NAPRO BIOTHERAPEUTICS INC
8-K, 1999-01-15
MEDICINAL CHEMICALS & BOTANICAL PRODUCTS
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                       SECURITIES AND EXCHANGE COMMISSION
                              WASHINGTON, DC 20549




                                    FORM 8-K

                                 CURRENT REPORT


     Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934



        Date of report (Date of earliest event reported): January 7, 1999

                           NAPRO BIOTHERAPEUTICS, INC.
               (Exact Name of Registrant as Specified in Charter)


 Delaware                         0-243201                 84-1187753
(State or Other Jurisdiction     (Commission File Number) (I.R.S. Employer
of Incorporation)                                         Identification Number)


                             6304 Spine Road, Unit A
                             Boulder, Colorado                   80301
                   (Address of Principal Executive Offices)   (Zip code)


       Registrant's telephone number, including area code: (303) 530-3891

<PAGE>
Item 5.  Other Events

     As  previously  reported,  on January 28, March 20 and March 31, 1998,  the
Company entered into definitive  agreements  relating to modification of certain
terms of its 5% Senior  Convertible  Notes due June 4,  2000 (the  "Notes")  and
Series C Senior Convertible  Preferred Stock (the "Preferred Stock"). On January
7, 1999 the Company entered into letter agreements with the holders of the Notes
and the holder of the Preferred  Stock,  respectively,  further  modifying  such
terms.

     The January 7, 1999 letter  agreements  have been filed as exhibits to this
Report  and are  incorporated  herein  by this  reference.  The  description  of
provisions  of the  letter  agreements  in this  Report  does not  purport to be
complete and is qualified in its entirety by reference to such exhibis.

Item 7.       Financial Statements, Pro Forma Financial Information and Exhibits

         (c)      Exhibits.


Exhibit No.                   Exhibit Description

4.1                         Letter  Agreement,  dated as of January 7, 1999,  by
                            and among the Registrant and the  noteholders  named
                            therein.

4.2                         Letter Agreement, dated as of January 7, 1999,
                            by and between the Registrant and Advantage Fund II,
                            Ltd.

99.1                        Press Release

<PAGE>

                                   SIGNATURES

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


                           NAPRO BIOTHERAPEUTICS, INC.



                           By: \s\ Gordon H. Link, Jr.
                               Gordon H. Link, Jr.
                               Chief Financial Officer

Date:  January 14, 1999

<PAGE>



                                 January 7, 1999

To the Holders of the Senior Convertible Notes of NaPro BioTherapeutics, Inc.

Gentlemen:

         Reference is made to (i) the Note  Purchase  Agreements  (as amended by
the January  Amendment and the March  Amendment  (each as defined  herein),  the
"Purchase  Agreements"),  dated as of May 30, 1997, among NaPro BioTherapeutics,
Inc., a Delaware  corporation  (the  "Company"),  and the various Buyers parties
thereto,  as amended to date,  (ii) the  Engagement  Letter  dated May 12,  1997
between  the  Company  and  Diaz  &  Altschul  Capital,   LLC  (the  "Engagement
Agreement");  (iii)  each of the Senior  Convertible  Notes of the  Company,  as
amended  to date by the  January  Amendment  and the March  Amendment  (each,  a
"Note");  (iv) the Amendment  Agreement  dated January 28, 1998 by and among the
Company and the holders  named therein (the  "January  Amendment");  and (v) the
Letter  Agreement dated March 20, 1998 by and among the Company and such holders
(the "March  Amendment").  Capitalized terms used in this letter agreement (this
"Agreement")  and not defined  shall have the  meanings  assigned to them in the
Purchase Agreements and the Notes.

         The holders of the Notes who are parties hereto (the  "Holders")  agree
severally with the Company as follows:

         A.  The  Holders  of  Convertible  Promissory  Note  Nos.  1,  5 and 6,
registered  in  the  names  of  Delta  Opportunity  Fund,  Ltd.,  OTATO  Limited
Partnership and Diaz & Altschul Group, LLC, respectively, hereby agree that such
Notes shall be amended as follows:

                  1. The first two sentences of Section 1.2(a) of each such Note
         are hereby amended and restated to read as follows:

                           (a)  The   following   provisions   shall   apply  to
                  redemptions  pursuant to  Optional  Redemption  Notices  given
                  during the Initial Redemption Notice Period. The Company shall
                  have the right by an Optional  Redemption  Notice given during
                  the Initial  Redemption  Notice  Period to redeem all, or from
                  time to time any part (as specified in the applicable Optional
                  Redemption  Notice),  of this Note  pursuant  to this  Section
                  1.2(a) up to the  Initial  Redemption  Amount (or such  lesser
                  amount of this Note as shall be  outstanding  at such time) at
                  the  Optional  Redemption  Price  so long as (x) no  Event  of
                  Default or  Repurchase  Event has occurred and is  continuing,
                  (y) the Company is in compliance in all material respects with
                  its obligations to the Holder (including,  without limitation,
                  its obligations under the Note Purchase Agreement) and (z) the
                  Company has funds  available  to pay the  Optional  Redemption
                  Price when it gives the Optional  Redemption  Notice. Any such
                  redemption  pursuant to this Section 1.2(a) shall otherwise be
                  made in accordance with paragraphs (b) and (c) of this Section
                  1.2,  except  that  the  Optional   Redemption  Notice  for  a
                  redemption pursuant to this Section 1.2(a)


                                      4.1-1

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 2


                  may only be  given on a date  during  the  Initial  Redemption
                  Notice  Period.  In order to exercise its right of  redemption
                  under this  Section  1.2,  the Company  shall give an Optional
                  Redemption  Notice to the Holder stating that: (1) the Company
                  is exercising its right to redeem a specified  portion of this
                  Note in  accordance  with this Section 1.2, (2) the  principal
                  amount  of  this  Note  to  be  redeemed,   (3)  the  Optional
                  Redemption Price and (4) the Optional Redemption Date.

                  2. The second  sentence of Section 1.2(b) of each such Note is
         hereby amended and restated to read as follows:

                  If the Company gives an Optional Redemption Notice pursuant to
                  this  Section 1.2, the Holder shall not be entitled to convert
                  any portion of this Note for which a Conversion Notice has not
                  been given prior to the date the Company  gives such  Optional
                  Redemption  Notice;  provided,  however,  that if the  Company
                  defaults  in payment of the  Optional  Redemption  Price,  the
                  Holder  shall  thereafter  be  entitled  to convert all or any
                  portion of this Note from time to time.

                  3.  Section  1.2(c) of each such  Note is  hereby  amended  by
         adding the following at the end thereof:

                  Notwithstanding the foregoing,  the Company shall be permitted
                  to make  the  following  redemptions  or  repurchases  without
                  making a pro rata redemption of this Note or repurchase  offer
                  to the Holder  (except as otherwise  specifically  provided in
                  clauses (x) through (z) below):

                                    (w) the  Company may at any time on or prior
                           to March 31, 1999 redeem Convertible  Promissory Note
                           No. 4 at a redemption  price equal to the  redemption
                           price  for  such  Note in  effect  for  such  Note on
                           January 1, 1999;

                                    (x) the  Company may at any time on or prior
                           to March 31, 1999 repurchase  Convertible  Promissory
                           Note No. 4 at a repurchase  price not in excess of an
                           amount   equal   to  125%  of  the  sum  of  (i)  the
                           outstanding   principal  amount  thereof,  plus  (ii)
                           accrued interest thereon to the date of payment;

                                    (y) the  Company may at any time on or prior
                           to June 30,  1999  redeem  the Other  Notes  that are
                           numbered 2 and 3 at a


                                      4.1-2

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 3


                           redemption  price  equal to the  redemption  price in
                           effect  (after  giving  effect to the 1999  Amendment
                           Agreement  but  no  amendment  of  such  Other  Notes
                           subsequent  to the 1999  Amendment  Agreement)  for a
                           redemption thereof pursuant to Section 1.2(a) thereof
                           on a basis that is not pro rata with a redemption  of
                           this Note if (1) on or prior to the date on which the
                           Company  proposes  to  redeem  such  Other  Notes the
                           Company  has  redeemed or called for  redemption  the
                           entire Initial Redemption Amount or the entire Middle
                           Redemption Amount, as applicable at such time and (2)
                           the  Company  offers to  purchase  from the Holder an
                           amount of this Note such  that,  if such  offer  were
                           accepted  in full by the  Holder,  this  Note will be
                           redeemed  or  repurchased  pro rata with  such  Other
                           Notes (based on the outstanding  principal amounts of
                           this  Note and such  Other  Notes  and  treating  the
                           principal  amount of this Note that is being redeemed
                           in  connection  with such  redemption  of such  Other
                           Notes  as  part  of  such  pro  rata  redemption  and
                           repurchase  of  this  Note)  at  a  repurchase  price
                           payable  in  cash  that  is  equal  to  the  Optional
                           Redemption  Price  that  would be  applicable  if the
                           portion  of this Note that the  Company  so offers to
                           repurchase were redeemable by the Company on the date
                           of such repurchase; and

                                    (z) the  Company  may at any time after June
                           30, 1999  redeem the Other Notes that are  numbered 2
                           and 3 at a redemption  price equal to the  redemption
                           price in  effect  (after  giving  effect  to the 1999
                           Amendment  Agreement  but no  amendment of such Other
                           Notes subsequent to the 1999 Amendment Agreement) for
                           a  redemption  thereof  pursuant  to  Section  1.2(a)
                           thereof  so long as the  Company  offers to  purchase
                           from the  Holder  an  amount of this Note that is pro
                           rata (based on the outstanding  principal  amounts of
                           this Note and the Other  Notes)  with the  portion of
                           such Other Notes to be so  redeemed  at a  repurchase
                           price  payable in cash that is equal to the  Optional
                           Redemption  Price  that  would be  applicable  if the
                           portion  of this Note that the  Company  so offers to
                           repurchase were redeemable by the Company on the date
                           of such repurchase.

                  4.  Section 1.2 of each such Note is hereby  amended by adding
         an additional paragraph (d) to read as follows:

                           (d)  The   following   provisions   shall   apply  to
                  redemptions  pursuant to  Optional  Redemption  Notices  given
                  during the Middle Redemption Notice


                                      4.1-3

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 4


                  Period.  The  Company  shall  have the  right  by an  Optional
                  Redemption  Notice given during the Middle  Redemption  Notice
                  Period  to  redeem  all,  or from  time to time  any  part (as
                  specified in the applicable  Optional  Redemption  Notice), of
                  this Note  pursuant  to this  Section  1.2(d) up to the Middle
                  Redemption Amount (or such lesser amount of this Note as shall
                  be outstanding at such time) at the Optional Redemption Price,
                  so long as (x) no Event of  Default  or  Repurchase  Event has
                  occurred and is  continuing,  (y) the Company is in compliance
                  in all material  respects with its  obligations  to the Holder
                  (including, without limitation, its obligations under the Note
                  Purchase Agreement) and (z) the Company has funds available to
                  pay the Optional  Redemption  Price when it gives the Optional
                  Redemption  Notice.  Any  such  redemption  pursuant  to  this
                  Section  1.2(d)  shall  otherwise be made in  accordance  with
                  paragraphs  (a), (b) and (c) of this Section 1.2,  except that
                  the Optional  Redemption  Notice for a redemption  pursuant to
                  this  Section  1.2(d)  may only be given on a date  during the
                  Middle Redemption Notice Period.

                  5.  Section 1.2 of each such Note is hereby  amended by adding
         an additional paragraph (e) to read as follows:

                           (e)  The   following   provisions   shall   apply  to
                  redemptions  pursuant to  Optional  Redemption  Notices  given
                  during the Final Redemption  Notice Period.  The Company shall
                  have the right by an Optional  Redemption  Notice given during
                  the Final  Redemption  Notice  Period on one occasion  only to
                  redeem  all or  any  part  (as  specified  in  the  applicable
                  Optional  Redemption  Notice)  of this Note  pursuant  to this
                  Section  1.2(e) up to the  Final  Redemption  Amount  (or such
                  lesser  amount  of this Note as shall be  outstanding  at such
                  time)  at the  Optional  Redemption  Price,  so long as (x) no
                  Event of  Default  or  Repurchase  Event has  occurred  and is
                  continuing,  (y) the Company is in  compliance in all material
                  respects  with  its  obligations  to  the  Holder  (including,
                  without  limitation,  its obligations  under the Note Purchase
                  Agreement) and (z) the Company has funds  available to pay the
                  Optional   Redemption   Price  when  it  gives  the   Optional
                  Redemption  Notice.  Any  such  redemption  pursuant  to  this
                  Section  1.2(e)  shall  otherwise be made in  accordance  with
                  paragraphs  (a), (b) and (c) of this Section 1.2,  except that
                  the Optional  Redemption  Notice for a redemption  pursuant to
                  this  Section  1.2(e)  may only be given on a date  during the
                  Final Redemption Notice Period.

                  6.  Section  2.6 of each  such  Note  is  hereby  amended  and
         restated to read as follows:



                                      4.1-4

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 5


                           (a) Subject to Sections 1.2(b) and 2.6(c), during the
                  period  beginning  on  January 1, 1999 and ending on March 31,
                  1999,  the Holder shall not be entitled to convert any portion
                  of this Note at a Conversion  Price that is less than $4.00 if
                  such conversion would result in the aggregate number of shares
                  of Common Stock issued hereunder  (whether through  conversion
                  or in payment of interest or otherwise) at a Conversion  Price
                  (or  Computed  Price,  in the case of Payment  Shares) of less
                  than  $4.00  during  the   calendar   month  of  the  proposed
                  conversion  for which the  determination  under this paragraph
                  (a) is being made exceeding the Monthly  Allotment;  provided,
                  however,   that   notwithstanding   the   foregoing   or   any
                  inconsistent  provisions  of Section  2.1, NP Partners  (f/k/a
                  Nelson  Partners)  and Olympus  Securities  Ltd.  (but not any
                  transferee of their  interests in the Notes),  taken together,
                  and Delta  Opportunity  Fund, Ltd. and OTATO L.P. (but not any
                  transferee of their  interests in the Notes),  taken together,
                  shall  each  have the  right at any time to  convert  from and
                  after January 28, 1998, an aggregate  principal  amount of and
                  interest on the Notes equal to $236,250 at a Conversion  Price
                  of $1.575,  which right and conversions  shall not be included
                  in   determining   compliance   with  the  Monthly   Allotment
                  restriction referred to above.

                           (b) "Monthly  Allotment"  shall mean, with respect to
                  this  Note and the Other  Notes,  a number of shares of Common
                  Stock equal to the number set forth below  opposite the number
                  of this Note and each Other Note:

                                    Note No.                  Monthly Allotment

                                        1                              110,272
                                        2                               65,740
                                        3                               65,706
                                        4                               42,682
                                        5                                7,174
                                        6                                8,427

                  ;  provided,   however,  that  from  and  after  the  date  of
                  redemption or repurchase, if any, of Note No. 4, the amount of
                  the Monthly Allotment for all of this Note and the Other Notes
                  that remain  outstanding  after such  redemption or repurchase
                  shall be  increased  by  reallocating  the  Monthly  Allotment
                  allocated  to Note No. 4 pro  rata  based on the  ratio of the
                  Monthly  Allotment of each such instrument then outstanding to
                  the   Monthly   Allotment   of  all  such   instruments   then
                  outstanding.



                                      4.1-5

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 6


                           (c) The  provisions  contained  in this  Section  2.6
                  shall be of no further  force and effect if (i) the Company is
                  acquired  by  any  other   person  by  means  of  any  merger,
                  consolidation,  sale of all or substantially all the assets of
                  the  Company,  share  exchange or other  business  combination
                  (each,  a  "Transaction"),  (ii) the  company  enters into any
                  Transaction where the shareholders of the Company  immediately
                  prior to such Transaction do not collectively own at least 51%
                  of  the  outstanding   voting   securities  of  the  surviving
                  corporation  of such  Transaction  immediately  following such
                  Transaction,  (iii) the Company  enters into any agreement for
                  any such  Transaction,  (iv) a Tender Offer is consummated for
                  at least 51% of the outstanding  shares of Common Stock or (v)
                  the Company  fails to comply in any material  respect with its
                  obligations to the Holder, including,  without limitation, the
                  Amendment Agreement,  the 1999 Amendment  Agreement,  the Note
                  Purchase  Agreement,  the  Warrants or this Note as amended by
                  the Amendment Agreement and the 1999 Amendment Agreement.

                  7. For redemptions of such Notes occurring on or after January
         1, 1999, the definition of "Subsequent Redemption Price" in Section 7.1
         of each such Note is  hereby  further  amended  by  deleting  "110%" in
         clause (1)(B) thereof and replacing it with "140%."

                  8.  Section 7.1 of each such Note is hereby  amended by adding
         the following definitions in the appropriate alphabetical order:

                           "Final Redemption  Amount" shall mean with respect to
                  this Note an amount  equal to the  principal  amount set forth
                  below  opposite  the  number of this  Note less the  aggregate
                  principal  amount of this Note that has been  redeemed  on any
                  Middle  Redemption  Date  (together  with  accrued  and unpaid
                  interest and accrued and unpaid Default  Interest,  if any, on
                  the  portion  of this Note  included  in the Final  Redemption
                  Amount to the date of determination):

                           Note No.                           Principal Amount

                               1                              $411,435

                               5                              $ 27,208

                               6                              $ 31,355



                                      4.1-6

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 7


                           "Final  Redemption  Date" means the date that is five
                  Business  Days after the date the  Company  gives an  Optional
                  Redemption  Notice to redeem any portion of this Note pursuant
                  to Section 1.2(e).

                           "Final  Redemption  Notice  Period"  means the period
                  that begins on August 1, 1999 and ends on August 7, 1999.

                           "Initial  Redemption  Amount" shall mean with respect
                  to this Note an amount equal to the principal amount set forth
                  below opposite the number of this Note less the sum of (x) the
                  aggregate   principal  amount  of  this  Note  that  has  been
                  converted  by the  Holder  or for  which  the  Holder  gives a
                  Conversion Notice on or after January 1, 1999 and prior to the
                  date the  Company  gives  the  Optional  Redemption  Notice to
                  redeem a portion of this Note pursuant to Section  1.2(a) plus
                  (y) the aggregate  principal amount of this Note that has been
                  redeemed or called for  redemption on or after January 1, 1999
                  and  prior  to  the  date  the  Company   gives  the  Optional
                  Redemption Notice to redeem a portion of this Note pursuant to
                  Section 1.2(a)  (together with accrued and unpaid interest and
                  accrued and unpaid Default Interest, if any, on the portion of
                  this Note  included  in the Initial  Redemption  Amount to the
                  date of determination):

                           Note No.                           Principal Amount

                               1                              $1,645,739

                               5                              $  108,830

                               6                              $  125,419

                           "Initial Redemption Date" means the date that is five
                  Business  Days after the date the  Company  gives an  Optional
                  Redemption  Notice to redeem any portion of this Note pursuant
                  to Section 1.2(a).

                           "Initial  Redemption  Notice Period" means the period
                  that begins on January 1, 1999 and ends on March 31, 1999.

                           "Middle Redemption Amount" shall mean with respect to
                  this Note an amount  equal to the  principal  amount set forth
                  below opposite the number of this Note less the sum of (x) the
                  aggregate   principal  amount  of  this  Note  that  has  been
                  converted  by the  Holder  or for  which  the  Holder  gives a
                  Conversion

                                      4.1-7

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 8


                  Notice on or after January 1, 1999 and prior to March 31, 1999
                  plus (y) the aggregate  principal amount of this Note that has
                  been redeemed or called for  redemption on or after January 1,
                  1999 and  prior to the date the  Company  gives  the  Optional
                  Redemption Notice to redeem a portion of this Note pursuant to
                  Section 1.2(d)  (together with accrued and unpaid interest and
                  accrued and unpaid Default Interest, if any, on the portion of
                  this Note included in the Middle Redemption Amount to the date
                  of determination):

                           Note No.                           Principal Amount

                               1                              $1,028,587

                               5                              $   68,019

                               6                              $   78,387

                           "Middle  Redemption Date" means the date that is five
                  Business Days after the date the Corporation gives an Optional
                  Redemption  Notice to redeem any portion of this Note pursuant
                  to Section 1.2(d).

                           "Middle  Redemption  Notice  Period" means the period
                  that begins on April 1, 1999 and ends on June 30, 1999.

                           "1999  Amendment  Agreement"  shall  mean the  letter
                  agreement,  dated January 7, 1999, between the Company and the
                  Holder of this Note and the  holders  of  certain of the Other
                  Notes.

                  8. The definition of the term  Subsequent  Redemption  Date in
         each such Note is hereby amended and restated to read as follows:

               "Subsequent  Redemption  Date" means each Final  Redemption Date,
               Initial Redemption Date and Middle Redemption Date.

         B.  The Holders of Convertible Promissory Note Nos. 2 and 3, registered
in the names of Nelson  Partners and  Olympus  Securities,  Ltd.,  respectively,
hereby agree that such Notes shall be amended as follows:

                  1.  Section  1.2(c) of each such  Note is  hereby  amended  by
         adding the following at the end thereof:



                                      4.1-8

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 9


                  Notwithstanding the foregoing,  the Company shall be permitted
                  to make  the  following  redemptions  or  repurchases  without
                  making a pro rata redemption of this Note or repurchase  offer
                  to the Holder:

                           (x) the  Company may at any time on or prior to March
                  31,  1999  redeem  Convertible  Promissory  Note  No.  4  at a
                  redemption  price equal to the redemption  price for such Note
                  calculated in the manner in effect for such Note on January 1,
                  1999;

                           (y) the  Company may at any time on or prior to March
                  31, 1999  repurchase  Convertible  Promissory  Note No. 4 at a
                  repurchase  price not in excess of an amount  equal to 125% of
                  the sum of (i) the outstanding  principal amount thereof, plus
                  (ii) accrued interest thereon to the date of payment; and

                           (z) the  Company  may redeem  Convertible  Promissory
                  Notes 1, 5 and 6 pursuant to Section 1.2(a),  1.2(d) or 1.2(e)
                  thereof at redemption prices equal to the redemption prices in
                  effect  thereunder  after giving effect to the 1999  Amendment
                  Agreement so long as  contemporaneously  therewith the Company
                  calls for redemption a pro rata portion of this Note (based on
                  the outstanding  principal amounts of this Note and such Other
                  Notes) at the applicable Optional Redemption Price.

                  Notwithstanding  any inconsistent  provision of this Note, the
                  Company  shall  not be  entitled  to call for  redemption  any
                  portion  of  this  Note   pursuant   to  Section   1.2  unless
                  contemporaneously  therewith the Company calls for  redemption
                  or  offers  to  repurchase  a pro rata  portion  (based on the
                  outstanding principal amount of this Note and the Other Notes)
                  of the  Other  Notes at the  respective  redemption  prices or
                  repurchase prices applicable to the Other Notes.

                  2.  Section  2.6 of each  such  Note  is  hereby  amended  and
         restated to read as follows:

                           (a)  Subject to Sections  1.2(b) and 2.6 (c),  during
                  the  period  beginning  on January 1, 1999 and ending on March
                  31,  1999,  the Holder  shall not be  entitled  to convert any
                  portion of this Note at a  Conversion  Price that is less than
                  $4.00 if such conversion  would result in the aggregate number
                  of shares of Common Stock issued  hereunder  (whether  through
                  conversion  or in  payment  of  interest  or  otherwise)  at a
                  Conversion  Price (or Computed  Price,  in the case of Payment
                  Shares) of less than $4.00 during the calendar

                                      4.1-9

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 10


                  month of the proposed  conversion for which the  determination
                  under this  paragraph (a) is being made  exceeding the Monthly
                  Allotment;   provided,   however,   that  notwithstanding  the
                  foregoing or any  inconsistent  provisions  of Section 2.1, NP
                  Partners (f/k/a Nelson  Partners) and Olympus  Securities Ltd.
                  (but not any  transferee  of their  interests  in the  Notes),
                  taken  together,  and Delta  Opportunity  Fund, Ltd. and OTATO
                  L.P. (but not any transferee of their interests in the Notes),
                  taken  together,  shall  each  have  the  right at any time to
                  convert  from  and  after   January  28,  1998,  an  aggregate
                  principal  amount  of and  interest  on  the  Notes  equal  to
                  $236,250  at a  Conversion  Price of $1.575,  which  right and
                  conversions  shall not be included in  determining  compliance
                  with the Monthly Allotment restriction referred to above.

                           (b) "Monthly  Allotment"  shall mean, with respect to
                  this  Note and the Other  Notes,  a number of shares of Common
                  Stock equal to the number set forth below  opposite the number
                  of this Note and each Other Note:

                                    Note No.                  Monthly Allotment

                                        1                              110,272
                                        2                               65,740
                                        3                               65,706
                                        4                               42,682
                                        5                                7,174
                                        6                                8,427;

                  provided,   however,  that  from   and   after   the  date  of
                  redemption or repurchase, if any, of Note No. 4, the amount of
                  the Monthly Allotment for all of this Note and the Other Notes
                  that remain  outstanding  after such  redemption or repurchase
                  shall be  increased  by  reallocating  the  Monthly  Allotment
                  allocated  to Note No. 4 pro  rata  based on the  ratio of the
                  Monthly  Allotment of each such instrument then outstanding to
                  the   Monthly   Allotment   of  all  such   instruments   then
                  outstanding.

                           (c) The  provisions  contained  in this  Section  2.6
                  shall be of no further  force and effect if (i) the Company is
                  acquired  by  any  other   person  by  means  of  any  merger,
                  consolidation,  sale of all or substantially all the assets of
                  the  Company,  share  exchange or other  business  combination
                  (each,  a  "Transaction"),  (ii) the  company  enters into any
                  Transaction where the shareholders of the Company  immediately
                  prior to such Transaction do not collectively own at least 51%
                  of the outstanding voting securities of the

                                     4.1-10

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 11


                  surviving   corporation   of  such   Transaction   immediately
                  following such Transaction,  (iii) the Company enters into any
                  agreement  for any such  Transaction,  (iv) a Tender  Offer is
                  consummated  for at least  51% of the  outstanding  shares  of
                  Common  Stock  or (v)  the  Company  fails  to  comply  in any
                  material   respect  with  its   obligations   to  the  Holder,
                  including,  without limitation,  the Amendment Agreement,  the
                  1999 Amendment  Agreement,  the Note Purchase  Agreement,  the
                  Warrants  or this Note as amended by the  Amendment  Agreement
                  and the 1999 Amendment Agreement.

                  3. For redemptions of such Notes occurring on or after January
         1, 1999, the  definitions of "Subsequent  Redemption  Price" in Section
         7.1 of each such Note is hereby further  amended by deleting  "110%" in
         clause (1)(B) thereof and replacing it with "130%."

                  4. The  proviso  at the end of the  definition  of  Conversion
         Price in  Section  7.1 of each such Note is  amended  and  restated  as
         follows:

                  provided,  however,  that (i) on any date on or after March 1,
                  1998, but prior to June 1, 1998,  the  Conversion  Price shall
                  not be  greater  than 110% of the  arithmetic  average  of the
                  Market Price of the Common Stock for the period of thirty (30)
                  consecutive Trading Days ending one Trading Day prior to March
                  1, 1998 (the "March  Cap");  (ii) on any date on or after June
                  1, 1998,  but prior to April 1,  1999,  the  Conversion  Price
                  shall not be greater  than $1.92;  and (iii) on any date on or
                  after April 1, 1999, the Conversion Price shall not be greater
                  than the lesser of (A) 110% of the  arithmetic  average of the
                  Market Price of the Common Stock for the period of thirty (30)
                  consecutive Trading Days ending one Trading Day prior to April
                  1, 1999 and (B) $1.92.

                  5.  Section 7.1 of each such Note is hereby  amended by adding
         the following definition in the appropriate alphabetical order:

                           "1999  Amendment  Agreement"  shall  mean the  letter
                  agreement,  dated January 7, 1999, between the Company and the
                  Holder of this Note and the  holders  of  certain of the Other
                  Notes.

         C. The Company  represents  and warrants to, and  covenants  and agrees
with, each Holder that:


                                     4.1-11

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 12


                  1.  This  Agreement  has  been  duly and  validly  authorized,
         executed  and  delivered  by the Company  and,  when duly  executed and
         delivered  by  the  Holders  will  be  the  legal,  valid  and  binding
         obligation of the Company enforceable in accordance with its terms; and
         the Notes,  as amended by this Agreement,  constitute the legal,  valid
         and binding obligations of the Company, enforceable against the Company
         in accordance with their respective terms.

                  2.  The  execution  and  delivery  of  this  Agreement  by the
         Company,   the   consummation  by  the  Company  of  the   transactions
         contemplated  by this  Agreement and the  performance by the Company of
         its obligations  under the Notes,  as amended  hereby,  do not and will
         not,  with or without the giving of notice or the  passage of time,  or
         both,  (i) result in any  violation of any term of the  certificate  or
         incorporation  or by-laws of the Company,  (ii) conflict with or result
         in a breach by the  Company  of any of the terms or  provisions  of, or
         constitute a default under, or result in the modification of, or result
         in the creation or imposition of any lien, security interest, charge or
         encumbrance  upon  any of  the  properties  or  assets  of the  Company
         pursuant to, any indenture,  mortgage, deed of trust or other agreement
         or  instrument  to which the  Company or any of its  subsidiaries  is a
         party or by which the Company or any of its subsidiaries,  any of their
         respective  properties or assets are bound or affected which  conflict,
         breach,  default,  modification,  lien,  security  interest,  charge or
         encumbrance  would  have a  material  adverse  effect on the  business,
         properties,  operations,  condition  (financial or other) or results of
         operations of the Company and its  subsidiaries,  taken as a whole,  or
         the  transactions  contemplated  by this  Agreement or the authority or
         ability of the Company to perform its obligations  under this Agreement
         or the Notes,  as amended  hereby,  or (iii) violate or contravene  any
         applicable law, rule or regulation or any applicable  decree,  judgment
         or order of any court,  United States federal or state regulatory body,
         administrative  agency or other  governmental body having  jurisdiction
         over the Company or any of its  subsidiaries or any of their respective
         properties  or assets  which  violation or  contravention  would have a
         material  adverse  effect  on  the  business,  properties,  operations,
         condition  (financial or other) or results of operations of the Company
         and  its   subsidiaries,   taken  as  a  whole,  or  the   transactions
         contemplated  by this  Agreement  or the  authority  or  ability of the
         Company to perform its  obligations  under this Agreement or the Notes,
         as amended hereby.

                  3. No  authorization,  approval or consent of, or filing with,
         any  court,  governmental  body,  regulatory  agency,   self-regulatory
         organization,  or stock exchange or market of the  stockholders  of the
         Company is required to be obtained or made by the Company in connection
         with the execution, delivery and performance of


                                     4.1-12

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 13


         this  Agreement or the  performance  by the  Company of its obligations
         under the Notes, as amended hereby.

                  4.  There  is  no  action,   suit,   proceeding,   inquiry  or
         investigation  before or by any court,  public board or body  presently
         pending or, to the  knowledge  of the  Company,  threatened  against or
         affecting the Company or any of its subsidiaries wherein an unfavorable
         decision, ruling or finding could have a material adverse effect on the
         transactions  contemplated  by this Agreement or which could  adversely
         affect the validity or  enforceablilty  of, or the authority or ability
         of the Company to perform its obligations  under, this Agreement or the
         Notes, as amended hereby.

                  5. The  Common  Stock is  listed  for  trading  on the  Nasdaq
         National  Market  ("Nasdaq")  and (i) the Company and the Common  Stock
         meet the criteria for continued listing and trading on Nasdaq, (ii) the
         Company has not been notified since January 1, 1995 by The Nasdaq Stock
         Market,  Inc. of any failure or potential  failure to meet the criteria
         for continued  listing and trading on Nasdaq and (iii) no suspension of
         trading  in the  Common  Stock is in effect.  The  Company  knows of no
         reason why the shares of Common Stock  issuable upon  conversion of the
         Notes will not be eligible for listing on Nasdaq.

         D. All  Holders who are parties  hereto  hereby  consent to all matters
provided for herein to the extent any such  consent is required  pursuant to the
Notes.

         E. So long as the Company is in  compliance  in all  material  respects
with its  obligations to the several  Holders,  each Holder shall cooperate with
the Company,  to the extent reasonable and practicable,  in effecting resales of
shares of Common Stock  acquired upon  conversion of such Holder's Note in block
sales to institutional  investors identified to the Holders from time to time by
the Company; provided,  however, that nothing herein shall require any Holder to
sell any shares of Common  Stock other than at such time,  in such  amounts,  at
such  principal  and on such  terms as  determined  by such  holder  in its sole
discretion.

         F. Within five business days of the date hereof, the Company shall file
a Current Report on Form 8-K describing the terms of this Agreement.

         G. Paragraph (g) of the January Amendment is hereby deleted.

         H. Except as  specifically  amended  hereby,  the Notes,  the  Purchase
Agreement and the Engagement Agreement shall remain in full force and effect and
the  Company  hereby  confirms  to the  Holders  that the  Notes,  the  Purchase
Agreements  and the  Engagement  Agreement  remain  binding  obligations  of the
Company that are not at the time of execution and delivery of this Agreement


                                     4.1-13

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 14


subject to any  defense,  offset,  counterclaim or other claim by the Company of
invalidity or unenforceability.

         If the foregoing correctly sets forth our agreement, please so indicate
by signing the appropriate line below, whereupon, when executed and delivered by
the  Company  and  all  of the  Holders  identified  below,  this  letter  shall
constitute  a binding  agreement  between the Company and each Holder  under the
laws of the State of New York; provided, however, that the effectiveness of this
Agreement is conditioned upon the amendment of the terms of the Company's Series
C Convertible Preferred Stock, substantially on the terms set forth on Exhibit A
hereto.

                       

                           NAPRO BIOTHERAPEUTICS, INC.

                           By: \s\ Gordon H. Link, Jr.
                               Gordon H. Link, Jr.
                               Chief Financial Officer


Agreed and accepted:

DELTA OPPORTUNITY FUND, LTD.

By: /s/ Keith R. Bishop
Name: Keith R. Bishop
Title: Director


NP PARTNERS (f/k/a Nelson Partners)

By: /s/ Kenneth A. Simpler
Name: Kenneth A. Simpler
Title: Authorized Signatory




                                     4.1-14

<PAGE>


Holders of Senior Convertible Notes
  of NaPro Bio Therapeutics, Inc.
January 7, 1999
Page 15

OLYMPUS SECURITIES, LTD.

By: /s/ Kenneth A. Simpler
Name: Kenneth A. Simpler
Title: Authorized Signatory


OTATO LIMITED PARTNERSHIP

By: /s/ Richard M. Cayne
Name: Richard M. Cayne
Title: General Counsel


DIAZ & ALTSCHUL GROUP, LLC

By: /s/ Renaldo M. Diaz
Name: Renaldo M. Diaz
Title: Member



                                     4.1-15

<PAGE>









                                 January 7, 1999


To the  Holder  of the  Series C  Senior  Convertible  Preferred  Stock of NaPro
BioTherapeutics, Inc.

Gentlemen:

         Reference is made to (i) the Subscription  Agreement (the "Subscription
Agreement")  dated as of December 8, 1997 by and between NaPro  BioTherapeutics,
Inc., a Delaware corporation (the "Company" or the "Corporation"), and Advantage
Fund II, Ltd. (the  "Holder");  (ii) the Certificate of Designations of Series C
Senior  Convertible  Preferred  Stock (the  "Certificate");  (iii) the Amendment
Agreement  dated January 28, 1998 by and between the Company and the Holder (the
"January Amendment");  and (iv) the Letter Agreement dated March 31, 1998 by and
between the Company and the Holder (the "March  Amendment").  Capitalized  terms
used  herein and not  defined  shall have the  meanings  assigned to them in the
Subscription Agreement and the Certificate, as modified by the January and March
Amendments.

         The Holder and the Company agree as follows:

         1. Section 1(c) of the  Certificate  is hereby deemed amended by adding
the following definitions in the appropriate alphabetical order:

                  "Final  Redemption  Amount"  shall  mean a number of shares of
         Series C Preferred Stock equal to 820,600 less the aggregate  number of
         shares of Series C  Preferred  Stock  that  have been  redeemed  on any
         Middle  Redemption Date (together with accrued and unpaid dividends and
         Arrearage  Interest,  if any, on the shares of Series C Preferred Stock
         included in the Final Redemption Amount to the date of determination).

                  "Final  Redemption  Date" means the date that is five Business
         Days after the date the Corporation gives a Redemption Notice to redeem
         shares of Series C Preferred Stock pursuant to Section 9(a)(6).

                  "Final  Redemption Notice Period" means the period that begins
         on August 1, 1999 and ends on August 7, 1999.

                  "Initial  Redemption  Amount" shall mean a number of shares of
         Series C  Preferred  Stock equal to  3,282,400  less the sum of (x) the
         aggregate  number  of  shares  of  Series C  Preferred  Stock  that are
         converted  by the holders of shares of Series C Preferred  Stock or for
         which the holders of shares of Series C Preferred Stock give Conversion
         Notices  on or  after  January  1,  1999  and  prior  to the  date  the
         Corporation  gives the related  Redemption  Notice to redeem  shares of
         Series C Preferred Stock

                                      4.2-1

<PAGE>


Holder of the Series C  Convertible  Preferred  Stock of NaPro  BioTherapeutics,
  Inc.
January 7, 1999
Page 2


         pursuant to Section 9(a)(1) plus (y) the aggregate  number of shares of
         Series C  Preferred  Stock  that  have  been  redeemed  or  called  for
         redemption  on or  after  January  1,  1999  and  prior to the date the
         Company  gives  the  Redemption  Notice  to  redeem  shares of Series C
         Preferred Stock pursuant to Section 9(a)(1)  (together with accrued and
         unpaid  dividends  and  Arrearage  Interest,  if any,  on the shares of
         Series C Preferred Stock included in the Initial  Redemption  Amount to
         the date of determination).

                  "Initial Redemption Date" means the date that is five Business
         Days after the date the Corporation gives a Redemption Notice to redeem
         shares of Series C Preferred Stock pursuant to Section 9(a)(1).

                  "Initial  Redemption  Notice  Period"  means the  period  that
         begins on January 1, 1999 and ends on March 31, 1999.

                  "Middle  Redemption  Amount"  shall mean a number of shares of
         Series C  Preferred  Stock equal to  2,051,500  less the sum of (x) the
         aggregate  number  of  shares  of  Series C  Preferred  Stock  that are
         converted  by the holders of shares of Series C Preferred  Stock or for
         which the holders of shares of Series C Preferred Stock give Conversion
         Notices on or after  January  1, 1999 and prior to March 31,  1999 plus
         (y) the  aggregate  number of shares of Series C  Preferred  Stock that
         have been redeemed or called for redemption on or after January 1, 1999
         and prior to the date the Company gives the Redemption Notice to redeem
         shares  of  Series  C  Preferred  Stock  pursuant  to  Section  9(a)(5)
         (together with accrued and unpaid dividends and Arrearage Interest,  if
         any, on the shares of Series C Preferred  Stock  included in the Middle
         Redemption Amount to the date of determination).

                  "Middle  Redemption Date" means the date that is five Business
         Days after the date the Corporation gives a Redemption Notice to redeem
         shares of Series C Preferred Stock pursuant to Section 9(a)(5).

                  "Middle Redemption Notice Period" means the period that begins
         on April 1, 1999 and ends on June 30, 1999.

         2. The definition of the term Subsequent Redemption Date in Section (g)
of the January Amendment is hereby amended and restated to read as follows:

          "Subsequent Redemption Date" means each Final Redemption Date, Initial
         Redemption Date and Middle Redemption Date.


                                      4.2-2

<PAGE>


Holder of the Series C  Convertible  Preferred  Stock of NaPro  BioTherapeutics,
  Inc.
January 7, 1999
Page 3


         3. The  Company and the Holder  agree that they will not enforce  their
rights under the first two sentences of Section  9(a)(1) of the  Certificate and
will instead have the rights and obligations set forth below as if the first two
sentences  of Section  9(a)(1) of the  Certificate  had been  amended to read as
follows:

                  (1)  The  following  provisions  shall  apply  to  redemptions
         pursuant to  Redemption  Notices  given  during the Initial  Redemption
         Notice Period. So long as (w) the Corporation shall be in compliance in
         all material respects with its obligations to the holders of the Series
         C Preferred  Stock  (including its obligations  under the  Subscription
         Agreement and the provisions of this Certificate of Designations),  (x)
         the  Registration   Statement  shall  be  effective  on  the  date  the
         Corporation  gives any such  Redemption  Notice  and on the  applicable
         Initial  Redemption  Date, (y) on the date the  Corporation  gives such
         Redemption  Notice and on the  applicable  Initial  Redemption  Date no
         Optional Redemption Event shall have occurred with respect to which any
         holder of shares of Series C Preferred  Stock shall be entitled at such
         time to exercise  optional  redemption  rights under  Section 11 or the
         Corporation  shall have failed to pay the Optional  Redemption Price of
         any  shares of Series C  Preferred  Stock as to which  any  holder  has
         exercised  such  optional  redemption  rights  and (z) on the  date the
         Corporation gives such Redemption Notice and on the applicable  Initial
         Redemption Date, the Corporation has Cash and Cash Equivalent  Balances
         (excluding  investment  securities)  that are sufficient,  after taking
         into account the Corporation's cash requirements during the period from
         the date  such  Redemption  Notice is given to the  Initial  Redemption
         Date, to pay the  Redemption  Price of the shares of Series C Preferred
         Stock  to be  redeemed,  the  Corporation  shall  have  the  right by a
         Redemption Notice given during the Initial  Redemption Notice Period to
         redeem  all or  from  time  to  time  any  part  (as  specified  in the
         applicable  Redemption  Notice) of the  outstanding  shares of Series C
         Preferred  Stock  pursuant  to this  Section  9(a)(1) up to the Initial
         Redemption  Amount  (or  such  lesser  number  of  shares  of  Series C
         Preferred Stock as shall be outstanding at such time) at the Redemption
         Price.  Any such  redemption  pursuant to this  Section  9(a)(1)  shall
         otherwise be made in  accordance  with  paragraphs  (2), (3) and (4) of
         this Section 9(a),  except that the Redemption  Notice for a redemption
         pursuant to this Section 9(a)(1) may be given only on a date during the
         Initial Redemption Notice Period.

         4. Section (e) of the January  Amendment,  which deemed Section 9(a)(2)
of the Certificate, to be amended is hereby amended by substituting a new deemed
amendment of Section 9(a)(2) of the Certificate, which reads as follows:

                  (2) The Corporation shall not be entitled to give a Redemption
         Notice or to redeem any shares of Series C Preferred Stock with respect
         to which a holder has

                                      4.2-3

<PAGE>


Holder of the Series C  Convertible  Preferred  Stock of NaPro  BioTherapeutics,
  Inc.
January 7, 1999
Page 4


         given a Conversion Notice. If the Corporation gives a Redemption Notice
         in accordance with this Section 9(a), the holders of shares of Series C
         Preferred  Stock shall not be entitled  to convert in  accordance  with
         Section  10 the  shares  of  Series C  Preferred  Stock  that are to be
         redeemed in accordance with such Redemption Notice; provided,  however,
         that if the Corporation  defaults in payment when due of the Redemption
         Price for such redemption,  the holders shall thereafter be entitled to
         convert  any or all  shares of Series C  Preferred  Stock  from time to
         time.

         5. Section 9(a) of the  Certificate  is hereby deemed amended by adding
an additional paragraph (5) to read as follows:

                  (5)  The  following  provisions  shall  apply  to  redemptions
         pursuant  to  Redemption  Notices  given  during the Middle  Redemption
         Notice Period. So long as (w) the Corporation shall be in compliance in
         all material respects with its obligations to the holders of the Series
         C Preferred  Stock  (including its obligations  under the  Subscription
         Agreement and the provisions of this Certificate of Designations),  (x)
         the  Registration   Statement  shall  be  effective  on  the  date  the
         Corporation  gives any such  Redemption  Notice  and on the  applicable
         Middle  Redemption  Date,  (y) on the date the  Corporation  gives such
         Redemption  Notice  and on the  applicable  Middle  Redemption  Date no
         Optional Redemption Event shall have occurred with respect to which any
         holder of shares of Series C Preferred  Stock shall be entitled at such
         time to exercise  optional  redemption  rights under  Section 11 or the
         Corporation  shall have failed to pay the Optional  Redemption Price of
         any  shares of Series C  Preferred  Stock as to which  any  holder  has
         exercised  such  optional  redemption  rights  and (z) on the  date the
         Corporation  gives such Redemption  Notice and on the applicable Middle
         Redemption Date, the Corporation has Cash and Cash Equivalent  Balances
         (excluding  investment  securities)  that are sufficient,  after taking
         into account the Corporation's cash requirements during the period from
         the date  such  Redemption  Notice  is given to the  applicable  Middle
         Redemption  Date, to pay the Redemption Price of the shares of Series C
         Preferred Stock to be redeemed, the Corporation shall have the right by
         a Redemption Notice given during the Middle Redemption Notice Period to
         redeem  all or  from  time  to  time  any  part  (as  specified  in the
         applicable  Redemption  Notice) of the  outstanding  shares of Series C
         Preferred  Stock  pursuant  to this  Section  9(a)(5)  up to the Middle
         Redemption  Amount  (or  such  lesser  number  of  shares  of  Series C
         Preferred Stock as shall be outstanding at such time) at the Redemption
         Price.  Any such  redemption  pursuant to this  Section  9(a)(5)  shall
         otherwise be made in accordance with the last sentence of paragraph (1)
         and with paragraphs (2), (3) and (4) of this Section 9(a),  except that
         the Redemption Notice for a redemption pursuant to this Section 9(a)(5)
         may be given only on a date during the Middle Redemption Notice Period.

                                      4.2-4

<PAGE>


Holder of the Series C  Convertible  Preferred  Stock of NaPro  BioTherapeutics,
  Inc.
January 7, 1999
Page 5


         6. Section 9(a) of the  Certificate  is hereby deemed amended by adding
an additional paragraph (6) to read as follows:

                  (6) The  following  provisions  shall  apply  to a  redemption
         pursuant  to a  Redemption  Notice  given  during the Final  Redemption
         Notice Period. So long as (w) the Corporation shall be in compliance in
         all material respects with its obligations to the holders of the Series
         C Preferred  Stock  (including its obligations  under the  Subscription
         Agreement and the provisions of this Certificate of Designations),  (x)
         the  Registration   Statement  shall  be  effective  on  the  date  the
         Corporation  gives the  Redemption  Notice and on the Final  Redemption
         Date, (y) on the date the Corporation  gives the Redemption  Notice and
         on the Final  Redemption Date no Optional  Redemption  Event shall have
         occurred  with  respect  to which  any  holder  of  shares  of Series C
         Preferred  Stock shall be  entitled  at such time to exercise  optional
         redemption rights under Section 11 or the Corporation shall have failed
         to pay  the  Optional  Redemption  Price  of any  shares  of  Series  C
         Preferred  Stock as to which any holder  has  exercised  such  optional
         redemption  rights  and  (z) on the  date  the  Corporation  gives  the
         Redemption Notice and on the Final Redemption Date, the Corporation has
         Cash and Cash Equivalent  Balances  (excluding  investment  securities)
         that are sufficient,  after taking into account the Corporation's  cash
         requirements  during the period from the date the Redemption  Notice is
         given to the Final  Redemption Date, to pay the Redemption Price of the
         shares of Series C  Preferred  Stock to be  redeemed,  the  Corporation
         shall have the right to redeem on one occasion only all or any part (as
         specified  in such  Redemption  Notice)  of the  outstanding  shares of
         Series C Preferred  Stock  pursuant to this  Section  9(a)(6) up to the
         Final  Redemption  Amount (or such lesser  number of shares of Series C
         Preferred Stock as shall be outstanding at such time) at the Redemption
         Price.  Any such  redemption  pursuant to this  Section  9(a)(6)  shall
         otherwise be made in accordance with the last sentence of paragraph (1)
         and with paragraphs (2), (3) and (4) of this Section 9(a),  except that
         the Redemption Notice for a redemption pursuant to this Section 9(a)(6)
         may be given only on a date during the Final Redemption Notice Period.

         7. Section (c)(2) of the January Amendment, which provided that Section
10 of the  Certificate was deemed have a new Section 10(c), is hereby amended by
adding a new paragraph (iv) to such Section 10(c) to read as follows:

                  (iv)  Notwithstanding  any other provision herein,  during the
         period  beginning  on January 1, 1999 and ending on March 31,  1999,  a
         holder of shares of Series C  Preferred  Stock shall not be entitled to
         convert shares of Series C Preferred  Stock at a Conversion  Price that
         is less than $4.00 if such  conversion  would  result in the  aggregate
         number of shares of Common Stock issued hereunder (whether through

                                      4.2-5

<PAGE>


Holder of the Series C  Convertible  Preferred  Stock of NaPro  BioTherapeutics,
  Inc.
January 7, 1999
Page 6


         conversion  or in payment of  dividends or  otherwise)  at a Conversion
         Price (or Computed Price, in the case of shares issued as dividends) of
         less than $4.00  during the calendar  month of the proposed  conversion
         for which the  determination  under this  paragraph  (iv) is being made
         exceeding  150,000  shares of Common Stock.  The  Conversion  Price set
         forth in this Section  10(c)(vi)  shall be subject to adjustment on the
         same basis set forth in the  parenthetical  phrase in clause (1) of the
         definition  of the term  Conversion  Price (as in  effect  prior to the
         January  Amendment) for any such events that occur on or after December
         31, 1998.

         8.  For  redemptions  occurring  on  or  after  January  1,  1999,  the
definition of "Subsequent  Redemption  Price" in the January Amendment is hereby
amended by  deleting  "110%" in clause  (a)(ii)  thereof and  replacing  it with
"140%."

         9. The Company  represents  and warrants to, and  covenants  and agrees
with, the Holder that:

                  (a) This  Agreement  has been  duly  and  validly  authorized,
executed and  delivered by the Company and,  when duly executed and delivered by
the  Holders,  will be the legal,  valid and binding  obligation  of the Company
enforceable in accordance  with its terms;  and the January  Amendment,  and the
terms of the shares of Series C Preferred  Stock,  as deemed amended thereby and
by this Agreement,  constitute the legal,  valid and binding  obligations of the
Company,  enforceable  against the Company in accordance  with their  respective
terms.

                  (b)  The  execution  and  delivery  of this  Agreement  by the
Company,  the  consummation by the Company of the  transactions  contemplated by
this Agreement and the performance by the Company of its  obligations  under the
January  Amendment and the terms of the shares of Series C Preferred  Stock,  as
deemed  amended  thereby  and hereby,  do not and will not,  with or without the
giving of notice or the passage of time, or both, (i) result in any violation of
any term of the  certificate of  incorporation  or by-laws of the Company,  (ii)
conflict  with or  result  in a breach  by the  Company  of any of the  terms or
provisions of, or constitute a default under, or result in the  modification of,
or result in the creation or imposition of any lien,  security interest,  charge
or encumbrance  upon any of the properties or assets of the Company pursuant to,
any indenture, mortgage, deed of trust or other agreement or instrument to which
the Company or any of its subsidiaries is a party or by which the Company or any
of its subsidiaries,  any of their respective  properties or assets are bound or
affected that conflict, breach, default, modification,  lien, security interest,
charge or  encumbrance  would have a material  adverse  effect on the  business,
properties,  operations, condition (financial or other) or results of operations
of the  Company  and its  subsidiaries,  taken as a whole,  or the  transactions
contemplated  by this  Agreement  or the  authority or ability of the Company to
perform its obligations under this Agreement, the January Amendment or the terms
of the shares of Series C Preferred Stock, as deemed amended thereby and hereby,
or (iii) violate or

                                      4.2-6

<PAGE>


Holder of the Series C  Convertible  Preferred  Stock of NaPro  BioTherapeutics,
  Inc.
January 7, 1999
Page 7


contravene  any  applicable  law, rule or regulation or any  applicable  decree,
judgment or order of any court,  United States federal or state regulatory body,
administrative  agency or other  governmental body having  jurisdiction over the
Company or any of its  subsidiaries  or any of their  respective  properties  or
assets, which violation or contravention would have a material adverse effect on
the business, properties,  operations, condition (financial or other) or results
of  operations  of the Company and its  subsidiaries,  taken as a whole,  or the
transactions  contemplated  by this Agreement or the authority or ability of the
Company to perform its obligations  under the January  Amendment or the terms of
the Series C Preferred Stock, as deemed amended thereby and hereby.

                  (c) No authorization,  approval or consent of, or filing with,
any court, governmental body, regulatory agency,  self-regulatory  organization,
or stock exchange or market of the stockholders of the Company is required to be
obtained or made by the Company in connection  with the execution,  delivery and
performance  of  this  Agreement  or  the  performance  by  the  Company  of its
obligations  under the January  Amendment or the terms of the Series C Preferred
Stock, as deemed amended thereby and hereby.

                  (d)  There  is  no  action,  suit,   proceeding,   inquiry  or
investigation before or by any court, public board or body presently pending or,
to the knowledge of the Company,  threatened against or affecting the Company or
any of its subsidiaries wherein an unfavorable decision, ruling or finding could
have  a  material  adverse  effect  on the  transactions  contemplated  by  this
Agreement or that could adversely affect the validity or  enforceability  of, or
the  authority or ability of the Company to perform its  obligations  under this
Agreement,  the January  Amendment or the terms of the Series C Preferred Stock,
as deemed amended thereby and hereby.

                  (e) The  Common  Stock is listed  for  trading  on the  Nasdaq
National  Market  ("Nasdaq")  and (i) the Company and the Common  Stock meet the
criteria for continued  listing and trading on Nasdaq,  (ii) the Company has not
been  notified  since  January 1, 1995 by The Nasdaq Stock  Market,  Inc. of any
failure or  potential  failure to meet the criteria  for  continued  listing and
trading on Nasdaq and (iii) no  suspension  of trading in the Common Stock is in
effect.  The Company knows of no reason why the shares of Common Stock  issuable
upon  conversion  of the  Preferred  Stock will not be  eligible  for listing on
Nasdaq.

         10. So long as the Company is in  compliance  in all material  respects
with its obligations to the Holder, the Holder shall cooperate with the Company,
to the extent  reasonable  and  practicable,  in effecting  resales of shares of
Common Stock  acquired upon  conversion  or exchange of such Holder's  shares of
Series C Preferred Stock in block sales to institutional investors identified to
the Holder from time to time by the  Company;  provided,  however,  that nothing
herein  shall  require the Holder to sell any such shares of Common  Stock other
than  at such  time,  in  such  amounts,  at such  price  and on such  terms  as
determined by such Holder in its sole discretion.


                                      4.2-7

<PAGE>


Holder of the Series C  Convertible  Preferred  Stock of NaPro  BioTherapeutics,
  Inc.
January 7, 1999
Page 8


         11. The  provisions of paragraph (c) of the January  Amendment (as such
provisions  are  modified by this  Agreement)  shall also be  applicable  to all
amendments  of the  Certificate  deemed  to be made by  this  Agreement  and any
reference to  conversion  rights in such deemed  amendments  of the  Certificate
shall also refer to the exchange rights provided in paragraph (c) of the January
Amendment (as modified by this Agreement).

         12.  Within five  business  days of the date hereof,  the Company shall
file a Current Report on Form 8-K describing the terms of this letter agreement.

         13.  Except as  specifically  amended  or deemed  amended  hereby,  the
Subscription  Agreement and the terms of the shares of Series C Preferred  Stock
shall  remain in full force and effect and the  Company  hereby  confirms to the
Holder that the Subscription  Agreements and the terms of the shares of Series C
Preferred Stock, as deemed amended by the January  Amendment and this Agreement,
remain binding  obligations of the Company that are not at the time of execution
and delivery of this Agreement subject to any defense,  offset,  counterclaim or
other claim by the Company of invalidity or unenforceability.

         If the foregoing correctly sets forth our agreement, please so indicate
by signing the appropriate line below,  whereupon this letter shall constitute a
binding agreement between the Company and the Holder under the laws of the State
of New York.

          

                           NAPRO BIOTHERAPEUTICS, INC.



                           By: \s\ Gordon H. Link, Jr.
                               Gordon H. Link, Jr.
                               Chief Financial Officer


Agreed and accepted:

ADVANTAGE FUND II, LTD.



By: /s/
Name: InterCaribbean Services Limited
Title: Secretary


                                      4.2-8

<PAGE>









NaPro Extends Monthly Limits On Outstanding
Convertible Securities

BOULDER,  Colo..--(BW  HealthWire)--Jan.  8, 1999--NaPro  BioTherapeutics,  Inc.
(Nasdaq: NPRO - news) announced today that it reached agreement with the holders
of its 5% Senior Convertible Notes and its Series C Convertible  Preferred Stock
to extend  through March 31, 1999 the  limitations on monthly  conversions  that
were originally scheduled to expire on December 31, 1998. NaPro also repurchased
one  convertible  note with a principal  balance of  approximately  $632,000 for
about  $790,000 in cash.  After the  redemptions  and  repurchases  to date, the
remaining  balances  in the  notes  and  convertible  preferred  stock  will  be
$5,061,000 and $4,103,000, respectively.

Commenting  on  modification  to the  convertible  securities  and the status of
NaPro's  ongoing  discussions  directed  at  securing  a  new  partner  for  its
paclitaxel  program,  Dr.  Sterling K.  Ainsworth,  NaPro's  President and Chief
Executive  Officer,  said,  "Although we have worked diligently to select one or
more new partners to help us develop and commercialize  our paclitaxel  program,
the  effort  has taken  longer  than we had  hoped.  Recognizing  the  potential
difficulties which might have been created for these discussions had the monthly
conversion limits expired, the holders of our convertible securities have agreed
to extend the monthly limits allowing us to continue these  discussions  without
new  uncertainties.  Our discussions  with potential  partners  continue to make
progress and although we had hoped to complete a transaction  prior to year end,
we remain  hopeful  that this can be  accomplished  during the first  quarter of
1999."

NaPro BioTherapeutics,  Inc. headquartered in Boulder, Colorado, with additional
manufacturing  and  plantation  operations  in British  Columbia,  Canada,  is a
biopharmaceutical  company focused on the development,  production and licensing
of complex natural-product pharmaceuticals.

Except for the historical  matters  contained  herein,  statements in this press
release are forward looking and are made pursuant to the safe harbor  provisions
of the Private  Securities  Litigation  Reform Act of 1995. Such forward looking
statements  include the  consequences  of  extending  the  conversion  limits on
NaPro's  convertible  securities  and the prospects  for, and the timing of, any
transaction  with a  strategic  partner  for NaPro's  paclitaxel  program.  Such
forward-looking statements involve known and unknown risks that may cause actual
results  to  be  materially   different  from  the  results  suggested  by  such
forward-looking statements.  Among the factors that could affect matters are all
aspects of competition from Bristol-Myers  Squibb Company and other producers of
paclitaxel and other drugs, the interests of other  pharmaceutical  companies in
forming  development  and  marketing  arrangements  with NaPro and the timing of
negotiations  relative  thereto,  the market for  NaPro's  securities  and other
factors  discussed  in  NaPro's  periodic  reports  and other  filings  with the
Securities and Exchange Commission.

Contact: 

     Gordon Link                     Lisa Burns (investors)
     NaPro BioTherapeutics, Inc.     Burns McClellan, Inc
     VP and Chief Financial Officer  (212) 213-0006
     Tel: (303) 530-3891


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