CREATIVE BIOMOLECULES INC
S-8, 1997-09-23
BIOLOGICAL PRODUCTS, (NO DIAGNOSTIC SUBSTANCES)
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<PAGE>   1

   As filed with the Securities and Exchange Commission on September 23, 1997

                              Registration No. 333-

                       SECURITIES AND EXCHANGE COMMISSION

                       FORM S-8 REGISTRATION STATEMENT AND
      POST-EFFECTIVE AMENDMENT NO. 1 TO REGISTRATION STATEMENT NO. 33-56706
                        UNDER THE SECURITIES ACT OF 1933

                           CREATIVE BIOMOLECULES, INC.
             (Exact name of registrant as specified in its charter)

                                   94-2786743
                      (I.R.S. Employer Identification No.)

                                    DELAWARE
         (State or other jurisdiction of incorporation or organization)

                 45 SOUTH STREET, HOPKINTON, MASSACHUSETTS 01748
                    (Address of Principal Executive Offices)

      CREATIVE BIOMOLECULES, INC. 1992 NON-EMPLOYEE DIRECTOR NON-QUALIFIED
                               STOCK OPTION PLAN
                            (Full Title of the Plan)

                                MICHAEL M. TARNOW
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                           CREATIVE BIOMOLECULES, INC.
                                 45 SOUTH STREET
                               HOPKINTON, MA 01748
                     (Name and address of agent for service)

                                 (508) 782-1100
          (Telephone number, including area code, of agent for service)
                     --------------------------------------



                         CALCULATION OF REGISTRATION FEE
                                                                                
<TABLE>
<CAPTION>
====================================================================================================================================
                                                                            Proposed                Proposed
                                                     Amount                  maximum                 maximum            Amount of
           Title of each class of                     to be              offering price             aggregate          registration
        securities to be registered               registered(1)           per share (2)        offering price (2)          fee
- ------------------------------------------------------------------------------------------------------------------------------------
<S>                                              <C>                        <C>                     <C>                 <C>
Common stock,
  par value $.01 per share..................        82,500                  $7.2349                  $596,879            $180.87
                                                    17,500                  $9.0938                  $159,142            $ 48.22
                                                   -------                                                               -------
Total.......................................       100,000                                                               $229.09
====================================================================================================================================
</TABLE>

(1) The number of shares of common stock, $.01 par value (the "Common Stock"),
stated above consists of (i) the aggregate number of shares of Common Stock
which may be issued upon the exercise of options which have previously been
granted under the Creative BioMolecules, Inc. 1992 Non-Employee Director
Non-Qualified Stock Option Plan (the "Plan") and (ii) shares of Common Stock
which may be issued upon the exercise of options which may hereafter be granted
under the Plan. The maximum number of shares which may be sold upon the exercise
of such options granted under the Plan is subject to adjustment in accordance
with certain anti-dilution and other provisions of the Plan. Accordingly,
pursuant to Rule 416 under the Securities Act of 1933, as amended (the "1933
Act"), this Registration Statement covers, in addition to the number of shares
stated above, an indeterminable number of shares which may be subject to grant
or otherwise issuable after the operation of any such anti-dilution and other
provisions.

(2) This calculation is made solely for the purpose of determining the
registration fee pursuant to the provisions of Rule 457(h) under the 1933 Act as
follows: in the case of shares of Common Stock for which options have not yet
been granted and the option price of which is therefore unknown, the fee is
calculated on the basis of the average of the high and low prices per share of
the Common Stock on The Nasdaq Stock Market ("Nasdaq") as of a date 
(September 18, 1997) within 5 business days prior to filing this Registration 
Statement.


<PAGE>   2




                                EXPLANATORY NOTE


     This Registration Statement and Post-Effective Amendment No. 1 relate, in
part, to the registration of 100,000 additional shares of Common Stock
authorized for issuance under the Plan, and the filing of a resale prospectus
with respect to such shares. It also constitutes a Post-Effective Amendment for
purposes of filing a resale prospectus with respect to 92,500 previously
registered shares of Common Stock authorized for issuance under the Plan. These
previously registered shares were registered on Registration Statement No.
33-56706. In accordance with the instructional Note to Part I of Form S-8 as
promulgated by the Securities and Exchange Commission (the "Commission"), the
information specified by Part I of Form S-8 has been omitted from this
Registration Statement on Form S-8 for offers of Common Stock pursuant to the
Plan. The Prospectus filed as part of this Registration Statement has been
prepared in accordance with the requirements of Form S-3 and may be used for
reoffering and resales of shares of Common Stock which have been and/or may
hereafter be issued upon the exercise of options which have been and/or may
hereafter be granted under the Plan.


<PAGE>   3



                                   PROSPECTUS

                           CREATIVE BIOMOLECULES, INC.

                         192,500 SHARES OF COMMON STOCK
                            PAR VALUE $.01 PER SHARE
                            ISSUABLE PURSUANT TO THE

                           CREATIVE BIOMOLECULES, INC.
           1992 NON-EMPLOYEE DIRECTOR NON-QUALIFIED STOCK OPTION PLAN


     The shares of Common Stock, par value $.01 per share (the "Common Stock"),
offered hereby (the "Shares") are shares which may have been or may in the
future be issued upon the exercise of stock options which may have been or may
be in the future granted under the Creative BioMolecules, Inc. 1992 Non-Employee
Director Non- Qualified Stock Option Plan (the "Plan") and which are to be sold
by the stockholders of Creative BioMolecules, Inc., a Delaware corporation (the
"Company "), referred to herein (the "Selling Stockholders"). The Company will
not receive any of the proceeds from the sale of the Shares. Some or all of the
Shares may be offered for sale from time to time by the Selling Stockholders, or
by pledgees, donees, transferees, or other successors in interest. Such sales
may be made on one or more exchanges, in the over-the-counter market, or
otherwise, at prices and on terms then prevailing, or at prices related to the
then current market price, or in negotiated transactions, or otherwise, or by
underwriters pursuant to an underwriting agreement in customary form, or in a
combination of any such methods of sale. The Selling Stockholders and any
broker-dealers (including underwriters) who may participate in a sale of the
Shares may be deemed to be statutory underwriters within the meaning of the
Securities Act of 1933, as amended (the "1933 Act"), and the commissions paid or
discounts or concessions allowed to any of such broker-dealers (including
underwriters) by any person, as well as any profits received on the resale of
the Shares, if any, if such broker-dealers (including underwriters) should
purchase any Shares as a principal, may be deemed to be underwriting discounts
and commissions under the 1933 Act. All discounts, commissions or fees incurred
in connection with the sale of the Shares offered hereby will be paid by the
Selling Stockholders or by the purchasers of the Shares, except that the
expenses of registering the Shares and preparing and filing this Prospectus with
the Securities and Exchange Commission (the "Commission"), and of registering or
qualifying the Shares under the blue sky laws of any jurisdiction necessary to
permit the distribution as described in this Prospectus, will be paid by the
Company.

     The Common Stock is listed on The Nasdaq Stock Market ("Nasdaq") under the
symbol CBMI. On September 22, 1997, the closing sale price for the Common Stock
of the Company, as reported by Nasdaq, was $9.96875.
                                           

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

         THE COMMON STOCK OFFERED HEREBY INVOLVES A HIGH DEGREE OF RISK.
        PROSPECTIVE INVESTORS SHOULD CONSIDER CAREFULLY THE RISK FACTORS
                    INDICATED UNDER "RISK FACTORS" ON PAGE 4

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

             THESE SECURITIES HAVE NOT BEEN APPROVED OR DISAPPROVED
             BY THE SECURITIES AND EXCHANGE COMMISSION OR ANY STATE
               SECURITIES AUTHORITY NOR HAS THE COMMISSION OR ANY
                   STATE SECURITIES AUTHORITY PASSED UPON THE
                  ACCURACY OR ADEQUACY OF THIS PROSPECTUS. ANY
              REPRESENTATION TO THE CONTRARY IS A CRIMINAL OFFENSE.

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

               The date of this Prospectus is September 23, 1997.


<PAGE>   4



     No person has been authorized in connection with any offering made hereby
to give any information or to make any representation not contained in this
Prospectus, and, if given or made, such information or representation must not
be relied upon as having been authorized by the Company or any of the Selling
Stockholders. This Prospectus does not constitute an offer to sell or a
solicitation of an offer to buy any security other than the Shares offered by
this Prospectus, nor does it constitute an offer to sell or a solicitation of
any offer to buy any shares of Common Stock offered hereby to any person in any
jurisdiction where it is unlawful to make such an offer or solicitation to such
person. Neither the delivery of this Prospectus nor any sale hereunder shall
under any circumstances create any implication that information contained herein
is correct as of any time subsequent to the date hereof.


                              AVAILABLE INFORMATION

     The Company is subject to the informational requirements of the Exchange
Act, and in accordance therewith files reports, proxy statements and other
information with the Securities and Exchange Commission (the "Commission"). Such
reports, proxy statements and other information can be inspected and copied at
the public reference facilities maintained by the Commission at Room 1024,
Judiciary Plaza, 450 Fifth Street, N.W., Washington, DC 20549, and at the
Commissions Regional Offices at 7 World Trade Center, Suite 1300, New York, NY
10048 and Citicorp Center, 500 West Madison Street, Suite 1400, Chicago, IL
60661-02511. Copies of such materials can be obtained from the Public Reference
Section of the Commission at Room 1024, Judiciary Plaza, 450 Fifth Street, N.W.,
Washington, DC 20549 at prescribed rates. The Commission maintains a Web site
(http://www.sec.gov) that contains reports, proxy and information statements and
other information regarding registrants that file electronically. Reports, proxy
statements and other information about the Company may also be inspected at the
offices of the National Association of Securities Dealers, Inc., 1735 K Street,
N.W., Washington, DC 20006.

     The Company has filed with the Commission a Registration Statement on Form
S-8 (together with all amendments and exhibits hereto, the "Registration
Statement") under the Securities Act, covering the securities offered hereby.
This Prospectus does not contain all of the information set forth in the
Registration Statement, certain parts of which are omitted in accordance with
the rules and regulations of the Commission. For further information, reference
is made to the Registration Statement and the exhibits thereto, copies of which
may be obtained at prescribed rates, or which may be examined free of charge, at
the Public Reference Section of the Commission at Judiciary Plaza, 450 Fifth
Street, N.W., Washington, D.C. 20549. This registration statement has been filed
electronically through the Commission's Electronic Data Gathering, Analysis, and
Retrieval System and may be obtained through the Commission's Web site
(http://www.sec.gov).

     The Company will provide without charge to each person, including
beneficial owners, to whom this Prospectus is delivered, on the written or oral
request of such person, a copy of any or all of the documents that have been or
may be incorporated by reference in this Prospectus, other than exhibits to such
documents, unless such exhibits are specifically incorporated by reference into
such documents. Requests for such copies should be directed to Wayne E. Mayhew
III, Chief Financial Officer, Creative BioMolecules, Inc., 45 South Street,
Hopkinton, Massachusetts 01748 (telephone (508) 782-1100).

                                        2

<PAGE>   5



                                TABLE OF CONTENTS

                                                                          PAGE


RISK FACTORS .............................................................  4

SELLING STOCKHOLDERS ..................................................... 10

PLAN OF DISTRIBUTION ..................................................... 12

LEGAL MATTERS ............................................................ 12

EXPERTS .................................................................. 12

INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE .......................... 13

                                        3

<PAGE>   6



                                  RISK FACTORS

     An investment in the shares being offered by this Prospectus involves a
high degree of risk. In addition to the other information contained in this
Prospectus or incorporated herein by reference, the following factors should be
considered carefully in evaluating an investment in the shares of Common Stock
offered by this Prospectus.

     EARLY STAGE OF DEVELOPMENT. Creative BioMolecules has not yet generated
revenues from the commercialization of its products, and there is substantial
uncertainty regarding the timing and amount of any such future revenues.
Although the Company cannot predict with accuracy the timing of marketing
approval for any products under development, the first such approval is not
expected for several years and no significant product revenues or royalties will
be generated before such approval is obtained. There can also be no assurance
that the Company's products will be proven safe and effective in clinical
trials, meet applicable regulatory standards, be capable of being produced in
commercial quantities at reasonable cost, be marketed successfully or achieve
customer acceptance. Moreover, there can be no assurance that government health
administration authorities, private health care providers or other third party
payors will accept the Company's products, even if the Company's products prove
to be safe and effective and are approved for marketing by the FDA and other
regulatory authorities.

     RELIANCE ON LEAD PRODUCT CANDIDATE. The Company's research and development
resources are primarily dedicated to its programs based on its proprietary
recombinant morphogenic protein, OP-1, the Company's lead product candidate for
several potential therapeutic indications. Clinical progress in the areas of
orthopaedic reconstruction and renal disease are within the control of Stryker
Corporation ("Stryker") and Biogen, Inc. ("Biogen"), respectively, the Company's
collaborative partners. Significant delays in Stryker's or Biogen's clinical
trials of OP-1, unfavorable results in these trials, failure to obtain
regulatory approval for the commercialization of an OP-1 products or failure to
achieve market acceptance of OP-1 would have a material adverse effect upon the
Company. See "-- Dependence on Efforts of Stryker and Biogen and Other
Collaborative Partners to Commercialize Products."

     CONTINUING OPERATING LOSSES AND ACCUMULATED DEFICIT. The Company has
experienced significant operating losses since its inception and, as of June 30,
1997, had an accumulated deficit of approximately $79.4 million. The Company
expects its operating expenses to increase and its operating losses to continue
over the next several years as it expands its research and development, clinical
testing and manufacturing efforts. The Company's ability to achieve
profitability is dependent in large part on obtaining regulatory approvals for
its products and entering into agreements for product development and
commercialization. There can be no assurance that the Company will ever become
profitable.

     UNCERTAINTIES RELATED TO COMPANY'S ABILITY TO RAISE ADDITIONAL NECESSARY
CAPITAL. The Company has spent and expects to continue to spend substantial
funds for continuation of the research and development of product candidates,
preclinical and clinical testing, the establishment of commercial-scale
manufacturing facilities, and filing, prosecuting and enforcing patent claims.
The Company may also require additional funds in order to acquire technologies
or products that complement the Company's efforts. To satisfy its capital
requirements, the Company may seek to raise funds in the public or private
capital markets or make collaborative arrangements with corporate partners or
from other sources. See "-- Reliance on Collaborative Arrangements as a Part of
the Company's Funding Strategy." No assurance can be given that such additional
funds will be available to the Company on acceptable terms, if at all. If
adequate funds are not available from operations or additional sources of
financing, the Company's business will be materially adversely affected and the
Company may be required to delay, scale back or eliminate one or more of its
development programs or obtain funds through arrangements with collaborative
partners or others that may require the Company to relinquish rights to certain
of its technologies, product candidates or products that the Company would
otherwise retain for itself. If additional funds are raised by issuing equity
securities, further substantial dilution to existing stockholders may result.

     RELIANCE ON COLLABORATIVE ARRANGEMENTS AS A PART OF THE COMPANY'S FUNDING
STRATEGY. The Company has relied and plans to continue to rely on collaborative
arrangements with established health care

                                        4

<PAGE>   7



companies to fund a portion of its research and development. Pursuant to such
arrangements, the Company would seek to have collaborative partners provide
capital in exchange for certain technology, product, manufacturing and/or
marketing rights related to the collaborative research. There can be no
assurance that the Company will be able to negotiate acceptable collaborative
arrangements or that such collaborative arrangements will succeed.

     The Company's collaborative partners, Stryker and Biogen, have provided a
substantial portion of the Company's revenues during the past several years. The
Company anticipates that a significant portion of its research revenues for the
next several years will be derived from Stryker and Biogen. However, such
continued funding is dependent upon the Company performing research for Stryker
and Biogen and supplying material for preclinical and clinical testing by
Stryker and Biogen.

     There can be no assurance that the Company will satisfy the requirements
for the receipt of payments from Stryker and Biogen. If the Company does not
receive anticipated payments from Stryker and Biogen and does not receive
adequate additional funds, the Company's business will be materially adversely
affected. See "-- Uncertainties Related to Company's Ability to Raise Additional
Necessary Capital."

     DEPENDENCE ON EFFORTS OF STRYKER AND BIOGEN AND OTHER COLLABORATIVE
PARTNERS TO COMMERCIALIZE PRODUCTS. The Company's collaborative arrangements
with Stryker and Biogen provide, and future arrangements between the Company and
other collaborative partners may provide, that the collaborative partner
complete product development, perform clinical trials, obtain regulatory
approvals and market products resulting from such collaboration. The Company
does not control the amount of resources or the schedule of product development
in its collaborations with Stryker and Biogen and may not be able to control the
efforts that any future collaborative partners may devote to their respective
programs with the Company. The timing and amount of any future royalties and
manufacturing revenues of the Company with respect to product development
pursuant to such collaborative arrangements will therefore depend on the level
of commitment, timing and success of such collaborative partners' efforts.
Should Stryker, Biogen or any other collaborative partner fail to develop and to
commercialize marketable products successfully, the Company's business would be
materially adversely affected.

     COMPETITION AND RISK OF TECHNOLOGICAL OBSOLESCENCE. The biotechnology and
pharmaceutical industries are rapidly evolving fields in which developments are
expected to continue at a rapid pace. Competitors of the Company in the United
States and abroad are numerous and include, among others, pharmaceutical and
biotechnology companies, universities and other research institutions. The
Company's success depends upon developing and maintaining a competitive position
in the development of products and technologies in its areas of focus.
Competition from other biotechnology and pharmaceutical companies is intense and
is expected to increase as new products enter the market and as new technologies
are discovered and commercialized. The Company's competitors may develop
technologies and products that are more effective than any which have been or
are being developed by the Company, or that render the Company's technologies or
products obsolete or noncompetitive. Furthermore, the Company's competitors may
obtain patent protection or other intellectual property rights that block the
Company from developing its potential products, or they may obtain regulatory
approval for the commercialization of their products more rapidly or for a wider
array of indications than those obtained by the Company. Finally, many of these
competitors have substantially greater research and development capabilities,
clinical, manufacturing, regulatory and marketing experience and financial and
managerial resources than the Company.

      Other companies are engaged in the research and development of morphogenic
proteins for various applications. The Company is aware that Genetics Institute,
Inc. ("Genetics Institute"), a wholly-owned subsidiary of American Home Products
Corporation, is pursuing the development of bone morphogenetic proteins.
Genetics Institute has also entered into relationships with Yamanouchi
Pharmaceuticals Co., Ltd. and Sofamor Danek Group, Inc. covering development and
marketing of bone morphogenetic proteins. The Company believes that other
biopharmaceutical companies also are developing recombinant human proteins,
primarily growth factors, for use in the local repair of orthopaedic and
skeletal defects and in other indications. A number of other companies are
pursuing traditional therapies that may compete with the Company's


                                       5

<PAGE>   8

products, including autografts, allografts and electrical stimulation devices
for the repair of orthopaedic and other skeletal defects.

     LACK OF EXPERIENCE IN COMMERCIAL MANUFACTURING; UNCERTAINTY AS TO
TRANSITION TO COMMERCIAL PRODUCTION. The Company has not yet introduced any
products commercially and has never engaged in large-scale commercial
manufacturing. To be successful, the Company's products must be manufactured in
commercial quantities, at acceptable costs and in compliance with regulatory
requirements. There can be no assurance that the Company's manufacturing
facility in Lebanon, New Hampshire will meet the Company's future needs or those
of its collaborative partners. In addition, manufacturing facilities must be
inspected and, in some cases, licensed by the FDA prior to the production of
commercial products and must be operated in compliance with current Good
Manufacturing Practices ("cGMP") for any products manufactured for either
clinical research or commercial use. No assurance can be given that the Company
will be able to make the transition to commercial production successfully.

     LACK OF COMMERCIAL SALES AND MARKETING EXPERIENCE. The Company does not
have experience in marketing, sales or distribution of commercial products. To
market any of its products, the Company will need to develop a substantial
marketing and sales force or will have to arrange for third parties to market
and distribute its products. To the extent that the Company determines not to,
or is unable to, arrange third party distribution for its products, significant
additional expenditures, management resources and time will be required to
develop a sales force. There can be no assurance that the Company will be able
to establish such a sales force or be successful in gaining market acceptance
for its products.

     DEPENDENCE ON PATENTS AND PROPRIETARY TECHNOLOGY. The biotechnology and
pharmaceutical industries place considerable emphasis on obtaining patent and
maintaining trade secret protection for new technologies, products and
processes, and the Company's success will depend, in part, on its ability to
obtain patent protection for its products and manufacturing processes, preserve
its trade secrets and operate without infringing the proprietary rights of third
parties. In addition to the Company's own patents and patent applications,
Stryker has exclusively and irrevocably licensed rights in certain patents and
patent applications to the Company.

     The Company expects to seek additional patents in the future, but there can
be no assurance as to the Company's success or timeliness in obtaining any such
patents or as to the breadth or degree of protection which any such patents may
afford the Company. The patent position of biotechnology and pharmaceutical
firms is often highly uncertain and usually involves complex legal and factual
questions. There is a substantial backlog of biotechnology patent applications
at the U.S. Patent and Trademark Office. No consistent policy has emerged
regarding the breadth of claims covered in biotechnology patents. Accordingly,
there can be no assurance that patent applications relating to the Company's
products or technology will result in patents being issued or that, if issued,
such patents will afford adequate protection to the Company, or that such
patents will not be challenged, invalidated or infringed. Furthermore, there can
be no assurance that others will not independently develop similar products and
processes, duplicate any of the Company's products or, if patents are issued to
the Company, design around such patents. In addition, the Company could incur
substantial costs in defending itself in suits brought against it or in suits in
which the Company may assert its patent rights against others. If the outcome of
any such litigation is adverse to the Company, the Company's business could be
materially adversely affected. To determine the priority of inventions, the
Company also may have to participate in interference proceedings declared by the
U.S. Patent and Trademark Office, which could result in substantial cost to the
Company.

     PATENT INFRINGEMENT RISK. The Company may be subject to claims that it
infringes the patents of others. Competitors of the Company may obtain patents
claiming products or processes that are necessary for or useful to the
development, use or manufacture of the Company's products. Such competitors
could bring legal actions against the Company claiming infringement and seeking
damages and injunctive relief. The Company may be required to obtain licenses
from others to continue to develop, manufacture or market its products or may be
required to cease those activities. There can be no assurance that the Company
will obtain such licenses on acceptable terms, if at all. There can be no
assurance that the Company's current and proposed future activities in the field
of morphogenic proteins will not be challenged in the future in the United
States or

                                        6

<PAGE>   9




abroad, that the Company necessarily will prevail in any such challenge, that
patents have not issued or will not issue containing claims which may materially
constrain the proposed activities of the Company, or that the Company will not
become involved in costly, time-consuming litigation or interference proceedings
regarding patents in the field of morphogenic proteins, including actions
brought to challenge or invalidate the Company's own patent rights.

     POTENTIAL INABILITY TO PROTECT UNPATENTED TECHNOLOGY. The Company also
seeks to protect its proprietary technology, including technology which may not
be patented or patentable, in part by confidentiality agreements and, in certain
cases, inventors' rights agreements with its collaborators, advisors, employees
and consultants. There can be no assurance that these agreements will not be
breached, that the Company will have adequate remedies for any breach, or that
the Company's trade secrets will not otherwise be disclosed to, or discovered
by, competitors.

     NO ASSURANCE OF FDA APPROVAL; COMPREHENSIVE GOVERNMENT REGULATION. The
production and marketing of products developed through the Company's
technologies and its ongoing research and development activities are subject to
regulation by numerous federal, state and local governmental authorities in the
United States and by similar regulatory agencies in other countries where the
Company or any collaborative partner may be testing or intend to test and market
products which have yet to be developed. All of the Company's products require
governmental approvals for commercialization which have not yet been obtained.
Clinical trials and manufacturing of many of the Company's products will be
subject to the rigorous testing and approval processes of the FDA and
corresponding foreign regulatory authorities. The regulatory process, which
includes preclinical testing and clinical trials of each potential product to
establish its safety and efficacy, can take many years and require the
expenditure of substantial resources. Data obtained from preclinical and
clinical activities are susceptible to varying interpretations which could
delay, limit or prevent regulatory approvals. In addition, delays or rejections
may be encountered based upon changes in regulatory policy for product approval
during the period of product development and regulatory review. There can be no
assurance that, even after such time and expenditures, regulatory approvals will
be obtained for any products developed utilizing the Company's technologies.
Moreover, if regulatory approval of a product is granted, such approval may
entail limitations on the indicated uses for which it may be marketed. Further,
even if such regulatory approval is obtained, a marketed product and its
manufacturer are subject to continual review, and discovery of previously
unknown problems with a product or manufacturer may result in restrictions on
such product or manufacturer, including withdrawal of the product from the
market. Regulatory approval of product prices is required in many countries
outside the United States, and various cost containment measures have been
proposed in the United States. There can be no assurance that such regulatory
limitations will not prevent the Company and its collaborative partners from
realizing an adequate return on their investment in product development. Both
the legislative and executive branches of the federal government are considering
reforms to the FDA and its regulatory processes and authority. The effect of
these reforms, if enacted, on the Company or its products cannot be predicted.

     USE AND DISPOSAL OF HAZARDOUS MATERIALS. The Company is subject to numerous
environmental and safety laws and regulations, including those governing the
controlled use and disposal of hazardous materials such as radioactive
compounds, toxins and other chemicals used in the Company's research,
development and manufacturing activities. Any violation of, and the cost of
compliance with, these regulations could adversely impact the Company's
operations. While the Company believes that its safety procedures relating to
the handling and disposing of such materials comply with applicable regulatory
standards, the risk of accidental contamination or injury from these materials
cannot be completely eliminated. If such an accident were to occur, the Company
could be held liable for any resulting damages and any such liability could
exceed the resources of the Company.

     DEPENDENCE ON KEY PERSONNEL. The Company's success depends in large part
upon Michael M. Tarnow, its President and Chief Executive Officer, and Charles
Cohen, Ph.D., its Chief Scientific Officer. The loss of the services of either
of these key employees could have a material adverse effect on the Company. The
Company is also dependent on certain key management and scientific personnel,
the loss of whose services could significantly impede the achievement of its
development objectives. The Company's continued expansion in areas and
activities requiring additional expertise will necessitate the recruitment of
additional

                                        7

<PAGE>   10



management and scientific personnel. There can be no assurance that the Company
will be able to attract and retain such personnel on acceptable terms, given the
competition for such personnel among numerous pharmaceutical and biotechnology
companies, government entities and research and academic institutions.

     DEPENDENCE ON ACADEMIC COLLABORATORS. The Company has relationships with
academic collaborators who investigate the potential utility of the Company's
proprietary technology for various therapeutic applications. The Company's
academic collaborators are not employees of the Company. The Company has limited
control over their activities, and only limited amounts of their time are
dedicated to the Company's projects. The Company's academic collaborators may
have relationships with other commercial entities, some of which compete with
the Company. Although the precise nature of each relationship varies, the
academic collaborators and their primary affiliated institutions generally sign
agreements which provide for confidentiality of the Company's proprietary
technology and results of studies. There can be no assurance, however, that the
Company will be able to maintain the confidentiality of its technology or study
results in connection with every collaboration, and dissemination of such
technology or study results could have an adverse effect on the Company's
business. Also, the Company seeks to obtain exclusive rights to license
developments that may result from these studies. However, there can be no
assurance that such licenses will be available on acceptable terms, if at all.

     UNCERTAINTY OF REIMBURSEMENT. The ability of the Company and its
collaborative partners to commercialize the Company's products successfully may
depend in part on the extent to which reimbursement for the cost of such
products and related treatment will be available from government health
administration authorities, private health insurers and other organizations.
Third-party payors are increasingly challenging the price of medical products
and services. Significant uncertainty exists as to the reimbursement status of
newly approved health care products, and there can be no assurance that adequate
third-party coverage will be available to enable the Company and its
collaborative partners to maintain price levels sufficient to realize an
appropriate return on its investment in product development. Legislation and
regulations affecting the pricing of pharmaceuticals may change before any of
the Company's proposed products are approved for commercialization. Adoption of
such legislation could further limit reimbursement for medical products and
services.

     PRODUCT LIABILITY AND INSURANCE. The testing, marketing and sale of health
care products entail an inherent risk of allegations of product liability, and
there can be no assurance that product liability claims will not be asserted
against the Company. The Company currently maintains product liability insurance
at a level which the Company believes is consistent with industry practice.
However, such existing coverage may not be adequate as the Company continues to
pursue clinical testing of its potential products or seeks to commercialize
products. In addition, there can be no assurance that the Company will be able
to maintain or increase its current insurance coverage in the future on
acceptable terms or that any claims against the Company will not exceed the
amount of such coverage.

     VOLATILITY OF STOCK PRICE. The market prices for securities of
biotechnology companies have been volatile. The market price for the Company's
Common Stock has fluctuated significantly since public trading commenced in
1992, and it is likely that the market price will continue to fluctuate in the
future. Announcements of technological innovations or new commercial products by
the Company or its competitors, developments concerning proprietary rights,
including patents and litigation matters, publicity regarding actual or
potential clinical trial and medical results relating to products under
development by the Company or its competitors, regulatory developments in both
the United States and foreign countries, public concern as to the safety of
biotechnology products and economic and other external factors may have a
significant impact on the Company's business and on the market price of the
Common Stock. In addition, the Company has experienced and expects to continue
to experience significant fluctuations in its quarterly operating results, due
primarily to the timing of revenue received under its manufacturing contract
with Biogen. The Company believes that fluctuations in quarterly results may
cause the market price of its Common Stock to fluctuate substantially.

     SHARES ELIGIBLE FOR FUTURE SALE. Substantially all of the Company's shares
are eligible for sale in the public market. Sales of substantial amounts of
Common Stock in the public market after this offering could

                                        8

<PAGE>   11



adversely affect the market price of the Common Stock. As of September 15, 1997,
there were options outstanding to purchase 4,765,312 shares of Common Stock with
an average exercise price of $4.72 per share, and warrants to purchase 1,147,600
shares of Common Stock with an average exercise price of $2.43 per share.
Additional shares may also become available for sale in the public market from
time to time in the future. Exercise of such options and warrants would dilute
the percentage ownership of existing holders of Common Stock and the sale of
such shares could have a significant adverse effect on the market price of the
Common Stock.

     DILUTION. Dilution is likely to occur upon the exercise of outstanding
options and warrants. If the Company raises additional funds by issuing equity
securities, further dilution to existing stockholders may result. See
"Uncertainties Related to Company's Ability to Raise Additional Necessary
Capital."

     ABSENCE OF DIVIDENDS. The Company has not paid any cash dividends on the
Common Stock since inception and does not anticipate paying cash dividends in
the foreseeable future.

     ANTI-TAKEOVER PROVISIONS. The Board of Directors has the authority to issue
shares of preferred stock with rights and preferences, including dividend and
liquidation rights, senior to those of the Common Stock without further action
by the stockholders of the Company. In addition, the Company's Restated
Certificate of Incorporation and Restated By-Laws contain certain provisions
that could have the effect of making it more difficult for a third party to
acquire, or discouraging a third party from attempting to acquire, control of
the Company. Such provisions could limit future prices that certain investors
might be willing to pay for shares of Common Stock. These provisions, which
include classification of the Board of Directors, could also make it more
difficult for stockholders to change the management of the Company or to effect
certain transactions. Certain provisions of Delaware and Massachusetts corporate
law also may have the effect of deterring a hostile takeover or delaying or
preventing changes in control or management of the Company.



                                        9

<PAGE>   12



                              SELLING STOCKHOLDERS

     The Selling Stockholders are offering hereby Shares which have been or may
hereafter be acquired by them upon the exercise of options granted under the
Plan. The names of additional Selling Stockholders and the number of Shares
offered hereby by them may be added to this Prospectus from time to time by an
addendum or supplement to this Prospectus. Other persons who acquire Shares from
the Selling Stockholders may also be identified as Selling Stockholders by means
of an addendum or supplement to this Prospectus.

     The following table sets forth certain information with respect to the
Selling Stockholders as of September 15, 1997.
<TABLE>
<CAPTION>

                                                                             Number of Shares Beneficially
                                  Number of                                    Owned Upon Completion of
                                   Shares                                             Offering(3)               
                                Beneficially         Number of               -----------------------------
Name                              Owned(1)       Shares Offered(2)              Number             Percent
- ----                            ------------     --------------              ------------          -------
<S>                             <C>                   <C>                    <C>                     <C>
Jeremy L. Curnock Cook          2,273,622(4)          25,000                 2,266,122(4)            6.4
Brian H. Dovey                  1,825,004(5)          25,000                 1,812,504(5)            5.2
Martyn D. Greenacre                12,500(6)          25,000                         -                *
Arthur J. Hale, M.D.            3,962,311(7)          25,000                 3,949,811(7)           10.7
Suzanne Denbo Jaffe                     -             25,000                         -                *
Michael Rosenblatt, M.D.           22,500(6)          25,000                    10,000(6)             *
James R. Tobin                      7,500(8)          25,000                         -                *
</TABLE>


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

*    Represents beneficial ownership of less than 1% of the outstanding Common
     Stock.

(1)  Includes shares of Common Stock owned by the Selling Stockholder and shares
     of Common Stock which such Selling Stockholder has the right to acquire,
     through the exercise of options, within 60 days after September 15, 1997.

(2)  Includes all shares of Common Stock the Selling Stockholder named has the
     rights to acquire, through the exercise of options granted under the Plan,
     whether or not such options have vested within 60 days after September 15,
     1997.

(3)  Includes shares of Common Stock owned by the Selling Stockholder and shares
     of Common Stock which such Selling Stockholder has the right to acquire
     through the exercise of options, within 60 days after September 15, 1997.
     Assumes all shares registered pursuant hereto will be sold, although there
     can be no assurance that any of the Selling Stockholders will offer for
     sale any or all of the shares offered by them pursuant to this Prospectus.
     Also assumes that no other shares are acquired or transferred by the
     Selling Stockholders.

(4)  Includes 7,500 shares of Common Stock subject to options exercisable on
     September 15, 1997 or within 60 days thereafter and 2,266,122 shares of
     Common Stock (after giving effect to the exercise of warrants) beneficially
     owned by Biotechnology Investments Limited ("BIL"). Mr. Curnock Cook is a
     director of Rothschild Asset Management (C.I.) Limited, which is the
     manager of BIL. Mr. Curnock Cook is also a shareholder, but is not an
     officer or director, of BIL. Rothschild Asset Management (C.I.) Limited is
     a wholly-owned subsidiary of Rothschild Asset Management Limited.
     Mr. Curnock Cook disclaims beneficial ownership of the shares owned by BIL.

(5)  Includes 1,188 shares of Common Stock owned directly by Mr. Dovey, 12,500
     shares of Common Stock subject to options exercisable on September 15, 1997
     or within 60 days thereafter and 1,811,316 shares of Common Stock (after
     giving effect to the exercise of warrants) held by Domain Partners III,
     L.P. and DP III Associates, L.P. (collectively "Entities associated with
     Domain Associates"). Mr. Dovey is a General Partner of Domain Associates
     and a General Partner of the




                                       10

<PAGE>   13



     general partner of the Entities associated with Domain Associates and may
     be deemed to be the beneficial owner of shares owned by the Entities
     associated with Domain Associates. Does not include 2,266,122 shares of
     Common Stock (after giving effect to the exercise of warrants)
     beneficially owned by BIL. Domain Associates is the U.S. venture capital
     advisor to BIL. Domain Associates has neither voting nor investment power
     over the shares owned by BIL and Mr. Dovey disclaims beneficial ownership
     of the shares owned by BIL.
        
(6)  Includes shares of Common Stock subject to options exercisable on
     September 15, 1997 or within 60 days thereafter.

(7)  Includes 112,061 shares of Common Stock owned directly by Dr. Hale, 11,900
     shares of Common Stock owned by Dr. Hale's wife, 12,500 shares of Common
     Stock subject to options exercisable on September 15, 1997 or within 60
     days thereafter, and 3,825,850 shares of Common Stock (after giving effect
     to the exercise of warrants) held by Coutts & Co (Jersey) Limited,
     Custodian for Apax Ventures II, Ltd., Apax Funds Nominees Ltd. "A" Account,
     Custodian for Apax Ventures III Trust, Apax Funds Nominees Ltd. "A"
     Account, Custodian for Apax Ventures III International Partners, L.P., Apax
     Funds Nominees Ltd. "B" Account, Custodian for Apax Ventures IV Trust and
     Apax Funds Nominees Ltd. "B" Account, Custodian for Apax Ventures IV
     International Partners, L.P. (collectively "Entities associated with Apax
     Partners & Co. Ventures Ltd."). Dr. Hale is partner and director of Apax
     Partners & Co. Ventures Ltd., the manager of or an advisor to the Entities
     associated with Apax Partners & Co. Ventures Ltd. Dr. Hale disclaims
     beneficial ownership of the shares associated with the Entities associated
     with Apax Partners & Co. Ventures Ltd.

(8)  Includes shares of Common Stock subject to options exercisable on
     September 15, 1997 or within 60 days thereafter. Does not include 1,542,680
     shares owned by Biogen. Mr. Tobin is a Director, President and Chief
     Executive Officer of Biogen. Mr. Tobin disclaims beneficial ownership of
     the shares owned by Biogen.



                                       11

<PAGE>   14



                              PLAN OF DISTRIBUTION

     The Shares may be offered and sold from time to time by the Selling
Stockholders, or by pledgees, donees, transferees or other successors in
interest. Such offers and sales may be made from time to time on one or more
exchanges or in the over-the-counter market, or otherwise, at prices and on
terms then prevailing or at prices related to the then-current market price, or
in negotiated transactions. The Shares may be sold by one or more of the
following: (a) a block trade in which the broker or dealer so engaged will
attempt to sell the Shares as agent but may position and resell a portion of the
block as principal to facilitate the transaction; (b) purchases by a broker or
dealer as principal and resale by such broker or dealer for its account; (c) an
exchange distribution in accordance with the rules of such exchange; (d)
ordinary brokerage transactions and transactions in which the broker solicits
purchasers; (e) privately negotiated transactions; and (f) a combination of any
such methods of sale. In effecting sales, brokers or dealers engaged by the
Selling Stockholders may arrange for other brokers or dealers to participate.
Brokers or dealers may receive commissions or discounts from Selling
Stockholders or from purchasers in amounts to be negotiated immediately prior to
the sale. Such brokers or dealers and any other participating brokers or dealers
may be deemed to be "underwriters" within the meaning of the 1933 Act in
connection with such sales.

     In addition, any securities covered by this Prospectus which qualify for
sale pursuant to Rule 144 promulgated under the 1933 Act ("Rule 144") may be
sold under Rule 144 rather than pursuant to this Prospectus.

     The Company and the Selling Stockholders may enter into customary
agreements concerning indemnification and the provision of information in
connection with the sale of the Shares.

     There is no assurance that any of the Selling Stockholders will offer for
sale or sell any or all the Common Stock covered by this Prospectus.


                                  LEGAL MATTERS

     The validity of the issuance of the shares of Common Stock offered has been
passed upon for the Company by Mintz, Levin, Cohn, Ferris, Glovsky and Popeo,
P.C. of Boston, Massachusetts.


                                     EXPERTS

     The consolidated financial statements incorporated in this Prospectus by
reference from the Company's Annual Report on Form 10-K have been audited by
Deloitte & Touche LLP, independent auditors, as stated in their report which is
incorporated herein by reference and have been so incorporated in reliance upon
the report of such firm given upon their authority as experts in accounting and
auditing.



                                       12

<PAGE>   15



                 INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE

     The following documents filed by the Company with the Commission are hereby
incorporated by reference in this Prospectus: Annual Report on Form 10-K for the
fiscal year ended December 31, 1996; Quarterly Reports on Form 10-Q for the
quarters ended June 30, 1997 and March 31, 1997; and the description of the
Company's capital stock contained in the Company's registration statement on
Form 8-A, filed with the Commission on December 3, 1992 and Amendment No. 1
thereto on Form 8, filed with the Commission on December 3, 1992 and 
December 29, 1992, respectively (File No. 0-19910), including amendments or
reports filed for the purpose of updating such description. All documents filed
by the Company with the Commission pursuant to Sections 13(a), 13(c), 14 or
15(d) of the Exchange Act after the date of this Prospectus and prior to the
termination of the offering of the Common Stock shall be deemed to be
incorporated by reference in this Prospectus and to be a part hereof from the
date of filing of such documents. Any statement contained in a document
incorporated by reference herein shall be deemed to be modified or superseded
for purposes of this Prospectus to the extent that a statement contained herein
or in any other subsequently filed document which is incorporated by reference
herein modifies or supersedes such earlier statement. Any such statement so
modified or superseded shall not be deemed, except as so modified or superseded,
to constitute a part of this Prospectus. Copies of all documents incorporated by
reference herein (other than exhibits to such documents which are not
specifically incorporated by reference into such documents) will be provided
without charge to each person who receives a copy of this Prospectus, upon
request of such person directed to Wayne E. Mayhew III, Vice President and Chief
Financial Officer, Creative BioMolecules, Inc., 45 South Street, Hopkinton, MA
01748, telephone (508) 782-1100.

     To the extent that any proxy statement is incorporated by reference herein,
such incorporation shall not include any information contained in such proxy
statement that is not, pursuant to the Commission's rules, deemed to be "filed"
with the Commission or subject to the liabilities of Section 18 of the Exchange
Act.




                                       13

<PAGE>   16




           PART II. INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3. INCORPORATION OF DOCUMENTS BY REFERENCE.

        The following documents filed by the Company with the Commission are
hereby incorporated by reference in this Registration Statement:

        (a) The Company's Annual Report on Form 10-K for the fiscal year ended
December 31, 1996, filed with the Commission on March 29, 1997 (File No.
0-19910).

        (b) The Company's Quarterly Report on Form 10-Q for the quarter ended 
March 31, 1997, filed with the Commission on May 14, 1997.

        (c) The Company's Quarterly Report on Form 10-Q for the quarter ended 
June 30, 1997, filed with the Commission on August 11, 1997.

        (d) The description of the Company's capital stock contained in the
Company's registration statement on Form 8-A, filed with the Commission on
December 3, 1992 and Amendment No. 1 thereto on Form 8, filed with the
Commission on December 3, 1992 and December 29, 1992, respectively (File No.
0-19910), including amendments or reports filed for the purpose of updating such
description.

        All documents filed by the Company with the Commission pursuant to
Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of this
Registration Statement and prior to the termination of the offering of the
Common Stock shall be deemed to be incorporated by reference in this
Registration Statement and to be a part hereof from the date of filing of such
documents. Any statement contained in a document incorporated by reference
herein shall be deemed to be modified or superseded for purposes of this
Registration Statement to the extent that a statement contained herein or in
any other subsequently filed document which is incorporated by reference herein
modifies or supersedes such earlier statement. Any such statement so modified
or superseded shall not be deemed, except as so modified or superseded, to
constitute a part of this Registration Statement. Copies of all documents
incorporated by reference herein (other than exhibits to such documents which
are not specifically incorporated by reference into such documents) will be
provided without charge to each person who receives a copy of this Registration
Statement, upon request of such person directed to Wayne E. Mayhew III, Vice
President and Chief Financial Officer, Creative BioMolecules, Inc., 45 South
Street, Hopkinton, MA 01748, telephone (508) 782-1100.
        
        To the extent that any proxy statement is incorporated by reference
herein, such incorporation shall not include any information contained in such
proxy statement that is not, pursuant to the Commission's rules, deemed to be
"filed" with the Commission or subject to the liabilities of Section 18 of the
Exchange Act.
        
ITEM 4. DESCRIPTION OF SECURITIES.

        Not applicable.

ITEM 5. INTERESTS OF NAMED EXPERTS AND COUNSEL.

        Jeffrey Wiesen, a member of Mintz, Levin, Cohn, Ferris, Glovsky and
Popeo, P.C., counsel to the Company, owns 13,000 shares of the Company's Common
Stock. Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. delivered an opinion
with respect to the validity of the issuance of the securities being registered.
        
ITEM 6. INDEMNIFICATION OF DIRECTORS AND OFFICERS.

        Incorporated herein by reference from Part II, Item 14 of the
Registrant's Registration Statement on Form S-3 (Registration No. 333-5477).
        

                                      II-1

<PAGE>   17



ITEM 7. EXEMPTION FROM REGISTRATION CLAIMED.

     Not applicable.

ITEM 8. Exhibits.

Exhibit No.                    Description
- -----------                    -----------

(4.1)  Form of Common Stock Certificate (filed as Exhibit 4.2 to the 
       Registration Statement on Form S-1, Registration Statement No. 33-46200,
       as amended, and incorporated herein by reference.)

(4.2)  Restated Certificate of Incorporation, as amended, of the Registrant.
       (Filed as Exhibit 3.1 to Registrant's Annual Report on Form 10-K for the
       period ended September 30, 1995 (File No. 0-19910), and incorporated 
       herein by reference.)

(4.3)  Restated By-Laws of the Registrant. (Filed as Exhibit 3.4 to Form S-1
       Registration Statement (Registration No. 33-46200), or amendments
       thereto, and incorporated herein by reference.)

(5)    Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C., with
       respect to the legality of the original issuance of securities being
       registered

(23.1) Independent Auditors' Consent

(23.2) Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. (included
       in Exhibit 5)

(24)   Power of Attorney to file future amendments (included in Part II of the
       Registration Statement)

(99)   Creative BioMolecules, Inc. 1992 Non-Employee Director Non-Qualified 
       Stock Option Plan, as amended on March 20, 1996 (filed as Exhibit 10.25 
       to the Registrant's Quarterly Report on Form 10-Q for the period ended 
       March 31, 1996 (File No. 0-19910), and incorporated herein by reference.)

ITEM 9. UNDERTAKINGS

(a)     The undersigned Registrant hereby undertakes:

        (1) To file, during any period in which offers or sales are being made,
a post-effective amendment to this Registration Statement (i) to include any
prospectus required by Section 10(a)(3) of the 1933 Act; (ii) to reflect in the
prospectus any facts or events arising after the effective date of the
Registration Statement (or the most recent post-effective amendment thereof)
which, individually or in the aggregate, represents a fundamental change in the
information set forth in the Registration Statement; (iii) to include any
material information with respect to the plan of distribution not previously
disclosed in the Registration Statement or any material change to such
information in the Registration Statement.
        
        Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) do not
apply if the Registration Statement is on Form S-3 or Form S-8, and the
information required to be included in a post-effective amendment by those
paragraphs is contained in periodic reports filed by the Registrant pursuant to
Section 13 or Section 15(d) of the 1934 Act that are incorporated by reference
in this Registration Statement.
        
        (2) That, for the purpose of determining any liability under the 1933
Act, each such post-effective amendment shall be deemed to be a new
registration statement relating to the securities offered therein, and the
offering of such securities at that time shall be deemed to be the initial bona
fide offering thereof. 

        (3) To remove from registration by means of a post-effective amendment
any of the securities being registered which remain unsold at the termination
of the offering.
        


                                      II-2

<PAGE>   18



(b)         The undersigned Registrant hereby undertakes that, for purposes of
determining any liability under the 1933 Act, each filing of the Registrant's
annual report pursuant to Section 13(a) or Section 15(d) of the 1934 Act (and,
where applicable, each filing of an employee benefit plan's annual report
pursuant to Section 15(d) of the 1934 Act) that is incorporated by reference in
this Registration Statement shall be deemed to be a new registration statement
relating to the securities offered therein, and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof.

(c)         Insofar as indemnification for liabilities arising under the 1933
Act may be permitted to directors, officers and controlling persons of the
Registrant pursuant to the foregoing provisions, or otherwise, the Registrant
has been advised that in the opinion of the Commission such indemnification is
against public policy as expressed in the 1933 Act and is, therefore,
unenforceable. In the event that a claim for indemnification against such
liabilities (other than the payment by the Registrant of expenses incurred or
paid by a director, officer or controlling person of the Registrant in the
successful defense of any action, suit or proceeding) is asserted by such
director, officer or controlling person in connection with the securities being
registered, the Registrant will, unless in the opinion of its counsel the matter
has been settled by controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is against public
policy as expressed in the 1933 Act and will be governed by the final
adjudication of such issue.



                                      II-3

<PAGE>   19



                                   SIGNATURES

     Pursuant to the requirements of the Securities Act of 1933, as amended, the
Registrant certifies that it has reasonable grounds to believe that it meets all
of the requirements for filing on Form S-8 and has duly caused this Registration
Statement to be signed on its behalf by the undersigned, thereunto duly
authorized, in the Town of Hopkinton, Massachusetts, on September 23, 1997.

                                  CREATIVE BIOMOLECULES, INC.

                                  By:/s/ Wayne E. Mayhew III
                                     -------------------------------------------
                                     Wayne E. Mayhew III
                                     Vice President and Chief Financial Officer,
                                     Treasurer and Secretary

                                POWER OF ATTORNEY

     KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears
below constitutes and appoints Michael M. Tarnow and Wayne E. Mayhew III, or any
of them, his attorney-in-fact, each with the power of substitution, for him in
any and all capacities, to sign any and all amendments to this registration
statement (including post-effective amendments), and to file the same, with all
exhibits thereto and other documents in connection therewith, with the
Securities and Exchange Commission, granting unto said attorneys-in-fact and
agents, and each of them, full power and authority to do and perform each and
every act and thing requisite or necessary to be done in and about the premises,
as fully to all intents and purposes as he might or could do in person, hereby
ratifying and confirming all that said attorneys-in-fact and agents or any of
them or their or his substitute or substitutes may lawfully do or cause to be
done by virtue hereof.

     Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities and on the dates indicated.

<TABLE>
<CAPTION>



Signatures                                              Title                                                  Date
- ----------                                              -----                                                  ----
<S>                                           <C>                                                       <C>

/s/ Brian H. Dovey                        Chairman of the Board and Director                             September 16, 1997
- ----------------------------------
Brian H. Dovey

/s/ Michael M. Tarnow                     President, Chief Executive Officer and Director                September 23, 1997
- ----------------------------------        (principal executive officer)
Michael M. Tarnow               

/s/Charles Cohen, Ph.D.                   Chief Scientific Officer and Director                          September 16, 1997
- ---------------------------------- 
Charles Cohen, Ph.D.

/s/ Wayne E. Mayhew III                   Vice President and Chief Financial Officer,                    September 23, 1997
- ----------------------------------        Treasurer and Secretary (principal executive officer)
Wayne E. Mayhew III                
                           
/s/ Susan B. Blanton                      Controller (principal accounting officer)                      September 23, 1997
- ----------------------------------
Susan B. Blanton

/s/ Jeremy L. Curnock Cook                Director                                                       September 16, 1997
- ----------------------------------
Jeremy L. Curnock Cook

/s/ Martyn D. Greenacre                   Director                                                       September 16, 1997
- ----------------------------------
Martyn D. Greenacre

/s/ Arthur J. Hale, M.D.                  Director                                                       September 22, 1997
- ----------------------------------
Arthur J. Hale, M.D.

/s/ Suzanne Denbo Jaffe                   Director                                                       September 16, 1997
- ----------------------------------
Suzanne Denbo Jaffe

/s/ Michael Rosenblatt, M.D.              Director                                                       September 16, 1997
- ----------------------------------
Michael Rosenblatt, M.D.

/s/ James R. Tobin                        Director                                                       September 16, 1997
- ----------------------------------
James R. Tobin
</TABLE>



<PAGE>   20


                                  EXHIBIT INDEX

Exhibit
   No.                         Description
- -------                        -----------

  4.1   Form of Common Stock Certificate (filed as Exhibit 4.2 to the
        Registration Statement on Form S-1, Registration Statement 
        No. 33-46200, as amended, and incorporated herein by reference.)

  4.2   Restated Certificate of Incorporation, as amended, of the Registrant.
        (Filed as Exhibit 3.1 to Registrant's Annual Report on Form 10-K for
        the period ended September 30, 1995 (File No. 0-19910), and
        incorporated herein by reference.)

  4.3   Restated By-Laws of the Registrant. (Filed as Exhibit 3.4 to Form S-1
        Registration Statement (Registration No. 33-46200), or amendments
        thereto, and incorporated herein by reference.)

  5     Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C., with
        respect to the legality of the original issuance of securities being
        registered

 23.1   Independent Auditors' Consent

 23.2   Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
        (included in Exhibit 5)

 24     Power of Attorney to file future amendments (included in Part II of
        the Registration Statement)

 99     Creative BioMolecules, Inc. 1992 Non-Employee Director Non-Qualified 
        Stock Option Plan, as amended on March 20, 1996 (filed as Exhibit 10.25
        to the Registrant's Quarterly Report on Form 10-Q for the period ended
        March 31, 1996 (File No. 0-19910), and incorporated herein by 
        reference.)







<PAGE>   1
                                                                     EXHIBIT 5



               Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
                              One Financial Center
                           Boston, Massachusetts 02111

701 Pennsylvania Avenue, N.W.                           Telephone: 617/542-6000
Washington, D.C. 20004                                  Fax: 617/652-2241
Telephone: 202/434-7300                                 www.Mintz.com
Fax: 202/434-7400




                               September 19, 1997


Creative BioMolecules, Inc.
45 South Street
Hopkinton, MA 01748

Ladies and Gentlemen:

     We have acted as counsel to Creative BioMolecules, Inc., a Delaware
corporation (the "Company"), in connection with the preparation and filing with
the Securities and Exchange Commission of a Registration Statement on Form S-8
(the "Registration Statement"), pursuant to which the Company is registering the
issuance under the Securities Act of 1933, as amended, of a total of 100,000
shares (the "Shares") of its common stock, par value $.01 per share (the "Common
Stock"). This opinion is being rendered in connection with the filing of the
Registration Statement. All capitalized terms used herein and not otherwise
defined shall have the respective meanings given to them in the Registration
Statement.

     In connection with this opinion, we have examined the Company's Restated
Certificate of Incorporation, both as currently in effect; such other records of
the corporate proceedings of the Company and certificates of the Company's
officers as we have deemed relevant; and the Registration Statement and the
exhibits thereto.

     In our examination, we have assumed the genuineness of all signatures, the
legal capacity of natural persons, the authenticity of all documents submitted
to us as originals, the conformity to original documents of all documents
submitted to us as certified or photostatic copies and the authenticity of the
originals of such copies.

     Based upon the foregoing, we are of the opinion that (i) the Shares have
been duly and authorized by the Company and (ii) the Shares, when sold, will
have been duly and validly issued, fully paid and non-assessable shares of the
Common Stock, free of preemptive rights.

     Our opinion is limited to the General Corporation Laws of the State of
Delaware, and we express no opinion with respect to the laws of any other
jurisdiction. No opinion is expressed herein with respect to the qualification
of the Shares under the securities or blue sky laws of any state or any foreign
jurisdiction.

     We understand that you wish to file this opinion as an exhibit to the
Registration Statement, and we consent thereto. We hereby further consent to the
reference to us under the caption "Legality of Common Stock" in the prospectus
included in the Registration Statement.

                                                  Very truly yours,



                                                  Mintz, Levin, Cohn, Ferris,
                                                  Glovsky and Popeo, P.C.

<PAGE>   1


                                                                 EXHIBIT 23.1




INDEPENDENT AUDITORS' CONSENT


We consent to the incorporation by reference in this Registration Statement and
Post-Effective Amendment No. 1 to Registration Statement No. 33-56706 of
Creative BioMolecules, Inc. on Form S-8 of our report dated February 21, 1997,
appearing in the Annual Report on Form 10-K of Creative BioMolecules, Inc. for
the year ended December 31, 1996 and to the reference to us under the heading
"Experts" in the Prospectus, which is part of this Registration Statement.


DELOITTE & TOUCHE LLP

Boston, Massachusetts
September 22, 1997





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