[LETTERHEAD]

                              SECOND AMENDMENT TO

                       COLLABORATION AND LICENSE AGREEMENT


          Second  amendment,  dated July 2nd, 2001, (this  "Amendment"),  to the
Collaboration  and License  Agreement  dated June 12, 1998,  as amended  through
Amendment No. 1 to the  Collaboration and License Agreement and the Subscription
Agreement dated May 1, 2000, each by and between Aphton  Corporation,  a company
organized under the laws of Delaware with its principal executive offices at the
World Trade Center, 80 SW Eight Street,  Suite 2160, Miami, Florida (hereinafter
"Aphton"),  and  GlaxoSmithKline  PLC, formerly SmithKline Beecham PLC, having a
place of business at New Horizon Court,  Great West Road,  Brentford,  Middlesex
TW8 9EP, United Kingdom  (hereinafter  "GSK"). All capitalized terms used herein
but not otherwise  defined  herein shall have the  respective  meanings given to
such terms in the Collaboration and License Agreement.


                              W I T N E S S E T H:

                              - - - - - - - - - -

          WHEREAS,  Aphton and GSK are  parties to a  Collaboration  and License
Agreement, dated June 12, 1998, (the "Agreement"), amended through Amendment No.
1 to the  Collaboration  and License  Agreement and the  Subscription  Agreement
dated May 10, 2000 (hereinafter "Amendment No. 1"); and

          WHEREAS,  Aphton  and GSK  wish to  amend  certain  provisions  of the
Agreement as amended through Amendment No. 1, as herein provided.

          NOW, THEREFORE, it is agreed:

          1. All  references  in the  Agreement to "SB" shall be amended to read
"GSK".

          2. Article 1.14 of the Agreement shall be amended to read as follows:

          ""Field" shall mean use for the diagnosis, treatment and prevention of
gonadotropin, gonadal steroid hormone(s) or GnRH receptor(s) associated diseases
and cancers in humans  including  but not limited to  endometriosis,  polycystic
ovaries,  uterine  fibroids,  contraception,  infertility,  precocious  puberty,
prostate cancer,  breast cancer,  ovarian cancer and endometrial cancer,  either
alone or in combination with chemotherapy."

          3. The  sixth  sentence  of  Section  3.1.(ii)  of the  Agreement,  as
previously  revised through Amendment No. 1, shall be further amended to read as
follows:

          "In no event shall the Presentation Date be later than [Redacted]*."

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          4.  The  first  sentence  of  Section  13.3.1  of  the  Agreement,  as
previously  revised through Amendment No. 1, shall be further amended to read as
follows:

     "Prior to the  Acceptance  Date, GSK shall have the right to terminate this
Agreement  by  serving  notice of no less than 30 days to Apthon  which  will be
effective at the earlier of (a) twenty-seven (27) months after the Delivery Date
(defined in 3.1(i)) or (b) as from September 30, 2002."

          5. This  Amendment is limited as specified and shall not  constitute a
modification,  acceptance or waiver of any other provision of the Agreement. For
the avoidance of doubt, the extension of the Presentation  Date of the Agreement
shall  not imply an  extension  by any  means of the Put  Option  period or Call
Option  period of the  Subscription  Agreement,  which  forms  Schedule C of the
Agreement,  which periods remain  governed by the provisions of Section 3 of the
Subscription Agreement.

          6. This Amendment may be executed in any number of counterparts and by
the  different   parties  hereto  on  separate   counterparts,   each  of  which
counterparts when executed and delivered shall be an original,  but all of which
shall together constitute one and the same instrument.

          7. This  Amendment  and the rights of the parties  hereunder  shall be
governed by, and  interpreted  in accordance  with, the laws of the State of New
York, without giving effect to the principles of conflict of law thereunder.

          8. This Amendment  shall become  effective on the date (the "Amendment
Effective Date") when each of the Parties shall have signed a counterpart hereof
(whether the same or different counterparts).

          9. From and after the Amendment  Effective Date, all references in the
Agreement  shall be deemed to be  references to the Agreement as amended by this
Amendment and Amendment No. 1.


                                      -2-

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          IN  WITNESS  WHEREOF,  the  parties  hereto  have duly  executed  this
Amendment as of the date and year first above written.




                                   APHTON CORPORATION


                                         /s/ Philip C. Gevas
                                   ---------------------------------------------
                                   Name:   Philip C. Gevas
                                   Title:  Chairman, President and
                                           Chief Executive Officer


                                   GLAXOSMITHKLINE PLC


                                        /s/ Simon Bicknell
                                   ---------------------------------------------
                                   Name:   Simon Bicknell
                                   Title:  Company Secretary