Document:

exv10w22

[ ** ] = Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

Exhibit 10.22

LICENSE AND SUPPLY AGREEMENT

     This License and Supply Agreement (this “Agreement”) is made this 12th day of
October, 2005 (the “Effective Date”), by and between CyDex, Inc., a Delaware corporation
with offices at 10513 W. 84th Terrace, Lenexa, Kansas 66214, (“CyDex”), and
Proteolix, Inc., a Delaware corporation with offices at 225 Gateway Boulevard, South San
Francisco, California 94080 (“Proteolix”).

Recitals

     Whereas, CyDex is engaged in the business of developing and commercializing novel
drug delivery technologies designed to enhance the solubility and effectiveness of existing and
development-stage drugs;

     Whereas, CyDex is the exclusive worldwide licensee of CAPTISOL®, a patented drug
formulation system designed to enhance the solubility and stability of drugs;

     Whereas, Proteolix desires to obtain a license to use such patented drug formulation
system in connection with its development and commercialization of a certain pharmaceutical
compound and CyDex is willing to grant such license to Proteolix under the terms and conditions set
forth herein; and

     Whereas, CyDex desires to sell CAPTISOL® to Proteolix, and Proteolix desires to
purchase CAPTISOL® from CyDex, in accordance with the terms and conditions contained herein.

     Now, Therefore, in consideration of the following mutual promises and other good and
valuable consideration, the receipt and sufficiency of which is acknowledged, the parties,
intending to be legally bound, agree as follows:

1. Definitions.

     For the purposes of this Agreement, the terms hereunder shall have the meanings as defined
below:

     1.1 “Affiliate” means, with respect to any party, any entity controlling, controlled by, or
under common control with such party, during and for such time as such control exists. For these
purposes, “control” shall refer to the ownership, directly or indirectly, of at least fifty percent
(50%) of the voting securities or other ownership interest of the relevant entity.

     1.2 “CAPTISOL” means CAPTISOL®, also known scientifically as sulfobutylether b(beta)
cyclodextrin, sodium salt.

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 1.

 

     1.3 “CAPTISOL Data Package” means (a) all toxicology/safety and other relevant scientific
safety data owned, licensed or developed by CyDex and its Affiliates; (b) all toxicology/safety and
other relevant scientific data owned, licensed or developed by the licensees or sublicensees of
CyDex or its Affiliates or other third parties (to the extent permitted in the applicable license
or other agreements between CyDex and/or its Affiliates and such licensees, sublicensees or other
third parties) on CAPTISOL alone (and not in conjunction with a product formulation); and (c) all
CMC and manufacturing process data relating to the preparation of CAPTISOL, in each case to the
extent necessary or useful for the formulation of the Product.

     1.4 “CAPTISOL Improvement” means any technology or improvement specifically related to the
physical properties of CAPTISOL, whether or not patentable, that is developed by Proteolix or its
Affiliates or Sublicensees, solely or jointly with a third party.

     1.5 “Claim” has the meaning specified in Section 10.1.

     1.6 “Clinical Grade CAPTISOL” means CAPTISOL which (a) has been manufactured under conditions
of current good manufacturing practices for bulk excipients as set forth in U.S. Pharmacopoeia
<1078> or any successor thereto, (b) is intended for use in humans, and (iii) is intended for
clinical trials for the Product.

     1.7 “Commercial Grade CAPTISOL” means CAPTISOL which (a) has been manufactured under
conditions of current good manufacturing practices for bulk excipients as set forth in U.S.
Pharmacopoeia <1078> or any successor thereto, (b) is intended for use in humans, and (iii)
is intended for commercial sale of the Product.

     1.8 “Commercial Launch Date” means, in any particular country, the first commercial sale of
the Product by Proteolix, or an Affiliate or Sublicensee of Proteolix to a third party.

     1.9 “Compound” means that certain pharmaceutical compound known as PR-171, owned by or
licensed to Proteolix and developed and manufactured by or on behalf of Proteolix.

     1.10 “Confidential Information” has the meaning specified in Section 8.1.

     1.11 “Detailed Forecast” has the meaning specified in Section 3.2(b).

     1.12 “Disclosing Party” has the meaning specified in Section 8.1 hereof.

     1.13 “DMF” means a Drug Master File for CAPTISOL, as currently filed, or as hereafter updated
from time to time, by CyDex with the FDA.

     1.14 “FDA” means the United States Food and Drug Administration, or any successor thereto.

     1.15 “Field” means the treatment of any and all diseases and conditions in humans, except:
(a) for the treatment or prophylaxis of fungal infections; or (b) as a topical ocular treatment of
dry eye.

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 2.

 

     1.16 “IND” means an Investigational New Drug application, as defined in the United States
Federal Food, Drug and Cosmetics Act and the regulations promulgated thereunder, or similar
application filed with an equivalent regulatory body in another country.

     1.17 “Indemnitee” has the meaning specified in Section 10.3.

     1.18 “Indemnitor” has the meaning specified in Section 10.3.

     1.19 “Initial Detailed Forecast” has the meaning specified in Section 3.2(b).

     1.20 “Licensed Patents” means all patents and patent applications in the Territory which cover
CAPTISOL and which now or at any time during the Term are owned by or licensed to CyDex or any
CyDex Affiliate with the right to sublicense, including any and all extensions, renewals,
continuations, substitutions, continuations-in-part, divisions, patents-of-addition, reissues,
reexaminations and/or supplementary protection certificates to any such patents. Set forth in
Exhibit A attached hereto is a list of the Licensed Patents as of the Effective Date. Such Exhibit
shall be updated by CyDex from time to time.

     1.21 “Product” means the Compound combined with or formulated using CAPTISOL in a parenteral
dosage form/formulation.

     1.22 “Losses” has the meaning set forth in Section 10.1.

     1.23 “Marketing Approval” means final approval of an NDA by the FDA, or final approval of a
comparable document filed with an equivalent health regulatory authority in any other country or in
the European Union (using the centralized process or mutual recognition), including all required
marketing, pricing or reimbursement approvals.

     1.24 “NDA” means a New Drug Application, as defined in the United States Federal Food, Drug
and Cosmetics Act and the regulations promulgated thereunder; or similar application filed with an
equivalent regulatory body in another country.

     1.25 “Net Sales” means gross amounts invoiced by Proteolix, its Affiliates and Sublicensees
for sales of the Product in the Field, less the following: (a) normal and customary trade,
quantity and/or cash discounts, allowances and rebates actually allowed or given; (b) returns and
credits actually allowed for rejections, defects or recalls of Product, outdated or returned
Product, or because of rebates or retroactive price reductions; (c) freight, postage, shipping
insurance and other transportation expenses (if separately identified on the invoice); and (d)
sales, value-added, excise or use taxes, tariffs, duties and customs fees and other taxes imposed
with respect to specific sales. “Net Sales” shall not include amounts for any Product furnished to
a third party for use in clinical trials and Product distributed as promotional and free goods.
Furthermore, “Net Sales” shall not include amounts from sales or other dispositions of Product
between Proteolix and any of its Affiliates or Sublicensees, unless such Affiliate or Sublicensee
is an end-user of such Product.

     1.26 “Notice of Termination” has the meaning specified in Section 13.2.

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 3.

 

     1.27 “Phase 1 Trial” means those clinical trials on sufficient numbers of normal volunteers
and patients that are designed to establish that a drug is safe for its intended use, and to
support its continued testing in Phase 2 Trials.

     1.28 “Phase 2 Trial” means those trials in sufficient numbers of patients that are designed to
establish the safety and biological activity of a drug for its intended use, and to define
warnings, precautions and adverse reactions that are associated with a drug in the dosage range to
be prescribed.

     1.29 “Pfizer” has the meaning specified in Section 8.5.

     1.30 “Purchase Volume Limitations” has the meaning specified in Section 3.2(c).

     1.31 “Receiving Party” has the meaning specified in Section 8.1.

     1.32 “Ql” has the meaning specified in Section 3.2(c).

     1.33 “Research Grade CAPTISOL” means CAPTISOL which has not been manufactured under required
conditions of current good manufacturing practices and is not suitable for use in humans, but which
meets the Specifications for Research Grade CAPTISOL.

     1.34 “Specifications” means the specifications for CAPTISOL set forth in Exhibit B hereto, as
such may be amended from time to time pursuant to Section 3.4.

     1.35 “Sublicensees” has the meaning specified in Section 2.3.

     1.36 “Term” has the meaning specified in Section 13.1.

     1.37 “Testing Methods” has the meaning specified in Section 3.5(a).

     1.38 “Third-Party Manufacturer” has the meaning specified in Section 3.6.

     1.39 “Territory” means the entire world.

2. Grant of Rights.

     2.1 License Grants from CyDex to Proteolix.

          (a) Licensed Patents. Subject to the terms and conditions of this Agreement, CyDex
hereby grants to Proteolix an exclusive, nontransferable license during the Term under the Licensed
Patents, solely to develop, make, have made, use, market, distribute, sell, offer for sale and
import the Product in the Field in the Territory. Notwithstanding the foregoing, to the extent
that any Licensed Patents are licensed to CyDex or its Affiliates by a third party on a
non-exclusive basis, the license granted to Proteolix in the foregoing sentence shall be exclusive
as to CyDex and non-exclusive as to any third party. Proteolix may not sublicense the Licensed
Patents, except as expressly set forth in Section 2.3 below. For purposes of clarification, CyDex
grants no rights to Proteolix to manufacture, import, sell or offer to sell bulk CAPTISOL, except
as otherwise provided in Section 3.7(c).

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 4.

 

          (b) CAPTISOL Data Package. Subject to the terms and conditions of this Agreement,
CyDex hereby grants to Proteolix a non-exclusive, nontransferable license during the Term under
CyDex’ right in and to the CAPTISOL Data Package, solely to develop, make, have made, use, market,
distribute, sell, offer for sale and import the Product in the Field in the Territory. Proteolix
may not sublicense its rights to the CAPTISOL Data Package, except as expressly set forth in
Section 2.3 below.

     2.2 Grant of License from Proteolix to CyDex. Proteolix hereby grants to CyDex a
non-exclusive, transferable, perpetual, royalty-free license, with the right to grant sublicenses,
under Proteolix’, its Affiliates’ and Sublicensees’ rights in and to CAPTISOL Improvements to
develop, make, have made, use, market, distribute, sell, offer for sale and import any CAPTISOL
Improvement in the Territory. Proteolix shall provide prompt notice of any such CAPTISOL
Improvement, and shall notify and consult with CyDex at least [ ** ] days prior to the filing of
any patent application with respect to such CAPTISOL Improvement.

     2.3 Sublicensing. Proteolix shall have the right to grant sublicenses to its Affiliates and
licensees of the Product (collectively “Sublicensees”) under the licenses granted to Proteolix
pursuant to Section 2.1; provided that (a) each such Sublicensee has agreed to be bound by all
applicable terms and obligations of the rights and licenses granted by CyDex to Proteolix under
this Agreement (including, without limitation, Proteolix’ confidentiality obligations), (b) the
terms and conditions of each such sublicense is consistent with and no less restrictive than the
terms and conditions of this Agreement, and (c) Proteolix provides to CyDex a copy of each such
sublicense agreement with respect to the Product, provided, however, Proteolix may redact any
proprietary or financial terms from any such copy. If necessary to engage a third party
manufacturer for the Product, Proteolix shall be permitted under this Agreement to treat any such
third party manufacturer as a Sublicensee, subject to the terms of this Section 2.3. In any event,
Proteolix shall procure from any third party manufacturer of the Product, such third party’s
agreement that all bulk CAPTISOL supplied pursuant to this Agreement shall be used solely for the
manufacture of the Product. Other than as specifically provided in and this Section 2.3, Proteolix
shall not have the right to grant sublicenses to any third party under the licenses granted
pursuant to Section 2.1.

     2.4 Reservation of Rights. This Agreement confers no right, license or interest by
implication, estoppel, or otherwise under any patents, patent applications, know-how or other
intellectual property rights of either party except as expressly set forth in this Section 2 and
elsewhere in this Agreement. Each party hereby expressly retains and reserves all rights and
interests with respect to patents, patent applications, know-how or other intellectual property
rights not expressly granted to the other party hereunder.

3. Manufacture and Supply of CAPTISOL.

     3.1 Purchase of CAPTISOL. Proteolix agrees that Proteolix and its Affiliates and Sublicensees
shall purchase CAPTISOL for use in Product exclusively from CyDex and that they shall not
manufacture (or have manufactured on their behalf) CAPTISOL for such use without CyDex’ prior
written consent. CyDex agrees that CyDex shall produce (or have produced for it) and sell to
Proteolix one hundred percent (100%) of Proteolix’ and its Affiliates’

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 5.

 

and Sublicensees’ requirements for CAPTISOL for use in Product, during the Term and subject to
the provisions of this Agreement. Purchases of CAPTISOL may include Research Grade CAPTISOL,
Clinical Grade CAPTISOL and/or Commercial Grade CAPTISOL. Proteolix may place orders for CAPTISOL
on behalf of its Affiliates and Sublicensees; provided, however, that: (a) Proteolix shall
instruct CyDex as to the location for the shipment thereof; (b) Proteolix shall guarantee payment
to CyDex of all amounts payable with respect thereto; and (c) if Proteolix requests that CyDex
deliver such orders to Proteolix for re-delivery thereof by Proteolix to its Affiliates or
Sublicensees, Proteolix shall comply with all applicable laws, rules and regulations applicable to
the transportation of CAPTISOL from Proteolix to its Affiliates and Sublicensees.

     3.2 Supply Terms.

          (a) Long-term Forecast. No later than [ ** ] months prior to the anticipated Commercial
Launch Date by Proteolix or its Affiliates or Sublicensees of a Product in any particular country,
Proteolix shall provide CyDex with a forecast setting forth Proteolix’ estimate of the required
quantities of Commercial Grade CAPTISOL for each of the following [ ** ] years. Such long-term
forecast shall thereafter be updated by Proteolix at least once every [ ** ] months.

          (b) Detailed Forecasts.

               (i) Commercial Forecasts: At least [ ** ] calendar quarters prior to the calendar quarter in
which Proteolix anticipates the placement of its first order for Commercial Grade CAPTISOL, and
thereafter on a calendar quarterly basis until the First Commercial Sale Date, Proteolix shall
deliver to CyDex a detailed rolling forecast setting forth Proteolix’ anticipated requirements and
anticipated delivery schedules for Commercial Grade CAPTISOL for the calendar quarter in which the
Commercial Launch Date of a Product is anticipated to occur and, in addition, for each full
calendar quarter during the [ ** ] month period following such anticipated Commercial Launch Date
(the “Initial Detailed Forecast”). No later than the first day of the first full calendar quarter
following the Commercial Launch Date, and no later than the first day of each full calendar quarter
thereafter, Proteolix shall deliver to CyDex a detailed rolling forecast setting forth Proteolix’
anticipated requirements and anticipated delivery schedules for Commercial Grade CAPTISOL for each
of the [ ** ] full calendar quarters during the [ ** ] month period following the delivery date of
such forecast (each, a “Detailed Forecast”). Each Detailed Forecast shall be firm and binding on
Proteolix with respect to Proteolix’ obligation to purchase quantities of Commercial Grade CAPTISOL
for the [ ** ] and [ ** ] full calendar quarter in such Detailed Forecast, subject to the
permissible variances set forth in Section 3.2(c) below, and estimates of Proteolix’ requirements
for the [ ** ] and [ ** ] full calendar quarters in such Detailed Forecast. If Proteolix fails to
provide any updated Detailed Forecast in accordance with this Section 3.2(b), the Detailed Forecast
last provided by Proteolix shall be deemed to be the updated Detailed Forecast, and the next full
calendar quarter estimate of Proteolix’ requirements for Commercial Grade CAPTISOL set forth in
such Detailed Forecast shall be a firm and binding obligation with respect to Proteolix’ obligation
to purchase Commercial Grade for such next full calendar quarter.

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 6.

 

               (ii) Clinical Forecasts: Beginning [ ** ] months after the Effective Date, Proteolix shall
deliver to CyDex at least every [ ** ] months, a rolling forecast of their estimated requirements
for Clinical Grade CAPTISOL for so long as Proteolix requires clinical grade material during the
Term. Upon commencement of the Detailed Forecast as specified in Section 3.2(b) above, the
Clinical Forecast shall be incorporated, as a separate subsection, into such Detailed Forecast.
The frequency of the Clinical Forecast shall then be the same as for the Detailed Forecast. The
Clinical Forecast shall be for planning purposes only, and thus shall not be binding in any manner
whatsoever until a PO has been placed by Proteolix for said Clinical Grade CAPTISOL and accepted by
CyDex.

          (c) Detailed Forecast Variances. Each updated Detailed Forecast may modify the amount of
Commercial Grade CAPTISOL estimated in the previous Detailed Forecast in accordance with the
following limitations (the “Purchase Volume Limitations”):

               (i) for the first calendar quarter covered by such updated Detailed Forecast (“Ql”), no change
may be made without the prior express written consent of CyDex;

               (ii) for the second calendar quarter covered by such updated Detailed Forecast, no change in
excess of a [ ** ] percent [ ** ] volume increase or decrease from the prior Detailed Forecast may
be made without the prior express written consent of CyDex;

               (iii) for the third calendar quarter covered by such updated Detailed Forecast, no change in
excess of a [ ** ] percent [ ** ] volume increase or decrease from the prior Forecast may be made
without the prior express written consent of CyDex; and

               (iv) for the fourth calendar quarter covered by such updated Detailed Forecast, no change in
excess of a [ ** ] percent [ ** ] volume increase or decrease from the prior Forecast may be made
without the prior express written consent of CyDex.

In each case CyDex’ consent may be conditioned on such payment or other terms as CyDex may require.

          (d) Purchase Orders. Together with each Detailed Forecast provided under Section 3.2(b)
above, Proteolix shall place a firm purchase order with CyDex in a form mutually agreed upon by the
parties, for Proteolix’ order of Commercial Grade CAPTISOL for Q1 delivery consistent with the
Detailed Forecast. Each purchase order, for all grades of CAPTISOL, shall specify: (i) the grade
of CAPTISOL ordered (i.e., Commercial Grade CAPTISOL, Clinical Grade CAPTISOL or Research Grade
CAPTISOL); (ii) quantities; (iii) delivery dates; and (iv) reasonable shipping instructions. CyDex
shall use commercially reasonable efforts to comply with Proteolix’ requested delivery dates;
provided, however, that the purchase order is received by CyDex at least [ ** ] days prior to the
stipulated delivery date. No purchase order shall be binding upon CyDex until accepted by CyDex in
writing; provided, however, that CyDex shall accept such orders for Commercial Grade CAPTISOL from
Proteolix to the extent that the quantities of CAPTISOL ordered do not exceed the Purchase Volume
Limitations. CyDex shall not be obligated to accept such orders to the extent that the quantities
of Commercial Grade CAPTISOL ordered exceed the Purchase Volume Limitations, but CyDex shall use
good faith efforts to fill such orders for such excess quantities from available supplies.

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 7.

 

If CyDex, despite the use of good faith efforts, is unable to supply such quantities that
exceed the Purchase Volume Limitations to Proteolix, such inability to supply shall not be deemed
to be a breach of this Agreement by CyDex or a failure by CyDex to supply for any purpose. Ordered
quantities of Commercial Grade CAPTISOL shall be specified in multiples of [ ** ] kilograms,
subject to a minimum order quantity of [ ** ] kilograms. CyDex shall use reasonable efforts to
notify Proteolix within [ ** ] business days after its receipt of Proteolix’ purchase order of its
ability to fill any amounts of such order that are in excess of the Purchase Volume Limitations.
If any purchase order or other document submitted by Proteolix hereunder or any other document
passing between the parties contains terms or conditions in addition to or inconsistent with the
terms of this Agreement, the terms of this Agreement shall control and prevail and such additional
or inconsistent terms are hereby expressly rejected.

     3.3 Delivery. CyDex shall deliver to Proteolix or Proteolix’ designee each order of CAPTISOL,
packed for shipment in accordance with CyDex’ customary practices and the Specifications, CIP
Proteolix designated location (Incoterms 2000). Title and risk of loss and/or damage to CAPTISOL
shall pass to Proteolix upon delivery of CAPTISOL to Proteolix or Proteolix’ designee at
Proteolix’s designed location. CyDex acknowledges the inherent risk that a batch of CAPTISOL may
be lost in production or shipment, and CyDex agrees to maintain an inventory of CAPTISOL sufficient
to supply at least [ ** ] days worth of Proteolix’ requirements in the event of production or
delivery delays.

     3.4 Modified Specifications. CyDex shall have the right to change the Specifications from
time to time during the Term; provided that such change has no adverse effect or consequence on
Proteolix’ development or commercialization of the Product including, for example, an effect or
consequence that requires Proteolix to conduct any clinical study requested by the FDA or other
regulatory agency. Any change in the Specifications that would have an adverse effect or
consequence on Proteolix’ development or commercialization of the Product will require Proteolix’
prior written consent. In the event that CyDex desires to change the Specifications, CyDex shall
give Proteolix at least [ ** ] days notice. CyDex shall cooperate with Proteolix to have any
change approved by the FDA and other regulatory agencies having jurisdiction. In the event that
the FDA or another regulatory agency having jurisdiction requires Proteolix to implement any
changes to the Specifications, CyDex shall use all reasonable efforts to make such changes. CyDex
shall promptly advise Proteolix as to any lead-time changes or other terms that may result from a
change to the Specifications, including but not limited to price adjustments necessary to enable
CyDex to recover costs it actually incurred for materials already purchased by CyDex expressly for
Proteolix, its Affiliates or Sublicensees and rendered unusable by a change in Specifications
requested by Proteolix or as necessary to comply with government regulatory requirements with
respect to the Product If a regulatory agency requires a change to the Specifications where such
change is specific to CAPTISOL and not specific to the Product then CyDex shall be responsible for
the costs incurred to generate such unique, modified Specifications.

     3.5 Quality Control; Acceptance and Rejection.

          (a) Quality Control. CyDex shall conduct or have conducted quality control testing of
CAPTISOL prior to shipment in accordance with the Specifications and other CyDex-

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 8.

 

approved quality control testing procedures (the “Testing Methods”). CyDex shall retain or
have retained accurate and complete records pertaining to such testing. Each shipment of CAPTISOL
hereunder shall be accompanied by a certificate of analysis for each lot of CAPTISOL therein.

          (b) Acceptance Testing. Proteolix shall have a period of [ ** ] days after the date of
receipt to test or cause to be tested CAPTISOL supplied under this Agreement. Proteolix or its
designee shall have the right to reject any shipment of CAPTISOL that does not conform in all
material respects with the Specifications at the time of delivery pursuant to Section 3.3 hereof
when tested in accordance with the Testing Methods. All shipments of CAPTISOL shall be deemed
accepted by Proteolix unless CyDex receives written notice of rejection from Proteolix within such
[ ** ] day period, describing the reasons for the rejection in reasonable detail. Once a delivery
of CAPTISOL is accepted or deemed accepted hereunder, Proteolix shall have no recourse against
CyDex in the event CAPTISOL is subsequently deemed unsuitable for use for any reason, except as
provided in Sections 7.4 and 10 below.

          (c) Confirmation. CyDex shall notify Proteolix as soon as reasonably practical (but in any
event within [ ** ] days) after its receipt of a notice of rejection from Proteolix pursuant to
Section 3.5(b) above, whether CyDex accepts Proteolix’ basis for rejection and Proteolix shall
cooperate with CyDex in determining whether such rejection was necessary or justified. If the
parties are unable to agree as to whether a shipment of CAPTISOL supplied by CyDex or its
Third-Party Manufacturer hereunder meets the Specifications, such question shall be submitted to an
independent quality control laboratory mutually agreed upon by the parties. The findings of such
independent laboratory shall be binding upon the parties. The cost of the independent quality
control laboratory shall be borne by the party whose results are shown by such laboratory to have
been incorrect.

          (d) Return or Destruction of Rejected Shipments. Proteolix may not return or destroy any
batch of CAPTISOL until it receives written notification from CyDex that CyDex does not dispute
that the batch fails to meet the Specifications; provided that if Proteolix does not receive such
written notice within [ ** ] days after its delivery of a notice of rejection to CyDex pursuant to
Section 3.5(b) above, CyDex shall be deemed to agree that such batch fails to meet the
Specifications. CyDex will indicate in its notice either that Proteolix is authorized to destroy
the rejected batch of CAPTISOL or that CyDex requires return of the rejected CAPTISOL. Upon
written authorization from CyDex to do so, Proteolix shall promptly destroy the rejected batch of
CAPTISOL and provide CyDex with written certification of such destruction. Upon receipt of CyDex’
request for return, Proteolix shall promptly return the rejected batch of CAPTISOL to CyDex. In
each case, CyDex will reimburse Proteolix for the documented, reasonable costs associated with the
destruction or return of the rejected CAPTISOL.

          (e) Refund or Replacement. Proteolix shall not be required to pay any invoice with respect to
any shipment of CAPTISOL properly rejected pursuant to this Section 3.5. Notwithstanding the
foregoing, Proteolix shall be obligated to pay in full for any rejected shipment of CAPTISOL that
is subsequently determined to meet the Specifications in accordance with Section 3.5(c),
irrespective of whether Proteolix has already paid CyDex for a replacement shipment. If Proteolix
pays in full for a shipment of CAPTISOL and subsequently

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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properly rejects such shipment in accordance with this Section 3.5, Proteolix shall be
entitled, upon confirmation that such shipment failed to meet the Specifications in all material
respects, either: (i) to a refund or credit equal to the purchase price paid with respect to such
rejected shipment; or (ii) to require CyDex to replace such rejected shipment at no additional cost
to Proteolix. Proteolix acknowledges and agrees that, except for the indemnification obligations
set forth in Section 10 below, Proteolix’ rights to a refund or credit for or to receive
replacement of properly rejected shipments of CAPTISOL hereunder shall be Proteolix’ sole and
exclusive remedy, and CyDex’ sole obligation, with respect to non-conforming CAPTISOL delivered
hereunder.

          (f) Exceptions. Proteolix’ rights of rejection, return, refund and replacement set forth in
this Section 3.5 shall not apply to any CAPTISOL that is non-conforming due to damage caused by
Proteolix, its Affiliates or Sublicensees or their respective employees or agents, including but
not limited to, misuse, neglect, improper storage, transportation or use beyond any dating
provided.

     3.6 Facilities and Inspections. Without limiting CyDex’ responsibility under this Agreement,
CyDex shall have the right at any time to satisfy its supply obligations to Proteolix hereunder
either in whole or in part through arrangements with third parties engaged to perform services or
supply facilities or goods in connection with the manufacture or testing of CAPTISOL (each, a
“Third-Party Manufacturer”). CyDex shall give Proteolix prior written notice of any such
arrangement. CyDex shall permit no more than [ ** ] of Proteolix’ authorized representatives,
during normal working hours and upon reasonable prior notice to CyDex but in no event less than [
** ] days prior notice, to inspect that portion of all CyDex facilities utilized for the
manufacture, preparation, processing, storage or quality control of CAPTISOL or such facilities of
any Third-Party Manufacturer, no more frequently than [ ** ] per calendar year. Notwithstanding
the foregoing, CyDex agrees to reasonably cooperate, and shall require any Third-Party Manufacturer
to reasonably cooperate, with all regulatory authorities and shall submit to reasonable
CAPTISOL-related inspections by such authorities. With respect to inspection of the facilities of
a Third Party Manufacturer by Proteolix, its Affiliates or Sublicensees, Proteolix shall be
responsible for any reasonable fees charged by CyDex’ Third Party Manufacturer in connection with
such inspections (as of the Effective Date, [ ** ] Dollars [ ** ] per person per day). Proteolix’
authorized representatives shall be accompanied by CyDex personnel at all times, shall be qualified
to conduct such manufacturing audits, shall comply with all applicable rules and regulations
relating to facility security, health and safety, and shall execute a written confidentiality
agreement with terms at least as restrictive as those set forth in Section 8 (Confidentiality)
hereof. In no event shall any such manufacturing audit exceed [ ** ] days in duration. Proteolix
shall ensure that its authorized representatives conduct each manufacturing audit in such a manner
as to not interfere with the normal and ordinary operation of CyDex or its Third-Party
Manufacturer. Except as expressly set forth in this Section 3.6, neither Proteolix nor its
Affiliates, sublicensees or their respective employees or representatives shall have access to
CyDex’ facilities or the facilities of any Third-Party Manufacturer.

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 10.

 

     3.7 Inability to Supply.

          (a) Notice. CyDex shall notify Proteolix if CyDex is unable to supply the quantity of (i)
Commercial Grade CAPTISOL ordered by Proteolix in accordance with the Purchase Volume Limitations
set forth in Section 3.2(c) or (ii) Research Grade CAPTISOL or Clinical Grade CAPTISOL ordered by
Proteolix as set forth in Section 3.2(d) above: (1) within [ ** ] days after CyDex’ receipt of a
purchase order from Proteolix as provided in Section 3.2(d); or (2) immediately upon becoming aware
of an event of force majeure or any other event that would render CyDex unable to supply to
Proteolix the quantity of CAPTISOL that CyDex is required to supply hereunder.

          (b) Allocation. If CyDex is unable to supply to Proteolix the quantity of CAPTISOL that CyDex
is required to supply hereunder, CyDex (i) shall allocate its available CAPTISOL among Proteolix
and any other purchasers of CAPTISOL with which CyDex then has an on-going contractual
relationship, in proportion to the quantity of CAPTISOL for which each of them has orders pending
at such time and (ii) shall take all reasonable steps necessary to minimize supply delays.

          (c) Right to Manufacture. If CyDex is not able to supply CAPTISOL to Proteolix which meets
Specifications or in the quantity requirements for CAPTISOL ordered in accordance with this Section
3, Proteolix shall be entitled to manufacture CAPTISOL but only for Proteolix’ clinical use,
marketing, sale and distribution of the Product. Notwithstanding the above, Proteolix may exercise
such right to manufacture CAPTISOL only if (i) CyDex’ inability to supply CAPTISOL could reasonably
be expected to result in a period of time during which no CAPTISOL would be available to Proteolix
for the clinical use, marketing, sale and distribution of the Product, (ii) there is no reason to
believe that CyDex would be able to re-start manufacture of CAPTISOL more quickly than Proteolix or
Proteolix’ designee could start manufacture of CAPTISOL, and (iii) CyDex’ inability to supply
CAPTISOL did not result, wholly or in part, from factors within the control of CyDex.

4. Compensation.

     4.1 Payments and Royalties for Licenses.

          (a) One-Time Fee. Proteolix shall pay to CyDex a [ ** ] one-time fee of [ ** ] dollars ($[ **
]) in partial consideration of the rights granted Proteolix under this Agreement, which amount
shall be due and payable in full upon the Effective Date.

          (b) Milestone Payments. Pursuant to Section 5.2(a), written notice of each of the milestone
events listed below with respect to the Product shall be provided to CyDex, and within [ ** ] days
after such written notice of each of the milestone events, Proteolix shall pay to CyDex the
applicable non-refundable milestone fee listed next to each such event in further consideration of
the rights granted Proteolix hereunder. The milestone payments are as follows:

	 	 	 
	Milestone	 	Milestone Payment
	[ ** ]

	 	[ ** ]

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 11.

 

	 	 	 
	Milestone	 	Milestone Payment
	[ ** ]

	 	[ ** ]
	[ ** ]

	 	[ ** ]
	[ ** ]

	 	[ ** ]
	[ ** ]

	 	[ ** ]
	[ ** ]

	 	[ ** ]
	Upon first achievement of [ ** ] in annual Net
Sales of Product

	 	[ ** ]
	Upon first achievement of [ ** ] in annual Net
Sales of Product

	 	[ ** ]
	Upon first achievement of [ ** ] in annual Net
Sales of Product

	 	[ ** ]

          (c) Royalties.

               (i) In addition to amounts payable pursuant to Sections 4.1(a) and 4.1(b) above, Proteolix
shall make royalty payments to CyDex on a calendar quarterly basis, in an amount equal to the
appropriate royalty rate, according to the following rate schedule, to the applicable Net Sales
during such quarter arising from the sale of the Product in the Territory. All royalties payable
to CyDex pursuant to this Section 4.1(c)(i) shall be due and payable within [ ** ] days after
receipt of the Quarterly Report as set forth in Section 5.2(a).

	 	 	 
	Aggregate Net Sales in	 	 
	Each Calendar Year	 	Royalty Rate
	Up to, and including, [ ** ]

	 	[ ** ]
	[ ** ] to [ ** ]

	 	[ ** ]
	[ ** ] to [ ** ]

	 	[ ** ]
	Above [ ** ]

	 	[ ** ]

For clarity, the royalty rates set forth above in Section 4.1(c) shall be applied to the total Net
Sales of Product falling within the applicable range of aggregate annual Net Sales during the
quarter. For example, if at the end of the first quarter of a particular calendar year, aggregate
Net Sales of such Product was [ ** ], then sales representing the first [ ** ] in such first
quarter would be subject to the [ ** ] royalty rate and the remaining [ ** ] would be subject to
the [ ** ] royalty rate under Section 4.1(c). In subsequent quarters of the same calendar year,
all sales of Product would be subject to the [ ** ] royalty rate until total aggregate sales of
Product in such calendar year reached [ ** ], at which point all further sales of Product up to [
** ] would be subject to the [ ** ] royalty rate. For aggregate sales exceeding [ ** ] in the same
calendar year, such sales of Product would be subject to the [ ** ] royalty rate.

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 12.

 

               (ii) The obligation of Proteolix to pay royalties to CyDex under this Section 4.1(c) shall
commence on the first Commercial Launch Date of the Product in the Field in the Territory and
continue, on a country-by-country basis, (1) until the expiration of the last to expire patent
within the Licensed Patents in such country, and (2) after the period described in (1), a period of
[ ** ] years with royalties to be calculated on aggregate annual Net Sales at a rate equal to [ **
] percent [ ** ] of the royalty rates set forth in Section 4.1(c)(i) above. Thereafter, Proteolix
shall have a paid up, royalty-free license with respect to the Product in the Field.

     4.2 Pricing for CAPTISOL.

          (a) Pricing. The purchase prices for CAPTISOL are as specified in Exhibit C attached hereto.
CyDex reserves the right to increase the purchase prices set forth on Exhibit C on each January 1
during the Term, by written notice to Proteolix, by a percentage equal to the aggregate percentage
increase, if any, in the Producer Price Index PCU325412 (Pharmaceutical preparations) as reported
by the Bureau of Labor Statistics, U.S. Department of Labor, for the twelve (12) month period
ending October 31 of the prior year. If Proteolix fails to place a firm purchase order for any Q1
for a quantity of Commercial Grade CAPTISOL to be delivered during such Q1 equal to or greater than
the quantity of Commercial Grade CAPTISOL Proteolix is obligated to purchase pursuant to the
applicable Detailed Forecast, allowing for the variances as defined in Section 3.2(c), CyDex may
adjust the purchase price of Commercial Grade CAPTISOL ordered under this Agreement so as to permit
CyDex to recover all reasonable costs and expenses incurred by CyDex in reliance upon Proteolix’
binding obligation, including but not limited to the costs of the raw materials and supplies of
CAPTISOL acquired or used in contemplation of fulfilling such order.

          (b) Invoicing; Payment. CyDex shall invoice Proteolix upon shipment of each order of
CAPTISOL. All invoices shall be sent to the address specified in the applicable purchase order, and
each invoice shall state the purchase price for CAPTISOL in such shipment, plus any insurance,
taxes, shipping costs or other costs incidental to such purchase or shipment initially paid by
CyDex but to be borne by Proteolix hereunder; provided, however, that if such insurance, taxes,
shipping costs or other costs incidental to such purchase or shipment initially paid by CyDex but
to be borne by Proteolix are not known at the time CyDex invoices Proteolix for the purchase price
for the CAPTISOL ordered by Proteolix, CyDex may invoice such costs at a later date. Payment of
such invoices shall be made within [ ** ] days after the date of delivery of such invoice pursuant
to Section 14.7.

     4.3 Currency. All amounts due hereunder are stated in, and shall be paid in, U.S. dollars.
Net Sales based on foreign revenue will be converted to U.S. dollars at the rate of exchange
published in The Wall Street Journal, Eastern U.S. Edition on the last day of each calendar
quarter. Proteolix shall provide CyDex, together with each royalty payment owed pursuant to
Section 4.1(c) above, a schedule detailing the calculation of Net Sales resulting from the
conversion of foreign revenue to U.S. dollars as set forth herein.

     4.4 Taxes. All amounts due hereunder exclude all applicable sales, use, and other taxes, and
Proteolix will be responsible for payment of all such taxes (other than taxes based on CyDex’
income), fees, duties, and charges, and any related penalties and interest, arising from

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 13.

 

the payment of amounts due hereunder or the sublicense or license, as the case may be, under
the Licensed Patents hereunder. Proteolix shall make all payments to CyDex hereunder free and
clear of, and without reduction for, any withholding taxes; any such taxes imposed on payments of
amounts to CyDex hereunder will be Proteolix’ sole responsibility, and Proteolix will provide CyDex
with official receipts issued by the appropriate taxing authority, or such other evidence as the
CyDex may reasonably request, to establish that such taxes have been paid. Proteolix shall
indemnify and hold CyDex harmless from any and all such taxes and any actions brought against CyDex
by any taxing authority with respect to such taxes.

     4.5 Late Payments. Unpaid balances shall accrue interest, from due date until paid, at a rate
equal to the lesser of (a) the prime rate, as reported in The Wall Street Journal, Eastern U.S.
Edition, on the date such payment is due, plus an additional [ ** ] percent [ ** ] or (b) the
maximum rate permitted under applicable law. If any amount due hereunder and not subject to a
reasonable, good-faith dispute by Proteolix remains outstanding for more than [ ** ] days after its
due date, CyDex may, in addition to any other rights or remedies it may have, refuse to ship
CAPTISOL hereunder except upon payment by Proteolix in advance.

5. Records; Reports; Audit.

     5.1 Records. During the Term and for a period of [ ** ] years thereafter, Proteolix shall,
and shall require its Affiliates and Sublicensees to, maintain complete and accurate records
relating to (a) subject enrollment in clinical studies for the Product; (b) the achievement of each
of the milestone events set forth in Section 4.1(b) above; and (c) Net Sales of Product.

     5.2 Reports.

          (a) Quarterly Reports. Within [ ** ] calendar days following the conclusion of each calendar
quarter during the Term, Proteolix shall provide CyDex with a written report with respect to such
calendar quarter that (i) indicates subject enrollment numbers during such calendar quarter with
respect to clinical studies conducted by Proteolix, its Affiliates or Sublicensees for the Product;
(ii) sets forth the achievement of each of the milestone events set forth in Section 4.1(b) above
during such calendar quarter whether achieved by Proteolix, its Affiliates and Sublicensees, and
(iii) sets forth in reasonable detail complete and accurate records of Proteolix’, its Affiliates’
and Sublicensees’ Net Sales of the Product in the Territory during such calendar quarter.

          (b) Annual Reports. Annually, by December 1st of each calendar year during the
Term, Proteolix shall provide CyDex with a written report that: (i) sets forth the achievement of
each of the milestone events set forth in Section 4.1(b) above during such calendar year whether
achieved by Proteolix, its Affiliates or Sublicensees; (ii) sets forth Proteolix’ anticipated
requirements of CAPITSOL for preclinical and clinical use during the next calendar year; (iii) sets
forth in reasonable detail complete and accurate records of Proteolix’, its Affiliates’ and
Sublicensees’ Net Sales of the Product in the Territory during such calendar year.

     5.3 Audit. During the Term and for a period of [ ** ] years thereafter, CyDex shall have the
right, during normal business hours and upon reasonable notice but no more often than [ ** ] per
year, to inspect and audit Proteolix’, its Affiliates’ and Sublicensees’ records relevant to

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 14.

 

Net Sales. The costs of such audits shall be borne solely by CyDex; provided, however, that
in the event such an audit reveals an underpayment by Proteolix of royalties owed hereunder of more
than [ ** ] percent [ ** ], Proteolix shall immediately (i) pay CyDex all amounts by which
Proteolix has underpaid CyDex as revealed by the audit, plus interest accrued thereon (from the
applicable original due date) at the rate set forth in Section 4.5 above and (ii) reimburse CyDex
for the costs of such audit. In the event such an audit reveals an overpayment by Proteolix of
royalties owed hereunder, CyDex shall immediately credit all amounts by which Proteolix has
overpaid CyDex as revealed by the audit against any amounts owed by Proteolix to CyDex in the next
payment period. All information concerning royalty payments and reports, and any information
learned in the course of any audit or inspection under this Section 5.3, shall be deemed to be
Confidential Information of Proteolix, subject to the terms and provisions of Section 8
(Confidentiality) below, except to the extent necessary for CyDex to enforce its rights under this
Agreement.

6. Development and Commercialization by Proteolix.

     6.1 Diligence. Proteolix agrees that, during the Term, it will use, and shall require its
Affiliates and Sublicensees to use, commercially reasonable efforts to conduct clinical development
of the Product, to obtain Marketing Approval in the United States, Japan and the European Union,
and to market, promote, and sell the Product thereafter in each country in which Marketing Approval
is obtained, in an effort to maximize Net Sales and, thus, royalties payable under this Agreement.

     6.2 Costs and Expenses. Proteolix shall be solely responsible for all costs and expenses
related to its development and commercialization of the Product, including without limitation costs
and expenses associated with all preclinical activities and clinical trials, and all regulatory
filings and proceedings relating to the Product.

     6.3 Preclinical In Vivo Studies. If Proteolix wishes to conduct any preclinical in vivo study
utilizing CAPTISOL (administered alone or in conjunction with the Compound) at doses greater than
those set forth in Exhibit D, Proteolix shall notify CyDex of any such study and of the protocol
therefor in writing at least [ ** ] days prior to commencing such study. If CyDex determines in
its reasonable good faith determination that such study would materially adversely affect a product
utilizing CAPTISOL, CyDex shall notify Proteolix within [ ** ] days after receipt of such notice
and protocol from Proteolix, and the parties shall discuss and attempt to resolve the matter in
good faith. If the parties cannot resolve such matter within [ ** ] days after CyDex notifies
Proteolix of such determination, then the dispute shall be presented to the chief executive officer
of each party, or his or her respective designee, for resolution. If the parties’ chief executive
officers, or their respective designees, cannot resolve the dispute within [ ** ] days after being
requested by a party to resolve such dispute, either party may initiate a short-form arbitration
proceeding pursuant to Section 14.4(b) (Short-Form Arbitration) below. If CyDex determines in its
reasonable good faith determination that such study would not materially adversely affect a product
utilizing CAPTISOL, CyDex shall notify Proteolix within [ ** ] days following receipt of Proteolix’
notice. Proteolix agrees to (a) immediately inform CyDex if any adverse effects are observed and
ascribed to CAPTISOL in any study conducted

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 15.

 

under this Section 6.3, and (b) provide CyDex with copies of the final and full reports of all
studies conducted under this Section 6.3, promptly upon completion thereof.

     6.4 Right of Reference. Proteolix shall have the right to reference the DMF solely in
connection with Proteolix’ regulatory filings submitted in connection with obtaining Marketing
Approval for the Product.

     6.5 Access to Proteolix’ Data. CyDex shall have the right to reference and utilize all
toxicology/safety and other relevant scientific data developed on CAPTISOL alone (and not in
conjunction with a product formulation) by Proteolix, its Sublicensees or Affiliates in connection
with CyDex’ development and commercialization of CAPTISOL, at no cost to CyDex. Upon request by
CyDex, Proteolix shall either provide CyDex with a copy of all such data or shall make such data
accessible to CyDex at such times and locations mutually agreed upon by the parties.

7. Regulatory Matters.

     7.1 CAPTISOL Information Submitted for Regulatory Review. Except as otherwise set forth
herein, Proteolix shall be solely responsible for all communications with regulatory agencies in
connection with the Product. Notwithstanding the foregoing, Proteolix shall provide CyDex with
copies of the portions of all regulatory submissions containing CAPTISOL data alone (and not in
conjunction with any product formulation) [ ** ] days prior to submission and shall allow CyDex to
review and comment upon said submissions. If CyDex determines in its reasonable good faith
determination that any such submission would materially adversely affect a product utilizing
CAPTISOL, CyDex shall notify Proteolix within [ ** ] days after receipt of such submission, and the
parties shall discuss and attempt to resolve the matter in good faith. If the parties cannot
resolve such matter within [ ** ] days after CyDex notifies Proteolix of such a determination, then
the dispute shall be presented to the chief executive officer of each party, or his or her
respective designee, for resolution. If the parties’ chief executive officers, or their respective
designees, cannot resolve the dispute within [ ** ] days after being requested by a party to
resolve such dispute, either party may initiate a short-form arbitration proceeding pursuant to
Section 14.4(b) below. Proteolix shall inform CyDex of meetings with the FDA (or other regulatory
agencies in the Territory) regarding the Product [ ** ] days prior to such event and shall allow
CyDex to participate in any FDA (or other regulatory agency) review that might reasonably include
inquiries regarding CAPTISOL. If Proteolix submits written responses to the FDA that include data
on CAPTISOL alone, CyDex shall be permitted to review such written materials prior to submission.
If CyDex reasonably objects to the contents of such written responses relating to CAPTISOL, the
parties agree to cooperate in working toward a reasonable and mutually agreeable response.

     7.2 Material Safety. CyDex shall provide Proteolix, in writing, from time to time, with (a)
relevant information currently known to it regarding handling precautions, toxicity and hazards
with respect to CAPTISOL, and (b) the then-current material safety data sheet for CAPTISOL.
Notwithstanding the foregoing or anything in this Agreement to the contrary, Proteolix is solely
responsible for (i) use of all documentation provided by CyDex, including without limitation, use
in any regulatory submission to the FDA or any other regulatory agency

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 16.

 

in the Territory, (ii) document control and retention, and (iii) determining the suitability
of any documentation provided by CyDex hereunder for use in any regulatory submission.

     7.3 Adverse Event Reporting.

          (a) Proteolix shall adhere, and shall require that its Affiliates, Sublicensees, co-marketers
and distributors adhere, to all requirements of applicable law and regulations that relate to the
reporting and investigation of any adverse event, including without limitation an unfavorable and
unintended confirmed diagnosis, symptom, sign, syndrome or disease, whether or not considered
CAPTISOL or Product-related, which occurs or worsens following administration of CAPTISOL or
Product. Proteolix shall provide CyDex with copies of all reports of any such adverse event
directly involving CAPTISOL that results in death, is life-threatening, requires or prolongs
inpatient hospitalization, results in disability, congenital anomaly or is medically important
(i.e., may require other medical or surgical intervention to prevent other serious criteria from
occurring) which Proteolix has reason to believe are associated with CAPTISOL within [ ** ]
business days following Proteolix’ (a) submission of any such report to any regulatory agency, or
(b) receipt from its Sublicensee, co-marketer or distributor of any such report to any regulatory
agency, as the case may be. Proteolix shall also advise CyDex regarding any proposed labeling or
registration dossier changes affecting CAPTISOL. Reports from Proteolix shall be delivered to the
attention of Vice President, Chief Scientific Officer, CyDex, with a copy to CEO, CyDex, at the
address set forth in Section 14.7 (Notices). The parties shall mutually cooperate with regard to
investigation of any such serious adverse event which is believed to be directly associated with
CAPTISOL, whether experienced by Proteolix, CyDex or any other Affiliate, Sublicensee, co-marketer
or distributor of CyDex or Proteolix.

          (b) CyDex shall adhere, and shall require that its Affiliates, Sublicensees, co-marketers and
distributors adhere, to all requirements of applicable law and regulations that relate to the
reporting and investigation of any adverse event, including without limitation an unfavorable and
unintended confirmed diagnosis, symptom, sign, syndrome or disease, whether or not considered
CAPTISOL-related, which occurs or worsens following administration of CAPTISOL alone or upon
administration of a CAPTISOL-enabled formulated product. CyDex shall provide Proteolix with copies
of all reports, some content of which may be redacted solely to protect the confidential
information of third parties, of any such adverse event directly involving CAPTISOL that results in
death, is life-threatening, requires or prolongs inpatient hospitalization, results in disability,
congenital anomaly or is medically important (i.e., may require other medical or surgical
intervention to prevent other serious criteria from occurring) which CyDex has reason to believe
are associated with CAPTISOL within [ ** ] business days following CyDex’ (a) submission of any
such report to any regulatory agency, or (b) receipt from its Sublicensee, co-marketer or
distributor of any such report to any regulatory agency, as the case may be. Reports from CyDex
shall be delivered to the attention of Vice President of Development, Proteolix, with a copy to
Chief Scientific Officer, Proteolix, at the address set forth in Section 14.7 (Notices). The
parties shall mutually cooperate with regard to investigation of any such serious adverse event
which is believed to be directly associated with CAPTISOL, whether experienced by Proteolix, CyDex
or any other Affiliate, Sublicensee, co-marketer or distributor of CyDex or Proteolix. Such
written notification to Proteolix as well as assistance

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 17.

 

with any resulting investigation shall be provided in a manner such that no third party
confidential information is compromised in doing so by either Proteolix or CyDex.

     7.4 Product Recalls. If any CAPTISOL should be alleged or proven not to meet the
Specifications, Proteolix shall notify CyDex immediately, and both parties shall cooperate fully
regarding the investigation and disposition of any such matter. If Proteolix should deem it
appropriate to recall any Product and such recall is due to the failure of CAPTISOL to conform to
the relevant Specifications at the time of delivery by CyDex, then CyDex agrees, upon
substantiation thereof, to bear all reasonable direct costs associated with said recall, including
refund of the purchase price for such CAPTISOL and the actual cost of conducting the recall in
accordance with the recall guidelines of the applicable governmental authority. Proteolix shall in
all events be responsible for conducting any such recalls with respect to the Product and shall
maintain records of all sales of Product and customers sufficient to adequately administer any such
recall, for a period of [ ** ] years after expiration or termination of this Agreement.

8. Confidentiality.

     8.1 Definition. Proteolix and CyDex each recognizes that during the Term, it may be necessary
for a party (the “Disclosing Party”) to provide Confidential Information to the other party (the
“Receiving Party”) that is highly valuable, the disclosure of which would be highly prejudicial to
the Disclosing Party. The disclosure and use of Confidential Information will be governed by the
provisions of this Section 8. Neither Proteolix nor CyDex shall use the other’s Confidential
Information except as expressly permitted in this Agreement. For purposes of this Agreement,
“Confidential Information” means all information disclosed by the Disclosing Party to the Receiving
Party and designated in writing by the Disclosing Party as “Confidential” (or equivalent), and all
material disclosed orally which is declared to be confidential by the Disclosing Party at the time
of such disclosure and confirmed in a writing marked as “Confidential” (or equivalent) and
delivered to the Receiving Party within thirty (30) days after such disclosure, including but not
limited to product specifications, data, know-how, formulations, product concepts, sample
materials, business and technical information, financial data, batch records, trade secrets,
processes, techniques, algorithms, programs, designs, drawings, and any other information related
to a party’s present or future products, sales, suppliers, customers, employees, investors or
business. Without limiting the generality of the foregoing, CyDex’ Confidential Information
includes all materials provided as part of the CAPTISOL Data Package.

     8.2 Obligation. The Receiving Party agrees that it will disclose the Disclosing Party’s
Confidential Information to its own officers, employees, consultants and agents only if and to the
extent necessary to carry out its responsibilities under this Agreement or in accordance with the
exercise of its rights under this Agreement, and such disclosure shall be limited to the maximum
extent possible consistent with such responsibilities and rights. The Receiving Party shall not
disclose Confidential Information of the Disclosing Party to any third party without such
Disclosing Party’s prior written consent, and any such disclosure to a third party shall be
pursuant to the terms of a non-disclosure agreement no less restrictive than this Section 8. The
Receiving Party shall take such action to preserve the confidentiality of the Disclosing Party’s
Confidential Information as it would customarily take to preserve the confidentiality of its own

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 18.

 

Confidential Information (but in no event less than a reasonable standard of care). The
Receiving Party, upon the Disclosing Party’s request, will return all of the Disclosing Party’s
Confidential Information, including all copies and extracts of documents, within sixty (60) days of
the request, and in any event, promptly following the expiration or termination of this Agreement;
provided, however; that each party may retain one archival copy of such Confidential Information
solely to be able to monitor its obligations that survive under this Agreement.

     8.3 Exceptions. The use and non-disclosure obligations set forth in this Section 8 shall not
apply to any Confidential Information, or portion thereof, that the Receiving Party can
demonstrate:

               (i) at the time of disclosure is in the public domain;

               (ii) after disclosure, becomes part of the public domain, by publication or otherwise, through
no fault of the Receiving Party;

               (iii) is in the Receiving Party’s possession prior to receipt from the Disclosing Party as
long as obtained lawfully;

               (iv) is made available to the Receiving Party by an independent third party, provided,
however, that to the Receiving Party’s knowledge, such information was not obtained by said third
party, directly or indirectly, from the Disclosing Party hereunder; or

               (v) is developed by Receiving Party without use of, application of or access to the Disclosing
Party’s Confidential Information as evidenced by the Receiving Party’s records.

     In addition, the Receiving Party may disclose information that is required to be disclosed by
law, by a valid order of a court or by order or regulation of a governmental agency including but
not limited to, regulations of the United States Securities and Exchange Commission, or in the
course of litigation, provided that in all cases the Receiving Party shall give the other party
prompt notice of the pending disclosure and makes a reasonable effort to obtain, or to assist the
Disclosing Party in obtaining, a protective order preventing or limiting the disclosure and/or
requiring that the Confidential Information so disclosed be used only for the purposes for which
the law or regulation required, or for which the order was issued.

     8.4 Injunction. Each party agrees that should it breach or threaten to breach any provisions
of this Section 8, the Disclosing Party may suffer irreparable damages and its remedy at law may be
inadequate. Upon any breach or threatened breach by the Receiving Party of this Section 8, the
Disclosing Party shall be entitled to seek injunctive relief in addition to any other remedy which
it may have, without need to post any bond or security.

     8.5 Third Party Information. Proteolix acknowledges that CyDex’ Confidential Information
includes information developed by Pfizer, Inc. (“Pfizer”) that is confidential to both CyDex and
Pfizer. In so far as Confidential Information of Pfizer is disclosed, Pfizer is a third-

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 19.

 

party beneficiary of this Section 8 of this Agreement and may enforce it or seek remedies
pursuant to it in accordance with its terms.

9. Representations and Warranties.

     9.1 Mutual Representations and Warranties. Each party represents and warrants to the other
that:

          (a) it is a corporation duly organized and validly existing under the laws of the state or
country of its incorporation;

          (b) it has the complete and unrestricted power and right to enter into this Agreement and to
perform its obligations hereunder;

          (c) this Agreement has been duly authorized, executed and delivered by such party and
constitutes a legal, valid and binding obligation of such party enforceable against such party in
accordance with its terms except as enforceability may be limited by applicable bankruptcy,
insolvency, reorganization, receivership, moratorium, fraudulent transfer, or other similar laws
affecting the rights and remedies of creditors generally and by general principles of equity;

          (d) the execution, delivery and performance of this Agreement by such party do not conflict
with any agreement, instrument or understanding, oral or written, to which such party is a party or
by which such party may be bound, nor violate any law or regulation of any court, governmental body
or administrative or other agency having authority over such party;

          (e) all consents, approvals and authorizations from all governmental authorities or other
third parties required to be obtained by such party in connection with the execution and delivery
of this Agreement have been obtained;

          (f) no person or entity has or will have, as a result of the transactions contemplated by this
Agreement, any right, interest or valid claim against or upon such party for any commission, fee or
other compensation as a finder or broker because of any act by such party or its agents, or, with
respect to Proteolix, because of any act by its Affiliates or Sublicensees; and

          (g) it has not entered into any agreement with any third party that is in conflict with the
rights granted to the other party pursuant to this Agreement.

     9.2 CyDex Representations, Warranties and Covenants. CyDex represents and warrants to
Proteolix that:

          (a) CyDex owns all title in and to the CAPTISOL to be provided to Proteolix under the terms
and conditions of this Agreement, and has the right to sell CAPTISOL to Proteolix pursuant to the
terms and conditions of this Agreement;

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 20.

 

          (b) As of the Effective Date, there are no actions, suits, investigations, claims or
proceedings pending or threatened relating to the Licensed Patents, and that CyDex will notify
Proteolix in writing within [ ** ] days if any such actions, suits, investigations, claims or
proceedings are initiated that could have material negative impact on Proteolix’ development of the
Product;

          (c) All CAPTISOL supplied to Proteolix under the terms and conditions of this Agreement (as
applicable for Research Grade CAPTISOL, Clinical Grade CAPTISOL or Commercial Grade CAPTISOL, as
the case may be) shall be manufactured in accordance with all laws, rules and regulations relating
to such manufacture, current and future; and

          (d) CyDex [ ** ].

     9.3 Disclaimer. The warranties set forth in this Section 9 above are provided in lieu of,
and each party hereby disclaims, all other warranties, express and implied, relating to the subject
matter of this Agreement, CAPTISOL or the licensed patents, including but not limited to the
implied warranties of merchantability and fitness for a particular purpose, title and
non-infringement of third party rights. CyDex warranties under this Agreement are solely for the
benefit of Proteolix and may be asserted only by Proteolix and not by any affiliate, sublicensee or
any customer of Proteolix, its affiliates or sublicensees. Proteolix, its affiliates and
sublicensees shall be solely responsible for all representations and warranties that Proteolix, its
affiliates or sublicensees make to any customer of Proteolix, its affiliates or sublicensees.

10. Indemnification.

     10.1 By CyDex. CyDex shall defend, indemnify and hold Proteolix and its Affiliates
and Sublicensees, and each of their respective directors, officers and employees, harmless from and
against any and all losses, damages, liabilities, costs and expenses (including the reasonable
costs and expenses of attorneys and other professionals) (collectively “Losses”) incurred by
Proteolix as a result of any claim, demand, action or other proceeding (each, a “Claim”) by a third
party, to the extent such Losses arise out of: (a) any claim by such third party that the practice
of the compositions or methods claimed in the Licensed Patents or the sale of CAPTISOL as included
as an excipient within the Product infringe upon such third party’s patent rights; (b) injury or
other harm arising from the use of CAPTISOL alone, or (c) CyDex’ breach of any of its
representations, warranties and covenants set forth in Section 9 above; provided, however, that the
foregoing obligation to indemnify shall not apply to the extent that Proteolix is obligated under
Section 10.2 below to indemnify CyDex with respect to a Claim, and CyDex shall be relieved of its
obligations under clause (a) of this Section 10.1 for any infringement claim that arises out of:
(i) the unauthorized use of the Licensed Patents by Proteolix; or (ii) the manufacture, handling,
marketing, sale, distribution or use of Product by Proteolix. If an

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 21.

 

injunction is issued preventing the practice of the Licensed Patents, CyDex may, at its
option, terminate this Agreement immediately upon written notice to Proteolix; provided that such
termination shall have no effect on CyDex’ indemnification obligations pursuant to this Section
10.1 incurred prior to the effective date of such termination. This Section 10 states CyDex’
sole obligation and entire liability, and Proteolix’, its affiliates’ and sublicensees’ sole and
exclusive remedy, for any claim of infringement of intellectual property rights relayed to the
Licensed Patents or Product.

     10.2 By Proteolix. Proteolix shall defend, indemnify and hold CyDex and its Affiliates, and
each of their respective directors, officers and employees, harmless from and against any and all
Losses incurred by CyDex as a result of any Claim by a third party, to the extent such Losses arise
out of: (a) the use or sale of the Product by Proteolix, its Affiliates, Sublicensees,
distributors, agents, or other parties (except to the extent such Losses arise from the use of
CAPTISOL); (b) the manufacture, use, handling, promotion, marketing, distribution, sale or use of
Product (except to the extent such Losses arise from the use of CAPTISOL); (c) interactions and
communications with governmental authorities, physicians or other third parties; or (d) Proteolix’
breach of any of its representations and warranties set forth in Section 9.1; provided, however,
the foregoing obligation to indemnify shall not apply to the extent that CyDex is obligated under
Section 10.1 above to indemnify Proteolix with respect to a Claim.

     10.3 Procedure. The party intending to claim indemnification under this Section 10 (an
“Indemnitee”) shall promptly notify the other party (the “Indemnitor”) of any Claim in respect of
which the Indemnitee intends to claim such indemnification, and the Indemnitor shall assume the
defense thereof whether or not such Claim is rightfully brought; provided, however, that an
Indemnitee shall have the right to retain its own counsel, with the fees and expenses to be paid by
the Indemnitee, unless Indemnitor does not assume the defense, in which case the reasonable fees
and expenses of counsel retained by the Indemnitee shall be paid by the Indemnitor. The
Indemnitee, and its employees and agents, shall cooperate fully with the Indemnitor and its legal
representatives in the investigations of any Claim.

11. Limitation of Liability.

     Except for damages for which CyDex is responsible pursuant to its indemnification
obligations set forth in Section 10 above, CyDex specifically disclaims all liability for and shall
in no event be liable for any incidental, special, indirect or consequential damages, expenses,
lost profits, lost savings, interruptions of business or other damages of any kind or character
whatsoever arising out of or related to this Agreement or resulting from the manufacture, handling,
marketing, sale, distribution or use of the product or use of the licensed patents and CAPTISOL
data package, regardless of the form of action, whether in contract, tort, strict liability or
otherwise, even if CyDex was advised of the possibility of such damages. Proteolix shall have no
remedy, and CyDex shall have no liability, other than as expressly set forth in this Agreement.
Except with respect to the indemnification specifically provided in Section 10 above, in no event
shall CyDex’ s total aggregate liability for all claims arising out of this Agreement exceed [ ** ]
the amounts paid by 

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 22.

 

Proteolix to CyDex pursuant to Section 4 (Compensation) of this Agreement
during  the [ ** ] month period immediately preceding the event giving rise to liability. No
action, regardless of form, arising out of or relayed to this Agreement may be brought by [ ** ]
after such party has knowledge of the occurrence that gave rise to the cause of such action.

12. Management of Licensed Patents.

     12.1 Prosecution and Maintenance. CyDex shall maintain, at its sole cost and expense and
using reasonable discretion, the Licensed Patents set forth on Exhibit A. CyDex shall have the
right to control the prosecution and maintenance of patent applications and the selection of
countries where patent applications are filed related to the Licensed Patents.

     12.2 Infringement by Third Parties. If Proteolix becomes aware that a third party may be
infringing a Licensed Patent, it will promptly notify CyDex in writing, providing all information
available to Proteolix regarding the potential infringement. CyDex shall take whatever, if any,
action it deems appropriate, in its sole discretion, against the alleged infringer. If CyDex
elects to take action, Proteolix shall, at CyDex’ request and expense, cooperate and shall cause
its employees to cooperate with CyDex in taking any such action, including but not limited to,
cooperating with the prosecution of any infringement suit by CyDex.

13. Term and Termination.

     13.1 Term. The term of this Agreement (the “Term”) shall commence on the Effective Date and
shall continue in effect thereafter until the expiration of Proteolix’ obligation to pay royalties
under Section 4.1(c), unless terminated earlier as set forth herein.

     13.2 Termination for Cause. If either party should violate or fail to perform any material
term or material covenant of this Agreement, then the non-breaching party may give written notice
of such default to the breaching party. If the breaching party should fail to cure such default
within thirty (30) days after the date of such notice, the non-breaching party shall have the right
to terminate this Agreement by a second written notice (a “Notice of Termination”) to the breaching
party, such termination to be effective as of the date of such notice. Notwithstanding the above,
failure to pay milestones or royalties as described in Section 4 above will result in termination
of this Agreement immediately upon delivery of a Notice of Termination by CyDex to Proteolix. In
addition, either party may terminate this Agreement immediately upon written notice to the other
party in the event such other party makes an assignment for the benefit of creditors or has a
petition in bankruptcy filed for or against it that is [ ** ].

     13.3 Termination by Proteolix. Proteolix shall have the right at any time to terminate this
Agreement in whole by giving CyDex at least [ ** ] days prior written notice.

     13.4 Effect of Expiration or Termination. Following the expiration or termination of this
Agreement, except as otherwise provided in Section 4.1(c)(ii), all rights granted to Proteolix
herein shall immediately terminate and, in the event of termination of this Agreement by Proteolix
pursuant to Section 13.2, all rights granted to CyDex herein shall immediately

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 23.

 

terminate, and each
party shall promptly return all relevant records and materials in its possession or control containing the other party’s Confidential Information with respect to
which the former party does not retain rights hereunder; provided, however that each party may
retain one archival copy of such records and materials solely to be able to monitor its obligations
that survive under this Agreement.

     13.5 Survival. Notwithstanding any other provisions of this Agreement, any liability or
obligation of either party to the other for acts or omissions prior to the termination or
expiration of this Agreement shall survive the termination or expiration of this Agreement. Such
termination or expiration shall not relieve either party from obligations that are expressly
indicated to survive termination or expiration of this Agreement, nor shall any termination or
expiration of this Agreement relieve Proteolix of its obligation to pay CyDex (a) royalties for all
Product sold by Proteolix, its Affiliates or Sublicensees prior to the effective date of such
expiration or termination, or (b) sums due in respect of CAPTISOL shipped prior to termination or
expiration of this Agreement. Sections 1 (Definitions); 2.1 (License Grants from CyDex to
Proteolix); 2.2 (Grant of License from Proteolix to CyDex); 5 (Records; Reports; Audits); 7.4
(Product Recalls); 8 (Confidentiality); 9.4 (Disclaimer); 10 (Indemnification); 11 (Limitation of
Liability); 13.4 (Effect of Termination); 13.5 (Survival); and 14 (General Provisions) shall
survive termination or expiration of this Agreement; provided, however, that Section 2.2 (Grant of
License from Proteolix to CyDex) shall not survive termination of this Agreement by Proteolix
pursuant to Section 13.2 and Section 2.1 (License Grants from CyDex to Proteolix) shall not survive
termination of this Agreement by CyDex pursuant to Section 13.2 or by Proteolix pursuant to Section
13.3. Proteolix’s exercise of the license under Section 2.1 (if it survives termination) is
subject to compliance with Proteolix’s continued compliance with Section 4 (Compensation).

14. General Provisions.

     14.1 Non-Solicitation. During the Term and for a period of [ ** ] year thereafter, neither
party shall solicit, induce, encourage or attempt to induce or encourage any employee of the other
party to terminate his or her employment with such other party or to breach any other obligation to
such other party. This section is not meant to encompass general solicitations such as may be
found in newspaper advertisements and the like.

     14.2 Relationship of Parties. Each of the parties hereto is an independent contractor and
nothing in this Agreement is intended or shall be deemed to constitute a partnership, agency,
employer-employee or joint venture relationship between the parties. No party shall incur any
debts or make any commitments for the other.

     14.3 Compliance with Law.

          (a) Proteolix agrees that use of the Licensed Patents by Proteolix, its Affiliates and
Sublicensees, and the manufacture, handling, marketing, sale, distribution and use of Product will
comply with all applicable international, federal, state and local laws, rules and regulations,
including, but not limited to, import/export restrictions, laws, rules and regulations governing
use and patent, copyright and trade secret protection.

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 24.

 

          (b) CyDex agrees the manufacture and supply of CAPTISOL to Proteolix (as applicable for
Research Grade CAPTISOL, Clinical Grade CAPTISOL or Commercial Grade CAPTISOL, as the case may be)
will comply with all applicable international, federal, state and local laws, rules and
regulations, including, but not limited to, import/export restrictions, laws, rules and regulations
governing use and patent, copyright and trade secret protection.

     14.4 Arbitration.

          (a) Procedure. Except as otherwise expressly set forth in Section 14.4(b) below, any and all
disputes or controversies arising out of or relating to this Agreement shall be settled and decided
by binding arbitration. The arbitration shall be conducted in New York, New York by an arbitrator
reasonably knowledgeable about the pharmaceutical industry and acceptable to CyDex and Proteolix.
If CyDex and Proteolix cannot agree on a single arbitrator within ten (10) days after a demand for
arbitration has been made, CyDex shall appoint an arbitrator, Proteolix shall appoint an
arbitrator, the two (2) arbitrators shall appoint a third arbitrator, and the three (3) arbitrators
shall hear and decide the issue in controversy. If either party fails to appoint an arbitrator
within twenty (20) days after service of the demand for arbitration, then the arbitrator appointed
by the other party shall arbitrate any controversy in accordance with this Section 14.4(a). Except
as to the selection of arbitrators, the arbitration proceedings shall be conducted promptly and in
accordance with the rules of the American Arbitration Association then in effect. The expenses of
any arbitration, including the reasonable attorney fees of the prevailing party, shall be borne by
the party deemed to be at fault or on a pro-rata basis should the arbitration conclude in a finding
of mutual fault.

          (b) Short-Form Arbitration. Any dispute subject to short-form arbitration as provided in this
Agreement shall be finally settled by binding arbitration conducted, in accordance with the rules
of the American Arbitration Association then in effect, in New York, New York by a single
arbitrator reasonably knowledgeable about the pharmaceutical industry and appointed in accordance
with such rules. Such arbitrator shall make his or her determination on the basis of “baseball
arbitration” principles. The foregoing remedy shall be each party’s sole and exclusive remedy
with respect to any such dispute. The expenses of any arbitration, including the reasonable
attorney fees of the prevailing party, shall be borne by the party deemed to be at fault or on a
pro-rata basis should the arbitration conclude in a finding of mutual fault. In each case, the
parties and arbitrator shall use all diligent efforts to complete such arbitration within thirty
(30) days after appointment of the arbitrator.

          (c) Confidentiality of Proceedings. All arbitration proceedings hereunder shall be
confidential and the arbitrator(s) shall issue appropriate protective orders to safeguard each
party’s Confidential Information. Except as required by law, no party shall make (or instruct the
arbitrator(s) to make) any public announcement with respect to the proceedings or decision of the
arbitrator(s) without prior written consent of the other party.

          (d) Exceptions. Notwithstanding the foregoing, neither party shall be bound to follow the
dispute resolution process described in this Section with respect to any dispute: (i) that
primarily involves or relates to the scope or validity of the Licensed Patents; or (ii) for

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 25.

 

which interim equitable relief from a court is necessary to prevent serious and irreparable injury
to a party.

     14.5 Costs and Expenses. Except as otherwise expressly provided in this Agreement, each party
shall bear all costs and expenses associated with the performance of such party’s obligations under
this Agreement.

     14.6 Force Majeure. Neither party shall be liable for failure to perform, or delay in the
performance of, its obligations under this Agreement (other than payment obligations) when such
failure or delay is caused by an event of force majeure; provided, however, that the affected party
resumes performance hereunder as soon as reasonably possible following cessation of such force
majeure event; and provided further that no such delay or failure in performance shall continue for
more than three (3) months. For purposes of this Agreement, an event of force majeure means any
event or circumstance beyond the reasonable control of the affected party, including but not
limited to, war, insurrection, riot, fire, flood or other unusual weather condition, explosion, act
of God, peril of the sea, strike, lockout or other industrial disturbance, sabotage, accident,
embargo, injunction, act of governmental authority, compliance with governmental order on national
defense requirements, or inability to obtain fuel, power, raw materials, labor, transportation
facilities. If, due to any event of force majeure, either party shall be unable to fulfill its
obligations under this Agreement (other than payment obligations), the affected party shall
immediately notify the other party of such inability and of the period during which such inability
is expected to continue. In the event that a delay or failure in performance by a party under this
Section 14.6 continues longer than three (3) months, the other party may terminate this Agreement
in accordance with the terms and conditions of Section 13.2.

     14.7 Notices. Any notice, request, or communication under this Agreement shall be effective
only if it is in writing and personally delivered; sent by certified mail, postage pre-paid;
facsimile with receipt confirmed; or by nationally recognized overnight courier with signature
required, addressed to the parties at the addresses stated below or such other persons and/or
addresses as shall be furnished in writing by any party in accordance with this Section 14.7.
Unless otherwise provided, all notices shall be sent:

     If to CyDex, to:

CyDex, Inc.

10513 W. 84th Terrace

Lenexa, KS 66214

Attention: CEO

Fax: (913) 685-8856

     If to Proteolix, to:

Proteolix, Inc.

225 Gateway Boulevard

South San Francisco, CA 94080

Attention: VP, Development

(Fax) 650-866-6351

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 26.

 

If sent by facsimile transmission, the date of transmission shall be deemed to be the date on which
such notice, request or communication was given. If sent by overnight courier, the next business
day after the date of deposit with such courier shall be deemed to be the date on which such
notice, request or communication was given. If sent by certified mail, the third business day
after the date of mailing shall be deemed the date on which such notice, request or communication
was given.

     14.8 Use of Name. Neither party shall have any right, express or implied, to use in any
manner the name or other designation of the other party or any other trade name or trademark of the
other party for any purpose, except as may be required by applicable law or regulation.

     14.9 Public Announcements. Except for such disclosure as is deemed necessary, in the
reasonable judgment of a party, to comply with applicable laws or regulations, securities filings
or the rules of the NYSE or NASDAQ, no announcement, news release, public statement, publication,
or presentation relating to the existence of this Agreement, or the terms hereof, will be made
without the other party’s prior written approval, which approval shall not be unreasonably
withheld. Notwithstanding the above, once the content and timing of a public announcement of the
fact that the parties have entered into this Agreement has been agreed to between the parties and
such announcement has been made, each party shall be free to disclose to third parties the fact
that it has entered into the Agreement (including a description of the Field), but without
disclosing the economic terms hereof, as well as any other information contained in said public
announcement. In the event of a required public announcement, the party making such announcement
shall provide the other party with a copy of the proposed text prior to such announcement
sufficiently in advance of the scheduled release of such announcement to afford such other party a
reasonable opportunity to review and comment upon the proposed text and the timing of such
disclosure.

     14.10 Governing Law. This Agreement shall be governed by and construed in accordance with the
laws of the State of New York (without giving effect to any conflicts of law principles that
require the application of the law of a different state).

     14.11 Entire Agreement; Amendment. This Agreement and all Exhibits attached hereto or thereto
contain the entire agreement of the parties relating to the subject matter hereof and supersede any
and all prior and contemporaneous agreements, written or oral, between CyDex and Proteolix relating
to the subject matter of this Agreement. This Agreement may not be amended unless agreed to in
writing by both parties.

     14.12 Binding Effect. This Agreement shall be binding upon, and the rights and obligations
hereof shall apply to the CyDex and the Proteolix and any successor(s) and permitted assigns. The
name of a party appearing herein shall be deemed to include the names of such party’s successors
and permitted assigns to the extent necessary to carry out the intent of this Agreement.

     14.13 Waiver. The rights of either party under this Agreement may be exercised from time to
time, singularly or in combination, and the exercise of one or more such rights shall not

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 27.

 

be deemed to be in waiver of any one or more of the other. No waiver of any breach of a term,
provision or condition of this Agreement shall be deemed to have been made by either party unless
such waiver is addressed in writing and signed by an authorized representative of that party. The
failure of either party to insist upon the strict performance of any of the terms, provisions or
conditions of this Agreement, or to exercise any option contained in this Agreement, shall not be
construed as a waiver or relinquishment for the future of any such term, provision, condition or
option or the waiver or relinquishment of any other term, provision, condition or option.

     14.14 Severability. If a final judicial determination is made that any provision of this
Agreement is unenforceable, this Agreement shall be rendered void only to the extent that such
judicial determination finds such provisions unenforceable, and such unenforceable provisions shall
be automatically reconstituted and become a part of this Agreement, effective as of the date first
written above, to the maximum extent they are lawfully enforceable.

     14.15 Assignment. Neither party may assign its rights or delegate its obligations under this
Agreement, in whole or in part, by operation of law or otherwise, to any third party without the
prior written consent of the other party, which consent shall not be unreasonably withheld.
Notwithstanding the foregoing, either party may assign its rights and delegate its obligations
under this Agreement to an Affiliate or to a third party successor, whether by way of merger, sale
of all or substantially all of its assets, sale of stock or otherwise, without the other party’s
prior written consent. As a condition to any permitted assignment hereunder, the assignor must
guarantee the performance of any assignee to the terms and obligations of this Agreement. Any
assignment not in accordance with this Section 14.15 shall be void.

     14.16 Headings. The descriptive headings of this Agreement are for convenience only, and
shall be of no force or effect in construing or interpreting any of the provisions of this
Agreement.

     14.17 Counterparts. This Agreement may be executed in two counterparts, each of which shall
constitute an original document, but both of which shall constitute one and the same instrument.

* * *

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 28.

 

     IN WITNESS WHEREOF, the parties have executed this Agreement as of the date first written
above.

CYDEX, INC.

	 	 	 	 	 
	By:

	 	/s/ John M. Siebert
 

	 	 
	Name:

	 	John M. Siebert	 	 
	Title:

	 	Chairman & CEO	 	 
	 
	 	 	 	 
	PROTEOLIX, INC.	 	 
	 
	 	 	 	 
	By: 

Name:

	 	/s/ Susan M. Molineaux
 

Susan M. Molineaux
	 	 
	Title:

	 	CSO	 	 

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 29.

 

EXHIBIT A

LICENSED PATENTS

			
	PATENT 1:	 	“Derivatives of Cyclodextrins Exhibiting Enhanced Aqueous Solubility and the Use Thereof’

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	Expiration
	Country	 	Filing Date	 	Serial No.	 	Patent No.	 	Date
	United States
	 	 	01/23/90	 	 	 	07/469087	 	 	 	5,134,127	 	 	 	01/23/10	 
	PCT

(U.S. 5,134,127)
	 	 	01/22/91	 	 	PCT/US91/00326	 	 	W091/11172	 	 	 	 	 
	Australia
	 	 	01/22/91	 	 	 	72364/91	 	 	 	646020	 	 	 	01/22/07	 
	EPO
	 	 	01/22/91	 	 	 	91903891.9	 	 	 	0512050	 	 	 	01/22/11	 
	Austria
	 	 	01/22/91	 	 	 	91903891.9	 	 	 	E-170742	 	 	 	01/22/11	 
	Belgium
	 	 	01/22/91	 	 	 	91903891.9	 	 	 	0512050	 	 	 	01/22/11	 
	France
	 	 	9/11/98	 	 	 	91903891.9	 	 	 	0512050	 	 	 	01/22/11	 
	Germany
	 	 	01/22/91	 	 	 	69130165.4	 	 	 	69130165	 	 	 	01/22/11	 
	Great Britain (UK)
	 	 	01/22/91	 	 	 	91903891.9	 	 	 	0512050	 	 	 	01/22/11	 
	Greece
	 	 	11/30/98	 	 	 	980402865	 	 	 	3028691	 	 	 	01/23/11	 
	Italy
	 	 	12/01/98	 	 	70988BE/98  	 	 	0512050	 	 	 	01/22/11	 
	Luxembourg
	 	 	01/22/91	 	 	 	91903891.9	 	 	 	0512050	 	 	 	01/22/11	 
	Netherlands
	 	 	12/03/98	 	 	 	91903891.9	 	 	 	0512050	 	 	 	01/22/11	 
	Sweden
	 	 	01/22/91	 	 	 	91903891.9	 	 	 	0512050	 	 	 	01/22/11	 
	Switzerland
	 	 	11/10/98	 	 	 	91903891.9	 	 	 	0512050	 	 	 	01/22/11	 
	Korea
	 	 	07/22/92	 	 	 	92-701734	 	 	 	166088	 	 	 	01/22/11	 
	Canada
	 	 	01/22/91	 	 	 	2,074,186	 	 	 	2,074,186	 	 	 	01/22/11	 
	Russia
	 	 	07/22/92	 	 	 	5052811.04	 	 	 	2099354	 	 	 	01/22/11	 
	Japan
	 	 	01/22/91	 	 	 	3-504051	 	 	 	2722277	 	 	 	1/22/11	 

 

			
	*	 	Awaiting confirmation documents
	 
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 1.

 

			
	PATENT 2:	 	CIP of 5,134,127 — “Derivatives of Cyclodextrins Exhibiting Enhanced Aqueous
Solubility and the Use Thereof”

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	Expiration
	Country	 	Filing Date	 	Serial No.	 	Patent No.	 	Date
	United States
	 	 	07/27/92	 	 	 	07/918,702	 	 	 	5,376,645	 	 	 	01/23/10	 
	PCT

(U.S. 5,376,645)
	 	 	07/26/93	 	 	PCT/US93/06880	 	 	W094/02518	 	 	 	 	 
	Australia
	 	 	07/26/93	 	 	 	47799/93	 	 	 	672814	 	 	 	07/26/13	 
	EPO
	 	 	07/26/93	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Austria
	 	 	07/26/93	 	 	 	93918302.6	 	 	 	E 217325	 	 	 	07/26/13	 
	Belgium
	 	 	07/26/93	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Denmark
	 	 	07/26/03	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/31/13	 
	Djibouti
	 	 	05/08/02	 	 	 	93918302.6	 	 	 	620828	 	 	 	05/08/22	 
	France
	 	 	07/26/93	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/31/13	 
	Germany
	 	 	07/26/93	 	 	 	69331900	 	 	 	69331900	 	 	 	07/31/13	 
	Great Britain (UK)
	 	 	05/17/02	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Greece
	 	 	07/26/93	 	 	 	93918302.6	 	 	 	3040489	 	 	 	07/26/13	 
	Ireland
	 	 	07/26/03	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/31/13	 
	Italy
	 	 	07/26/03	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Luxembourg
	 	 	07/26/03	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Monaco
	 	 	07/26/03	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Netherlands
	 	 	07/26/03	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Portugal
	 	 	07/26/93	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Spain
	 	 	07/26/93	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Sweden
	 	 	07/26/93	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Switzerland/Liechtenstein
	 	 	07/26/93	 	 	 	93918302.6	 	 	 	620828	 	 	 	07/26/13	 
	Korea
	 	 	03/23/94	 	 	 	94-700951	 	 	 	279111	 	 	 	07/26/13	 
	Canada
	 	 	07/26/93	 	 	 	2,119,154	 	 	 	2,119,154	 	 	 	07/26/13	 
	Japan
	 	 	07/26/93	 	 	 	6-504678	 	 	 	3393253	 	 	 	07/26/13	 
	Russia
	 	 	07/26/93	 	 	 	94028890/04	 	 	 	2113442	 	 	 	07/26/13	 
	Georgia
	 	 	03/17/95	 	 	 	691/01-95	 	 	 	1649	 	 	 	07/26/13	 

 

			
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 2.

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	Expiration
	Country	 	Filing Date	 	Serial No.	 	Patent No.	 	Date
	Armenia
	 	 	07/26/93	 	 	 	96237	 	 	 	822	 	 	 	07/22/13	 
	Kyrgyzstan
	 	 	08/09/96	 	 	 	960481.1	 	 	 	333	 	 	 	05/10/16	 
	Moldova
	 	 	08/08/96	 	 	960306/PCT	 	 	1813	 	 	 	07/26/13	 
	Tajikistan
	 	 	07/26/93	 	 	 	96000377	 	 	 	275	 	 	 	07/26/13	 
	Turkmenistan
	 	 	08/08/96	 	 	 	393	 	 	 	430	 	 	 	07/26/13	 
	Uzbeckistan
	 	 	09/15/94	 	 	IHAP9400808.2	 	 	5799	 	 	 	04/28/19	 

 

			
	*	 	Awaiting confirmation documents
	 
	[ ** ] =	 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

 3.

 

EXHIBIT B

SPECIFICATIONS — Commercial Grade and Clinical Grade CAPTISOL

	 	 	 	 	 
	Test	 	Specification	 	Test Method
	Appearance

	 	White to off-white solid essentially free from foreign matter
	 	CY-VI-005
	 
	 	 	 	 
	Identification (IR)

	 	Spectrum is consistent with the SBECD standard
	 	CY-IR-100
	 
	 	 	 	 
	Sodium Identity

	 	Sodium identity tests are positive
	 	CY-PR-200
	 
	 	 	 	 
	Solution Clarity

	 	A 30% w/v solution in water is clear, colorless and essentially free from particles of foreign matter
	 	CY-VI-002
	 
	 	 	 	 
	Average Degree of Substitution (CE)

	 	6.0-7.1
	 	CY-CE-603
	 
	 	 	 	 
	Solution pH

	 	The pH of a 30% w/v solution in water is within the range of 5.4 — 6.8
	 	CY-PH-100
	 
	 	 	 	 
	b-cyclodextrin Content

	 	Maximum 0.2%
	 	CY-IC-203
	 
	 	 	 	 
	Sodium Chloride

	 	Maximum 0.2%
	 	CY-IC-303
	 
	 	 	 	 
	1,4-Butane Sultone

	 	Maximum 1 ppm
	 	CY-GC-104
	 
	 	 	 	 
	Water (by KF)

	 	Maximum 10.0%
	 	CY-KF-100
	 
	 	 	 	 
	Heavy Metals

	 	Maximum 10 ppm
	 	CY-HM-222
	 
	 	 	 	 
	Specific Rotation

(anhydrous basis)

	 	For information only
	 	CY-SR-163
	 
	 	 	 	 
	Assay (anhydrous basis)

	 	Minimum 95%
	 	CY-LC-903
	 
	 	 	 	 
	Bacterial Endotoxins

	 	Not more than 50 EU/g
	 	CY-LAL-002
	 
	 	 	 	 
	Microbiology
	 	 	 	 
	 
	 	 	 	 
	     Aerobic microorganisms

	 	1000 CFU/g Maximum
	 	CY-MB-105
	     Escherichia coli

	 	Meets test requirements for absence	 	 
	     Salmonella species

	 	Meets test requirements for absence	 	 
	     Molds & Yeasts

	 	For Information Only	 	 

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been
omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of
the Securities Exchange Act of 1934, as amended.

 

 

EXHIBIT C

PURCHASE PRICE FOR CAPTISOL

1. Clinical Grade CAPTISOL: US$[ ** ] per kg, until such time as Proteolix orders more than [ ** ]
of Clinical Grade CAPTISOL, at which time the price of Clinical Grade CAPTISOL will [ ** ] US$[ **
] per kg.

2. Commercial Grade CAPTISOL: The price of Commercial Grade CAPTISOL shall be determined pursuant
to the following table, but subject to adjustment pursuant to Section 4.2(a) of the Agreement.

	 	 	 
	Supplied CAPTISOL	 	Cost
	(Metric Tons Per Year)	 	(US$ per kg)
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]

3. Research Grade CAPTISOL:

	 	 	 	 	 
	Catalog No.	 	Package Size	 	Price (USD)
	NC-CAP-103
	 	100 grams
	 	[ ** ]
	NC-CAP-105
	 	500 grams
	 	[ ** ]
	NC-CAP-106
	 	1 kilogram
	 	[ ** ]
	NC-CAP-107
	 	5 kilograms
	 	[ ** ]
	 
	 	> 5 kilograms
	 	[ ** ]

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been
omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of
the Securities Exchange Act of 1934, as amended.

 

 

EXHIBIT D

DOSING MATRIX FOR IN-VIVO PRE-CLINICAL STUDIES

The following eight tables specify the maximum allowable CAPTISOL doses for intravenous,
intramuscular, intraperitoneal, subcutaneous and oral routes of administration. These doses do not
necessarily represent the highest safe dosing conditions but represent the current knowledge base.
For many of these routes, available data is limited to only a few studies and species. Therefore,
some doses have been based on assumptions and extrapolation from those studies and species.
Adaptive responses may still be present at some of the doses identified in these tables; however,
toxic responses affecting organ function should not be elicited at these doses. As additional data
becomes available, these tables may be revised.

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been
omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of
the Securities Exchange Act of 1934, as amended.

 

 

			
	
	 	Version 1, Page 4

07/17/00

CONTRACTUAL PROVISIONS ATTACHMENT

These pages contain mandatory contractual provisions and must be attached to or incorporated in all copies of the foregoing
Agreement.

Captisol® Dosing Matrix

In-Vivo Preclinical Studies

	 	 	 	 	 
	BACKGROUND INFORMATION FOR USING THE CAPTISOL® DOSING MATRIX
	 	 	5	 
	Table 1: Allowable IV Bolus Captisol® Doses by Duration of Study
	 	 	6	 
	Table 2: Allowable IV Infusion Captisol® Doses by Duration of Study
	 	 	7	 
	Table 3: Allowable IM Captisol® Doses by Duration of Study
	 	 	8	 
	Table 4: Allowable IP Captisol® Doses by Duration of Study
	 	 	9	 
	Table 5: Allowable SC Injection Captisol® Doses by Duration of Study
	 	 	10	 
	Table 6: Allowable SC Implantable Device Captisol® Doses by Duration of Study
	 	 	11	 
	Table 7: Allowable Oral Solution Captisol® Doses by Duration of Study
	 	 	12	 
	Table 8: Allowable Oral Solid Captisol® Doses by Duration of Study
	 	 	13	 
	Appendix A
	 	 	14	 
	Parenteral Formulation Protocol
	 	 	16	 
	Oral Solution Formulation Protocol
	 	 	15	 
	Oral Solid Formulation Protocol
	 	 	17	 
	Appendix B
	 	 	18	 
	Results Summary
	 	 	1	 

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been
omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of
the Securities Exchange Act of 1934, as amended.
	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913)
685-8856 • E-mail: CDInfo@cydexinc,com

 

 

Version
1, Page 5

07/17/00

BACKGROUND INFORMATION FOR USING THE CAPTISOL® DOSING MATRIX

The enclosed tables contain summary dosing information for Captisol® by different routes
for various species. There is one summary page for each route, which contains information for mice,
rats, rabbits, dogs, and non-human primates. Routes of administration discussed include
intravenous, subcutaneous, intramuscular, intraperitoneal and oral. For intravenous studies, an
extensive database is available for the rat and dog, with less information being available for the
mouse, rabbit and monkey. For other routes of administration data are limited to rats, rabbits and
monkeys for subcutaneous administration, rats for intramuscular administration, and rats and dogs
for oral administration. Because data is limited for some routes and species, extrapolations were
sometimes used in determining the allowable dose. In other instances where data is limited, CyDex
requires consultation prior to dosing.

In each case the allowable dose is the Captisol® dose that can be administered without prior
consultation and/or specific approval of CyDex. The doses listed are based on data from studies
conducted with Captisol® or are an extrapolation from those studies. At the doses listed in the
matrix adaptive responses may be present, but toxic effects would not be anticipated. In addition
to considering the allowable Captisol® dose, one must be cognizant of the two variables
(concentration and dose volume) determining the dose. In using the matrix table, these two
variables may be adjusted to best fit the needs of the client. However, the allowable Captisol®
dose and allowable Captisol® concentration may not be exceed without prior approval from
CyDex. The concentration listed on the matrix is based on the concentration used in the majority of
the toxicity studies conducted with Captisol®. As implied above, lesser concentrations
may be administered as long as the total dose does not exceed the approved limit set forth in the
Dosing Matrix.

With respect to dose volumes, those listed in the Captisol® dosing matrix represent
volumes that are recognized as appropriate for the species and route (based on published
literature). CyDex recognizes that individual laboratories may have established different dosing
volumes for use in a particular species for a given route. In those instances, CyDex does not wish
to restrict the laboratory to the volumes listed in the matrix table. However without prior
consultation and permission of CyDex, the total Captisol® dose administered must remain
at or below the dose listed in the dosing matrix for the route and species. For example, in the rat
a single intravenous bolus dose of 4000 mg/kg can be administered using a dosing volume of 13.3
mL/kg with a Captisol® concentration of 300 mg/mL (30% w/v). If your laboratory
routinely uses a higher dose volume, say 15 ml/kg for a single intravenous bolus dose in rats, then
the concentration would need to be adjusted to 267 mg/mL (26.7% w/v) for a 4000 mg/kg dose.

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been
omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of
the Securities Exchange Act of 1934, as amended.
	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913)
685-8856 • E-mail: CDInfo@cydexinc,com

 

 

			
	
	 	a                                                                      
     Table 1

Captisol®: Allowable Dosing Matrix – Intravenous (IV) Bolus Summary

	NOTES:	1) 	 	The allowable dose may not be exceeded without CyDex approval. These doses and the 30%
w/v concentration do not necessarily represent the highest safe dosing conditions. However,
they are the highest values to which CyDex has given limited approval for use.
	 
	 	2)	 	If Captisol concentration used is < 30% w/v, then the volume administered
may be increased accordingly, but the dose delivered may not exceed that granted under
this limited approval.

Table 1: Allowable IV Bolus Captisol® Doses by Duration of Study

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	Example Volume2	 	 	 	 	 	 	 	 	 	Daily Allowable
	IV Bolus	 	 	(based on use of 30% w/v Captisol delivering indicated dose)	 	Example Concentration	 	 	Captisol® Dose1
	Species	 	Duration	 	 	(mL/dose)	 	(mL/kg)2	 	(% w/v)	 	 	(mg/mL)	 	 	(mg/kg)
	mouse
	 	single dose	 	 	0.27	 	 	 	13.33	 	 	 	 	 	 	 	 	 	 	 	4000	 
	 
	 	14 days	 	 	0.20	 	 	 	10.00	 	 	 	 	 	 	 	 	 	 	 	3000	 
	 
	 	1 month	 	 	0.07	 	 	 	3.33	 	 	 	 	 	 	 	 	 	 	 	1000	 
	rat
	 	single dose	 	 	3.33	 	 	 	13.33	 	 	 	 	 	 	 	 	 	 	 	4000	 
	 
	 	14 days	 	 	2.50	 	 	 	10.00	 	 	 	 	 	 	 	 	 	 	 	3000	 
	 
	 	1 month	 	 	0.83	 	 	 	3.33	 	 	 	 	 	 	 	 	 	 	 	1000	 
	rabbit
	 	single dose	 	 	25.00	 	 	 	10.00	 	 	The highest concentration granted under this limited approval is 30% w/v (300 mg/mL).1	 	 	3000	 
	 
	 	14 days	 	 	16.67	 	 	 	6.67	 	 	 	 	2000	 
	 
	 	1 month	 	 	8.33	 	 	 	3.33	 	 	 	 	1000	 
	dog
	 	single dose	 	 	100.00	 	 	 	10.00	 	 	 	 	 	 	 	 	 	 	 	3000	 
	 
	 	14 days	 	 	66.67	 	 	 	6.67	 	 	 	 	 	 	 	 	 	 	 	2000	 
	 
	 	1 month	 	 	50.00	 	 	 	5.00	 	 	 	 	 	 	 	 	 	 	 	1500	 
	non-human primate
	 	single dose	 	 	50.00	 	 	 	10.00	 	 	 	 	 	 	 	 	 	 	 	3000	 
	 
	 	14 days	 	 	33.33	 	 	 	6.67	 	 	 	 	 	 	 	 	 	 	 	2000	 
	 
	 	1 month	 	 	25.00	 	 	 	5.00	 	 	 	 	 	 	 	 	 	 	 	1500	 

 

			
	FOOTNOTES:

	 	 	 
	a — conversions between mL/dose and mL/kg assumes mouse weight of 0.02 kg

	 	
	 
	 	 
	a — conversions between mL/dose and mL/kg assumes rat weight of 0.25 kg

	 	
	 
	 	 
	a — conversions between mL/dose and mL/kg assumes rabbit weight of 2.5 kg
	 	 
	 
	a — conversions between mL/dose and mL/kg assumes dog weight of 10 kg
	 	 
	 
	a — conversions between mL/dose and mL/kg assumes monkey weight of 5 kg
	 	 

 
 

	 	 	 
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been
omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of
the Securities Exchange Act of 1934, as amended.

	 	 	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913)
685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,
	 	

	 	 	 
	 
	 	Page 6

07/17/00

 

 

	 	 	 
	

	 	Table 2

Captisol®: Allowble Dosing Matrix – Intravenous (IV) Infusion Summary

	 	 	 	 	 	 	 
	NOTES:

	 	 	1	)	 	The allowable dose may not be exceeded without CyDex approval. These doses and the 30%
w/v concentration do not necessarily represent the highest safe dosing conditions. However,
they are the highest values to which CyDex has given limited approval for use.
	 
	 	 	 	 	 	 
	 

	 	 	2	)	 	If Captisol concentration used is < 30% w/v, then the volume administered
may be increased accordingly, but the dose delivered may not exceed that granted under
this limited approval.

The current continuous intravenous infusion dosing matrix only provides information for 24-hour continuous infusion with the Captisol concentration limited to 30% (300 mg/mL) and the maximum dose limited to that listed in the dosing matrix.

Table 2: Allowable IV Infusion Captisol® Doses by Duration of Study

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	Example Volume2	 	Example	 	Daily Allowable
	IV Continuous Infusion	 	(based on use 0130% w/v Captisol delivering indicated dose)	 	Concentration	 	Captisol®Dose
	Species	 	Duration	 	mL/dose/HR)	 	(mL/dose/DAY)	 	(mL/kg/HR)a	 	(roL/kg/DAY)a	 	(% w/v)	 	(mg/mL)	 	(mg/kg/HR)b	 	(mg/kg/DAY)b
	mouse	 	14 days	 	 	0.01	 	 	 	0.20	 	 	 	0.42	 	 	 	10.00	 	 	The highest	 	 	125	 	 	 	3000	 
	rat
	 	14 days	 	 	0.10	 	 	 	2.50	 	 	 	0.42	 	 	 	10.00	 	 	concentration	 	 	125	 	 	 	3000	 
	rabbit
	 	14 days	 	 	1.04	 	 	 	25.00	 	 	 	0.42	 	 	 	10.00	 	 	granted under this	 	 	125	 	 	 	3000	 
	dog
	 	14 days	 	 	4.20	 	 	 	100.00	 	 	 	0.42	 	 	 	10.00	 	 	limited approval is	 	 	125	 	 	 	3000	 
	non-human primate
	 	14 days	 	 	2.08	 	 	 	50.00	 	 	 	0.42	 	 	 	10.00	 	 	30% w/v (300 mg/mL).1	 	 	125	 	 	 	3000	 

 

FOOTNOTES:

			
	 
	a	 	— conversions between mi./dose and mL/kg assumes mouse weight of 0,02 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes rabbit weight of 2,5 kg
	 
	a	 	— conversions between mi./dose and mL/kg assumes monkey weight of 5 kg
	 
	a	 	— conversions between triL/dose and mL/kg assumes rat weight of 0.25 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes dog weight of 10 kg
	 
	b	 	— doses are mg/kg/day except for continuous infusion which is reported as both mg/kg/hour and
mg/kg/day

CyDex recognizes that continuous IV infusion protocols vary greatly from study to study and that when designing

continuous IV infusion protocols several variables must be considered, such as infusion rate, infusion duration,

use of a bolus plus infusion, etc. The doses permitted under this limited agreement are based upon a protocol

that requires 24-hour continuous IV infusion per the dosing matrix.

For all other intravenous infusion study designs we require that CyDex be consulted for approval prior to initiation of the study.

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with
the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: 

CDInfo@cydexinc,comVersion 1,

	 	 	 
	

	 	Page 7
	 

	 	07/17/00

 

 

	 	 	 
	

	 	Table 3

Captisol®: Allowble Dosing Matrix — Intramuscular (IM) Summary

	 	 	 	 	 	 	 
	NOTES:

	 	 	1	)	 	The allowable dose may not be exceeded without CyDex approval. These
doses and the 30% w/v concentration do not necessarily represent the highest safe dosing
conditions. However, they are the highest values to which CyDex has given limited
approval for use.
	 
	 	 	 	 	 	 
	 

	 	 	2	)	 	If Captisol concentration used is < 30% w/v, then the volume administered
may be increased accordingly, but the dose delivered may not exceed that granted under
this limited approval.

Table 3: Allowable IM Captisol® Doses by Duration of Study

	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	Example Volume2	 	 	 	 	 	Daily Allowable
	Intramuscular	 	(based on use of 30% w/v Captisol delivering indicated dose)	 	Example Concentration	 	Captisol® Dose1
	Species	 	Duration	 	(mL/dose)	 	(mL/kg)	 	(% w/v)	 	(mg/mL)	 	(mg/kg)
	mouse
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	rat
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	rabbit
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	dog
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	non-human primate
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*

*Limited to no data exists for these species. Contact CyDex for approval of dosing conditions.

 

FOOTNOTES:

	 		
	a	 	— conversions between mL/dose and mL/kg assumes mouse weight of 0.02 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes rat weight of 0.25 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes rabbit weight of 2.5 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes dog weight of 10 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes monkey weight of 5 kg
	 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with
the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

	 	 	 
	

	 	Page 8
	 

	 	07/17/00

 

 

	 	 	 
	

	 	Table 4

Captisol®: Allowble Dosing Matrix — Intraperitoneal (IP) Summary

	 	 	 	 	 	 	 
	NOTES:

	 	 	1	)	 	The allowable dose may not be exceeded without CyDex approval. These
doses and the 30% w/v concentration do not necessarily represent the highest safe dosing
conditions. However, they are the highest values to which CyDex has given limited
approval for use.
	 
	 	 	 	 	 	 
	 

	 	 	2	)	 	If Captisol concentration used is < 30% w/v, then the volume administered
may be increased accordingly, but the dose delivered may not exceed that granted under
this limited approval.

Table 4: Allowable IP Captisol® Doses by Duration of Study

	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	Example Volume2	 	 	 	 	 	Daily Allowable
	Intraperitoneal	 	(based on use of 30% w/v Captisol delivering indicated dose)	 	Example Concentration	 	Captisol®
Dose1
	Species	 	Duration	 	(mL/dose)	 	(mL/kg)	 	(% w/v)	 	(mg/mL)	 	(mg/kg)
	mouse
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	rat
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	rabbit
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	dog
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	non-human primate
	 	single dose

14 days

1 month
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*
	 	*

*

*

*Limited to no data exists for these species. Contact CyDex for approval of dosing conditions.

 

FOOTNOTES:

	 		
	a	 	—  conversions between mL/dose and mL/kg assumes mouse weight of 0.02 kg
	 
	a	 	—  conversions between mL/dose and mL/kg assumes rat weight of 0.25 kg
	 
	a	 	—  conversions between mL/dose and mL/kg assumes rabbit weight of 2.5 kg
	 
	a	 	—  conversions between mL/dose and mL/kg assumes dog weight of 10 kg
	 
	a	 	—  conversions between mL/dose and mL/kg assumes monkey weight of 5 kg

 	 		
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with
the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

	 	 	 
	

	 	Page 9
	 

	 	07/17/00

 

 

			
	
	 	Table 5

Captisol®: Allowble Dosing Matrix — Subcutaneous (SC) Injection Summary

	 	 	 
	NOTES: 1)

	 	The allowable dose may not be exceeded without CyDex approval. These doses and the 30%
w/v concentration do not necessarily represent the highest safe dosing conditions. However,
they are the highest values to which CyDex has given limited approval for use.
	 
	 	 
	2)

	 	If Captisol concentration used is < 30% w/v, then the volume administered
may be increased accordingly, but the dose delivered may not exceed that granted under
this limited approval.

Table 5: Allowable SC Injection Captisol®Doses by Duration of Study

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	Example Volume2	 	 	 	 	 	
	 	 	 	 	 	 	(based on use of 30% w/v Captisol delivering	 	Example	 	Daily Allowable
	Subcutaneous Injection	 	indicated dose)	 	Concentration	 	Captisol® Dose1
	Species	 	 	 	Duration	 	(mL/dose)	 	(mL/kg)	 	(% w/v)	 	(mg/mL)	 	(mg/kg)
	 
	mouse
	 	1 site possible	 	single dose	 	0.27	 	13.33	 	 	 	 	 	4000
	 
	 	 	 	14 days	 	0.20	 	10.00	 	 	 	 	 	3000
	 
	 	 	 	1 month	 	0.07	 	3.33	 	 	 	 	 	1000
	rat
	 	1 site possible	 	single dose	 	3.33	 	13.33	 	 	 	 	 	4000
	 
	 	 	 	14 days	 	2.50	 	10.00	 	 	 	 	 	3000
	 
	 	 	 	1 month	 	0.83	 	3.33	 	 	 	 	 	1000
	rabbit
	 	1 site possible	 	single dose
14 days
1 month	 	25.00

16.67

8.33	 	10.00

6.67

3.33	 	The highest 

concentration

granted under 

this limited 

approval is 30%

w/v (300 

mg/mL).1
	 	3000

2000

1000
	dog
	 	3 sites of 2 ml/kg each	 	single dose	 	20.00	 	6.00	 	 	 	 	 	1800
	 
	 	3 sites of 2 ml/kg each	 	14 days	 	20.00	 	6.00	 	 	 	 	 	1800
	 
	 	3 sites of 1.67 ml/kg each 	 	1 month	 	16.67	 	5.00	 	 	 	 	 	1500
	 
	 		 	 	 	 	 	 	 	 	 	 	 	 
	non-human primate
	 	2 sites of 5 ml/kg each	 	single dose	 	25.00	 	10.00	 	 	 	 	 	3000
	 
	 	2 sites of 3.33 ml/kg each	 	14 days	 	16.67	 	6.66	 	 	 	 	 	2000
	 
	 	2 site of 2.5 ml/kg	 	1 month	 	12.50	 	5.00	 	 	 	 	 	1500
	 
	 	each	 	 	 	 	 	 	 	 	 	 	 	 

 

			
	FOOTNOTES:
	 
	a	 	— conversions between mL/dose and mL/kg assumes mouse weight of 0.02 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes rat weight of 0.25 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes rabbit weight of 2.5 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes dog weight of 10 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes monkey weight of 5 kg

 

			
	 
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

Page 10

07/17/00

 

 

			
	
	 	Table 6
Captisol®: Allowble Dosing Matrix — Subcutaneous (SC) Implantable Device Summary

	 	 	 
	NOTES: 1)

	 	The allowable dose may not be exceeded without CyDex approval. These doses and the 30%
wlv concentration do not necessarily represent the highest safe dosing conditions. However,
they are the highest values to which CyDex has given limited approval for use.
	 
	 	 
	2)

	 	If Captisol concentration used is < 30% w/v, then the volume administered
may be increased accordingly, but the dose delivered may not exceed that granted under
this limited approval.

Table 6: Allowable SC Implantable Device Captisol® Doses by Duration of Study

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	Example Volume2	 	 	 	 	 	
	 	 	 	 	 	 	(based on use of 30% w/v Captisol	 	Example	 	Daily Allowable
	Subcutaneous Implantable Device	 	delivering indicated dose)	 	Concentration	 	Captisol®Dose1
	Species	 	MiniPumps	 	Duration	 	(mL/dose)	 	(mL/kg)	 	(% w/v)	 	(mg/mL)	 	(mg/kg)
	 
	mouse	 	1 pump @ 1 uL/hr = 0.024 mL/day

1 pump @ 0.5 uL/hr = 0.012 mL/day each

1 pump @ 0.25 uL/hr = 0.006 mL/day	 	7 days
14 days
1 month	 	0.024
0.012
0.006	 	1.20

0.60

0.30	 	The highest concentration granted under this limited
approval is 30% w/v (300 mg/mL).1	 	360

180

 90
	rat 
	 	2 pumps @ 10 uL/hr = 0.24 mL/day each	 	7 days	 	0.480	 	1.92	 	 	 	 	 	576
	 
	 	2 pumps @ 5 uL/hr = 0.12 mL/day each	 	14 days	 	0.240	 	0.96	 	 	 	 	 	288
	 
	 	2 pumps @ 2.5 uL/hr = 0.06 mL/day each	 	1 month	 	0.120	 	0.48	 	 	 	 	 	144
	rabbit
	 	*	 	*	 	*	 	*	 	*	 	*
	dog
	 	*	 	*	 	*	 	*	 	*	 	*
	non-human primate
	 	*	 	*	 	*	 	*	 	*	 	*

* Limited to no data exists for these species. Contact CyDex for approval of dosing conditions.

 

			
	FOOTNOTES:
	 
	a	 	— conversions between mL/dose and mL/kg assumes mouse weight of 0.02 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes rat weight of 0.25 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes rabbit weight of 2.5 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes dog weight of 10 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes monkey weight of 5 kg

 

 			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

Page 11

07/17/00

 

 

			
	
	 	Table 7

Captisol®:
Allowble Dosing Matrix — Oral Solution Summary

	 	 	 
	NOTES: 1)

	 	The allowable dose may not be exceeded without CyDex approval. These doses and the 30%
w/v concentration do not necessarily represent the highest safe dosing conditions. However,
they are the highest values to which CyDex has given limited approval for use.
	 
	 	 
	2)

	 	If Captisol concentration used is < 30`)/0 w/v, then the volume
administered may be increased accordingly, but the dose delivered may not exceed that
granted under this limited approval.

Table 7: Allowable Oral Solution Captisol® Doses by Duration of Study

	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	Example Volume2	 	 	 	 	 	
	 	 	 	 	(based on use of 30% w/v Captisol	 	 	 	 	 	Daily Allowable
	Oral Solution (Gavage)	 	delivering indicated dose)	 	Example Concentration	 	Captisol® Dose1
	Species	 	Duration	 	(mL/dose)	 	(mL/kg)	 	(% w/v)	 	(mg/mL)	 	(mg/kg)
	 
	mouse	 	single dose 

14 days	 	0.33

0.27	 	16.67
13.33	 	The highest concentration

 granted under
this limited
	 	5000

4000
	 
	 	1 month	 	0.13	 	6.67	 	approval is 30% w/v 
(300 mg/mL).1	 	2000
	rat
	 	single dose	 	4.17	 	16.67	 	 	 	 	 	5000
	 
	 	14 days	 	3.33	 	13.33	 	 	 	 	 	4000
	 
	 	1 month	 	1.67	 	6.67	 	 	 	 	 	2000
	rabbit
	 	single dose	 	*	 	*	 	*	 	*	 	*
	 
	 	14 days	 	*	 	*	 	*	 	*	 	*
	 
	 	1 month	 	*	 	*	 	*	 	*	 	*
	dog
	 	single dose	 	*	 	*	 	*	 	*	 	*
	 
	 	14 days	 	*	 	*	 	*	 	*	 	*
	 
	 	1 month	 	*	 	*	 	*	 	*	 	*
	 
	 	 	 	 	 	 	 	 	 	 	 	 
	non-human primate
	 	single dose	 	*	 	*	 	*	 	*	 	*
	 
	 	14 days	 	*	 	*	 	*	 	*	 	*
	 
	 	1 month	 	*	 	*	 	*	 	*	 	*

*Limited to no data exists for these species. Contact CyDex for approval of dosing conditions.

 

			
	FOOTNOTES:
	 
	a	 	— conversions between mL/dose and mL/kg assumes mouse weight of 0.02 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes rat weight of 0.25 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes rabbit weight of 2.5 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes dog weight of 10 kg
	 
	a	 	— conversions between mL/dose and mL/kg assumes monkey weight of 5 kg

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has
been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

Page 12

07/17/00

 

 

			
	 	 	 
	
	 	Table 8

Captisol®: Allowble Dosing Matrix — Oral Solid Summary
	 
	 	

			
	NOTES:      1)	 	The allowable dose may not be exceeded without CyDex approval. At
this time, limited data exists for the oral dosing of solid Captisol. Please contact
CyDex for approval of dosing conditions.

Table 8: Allowable Oral Solid Captisol®Doses by Duration of Study

	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	Daily Allowable
	Oral Solid	 	Example Formulation	 	Example Dosage Forms	 	Captisol® Dose
	Species	 	Duration	 	(mg/dose)	 	(Number of Doses)	 	 	 	(mg/kg)
	 
	mouse
	 	single dose	 	*	 	*	 	Powders	 	*
	 
	 	14 days	 	*	 	*	 	Capsules	 	*
	 
	 	1 month	 	*	 	*	 	Tablets	 	*
	rat
	 	single dose	 	*	 	*	 	 	 	*
	 
	 	14 days	 	*	 	*	 	 	 	*
	 
	 	1 month	 	*	 	*	 	 	 	*
	rabbit
	 	single dose	 	*	 	*	 	At this time, limited data exists for the oral	 	*
	 
	 	14 days	 	*	 	*	 	dosing of solid Captisol.	 	*
	 
	 	1 month	 	*	 	*	 	Please contact CyDex for approval of dosing conditions.	 	*
	dog
	 	single dose	 	*	 	*	 	 	 	*
	 
	 	14 days	 	*	 	*	 	 	 	*
	 
	 	1 month	 	*	 	*	 	 	 	*
	non-human primate
	 	single dose	 	*	 	*	 	 	 	*
	 
	 	14 days	 	*	 	*	 	 	 	*
	 
	 	1 month	 	*	 	*	 	 	 	*

*Limited to no data exists for these species. Contact CyDex for approval of dosing conditions.

 

	 	 	 
	FOOTNOTES:	 	 
	 
	a — conversions between mL/dose and mL/kg assumes mouse weight of 0.02 kg

	 	
	a — conversions between mL/dose and mL/kg assumes rat weight of 0.25 kg

	 	
	a  — conversions between mL/dose and mL/kg assumes rabbit weight of 2.5 kg
	 	 
	a — conversions between mL/dose and mL/kg assumes dog weight of 10 kg
	 	
	a — conversions between mL/dose and mL/kg assumes monkey weight of 5 kg
	 	

 

			
	 
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.
	 
	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

Page 13

07/17/00

 

			
	 	 	 
	
	 	Page 14

07/17/00

Appendix A

 

			
	[ ** ]  	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

 

 

			
	 	 	 
	
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Oral Solution Formulation Protocol

	 	 	 
	CyDex Protocol Tracking form

	 	Protocol # _____
	 
	 	 
	Title of Study:
	 	 
	 
	 	 
	Purpose:
	 	 
	 
	 	 
	Animal: (include species, age, and weight)
	 	 

Study Design

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Formulation	 	 	Drug Exposure (optional)	 	 	Captisol Exposure	 	 	# of Animals	 
	Volume	 	Doses	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	(ml/kg)	 	per Day	 	 	mg/ml	 	 	mg/kg	 	 	mg/kg/day	 	 	mg/ml	 	 	mg/kg	 	 	mg/kg/day	 	 	Male	 	 	Female	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 

Route:

Dosing Regine:

Vehicle:

Examination: (check all that apply)

	 	 	 	 	 
	o Clinical Observation

	 	o Body Weight
	 	o Clinical Chemistry
	o Food Consumption

	 	o Electrocardiograms
	 	o Toxicokinetics
	o Ophthalmology

	 	o Urinalysis
	 	o Hematology
	o Organ Weight

	 	o Necropsy
	 	o Microscopy
	o Others
	 	 	 	 

Performing Laboratory:

Dosing Schedule:

Expected Report Submission:

	 
	GLP:	 	 This study             
                
             be conducted in accordance with GLP standards.
(will or will not)

Necessary amount of Captisol needed for study:

 

			
	[ ** ] =	 	 Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

 

 

			
	 	 	 
	
	 	Page 16

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Parenteral Formulation Protocol

	 	 	 
	CyDex Protocol Tracking form

	 	Protocol # _____
	 
	 	 
	Title of Study:
	 	 
	 
	 	 
	Purpose:
	 	 
	 
	 	 
	Animal: (include species, age, and weight)
	 	 

Study Design

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Formulation	 	 	Drug Exposure (optional)	 	 	Captisol Exposure	 	 	# of Animals	 
	Volume	 	Doses	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	(ml/kg)	 	per Day	 	 	mg/ml	 	 	mg/kg	 	 	mg/kg/day	 	 	mg/ml	 	 	mg/kg	 	 	mg/kg/day	 	 	Male	 	 	Female	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 

Route:

Duration

Injection Speed:

Injection Volume

Vehicle:

Examination: (check all that apply)

	 	 	 	 	 
	o Clinical Observation

	 	o Body Weight
	 	o Clinical Chemistry
	o Food Consumption

	 	o Electrocardiograms
	 	o Toxicokinetics
	o Ophthalmology

	 	o Urinalysis
	 	o Hematology
	o Organ Weight

	 	o Necropsy
	 	o Microscopy
	o Others
	 	 	 	 

Performing Laboratory:

Dosing Schedule:

Expected Report Submission:

	 
	GLP:	 	 This study             
                
             be conducted in accordance with GLP standards.
(will or will not)

Necessary amount of Captisol needed for study:

 

			
	[ ** ] =	 	 Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

 

 

			
	 	 	 
	
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Oral Solid Formulation Protocol

	 	 	 
	CyDex Protocol Tracking form

	 	Protocol # _____
	 
	 	 
	Title of Study:
	 	 
	 
	 	 
	Purpose:
	 	 
	 
	 	 
	Animal: (include species, age, and weight)
	 	 
	 
	 	 
	Mean Weight Range:
	 	 

Study Design

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Formulation	 	 	Drug Exposure (optional)	 	 	Captisol Exposure	 	 	# of Animals	 
	Volume	 	Doses	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	(ml/kg)	 	per Day	 	 	mg/ml	 	 	mg/kg	 	 	mg/kg/day	 	 	mg/ml	 	 	mg/kg	 	 	mg/kg/day	 	 	Male	 	 	Female	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 

Dosing Regime:

Vehicle:

Examination: (check all that apply)

	 	 	 	 	 
	o Clinical Observation

	 	o Body Weight
	 	o Clinical Chemistry
	o Food Consumption

	 	o Electrocardiograms
	 	o Toxicokinetics
	o Ophthalmology

	 	o Urinalysis
	 	o Hematology
	o Organ Weight

	 	o Necropsy
	 	o Microscopy
	o Others
	 	 	 	 

Performing Laboratory:

Dosing Schedule:

Expected Report Submission:

	 
	GLP:	 	 This study             
               
              be conducted in accordance with GLP standards.
(will or will not)

Necessary amount of Captisol needed for study:

 

			
	[ ** ] =	 	 Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

 

 

			
	 	 	 
	
	 	Page 18

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Appendix B

 

			
	[ ** ] = 	 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

 

 

			
	 	 	 
	
	 	Page 1

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RESULTS SUMMARY

Protocol #                     

	 	 	 
	Title:
	 	 
	 

	 	 
	 
	 	 
	 

Studies conducted under protocol:

	 	 	 	 	 
	Study Number	 	Dates of Study	 	Variations from Protocol? (If so, please explain)
	 
	 
	 	 	 	 
	 
	 
	 	 	 	 
	 
	 
	 	 	 	 
	 
	 
	 	 	 	 
	 
	 
	 	 	 	 

Results Summary

 

 

 

 

 

 

 

 

 

 

 

Attach any supporting documents as needed.

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities
and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.
	 
	 	 	CyDex Inc. 12980 Metcalf Ave., Suite 470, Overland Park, KS 66213 • (913) 685-8850 • FAX (913) 685-8856 • E-mail: CDInfo@cydexinc,comVersion 1,

 

 

March 6, 2007

Dr. Susan Molineaux

CSO

Proteolix

230 East Grand Avenue, Suite A

South San Francisco, CA 94080

Dear Dr. Molineaux:

     Per section 4.2(a) of our license and supply agreement dated October 12th, 2005, the purchase
price of clinical and research grades of Captisol is subject to an annual increase equal to the
average percentage indicated by the Producer Price Index (Pharmaceutical Preparations) as reported
by the Bureau of Labor Statistics, U.S. Department of Labor, for the 12-month period ending October
31 of the prior year (http://data.bls.gov/cgi-bin/surveymost?wp).

     Said increase for the captioned period is 4.7%. This change is effective as of January 1st,
2007 and for the remainder of the calendar year. Kindly reflect price change on any purchases
during 2007.

     This letter serves as an amendment to the supply agreement. Attached you will find amendment
to Exhibit C detailing the new price list.

     If you have any questions, please contact Allen Roberson at (913) 402-3536 or via email at
aroberson@cydexinc.com.

With best regards,

/s/ Michelle Baragary

Michelle Baragary

Business Development Coordinator

enclosure

			
	cc:	 	Jeff Stegall

Allen Roberson

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed
separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

 

 

AMENDMENT TO EXHIBIT C

PURCHASE PRICE FOR CAPTISOL

Effective January 1, 2007

1. Clinical Grade CAPTISOL: US$[ ** ] per kg, until such time as Proteolix orders more than [ ** ]
of Clinical Grade CAPTISOL, at which time the price of Clinical Grade CAPTISOL will [ ** ] US$[ **
] per kg.

2. Commercial Grade CAPTISOL: The price of Commercial Grade CAPTISOL shall be determined pursuant
to the following table, but subject to adjustment pursuant to Section 4.2(a) of the Agreement.

	 	 	 
	SUPPLIED CAPTISOL	 	COST
	(METRIC TONS PER YEAR)	 	(US$ PER KG)
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]

3. Research Grade CAPTISOL:

	 	 	 	 	 
	Catalog No.	 	Package Size	 	Price (USD)
	NC-CAP-103
	 	100 grams
	 	[ ** ]
	NC-CAP-105
	 	500 grams
	 	[ ** ]
	NC-CAP-106
	 	1 kilogram
	 	[ ** ]
	NC-CAP-107
	 	5 kilograms
	 	[ ** ]
	 
	 	> 5 kilograms
	 	[ ** ]

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document,
marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission
pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

 

 

2 January 2008

Dr. Susan Molineaux

CSO

Proteolix

230 East Grand Avenue, Suite A

South San Francisco, CA 94080

Dear Dr. Molineaux,

Per section 4.2(a) of our License and Supply Agreement dated October 12, 2005, the purchase price
of research, clinical and commercial grades of Captisol is subject to an annual increase equal to
the average percentage indicated by the Producer Price Index (Pharmaceutical Preparations) as
reported by the Bureau of Labor Statistics, U.S. Department of Labor, for the 12-month period
ending October 31 of the prior year (http://data.bls.gov/cgi-bin/surveymost?wp).

Said increase for the captioned period is 5.0%. However, CyDex has made the decision to increase
only the clinical grade of Captisol by [ ** ]%. This change is effective as of January 1, 2008 and
for the remainder of the calendar year. Kindly reflect price change on future purchase orders.

This letter serves as an amendment to the license and supply agreement. Attached you will find the
2nd Amendment to Exhibit C detailing the new price list.

If you have any questions, please contact Allen Roberson at (913) 402-3536 or via email at
aroberson@cydexinc.com.

With best regards,

	 
	/s/ Michelle Baragary

	 
	Michelle Baragary 

Business Development Coordinator 

Enclosure

			
	cc:	 	Jeff Stegall

Leon Ku

Allen Roberson

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately
with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

 

 

2nd AMENDMENT TO EXHIBIT C

PURCHASE PRICE FOR CAPTISOL

Effective January 1, 2008

1. Clinical Grade CAPTISOL: US$[ ** ] per kg, until such time as Proteolix orders more than [ ** ]
of Clinical Grade CAPTISOL, at which time the price of Clinical Grade CAPTISOL will [ ** ] US$[ **
] per kg.

2. Commercial Grade CAPTISOL: The price of Commercial Grade CAPTISOL shall be determined pursuant
to the following table, but subject to adjustment pursuant to Section 4.2(a) of the Agreement.

	 	 	 
	Supplied CAPTISOL	 	Cost
	(Metric Tons Per Year)	 	(US$ per kg)
	[ ** ]

	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]

3. Research Grade CAPTISOL:

	 	 	 	 	 
	Catalog No.	 	Package Size	 	Price (USD)
	NC-CAP-103
	 	100 grams
	 	[ ** ]
	NC-CAP-105
	 	500 grams
	 	[ ** ]
	NC-CAP-106
	 	1 kilogram
	 	[ ** ]
	NC-CAP-107
	 	5 kilograms
	 	[ ** ]
	 
	 	> 5 kilograms
	 	[ ** ]

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately
with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

 

 

February 9, 2009

Dr. Susan Molineaux

CSO

Proteolix

230 East Grand Avenue, Suite A

South San Francisco, CA 94080

Dear Dr. Molineaux,

Per section 4.2(a) of our License and Supply Agreement dated October 12, 2005, the purchase price
of research, clinical and commercial grades of Captisol is subject to an annual increase equal to
the average percentage indicated by the Producer Price Index (Pharmaceutical Preparations) as
reported by the Bureau of Labor Statistics, U.S. Department of Labor, for the 12-month period
ending October 31 of the prior year (http://data.bls.gov/cgi-bin/surveymost?wp).

Said increase for the captioned period is 6.2%. However, CyDex has made the decision to increase
only clinical grade of Captisol by [ ** ]% and research grade of Captisol by [ ** ]%. This change
is effective as of March 1, 2009 and for the remainder of the calendar year. Kindly reflect price
change on future purchase orders.

This letter serves as an amendment to the license and supply agreement. Attached you will find the
3rd Amendment to Exhibit C detailing the new price list.

If you have any questions, please contact Allen Roberson at (913) 402-3536 or via email at
aroberson@cydexinc.com.

With best regards,

/s/ Marylyn Rives

Marylyn Rives

Business Development Coordinator

Enclosure

			
	cc:	 	Jeff Stegall

Leon Ku

Allen Roberson

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities
and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

 

 

3rd AMENDMENT TO EXHIBIT C

PURCHASE PRICE FOR CAPTISOL

Effective March 1, 2009

1. Clinical Grade CAPTISOL: US$[ ** ] per kg, until such time as Proteolix orders more than [ ** ]
of Clinical Grade CAPTISOL, at which time the price of Clinical Grade CAPTISOL will [ ** ] US$[ **
] per kg.

2. Commercial Grade CAPTISOL: The price of Commercial Grade CAPTISOL shall be determined pursuant
to the following table, but subject to adjustment pursuant to Section 4.2(a) of the Agreement.

	 	 	 
	Supplied CAPTISOL	 	Cost
	(Metric Tons Per Year)	 	(US$ per kg)
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]

3. Research Grade CAPTISOL:

	 	 	 	 	 
	Catalog No.	 	Package Size	 	Price (USD)
	NC-CAP-103
	 	100 grams
	 	[ ** ]
	NC-CAP-105
	 	500 grams
	 	[ ** ]
	NC-CAP-106
	 	1 kilogram
	 	[ ** ]
	NC-CAP-107
	 	5 kilograms
	 	[ ** ]
	 
	 	> 5 kilograms
	 	[ ** ]

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by brackets, has been omitted and
filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

 

 

10513 W. 84th Terrace

Lenexa, KS 65214

P 913.685.8850

F: 913.685.8856

www.cydexpharma.com

January 20, 2010

Leon Ku

Director, Supply Chain Management

Onyx Pharmaceuticals

333 Allerton Avenue

South San Francisco, CA 94080

Dear Mr. Ku,

Per section 4.2(a) of our License and Supply Agreement dated October 12, 2005, the purchase price
of research, clinical and commercial grades of Captisol is subject to an annual increase equal to
the average percentage indicated by the Producer Price Index (Pharmaceutical Preparations) as
reported by the Bureau of Labor Statistics, U.S. Department of Labor, for the 12-month period
ending October 31 of the prior year (http://data.bls.gov/cgi-bin/surveymost?wp).

Said increase for the captioned period is 6.3%. However, CyDex has made the decision to increase
the price of clinical grade of Captisol by [ ** ]% and research grade of Captisol by [ ** ]%. This
change is effective as of February 15, 2010 and for the remainder of the calendar year. Kindly
reflect price change on future purchase orders.

This letter serves as an amendment to the license and supply agreement. Attached you will find the
4th Amendment to Exhibit C detailing the new price list.

If you have any questions, please contact Marylyn Rives at (913) 685-8850 or via email at
mrives@cydexpharma.com.

With best regards,

/s/ Jessica Smith

Jessica Smith

Business Development & Marketing Assistant

Enclosure

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document,
marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission
pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

 

 

10513 W. 84th Terrace

Lenexa, KS 65214

P 913.685.8850

F: 913.685.8856

www.cydexpharma.com

			
	cc:	 	Jeff Stegall

Evan Lewis

Allen Roberson

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuant
to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

 

 

10513 W. 84th Terrace

Lenexa, KS 65214

P 913.685.8850

F: 913.685.8856

www.cydexpharma.com

4th AMENDMENT TO EXHIBIT C

PURCHASE PRICE FOR CAPTISOL

Effective February 15, 2010

1. Clinical Grade CAPTISOL: US$[ ** ] per kg, until such time as Proteolix orders more than [ ** ]
of Clinical Grade CAPTISOL, at which time the price of Clinical Grade CAPTISOL will [ ** ] US$[ **
] per kg.

2. Commercial Grade CAPTISOL: The price of Commercial Grade CAPTISOL shall be determined pursuant
to the following table, but subject to adjustment pursuant to Section 4.2(a) of the Agreement.

	 	 	 
	Supplied CAPTISOL	 	Cost
	(metric tons per year)	 	(US$ per kg)
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]
	[ ** ]
	 	[ ** ]

3. Research Grade CAPTISOL:

	 	 	 	 	 
	Catalog No.	 	Package Size	 	Price (USD)
	NC-CAP-103
	 	100 grams
	 	[ ** ]
	NC-CAP-105
	 	500 grams
	 	[ ** ]
	NC-CAP-106
	 	1 kilogram
	 	[ ** ]
	NC-CAP-107
	 	5 kilograms
	 	[ ** ]
	 
	 	> 5 kilograms
	 	[ ** ]

 

			
	[ ** ] 	 = 	Certain confidential information contained in this document,
marked by brackets, has been omitted and filed separately with the Securities and
Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.exv10w1

Exhibit 10.1

GLOBAL MED TECHNOLOGIES, INC.

INDEMNIFICATION AGREEMENT

     This Indemnification Agreement (this “Agreement”) is made and entered into as of the
17th day of February, 2010 by and between Global Med Technologies, Inc., a Colorado
corporation (the “Corporation”), and                                          (“Indemnitee”).

WITNESSETH:

     WHEREAS, the Corporation has entered into an Agreement and Plan of Merger dated January 31,
2010 (the “Agreement and Plan of Merger”) by and among the Corporation, Haemonetics
Corporation, a Massachusetts corporation (“Parent”), and Atlas Acquisition Corp., a
Colorado corporation and a wholly-owned subsidiary of Parent (“Purchaser”);

     WHEREAS, under the terms of the Agreement and Plan of Merger, Purchaser will commence a tender
offer (the “Offer”) for shares of the Corporation’s common stock, par value $0.01 per
share, and for shares of the Corporation’s Series A Convertible Preferred Stock, par value $0.01
per share;

     WHEREAS, following the consummation of the Offer and subject to the satisfaction or waiver of
the conditions set forth in the Agreement and Plan of Merger, Purchaser will merge into the
Corporation and the Corporation shall continue as the surviving corporation (the “Merger”);

     WHEREAS, in connection with the Corporation becoming a party to the Agreement and Plan of
Merger, on February 11, 2010, a complaint (the “Complaint”) was filed in the District Court
of Jefferson County, Colorado against the Corporation, Parent, Purchaser, Michael Ruxin, Thomas
Marcinek, Sarah Eames, T. Kendall Hunt and Robert Gilmore on behalf of a purported class of public
shareholders of the Corporation;

     WHEREAS, in connection with the events forming the allegations in the Complaint and leading to
the Agreement and Plan of Merger, Indemnitee has furnished to the Corporation his affirmation of
his good faith conduct and undertaking to repay expenses required by CBCA § 7-109-104(a) and (b);

     WHEREAS, independent counsel selected by the Board of Directors pursuant to CBCA § 7-109-106
has determined that the facts known to the Corporation and to Counsel at the time of such
determination would not preclude indemnification under CBCA title 7, Article 109;

     WHEREAS, highly competent persons have become more reluctant to serve corporations as
directors, officers or in other capacities unless they are provided with adequate indemnification
against inordinate risks of claims and actions against them arising out of their service to and
activities on behalf of the corporation;

     WHEREAS, the uncertainties relating to indemnification have increased the difficulty of
attracting and retaining such persons;

 

 

     WHEREAS, the Board of Directors of the Corporation has determined that the increased
difficulty in attracting and retaining such persons is detrimental to the best interests of the
Corporation’s shareholders and that in light of the Complaint and the contemplated Offer and Merger
that the Corporation should act to assure such persons that there will be increased certainty of
such protection in the future;

     WHEREAS, it is reasonable, prudent and necessary for the Corporation contractually to obligate
itself to indemnify, and to advance expenses on behalf of, such persons to the fullest extent
permitted by applicable law so that they will serve or continue to serve the Corporation free from
undue concern that they will not be so indemnified; and

     WHEREAS, the Indemnitee does not regard the protection available under the Corporation’s
Articles of Incorporation, Bylaws and insurance as adequate in the present circumstances, and may
not be willing to serve the Corporation without adequate protection, and the Corporation desires
the Indemnitee to continue to serve the Corporation.

     NOW, THEREFORE, in consideration of Indemnitee’s agreement to provide services to the
Corporation and/or certain of its affiliates as contemplated hereby, the mutual agreements
contained herein and other good and valuable consideration, the receipt and sufficiency of which
are hereby acknowledged, the parties hereto stipulate and agree as follows:

ARTICLE I

Definitions

     Section 1.1. As used herein, the following words and terms shall have the following respective
meanings (whether singular or plural):

     “Acceptance Date” has the meaning set forth in the Agreement and Plan of Merger.

     “Agreement and Plan of Merger” has the meaning set forth in the recitals hereto.

     “Articles of Incorporation” means the Articles of Incorporation of the Corporation (as
they may be amended or restated from time to time).

     “Board of Directors” means the board of directors of the Corporation.

     “Bylaws” means the bylaws of the Corporation (as they may be amended or restated from
time to time).

     “CBCA” means the Colorado Business Corporation Act.

2

 

     “Change of Control” means:

     (i) The acquisition by any individual, entity or group (within the meaning of Section
13(d)(5) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”)) (a
“Person”) of beneficial ownership (within the meaning of Rule 13d-3 promulgated
under the Exchange Act) of forty percent (40%) or more of either (1) the then outstanding shares of common stock of the Corporation (the “Outstanding 
Corporation Common Stock”) or (2) the combined voting power of the then
outstanding voting securities of the Corporation entitled to vote generally in the election
of directors (the “Outstanding Corporation Voting Securities”); provided, however,
that for purposes of this subsection (i), the following acquisitions shall not constitute a
Change of Control: (A) any acquisition by the Corporation, (B) any acquisition by any
employee benefit plan (or related trust) sponsored or maintained by the Corporation or any
entity controlled by the Corporation or (C) any acquisition by any entity pursuant to a
transaction which complies with clauses (1) and (2) of subsection (iii) of this definition;

     (ii) Individuals who, as of the date hereof, constitute the Board of Directors (the
“Incumbent Board”) cease for any reason to constitute at least a majority of the
Board of Directors; provided, however, that any individual becoming a director subsequent to
the date hereof whose election, or nomination for election by the Corporation’s
shareholders, was approved by a vote of at least a majority of the directors then comprising
the Incumbent Board shall be considered as though such individual were a member of the
Incumbent Board, but excluding, for this purpose, any such individual whose initial
assumption of office occurs as a result of an actual or threatened election contest with
respect to the election or removal of directors or other actual or threatened solicitation
of proxies or consents by or on behalf of a Person other than the Board of Directors;

     (iii) Consummation of a reorganization, merger or consolidation or sale or other
disposition of all or substantially all of the assets of the Corporation (a “Business
Combination”), in each case, unless, following such Business Combination, (1) all or
substantially all of the individuals and entities who were the beneficial owners,
respectively, of the Outstanding Corporation Common Stock and Outstanding Corporation Voting
Securities immediately prior to such Business Combination beneficially own, directly or
indirectly, more than forty percent (40%) of, respectively, the then outstanding shares of
common stock and the combined voting power of the then outstanding voting securities
entitled to vote generally in the election of directors, as the case may be, of the entity
resulting from such Business Combination (including, without limitation, an entity that as a
result of such transaction owns the Corporation or all or substantially all of the
Corporation’s assets either directly or through one or more subsidiaries) in substantially
the same proportions as their ownership, immediately prior to such Business Combination, of
the Outstanding Corporation Common Stock and Outstanding Corporation Voting Securities, as
the case may be, and (2) at least a majority of the members of the board of directors of the
corporation, or the similar managing body of a non-corporate entity, resulting from such
Business Combination were members of the Incumbent Board at the time of the execution of the
initial agreement, or of the action of the Board of Directors, providing for such Business
Combination; or

     (iv) the occurrence of the Acceptance Date.

3

 

     “Covered Capacity” means, with respect to any person, that such person (or a person
for whom he is serving as a legal representative) is or was a director, officer, fiduciary,
employee or agent of the Corporation, or is or was serving at the request of the Corporation as
director,
manager, officer, trustee, partner, promoter, associate, member, fiduciary, employee or agent
of another domestic or foreign entity or an employee benefit plan.

     “Expenses” include all direct and indirect costs, fees and expenses of any type or
nature, including, without limitation, all attorneys’ fees and costs, retainers, court costs,
transcript costs, fees of experts, witness fees, travel expenses, fees of private investigators and
professional advisors, duplicating costs, printing and binding costs, telephone charges, postage,
delivery service fees, fax transmission charges, secretarial services and all other disbursements
or expenses in connection with prosecuting, defending, preparing to prosecute or defend,
investigating, being or preparing to be a witness in, settlement or appeal of or otherwise
participating in a Proceeding, including reasonable compensation for time spent by Indemnitee for
which he is not otherwise compensated by the Corporation or any third party. “Expenses” also
include expenses incurred in connection with any appeal resulting from any Proceeding, including
the premium for, security for, and other costs relating to, any cost bond, supersedeas bond or
other appeal bond or its equivalent. “Expenses” do not include amounts paid in settlement by
Indemnitee or the amount of judgments or fines against Indemnitee.

     “Independent Counsel” means a law firm, or a member of a law firm, that is experienced
in matters of corporation law and neither presently is, nor in the five (5) years previous to his
selection or appointment has been, retained to represent: (i) the Corporation or Indemnitee in any
matter material to either such party or (ii) any other party to the Proceeding giving rise to a
claim for indemnification hereunder. The term “Independent Counsel” does not include any person
who, under the applicable standards of professional conduct then prevailing, would have a conflict
of interest in representing either the Corporation or Indemnitee in an action to determine
Indemnitee’s rights under this Agreement, the Bylaws of the Corporation or under any agreement
between Indemnitee and the Corporation.

     “Proceeding” includes a threatened, pending or completed action, suit, arbitration,
alternate dispute resolution, investigation, inquiry, administrative hearing, appeal or any other
actual, threatened or completed proceedings with or brought in the right of the Corporation or
otherwise and whether civil, criminal, administrative or investigative in nature.

ARTICLE II

Services by Indemnitee

     Section 2.1. Indemnitee agrees to serve or continue to serve in his current capacity or
capacities as a director, officer, employee, agent or fiduciary of the Corporation. Indemnitee may
also serve, as the Corporation may reasonably request from time to time, as a director, officer,
employee, agent or fiduciary of any other corporation, partnership, limited liability company,
association, joint venture, trust, employee benefit plan or other enterprise in which the
Corporation has an interest. Indemnitee and the Corporation each acknowledge that they have
entered into this Agreement as a means of inducing Indemnitee to serve the Corporation in such
capacities. Indemnitee may at any time and for any reason resign from such position or positions
(subject to any other contractual obligation or any obligation imposed by operation of law). The
Corporation shall have no obligation under this Agreement to continue Indemnitee in any such
position for any period of time and shall not be precluded by the provisions of this Agreement from
removing Indemnitee from any such position at any time.

4

 

ARTICLE III

Third Party Proceedings

     Section 3.1. The Corporation shall indemnify Indemnitee if he was or is a party or is
threatened to be made a party to any Proceeding, except an action by or in the right of the
Corporation, by reason of the fact that he is or was serving or acting in a Covered Capacity,
against Expenses, judgments, fines and amounts paid in settlement actually and reasonably incurred
by Indemnitee in accordance with Article VIII in connection with the Proceeding if (i) he
acted in good faith, (ii) (A) in the case of conduct in an official capacity, in a manner which
Indemnitee reasonably believed to be in the best interests of the Corporation and (B) in the case
of conduct other than in an official capacity, in a manner which Indemnitee reasonably believed to
be not opposed to the best interests of the Corporation and, (iii) with respect to any criminal
Proceeding, had no reasonable cause to believe his or her conduct was unlawful. The termination of
any Proceeding by judgment, order, settlement, conviction or upon a plea of nolo contendere or its
equivalent, does not, of itself, create a presumption that Indemnitee did not meet the standard of
conduct described in this Section 3.1.

ARTICLE IV

Derivative Actions

     Section 4.1. The Corporation shall indemnify Indemnitee if he was or is a party or is
threatened to be made a party to any threatened, pending or completed action or suit by or in the
right of the Corporation to procure a judgment in its favor, by reason of the fact that Indemnitee
is or was serving or acting in a Covered Capacity, against Expenses actually and reasonably
incurred by Indemnitee in accordance with Article VIII and amounts paid in settlement
thereof if (i) Indemnitee acted in good faith and (ii) (A) in the case of conduct in an official
capacity, in a manner which Indemnitee reasonably believed to be in the best interests of the
Corporation and (B) in the case of conduct other than in an official capacity, in a manner which
Indemnitee reasonably believed to be not opposed to the best interests of the Corporation.
Indemnification may not be made for any claim, issue or matter as to which Indemnitee has been
adjudged by a court of competent jurisdiction, after exhaustion of all appeals therefrom, to be
liable to the Corporation or for amounts paid in settlement to the Corporation, unless and only to
the extent that the court in which the action or suit was brought or other court of competent
jurisdiction determines upon application that in view of all the circumstances of the case, the
person is fairly and reasonably entitled to indemnity for such Expenses as the court deems proper.

ARTICLE V

Party Who is Wholly or Partially Successful

     Section 5.1. Notwithstanding any other provisions of this Agreement, to the extent that
Indemnitee is a party to or a participant in and is successful on the merits or otherwise in any
Proceeding or in defense of any claim, issue or matter in any Proceeding, in whole or in part, to
which Indemnitee was or is a party or is otherwise involved by reason of the fact that he is or was
serving or acting in a Covered Capacity, the Corporation shall indemnify and hold harmless
Indemnitee against all Expenses actually and reasonably incurred by Indemnitee in accordance with
Article VIII in connection with any Proceeding or defense. If Indemnitee is not wholly
successful in the Proceeding, the Corporation shall indemnify and hold harmless Indemnitee
against all Expenses actually and reasonably incurred by him or on his behalf to the fullest
extent permitted by applicable law. The termination of any claim, issue or matter in the
Proceeding by dismissal, with or without prejudice, by reason of settlement, judgment, order or
otherwise, shall be deemed to be a successful result as to such Proceeding, claim, issue or matter,
so long as there has been no finding that Indemnitee (i) derived an improper personal benefit
pursuant to CBCA Section 7-109-102, (ii) did not act in good faith, (iii) in the case of conduct in
an official capacity, did not act in a manner which Indemnitee reasonably believed to be in the
best interests of the Corporation, (iii) in the case of conduct other than in an official capacity,
did not act in a manner which Indemnitee reasonably believed to be not opposed to the best
interests of the Corporation or (iv) with respect to any criminal proceeding or action, had
reasonable cause to believe his or her conduct was unlawful.

5

 

ARTICLE VI

Expenses as Witness

     Section 6.1. To the extent Indemnitee is, by reason of his or her serving or acting in a
Covered Capacity, a witness in any Proceeding to which Indemnitee is not a party, Indemnitee shall
be indemnified and held harmless against all Expenses actually and reasonably incurred by him or on
his behalf in accordance with Article VIII in connection with the Proceeding and his or her
acting as a witness in it.

ARTICLE VII

Exclusions

     Section 7.1. Notwithstanding the foregoing, indemnification, unless ordered by a court
pursuant to CBCA 7-109-105 or for the advancement of Expenses made pursuant to Section 8.1,
shall not be made to or on behalf of the Indemnitee if such indemnification is in connection with a
Proceeding, other than a Proceeding by or in the right of the Corporation, charging that the
Indemnitee derived an improper personal benefit in which Proceeding the Indemnitee was adjudged
liable on the basis that the Indemnitee derived an improper personal benefit.

     Section 7.2. Notwithstanding any provision in this Agreement, the Corporation is not obligated
under this Agreement to make any indemnification payments in connection with any claim made against
Indemnitee:

     (a) For which payment has actually been received by or on behalf of Indemnitee under
any insurance policy or other indemnity provision, except with respect to any excess beyond
the amount actually received under any insurance policy, contract, agreement or other
indemnity provision or otherwise; or

     (b) Except as provided for in Sections 8.1 or 12.3 of this Agreement,
in connection with any Proceeding or any part of any Proceeding, initiated by Indemnitee,
including those initiated against the Corporation or its officers, directors or employees,
unless (i) the Board of Directors authorizes the Proceeding or part thereof before its
initiation or (ii) the Corporation provides the indemnification in its sole discretion,
pursuant to the powers vested in the Corporation under applicable law.

6

 

ARTICLE VIII

Advancement of Expenses

     Section 8.1. Notwithstanding any other provision of this Agreement and to the fullest
permitted by applicable law, the Corporation shall advance the Expenses incurred by Indemnitee in
connection with any Proceeding to which Indemnitee was or is a party or is otherwise involved by
reason of the fact that he is or was serving or acting in a Covered Capacity, as soon as
practicable but in any event not more than ten (10) days after receipt by the Corporation of a
statement requesting the advances, whether the statement is submitted before or after final
disposition of any Proceeding. Unless otherwise required by law, the Corporation shall not require
that Indemnitee provide any form of security for repayment of or charge any interest on any amounts
advanced pursuant to this Section 8.1. The advances shall be made without regard to
Indemnitee’s ability to repay the Expenses and without regard to any belief or determination as to
Indemnitee’s ultimate entitlement to be indemnified. Advances shall include any and all reasonable
Expenses incurred in pursuing a Proceeding to enforce the right of advancement, including Expenses
incurred in preparing statements to the Corporation to support the advances claimed. Indemnitee
qualifies for advances, to the fullest extent permitted by applicable law, solely upon the
execution and delivery to the Corporation of (i) a written affirmation of the Indemnitee’s good
faith belief that the Indemnitee has met the standard of conduct described in Section 7-109-102 of
the CBCA and (ii) a written undertaking providing that Indemnitee undertakes to repay the advance
to the extent it is ultimately determined that Indemnitee did not meet the standard of conduct
described in Section 7-109-102 of the CBCA. This section does not apply to any claim made by
Indemnitee for any indemnification payment that is excluded pursuant to Section 7.2 of this
Agreement.

ARTICLE IX

Notices

     Section 9.1. Indemnitee agrees to notify the Corporation in writing promptly after being
served with any summons, citation, subpoena, complaint, indictment, inquiry, information request or
other document relating to any Proceeding or matter which may be subject to indemnification, hold
harmless or exoneration rights or the advancement of expenses; provided, however, that the failure
of Indemnitee to so notify the Corporation shall not relieve the Corporation of any obligation it
may have to Indemnitee under this Agreement or otherwise. Indemnitee may deliver to the
Corporation a written application to indemnify and hold harmless Indemnitee in accordance with this
Agreement. The application may be delivered from time to time and may be amended and supplemented
and at such times as Indemnitee deems appropriate in his or her sole discretion. After a written
application for indemnification is delivered by Indemnitee, Indemnitee’s entitlement to
indemnification shall be determined pursuant to Articles X, XI and XII of
this Agreement.

7

 

ARTICLE X

Procedures

     Section 10.1. To the fullest extent permitted by law, the indemnification provided for in this
Agreement shall be deemed mandatory. To the extent that, under applicable law, any indemnification
provided for in this Agreement is treated as discretionary, any indemnification
determination, unless ordered by a court or advanced pursuant to Section 8.1 of this
Agreement, may be made by the Corporation only as authorized in the specific case upon a
determination that the indemnification of Indemnitee is proper in the circumstances. Such
determination must be made:

     (i) by the Board of Directors by a majority vote of those present at a meeting at which
a quorum is present, and only those directors not parties to the proceeding shall be counted
in satisfying the quorum;

     (ii) if a quorum cannot be obtained, by a majority vote of a committee of the Board of
Directors designated by the Board of Directors, which committee shall consist of two (2) or
more directors not parties to the proceeding; except that directors who are parties to the
proceeding may participate in the designation of directors for the committee; or

     (iii) if a quorum cannot be obtained as contemplated in paragraph (i) of this
Section 10.1, and a committee cannot be established under paragraph (ii) of this
Section 10.1, or, even if a quorum is obtained or a committee is designated, if a
majority of the directors constituting such quorum or such committee so directs, the
determination may be made:

	 	(1)	 	By Independent Counsel selected
by a vote of the Board of Directors or the committee in the
manner specified in paragraph (i) or (ii) of this Section
10.1 or, if a quorum of the full Board of Directors cannot
be obtained and a committee cannot be established, by
Independent Counsel selected by a majority vote of the full
Board of Directors; or
	 
	 	(2)	 	By the Corporation’s
shareholders.

     Notwithstanding the foregoing, if at any time during the two (2) year period prior to the date
of any written application for indemnification submitted by Indemnitee in connection with a
particular Proceeding there shall have occurred a Change of Control, the Board of Directors shall
direct (unless Indemnitee otherwise agrees in writing) that the indemnification determination shall
be made by Independent Counsel in a written opinion. Notwithstanding the foregoing, if the
determination that indemnification or advance of Expenses is permissible is made by Independent
Counsel then the Board of Directors shall authorize and direct such indemnification and advancement
of Expenses.

     Section 10.2. If the determination of Indemnitee’s entitlement to indemnification is to be
made by Independent Counsel following a Change of Control, the Independent Counsel must be selected
as provided in this Section 10.2. The Independent Counsel shall be selected by Indemnitee
(which selection shall be ratified by the Board of Directors).

8

 

     Section 10.3. The Corporation agrees to pay the reasonable fees and Expenses of Independent
Counsel in accordance with Article VIII and to fully indemnify and hold the
Independent Counsel harmless against any and all Expenses, claims, liabilities and damages
arising out of or relating to this Agreement or the Independent Counsel’s engagement.

     Section 10.4. The Corporation must promptly advise Indemnitee in writing if a determination is
made that Indemnitee is not entitled to indemnification and must include a description of the
reasons or basis for denial. If it is determined Indemnitee is entitled to indemnification, the
payment to Indemnitee must be made as soon as practicable but in no event more than ten (10) days
after the determination. Indemnitee must reasonably cooperate with the persons making the
determination and, upon request, must provide such persons with documents and information (which
are not privileged or otherwise protected) reasonably available to Indemnitee and reasonably
necessary to the determination. All Expenses incurred by Indemnitee in cooperating with the
persons making the determination shall be paid by the Corporation (irrespective of the
determination as to indemnification) and the Corporation hereby indemnifies and agrees to hold
Indemnitee harmless from those Expenses.

ARTICLE XI

Presumptions

     Section 11.1. In determining whether Indemnitee is entitled to indemnification under this
Agreement, the person or persons making the determination must presume that Indemnitee is entitled
to indemnification under this Agreement and the Corporation has the burden of proof to overcome
that presumption. Moreover, if at any time during the two (2) year period prior to the date of any
written application for indemnification submitted by Indemnitee in connection with a particular
Proceeding or other matter there shall have occurred a Change of Control, the foregoing presumption
may only be overcome by clear and convincing evidence. Neither of the following is a defense to an
action seeking a determination granting indemnity to Indemnitee or creates a presumption that
Indemnitee has not met the applicable standard of conduct: (i) the failure of the Corporation
(including its directors or Independent Counsel) to have made a determination before the beginning
of an action seeking a ruling that indemnification is proper nor (ii) an actual determination by
the Corporation (including its directors or Independent Counsel) that Indemnitee has not met the
applicable standard of conduct.

     Section 11.2. If the persons or entity selected under Article X of this Agreement to
determine whether Indemnitee is entitled to indemnification has not made a determination within
thirty (30) days after receipt by the Corporation of the request for it, the requisite
determination of entitlement to indemnification shall be deemed to have been made and Indemnitee is
entitled to such indemnification, absent (i) a misstatement by Indemnitee of a material fact or an
omission of material fact necessary to make his or her statements not materially misleading made in
connection with the request for indemnification (which misstatement or omission is shown by the
Corporation to be of sufficient importance that it would likely alter the applicable determination)
or (ii) a final judicial determination that indemnification is expressly prohibited under
applicable law. The thirty (30) day period may be extended for a reasonable time, not to exceed
fifteen (15) additional days, if the persons or entity making the determination requires the
additional time for obtaining or evaluating documents or information.

9

 

     Section 11.3. The termination of any Proceeding or any claim therein, by judgment, order,
settlement or conviction, or upon a plea of nolo contendere does not (except as expressly
provided elsewhere in this Agreement) of itself adversely affect the right of Indemnitee to
indemnification or create a presumption that Indemnitee did not meet any particular standard of
conduct, did not act in good faith and in a manner which Indemnitee reasonably believed to be in or
not opposed to the best interests of the Corporation or, with respect to any criminal Proceeding,
that Indemnitee had reasonable cause to believe his or her conduct was unlawful.

     Section 11.4. In determining good faith, Indemnitee must be deemed to have acted in good faith
and in a manner which he reasonably believed to be in or not opposed to the best interests of the
Corporation if Indemnitee’s action is based on the records or books of account of the Corporation,
including financial statements, or on information, opinions, reports or statements supplied to
Indemnitee by the directors or officers of the Corporation or other enterprise in the course of
their duties, or on the advice of legal counsel for the Corporation or the enterprise or on
information or records given or reports made by an independent certified public accountant or by an
appraiser or other expert.

     Section 11.5. The knowledge and actions or failures to act of any other director, officer,
trustee, partner, member, fiduciary, agent or employee of the Corporation or other enterprise shall
not be imputed to Indemnitee for the purposes of determining his or her right to indemnification.

ARTICLE XII

Remedies of Indemnitee

     Section 12.1. If a determination is made that Indemnitee is not entitled to indemnification
under this Agreement, any judicial Proceeding or arbitration begun pursuant to this Agreement must
be conducted in all respects as a de novo trial or arbitration, on the merits, and Indemnitee shall
not be prejudiced by reason of the adverse determination. In such a Proceeding or arbitration,
Indemnitee is presumed to be entitled to indemnification and the Corporation has the burden of
proving Indemnitee is not entitled to be indemnified. Moreover, if at any time during the two (2)
year period prior to the date of any written application for indemnification submitted by
Indemnitee in connection with a particular Proceeding or other matter there shall have occurred a
Change of Control, the Corporation will be deemed to have satisfied such burden only if it meets
the standard of proof by clear and convincing evidence. The Corporation may not refer to or
introduce into evidence any determination made pursuant to Section 11.1 of this Agreement
adverse to Indemnitee for any purpose. If Indemnitee begins a judicial Proceeding or arbitration
seeking indemnification, Indemnitee is not required to reimburse the Corporation for any advances
pursuant to Section 8.1 of this Agreement until a final determination is made with respect
to Indemnitee’s right to indemnification, after all rights of appeal have been exhausted or lapsed.

     Section 12.2. If it has been determined that Indemnitee is entitled to indemnification, the
Corporation is bound by that determination in any judicial Proceeding or arbitration commenced by
Indemnitee seeking to compel the indemnification, absent (i) a misstatement by Indemnitee of a
material fact or an omission of a material fact necessary to make Indemnitee’s statement not
materially misleading connected with the request for indemnification (which misstatement or
omission is shown by the Corporation to be of sufficient importance that it would likely alter the
applicable determination) or (ii) a prohibition of the indemnification under applicable law. In
any Proceeding or arbitration commenced by Indemnitee seeking indemnification, the Corporation
is precluded from asserting that the procedures and presumptions of this Agreement are not valid,
binding and enforceable and must stipulate that the Corporation is bound by all the provisions of
this Agreement.

10

 

ARTICLE XIII

Contribution; Joint Liability

     Section 13.1. To the fullest extent permissible under applicable law, if the indemnification
rights provided for in this Agreement are unavailable to Indemnitee in whole or in part for any
reason whatsoever (other than by reason of the language of any express exclusion contained in this
Agreement), the Corporation, instead of indemnifying and holding harmless Indemnitee, must
contribute to the payment thereof, in the first instance, by paying the entire amount incurred by
Indemnitee, whether for judgments, liabilities, fines, penalties, amounts paid or to be paid in
settlement and/or for Expenses, in connection with any Proceeding without requiring Indemnitee to
contribute to the payment, and the Corporation hereby waives and relinquishes any right of
contribution it may have at any time against Indemnitee. The Corporation shall not enter into any
settlement of any Proceeding in which the Corporation is jointly liable with Indemnitee, or would
be joined in the Proceeding, unless the settlement provides for a full and final release of all
claims asserted against Indemnitee. The Corporation hereby agrees to fully indemnify and hold
harmless Indemnitee from any claims for contribution which may be brought by officers, directors or
employees of the Corporation other than Indemnitee who may be jointly liable with Indemnitee.

ARTICLE XIV

Subrogation

     Section 14.1. If any payment is made under this Agreement, the Corporation is subrogated to
the extent of such payment to all the rights of recovery of Indemnitee, who must within a
reasonable period of time after payment execute all papers required and take all action necessary
to secure those rights, including the execution of such documents as are necessary to enable the
Corporation to bring suit to enforce those rights.

ARTICLE XV

Severability

     Section 15.1. If any provision or provisions of this Agreement shall be held to be invalid,
illegal or unenforceable for any reason whatsoever: (a) the validity, legality and enforceability
of the remaining provisions of this Agreement (including, but not limited to, each portion of any
paragraph containing any such provision held to be invalid, illegal or unenforceable, that is not
itself held to be invalid, illegal or unenforceable) shall not in any way be affected or impaired
thereby; and (b) to the fullest extent possible, the provisions of this Agreement (including, but
not limited to, each such portion of any paragraph containing any such provision held to be
invalid, illegal or unenforceable) shall be construed so as to give effect to the intent manifested
by the provision held invalid, illegal or unenforceable.

11

 

ARTICLE XVI

Miscellaneous

     Section 16.1. Non-Exclusivity of Rights. The rights of Indemnitee under this
Agreement are not exclusive of any other rights to which Indemnitee may at any time be entitled
under the law, the Articles of Incorporation, the Bylaws or any agreement. The indemnification and
advancement of Expenses for Indemnitee who has ceased to be a director, officer, employee or agent
shall continue in full force and effect and shall inure to the benefit of the heirs, executors and
administrators of Indemnitee. The rights of Indemnitee under this Agreement shall be contract
rights. No amendment, alteration or repeal of this Agreement can limit or restrict any right of
Indemnitee under this Agreement with respect to any action taken before the amendment, alteration
or repeal. If a change in applicable law permits greater indemnification than that which would be
afforded under this Agreement, it is the intent of the Corporation that Indemnitee shall enjoy by
this Section 16.1 the greater benefits so afforded. Except as provided in this Section
16.1 with respect to changes in applicable law which broaden the right of Indemnitee to be
indemnified by the Corporation, no supplement, modification or amendment of this Agreement shall be
binding unless executed in writing by each of the parties hereto.

     Section 16.2. Acknowledgment of Certain Matters. Both the Corporation and Indemnitee
acknowledge that in certain instances, applicable law or public policy may prohibit indemnification
of Indemnitee by the Corporation under this Agreement or otherwise. Indemnitee understands and
acknowledges that the Corporation has undertaken or may be required in the future to undertake, by
the Securities and Exchange Commission, to submit the question of indemnification to a court in
certain circumstances for a determination of the Corporation’s right under public policy to
indemnify Indemnitee.

     Section 16.3. Waivers. The observance of any term of this Agreement may be waived
(either generally or in a particular instance and either retroactively or prospectively) by the
party entitled to enforce such term only by a writing signed by the party against which such waiver
is to be asserted. Unless otherwise expressly provided herein, no delay on the part of any party
hereto in exercising any right, power or privilege hereunder shall operate as a waiver thereof, nor
shall any waiver on the part of any party hereto of any right, power or privilege hereunder operate
as a waiver of any other right, power or privilege hereunder nor shall any single or partial
exercise of any right, power or privilege hereunder preclude any other or further exercise thereof
or the exercise of any other right, power or privilege hereunder.

     Section 16.4. Entire Agreement. This Agreement and the documents referred to herein
constitute the entire agreement between the parties hereto with respect to the matters covered
hereby, and any other prior or contemporaneous oral or written understandings or agreements with
respect to the matters covered hereby are superseded by this Agreement.

     Section 16.5. Certain Rights. The right to be indemnified or to the advancement or
reimbursement of Expenses (i) is intended to be retroactive and shall be available as to events
occurring prior to the date of this Agreement and (ii) shall continue after any rescission or
restrictive modification of such provisions as to events occurring prior thereto. Nothing in this
Agreement, expressed or implied, is intended to confer any rights or remedies under or by reason
of this Agreement on any person other than the parties to this Agreement and their respective
heirs, personal representatives, successors and assigns.

12

 

     Section 16.6. Governing Law; Venue. This Agreement shall be construed in accordance
with and governed by the laws of the State of Colorado without regard to any principles of conflict
of laws that, if applied, might permit or require the application of the laws of a different
jurisdiction. The parties hereby agree that any dispute that may arise between them arising out of
or in connection with this Agreement shall be adjudicated before a court located in Jefferson
County, Colorado and they hereby submit to the exclusive jurisdiction of the courts of the State
of Colorado located in Lakewood, Colorado, and of the federal courts having jurisdiction in such
district with respect to any action or legal proceeding commenced by either party, and irrevocably
waive any objection they now or hereafter may have respecting the venue of any such action or
proceeding brought in such a court or respecting the fact that such court is an inconvenient forum,
relating to or arising out of this Agreement.

     Section 16.7. Headings. The Article and Section headings in and referred to in this
Agreement are for convenience of reference only, and shall not be deemed to alter or affect the
meaning or interpretation of any provisions hereof.

     Section 16.8. Counterparts. This Agreement may be executed in counterparts, each of
which shall be deemed to be an original and all of which together shall be deemed to be one and the
same instrument.

     Section 16.9. Use of Certain Terms. As used in this Agreement, the words “herein,”
“hereof,” and “hereunder” and other words of similar import refer to this Agreement as a whole and
not to any particular paragraph, subparagraph, section, subsection, or other subdivision. Whenever
the context may require, any pronoun used in this Agreement shall include the corresponding
masculine, feminine or neuter forms, and the singular form of nouns, pronouns and verbs shall
include the plural and vice versa.

[signatures appear on following page]

13

 

     IN WITNESS WHEREOF, this Agreement has been duly executed and delivered to be effective as of
the date first above written.

	 	 	 	 	 
	 	GLOBAL MED TECHNOLOGIES, INC.

 	 
	 	By:  	
 	 
	 	 	Name:  	 	 
	 	 	Title:  	 	 
	 

	 	 	 	 	 
	 	INDEMNITEE

 	 
	 	
 	 
	 	Name:  	 	 
	 	 	 
	 

14

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