority of the Disinterested
     Directors (as defined below) determine in good faith does not have a
     material financial interest in such transaction other than such Person's
     ownership of voting capital stock of the Company. "Disinterested Directors"
     shall mean the directors of the Company other than any director nominated
     solely by the Person regarding whom the determination of an Interested
     Transaction is to be made.

     In the event that the Secretary of the Company is unwilling or unable to
     act as attorney in fact as set forth in this Section 7, the holders of a
     majority of the shares held by the Purchasers shall be entitled to appoint
     a new attorney in fact in substitution thereof.

     8. Inapplicability of Certain Restrictions to Approved Sales. The
restrictions contained in Sections 2, 3, 4, 5 and 6 shall not apply to any
Transfer of Shares by any party hereto in connection with any Approved Sale.

     9. Required Exercise of Convertible Securities.

          (a) In connection with a firm-commitment underwritten public offering
of the Common Stock pursuant to a registration statement under the Securities
Act (a "Public Offering"), Vertex will exercise a sufficient number of its then
outstanding warrants for Common Stock ("Vertex Warrants") such that all
outstanding warrants (Vertex Warrants together with all other outstanding
warrants for Common Stock and capital stock of the Company convertible into
Common Stock, other than (i) warrants with a per share exercise price of less
than $.05 and (ii) the Purchaser Warrants other than the Vertex Warrants (the
"Outstanding Warrants")) shall equal not more than 10% of the Common Stock
outstanding after the closing of the Public Offering, including the exercise of
any over-allotment option (assuming for the purpose of determining the number of
shares of Common Stock outstanding, the conversion of all outstanding
convertible securities (other than stock options held by current and former
directors, officers and employees) and the exercise of all outstanding warrants
for Common Stock (the "Outstanding Common Stock Equivalents")).

          (b) [Intentionally Omitted]

          (c) In the event the Company intends to sell shares of its voting
capital stock in a Public Offering, it shall provide Vertex with notice of such
intent. Such notice shall contain a detailed analysis of the general parameters
of the expected offering with the Company's best estimates of the number of
shares that will be sold, the aggregate number of shares of voting capital stock
that are likely to be outstanding after the closing of the Public Offering
(including the closing of any over-allotment option) and the number of Vertex
Warrants that the Company expects Vertex will be required to exercise.

                                       7
<PAGE>
          (d) Upon the closing of the Public Offering, including the closing of
the exercise of any over-allotment option or the expiration of the
over-allotment option, the Company shall deliver notice (the "Vertex Notice") to
Vertex, including a detailed calculation of the number of Vertex Warrants Vertex
is required to exercise (the "Required Amount") such that the Outstanding
Warrants shall equal not more than 10% of the Common Stock outstanding after the
closing of the Public Offering, calculated as provided in Section 9(a) above.
Vertex shall within three (3) business days of the Vertex Notice, complete the
required exercise, including payment of the aggregate exercise price.

          (e) In the event Vertex does not complete an exercise of the Required
Amount within two (2) business days of the Vertex Notice, Vertex shall contact
the President of the Company and schedule to meet in person with the President
of the Company and its representatives as soon as practicable but in any event
such meeting shall occur within seven (7) business days of the Vertex Notice to
discuss the disputed Required Amount. If such dispute cannot be resolved at such
meeting, then within two (2) business days of such meeting (or if such meeting
does not occur within such seven (7) business day-period, then within ten (10)
business days of the Vertex Notice), the Company's independent accountants shall
certify by notice delivered to Vertex the independent accountants' understanding
and belief as to the Required Amount (the "Accountants Required Amount").

          (f) If as of the close of business on the fifth (5th) business day
following the accountants' notice, Vertex has not yet exercised the Accountants
Required Amount and delivered to the Company the aggregate exercise price
therefor, the Company shall be entitled to deem the Accountants Required Amount
exercised by Vertex as of the close of business on such date, to cancel the
exercised Vertex Warrants constituting the Accountants Required Amount, to
reflect such exercise and cancellation in the stock records of the Company and
to hold the shares of Common Stock issued in respect of such deemed exercise as
collateral against payment of the aggregate exercise price for the Accountants
Required Amount. In the event of such a deemed exercise, Vertex shall have an
obligation to pay to the Company the aggregate exercise price as of the date of
such deemed exercise. Vertex agrees not to assert against the Company any
defense, set-off, recoupment, claim or counterclaim, against or in respect of
such payment. Upon payment of the exercise price for the Accountants Required
Amount, the Company shall deliver to Vertex a stock certificate representing the
shares of Common Stock issued upon such deemed exercise. In the event the
exercise price is not paid as of the date of such deemed exercise, the aggregate
exercise price shall accrue interest at a rate that shall initially be 10% per
annum. Such interest rate shall increase two percent per month (e.g., 10%
interest to 12% interest to 14% interest, etc.) until such interest rate reaches
20%, at which time such interest rate shall remain at 20% per annum until
payment has been made in full. If the aggregate exercise price remains unpaid on
the thirtieth (30th) day following such deemed exercise, the Company shall be
entitled at its option to sell such shares and apply the proceeds of the sale to
the satisfaction of the aggregate exercise price and shall be entitled to retain
any remaining amounts for the account of the Company, and Vertex shall have no
further rights with respect to such amounts or such shares. For the avoidance of
doubt, Sections 4, 5 and 6 of this Agreement shall not apply to any sale of
shares of capital stock of the Company pursuant to the preceding sentence.

                                       8
<PAGE>
     10. Termination of Agreement.

          10.1 This Agreement shall terminate upon the earlier of the following
events:

          (a) The sale of all or substantially all of the assets or business of
the Company, by merger, sale of assets or otherwise (except a merger or
consolidation in which the holders of capital stock of the Company immediately
prior to such merger or consolidation continue to hold immediately following
such merger or consolidation at least 50% by voting power of the capital stock
of the surviving corporation); or

          (b) The closing of the public offering of shares of the Common Stock
that triggers mandatory conversion of the Company's Preferred Stock pursuant to
the terms of the Company's Certificate of Incorporation as in effect from time
to time (the "Charter").

          10.2 The provisions of Sections 4, 5 and 6 hereof shall not apply to
any sale of Shares pursuant to a transaction referred to in Section 10.1 above.

     11. Transfers. No Transfer of Shares by a party hereto shall be valid
unless the transferee provides written notice of such transfer to the Company
and agrees in writing to be bound hereby in the same capacity and to the same
extent as the transferring party.

     12. General.

          12.1 Severability. The invalidity or unenforceability of any provision
of this Agreement shall not affect the validity or enforceability of any other
provision of this Agreement.

          12.2 Specific Performance. In addition to any and all other remedies
that may be available at law in the event of any breach of this Agreement, each
Stockholder shall be entitled to specific performance of the agreements and
obligations of the Company, the other Stockholders, the Executives, the Former
Employees and the Obligees hereunder and to such other injunctive or other
equitable relief as may be granted by a court of competent jurisdiction.

          12.3 Governing Law. This Agreement shall be governed by and construed
in accordance with the internal laws of The State of Delaware (without reference
to the conflicts of law provisions thereof).

          12.4 Notices. All notices, requests, consents, and other
communications under this Agreement shall be in writing and shall be deemed
delivered (i) two (2) business days after being sent by registered or certified
mail, return receipt requested, postage prepaid or (ii) one (1) business day
after being sent via a reputable nationwide overnight courier service
guaranteeing next business day delivery, in each case to the intended recipient
as set forth below:

     If to the Company, at 125 Sidney Street, Cambridge, Massachusetts 02139,
Attention: President, or at such other address or addresses as may have been
furnished in writing by the Company to the Purchasers, with a copy to Mintz,
Levin, Cohn, Ferris, Glovsky and Popeo, P.C., One Financial Center, Boston,
Massachusetts 02111, Attention: Jonathan L. Kravetz, Esq.;

                                       9
<PAGE>
     If to a Purchaser, at his or its address set forth in Schedule A hereto, or
at such other address or addresses as may have been furnished to the Company in
writing by such Purchaser. If the Purchaser is a holder of Series B Preferred, a
copy of such notice shall be delivered to Tomlinson Zisko LLP, 200 Page Mill
Road, Second Floor, Palo Alto, California 94306, Attention: Jill E. Fishbein,
Esq, and if the Purchaser is a holder of Series C Preferred, a copy of such
notice shall be delivered to Willkie Farr & Gallagher LLP, 787 Seventh Avenue,
New York, New York 10019, Attention: Steven J. Gartner, Esq.;

     If to an Other Holder, at his or its address set forth on Exhibit C hereto,
or at such other address or addresses as may have been furnished to the Company
in writing by such Other Holder;

     If to Vertex, at 130 Waverly Street, Cambridge, Massachusetts 02139,
Attention: General Counsel, or at such other address or addresses as may have
been furnished to the Company in writing by Vertex;

     If to a person in its capacity as attorney under Section 7, at such address
or addresses as may be furnished to the parties hereto at the time of the grant
of the irrevocable proxy under Section 7; and

     If to an Executive or Former Employee, at the address of the Company, or at
such other address or addresses as may have been furnished to the Company in
writing by such Executive or Former Employee.

     Any party may give any notice, request, consent or other communication
under this Agreement using any other means (including, without limitation,
personal delivery, messenger service, telecopy, first class mail or electronic
mail), but no such notice, request, consent or other communication shall be
deemed to have been duly given unless and until it is actually received by the
party for whom it is intended. Any party may change the address to which
notices, requests, consents or other communications hereunder are to be
delivered by giving the other parties notice in the manner set forth in this
Section.

          12.5 Complete Agreement; Amendments. This Agreement constitutes the
entire agreement and understanding of the parties hereto with respect to the
subject matter hereof, and supersedes all prior agreements and understandings
relating to such subject matter. No amendment, modification or termination of,
or waiver under, any provision of this Agreement shall be valid unless in
writing and signed by the Company and Stockholders holding at least 55% of the
voting power of the Shares then held by all of the Stockholders (giving effect
to the conversion into Common Stock of all securities convertible thereinto,
i.e. on an as converted basis); provided, however, this Agreement may be amended
or terminated, and any right hereunder may be waived with respect to all parties
to this Agreement with the consent of less than all parties to this Agreement,
and shall be binding upon each party, even if they do not execute such consent,
only if such amendment, modification or termination applies in the same fashion
to all parties to this Agreement whose rights are being terminated, amended or
waived; provided further, however, any amendment or modification of this
Agreement which would adversely affect the rights or obligations of the
Executives or Former Employees shall require the consent of the Executives and
Former Employees holding at least a majority of the voting power

                                       10
<PAGE>
of the Shares held by all Executives and Former Employees. For the sake of
clarity, no amendment to this Agreement which adds additional Stockholders,
Executives or Former Employees as parties hereto shall be deemed to adversely
affect any Person who or which is already a party hereto. The Company shall give
prompt written notice of any amendment or termination hereof or waiver hereunder
to any party hereto that did not consent in writing to such amendment,
termination or waiver. Notwithstanding anything to the contrary herein, any
amendment to the Threshold Price in Section 7 hereof shall require the prior
written consent of Vertex only if such amendment occurs between the date hereof
and the second anniversary of the date hereof and is to a price less than
$4.2747100.

          12.6 Pronouns. Whenever the context may require, any pronouns used in
this Agreement shall include the corresponding masculine, feminine or neuter
forms, and the singular form of nouns and pronouns shall include the plural, and
vice versa.

          12.7 Counterparts; Facsimile Signatures. This Agreement may be
executed in any number of counterparts, each of which shall be deemed to be an
original, and all of which together shall constitute one and the same document.
This Agreement may be executed by facsimile signatures.

          12.8 Section Headings. The section headings are for the convenience of
the parties and in no way alter, modify, amend, limit or restrict the
contractual obligations of the parties.

          12.9 Additional Stockholders. Persons or entities that, after the date
hereof, purchase shares of the Company's capital stock such that they become
holders of at least one percent (1%) of the outstanding voting capital stock of
the Company may, with the prior written approval of the Company (but without the
need for approval by any other party to this Agreement), become parties to this
Agreement by executing and delivering an Instrument of Accession hereto,
whereupon they shall be deemed "Stockholders" for all purposes of this
Agreement.

          12.10 Changes in Executives. Anyone who, on or after the date hereof,
becomes an executive officer of the Company shall become party to this Agreement
by executing and delivering an Instrument of Accession hereto, whereupon they
shall be deemed an "Executive" for all purposes of this Agreement. The Company
shall use its best efforts to ensure that anyone who becomes an executive
officer of the Company executes and delivers such an Instrument of Accession.

          12.11 Stop Transfer Order. The parties hereto agree that the Company
may instruct its transfer agent to impose transfer restrictions on the Shares to
enforce the provisions of this Agreement, and the Company agrees to do so
promptly.

          12.12 Ownership. Each party hereto represents and warrants that he,
she or it is the sole legal and beneficial owner of the Shares he, she or it
currently holds and that no other person has any interest (other than a
community property interest) in such Shares, except as specified on Exhibit A, B
or C hereto. In every case where Exhibit A, B or C indicates that a party is not
the sole legal and beneficial owner of the Shares, such party represents and
warrants

                                       11
<PAGE>
that each legal and/or beneficial owner of those Shares (other than a
community property interest) is listed on the Exhibit and that no other person
has any interest in such Shares.

          12.13 Further Assurances. Each of the parties hereto shall execute and
deliver such instruments and take such other actions as the other parties may
reasonably request in order to carry out the intent of this Agreement.

          12.14 Rights of Purchasers. Each Purchaser shall have the absolute
right to exercise or refrain from exercising any right or rights that such
Purchaser may have by reason of this Agreement including without limitation, the
right to consent to any wavier or amendment of this Agreement. Each such
Purchaser shall not incur any liability to any other Purchaser with respect to
exercising or refraining from exercising any such right or rights.

          12.15 Delays or Omissions. No delay or omission to exercise any right,
power or remedy accruing to any party under this Agreement, upon any breach or
default of any other party under this Agreement, shall impair any such right,
power or remedy of such non-breaching or non-defaulting party nor shall it be
construed to be a waiver of any such breach or default, or an acquiescence
therein, or of or in any similar breach or default thereafter occurring; nor
shall any waiver of any single breach or default be deemed a waiver of any other
breach or default theretofore or thereafter occurring. Any waiver, permit,
consent or approval of any kind or character on the part of any party of any
breach or default under this Agreement, or any waiver on the part of any party
of any provisions or conditions of this Agreement, must be in writing and shall
be effective only to the extent specifically set forth in such writing. All
remedies, either under this Agreement or by law or otherwise afforded to any
party, shall be cumulative and not alternative.

          12.16 Successors and Assigns. 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, except as expressly limited in this
Agreement. 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.

          12.17 Construction and Titles. This Agreement has been negotiated
between the parties hereto, and the language hereof shall not be construed for
or against any party. 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. A reference herein to any Section shall be deemed to include a
reference to every subsection thereof.

          12.18 Attorney's Fees. If any action at law or in equity (including
arbitration) is instituted to enforce or interpret the terms of the Agreements,
the prevailing party shall be entitled to reasonable attorney's fees, costs and
necessary disbursements in addition to any other relief to which such party may
be entitled.

          12.19 Aggregation of Stock. All Shares held by affiliated entities or
persons shall be aggregated together for purposes of determining the
availability of any rights under this

                                       12
<PAGE>
Agreement (provided that no shares shall be attributed to more than one entity
or person within any such group of affiliated entities or persons).

                  [Remainder of Page Intentionally Left Blank]

                                       13
<PAGE>
     IN WITNESS WHEREOF, this Agreement has been executed by the parties hereto
as of the day and year first above written.

                                   COMPANY:

                                   ALTUS PHARMACEUTICALS INC.

                                   By: /s/ Peter L. Lanciano
                                       -----------------------------------------
                                   Name: Peter L. Lanciano
                                   Title: President and CEO

                                   VERTEX PHARMACEUTICALS
                                   INCORPORATED

                                   By: /s/ Kenneth S. Boger
                                       -----------------------------------------
                                   Name: Kenneth S. Boger
                                         ---------------------------------------
                                   Title: Sr. Vice President and General Counsel
                                          --------------------------------------

                                   PETER L. LANCIANO

                                   /s/ Peter L. Lanciano
                                   ---------------------------------------------
                                   Title: President and CEO

                                   ALEXEY L. MARGOLIN

                                   /s/ Alexey L. Margolin
                                   ---------------------------------------------
                                   Title: Vice President of Science

                                   NOMURA INTERNATIONAL PLC
                                         By: /s/ Denise Pollard-Knight
                                             -----------------------------------
                                         Name: Denise Pollard-Knight
                                               ---------------------------------
                                         Title: Head of Nomura Phase 4 Ventures
                                                --------------------------------

       [Amended and Restated Right of First Refusal and Co-Sale Agreement]
<PAGE>
                                         U.S. VENTURE PARTNERS VIII, L.P.
                                         USVP VIII AFFILIATES FUND, L.P.
                                         USVP ENTREPRENEUR PARTNERS VIII-A, L.P.
                                         USVP ENTREPRENEUR PARTNERS VIII-B, L.P.

                                         By Presidio Management Group VIII,
                                         L.L.C.
                                         The General Partner of Each

                                         By:  /s/ Michael P. Maher
                                             -----------------------------------
                                         Name: Michael P. Maher
                                         Title: Attorney In-Fact

                                         CMEA VENTURES LIFE SCIENCES 2000, L.P

                                         By:  /s/ David Collier
                                             -----------------------------------
                                         Name:
                                               ---------------------------------
                                         Title:
                                                --------------------------------

                                         CMEA VENTURES LIFE SCIENCES 2000,
                                         CIVIL LAW PARTNERSHIP

                                         By:  /s/ David Collier
                                             -----------------------------------
                                         Name:
                                               ---------------------------------
                                         Title:
                                                --------------------------------

       [Amended and Restated Right of First Refusal and Co-Sale Agreement]
<PAGE>
                                         P/S BI BIOMEDICINSK VENTURE III

                                         By:  /s/ Jesper Zeuthen
                                             -----------------------------------
                                         Name:  Jesper Zeuthen
                                               ---------------------------------
                                         Title: Managing Director

                                         CLARIDEN BANK

                                         By:  /s/ Eric Bernhardt
                                             -----------------------------------
                                         Name: Eric Bernhardt
                                         Title: Senior Vice President

       [Amended and Restated Right of First Refusal and Co-Sale Agreement]
<PAGE>
                                    Exhibit A

                               List of Purchasers

WARBURG PINCUS PRIVATE EQUITY VIII, L.P.
466 Lexington Avenue
New York, NY 10017
Attention: Stewart Hen

U.S. VENTURE PARTNERS VIII, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

USVP VIII AFFILIATES FUND, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

USVP ENTREPRENEUR PARTNERS VIII-A, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

USVP ENTREPRENEUR PARTNERS VIII-B, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

NOMURA PHASE4 VENTURES LP
c/o Nomura International plc
Nomura House
1 St. Martin's-le-Grand
London EC1A 4NP
United Kingdom
Attention: Charles Sermon

P/S BI BIOMEDICINSK VENTURE III
Sundkrogsgade 7
P.O. Box 2672
DK-2100 Copenhagen
Denmark
Attention: Jens W. Kindtler
<PAGE>
CLARIDEN BANK
Claridenstrasse 26
CH-8022 Zurich
Switzerland
Attention: Eric Bernhardt

CMEA VENTURES LIFE SCIENCES 2000, L.P.
One Embarcadero Center, Suite 3250
San Francisco, CA 94111
415.352.1520 ext. 200 (voice)
415.352.1524 (fax)
Attention: David Collier and Meryl Schreibstein

CMEA VENTURES LIFE SCIENCES 2000, CIVIL LAW PARTNERSHIP
One Embarcadero Center, Suite 3250
San Francisco, CA 94111
415.352.1520 ext. 200 (voice)
415.352.1524 (fax)
Attention: David Collier and Meryl Schreibstein

KIM FENNEBRESQUE
c/o SG Cowen Ventures I, L.P.
1221 Avenue of the Americas, 10th Floor
New York, NY 10020
(212) 278-4000 (office)
(212) 278-1641 (fax)

DAVID M. MALCOLM
460 Long Ridge
Bedford, NY 10530
(212) 278-4000 (office)
(212) 278-5599 (fax)

STELIOS PAPADOPOULOS
3 Summerset Drive South
Great Neck, NY 11020
(516) 487-5654 (home)
(516) 487-0245 (fax)

PETER REIKES
200 East 64th Street, #23A
New York, NY 10021
(212) 278-4000 (office)
(212) 278-4289 (fax)
<PAGE>
SENGAL M. SELASSIE
187 Gates Avenue
Montclair, NJ 01042
(973) 744-7525 (home)
(973) 744-7569 (fax)
(212) 278-4000 (office)
(212) 278-5454 (fax)

CHRISTOPHER A. WHITE
247 West 87th Street, #18F
New York, NY 10024
(212) 278-4000 (office)
(212) 278-5454 (fax)

NOMURA INTERNATIONAL PLC
Nomura House
1 St. Martin's-le-Grand
London EC1A 4NP
United Kingdom
Attention: Charles Sermon

SG COWEN VENTURES I, L.P.
1221 Avenue of the Americas
New York, NY 10020

PAUL J. LEACH
1134 Federal Avenue East
Seattle, WA 98102

ML INVESTMENTS LLC
One Financial Center
Boston, MA 02111

CHINA DEVELOPMENT INDUSTRIAL BANK INCORPORATED
125, Nanking East Road, Section 5
Taipei 105
Taiwan, R.O.C.
Attn: James Yen

PALLADIN OPPORTUNITY FUND LLC
195 Maplewood Avenue
Maplewood, NJ 07040
Attn: Ira Leiderman
<PAGE>
CDIB BIOTECH USA INVESTMENT, CO.
21 North Skokie Highway, Suite 104
Lake Bluff, IL 60044
Attn:Geoffrey Bonn

BAOTUNG VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.

WANTUNG VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.

CHUNG-SHAN VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.

CHUNG-SHAN II VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.
<PAGE>
                                    Exhibit B

                     List of Executives and Former Employees

Executives:
-----------
Peter Lanciano
Alexey Margolin

Former Employee:
----------------
Joseph Blanchard
<PAGE>
                                    Exhibit C

                              List of Other Holders

Eastcastle Limited
Scott Rakestraw
<PAGE>
                                                                         ANNEX 1

                           ALTUS PHARMACEUTICALS INC.

                             INSTRUMENT OF ACCESSION

     The undersigned, _______________________, as a condition precedent to
becoming an executive of Altus Pharmaceuticals Inc., a Delaware corporation (the
"Company"), hereby agrees to become an Executive party to that certain Amended
and Restated Right of First Refusal and Co-Sale Agreement dated as of May 21,
2004 by and among the Company, the Stockholders and other Executives (each as
defined therein). This Instrument of Accession shall take effect and shall
become an integral part of, and the undersigned shall become a party to and be
bound by, said Amended and Restated Right of First Refusal and Co-Sale Agreement
immediately upon execution and delivery to the Company of this Instrument of
Accession.

     IN WITNESS WHEREOF, this INSTRUMENT OF ACCESSION has been duly executed by
or on behalf of the undersigned, as a sealed instrument under the laws of the
State of Delaware, as of the date below written.

                                         Signature:

                                         ---------------------------------------
                                         (Print Name)

                                         Address:
                                                  ------------------------------

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

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

                                         ACCEPTED:

                                         ALTUS PHARMACEUTICALS INC.

                                         By:
                                             -----------------------------------
                                         Name:
                                               ---------------------------------
                                         Title:
                                                --------------------------------
Date:
      -------------------
<PAGE>
                                                                         ANNEX 2

                           ALTUS PHARMACEUTICALS INC.

                             INSTRUMENT OF ACCESSION

     The undersigned, ______________________, as a condition precedent to
becoming the owner or holder of record of shares of capital stock, of Altus
Pharmaceuticals Inc., a Delaware corporation (the "Company"), hereby agrees to
become a Stockholder party to that certain Amended and Restated Right of First
Refusal and Co-Sale Agreement dated as of May 21, 2004 by and among the Company,
the other Stockholders and the Executives (each as defined therein). This
Instrument of Accession shall take effect and shall become an integral part of,
and the undersigned shall become a Stockholder party to and be bound by, said
Amended and Restated Right of First Refusal and Co-Sale Agreement immediately
upon execution and delivery to the Company of this Instrument of Accession.

     IN WITNESS WHEREOF, this INSTRUMENT OF ACCESSION has been duly executed by
or on behalf of the undersigned, as a sealed instrument under the laws of the
State of Delaware, as of the date below written.

                                         Signature:

                                         ---------------------------------------
                                         (Print Name)

                                         Address:
                                                  ------------------------------

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

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

                                         ACCEPTED:

                                         ALTUS PHARMACEUTICALS INC.

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

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