<PAGE>



                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549
                             ----------------------

                                    FORM 10-Q

[ X ] QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES
                              EXCHANGE ACT OF 1934

                      FOR THE QUARTER ENDED MARCH 31, 2000


                         COMMISSION FILE NUMBER 0-21481

                          TRANSKARYOTIC THERAPIES, INC.
             (Exact name of registrant as specified in its charter)

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

             DELAWARE                                           04-3027191
 (State or other jurisdiction of                             (I.R.S. Employer
 incorporation or organization)                             Identification No.)

            195 ALBANY STREET
         CAMBRIDGE, MASSACHUSETTS                                   02139
 (Address of principal executive offices)                        (Zip Code)

       Registrant's telephone number, including area code: (617) 349-0200

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


     Indicate by check mark whether the registrant (1) has filed all reports
required to be filed by Section 13 or 15(d) of the Securities Exchange Act of
1934 during the preceding 12 months (or for such shorter period that the
registrant was required to file such reports), and (2) has been subject to such
filing requirements for the past 90 days.

                            Yes / X /      No /  /


     At April 30, 2000, there were 22,683,306 shares of Common Stock, $.01 par
value, issued and outstanding. There were no issued and outstanding shares of
Preferred Stock.



<PAGE>


                          Transkaryotic Therapies, Inc.




                                      INDEX

<TABLE>
<CAPTION>

                                                                                                        Page Number
                                                                                                        -----------
<S>               <C>                                                                                   <C>

PART  I.          FINANCIAL INFORMATION

Item  1.          Condensed Consolidated Financial Statements (unaudited)

                  Condensed Consolidated Balance Sheets as of
                  March 31, 2000 and December 31, 1999                                                            3

                  Condensed Consolidated Statements of Operations for the Three Months
                  Ended March 31, 2000 and 1999                                                                   4

                  Condensed Consolidated Statements of Cash Flows for the Three
                  Months Ended March 31, 2000 and 1999                                                            5

                  Notes to Condensed Consolidated Financial Statements                                        6 - 8

Item  2.          Management's Discussion and Analysis of Financial Condition and
                  Results of Operations                                                                      9 - 12

Item  3.          Quantitative and Qualitative Disclosures about Market                                          12
                  Risk


PART  II.         OTHER INFORMATION

Item 1.           Legal  Proceedings                                                                             13

Item 6.           Exhibits and Reports on Form 8-K                                                               13


SIGNATURES                                                                                                       14

EXHIBIT INDEX                                                                                                    15

</TABLE>


                                                                               2
<PAGE>


Part 1 -- Item 1 -- Condensed Consolidated Financial Statements

                          Transkaryotic Therapies, Inc.
                      Condensed Consolidated Balance Sheets
                                   (unaudited)

<TABLE>
<CAPTION>

(in thousands, except par values)                           March 31,      December 31,
                                                              2000            1999
                                                          -------------   -------------
<S>                                                       <C>             <C>

ASSETS
Current assets:
   Cash and cash equivalents                                   $79,786        $151,202
   Marketable securities                                       100,136          41,293
   Prepaid expenses and other current assets                     2,325           2,054
                                                          -------------   -------------
      Total current assets                                     182,247         194,549
Property and equipment, net                                     20,723          20,384
Other assets                                                       279             358
                                                          -------------   -------------
Total assets                                                  $203,249        $215,291
                                                          =============   =============
LIABILITIES AND STOCKHOLDERS' EQUITY
Current liabilities:
   Accounts payable                                            $ 2,128         $ 2,000
   Accrued expenses                                              3,904           4,009
   Current maturities of long-term debt                          2,000           2,000
                                                          -------------   -------------
      Total current liabilities                                  8,032           8,009
Long-term debt, less current maturities                         11,000          11,500
                                                          -------------   -------------
      Total liabilities                                         19,032          19,509
                                                          -------------   -------------

Stockholders' equity:
   Preferred stock, $.01 par value, 10,000 shares authorized;
      no shares issued and outstanding                             --               --
   Common stock, $.01 par value;  30,000 shares authorized;
      22,683 and 22,592 shares issued and outstanding at
      March 31, 2000 and December 31, 1999, respectively           227             226
   Additional paid-in capital                                  313,102         311,817
   Accumulated deficit                                        (127,507)       (114,408)
   Deferred compensation                                        (1,422)         (1,645)
   Accumulated other comprehensive loss                           (183)           (208)
                                                          -------------   -------------
      Total stockholders' equity                               184,217         195,782
                                                          =============   =============
Total liabilities and stockholders' equity                    $203,249        $215,291
                                                          =============   =============

</TABLE>



     See accompanying Notes to Condensed Consolidated Financial Statements.


                                                                               3

<PAGE>


Part 1 -- Item 1 -- Condensed Consolidated Financial Statements


                          Transkaryotic Therapies, Inc.
                 Condensed Consolidated Statements of Operations
                                   (unaudited)

<TABLE>
<CAPTION>

(in thousands, except per share amounts)     Three Months Ended
                                                   March 31,
                                              2000         1999
                                            ---------    --------
<S>                                         <C>          <C>

License and research revenues               $     --     $   721
Operating expenses:
   Research and development                   12,684       9,958
   General and administrative                  3,037       1,564
                                            ---------    --------
                                              15,721      11,522
                                            ---------    --------
Loss from operations                         (15,721)    (10,801)
Interest income                                2,622       1,343
                                            ---------    --------
Net loss                                    $(13,099)    $(9,458)
                                            =========    ========

Basic and diluted net loss per share          $(0.58)     $(0.49)
                                            =========    ========
Shares used to compute basic and diluted
   net loss per share                         22,630      19,154
                                            =========    ========

</TABLE>


     See accompanying Notes to Condensed Consolidated Financial Statements.


                                                                               4

<PAGE>

Part 1-- Item 1 -- Condensed Consolidated Financial Statements

                          Transkaryotic Therapies, Inc.
                 Condensed Consolidated Statements of Cash Flows
                                   (unaudited)

<TABLE>
<CAPTION>

(in thousands)                                                Three Months Ended
                                                                  March 31,
                                                             2000            1999
                                                         -------------    ------------
<S>                                                      <C>              <C>

OPERATING ACTIVITIES:
Net loss                                                     $(13,099)        $(9,458)
Adjustments to reconcile net loss to net
   cash provided by operating activities:
      Depreciation and amortization                               556             495
      Compensation expense related to
         equity issuances                                         193             264
Changes in operating assets and liabilities                      (248)          2,237
                                                         -------------    ------------
Net cash used for operating activities                        (12,598)         (6,462)
                                                         -------------    ------------
INVESTING ACTIVITIES:
Proceeds from maturities of marketable securities              11,984          31,688
Purchases of marketable securities                            (70,802)        (25,616)
Purchases of property and equipment                              (895)         (3,422)
Changes in other assets                                            79             (26)
                                                         -------------    ------------
Net cash provided by (used for) investing activities          (59,634)          2,624
                                                         -------------    ------------
FINANCING ACTIVITIES:
Issuance of common stock                                        1,316              58
Repayment of long-term debt                                      (500)              -
Proceeds from issuance of long-term debt                            -           2,364
                                                         -------------    ------------
Net cash provided by financing activities                         816           2,422
                                                         -------------    ------------
Net decrease in cash and cash equivalents                     (71,416)         (1,416)
Cash and cash equivalents at January 1                        151,202          31,760
                                                         =============    ============
Cash and cash equivalents at March 31                         $79,786         $30,344
                                                         =============    ============

</TABLE>


     See accompanying Notes to Condensed Consolidated Financial Statements.


                                                                               5
<PAGE>

PART I -- Item 1 -- Condensed Consolidated Financial Statements


                          Transkaryotic Therapies, Inc.
        Notes to Condensed Consolidated Financial Statements (unaudited)
                             March 31, 2000 and 1999

1.       NATURE OF BUSINESS AND BASIS OF PRESENTATION

         Transkaryotic Therapies, Inc. ("TKT" or "the Company") is a
biopharmaceutical company engaged in the development and commercialization of
products based on its three proprietary product development platforms:
Gene-ActivatedTM proteins, Niche ProteinTM products and Gene Therapy.

         The accompanying unaudited condensed consolidated financial statements
have been prepared in accordance with generally accepted accounting principles
for interim financial information and with the instructions to Form 10-Q and
Article 10 of Regulation S-X. Accordingly, they do not include all of the
information and footnotes required by generally accepted accounting principles
for complete financial statements. In the opinion of management, the
accompanying financial statements include all adjustments, consisting only of
normal recurring adjustments, necessary for a fair presentation of the financial
condition, results of operations and cash flows for the periods presented. The
results of operations for the interim period ended March 31, 2000 are not
necessarily indicative of the results to be expected for the year ending
December 31, 2000.

         These financial statements should be read in conjunction with the
audited financial statements and notes thereto for the year ended December 31,
1999 included in the Company's Annual Report on Form 10-K as filed with the
Securities and Exchange Commission.


2.       BASIC AND DILUTED NET LOSS PER SHARE

         Basic and diluted net loss per share is calculated under Statement of
Financial Accounting Standard ("SFAS") No. 128, "Earnings Per Share." Basic
earnings per share is calculated by dividing income available to common
stockholders by the weighted average common shares outstanding. Diluted earnings
per share is calculated by dividing net income by the sum of weighted average
common shares outstanding during the period plus common stock equivalents.
Common stock equivalents are shares assumed to be issued if outstanding stock
options and warrants were exercised. Basic and diluted net loss per share are
the same for the three months ended March 31, 2000 and 1999 since common
equivalent shares from stock options and warrants have been excluded as their
effect is antidilutive.


                                                                               6

<PAGE>


3.       COMPREHENSIVE INCOME

         During the first quarter of 2000 and 1999, total comprehensive loss
amounted to $13,074,000 and $9,527,000, respectively.


4.       LEGAL PROCEEDINGS

         In April 1997, Amgen Inc. filed a civil action in the U.S. District
Court for the District of Massachusetts against the Company and Aventis Pharma
("Aventis"), formerly Hoechst Marion Roussel, Inc., the Company's collaborative
partner. The complaint in the action alleges that Gene-Activated(TM)
erythropoietin ("GA-EPOTM") and the processes for producing GA-EPO infringe
certain of Amgen's U.S. patents and requests that TKT and Aventis be enjoined
from making, using, or selling GA-EPO and that the District Court award Amgen
monetary damages.

         In November 1997, the Company and Aventis filed a Motion for Summary
Judgment. On the same date, Amgen filed a Motion for Summary Judgment of
Infringement. The Company and Aventis opposed that Motion, stating that there
had been no infringement. In April 1998, the District Court granted TKT and
Aventis' Motion for Summary Judgment and denied Amgen's Motion for Summary
Judgment on the ground that all of the Company and Aventis' GA-EPO related
activities to that date had been solely for uses reasonably related to the
production of information for the submission to the U.S. Food and Drug
Administration for regulatory approval and, under the Waxman-Hatch Act, do
not constitute acts of patent infringement. The District Court, therefore,
administratively closed the case at that time.

         At the request of the Company and Aventis, the District Court reopened
the case in June 1999. The District Court has set a trial date for May 2000.

         After hearing pre-trial motions, in April 2000, the Court granted
Amgen's Motion for Summary Judgment of literal infringement on Claim 1 of U.S.
Patent No 5,955,422 against the Company and Aventis. The Court has not ruled
whether this claim is invalid or unenforceable. Those issues will be
determined at trial. The Court did not grant Summary Judgment on any of the
other claims of the patents involved in this suit. Issues concerning
infringement, invalidity, and unenforceability of those patents will be
argued and determined at the trial.

         In addition, in July 1999, the Company commenced legal proceedings in
the U.K. against Kirin-Amgen, Inc. seeking a declaration that a U.K. patent held
by Kirin-Amgen will not be infringed by the sale of GA-EPO and that numerous
claims of Kirin-Amgen's U.K. patent are invalid. The trial is scheduled to
commence in 2001.

         The Company can provide no assurance as to the outcome of either the
U.S. or U.K. proceedings. A decision by a court in Amgen's or Kirin-Amgen's
favor, including the issuance of an injunction against the making, using, or
selling of GA-EPO by the Company and Aventis in the U.S. or the U.K., or any
other conclusion of either litigation in a manner adverse to the Company and
Aventis, would have a material adverse effect on the Company's business,
financial condition, and results of operations.

         Pursuant to the Amended and Restated License Agreement, dated March
1995, by and between Aventis and the Company, Aventis has assumed the legal cost
of the Amgen and Kirin-


                                                                               7

<PAGE>

Amgen litigations. The Company is required to reimburse Aventis for the
Company's share of litigation expenses, as defined, from future royalties, if
any, received from the sale of GA-EPO and in certain other circumstances. The
Company and Aventis believe that they have substantial defenses to the
allegations in the complaint on the Massachusetts action and substantial grounds
for favorable action in the U.K. litigation.


5.       RECENT ACCOUNTING PRONOUNCEMENTS

         In December 1999, the Securities and Exchange Commission ("SEC") issued
Staff Accounting Bulletin 101 ("SAB 101"), "Revenue Recognition in Financial
Statements," which provides guidance related to revenue recognition based on
interpretations and practices followed by the SEC. The effective date of this
bulletin was deferred to no later than the second fiscal quarter beginning after
December 15, 1999. SAB 101 requires companies to report any changes in revenue
recognition as a cumulative change in accounting principle at the time of
implementation in accordance with Accounting Principles Board Opinion No. 20,
"Accounting Changes." The Company has concluded that SAB 101 will not have a
material impact on the financial position or results of operations of the
Company.

         In April 2000, the Financial Accounting Standards Board issued
Interpretation No. 44, "Accounting for Certain Transactions Involving Stock
Compensation, an Interpretation of APB No. 25." The Interpretation will be
applied prospectively to new awards, modifications to outstanding awards, and
changes in employee status on or after July 1, 2000, except in certain
circumstances. The Company is currently in the process of evaluating the impact
this interpretation will have on its financial position and results of
operations.


















                                                                               8
<PAGE>

PART I -- Financial Information

Item 2.  Management's Discussion and Analysis of Financial Condition and Results
         of Operations

Overview

         Since its inception in 1988, Transkaryotic Therapies, Inc. ( "TKT" or
"the Company") has been primarily engaged in the development and
commercialization of products based on the Company's three proprietary
development platforms: Gene-Activated proteins, Niche Protein products and Gene
Therapy. No revenues have been derived from the sale of any products, and the
Company does not expect to receive revenues from product sales until late 2000,
at the earliest. The Company expects that its research and development
expenditures will increase substantially in future years as product development
efforts accelerate. With the exception of 1995, the Company has incurred
substantial annual operating losses since inception and expects to incur
substantial operating losses in the future. At March 31, 2000, the Company's
accumulated deficit was $127,507,000. As a result, the Company is dependent upon
existing cash resources, interest income, external financing from equity
offerings, debt financings or collaborative research and development
arrangements with corporate sponsors to finance its operations.

         Results of operations may vary significantly from period to period
depending on, among other factors, the progress of the Company's research and
development efforts, the receipt, if any, of additional license fees and
milestone payments, the timing of certain expenses, and the establishment of
additional collaborative research agreements.

         The following discussion of the financial condition and results of
operation of the Company should be read in conjunction with the accompanying
condensed consolidated financial statements and the related footnotes thereto.

RESULTS OF OPERATIONS

FOR THE THREE MONTHS ENDED MARCH 31, 2000 AND 1999

         There were no revenues earned for the three months ended March 31,
2000. License and research revenues totaled $721,000 for the three months ended
March 31, 1999. Revenues in 1999 were earned under collaborative agreements with
Sumitomo Pharmaceuticals Co. Ltd. and Aventis Pharma.

         Research and development expenses totaled $12,684,000 for the three
months ended March 31, 2000, as compared to $9,958,000 during the same period in
1999. The increase in 2000 of $2,726,000, or 27%, was principally due to
increases in external development services and research and development staffing
in each of the Company's product development


                                                                               9

<PAGE>

platforms. In particular, preclinical and clinical costs for the Company's Fabry
disease, Hunter syndrome and hemophilia A programs were significant components
of the increase. During the remainder of 2000, the costs related to both
preclinical and clinical programs are expected to increase significantly as
product development activities are initiated or expanded.

         General and administrative expenses were $3,037,000 for the three
months ended March 31, 2000, compared with $1,564,000 during the same period in
1999. The increase in 2000 of $1,473,000, or 94%, was principally due to costs
in building a business development commercialization infrastructure,
particularly sales and marketing capabilities related to the commercialization
of products in the Company's Niche Protein product platform. During the
remainder of 2000, general and administrative costs are expected to increase
significantly as pre-launch activities related to the Company's Niche Protein
product platform accelerate.

         Interest income was $2,622,000 and $1,343,000 for the three months
ended March 31, 2000 and 1999, respectively. The average cash and marketable
securities balances were $186,425,000 and $105,877,000 for the three months
ended March 31, 2000 and 1999, respectively. The increase in interest income of
$1,279,000 resulted from higher average cash and marketable securities balances,
as well as higher yields, in 2000.

         The Company had a net loss of $13,099,000 and $9,458,000 for the three
months ended March 31, 2000 and 1999, respectively. Basic net loss per share was
$0.58 for the three months ended March 31, 2000, compared to a basic net loss
per share of $0.49 for the same period in 1999.

LIQUIDITY AND SOURCES OF CAPITAL

         Since its inception, the Company has financed its operations through
the sale of common and preferred stock, borrowings under debt agreements,
revenues from collaborative agreements, and interest income.

         The Company had unrestricted cash, cash equivalents and marketable
securities totaling $179,922,000 at March 31, 2000. Cash equivalents and
marketable securities are invested in U.S. Treasury notes, agencies of the U.S.
government, and money market funds.

         In November 1999, the Company completed a private placement of
3,300,000 shares of Common Stock, resulting in net proceeds to the Company of
approximately $124,576,000.

         The Company leased additional facilities in the fourth quarter of 1998
which will be used for research and development. In December 1998, the Company
obtained an unsecured term loan facility for up to $14,000,000 to finance the
capital costs related to the leased space. The loan is payable beginning in
December 1999 on the basis of a seven year amortization schedule over a five
year period, with a final payment for any remaining amount in September 2004.
The loan bears interest at either the prime rate or LIBOR plus 1.50% at the
Company's election. The weighted average interest rate of the loan was 7.6% as
of March 31, 2000. The note contains


                                                                              10

<PAGE>

certain restrictive covenants, including, among other things, minimum cash and
tangible net asset requirements and limitations on the payment of dividends. At
March 31, 2000, $13,000,000 was outstanding under the term loan.

         Even after lease of the new space referred to in the prior paragraph,
the Company's facilities may not be adequate to accommodate the Company's needs
beyond 2000. The Company currently expects to meet any additional facilities
requirements through development of a new facility or conversion of an existing
building. The Company intends to seek financing for all or a significant portion
of the cost of any additional facilities. There can be no guarantee that
financing will be available on favorable terms, if at all.

         At December 31, 1999, the Company had net operating loss carryforwards
of approximately $100,287,000, which expire at various times through 2019. Due
to the degree of uncertainty related to the ultimate use of loss carryforwards
and tax credits, the Company has fully reserved against any potential tax
benefit. The future utilization of net operating loss carryforwards and tax
credits may be subject to limitation under the changes in stock ownership rules
of the Internal Revenue Code. Because of this limitation, it is possible that
taxable income in future years, which would otherwise be offset by net operating
losses, will not be offset and, therefore, will be subject to tax.

         Substantial additional funds will be required to support the Company's
research and development programs, for acquisition of technologies, for
preclinical and clinical testing of its products, pursuit of regulatory
approvals, acquisition of capital equipment, expansion of laboratory and office
facilities, establishment of production capabilities, establishment of sales and
marketing capabilities, and for general and administrative expenses. Until such
time, if any, as the Company's operations generate significant revenues from
product sales, cash resources and proceeds from equity offerings, debt
financings and funding from collaborative arrangements will be required to fund
operations.

         The Company expects to pursue opportunities to obtain additional
financing in the future through equity offerings, debt financings, lease
arrangements related to facilities and capital equipment and collaborative
research agreements. The source, timing and availability of any future financing
will depend principally upon equity and debt market conditions, interest rates
and, more specifically, on the Company's continued progress in its exploratory,
preclinical and clinical development programs. There can be no assurance that
such funds will be available on favorable terms, if at all.

         The Company expects that its existing capital resources, together with
revenues from collaborative agreements and interest income, will be sufficient
to fund its operations into 2002. The Company's cash requirements may vary,
however, depending on numerous factors. Lack of necessary funds may require the
Company to delay, scale back or eliminate some or all of its research and
product development programs or to license its potential products or
technologies to third parties.



                                                                              11

<PAGE>

         The Company is engaged in litigation with Amgen Inc. and Kirin-Amgen,
Inc. with respect to the development of GA-EPO. See Note 4 to Notes to Condensed
Consolidated Financial Statements. Pursuant to TKT's agreements with Aventis,
Aventis has assumed the cost of the litigation. The Company is required to
reimburse Aventis for the Company's share of litigation expenses from future
royalties, if any, otherwise payable by Aventis as to the sale of GA-EPO and in
certain other circumstances.

FORWARD-LOOKING STATEMENTS

         Statements that are not historical facts, including statements
about the Company's confidence and strategies and its expectations about future
products, technologies and opportunities, market demand or acceptance of future
products are forward-looking statements. Without limiting the foregoing, the
words "believes," "anticipates," "plans," "expects," "intends" and similar
expressions are intended to identify forward-looking statements. There are a
number of important factors that could cause the Company's actual results to
differ materially from those indicated by such forward-looking statements,
including, without limitation, whether any of the Company's Gene-Activated
protein, Niche Protein product, or Gene Therapy product candidates will advance
in the clinical trial process, the timing of such clinical trials, whether the
clinical trial results will warrant continued product development, the timing of
making required regulatory filings such as Investigational New Drug applications
and Biologics License Applications, whether the Company's products will receive
approval from the U.S. Food and Drug Administration or equivalent foreign
regulatory agencies, and, if such products receive approval, whether they will
be successfully marketed; the results of patent litigation in which the Company
is involved or may become involved; competition; the Company's dependence on
collaborators; and other risks set forth under the caption "Certain Factors That
May Affect Future Results" in the Company's Annual Report on Form 10-K for the
year ended December 31, 1999, which are incorporated by reference herein.


Item 3.       Quantitative and Qualitative  Disclosures about Market Risk

         The Company does not believe that there is any material market
risk exposure with respect to derivative or other financial instruments that
would require disclosure under this item.


                                                                              12


<PAGE>

PART II - Other Information

Item 1.  Legal Proceedings

     The Company is engaged in litigation with Amgen Inc. and Kirin-Amgen, Inc.
     with respect to the development of GA-EPO. See Note 4 to Notes to Condensed
     Consolidated Financial Statements, which is incorporated by reference
     herein.


Item 6.  Exhibits and Reports on Form 8-K

         (a)      Exhibits

                  The Exhibits filed as part of this Form 10-Q are listed on the
                  Exhibit Index immediately preceding such Exhibits, which
                  Exhibit Index is incorporated herein by reference.

         (b)      Reports on Form 8-K

                  Current Report on Form 8-K dated April 26, 2000.








                                                                              13
<PAGE>

                                   SIGNATURES

         Pursuant to the requirements of the Securities Exchange Act of 1934,
the Registrant has duly caused this report to be signed on its behalf by the
undersigned thereunto duly authorized.

                                       TRANSKARYOTIC THERAPIES, INC.



Date:      May 12, 2000                By:    /s/  Daniel E. Geffken
                                          -------------------------------------
                                          Daniel E. Geffken
                                          Vice President, Finance and
                                          Chief Financial Officer (Principal
                                          Financial and Accounting Officer)







                                                                              14
<PAGE>


                          Transkaryotic Therapies, Inc.




                                  EXHIBIT INDEX


<TABLE>
<CAPTION>

       Exhibit No.             Description
       -----------             -----------
       <S>                     <C>

             10.33             Employment agreement dated February 4, 2000 by and between
                                    Dr. Joseph G. Harbarta and the Registrant


                27             Financial Data Schedule (for EDGAR filing purposes only)


              99.1             Certain Factors That May Affect Future Results
                                    (as filed with the Company's Annual Report on Form 10-K for the
                                    year ended December 31, 1999).



</TABLE>








                                                                              15