<PAGE>   1
    As filed with the Securities and Exchange Commission on October 5, 1998.

                                                    Registration No. 333 -      

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                    FORM S-8

                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                             TREGA BIOSCIENCES, INC.
             (Exact name of registrant as specified in its charter)

           Delaware                                         51-0336233
------------------------------                    ------------------------------
(State or other jurisdiction of                          (I.R.S. Employer
incorporation or organization)                          Identification No.)

    9880 Campus Point Drive
     San Diego, California                                     92121
------------------------------                    ------------------------------
     (Address of Principal                                  (Zip Code)
      Executive Offices)

          1996 EMPLOYEE STOCK PURCHASE PLAN OF TREGA BIOSCIENCES, INC.
         ---------------------------------------------------------------
                            (Full title of the plan)

                                                           Copy to:
                 ROBERT S. WHITEHEAD                     T. MICHAEL HIRD
               Trega Biosciences, Inc.             Pillsbury Madison & Sutro LLP
               9880 Campus Point Drive              101 W. Broadway, Suite 1800
           San Diego, California 92121              San Diego, California 92101
                   (619) 410-6500                         (619) 544-3176
           ------------------------------          -----------------------------
            (Name, address and telephone
            number, including area code,
                of agent for service)

                         CALCULATION OF REGISTRATION FEE

<TABLE>
<CAPTION>
---------------------------------------------------------------------------------------------------
   Title of                   Amount         Proposed Maximum        Proposed            Amount of
 Securities To                 To Be          Offering Price     Maximum Aggregate     Registration
 Be Registered              Registered         per Share(1)      Offering Price(1)          Fee
---------------------------------------------------------------------------------------------------
<S>                         <C>              <C>                 <C>                   <C>   
 Common Stock,              150,000 shares        $1.875            $281,250.00           $83.00
par value $.001
---------------------------------------------------------------------------------------------------
</TABLE>


(1)      Pursuant to Rule 457(c) under the Securities Act of 1933, the
         registration fee is based upon the average of the high and low prices
         of the Common Stock as quoted on the Nasdaq National Market on October
         1, 1998.

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

This Registration Statement shall become effective upon filing in accordance
with Rule 462 under the Securities Act of 1933.



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



<PAGE>   2

GENERAL INSTRUCTION E INFORMATION


        This Registration Statement is being filed for the purpose of increasing
the number of securities of the same class as other securities for which a
Registration Statement of the Registrant on Form S-8 relating to the same
employee benefit plan is effective.

        The contents of the Registrant's Form S-8 Registration Statement filed
with the Securities and Exchange Commission on March 29, 1996, File No. 333-2908
(the "1996 Registration Statement"), are hereby incorporated by reference
(except for the Section which incorporates certain documents by reference, which
Section, for purposes of this Registration Statement, is set forth below under
"Incorporation of Documents by Reference").

        In addition to the increase in the number of securities described above,
the title of the employee benefit plan and the name of the Registrant have
changed. The title of the employee benefit plan in the 1996 Registration
Statement was the "1996 Employee Stock Purchase Plan of Houghten
Pharmaceuticals, Inc." and the name of the Registrant was "Houghten
Pharmaceuticals, Inc." The title of the employee benefit plan is now the "1996
Employee Stock Purchase Plan of Trega Biosciences, Inc." and the name of the
Registrant is now "Trega Biosciences, Inc."

INCORPORATION OF DOCUMENTS BY REFERENCE

        The following documents filed by Registrant with the Securities and
Exchange Commission (the "SEC") are incorporated by reference in this
Registration Statement:

        (1)    Registrant's Annual Report on Form 10-K (File No. 000-27972) for
               the fiscal year ended December 31, 1997, which contains, among
               other things, the consolidated financial statements of the
               Registrant and certain supplementary data for the fiscal year
               ended December 31, 1997 together with the report thereon of Ernst
               & Young LLP, independent auditors.

        (2)    Registrant's Quarterly Reports on Form 10-Q for the quarters
               ended March 31, 1998 and June 30, 1998.

        (3)    The description of the Registrant's Common Stock contained in the
               Registrant's Registration Statement on Form 8-A filed on March
               13, 1996.

        In addition, all documents subsequently filed by Registrant with the SEC
pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Securities Exchange Act
of 1934, as amended, prior to the filing of a post-effective amendment which
indicates that all securities offered have been sold or which deregisters all
securities then remaining unsold, 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.



                                       -2-
<PAGE>   3

                                   SIGNATURES

        Pursuant to the requirements of the Securities Act of 1933, 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 City of San Diego, State of California, on this 5th day of
October, 1998.

                                        TREGA BIOSCIENCES, INC.



                                        By /s/ Robert S. Whitehead
                                           -------------------------------------
                                           Robert S. Whitehead
                                           President, Chief Executive Officer 
                                           and Acting Chief Financial Officer 
                                           (Principal Executive, Financial
                                           and Accounting Officer)

        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 date indicated:

<TABLE>
<CAPTION>
Name                               Title                                  Date
----                               -----                                  ----
<S>                               <C>                                    <C>
 /s/ Robert S. Whitehead          President, Chief Executive Officer     October 5, 1998
-------------------------------   and Acting Chief Financial Officer  
     Robert S. Whitehead          (Principal Executive, Financial and 
                                  Accounting Officer) and Chairman    
                                  of the Board of Directors           
                                  

*/s/ Lawrence D. Muschek          President of Research and              October 5, 1998
-------------------------------   Development and Director
     Lawrence D. Muschek          



*/s/ James C. Blair               Director                               October 5, 1998
-------------------------------
     James C. Blair



*/s/ Harry D. Lambert             Director                               October 5, 1998
-------------------------------
     Harry D. Lambert



*/s/ Jeremy M. Levin              Director                               October 5, 1998
-------------------------------
     Jeremy M. Levin
</TABLE>



                                       -3-
<PAGE>   4

<TABLE>
<CAPTION>
Name                               Title                                  Date
----                               -----                                  ----
<S>                               <C>                                    <C>

*/s/ Harvey S. Sadow              Director                               October 5, 1998
-------------------------------
     Harvey S. Sadow



*/s/ Ronald R. Tuttle             Director                               October 5, 1998
-------------------------------
     Ronald R. Tuttle



*/s/ Anders P. Wiklund            Director                               October 5, 1998
-------------------------------
     Anders P. Wiklund



* By /s/ Robert S. Whitehead
-------------------------------
    Attorney-in-fact
</TABLE>



                                       -4-
<PAGE>   5

                                INDEX TO EXHIBITS


<TABLE>
<CAPTION>
Exhibit
Number            Exhibit
<S>               <C>
5.1               Opinion regarding legality of
                  securities to be offered.

23.1              Consent of Ernst & Young LLP,
                  Independent Auditors.

23.2              Consent of Pillsbury Madison &
                  Sutro LLP (included in Exhibit 5.1).

24.1              Power of Attorney.

*99.1             1996 Employee Stock Purchase Plan of Trega Biosciences, Inc.,
                  as amended and restated.

</TABLE>



--------

* The Plan was filed by the Registrant with the Registrant's definitive Proxy
Statement in respect of its 1998 Annual Meeting of Stockholders (File No.
000-27972) as Appendix B thereto and is incorporated herein by reference.



                                       -5-
[{"type": "S-8", "sequence": "1", "description": "FORM S-8", "secsgml_size_bytes": 10540}]
{"company-data": {"conformed-name": "TREGA BIOSCIENCES INC", "cik": "0000887920", "assigned-sic": "2836", "irs-number": "510336233", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-65343", "film-number": "98721059"}, "business-address": {"street1": "9880 CAMPUS POINT DRIVE", "city": "SAN DIEGO", "state": "CA", "zip": "92121", "phone": "6194106500"}, "mail-address": {"street1": "9880 CAMPUS POINT DRIVE", "city": "SANSAN DIEGO", "state": "CA", "zip": "92121"}, "former-company": {"former-conformed-name": "HOUGHTEN PHARMACEUTICALS INC", "date-changed": "19960215"}}
1
    As filed with the Securities and Exchange Commission on October 5, 1998.

                                                    Registration No. 333 -      

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                    FORM S-8

                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                             TREGA BIOSCIENCES, INC.
             (Exact name of registrant as specified in its charter)

           Delaware                                         51-0336233
------------------------------                    ------------------------------
(State or other jurisdiction of                          (I.R.S. Employer
incorporation or organization)                          Identification No.)

    9880 Campus Point Drive
     San Diego, California                                     92121
------------------------------                    ------------------------------
     (Address of Principal                                  (Zip Code)
      Executive Offices)

          1996 EMPLOYEE STOCK PURCHASE PLAN OF TREGA BIOSCIENCES, INC.
         ---------------------------------------------------------------
                            (Full title of the plan)

                                                           Copy to:
                 ROBERT S. WHITEHEAD                     T. MICHAEL HIRD
               Trega Biosciences, Inc.             Pillsbury Madison & Sutro LLP
               9880 Campus Point Drive              101 W. Broadway, Suite 1800
           San Diego, California 92121              San Diego, California 92101
                   (619) 410-6500                         (619) 544-3176
           ------------------------------          -----------------------------
            (Name, address and telephone
            number, including area code,
                of agent for service)

                         CALCULATION OF REGISTRATION FEE
---------------------------------------------------------------------------------------------------
   Title of                   Amount         Proposed Maximum        Proposed            Amount of
 Securities To                 To Be          Offering Price     Maximum Aggregate     Registration
 Be Registered              Registered         per Share(1)      Offering Price(1)          Fee
---------------------------------------------------------------------------------------------------
Common Stock,              150,000 shares        $1.875            $281,250.00           $83.00
par value $.001
---------------------------------------------------------------------------------------------------
(1)      Pursuant to Rule 457(c) under the Securities Act of 1933, the
         registration fee is based upon the average of the high and low prices
         of the Common Stock as quoted on the Nasdaq National Market on October
         1, 1998.

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

This Registration Statement shall become effective upon filing in accordance
with Rule 462 under the Securities Act of 1933.

--------------------------------------------------------------------------------
2

GENERAL INSTRUCTION E INFORMATION

        This Registration Statement is being filed for the purpose of increasing
the number of securities of the same class as other securities for which a
Registration Statement of the Registrant on Form S-8 relating to the same
employee benefit plan is effective.

        The contents of the Registrant's Form S-8 Registration Statement filed
with the Securities and Exchange Commission on March 29, 1996, File No. 333-2908
(the "1996 Registration Statement"), are hereby incorporated by reference
(except for the Section which incorporates certain documents by reference, which
Section, for purposes of this Registration Statement, is set forth below under
"Incorporation of Documents by Reference").

        In addition to the increase in the number of securities described above,
the title of the employee benefit plan and the name of the Registrant have
changed. The title of the employee benefit plan in the 1996 Registration
Statement was the "1996 Employee Stock Purchase Plan of Houghten
Pharmaceuticals, Inc." and the name of the Registrant was "Houghten
Pharmaceuticals, Inc." The title of the employee benefit plan is now the "1996
Employee Stock Purchase Plan of Trega Biosciences, Inc." and the name of the
Registrant is now "Trega Biosciences, Inc."

INCORPORATION OF DOCUMENTS BY REFERENCE

        The following documents filed by Registrant with the Securities and
Exchange Commission (the "SEC") are incorporated by reference in this
Registration Statement:

        (1)    Registrant's Annual Report on Form 10-K (File No. 000-27972) for
               the fiscal year ended December 31, 1997, which contains, among
               other things, the consolidated financial statements of the
               Registrant and certain supplementary data for the fiscal year
               ended December 31, 1997 together with the report thereon of Ernst
               & Young LLP, independent auditors.

        (2)    Registrant's Quarterly Reports on Form 10-Q for the quarters
               ended March 31, 1998 and June 30, 1998.

        (3)    The description of the Registrant's Common Stock contained in the
               Registrant's Registration Statement on Form 8-A filed on March
               13, 1996.

        In addition, all documents subsequently filed by Registrant with the SEC
pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Securities Exchange Act
of 1934, as amended, prior to the filing of a post-effective amendment which
indicates that all securities offered have been sold or which deregisters all
securities then remaining unsold, 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.

                                       -2-
3

                                   SIGNATURES

        Pursuant to the requirements of the Securities Act of 1933, 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 City of San Diego, State of California, on this 5th day of
October, 1998.

                                        TREGA BIOSCIENCES, INC.

                                        By /s/ Robert S. Whitehead
                                           -------------------------------------
                                           Robert S. Whitehead
                                           President, Chief Executive Officer 
                                           and Acting Chief Financial Officer 
                                           (Principal Executive, Financial
                                           and Accounting Officer)

        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 date indicated:
Name                               Title                                  Date
----                               -----                                  ----
/s/ Robert S. Whitehead          President, Chief Executive Officer     October 5, 1998
-------------------------------   and Acting Chief Financial Officer  
     Robert S. Whitehead          (Principal Executive, Financial and 
                                  Accounting Officer) and Chairman    
                                  of the Board of Directors           
                                  

*/s/ Lawrence D. Muschek          President of Research and              October 5, 1998
-------------------------------   Development and Director
     Lawrence D. Muschek          

*/s/ James C. Blair               Director                               October 5, 1998
-------------------------------
     James C. Blair

*/s/ Harry D. Lambert             Director                               October 5, 1998
-------------------------------
     Harry D. Lambert

*/s/ Jeremy M. Levin              Director                               October 5, 1998
-------------------------------
     Jeremy M. Levin
-3-
4
Name                               Title                                  Date
----                               -----                                  ----
*/s/ Harvey S. Sadow              Director                               October 5, 1998
-------------------------------
     Harvey S. Sadow

*/s/ Ronald R. Tuttle             Director                               October 5, 1998
-------------------------------
     Ronald R. Tuttle

*/s/ Anders P. Wiklund            Director                               October 5, 1998
-------------------------------
     Anders P. Wiklund

* By /s/ Robert S. Whitehead
-------------------------------
    Attorney-in-fact
-4-
5

                                INDEX TO EXHIBITS
Exhibit
Number            Exhibit
5.1               Opinion regarding legality of
                  securities to be offered.

23.1              Consent of Ernst & Young LLP,
                  Independent Auditors.

23.2              Consent of Pillsbury Madison &
                  Sutro LLP (included in Exhibit 5.1).

24.1              Power of Attorney.

*99.1             1996 Employee Stock Purchase Plan of Trega Biosciences, Inc.,
                  as amended and restated.
--------

* The Plan was filed by the Registrant with the Registrant's definitive Proxy
Statement in respect of its 1998 Annual Meeting of Stockholders (File No.
000-27972) as Appendix B thereto and is incorporated herein by reference.

                                       -5-