EXHIBIT 10.10A
CONFIDENTIAL TREATMENT REQUESTED
(*) Denotes information for which confidential treatment has been requested.
Confidential portions omitted have been filed separately with the Commission.
AMENDMENT TO NEUREX/WARNER
RESEARCH AND DEVELOPMENT COLLABORATION AGREEMENT
Amendment dated September 25, 1996 (this "Amendment"), to the Research
and Development Collaboration Agreement dated as of May 25, 1993 (the
"Agreement"), between NEUREX CORPORATION, a Delaware corporation ("Neurex"), and
XXXXXX-XXXXXXX COMPANY, a Delaware corporation ("Warner").
WHEREAS, Neurex and Warner have made promising advances in the field of
neuronal-specific calcium channels under the Agreement; and
WHEREAS, Neurex and Warner desire to extend the term of the
Collaboration under the Agreement;
NOW, THEREFORE, Neurex and Warner hereby agree as follows:
1. Definitions. Capitalized terms used but not defined herein will
have the meanings set forth in the Agreement. The following additional terms
will have the following meanings:
"Extended Collaboration Term" shall mean the extension of the term of
the Collaboration agreed to pursuant to this Amendment, beginning on September
30, 1996 and terminating pursuant to Section 1.3 (as amended hereby).
"R-Channel Antagonist Milestone I" shall mean a compound having the
following potency and selectivity:
potency: [*]
selectivity: [*]
evidence of in vivo pharmacology (efficacy)
"R-Channel Antagonist Milestone II" shall mean definition of in vivo
pharmacological activity for a selective R-channel antagonist that would predict
a clinical application. Such predictability must be shown by:
Dose-dependent efficacy in an animal disease model. Data and
experimental design (dose, potency, route of administration,
time course, tissue or neurochemical response) must yield
convincing evidence that the relevant neuropharmacological
pharmacology action is principally mediated through blockade
of R-channels and supports follow-up study in the areas of
neurologic and/or psychiatric disease. Demonstrated efficacy
in two replicate experiments giving a p value of less than or
equal to 0.05 (one-tailed t-test) for test treatment vs.
control treatment in a relevant disease model.
2. Personnel and Resources. The following is hereby added to Section
1.2 of the Agreement:
"Notwithstanding the foregoing, during the Extended Collaboration Term
Neurex will be obligated to maintain a minimum of 7 full-time staff
devoted to cooperative discovery research in NSCC. Warner agrees to pay
Neurex $1,166,662 per year in consideration for Neurex's dedication of
such staff. Such amount will be payable in advance in equal
installments of $291,665.50 on each October 1, January 1, April 1 and
July 1 during the Extended Collaboration Term; provided, however, that
the October 1, 1996 payment will instead be made on September 30, 1996.
It is understood that the Collaboration Committee currently intends to
focus Warner's 12 full-time staff and Neurex's 7 full-time staff on
N-channel research during the Extended Collaboration Term, but it is
further understood that the Collaboration Committee has the authority
at its discretion at any time to refocus such staff to work on any
other aspect of the Field, including R-channels."
3. R-Channel. (a) During the Extended Collaboration Term, Neurex and Warner may
each independently devote resources to discovery research in areas of the Field
not then actively being pursued by the Warner and Neurex staff referred to in
Section 1.2, including discovery research in R-channels. Such research will be
deemed to be performed pursuant to the Collaboration. Each party agrees to
report on the status of its independent research in the Field to the other party
within 10 days of any material discoveries or advancements and generally at each
meeting of the Collaboration Committee, and to provide the other party access to
all results of such research at such other party's request.
(b) Each party will notify the other within 1 month of confirming that a
compound satisfies the terms of the R-Channel Antagonist Milestone I. Within 3
months of receipt or provision of such notice, Warner will either (i) pay Neurex
$1,000,000 or (ii) revoke its marketing rights to such compound and all other
compounds of the same chemical class. If Warner chooses option (i), Neurex will
apply reasonable efforts to achieve Milestone II, at Neurex' cost and direction;
provided, however, that simultaneously with paying such $1,000,000 Warner may
elect to support 5 full-time Neurex staff devoted to cooperative discovery
research in R-channels (in addition to Warner's and Neurex' commitments under
Section 1.2) at the rate of $166,666 each per year, payable quarterly in advance
from and after the date of such election, in which case (a) the efforts of such
staff, including the research, development and marketing of all compounds acting
on R-channels, will become subject to the committee governance structure of
Article 2 of the Agreement and (b) Section 3(c) of this Amendment will be
deleted and have no further force or effect (except that Warner would not regain
any marketing rights previously revoked under such Section). If Warner chooses
option (ii), Neurex may pursue development of such compound and all other
compounds of the same chemical class and each such compound will be deemed a
"Neurex Product" for purposes of the Agreement.
(c) Within 3 months following the date that a compound (other than one as to
which Warner has previously revoked marketing rights) satisfies the terms of the
R-Channel Antagonist Milestone II (as reasonably determined by Warner), Warner
will either (i) pay Neurex $1,500,000 or (ii) revoke its marketing rights to
such compound and all other compounds of the same chemical class. If Warner
chooses option (i), Warner will thereafter support 5 full-time Neurex staff
devoted to cooperative discovery research in R-channels (in addition to Warner's
and Neurex' commitments under Section 1.2) at the rate of $166,666 each per
year, payable quarterly in advance from and after the date of electing such
option (i), and the research, development and marketing of all compounds that
act on R-channels shall become subject to the committee governance structure of
Article 2 of the Agreement. If Warner chooses option (ii), Neurex may pursue
development of such compound and all other compounds of the same chemical class
and each such compound will be deemed a "Neurex Product" for purposes of the
Agreement.
(d) Warner will not be required to make the $1,000,000 or $1,500,000 payments
referred to in Sections 3(b) and 3(c) of this Amendment, respectively, more than
once regardless of how many compounds satisfy either relevant milestone;
provided, however, that Warner will not regain any marketing rights revoked
prior to making the relevant milestone payment.
4. R-Channel Personnel and Resources. Warner will in good faith consider
requests from Neurex to assist Neurex in its R-channel discovery research
efforts during 1996 and 1997; provided, however, that Neurex acknowledges that
Warner will have no obligation to provide any such assistance, and in no event
will Warner be required to provide more than two full-time staff equivalents at
any time during such period for such purpose.
5. Development Costs. Section 4.2 of the Agreement is hereby amended by (i)
deleting the phrase "2/3" found twice in such Section and replacing it with the
phrase "3/4" in both instances and (ii) deleting the phrase "1/3" found twice in
such Section and replacing it with the phrase "1/4" in both instances. Subject
to such revised cost sharing percentages, all costs to be shared under Section
4.2 of the Agreement will be governed by the guidelines set forth on June 6,
1996 for the sharing of costs under the SNX-111 License Agreement, dated May 25,
1993. A copy of such guidelines is attached hereto as Exhibit 1.
6. Co-Promotion Participation. Section 8.1 of the Agreement is hereby amended by
(i) deleting the phrase "until the end of the twelfth full calendar quarter
thereafter, Neurex' Detail Percentage will not exceed 12% and thereafter will
not exceed 16%" and (ii) replacing such phrase with "Neurex' Detail Percentage
will not exceed 20%".
7. Term. Section 1.3 of the Agreement is hereby amended by (i) deleting the
phrase "shall terminate on the third anniversary hereafter" and (ii) replacing
such phrase with "shall terminate on September 29, 1999; provided, however, that
Warner may terminate this Agreement in its sole discretion on September 29, 1997
or September 29, 1998, by providing written notice thereof to Neurex on or
before July 31, 1997 or July 31, 1998, respectively." Furthermore, the following
is added at the end of Section 1.3: "The parties agree to discuss adjustment to
the size and focus of their commitment to the Collaboration during the third
calendar quarter of each year of the Term of the Collaboration depending on
mutually agreed research goals for the following year of the Collaboration."
Upon termination or expiration of this Agreement, Neurex will promptly return a
pro rata amount of any advances made by Warner under Section 1.2, based on the
amount of time remaining in the relevant quarter following such termination or
expiration.
8. Section 3(b) Neurex Products. Notwithstanding the terms of Section 5.4 of the
Agreement, Neurex will pay Warner 4% of Net Sales as a royalty on all sales of
Neurex Products that are originally designated "Neurex Products" pursuant to
Section 3(b) of this Amendment. Neurex will notify Warner promptly after filing
an IND with the Food and Drug Administration relating to any Neurex Product that
is originally designated a Neurex Product pursuant to Section 3(b) of this
Amendment. Warner and Neurex agree, at Warner's option, to negotiate in good
faith exclusively with each other for 90 days from Warner's receipt of such
notice regarding a development and marketing collaboration on such Neurex
Product. If the parties do not reach agreement on such a collaboration within
such 90 day period, Neurex will be free to negotiate with all other parties, or
pursue development and marketing of the Neurex Product by itself; provided,
however, that in no event will Neurex be entitled to collaborate with any third
party regarding such Neurex Product on terms that are less favorable to Neurex
than those last proposed by Warner during the 90 day exclusive negotiation
period.
IN WITNESS WHEREOF, the undersigned have signed this Amendment as of
the date first written above.
XXXXXX-XXXXXXX COMPANY
By:________________________________
Name:
Title
NEUREX CORPORATION
By:________________________________
Name:
Title:
