<PAGE>
                                                                     EXHIBIT 4.2

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             SECOND AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

                                  by and among

                           AMICUS THERAPEUTICS, INC.,

                                      and

                         THE STOCKHOLDERS NAMED HEREIN

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

                             DATED: AUGUST 17, 2005

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

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                                      -i-
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                               TABLE OF CONTENTS
<TABLE>
<CAPTION>
                                                                           Page
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<S>  <C>                                                                <C>
1.   Definitions ....................................................    1
2.   Grant Of Rights ................................................    4
3.   Demand Registration ............................................    4
     (a)   Request for Demand Registration for Holders ..............    4
     (b)   Incidental or "Piggy-Back" Rights with Respect to a Demand
           Registration. ............................................    5
     (c)   Effective Demand Registration ............................    5
     (d)   Expenses .................................................    6
     (e)   Underwriting Procedures ..................................    6
     (f)   Selection of Underwriters ................................    6
4    Incidental or "Piggy-Back" Registration ........................    6
     (a)   Request for Incidental Registration ......................    6
     (b)   Expenses. ................................................    7
5.   Form S-3 Registration ..........................................    7
     (a)   Request for a Form S-3 Registration ......................    7
     (b)   Limitations on Form S-3 Registrations ....................    7
     (c)   Expenses .................................................    8
     (d)   No Demand Registration ...................................    8
6.   Holdback Agreements ............................................    8
     (a)   Restrictions on Public Sale by Holders ...................    8
     (b)   Legend ...................................................    9
7.   Registration Procedures ........................................    9
     (a)   Obligations of the Company ...............................    9
     (b)   Seller Information .......................................   11
     (c)   Notice to Discontinue ....................................   11
     (d)   Registration Expenses ....................................   12
8.   Indemnification; Contribution ..................................   12
     (a)   Indemnification by the Company ...........................   12
     (b)   Indemnification by Holders ...............................   13
     (c)   Conduct of Indemnification Proceedings ...................   14
     (d)   Contribution .............................................   14
</TABLE>
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                               TABLE OF CONTENTS
<TABLE>
<S>  <C>                                                                <C>
9.   Rule 144 .......................................................   15
10.  Limitations on Subsequent Registration Rights; No Inconsistent
     Agreements .....................................................   15
11.  Miscellaneous ..................................................   15
     (a)   Recapitalizations Exchanges, Etc .........................   16
     (b)   Remedies .................................................   16
     (c)   Amendments and Waivers ...................................   16
     (d)   Notices ..................................................   16
     (e)   Successors and Assigns; Third Party Beneficiaries ........   17
     (f)   Counterparts... ..........................................   17
     (g)   Headings .................................................   17
     (h)   Governing Law ............................................   17
     (i)   Entire Agreement .........................................   18
     (j)   Severability .............................................   17
     (k)   Further Assurances .......................................   18
     (l)   Other Agreements .........................................   18
     (m)   Jury Trial Waiver ........................................   18
     (n)   Expenses .................................................   18
</TABLE>
                                      -ii-
<PAGE>

                           SECOND AMENDED AND RESTATED
                            INVESTOR RIGHTS AGREEMENT

            SECOND AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT, dated August
17, 2005 (this "Agreement"), by and among Amicus Therapeutics, Inc,. a Delaware
corporation (the "Company"), the parties listed on Schedule I hereto (the
"Investors") and the parties listed on Schedule II hereto.

            WHEREAS, the Company and certain of the Investors are parties to the
Amended and Restated Investor Rights Agreement, dated May 4, 2004 (the "Existing
Investor Rights Agreement") and hold sufficient voting power to amend the
Existing Investor Rights Agreement (the "Amending Investors"); and

            WHEREAS, pursuant to the Series C Preferred Stock Purchase
Agreement, dated August 17, 2005 (the "Series C Stock Purchase Agreement"), by
and between the Company and each of the parties identified on Schedule  I
thereto, the Company has agreed to issue and sell to such parties an aggregate
of 43,650,262 shares, par value $0.01 per share, of Series C Convertible
Preferred Stock of the Company (the "Series C Preferred Stock"); and

            WHEREAS, in order to induce each of the Investors to purchase its
shares of Series C Preferred Stock, the Company and the Amending Investors are
entering into this Agreement to, among other things, amend and restate the
Existing Investor Rights Agreement in its entirety.

            NOW, THEREFORE, in consideration of the mutual covenants and
agreements set forth herein and for good and valuable consideration, the receipt
and adequacy of which are hereby acknowledged, the parties hereto amend and
restate the Existing Investor Rights Agreement as follows:

      1. Definitions. As used in this Agreement the following terms have the
meanings indicated:

      "Agreement" means this Second Amended and Restated Investor Rights
Agreement as the same may be amended, supplemented or modified in accordance
with the terms hereof.

      "Approved Underwriter" has the meaning set forth in Section 3(f) of this
Agreement.

      "Bridge Loan Warrants" mean the warrants to purchase Common Stock issued
pursuant to the Note and Warrant Purchase Agreements.

      "Business Day" means any day other than a Saturday, Sunday or other day on
which commercial banks in the State of Delaware are authorized or required by
law or executive order to close.

      "Closing Price" means, with respect to the Registrable Securities, as of
the date of determination, (a) the closing price per share of a Registrable
Security on such date published in

<PAGE>

The Wall Street Journal or, if no such closing price on such date is published
in The Wall Street Journel, the average of the closing bid and asked prices on
such date, as officially reported on the principal national securities exchange
(including, without limitation, The Nasdaq Stock Market, Inc.) on which the
Registrable Securities are then listed or admitted to trading; or (b) if the
Registrable Securities are not then listed or admitted to trading on any
national securities exchange but are designated as national market system
securities by the NASD, the last trading price per share of a Registrable
Security on such date; or (c) if there shall have been no trading on such date
or if the Registrable Securities are not so designated, the average of the
reported closing bid and asked prices of the Registrable Securities on such date
as shown by The Nasdaq Stock Market Inc. (or its successor) and reported by any
member firm of The New York Stock Exchange, Inc. selected by the Company; or (d)
if none of (a), (b) or (c) is applicable, a market price per share determined in
good faith by the Company's Board of Directors. If trading is conducted on a
continuous basis on any exchange, then the closing price shall be at 4:00 P.M.
New York City time.

      "Common Stock" means the Common Stock, par value $0.01 per share, of the
Company or any other capital stock of the Company into which such stock is
reclassified or reconstituted.

      "Company" meaning set forth in the preamble to this Agreement.

      "Company Underwriter" has the meaning set Forth in Section 4(a) of this
Agreement.

      "Demand Registration" has the meaning set forth in Section 3(a) of this
Agreement.

      "Exchange Act" means the Securities Exchange Act of 1934, as amended, and
the rules and regulations of the SEC thereunder.

      "GECC" means General Electric Capital Corporation, a Delaware corporation.

      "GECC Warrant" means the warrant to purchase 40,000 shares of Common Stock
at an exercise price of $0.75 per share, issued by the Company to GECC on August
28, 2002.

      "Holder" means any person owning Registrable Securities.

      "Holders' Counsel" has the meaning set forth in Section 7(a)(i) of
this Agreement.

      "Incidental Registration" has the meaning set forth in Section 4(a) of
this Agreement.

      "Indemnified Party" has the meaning set forth in Section 8(c) of this
Agreement.

      "Indemnifying Party" has the meaning set forth in Section 8(c) of this
Agreement.

      "Initial Public Offering" means the initial public offering of the shares
of Common Stock of the Company pursuant to an effective Registration Statement
filed under the Securities Act.

      "Initiating Holders" has the meaning set forth in Section 3(a) of this
Agreement.

      "Inspector" has the meaning set forth in Section 7(a)(vii) of this
Agreement.

                                      -2-
<PAGE>

      "Investors" has the meaning set forth in the preamble to this Agreement.

      "IPO Effectiveness Date" means the date upon which the Company closes its
Initial Public Offering.

      "Liabilities" has the meaning set forth in Section 8(a) of this Agreement,

      "Market Price" means, on any date of determination, the average of the
daily Closing Price of the Registrable Securities for the immediately preceding
thirty (30) days on which the national securities exchanges are open for
trading.

      "Mount Sinai" means Mount Sinai School of Medicine of New York University

      "Mount Sinai Shares" means the 1,742,000 shares of Common Stock issued to
Mount Sinai on April 15, 2002 and held by Mount Sinai.

      "NASD" means the National Association of Securities Dealers, Inc.

      "Note and Warrant Purchase Agreements" mean the Note and Warrant Purchase
Agreement dated as of August 25, 2003 and the Note and Warrant Purchase
Agreement November 26, 2003, as amended as of February 5, 2004 and April 20,
2004, between the Company and the investors signatory thereto.

      "Permitted Transferee" has the meaning set forth in Section 2.2 of the
Stockholders Agreement.

      "Person" means any individual, firm, corporation, partnership, limited
liability company, trust, incorporated or unincorporated association, joint
venture, joint stock company, government (or an agency or political subdivision
thereof) or other entity of any kind, and shall include any successor (by merger
or otherwise) of such entity.

      "Records" has the meaning set forth in Section 7(a)(vii) of this
Agreement.

      "Registration Expenses" has the meaning set forth in Section 7(d) of this
Agreement,

      "Registrable Securities" means (a) the Common Stock of the Company issued
or issuable upon conversion of the Series A Preferred Stock, the Series B
Preferred Stock, the Series C Preferred Stock, or upon the conversion of the
Warrants; (b) the Mount Sinai Shares; (c) any Common Stock of the Company issued
as (or issuable upon the conversion or exercise of any warrant, right or other
security which is issued as) a dividend or other distribution with respect to,
or in exchange for or in replacement of the Series A Preferred Stock, Series B
Preferred Stock, Series C Preferred Stock or the Mount Sinai Shares; (d) any
Common Stock acquired (i) by any Investor or Mount Sinai subsequent to the date
hereof or (ii) by CHL Medical Partners II, L.P. or CHL Medical Partners II Side
Fund, L.P. upon the exercise of the Bridge Loan Warrants and (e) the Common
Stock issuable upon the exercise of the GECC Warrant. Notwithstanding the
foregoing, that as to any particular Registrable Securities that have been
issued, such securities shall cease to be Registrable Securities when (i) a
registration statement with respect to the sale of such securities shall have
become effective under the Securities Act and such

                                      -3-
<PAGE>

securities shall have been disposed of under such registration statement, (ii)
they shall have been distributed to the public pursuant to Rule 144, (iii) they
shall have been otherwise transferred or disposed of, and new certificates
therefor not bearing a legend restricting further transfer shall have been
delivered by the Company, and subsequent transfer or disposition of them shall
not require their registration or qualification under the Securities Act or any
similar state law then in force, or (iv) they shall have ceased to be
outstanding.

      "Registration Statement" means a registration statement filed by the
Company with the SEC 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).

      "S-3 Initiating Holders" has the meaning set forth in Section 5(a) of this
Agreement.

      "S-3 Registration" has the meaning set forth in Section 5(a) of this
Agreement.

      "SEC" means the Securities and Exchange Commission or any similar agency
then administering the Securities Act.

      "Securities Act" means the Securities Act of 1933, as amended, and the
rules and regulations of the SEC promulgated thereunder.

      "Series A Preferred Stock" means the Series A Convertible Preferred Stock
of the Company, par value $0.01 per share.

      "Series B Preferred Stock" means the Series B Convertible Preferred Stock
of the Company, par value $0.01 per share.

      "Series C Preferred Stock" has the meaning set forth in the preamble to
this Agreement.

      "Stockholders Agreement" means the Second Amended and Restated
Stockholders Agreement, dated the date hereof, as amended from time to time,
among the Company, the Investors, and the other stockholders named therein.

      "Warrants" has means warrants to purchase up to 555,003 shares of Series B
Preferred Stock.

      2. Grant Of Rights. The Company hereby grants Registration Rights to the
Holders upon the terms and conditions set forth in this Agreement.

      3. Demand Registration.

            (a) Request for Demand Registration for Holders. At any time after
the IPO Effectiveness Date, the Holders of a majority of the Registrable
Securities held in the aggregate by all Holders (the "Initiating Holders"), may
make a written request to the Company to register, and the Company shall
register, under the Securities Act (other than pursuant to a Registration
Statement on Form S-4 or S-8 or any successor thereto) (a "Demand
Registration"), the number of Registrable Securities stated in such request;
provided, however, that the Company shall not be obligated to effect (i) more
than two such Demand Registrations under this Section 3(a) and

                                      -4-
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(ii) a Demand Registration if the Initiating Holders propose to sell their
Registrable Securities at an aggregate price (calculated based upon the Market
Price of the Registrable Securities on the date of filing of the Registration
Statement with respect to such Registrable Securities) to the public of less
than $5,000,000. For purposes of the preceding sentence, two or more
Registration Statements filed in response to one demand shall be counted as one
Registration Statement. If at the time of any request to register Registrable
Securities pursuant to this Section 3(a), the Company is engaged in a registered
public offering or the Company determines in good faith certifies in writing
that any such registration would require the Company to include disclosure that
would reasonably be expected to have a materially detrimental effect on any
proposal, negotiations or plan by the Company or any of its subsidiaries to
engage in any material acquisition or disposition of assets or any material
merger, consolidation, tender offer, reorganization or similar transaction or
any other material corporate event contemplated by the Company, then the Company
may at its option direct that such request be delayed for a reasonable period
not in excess of three (3) months, such right to delay a request to be exercised
by the Company not more than once in any twelve (12) month period. Each request
for a Demand Registration by the Initiating Holders shall state the amount of
the Registrable Securities proposed to be sold and the intended method of
disposition thereof.

            (b) Incidental or "Piggy-Back" Rights with Respect to a Demand
Registration. Each of the Holders (other than Initiating Holders which have
requested a registration under Section 3(a)) may include its or his Registrable
Securities in any Demand Registration pursuant to this Section 3(b). Within ten
(10) days after the receipt of a request for a Demand Registration from an
Initiating Holder, the Company shall (i) give written notice thereof to all of
the Holders (other than Initiating Holders which have requested a registration
under Section 3(a)) and (ii) subject to Section 3(e), include in such
registration all of the Registrable Securities held by such Holders from whom
the Company has received a written request for inclusion therein within twenty
(20) days of the receipt by such Holders of such written notice referred to in
clause (i) above. Each such request by such Holders shall specify the number of
Registrable Securities proposed to be registered. The failure of any Holder to
respond within such 20-day period referred to in clause (ii) above shall be
deemed to be a waiver of such Holder's rights under this Section 3 with respect
to such Demand Registration, provided that any Holder may waive its rights under
this Section 3 prior to the expiration of such 20-day period by giving written
notice to the Company, with a copy to the Initiating Holders.

            (c) Effective Demand Registration. A registration shall not
constitute a Demand Registration until it has become effective and remains
continuously effective for the lesser of (i) the period during which all
Registrable Securities registered in the Demand Registration are sold and (ii)
120 days; provided, however, that a registration shall not constitute a Demand
Registration if (x) after such Demand Registration has become effective, such
registration or the related offer, sale or distribution of Registrable
Securities thereunder is interfered with by any stop order, injunction or other
order or requirement of the SEC or other governmental agency or court for any
reason not attributable to the Initiating Holders and such interference is not
thereafter eliminated or (y) the conditions specified in the underwriting
agreement, if any, entered into in connection with such Demand Registration are
not satisfied or waived, other than by reason of a failure by the Initiating
Holder.

                                      -5-
<PAGE>

            (d) Expenses. The Company shall pay all Registration Expenses in
connection with a Demand Registration, whether or not such Demand Registration
becomes effective.

            (e) Underwriting Procedures. If the Company or the Initiating
Holders holding a majority of the Registrable Securities held by all of the
Initiating Holders so elect, the Company shall use its reasonable best efforts
to cause such Demand Registration to be in the form of a firm commitment
underwritten offering and the managing underwriter or underwriters selected for
such offering shall be the Approved Underwriter selected in accordance with
Section 3(f). In connection with any Demand Registration under this Section 3
involving an underwritten offering, none of the Registrable Securities held by
any Holder making a request for inclusion of such Registrable Securities
pursuant to Section 3 hereof shall be included in such underwritten offering
unless such Holder accepts the terms of the offering as agreed upon by the
Company, the Initiating Holders and the Approved Underwriter, and then only in
such quantity as will not, in the opinion of the Approved Underwriter, have a
material adverse effect on the success of such offering by the Initiating
Holders. If the Approved Underwriter advises the Company that the aggregate
amount of such Registrable Securities requested to be included in such offering
is sufficiently large to have a material adverse effect on the success of such
offering, then the Company shall include in such registration only the aggregate
amount of Registrable Securities that the Approved Underwriter believes may be
sold without any such internal adverse effect and shall reduce the amount of
Registrable Securities to be included in such registration by removing
Registrable Securities owned, first by the Company, second by the entities
listed on Schedule II hereto, Mount Sinai and GECC, pro rata based on the number
of Registrable Securities owned by each such Person and third by all other
Holders, pro rata based on the number of Registrable Securities owned by each
such Holder.

            (f) Selection of Underwriters. If any Demand Registration or S-3
Registration, as the case may be, of Registrable Securities is in the form of an
underwritten the Company shall select and obtain an investment banking firm of
national reputation to act as the managing underwriter of the offering (the
"Approved Underwriter"), provided. however, that the Approved Underwriter shall,
in any case, also be approved by the Initiating Holders or S-3 Initiating
Holders, as the case may be, such approval not to be unreasonably withheld,

      4. Incidental or "Piggy-Back" Registration.

            (a) Request for Incidental Registration. At any time after the IPO
Effectiveness Date, if the Company proposes to file a Registration Statement
under the Securities Act with respect to an offering by the Company for its own
account (other than a Registration Statement on Form S-4 or S-8 or any successor
thereto) or for the account of any stockholder of the Company other than the
Initiating Holders pursuant to a Demand Registration, then the Company shall
give written notice of such proposed filing to each of the Holders at least
twenty (20) days before the anticipated filing date, and such notice shall
describe the proposed registration and distribution and offer such Holders the
opportunity to register the number of Registrable Securities as each such Holder
may request (an "Incidental Registration"). The Company shall use its reasonable
best efforts (within ten (10) days of the notice provided for in the preceding
sentence) to cause the managing underwriter or underwriters in the case of a

                                      -6-
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proposed underwritten offering (the "Company Underwriter") to permit each of the
Holders who have requested in writing to participate in the Incidental
Registration to include its or his Registrable Securities in such offering on
the same terms and conditions as the securities of the Company or the account of
such other stockholder, as the case may be, included therein. In connection with
any Incidental Registration under this Section 4(a) involving an underwritten
offering, the Company shall not be required to include any Registrable
Securities in such underwritten offering unless the Holders thereof accept the
terms of the underwritten offering as agreed upon between the Company, such
other stockholders, if any, and the Company Underwriter, and then only in such
quantity as the Company Underwriter believes will not have a material adverse
effect on the success of such offering. If the Company Underwriter determines
that the registration of all or part of the Registrable Securities which the
Holders have requested to be included would have a material adverse effect on
the success of such offering, then the Company shall be required to include in
such Incidental Registration, to the extent of the amount that the Company
Underwriter believes may be sold without causing such adverse effect, first, all
of the securities to be offered for the account of the Company or the account of
any other stockholder at the request of which the Company intends to file a
Registration Statement, as the case may be; second, the Registrable Securities
to be offered for the account of the Holders, pro rata based on the number of
Registrable Securities owned by each such Holder; and third, any other
securities requested to be included in such underwritten offering.

            (b) Expenses. The Company shall bear all Registration Expenses in
connection with any Incidental Registration pursuant to this Section 4, whether
or not such Incidental Registration becomes effective.

      5. Form S-3 Registration.

            (a) Request for a Form S-3 Registration. Upon the Company becoming
eligible for use of Form S-3 (or any successor form thereto) under the
Securities Act in connection with a public resale of its securities, in the
event that the Company shall receive from one or more of the Holders (the "S-3
Initiating Holders"), a written request that the Company register, under the
Securities Act on Form S-3 (or any successor form then in effect) (an "S-3
Registration"), all or a portion of the Registrable Securities owned by such S-3
Initiating Holders, the Company shall give written notice of such request to all
of the Holders (other than S-3 Initiating Holders which have requested an S-3
Registration under this Section 5(a)) at least thirty (30) days before the
anticipated filing date of such Form S-3, and such notice shall describe the
proposed registration and offer such Holders the opportunity to register the
number of Registrable Securities as each such Holder may request in writing to
the Company, given within fifteen (15) days after their receipt from the Company
of the written notice of such registration. With respect to each S-3
Registration, the Company shall, subject to Section 5(b), (i) include in such
offering the Registrable Securities of the S-3 Initiating Holders and (ii)
include such offering the Registrable Securities of the Holders (other than S-3
Initiating Holders which have requested an S-3 Registration under this Section
5(a)) who have requested in writing to participate in such registration on the
same terms and conditions as the Registrable Securities of the S-3 Initiating
Holders included therein.

            (b) Limitations on Form S-3 Registrations. If at the time of any
request to register Registrable Securities pursuant to Section 5(a), the Company
is engaged in a registered

                                      -7-
<PAGE>

public offering or if the Company shall in good faith certify in writing that
any such registration would require the Company to include disclosure that would
reasonably be expected to have a materially detrimental effect on any proposal,
negotiations or plan by the Company or any of its subsidiaries to engage in any
material acquisition or disposition of assets or any material merger,
consolidation, tender offer, reorganization or similar transaction or any other
material corporate events, contemplated by the Company, then the Company may at
its option direct that such request be delayed for a reasonable period not in
excess of three (3) months, such right to delay a request to be exercised by the
Company not more than once in any twelve (12) month period. In addition, the
Company shall not be required to effect any registration pursuant to Section
5(a), (i) within ninety (90) days after the effective date of any other
Registration Statement of the Company, (ii) if within the twelve (12) month
period preceding the date of such request, the Company has effected two (2)
registrations on Form S-3 pursuant to Section 5(a), (iii) if Form S-3 is not
available for such offering by the S-3 Initiating Holders or (iv) if the S-3
Initiating Holders, together with the Holders (other than S-3 Initiating Holders
which have requested an S-3 Registration under Section 5(a)) registering
Registrable Securities in such registration, propose to sell their Registrable
Securities at an aggregate price (calculated based upon the Market Price of the
Registrable Securities on the date of filing of the Form S-3 with respect to
such Registrable Securities) to the public of less than $2,500,000.

            (c) Expenses. The Company shall bear all Registration Expenses in
connection with any S-3 Registration pursuant to this Section 5, whether or not
such S-3 Registration becomes effective.

            (d) No Demand Registration. No registration requested by any Holder
pursuant to this Section 5 shall be deemed a Demand Registration pursuant to
Section 3.

      6. Holdback Agreements.

            (a) Restrictions on Public Sale by Holders. In connection with any
public offering, each Holder, if requested by the Company and the underwriters
managing such public offering, shall agree not to sell or otherwise transfer or
dispose of any Registrable Securities or other securities of the Company held by
such Holder (other than those Registrable Securities, if any, included in the
public offering) for a specified period of time determined by the Company and
the underwriters following the effective date of a Registration Statement;
provided, however, that: (i) such agreement shall not exceed 180 days from the
effective date of such registration; (ii) all holders of Common Stock holding
not less than the number of shares of Common Stock held by such Holder
(including shares of Common Stock issuable upon the conversion of Series A
Preferred Stock, Series B Preferred Stock, Series C Preferred Stock or other
convertible or exchangeable securities, or upon the exercise of options,
warrants or other rights) and all officers and directors of the Company enter
into similar agreements; provided, however, that all restrictions set forth in
this Section 6 on all such Holders shall terminate and be of no further force or
effect if any such holder, officer, other Holder, or director is released from,
or otherwise no longer bound by, such restrictions; and (iii) such agreement
shall only apply to the first such Registration Statement covering Common Stock
of the Company to be sold on its behalf to the public in the Initial Public
Offering.

                                      -8-
<PAGE>

            (b) Legend. Each certificate representing the Registrable Securities
shall bear a legend substantially in the following form (until such time as such
Registrable Securities cease to be Registrable Securities as set forth herein):

            "THE SECURITIES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO THE
TERMS OF AN INVESTOR RIGHTS AGREEMENT BETWEEN THE COMPANY AMD THE REGISTERED
OWNER OF THIS CERTIFICATE (OR THE REGISTERED OWNER'S PREDECESSOR IN INTEREST),
AND SUCH AGREEMENT IS AVAILABLE FOR INSPECTION WITHOUT CHARGE AT THE OFFICES OF
THE COMPANY."

      7. Registration Procedures.

            (a) Obligations of the Company. Whenever registration of Registrable
Securities has been requested pursuant to Section 3 or Section 5 of this
Agreement, the Company shall use its reasonable best efforts to cause any such
registration to become and remain effective as soon as practicable, but in any
event not later than forty-five (45) days after it receives a request
thereunder, and whenever registration of Registrable Securities has been
requested pursuant to Section 5 of this Agreement, the Company shall use its
reasonable best efforts to effect the registration and sale of such Registrable
Securities in accordance with, the intended method of distribution thereof as
quickly as practicable, and in connection with any such request under Section 3,
Section 4 or Section 5 of this Agreement, the Company shall, as expeditiously as
possible:

                  (i) prepare and file with the SEC a Registration Statement on
any form for which the Company then qualifies or which counsel for the Company
shall deem appropriate and which form shall be available for the sale of such
Registrable Securities in accordance with the intended method of distribution
thereof, and cause such Registration Statement to become effective; provided,
however, that (x) before filing a Registration Statement or prospectus or any
amendments or supplements thereto, the Company shall provide one counsel
selected by the Holders holding a majority of the Registrable Securities being
registered in such registration ("Holders' Counsel") with an adequate and
appropriate opportunity to review and comment on such Registration Statement and
each prospectus included therein (and each amendment or supplement thereto) to
be filed with the SEC, subject to such documents being under the Company's
control, and (y) the Company shall notify the Holders' Counsel and each seller
of Registrable Securities of any stop order issued or threatened by the SEC and
take all action required to prevent the entry of such stop order or to remove it
if entered;

                  (ii) prepare and file with the SEC such amendments and
supplements to such Registration Statement and the prospectus used in connection
therewith as may be necessary to keep such Registration Statement effective for
the lesser of (x) 120 days and (y) such shorter period which will terminate when
all Registrable Securities covered by such Registration Statement have been
sold, and comply with the provisions of the Securities Act with respect to the
disposition of all securities covered by such Registration Statement during such
period in accordance with the intended methods of disposition by the sellers
thereof set forth in such Registration Statement;

                                      -9-
<PAGE>

                  (iii) furnish to each seller of Registrable Securities, prior
to filing a Registration) Statement, at least one copy of such Registration
Statement as is proposed to be filed, and thereafter such number of copies of
such Registration Statement, each amendment and supplement thereto (in each case
including all exhibits thereto), and the prospectus included in such
Registration Statement (including each preliminary prospectus) as each such
seller may reasonably request in order to facilitate the disposition of the
Registrable Securities owned by such seller;

                  (iv) register or qualify such Registrable Securities under
such other securities or "blue sky" laws of such jurisdictions as any seller of
Registrable Securities may request, and to continue such qualification in effect
in such jurisdiction for as long as permissible pursuant to the laws of such
jurisdiction, or for as long as any such seller requests or until all of such
Registrable Securities are sold, whichever is shortest, and do any and all other
acts and things which may be reasonably necessary or advisable to enable any
such seller to consummate the disposition in such jurisdictions of the
Registrable Securities owned by such seller; provided, however, that the Company
shall not be required to (x) qualify generally to do business in any
jurisdiction where it would not otherwise be required to qualify but for this
Section 7(a)(iv), (y) subject itself to taxation in any such jurisdiction or (z)
consent to general service of process in any such jurisdiction;

                  (v) notify each seller of Registrable Securities at any time
when a prospectus relating thereto is required to be delivered under the
Securities Act, upon discovery that, or upon the happening of any event as a
result of which, the prospectus included in such Registration Statement contains
an untrue statement of a material fact or omits to state any 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 and the
Company shall promptly prepare a supplement or amendment to such prospectus and
furnish to each seller of Registrable Securities a reasonable number of copies
of such supplement to or an amendment of such prospectus as may be necessary so
that, after delivery to the purchasers of such Registrable Securities, such
prospectus shall not contain an untrue statement of a material fact or omit to
state any 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;

                  (vi) enter into and perform customary agreements (including an
underwriting agreement in customary form with the Approved Underwriter or
Company Underwriter, if any, selected as provided in Section 3, Section 4 or
Section 5, as the case may be) and take such other actions as are prudent and
reasonably required in order to expedite or facilitate the disposition of such
Registrable Securities, including causing its officers to participate in "road
shows" and other information meetings organized by the Approved Underwriter or
Company Underwriter;

                  (vii) make available at reasonable times for inspection by any
seller of Registrable Securities, any managing underwriter participating in any
disposition of such Registrable Securities pursuant to a Registration Statement,
Holders' Counsel and any attorney, accountant or other agent retained by any
such seller or any managing underwriter (each, an "Inspector" and collectively,
the "Inspectors"), all financial and other records, pertinent corporate
documents and properties of the Company and its subsidiaries (collectively, the

                                      -10-
<PAGE>

"Records") as shall be reasonably necessary to enable them to exercise their due
diligence responsibility, and cause the Company's and its subsidiaries'
officers, directors and employees, and the independent public accountants of
the Company, to supply all information reasonably requested by any such
Inspector in connection with such Registration Statement;

                  (viii) if such sale is pursuant to an underwritten offering,
obtain a "cold comfort" letter from the Company's independent public accountants
in customary form and covering such matters of the type customarily covered by
"cold comfort" letters as Holders' Counsel or the managing underwriter
reasonably requests;

                  (ix) furnish, at the request of any seller of Registrable
Securities on the date such securities are delivered to the underwriters for
sale pursuant to such registration or, if such securities are not being sold
through underwriters, on the date the Registration Statement with respect to
such securities becomes effective, an opinion, dated such date, of counsel
representing the Company for the purposes of such registration, addressed to the
underwriters, if any, and to the seller making such request, covering such legal
matters with respect to the registration in respect of which such opinion is
being given as the underwriters, if any, and such seller may reasonably request
and are customarily included in such opinions;

                  (x) comply with all applicable rules and regulations of the
SEC, and make available to its security holders, as soon as reasonably
practicable but no later than fifteen (15) months after the effective date of
the Registration Statement, an earnings statement covering a period of twelve
(12) months beginning after the effective date of the Registration Statement, in
a manner which satisfies the provisions of Section 11(a) of the Securities Act
and Rule 158 thereunder;

                  (xi) cause all such Registrable Securities to be listed on
each securities exchange on which similar securities issued by the Company are
then listed, provided that the applicable listing requirements are satisfied;

                  (xii) keep Holders' Counsel advised in writing as to the
initiation and progress of any registration under Section 3, Section 4 or
Section 5 hereunder;

                  (xiii) cooperate with each seller of Registrable Securities
and each underwriter participating in the disposition of such Registrable
Securities and their respective counsel in connection with any filings required
to be made with the NASD; and

                  (xiv) take all other steps reasonably necessary to effect the
registration of the Registrable Securities contemplated hereby.

            (b) Seller Information. The Company may require each seller of
Registrable Securities as to which any registration is being effected to
furnish, and such seller shall furnish, to the Company such information
regarding such seller and the distribution of such securities as the Company may
from time to time reasonably request in writing.

            (c) Notice to Discontinue. Each Holder of Registrable Securities
agrees that, upon receipt of any notice from the Company of the happening of any
event of the kind described in Section 7(a)(v). such Holder shall forthwith
discontinue disposition of Registrable

                                      -11-
<PAGE>
Securities pursuant to the Registration Statement covering such Registrable
Securities until such Holder's receipt of the copies of the supplemented or
amended prospectus contemplated by Section 7(a)(v) and, if so directed by the
Company, such Holder shall deliver to the Company (at the Company's expense) all
copies, other than permanent file copies then in such Holder's possession, of
the prospectus covering such Registrable Securities which is current at the time
of receipt of such notice. If the Company shall give any such notice, the
Company shall extend the period during which such Registration Statement shall
be maintained effective pursuant to this Agreement (including, without
limitation, the period referred to in Section 7(a)(ii)) by the number of days
during the period from and including the date of the giving of such notice
pursuant to Section 7(a)(v) to and including the date when sellers of such
Registrable Securities under such Registration Statement shall have received the
copies of the supplemented or amended prospectus contemplated by and meeting the
requirements of Section 7(a)(v).

            (d) Registration Expenses. The Company shall pay all expenses
arising from or incident to its performance of, or compliance with, this
Agreement, including, without limitation, (i) SEC, stock exchange and NASD
registration and filing fees, (ii) all fees and expenses incurred in complying
with securities or "blue sky" laws (including reasonable fees, charges and
disbursements of counsel to any underwriter incurred in connection with "blue
sky" qualifications of the Registrable Securities as may be set forth in any
underwriting agreement), (iii) all printing, messenger and delivery expenses,
(iv) the fees, charges and disbursements of counsel to the Company and of its
independent public accountants and any other accounting fees, charges and
expenses incurred by the Company (including, without limitation, any expenses
arising from any "cold comfort" letters or any special audits incident to or
required by any registration or qualification) and any legal fees, charges and
expenses incurred by the Company and, in the case of a Demand Registration, an
Incidental Registration or an S-3 Registration, the Holders' Counsel, and (v)
any liability insurance or other premiums for insurance obtained in connection
with any Demand Registration or piggy-back registration thereon. Incidental
Registration or S-3 Registration pursuant to the terms of this Agreement,
regardless of whether such Registration Statement is declared effective.
Notwithstanding the foregoing, the Company shall not be obligated to pay the
fees, expenses or charges of any Inspector other than Holders' Counsel. All of
the expenses described in the preceding sentence of this Section 7(d) are
referred to herein as "Registration Expenses." The Holders of Registrable
Securities sold pursuant to a Registration Statement shall bear the expense of
any broker's commission or underwriter's discount or commission relating to
registration and sale of such Holders' Registrable Securities and, subject to
clause (iv) above, shall bear the fees and expenses of their own counsel.

      8. Indemnification; Contribution.

            (a) Indemnification by the Company. The Company agrees to indemnify
and hold harmless each Holder (including each member, partner, officer and
director thereof and legal counsel and independent accountant thereto) and each
Person who or that controls (within the meaning of the Securities Act or the
Exchange Act) such Holder from and against any and all losses, claims, damages,
liabilities and expenses, joint or several (including reasonable costs of
investigation and including any of the foregoing incurred in connection with the
settlement of any commenced or threatened litigation) (collectively,
"Liabilities"), arising out of or based upon any untrue, or allegedly untrue,
statement of a material fact contained in any Registration

                                      -12-
<PAGE>
Statement, prospectus or preliminary prospectus or notification or offering
circular (as amended or supplemented if the Company shall have furnished any
amendments or supplements thereto) or arising out of or based upon any omission
or alleged omission to state therein a material fact required to be stated
therein or necessary to make the statements therein not misleading under the
circumstances such statements were made or any violation or alleged violation by
the Company of the Securities Act, the Exchange Act, any state securities law or
any rule or regulation Promulgated under the Securities Act the Exchange Act or
any state securities laws or otherwise in connection with the offering covered
by such Registration Statement, except insofar as such Liability arises out of
or is based upon any untrue statement or alleged untrue statement or omission or
alleged omission contained in such Registration Statement, preliminary
prospectus or final prospectus in reliance upon information concerning such
Holder furnished in writing to the Company by such holder expressly for use
therein, including, without limitation, the information furnished to the Company
pursuant to Section 7(b) and except insofar as such Liability arises out of such
indemnified person's failure to send or give a copy of the final prospectus, as
the same may be then supplemented or amended, to the person asserting an untrue
statement or alleged untrue statement or omission or alleged omission at or
prior to the written confirmation of the sale of Registrable Securities to such
person if such statement or omission was corrected in such final prospectus so
long as such final prospectus, and any amendments or supplements thereto, have
been furnished to such indemnified person. The Company shall also provide
customary indemnities to any underwriters of the Registrable Securities, their
officers, directors and employees and each Person who controls such underwriters
(within the meaning of Section 15 of the Securities Act) to the same extent as
provided above with respect to the indemnification of the Holders of Registrable
Securities.

            (b) Indemnification by Holders. In connection with any Registration
Statement in which a Holder is participating pursuant to Section 3, Section 4 or
Section 5 hereof, each such Holder shall promptly furnish to the Company in
writing such information with respect to such Holder as the Company may
reasonably request or as may be required by law for use in connection with any
such Registration Statement or prospectus and all information required to be
disclosed in order to make the information previously furnished to the Company
by such Holder not materially misleading or necessary to cause such Registration
Statement not to omit a material fact with respect to such Holder necessary in
order to make the statements therein not misleading. Each Holder agrees to
indemnify and hold harmless the Company, the underwriters, if any, each other
Holder, each Person who controls the Company, any such underwriter or such other
Holder (within the meaning of Section 15 of the Securities Act) and their
respective officers, directors, partners, employees, agents and representatives
for any Liabilities arising out of or based upon any such information with
respect to such Holder furnished in writing to the Company by such Holder
expressly for use in such registration statement or prospectus, including,
without limitation, the information furnished to the Company pursuant to this
Section 8(b) in the event that such information is untrue, omits a material fact
required to be stated therein or necessary to make such information not
misleading under the circumstances; provided, however, that the total amount to
be indemnified by such Holder Pursuant to this Section 8(b) shall be limited to
the net proceeds received by such Holder in the offering to which the
Registration Statement or prospectus relates; provided, further, however, that
no such Holder will be liable for any amount paid in settlement of any such
claim, loss, damage, liability or action if such settlement is effected without
the consent of such Holder, which consent shall not be unreasonably withheld,
conditioned or delayed.

                                      -13-
<PAGE>

            (c) Conduct of Indemnification Proceedings. Any Person entitled to
indemnification hereunder (the "Indemnified Party") agrees to give prompt
written notice to the indemnifying party (the "Indemnifying Party") after the
receipt by the Indemnified Party of any written notice of the commencement of
any action, suit, proceeding or investigation or threat thereof made in writing
for which the Indemnified Party intends to claim indemnification or contribution
pursuant to this Agreement; provided, however, that the failure so to notify the
Indemnifying Party shall not relieve the Indemnifying Party of any Liability
that it may have to the Indemnified Party hereunder (except to the extent that
the Indemnifying Party is materially prejudiced or otherwise forfeits material
rights or defenses by reason of such failure). If notice of commencement of any
such action is given to the Indemnifying Party as above provided, the
Indemnifying Party shall be entitled to participate in and, to the extent it may
wish, jointly with any other Indemnifying Party similarly notified, to assume
the defense of such action at its own expense, with counsel chosen by it and
reasonably satisfactory to such Indemnified Party. The indemnified Party shall
have the right to employ separate counsel in any such action and participate in
the defense thereof, but the fees and expenses of such counsel shall be paid by
the Indemnified Party unless (i) the Indemnifying Party agrees to pay the same,
(ii) the Indemnifying Party fails to assume the defense of such action with
counsel reasonably satisfactory to the Indemnified Party or (iii) the named
parties to any such action (including any impleaded parties) include both the
Indemnifying Party and the Indemnified Party and either of such parties has been
advised by its counsel that either (x) representation of such Indemnified Party
and the Indemnifying Party by the same counsel would be inappropriate under
applicable standards of professional conduct or (y) there may be one or more
legal defenses available to the Indemnified Party which are different from or
additional to those available to the Indemnifying Party. In any such case, the
Indemnifying Party shall not have the right to assume the defense of such action
on behalf of such Indemnified Party, it being understood, however, that the
Indemnifying Party shall not be liable for the fees and expenses of more than
one separate firm of attorneys (in addition to any local counsel) for all
similarly situated Indemnified Parties. No Indemnifying Party shall be liable
for any settlement entered into without its written consent, which consent
Shall not be unreasonably withheld. No Indemnifying Party shall, without the
consent of such Indemnified Party, effect any settlement of or consent to the
entry of any judgment of any pending or threatened proceeding in respect of
which such Indemnified Party is a party and indemnity has been sought hereunder
by such Indemnified Party, unless such settlement includes an unconditional
release of such Indemnified Party from all liability for claims that are the
subject matter of such proceeding.

            (d) Contribution. If the indemnification provided for in this
Section 8 from the Indemnifying Party is unavailable to an Indemnified Party
hereunder in respect of any Liabilities referred to therein, then the
Indemnifying Party, in lieu of indemnifying such Indemnified Party, shall
contribute to the amount paid or payable by such Indemnified Party as a result
of such Liabilities in such proportion as is appropriate to reflect the relative
fault of the Indemnifying Party and Indemnified Party in connection with the
actions which resulted in such Liabilities, as well as any other relevant
equitable considerations. The relative faults of such Indemnifying Party and
Indemnified Party shall be determined by reference to, among other things,
whether any action in question, including any untrue or alleged untrue statement
of a material fact or omission or alleged omission to state a material fact, has
been made by, or relates to information supplied by, such Indemnifying Party or
Indemnified Party, and the parties' relative intent, knowledge, access to
information and opportunity to correct or prevent such

                                      -14-
<PAGE>

action. The amount paid or payable by a party as a result of the Liabilities
referred to above shall be deemed to include, subject to the limitations set
forth in Sections 8(a), 8(b) and 8(c), any legal or other fees, charges or
expenses reasonably incurred by such party in connection with any investigation
or proceeding; provided that the total amount to be contributed by any Holder
shall be limited to the net proceeds received by such Holder in the offering.

The parties hereto agree that it would not be just and equitable if contribution
pursuant to this Section 8(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 in the immediately preceding paragraph. 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.

      9. Rule 144. The Company covenants that from and after the earliest of (a)
the IPO Effectiveness Date, (b) the registration by the Company of a class of
securities under Section 12 of the Exchange Act and (c) the issuance by the
Company of an offering circular pursuant to Regulation A under the Securities
Act it shall (i) file any reports required to be filed by it under the Exchange
Act and the Securities Act and (ii) take such further action as each Holder of
Registrable Securities may reasonably request (including providing any
information necessary to comply with Rule 144 under the Securities Act), all to
the extent required from time to time to enable such Holder to sell Registrable
Securities without registration under the Securities Act within the limitation
of the exemptions provided by (A) Rule 144 under the Securities Act, as such
rule may be amended from time to time or (B) any similar rules or regulations
hereafter adopted by the SEC. The Company shall, upon the request of any Holder
of Registrable Securities, deliver to such Holder a written statement as to
whether it has complied with such requirements.

      10. Limitations on Subsequent Registration Rights; No Inconsistent
Agreements.

            (i) The Company shall not, without the prior written consent of the
Investors holding at least 60% of the Registrable Securities held by all
Investors, enter into any other agreement with any holder or prospective holder
of any securities of the Company that would allow such holder or prospective
holder (a) to make a demand registration that could result in such registration
statement being declared effective prior to twelve (12) months after the Initial
Public Offering or (b) to have registration rights that are pari passu with or
superior to the rights granted to the Investors under this Agreement. The
Company represents and warrants that it has not granted to any Person the right
to request or require the Company to register any securities issued by the
Company, other than the rights granted to the Holders herein.

            (ii) The Company shall not enter into any agreement with respect to
its securities that is inconsistent with the rights granted to the Holders in
this Agreement or grant any additional registration rights to any Person or with
respect to any securities which are not Registrable Securities which are prior
in right to or inconsistent with the rights granted in this Agreement,

                                      -15-
<PAGE>

      11. Miscellaneous.

            (a) Recapitalizations, Exchanges, Etc. The provisions of this
Agreement shall apply to the full extent set forth herein with respect to (i)
the shares of Common Stock, (ii) any and all shares of voting common stock of
the Company into which the shares of Common Stock are converted, exchanged or
substituted in any recapitalization or other capital reorganization by the
Company and (iii) any and all equity securities of the Company or any successor
or assign of the Company (whether by merger, consolidation, sale of assets or
otherwise) which may be issued in respect of, in conversion of, in exchange for
or in substitution of, the shares of Common Stock and shall be appropriately
adjusted for any stock dividends, splits, reverse splits, combinations,
recapitalizations and the like occurring after the date hereof. The Company
shall cause any successor or assign (whether by merger, consolidation, sale of
assets or otherwise) to enter into an agreement with the Holders on terms
substantially the same as this Agreement as a condition of any such transaction.

            (b) Remedies. The Holders, in addition to being entitled to exercise
all rights granted by law, including recovery of damages, shall be entitled to
specific performance of their rights under this Agreement. The Company agrees
that monetary damages would not be adequate compensation for any loss incurred
by reason of a breach by it of the provisions of this Agreement and hereby
agrees to waive in any action for specific performance the defense that a remedy
at law would be adequate.

            (c) Amendments and Waivers. Except as otherwise provided herein, the
provisions of this Agreement may not be amended, modified or supplemented, and
waivers or consents to departures from the provisions hereof may not be given
unless consented to in writing by (i) the Company and (ii) the Investors holding
at least 60% of the aggregate number of shares of Common Stock issued or
issuable upon conversion of the Series A Preferred Stock, the Series B Preferred
Stock and the Series C Preferred Stock owned by all of the Investors; provided,
however, that if any such amendment, modification, supplement, waiver or consent
would adversely change a specifically enumerated right or obligation hereunder
of one or more parties hereto (the "Adversely Affected Parties") in a way that
is adverse to the Adversely Affected Parties and in a manner different from the
manner in which such specifically enumerated right or obligation is changed with
respect to other parties hereto, such amendment or waiver shall also require the
written consent of each such Adversely Affected Party, Any such written consent
shall be binding upon the Company and all of the Holders.

            (d) Notices. All notices, demands and other communications provided
for or permitted hereunder shall be made in writing and shall be made by
registered or certified first- class mail, return receipt requested, facsimile,
courier service or personal delivery:

                        (i)   if to the Company:

                              Amicus Therapeutics, Inc.
                              6 Cedar Brook Drive
                              Cranbury, NJ 08512
                              Facsimile: (732) 745-9769
                              Attention: Chief Executive Officer

                        with a copy to:

                                      -16-
<PAGE>

                              Paul, Hastings, Janofsky & Walker LLP
                              1055 Washington Boulevard
                              Stamford, CT 06901-2217
                              Facsimile: (203)359-3031
                              Attention: Elizabeth A. Brower, Esq.

                  (ii) if to any Holder, at its address as it appears on the
record books of the Company.

All such notices, demands and other communications shall be deemed to have been
duly given when delivered by hand, if personally delivered; when delivered by
courier, if delivered by commercial courier service; five (5) Business Days
after being deposited in the mail, postage prepaid, if mailed; and when receipt
is mechanically acknowledged, if sent by facsimile.

            (e) Successors and Assigns; Third Party Beneficiaries. This
Agreement shall inure to the benefit of and be binding upon the heirs, legatees,
legal representatives, successors and permitted assigns of each of the parties
hereto as hereinafter provided. The rights of the Holders set forth in this
Agreement shall be, with respect to any Registrable Security, automatically
transferred to any Person who is the transferee of such Registrable Security.
All of the obligations of the Company hereunder shall survive any such transfer.
Except as provided in Section 8, no Person other than the parties hereto and
their heirs, legatees, legal representatives, successors and permitted assigns
is intended to be a beneficiary of any of the rights granted hereunder.

            (f) Counterparts. This Agreement may be executed in any number of
counterparts and by the parties hereto in separate counterparts, each of which
when so executed shall be deemed to be an original and all of which taken
together shall constitute one and the same agreement.

            (g) Headings. The headings in this Agreement are for convenience of
reference only and shall not limit or otherwise affect the meaning hereof.

            (h) Governing Law. THIS AGREEMENT SHALL BE GOVERNED BY AND CONSTRUED
IN ACCORDANCE WITH THE LAWS OF THE STATE OF DELAWARE, WITHOUT REGARD TO THE
PRINCIPLES OF CONFLICTS OF LAW OF ANY JURISDICTION.

            (i) Severability. If any one or more of the provisions contained
herein, or the application thereof in any circumstance, is held invalid, illegal
or unenforceable in any respect for any reason, the validity, legality and
enforceability of any such provision in every other respect and of the remaining
provisions hereof shall not be in any way impaired, it being intended that all
of the rights and privileges of the Holders shall be enforceable to the fullest
extent permitted by law.

                                      -17-
<PAGE>

            (j) Entire Agreement. This Agreement is intended by the parties as a
final expression of their agreement and intended to be a complete and exclusive
statement of the agreement and understanding of the parties hereto in respect of
the subject matter contained herein. There are no restrictions, promises,
warranties or undertakings, other than those set forth or referred to herein and
in the Series C Stock Purchase Agreement and the Stockholders Agreement. This
Agreement supersedes all prior agreements, understandings, or commitments,
whether oral or written, regarding the subject matter of this Agreement,
including without limitation, the Existing Investor Rights Agreement.

            (k) Further Assurances. Each of the parties shall execute such
documents and perform such further acts as may be reasonably required or
necessary to carry out or to perform the provisions of this Agreement.

            (l) Other Agreements. Nothing contained in this Agreement shall be
deemed to be a waiver of, or release from, any obligations any party hereto may
have under, or any restrictions on the transfer of Registrable Securities or
other securities of the Company imposed by, any other agreement including, but
not limited to, the Series B Stock Purchase Agreement or the Stockholders
Agreement.

            (m) Jury Trial Waiver. To the fullest extent permitted by law, and
as separately bargained-for-consideration, each party hereby waives any right to
trial by jury in any action, suit, proceeding or counterclaim of any kind
arising out of or relating to this Agreement.

            (n) Expenses. The Company shall pay, and hold the Investors and all
holders of Registrable Securities harmless against liability for the payment of
the reasonable fees and expenses incurred with respect to the enforcement of the
rights granted under this Agreement.

                  [REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

                                      -18-
<PAGE>

      IN WITNESS WHEREOF, the parties hereto have executed this SECOND AMENDED
AND RESTATED INVESTOR RIGHTS AGREEMENT as of the date set forth in the first
paragraph hereof.

                                    AMICUS THERAPEUTICS, INC.,
                                    a Delaware corporation

                                    By: /s/ John Crowley
                                        --------------------------------------
                                        Name: John Crowley
                                        Title: Chief Executive Officer

                                    CHL MEDICAL PARTNERS II, L.P.
                                    By: Collinson, Howe & Lennox II, LLC
                                    Its: General Partner

                                    By: /s/ Gregory M. Weinhoff
                                        --------------------------------------
                                        Name: Gregory M. Weinhoff
                                        Title: Vice President

                                    CHL MEDICAL PARTNERS II, SIDE FUND L.P.
                                    By: Collinson, Howe & Lennox II, LLC
                                    Its: General Partner

                                    By: /s/ Gregory M. Weinhoff
                                        --------------------------------------
                                        Name: Gregory M. Weinhoff
                                        Title: Vice President

                 [SIGNATURE PAGE TO SECOND AMENDED AND RESTATED
                           INVESTOR RIGHTS AGREEMENT]

<PAGE>

                                    CANAAN EQUITY III L.P.

                                    By: Canaan Equity Partners III LLC
                                        Member

                                    By: /s/ Seth A. Rudnick
                                        --------------------------------------
                                        Name: Seth A. Rudnick, M.D.
                                        Title:

                                    CANAAN EQUITY III ENTREPRENEURS LLC
                                    By: Canaan Equity Partners III LLC
                                        Member/Manager

                                    By: /s/ Seth A. Rudnick
                                        --------------------------------------
                                        Name: Seth A. Rudnick, M.D.
                                        Title:

                                    NEW ENTERPRISE ASSOCIATES II, LIMITED
                                    PARTNERSHIP
                                    By: NEA Partners II, Limited Partnership
                                    Its: General Partner

                                    By: NEA II GP, LLC
                                    Its: General Partner

                                    By: /s/ Charles W. Newhall III
                                        --------------------------------------
                                        Name: Charles W. Newhall III
                                        Title: General Partner

                 [SIGNATURE PAGE TO SECOND AMENDED AND RESTATED
                           INVESTOR RIGHTS AGREEMENT]

<PAGE>

                                    NEA VENTURES 2004, LIMITED PARTNERSHIP

                                    By: /s/ Pamela J. Clark
                                        --------------------------------------
                                        Name: Pamela J. Clark
                                        Title: Vice President

                                    PROSPECT VENTURE PARTNERS II, L,P.
                                    By: Prospect Management Co. II, LLC
                                    Its: General Partner

                                    By: /s/ Alex Barkas
                                        --------------------------------------
                                        Name:
                                        Title:

                                    PROSPECT ASSOCIATES II, L.P.
                                    By: Prospect Management Co. II, LLC
                                    Its: General Partner

                                    By: /s/ Alex Barkas
                                        --------------------------------------
                                        Name:
                                        Title:

                                    RADIUS VENTURE PARTNERS II, L.P.
                                    By: /s/ Radius Venture Partners II, L.P.
                                    Its: General Partner

                                    By: /s/ Jordan Davis
                                        --------------------------------------
                                        Name: JORDAN DAVIS
                                        Title: Managing Member

                 [SIGNATURE PAGE TO SECOND AMENDED AND RESTATED
                           INVESTOR RIGHTS AGREEMENT]

<PAGE>

                                    FRAZIER HEALTHCARE IV, L.P.
                                    By: FHM IV, LP
                                    Its: General Partner

                                    By: FHM IV, LLC
                                    Its: General Partner

                                    By: /s/ Nader Naini
                                        -------------------------------------
                                        Name: Nader Naini
                                        Title: Manager

                                    FRAZIER AFFILIATES IV, L.P.
                                    By: FHM IV, LP
                                    Its: General Partner

                                    By: FHM IV, LLC
                                    Its: General Partner

                                    By: /s/ Nader Naini
                                        -------------------------------------
                                        Name: Nader Naini
                                        Title: Manager

                                    HUTTON LIVING TRUST
                                    dated 12/10/96

                                    By: /s/ Wende Hutton
                                        -------------------------------------
                                        Wende Hutton, Trustee

                 [SIGNATURE PAGE TO SECOND AMENDED AND RESTATED
                           INVESTOR RIGHTS AGREEMENT]

<PAGE>

                                    QUAKER BIOVENTURES, L.P.

                                    By: Quaker Bioventures Capital, L.P., its
                                    general partner

                                    By: Quaker Bioventures Capital, LLC, its
                                    general partner

                                    By: /s/ R. Eric Emrich
                                        --------------------------------------
                                        Name: R. Eric Emrich
                                        Title: CFO/VP

                                    GARDEN STATE LIFE SCIENCES
                                    VENTURE FUND, L.P.

                                    By: Quaker Bioventures Capital, L.P., its
                                    general partner

                                    By: Quaker Bioventures Capital. LLC, its
                                    general partner

                                    By: /s/ R. Eric Emrich
                                        --------------------------------------
                                        Name: R. Eric Emrich
                                        Title: CFO/VP

                                    DILIP MEHTA

                                    /s/ Dilip Mehta
                                    -----------------------------------------
                                    Dilip Mehta

                 [SIGNATURE PAGE TO SECOND AMENDED AND RESTATED
                           INVESTOR RIGHTS AGREEMENT]

<PAGE>

                                  PALO ALTO HEALTHCARE FUND, L.P.

                                  By: Palo Alto Investors, LLC., General Partner

                                  By: Palo Alto Investors, Manager

                                  By: /s/ William L. Edwards
                                      --------------------------------------
                                      William L. Edwards, President

                                  PALO ALTO FUND II, L.P.

                                  By: Palo Alto Investors, LLC., General Partner

                                  By: Palo Alto Investors, Manager

                                  By: /s/ William L. Edwards
                                      --------------------------------------
                                      William L. Edwards, President

                                  MICRO CAP PARTNERS, L.P.

                                  By: Palo Alto Investors, LLC., General Partner

                                  By: Palo Alto Investors, Manager

                                  By: /s/ William L. Edwards
                                      --------------------------------------
                                      William L. Edwards, President

                                  UBTI FREE, L.P.

                                  By: Palo Alto Investors, LLC., General Partner

                                  By: Palo Alto Investors, Manager

                                  By: /s/ William L. Edwards
                                      --------------------------------------
                                      William L. Edwards, President

                 [SIGNATURE PAGE TO SECOND AMENDED AND RESTATED
                           INVESTOR RIGHTS AGREEMENT]

<PAGE>

                                   Schedule I
                                    Investors

Canaan Equity III, L.P,

Canaan Equity III Entrepreneurs, LLC

CHL, Medical Partners II, L.P.

CHL, Medical Partners II Side Fund, L.P.

Frazier Healthcare IV, L.P.

Frazier Affiliates IV, L.P.

Hutton Living Trust dated 12/10/96

New Enterprise Associates II, Limited Partnership

Prospect Venture Partners II, L.P.

Prospect Associates II, L.P.

Radius Venture Partners II, L.P.

Dilip Mehta

Quaker Bio Ventures, L.P,

Garden State Life Sciences Venture Fund, L.P.

Micro Cap Partners, L.P.

UBTI Free L.P.

Palo Alto Healthcare Fund, L.P.

Palo Alto Fund II, L.P.

<PAGE>

                                   Schedule II

Mount Sinai School of Medicine

General Electric Capital Corporation

<PAGE>

                                    AMENDMENT
                                       TO
                           SECOND AMENDED AND RESTATED
                            INVESTOR RIGHTS AGREEMENT

      This AMENDMENT, dated as of May 16, 2006, amends that certain Second
Amended And Restated Investor Rights Agreement, dated as of August 17, 2005 (the
"Investor Rights Agreement"), by and among Amicus Therapeutics, Inc., a Delaware
corporation (the "Company"), and the parties listed on Schedule I thereto and
the parties listed on Schedule II thereto. Capitalized terms used herein without
definition shall have the meaning for such terms as set forth in the Investor
Rights Agreement.

      WHEREAS, the Company and certain of its stockholders are parties to the
Investor Rights Agreement;

      WHEREAS, the undersigned persons represent at least 60% of the shares of
Common Stock issued or issuable upon the conversion of outstanding Series A
Preferred Stock, Series B Preferred Stock and Series C Preferred Stock, together
as a single class, which constitute the persons necessary to effect the
amendments set forth herein; and

      WHEREAS, the Company and the undersigned wish to amend the Investor Rights
Agreement to ensure that the demand registration rights are not permitted to be
exercised prior to the 180 day period following the consummation of the initial
public offering of shares of Common Stock of the Company;

      NOW, THEREFORE, in consideration of the mutual covenants and agreements
set forth herein and for good and valuable consideration, the receipt and
adequacy of which are hereby acknowledged, the parties hereto amend the Investor
Rights Agreement as follows:

      1. Section 3 (a) of the Investor Rights Agreement is amended by adding the
phrase "the 180-day period following" after the phrase "At any time" and before
"the IPO Effectiveness Date" in the first sentence thereof.

      2. The Investor Rights Agreement, as amended by this Amendment, contains
the entire understanding of the parties, and any reference on or after the date
of this Amendment to the Investor Rights Agreement shall mean such Investor
Rights Agreement as amended by this Amendment. This Amendment shall be binding
on all parties to the Investor Rights Agreement, whether or not such party has
signed below, in accordance with the original terms of the Investor Rights
Agreement.

      3. In all other respects, the Investor Rights Agreement survives the
execution of this Amendment and continues in full force and effect

<PAGE>

      IN WITNESS WHEREOF, the undersigned have caused this Amendment to the
Investor Rights Agreement to be duly executed as an instrument under seal as of
the date first set forth above.

                                    AMICUS THERAPEUTICS, INC.

                                    By: /s/ John F. Crowley
                                        -------------------------------------
                                        Name: John F. Crowley
                                        Title: Chief Executive Officer

                                    CANAAN EQUITY III L.P.
                                    By: Canaan Equity Partners III LLC, Member

                                    By: /s/ Guy M. Russo
                                        -------------------------------------
                                        Name: Guy M. Russo
                                        Title: CFO & Administrative Partner

                                    CANAAN EQUITY III ENTREPRENEURS LLC
                                    By: Canaan Equity Partners III LLC,
                                                 Member/Manager

                                    By: /s/ Guy M. Russo
                                        -------------------------------------
                                        Name: Guy M. Russo
                                        Title: CFO & Administrative Partner

                                    CHL MEDICAL PARTNERS II, L.P.
                                    By: Collinson, Howe & Lennox II, LLC,
                                               Its General Partner

                                    By: /s/ Gregory M. Weinhoff
                                        -------------------------------------
                                        Name: Gregory M. Weinhoff
                                        Title: Vice President

<PAGE>

                                    CHL MEDICAL PARTNERS II SIDE FUND, L.P.
                                    By: Collinson, Howe & Lennox II, LLC,
                                            Its General Partner


                                    By: /s/ Gregory M. Weinhoff
                                        -------------------------------------
                                        Name: Gregory M. Weinhoff
                                        Title: Vice President

                                    NEW ENTERPRISE ASSOCIATES II, LIMITED
                                    PARTNERSHIP
                                    By: NEA Partners II, Limited Partnership,
                                           Its General Partner

                                    By: /s/ Eugene A. Treinor III
                                        --------------------------------------
                                        Name: Eugene A. Treinor
                                        Title: Manager

                                    NEA VENTURES 2004, LIMITED PARTNERSHIP

                                    By: /s/ Pamela J. Clark
                                        --------------------------------------
                                        Name: Pamela J. Clark
                                        Title: Vice President

                                    PROSPECT VENTURES PARTNERS
                                    By: Prospect Management Co. II, LLC,
                                           Its General Partner

                                    By: /s/ Alex Barkas
                                        --------------------------------------
                                        Name: Alex Barkas
                                        Title: Managing Member

<PAGE>

                                    PROSPECT ASSOCIATES II, L.P.
                                    By: Prospect Management Co. II, LLC
                                           Its General Partner

                                    By: /s/ Alex Barkas
                                        --------------------------------------
                                        Name: Alex Barkas
                                        Title: Managing Member

                                    RADIUS VENTURE PARTNERS II, L.P.
                                    By: Radius Venture Partners II, LLC
                                            Its General Partner

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

                                    FRAZIER HEALTHCARE IV, L.P.
                                    By: FHM IV, LP, Its General Partner

                                    By: /s/ James Topper
                                        --------------------------------------
                                        Name: James Topper
                                        Title: General Partner

                                    FRAZIER AFFILIATES IV, L.P.
                                    By: FHM IV, LP, Its General Partner

                                    By: /s/ James Topper
                                        --------------------------------------
                                        Name: James Topper
                                        Title: General Partner

                                    HUTTON LIVING TRUST, DATED 12/10/06

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

<PAGE>

                                    QUAKER BIOVENTURES, L.P.

                                    By: Quaker Bioventures Capital, L.P., Its
                                            General Partner
                                    By: Quaker Bioventures Capital, LLC, Its
                                            General Partner

                                    By: /s/ Sherrill Neff
                                        --------------------------------------
                                        Name: Sherrill Neff
                                        Title: Managing Partner

                                    GARDEN STATE LIFE SCIENCES VENTURE
                                    FUND, L.P.

                                    By: Quaker Bioventures Capital, L.P., Its
                                            General Partner
                                    By: Quaker Bioventures Capital, LLC, Its
                                            General Partner

                                    By: /s/ Sherrill Neff
                                        --------------------------------------
                                        Name: Sherrill Neff
                                        Title: Managing Partner

                                    DILIP MEHTA

                                    ------------------------------------------
                                    Dilip Mehta

                                    PALO ALTO HEALTHCARE FUND, L.P.

                                    By: Palo Alto Investors, LLC, General
                                    Partner
                                    By: Palo Alto Investors, Manager

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

<PAGE>

                                    PALO ALTO FUND II, L.P.
                                    By: Palo Alto Investors, LLC, General
                                    Partner
                                    By: Palo Alto Investors, Manager

                                    By: ______________________________________
                                    Name:
                                    Title:

                                    MICRO CAP PARTNERS, L.P.
                                    By: Palo Alto Investors, LLC, General
                                    Partner
                                    By: Palo Alto Investors, Manager

                                    By: ______________________________________
                                    Name:
                                    Title:

                                    UBTI FREE, L.P.
                                    By: Palo Alto Investors, LLC, General
                                    Partner
                                    By: Palo Alto Investors, Manager

                                    By: ______________________________________
                                    Name:
                                    Title: