Document:

Exhibit
10.28

 

CONTRACT

 

Between Axonyx Europe, with its registered office at bilderdijkstraat
9, 2311 XD Leiden, The Netherlands and NOTOX Safety & Environmental
Research B.V., with its registered office at Hambakenwetering 7, 5231 DD
‘s-Hertogenbosch, The Netherlands.

 

Herewith NOTOX offers to perform a 104-weeks rate carcinogenicity study
with Phenserine tartrate, a compound being developed as a drug for use in the
treatment of Alzheimer’s disease.  The
study will be carried out in accordance with the respective test guidelines
(ICH) and in conformity with the OECD principles for “Good Laboratory
Practice”.

 

The study is based on the following study outline and will in detail
follow the enclosed protocol that was fully accepted by Dr. Black of Hugh E.
Black & Associates, Inc., who acts as the sponsor’s consultant in this
project.

 

Study
outline:

 

104-Weeks
oral gavage carcinogenicity study of Phenserine tartrate in Wistar Han rats.

 

	
  Number of groups:

  	
   

  	
  2 controls and 3 treatments; group housing.

  
	
  Group size:

  	
   

  	
  60 males, 60 females/ main group; 30 health check
  animals: in total 630 animals.

  
	
  Age:

  	
   

  	
  4 weeks at arrival, 6 weeks at start of dosing

  
	
  Administration:

  	
   

  	
  Daily oral gavage for 104 weeks.

  
	
  Observations:

  	
   

  	
  • Clinical
  signs daily, before and 1-2 hours after dosing.

  
	
   

  	
   

  	
  • Viability
  / mortality:  twice daily.

  
	
   

  	
   

  	
  • Weekly
  palpatation for tumours.

  
	
  Body weight / food consumption:

  	
   

  	
  Weekly during first 14 weeks and every 2 weeks
  thereafter; one week pretest.

  
	
   

  	
   

  	
   

  
	
  Ophthalmoscopy:

  	
   

  	
  15 animals / sex / group: pretest and during week
  52.

  
	
  Haematology:

  	
   

  	
  15 animals / sex / group during pretest; all animals
  killed in extremis or at terminal necropsy.

  
	
  Toxicokinetic sampling:

  	
   

  	
  At 3 time points / day at day 1, week 26 and week
  104; 4 TK-samples / sex / group / time point: 216 samples in total.

  
	
  Pathology:

  	
   

  	
  • Full
  necropsy on all animals.

  
	
   

  	
   

  	
  • Full
  histopathology on unscheduled deaths, both control groups and high dose group
  animals.  Limited histopathology on
  low and mid dose group animals killed after two years.

  

 

Toxicokinetic assessment and evaluation.

 

	
  Costs
  2-years study:

  	
   

  	
  Î  1,045,000.00

  

 

The formulations necessary for daily oral gavage of the test compound
will weekly be prepared at NOTOX.  The
formulations will be analysed according to the schedule, depicted in the study
protocol.  Blood samples taken at three
time points on three days during the study will be analysed using LC-MS/MS in
NOTOX’ bio-analytical department.  After
toxicokinetic assessment the evaluation will be included in the study report.

 

1

 

Analytical
Chemistry:

 

Formulation Analysis

 

	
  •

  	
   

  	
  Implementation and validation of an analytical
  method on HPLC (includes determination of linearity, detection limit,
  repeatability of injections and stability tests) for rat oral gavage
  formulations

  	
  Î

  	
  8,500.00

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  •

  	
   

  	
  Analyses: 
  estimated 6 occasions of analysis (Î 1,800.00 / analysis day)

  	
  Î

  	
  10,800.00

  

 

Bio-analysis

 

	
  •

  	
   

  	
  Protocol and report method development and
  validation:

  	
  Î

  	
  5,000.00

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  •

  	
   

  	
  Method development and validation in one matrix

  	
   

  	
   

  
	
   

  	
   

  	
  • parent compound only; expected work: 3-7 weeks

  	
   

  	
   

  
	
   

  	
   

  	
  • costs per week: Î 6,250.00

  	
   

  	
   

  
	
   

  	
   

  	
  • Assuming 5 weeks of development/validation:

  	
  Î

  	
  31,250.000

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  •

  	
   

  	
  Analysis of initially 216 rat samples (from dose
  group animals only; price per sample Î 90.00):

  	
  Î

  	
  19,440.00

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  •

  	
   

  	
  Protocol and report sample analysis:

  	
  Î

  	
  5,000.00

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Estimated costs analytical chemistry:

  	
  Î

  	
  79,990.00

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total
  costs (excl. V.A.T.):

  	
  Î

  	
  1,124,990.00

  

 

 

Remarks:

 

•                                          The amount of
test substance needed to carry out the study will be determined in consultation
with the sponsor.

•                                          The
prices include sampling and storage for formulation and bio-analysis.

•                                          Reserve
samples of the test and control articles (2 ml) will be taken at initiation and
after 6 months, 12 months, 18 months and at the end of the study and will be
retained until completion of the in-life phase,

•                                          30
Extra animals for health check by serology will be added to the study on NOTOX’
costs.

•                                          All
data and the final report will be submitted to the sponsor as a PDF file for
possible inclusion in an electronic submission to regulatory agencies.

•                                          Costs
are calculated assuming regular protocol and report formats.  Special requests for protocol (study design)
and report format may lead to additional costs.

•                                          Interim
results (see protocol for frequency) and a draft report will be provided
without additional costs.

 

2

 

Timelines:

 

•                                          The
method development and validation for formulation analysis will be performed
during week 19-21.  The method will be
available then in week 24, 2002.  This
schedule can be met if we have received a completed test substance data sheet,
relevant analytical information, sufficient test substance and necessary
reference compounds in week 17, 2002, at the latest.

•                                          The
method development and validation for bio-analysis will be started in week 30,
2002, assuming the necessary information and/or substances have been provided
by the sponsor in week 28, 2002, at the latest.  The validation report will be issued then at least 4 weeks before
the start of the 2-years rat study.

•                                          For
the carcinogenicity study the rats will arrive at NOTOX in the third week of
October 2002.

•                                          After
allocation and acclimitization the study will start in the first week of
November 2002.

•                                          At
the end of the study the remaining animals will be sacrificed and subjected to
pathology in November 2004.

•                                          Friday
29th April 2005 a non-QA-audited, finalised report on the
carcinogenic potential of Phenserine tartrate in rats 14 days after receipt of
all comments of NOTOX.

 

Terms of
payment and additional remarks:

 

•                                          Payment
for the carcinogenicity study should be carried out in eight terms.  The first installment of 30% of the total
estimated costs will be at acceptance of this contract.  The next installments of six times 10% each
will be divided over the project and the last 10% should be paid at receipt of
the draft report.

•                                          Payments
should be made within 14 days after the date mentioned in the respective
invoices.

•                                          By
signing this contract the sponsor also agrees to NOTOX’ general terms and
conditions.

 

Premium
–penalty settlement:

 

•                                          For
delivery of the final report before the reference date (reviewing time + 14
days after 29th April 2005) NOTOX will receive a premium amount of €
10,000.00 / week until a maximum of € 40,000.00.

•                                          For
delivery of the final report after this reference date NOTOX will pay a penalty
amount of € 5,000.00/ week until a maximum of € 40,000.00.

•                                          A
penalty will only be accepted if the delay can fully be attributed to
negligence and/or demonstrable falure by NOTOX.

•                                          A
penalty will not be accepted if the delay is caused by one or more of the
following reasons:

• The test
substance is not or not sufficient available during any moment in the study.

• Relevant
information on the analyses, toxicity pattern, etc. of the compound is not
available at NOTOX when needed.

• Unexpected
illness or deaths of rats that significantly damage the progression in the
study.

• A toxicity /
tumour pattern leading to unexpected and significantly more work during
pathology.

• A reviewing
time of the report exceeding the proposed 2 weeks (incl. transfer time).

• Extra
requests during the project that will result into extension of the reporting
period.

• The penalty
clause will not be applicable in case not all payments are received on time.

 

	
  ‘s-Hertogenbosch, 11th April 2002

  	
   

  	
   

  
	
   

  	
   

  	
  For confirmation:

  
	
  NOTOX Safety & Environmental Research B.V.

  	
   

  	
  AXONYX

  

 

 

	
   /s/ Dr.
  R.E.J. ten Berge

  	
   

  	
  /s/ Ir. J.C.M. van der Hoeven

  	
   

  	
  /s/ G.B. Bruinsma, M.D.

  	
   

  
	
  Dr. R.E.J. ten Berge

  	
  Ir. J.C.M. van der Hoeven

  	
  G.B. Bruinsma, M.D.

  
	
  Sales & Marketing Manager

  	
  Managing Director

  	
  Chief Operating Officer

  
	
  Pharmaceuticals

  	
   

  	
   

  

 

3Exhibit 10.7

 

 

AMENDMENT NO. 6 TO LOAN AGREEMENT

 

 

This Amendment No. 6 to Loan
Agreement dated as of November 6, 2002 (“Amendment”) is entered into with
reference to the Loan Agreement dated as of March 23, 1998, by and among Hard
Rock Hotel, Inc., a Nevada corporation (“Borrower”), the Lenders named therein,
and Bank of America, N.A. as Administrative Agent (as amended by an Amendment
No. 1 dated April 10, 1998, an Amendment No. 2 dated March 31, 1999, an
Amendment No. 3 dated June 30, 2000, an Amendment No. 4 dated March, 2001 and
an Amendment No. 5 dated December, 2001, the “Loan Agreement”).  The Administrative Agent, acting with the
consent of all the Lenders in accordance with the terms of the Loan Agreement,
and Borrower hereby agree as follows:

 

1.             Section 1.1-Definitions.  The following new definitions are hereby
added to Section 1.1 of the Loan Agreement.

 

“Pink Taco - L.A.”
means the Pink Taco restaurant located in Los Angeles, California.

 

“Pink
Taco Subsidiary” means a Subsidiary of Borrower formed for the purpose of
owning and operating the Pink Taco - L.A., of which the Borrower directly or
indirectly shall own not less than 80% of the equity capital interests.

 

2.             Section 6.14 - Capital Expenditures.  Section 6.14 of the Loan Agreement is hereby
amended to add new clause (c) thereto:

 

(c)           Capital Expenditures made by the Pink
Taco Subsidiary in connection with the development, design and construction of
the Pink Taco - L.A. or Capital Expenditures made by Borrower for expansion
projects to the Hard Rock Hotel in an amount not to exceed $13,000,000,
provided that the aggregate amount of Capital Expenditures made pursuant to
this clause (c) shall not exceed $7,500,000 in any Fiscal Year (or portion
thereof), provided further that not more than $2,000,000 in Capital
Expenditures not made under this clause (c) in any Fiscal Year may be expended
in the following Fiscal Year.

 

3.             Section 6.15 - Investments. Section 6.15 of the
Loan Agreement is hereby amended to add new clause (e) thereto:

 

(e)           Investments made in the Pink Taco
Subsidiary to finance Capital Expenditures made pursuant to Section 6.14(c).

 

4.             Excess Cash Flow.  Pursuant to Section 2.7 of the Loan Agreement, the Commitment was
required to have been reduced by 50% of the amount of Excess Cash flow for the
Fiscal Year ended December 31, 2001 as of September 30, 2002.  The Lenders and the Borrower (a) agree that
this reduction shall be omitted in respect of the Fiscal Year 2001 (it being
understood that Section 2.7 will apply as to any Excess Cash Flow in any
subsequent Fiscal Years), and (b) confirm that the principal amount of the
Commitment is now $34,000,000.

 

 

5.             Comment to the Formation of Pink Taco Subsidiary.
Pursuant to Section 6.16 of the Loan Accountant, the Lenders hereby consent to
the formation of the Pink Taco Subsidiary.

 

6.             Conditions Precedent.  The altered venues of this Amendment shall be conditioned upon
the receipt by the Administrative Agent of the following:

 

(a)           counterparts of this Amendment
executed by Borrower and the Administrative Agent, seeing on behalf of the
Lenders;

 

(b)           written consensus to the execution,
delivery and performance hereof from all of the Lenders; and

 

(c)           a fee of 7.5 basis points times the
amounts of Commitment ($25,500)

 

7.             Conditions Subsequent.  Concurrently with the formation of the Pink Taco Subsidiary, (a)
the Pink Taco Subsidiary will execute and deliver to Administrative Agent (i) a
guaranty of the Obligations, (ii) a security agreement and a deed of trust or
leasehold deed of trust (as appropriate) encumbering substantially all of its
assets to secure the Obligations by a first priority Lien, and (iii) such other
documents as the Administrative Agents may require, and (b) each of the owners
of equity securities in the Pink Taco Subsidiary will pledge (and thereafter
maintain in pledge) such ownership interests to the Administrative Agent
pursuant to a pledge agreement in favor of the Administrative Agent.  Each of the agreements referred to in this
Section shall be in form and substance acceptable to the Administrative Agent.

 

8.             Representation and Warranty.  Borrower represents and warrants to the
Administrative Agent and the Lenders that no Default or Event of Default has
occurred and remains continuing.

 

9.             Confirmation. 
In all other respects, the terms of the Loan Agreement and the other
Loan Documents are hereby confirmed.

 

IN WITNESS WHEREOF, the
parties hereto have caused the Amendment to be duly executed as of the date
first above written.

 

	
   

  	
  HARD ROCK HOTEL, Inc., a
  Nevada corporation

  
	
   

  	
  By: 

  	
  /s/ James D. Bowen

  
	
   

  	
  Title:

  	
   Vice President,

  
	
   

  	
   

  	
  Chief Financial Officer
  and Treasurer

  
	
   

  	
   

  	
   

  
	
   

  	
  BANK OF AMERICA, N.A., as
  Administrative Agent

  
	
   

  	
   

  	
   

  
	
   

  	
  By:

  	
   /s/ Janice Hammond

  
	
   

  	
   

  	
  Janice Hammond, Vice
  President

  

 

 

2

 

 

CONSENT OF LENDER

 

This Consent of Lender is
delivered with reference to the Loan Agreement dated as of March 23, 1998, by
and among Hard Rock Hotel, Inc., a Nevada corporation, the Lenders named
therein, and Bank of America, N.A., as Administrative Agent (as amended, the
“Loan Agreement”). Capitalized terms used but not defined herein are used with
the meanings set forth for those terms in the Loan Agreement.

 

The undersigned Lender
hereby consents to the execution, delivery and performance of the proposed
Amendment No. 6 to Loan Agreement by the Administrative Agent on behalf of the
Lenders, substantially in the form presented to the undersigned as a draft.

 

	
  Bank of America NA

  	
   

  	
   

  
	
  [Typed/Printed Name of
  Lender]

  	
   

  
	
   

  
	
  By:

  	
  /s/ Scott L. Faber

  	
   

  
	
   

  	
   

  
	
  Title:

  	
  Managing Director

  	
   

  
	
   

  	
   

  	
   

  
	
  Date:

  	
  11/12/02

  	
   

  
							

 

 

3

 

CONSENT OF LENDER

 

This Consent of Lender is
delivered with reference to the Loan Agreement dated as of March 23, 1998, by
and among Hard Rock Hotel, Inc., a Nevada corporation, the Lenders named
therein, and Bank of America, N.A., as Administrative Agent (as amended, the
“Loan Agreement”). Capitalized terms used but not defined herein are used with
the meanings set forth for those terms in the Loan Agreement.

 

The undersigned Lender
hereby consents to the execution, delivery and performance of the proposed
Amendment No. 6 to Loan Agreement by the Administrative Agent on behalf of the
Lenders, substantially in the form presented to the undersigned as a draft.

 

	
  BANK OF SCOTLAND

  	
   

  	
   

  
	
  [Typed/Printed Name of
  Lender]

  	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
   /s/ Joseph Fratus

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Title:

  	
   JOSEPH FRATUS

  	
   

  	
   

  
	
   

  	
  Vice
  President

  	
   

  	
   

  
	
  Date:

  	
   11/8/02

  	
   

  	
   

  
						

 

 

 

4

 

CONSENT OF LENDER

 

This Consent of Lender is delivered
with reference to the Loan Agreement dated as of March 23, 1998, by and among
Hard Rock Hotel, Inc., a Nevada corporation, the Lenders named therein, and
Bank of America, N.A., as Administrative Agent (as amended, the “Loan
Agreement”). Capitalized terms used but not defined herein are used with the
meanings set forth for those terms in the Loan Agreement.

 

The undersigned Lender
hereby consents to the execution, delivery and performance of the proposed
Amendment No. 6 to Loan Agreement by the Administrative Agent on behalf of the
Lenders, substantially in the form presented to the undersigned as a draft.

 

	
  Comerica West Incorporated

  	
   

  	
   

  
	
  [Typed/Printed Name of
  Lender]

  	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ Eoin P. Collins

  	
   

  	
   

  
	
   

  	
  Eoin
  P. Collins

  	
   

  
	
  Title:

  	
  Vice President

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Date:

  	
  10/13/02

  	
   

  	
   

  
						

 

 

5

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