Exhibit 10.77


 


	
  AMENDMENT OF SOLICITATION/MODIFICATION OF
  CONTRACT

  	
  1.
  CONTRACT ID CODE

  	
  PAGE OF PAGES

  
	
  

  U

  	
  

  1

  	
  

  6

  
	
  2.
  AMENDMENT/MODIFICATION NO.

  	
  3.
  EFFECTIVE DATE

  	
  4.
  REQUISITION/PURCHASE REQ. NO.

  	
  5.
  PROJECT NO.(If applicable)

  
	
  P00008

   

  	
  30-Sep-2009

  	
  SEE SCHEDULE

  	
   

  
	
  6. ISSUED BY

  	
  CODE

  	
   HDTRA1

  	
  7.
  ADMINISTERED BY (If other than item 6)

  	
  CODE

  	
   S2401A

  
	
   

  	
   

  	
       DEFENSE CONTRACT MANAGEMENT AGENCY

  	
   

  	
   

  
	
       DEFENSE THREAT REDUCTION AGENCY/BE-BC

  	
       1
  FEDERAL DRIVE, ROOM 1150

  	
   

  
	
       8725 JOHN J. KINGMAN ROAD, MSC 6201

  	
       FORT
  SNELLING MN 55111-4080

  	
   

  
	
       FORT SELVOIR VA 22060-6201

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  8. NAME AND ADDRESS OF
  CONTRACTOR (No., Street, County, State and Zip Code)

  	
   

  	
  9A. AMENDMENT OF
  SOLICITATION NO.

  
	
       AVI
  BIOPHARMA INC.

  	
   

  	
   

  
	
       J. DAVID BOYLE II

  	
   

  	
  9B. DATED (SEE ITEM 11)

  
	
       4575 SWRESEARCH WAY STE 200

  	
   

  	
   

  
	
       CORVALLIS
  OR 97333-1299

  	
  x

  	
  10A. MOD. OF
  CONTRACT/ORDER NO.

  HDTRA1-07-C-0010

  
	
   

  	
   

  	
  10B. DATED (SEE ITEM 13)

  
	
  CODE    49WU1

  	
  FACILITY CODE

  	
  x

  	
  29-Nov-2006

  
	
   

  11. THIS ITEM
  ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

   

  
	
  o

  	
  The above numbered
  solicitation is amended as set forth in Item 14. The hour and date specified
  for receipt of Offer

  	
  o is extended,

  	
  o is not extended.

  
	
   

  	
   

  Offer must acknowledge
  receipt of this amendment prior to the hour and date specified in the
  solicitation or as amended by one of the following methods:

  (a) By completing
  Items 8 and 15, and returning               copies of the amendment; (b) By
  acknowledging receipt of this amendment on each copy of the offer submitted; or
  (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers.
  FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE
  RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN
  REJECTION OF YOUR OFFER. Ifby virtue of this amendment you desire to change
  an offer already submitted, such change may be made by telegram or letter,
  provided each telegram or letter makes reference to the solicitation and this
  amendment, and is received prior to the opening hour and date specified.

  
	
   

  12. ACCOUNTING AND
  APPROPRIATION DATA (If required)

        See Schedule

  
	
   

  13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF
  CONTRACTS/ORDERS,

  IT MODIFIES THE
  CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

   

  
	
  o

  	
  A.  THIS CHANGE ORDER IS ISSUED PURSUANT TO:
  (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT
  ORDER NO. IN ITEM 10A.

  
	
  o

  	
  B.  THE ABOVE NUMBERED CONTRACT/ORDER IS
  MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying
  office, appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE
  AUTHORITY OF FAR 43.103(B).

  
	
  x

  	
  C.  THIS
  SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

  52.243-2 ALTV Changes

  
	
  o

  	
  D.  OTHER
  (Specify type of modification and authority)

   

  
	
  E.   IMPORTANT:    Contractor    o    
  is not,   x    
  is required to sign this document and return        1     
    copies to the issuing office.

  
	
  14. DESCRIPTION
  OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including
  solicitation/contract subject matter where feasible.)

  
	
   

  	
  Modification Control
  Number:      pottst092379

  
	
  The
  purpose of this modification is to add tasking to the Statement of Work and
  to add incremental funding in the amount of $5,601,194.00

  
	
   

  
	
   

  
	
   

  
	
   

  
	
  Except as provided
  herein, all terms and conditions of the document referenced in Item 9A or
  10A, as heretofore changed, remains unchanged and in full force and effect.

  
	
  15A. NAME AND TITLE OF
  SIGNER (Type or print)

  	
  16A. NAME AND TITLE OF
  CONTRACTING OFFICER (Type or print)

  
	
   

  	
  Terese M Herston Contracting
  Officer Defense Threat Reduction Agency

  
	
  /s/
  J. David Boyle II

  	
  TEL:  

  	
  EMAIL:  

  
	
  15B. CONTRACTOR/OFFEROR

  	
  15C. DATE SIGNED

  	
  16B. UNITED STATES OF
  AMERICA

  	
  16C. DATE SIGNED

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  /s/ J. David
  Boyle II

  	
   

  	
   

  	
   

  	
  BY  /s/ Terese
  M. Herston

  	
   

  	
   

  
	
   

  	
  (Signature of
  person authorized to sign)

  	
   

  	
  9/30/2009

  	
   

  	
  (Signature
  of Contracting Officer)

  	
   

  	
  9/30/2009

  
	
  EXCEPTION TO SF 30

  	
  30-105-04

  	
  STANDARD FORM 30
  (Rev. 10-83)

  
	
  APPROVED BY OIRM 11-84

  	
   

  	
  Prescribed by GSA

  
	
   

  	
   

  	
  FAR (48 CFR) 53.243

  
																										



 

















 


	
  AMENDMENT OF SOLICITATION/MODIFICATION OF
  CONTRACT

  	
  1.
  CONTRACT ID CODE

  	
  PAGE OF PAGES

  
	
  

  U

  	
  

  1

  	
  

  6

  
	
  2.
  AMENDMENT/MODIFICATION NO.

  	
  3.
  EFFECTIVE DATE

  	
  4.
  REQUISITION/PURCHASE REQ. NO.

  	
  5.
  PROJECT NO.(If applicable)

  
	
  P00008

   

  	
  30-Sep-2009

  	
  SEE SCHEDULE

  	
   

  
	
  6. ISSUED BY

  	
  CODE

  	
   HDTRA1

  	
  7.
  ADMINISTERED BY (If other than item 6)

  	
  CODE

  	
   S2401A

  
	
   

  	
   

  	
       DEFENSE CONTRACT MANAGEMENT AGENCY

  	
   

  	
   

  
	
       DEFENSE THREAT REDUCTION AGENCY/BE-BC

  	
       1
  FEDERAL DRIVE, ROOM 1150

  	
   

  
	
       8725 JOHN J. KINGMAN ROAD, MSC 6201

  	
       FORT
  SNELLING MN 55111-4080

  	
   

  
	
       FORT BELVOIR VA 22060-6201

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  8. NAME AND ADDRESS OF
  CONTRACTOR (No., Street, County, State and Zip Code)

  	
   

  	
  9A. AMENDMENT OF
  SOLICITATION NO.

  
	
       AVI
  BIOPHARMA INC.

  	
   

  	
   

  
	
       J. DAVID BOYLE II

  	
   

  	
  9B. DATED (SEE ITEM 11)

  
	
       4575 SWRESEARCH WAY STE 200

  	
   

  	
   

  
	
       CORVALLIS
  OR 97333-1299

  	
  x

  	
  10A. MOD. OF
  CONTRACT/ORDER NO.

  HDTRA1-07-C-0010

  
	
   

  	
   

  	
  10B. DATED (SEE ITEM 13)

  
	
  CODE    49WU1

  	
  FACILITY CODE

  	
  x

  	
  29-Nov-2006

  
	
   

  11. THIS ITEM
  ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

   

  
	
  o

  	
  The above numbered
  solicitation is amended as set forth in Item 14. The hour and date specified
  for receipt of Offer

  	
  o is extended,

  	
  o is not extended.

  
	
   

  	
   

  Offer must acknowledge
  receipt of this amendment prior to the hour and date specified in the
  solicitation or as amended by one of the following methods:

  (a) By completing
  Items 8 and 15, and returning               copies of the amendment; (b) By
  acknowledging receipt of this amendment on each copy of the offer submitted; or
  (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers.
  FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE
  RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN
  REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change
  an offer already submitted, such change may be made by telegram or letter,
  provided each telegram or letter makes reference to the solicitation and this
  amendment, and is received prior to the opening hour and date specified.

  
	
   

  12. ACCOUNTING AND
  APPROPRIATION DATA (If required)

        See Schedule

  
	
   

  13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF
  CONTRACTS/ORDERS,

  IT MODIFIES THE
  CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

   

  
	
  o

  	
  A.  THIS CHANGE ORDER IS ISSUED PURSUANT
  TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT
  ORDER NO. IN ITEM 10A.

  
	
  o

  	
  B.  THE ABOVE NUMBERED CONTRACT/ORDER IS
  MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying
  office, appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE
  AUTHORITY OF FAR 43.103(B).

  
	
  x

  	
  C.  THIS
  SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

  52.243-2 ALTV Changes

  
	
  o

  	
  D.  OTHER
  (Specify type of modification and authority)

   

  
	
  E.   IMPORTANT:    Contractor    o     is not,   x    
  is required to sign this document and return        1        copies to the issuing office.

  
	
  14. DESCRIPTION
  OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including
  solicitation/contract subject matter where feasible.)

  
	
   

  	
  Modification Control
  Number:      pottst092379

  
	
  The
  purpose of this modification is to add tasking to the Statement of Work and
  to add incremental funding in the amount of $5,601,194.00

  
	
   

  
	
   

  
	
   

  
	
   

  
	
  Except as provided
  herein, all terms and conditions of the document referenced in Item 9A or
  10A, as heretofore changed, remains unchanged and in full force and effect.

  
	
  15A. NAME AND TITLE OF
  SIGNER (Type or print)

  	
  16A. NAME AND TITLE OF
  CONTRACTING OFFICER (Type or print)

  
	
   

  	
  TERESE HERSTON/CONTRACT
  SPECIALIST

  
	
   

  	
  TEL:  703-767-4257

  	
  EMAIL:  terese.herston@dtra.mil

  
	
  15B. CONTRACTOR/OFFEROR

  	
  15C. DATE SIGNED

  	
  16B. UNITED STATES OF
  AMERICA

  	
  16C. DATE SIGNED

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  BY  /s/ Terese
  M. Herston

  	
   

  	
   

  
	
   

  	
  (Signature of
  person authorized to sign)

  	
   

  	
   

  	
   

  	
  (Signature
  of Contracting Officer)

  	
   

  	
  30-Sep-2009

  
	
  EXCEPTION TO SF 30

  	
  30-105-04

  	
  STANDARD FORM 30
  (Rev. 10-83)

  
	
  APPROVED BY OIRM 11-84

  	
   

  	
  Prescribed by GSA

  
	
   

  	
   

  	
  FAR (48 CFR) 53.243

  
																										



 
















 


HDTRA1-07-C-0010


P00008


Page 2
of 6


 


SECTION SF
30 BLOCK 14 CONTINUATION PAGE


 


SUMMARY OF CHANGES


 


SECTION A
- SOLICITATION/CONTRACT FORM


 


The
total cost of this contract was increased by $11,520,901.97 from $33,838,652.20
to $45,359,554.17.


The
number of invoices to be submitted has decreased by 3 from 4 to 1.


The
discount terms Net 30 Days has been added.


 


SECTION B
- SUPPLIES OR SERVICES AND PRICES


 


CLIN
0001


 


The CLIN extended description has changed from A New
Antiviral (AntiSense) Platform Targeting Hemorrhagic Fever Viruses and Models
of Antibotic-Resistant Intracellular Bacterial Pathogens in accordance with the
attached Statement of Work dated November 21, 2006 to A New Antiviral
(AntiSense) Platform Targeting Hemorrhagic Fever Viruses and Models of
Antibotic-Resistant Intracellular Bacterial Pathogens in accordance with the
attached Statement of Work dated November 21, 2006 and revised Statement
of Work dated September 29, 2009..


 


The
estimated/max cost has increased by $10,719,046.93 from $25,957,424.00 to
$36,676,470.93. 


The
fixed fee has increased by $801,855.04 from $2,076,594.00 to $2,878,449.04.


The
total cost of this line item has increased by $11,520,901.97 from
$28,034,018.00 to $39,554,919.97.


 


SUBCLIN
000105 is added as follows:


 


	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES

  	
   

  	
  QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT
  PRICE

  	
   

  	
  AMOUNT

  	
   

  
	
  000105

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  0.00

  	
   

  
	
   

  	
   

  	
  Funding

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPFF

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB:
  Destination

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  ESTIMATED COST

  	
   

  	
  $

  	
  0.00

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  FIXED FEE

  	
   

  	
  $

  	
  0.00

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  TOTAL EST COST + FEE

  	
   

  	
  $

  	
  0.00

  	
   

  
	
   

  	
   

  	
  ACRN
  AF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CIN:
  CBM090013892000105

  	
   

  	
   

  	
   

  	
  $

  	
  5,601,194.00

  	
   

  



 


The
following have been modified:


 


252.232-9000       CONTRACT
FUNDING PROFILE (OCT 1998)


 


2

















 


HDTRA1-07-C-0010


P00008


Page 3
of 6


 


Subject
to FAR Clause 52.232-22, Limitation of Funds, the amount of $39,439,846.20 is
obligated for work to be performed during the period beginning with contract
award and continuing through September 29, 2010.


 


(End
of clause)


 


252.232-9001           PRICES/COST


 


a.
Subject to the provisions of the Clauses of this Contract entitled LIMITATION
OF FUNDS, ALLOWABLE COST AND PAYMENT, and FIXED FEE, the total allowable cost
under this Contract shall not exceed $42,078,432.93,
which is the total estimated cost of the Contractor’s performance hereunder,
exclusive of fixed fee. In addition, the Government shall pay the Contractor a
fixed fee of $3,281,121 for the performance of this Contract. It is
understood and agreed that the Government’s obligation is limited to
INCREMENTAL FUNDING in the amount of $39,439,846.20
Within this amount ($39,439,846.20)
 the fixed fee shall bear the same relationship
to the total fixed fee, as the costs incurred bear to the total estimated cost.


 


b.
Interim payment vouchers may be submitted for provisional payment pursuant to
the Clauses of this Contract entitled ALLOWABLE COST AND PAYMENT and FIXED FEE.


 


SECTION E
- INSPECTION AND ACCEPTANCE


 


The
following Acceptance/Inspection Schedule was added for SUBCLIN 000105:


 


	
  INSPECT
  AT

  	
   

  	
  INSPECT BY

  	
   

  	
  ACCEPT AT

  	
   

  	
  ACCEPT BY

  
	
  N/A

  	
   

  	
  N/A

  	
   

  	
  N/A

  	
   

  	
  Government

  



 


SECTION F
- DELIVERIES OR PERFORMANCE


 


The
following Delivery Schedule item for CLIN 0001 has been changed from:


 


	
  DELIVERY
  DATE

  	
   

  	
  QUANTITY

  	
   

  	
  SHIP TO ADDRESS

  	
   

  	
  UIC

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  POP
  30-NOV-2006 TO 

  31-MAY-2009

  	
   

  	
  N/A

  	
   

  	
  DEFENSE
  THREAT REDUCTION 

  AGENCY/RD-CBM
  

  ROBERT
  KIMBROUGH  

  8725
  JOHN J KINGMAN ROAD, MAIL 

  STOP
  6201,  

  FORT
  BELVOIR VA 22060  

  703-767-2346
  

  FOB:
  Destination

  	
   

  	
  HDTRA1

  



 


To:


 


	
  DELIVERY
  DATE

  	
   

  	
  QUANTITY

  	
   

  	
  SHIP TO ADDRESS

  	
   

  	
  UIC

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  POP
  30-NOV-2006 TO 

  28-FEB-2011

  	
   

  	
  N/A

  	
   

  	
  DEFENSE
  THREAT REDUCTION 

  AGENCY/RD-CBM
  

  SEE
  SEPARATE LETTER  

  8725
  JOHN J KINGMAN ROAD, MAIL 

  STOP
  6201,  

  FORT
  BELVOIR VA 22060  

  FOB:
  Destination

  	
   

  	
  HDTRA1

  



 


3

















 


HDTRA1-07-C-0010


P00008


Page 4 of 6


 


SECTION G
- CONTRACT ADMINISTRATION DATA


 


Accounting
and Appropriation


 


Summary
for the Payment Office


 


As
a result of this modification, the total funded amount for this document was
increased by $5,601,194.00 from $33,838,652.20 to $39,439,846.20.


 


SUBCLIN
000105:


Funding
on SUBCLIN 000105 is initiated as follows:


 


ACRN:
AF


 


CIN:
CBM090013892000105


 


Acctng
Data: 9790400.2620 1000 B63D 255999 BD29576000 S49012


 


Increase:
$5,601,194.00


 


Total:
$5,601,194.00


 


The
following have been deleted:


 




	
  252.232-9002

  	
   

  	
  Accounting
  and Appropriation Data

  	
   

  	
  AUG
  2001

  






 


SECTION H - SPECIAL CONTRACT REQUIREMENTS


 


The
following have been deleted:


 


INDIRECT COST CEILING


 


SECTION I
- CONTRACT CLAUSES


 


The
following have been added by reference:


 




	
  252.211-7003

  	
   

  	
  Item
  Identification and Valuation

  	
   

  	
  AUG
  2008

  






 


4
















 


HDTRA1-07-C-0010

P00008

Page 5 of 6




	
  252.211-7007

  	
  Reporting
  of Government-Furnished Equipment in the DoD

  Item Unique Identification (IUID) Registry

  	
  NOV
  2008

  
	
  252.215-7004
  Alt I

  	
  Excessive
  Pass-Through Charges - Alternate I

  	
  MAY 2008

  



 


The
following have been added by full text:


 


252.216-9003
CONSULTANTS (OCT 1998)


 


Services
of consultants shall be at rates and for periods approved in advance by the
Contracting Officer. Requests for approval shall be submitted to the
Contracting Officer sufficiently in advance of the need to use a consultant
under this Contract. The request shall include (a) a copy of the proposed
consultant agreement, (b) a brief biography of the consultant, and (c) an
indication of the area(s) in which consultant’s expertise will be utilized
and why it is essential for contract performance. In addition, significant
deviations from the dollar amount approved for consultant services, or changes
in the consultants to be utilized, must likewise be approved in advance upon
submission of adequate justification.


 


252.216-9005
PROFIT OR FEE ON TRAVEL COSTS (JUL 2008)


 


Travel shall not be a profit or fee bearing cost element.


 


(End of clause)


 


252.245-9000
Government Property (AUG 2009)


 


(a)   In accordance with FAR 52.245-1 (b), Property
Management, and FAR 52.245-1 (f), Contractor Plans and Systems, the Contractor
shall have a system to manage (control, use, preserve, protect, repair and
maintain) Government property in its possession.


 


(b)   The Contract Data Requirements Lists (CDRLs)
associated with the Property for this Contract are contained in Exhibit “A”
and included in Section J of this contract. The spreadsheet required by
the CDRL entitled “Master Government Property List (MGPL) will be incorporated
in Section J of this contract.


 


(c)   The Contractor shall provide to the
Government an updated MGPL according to the CDRL.


 


(d)   The Government Site Visits/Physical Inventory
— The DTRA will annually verify the Property in the Possession of the
Contractor. The Contactor’s Point of Contact shall coordinate with the Program
Manager/Contracting Officer Representative or DTRA Accountable Property Officer
(APO) on prearranged site visits upon request.


 


(e)   The Contractor shall annually conduct and
provide to the DTRA a physical inventory report of ALL Government Property in
its possession according to the Master Government Property List (Physical
Inventory) CDRL.


 


(f)    The physical inventory report shall be
validated/confirmed via signature by both the Contractor’s Property
Administrator and the DTRA’s Government Representative (i. e. COR, APO, etc.).
Inventory discrepancies must be reported immediately to the Contracting
Officer, COR/Program Manager and resolved by the DTRA APO.


 


5

















 


HDTRA1-07-C-0010

P00008

Page 6 of 6




(g)   The Contractor shall provide all CDRL reports
to the Government electronically in a spreadsheet using Microsoft Office Excel.
Unless otherwise specified, the contractor shall submit all data through the
IUID Registry.


 


(End of Clause)


 


The following have been
deleted:


 


	
  252.247-9000

  	
  Government Contractor
  Travel

  	
  JUL 2007

  



 


(End of Summary of
Changes)


 


6

















 


	
  SECTION
  J – EXHIBIT A

  	
  CONTRACT
  #:  HDTRA1-07-C-0010

  



 


Contract Data Requirement List (CDRL) Supplement


 


Distribution
Addresses:


 


CDRL ADDRESS LIST


 


	
  OFFICE
  SYMBOL

  	
  ADDRESS

  
	
   

  	
   

  
	
  DTRA/BE-BL

  	
  8725
  John J Kingman Road

  
	
   

  	
  Fort
  Belvoir, VA 22060-6201

  
	
   

  	
  First name. Last name@dtra.mil

  
	
   

  	
   

  
	
  DTRA/BE-BF

  	
  8725
  John J Kingman Road

  
	
   

  	
  Fort
  Belvoir, VA 22060-6201

  
	
   

  	
  First name. Last name@dtra.mil

  
	
   

  	
   

  
	
  DTRA/BE-BC

  	
  8725
  John J Kingman Road

  
	
   

  	
  Fort
  Belvoir, VA 22060-6201

  
	
   

  	
  First name. Last name@dtra.mil

  
	
   

  	
   

  
	
  DTRA/BE-BI

  	
  8725
  John J Kingman Road

  
	
   

  	
  Fort
  Belvoir, VA 22060-6201

  
	
   

  	
  First name. Last name@dtra.mil

  
	
   

  	
   

  
	
  DTRA/COR

  	
  8725
  John J Kingman Road

  
	
   

  	
  Fort
  Belvoir, VA 22060-6201

  
	
   

  	
  First name. Last name@dtra.mil

  



 


CDRL EXHIBIT A

TABLE OF CONTENTS


 


	
   

  	
   

  	
  AUTHORITY

  	
   

  	
   

  
	
  CDRL

  	
   

  	
  REQUIRING OFFICE

  	
   

  	
  TITLE/SUBTITLE

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  A
  001

  	
   

  	
  DI-MGMT-80269

  	
   

  	
  MASTER
  GOVERNMENT PROPERTY LIST LOGISTICS

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  A
  002

  	
   

  	
  DI-MGMT-80441
  LOGISTICS

  	
   

  	
  MASTER
  GOVERNMENT PROPERTY LIST — PHYSICAL INVENTORY

  



 


BE-BC SOP 09-03 Enclosure 1


 


1

















 


SECTION J – EXHIBIT A


 


	
  CONTRACT
  DATA REQUIREMENTS LIST

  (1 Data item)

  	
  Form Approved

  OMB No. 0704-0188

  
	
   

  	
   

  
	
  Public reporting burden
  for this collection of information is estimated to average 110 hours per
  response, including the time for reviewing instructions, searching existing
  data sources, gathering and maintaining the data needed, and completing and
  reviewing the collection of information. Send comments regarding thus burden
  estimate or any other aspect of this collection o f information, including
  suggestions for reducing this burden, to Department of Defense, Washington
  Headquarters Services, Directorate for Information Operations and Reports,
  1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and
  to the Office of Management and Budget. Paperwork Reduction Project
  (0704-0188), Washington, DC 20503. Please DO NOT RETURN your form to either
  of these addresses. Send completed form to the Government Issuing Contracting
  Officer for the Contract|PR No. listed in Block E.

  
	
   

  
	
  A.
  CONTRACT LINE ITEM NO.

   

  0002

  	
  B.
  EXHIBIT

   

  	
  C. CATEGORY:

   

  TDP            TM            OTHER                                               

   

  
	
  D.
  SYSTEM|ITEM

   

  	
  E.
  CONTRACT/PR NO.

   

  HDTRA
  1-07-C-0010

  	
  F.
  CONTRACTOR

   

  AVI
  BioPharma

  
	
   

  	
   

  	
   

  
	
  1.
  DATA ITEM NO.

   

  A001

  	
  2.
  TITLE OF DATA ITEM

   

  Master
  Government Property List

  	
  3.
  SUBTITLE

   

  GFP,
  GFE, GFM, and Contractor

  Acquired
  Property)

  
	
   

  	
   

  	
   

  
	
  4.
  AUTHORITY  (Data Acquisition
  Document No.)

   

  DI-MGMT-80269

  	
  5.
  CONTRACT REFERENCE

   

  SOW
  PARA

  	
  6.
  REQUIRING OFFICE

   

  DTRA/BE-BL

  
	
   

  	
   

  	
   

  
	
  7.
  DD 250 REQ

   

  	
  9.
  DIST STATEMENT REQUIRED



  	
  10.
  FREQUENCY

   

  SEE
  BLOCK 16

   

  	
  12.
  DATE OF FIRST SUBMISSION

   

  SEE
  BLOCK 16

  	
  14.          DISTRIBUTION

   

  
	
  a. ADDRESSEE

  	
  b. COPIES

  
	
  8.
  APP CODE

   

  	
  11.
  AS OF DATE

   

  SEE
  BLOCK 16

  	
  13.
  DATE OF SUBSEQUENT SUBMISSION

  SEE
  BLOCK 16

  	
  DRAFT

  	
  FINAL

   

  
	
  Reg

  	
  Repro

  
	
  16.
  REMARKS

   

  BLOCK
  4: This DID is for reference only. The report shall be prepared according to
  the remarks below.

  BLOCK
  10: Monthly

  BLOCK
  11: Award of Contract/Task Order

  BLOCK
  12: 45th calendar day following Contract/Task Order
  award

  BLOCK
  13: Tenth calendar day of each month

   

  Remarks: During
  performance of the Contract, the Contractor may purchase material or
  equipment using government Funds [Contractor Acquired Property (CAP) ] if
  approved by Contract Officer. The Contractor shall provide a Master
  Government Property List (MGPL), inclusive of all CAP, on the 45 th calendar day
  following Contract/Task Order award and the tenth calendar day of each
  subsequent month.

   

  The Master Government
  Property List shall include all equipment/property provided to the contract,
  including equipment transferred between projects, broken and obsolete
  equipment, and items purchased outside the United States. The Master
  Government Property List shall consist of the following data elements at a
  minimum: Accountable Contract/Task Order Number, Original Manufacturer’s Name
  Noun Name Description/Commercial Use, Original Manufacturer’s
  Part Number, Model Number, Serial Number, DTRA Asset ID #, Equipment
  Identification Number Quantity, Task Order to which equipment is assigned,
  Work Breakdown Schedule (WBS) Project Number, Item Unique Identifier or
  equivalent, Project Descriptor, Equipment Location, Date Placed in Service,
  Condition of Property, Status (active, stored, in-transit or waiting
  disposal), Government Property Type [Government Furnished Equipment (GFE),
  Government Furnished Material (GFM), Government Furnished Property (GFP),
  Contractor Acquired Property (CAP) ], Unit Acquisition Cost (From Accounting
  System) and Remarks.

   

  The Master Government
  Property List shall be delivered electronically in a spreadsheet using
  Microsoft Office Excel. Abbreviations are not allowed.

   

  Ninety (90) days
  prior to Contract expiration, the Contractor shall submit a final Master
  Government Equipment List suitable for close-out purposes containing
  use/disposition recommendations.

  	
  DTRA/BE-BL

  	
   

  	
   

  	
   

  
	
  DTRA/BE-BF

  	
   

  	
   

  	
   

  
	
  DTRA/BE-BI

  	
   

  	
   

  	
   

  
	
  DTRA/BE-BC

  	
   

  	
   

  	
   

  
	
  DTRA/COR

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  15.
  Total

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  G.
  PREPARED BY

  	
  H. DATE

  	
  I.
  APPROVED BY

  	
  J. DATE

  
														



 


	
  17. PRICE GROUP

  
	
  18. ESTIMATED TOTAL PRICE

  



 


DD FORM 1423-1,
JUN 90 (EG)                     Previous
editions are obsolete         Page       1              of            1              Pages


 


BE-BC SOP 09-03 Enclosure 1


 


2

















 


SECTION J – EXHIBIT A


 


	
  CONTRACT
  DATA REQUIREMENTS LIST

  (1 Data item)

  	
  Form Approved

  OMB No. 0704-0188

  
	
   

  	
   

  
	
  Public reporting burden
  for this collection of information is estimated to average 110 hours per
  response, including the time for reviewing instructions, searching existing
  data sources, gathering and maintaining the data needed, and completing and
  reviewing the collection of information. Send comments regarding thus burden
  estimate or any other aspect of this collection o f information, including
  suggestions for reducing this burden, to Department of Defense, Washington
  Headquarters Services, Directorate for Information Operations and Reports,
  1215 Jefferson Davis Highway, Suite 1204, Adington, VA 22202-4302, and
  to the Office of Management and Budget. Paperwork Reduction Project
  (0704-0188), Washington, DC 20503. Please DO NOT RETURN your form to either of
  these addresses. Send completed form to the Government Issuing Contracting
  Officer for the Contract|PR No. listed in Block E.

  
	
   

  	
   

  	
   

  
	
  A.
  CONTRACT LINE ITEM NO.

   

  0002

  	
  B.
  EXHIBIT

   

  	
  C. CATEGORY:

   

  TDP            TM            OTHER                                               

   

  
	
  D.
  SYSTEM|ITEM

   

  	
  E.
  CONTRACT/PR NO.

   

  HDTRA
  1-07-C-0010

  	
  F.
  CONTRACTOR

   

  AVI
  BioPharma

  
	
   

  	
   

  	
   

  
	
  1.
  DATA ITEM NO.

   

  A002

  	
  2.
  TITLE OF DATA ITEM

   

  Master
  Government Property.— Physical 

  Inventory

  	
  3.
  SUBTITLE

   

  GFP,
  GFE, GFM, and Contractor 

  Acquired Property)

  
	
   

  	
   

  	
   

  
	
  4.
  AUTHORITY  (Data Acquisition
  Document No.)

   

  DI-MGMT-80441

  	
  5.
  CONTRACT REFERENCE

   

  SOW
  PARA

  	
  6.
  REQUIRING OFFICE

   

  DTRA/BE-BL

  
	
   

  	
   

  	
   

  
	
  7.
  DD 250 REQ

   

  	
  9.
  DIST STATEMENT REQUIRED

   

   

  	
  10.
  FREQUENCY

   

  SEE
  BLOCK 16

  	
  12.
  DATE OF FIRST SUBMISSION

   

  SEE
  BLOCK 16

  	
  14.          DISTRIBUTION

   

  
	
  a. ADDRESSEE

  	
  b. COPIES

   

  
	
  8.
  APP CODE

  A

  	
  11.
  AS OF DATE

   

  SEE
  BLOCK 16

  	
  13.
  DATE OF SUBSEQUENT SUBMISSION

  SEE
  BLOCK 16

  	
  DRAFT

  	
  FINAL

   

  
	
  Reg

  	
  Repro

  
	
  16.
  REMARKS

   

  BLOCK 4: This DID is for
  reference only. The report shall be prepared according

  to the remarks below.

  BLOCK 10: Annually

  BLOCK 11: Award of
  Contract/Task Order

  BLOCK 12: 1 Month after
  Contract/Task Order Award

  BLOCK 13: Annually

   

  Remarks: The Contractor shall annually perform, record and disclose
  physical inventory results of all Contractor Acquired Property in the
  Contractor’s possession. This report shall include ALL Government
  Property/Contractor Acquired Property/Equipment/Material. A final coordinated
  physical inventory shall be performed upon contract completion or termination
  and approved by the DTRA Accountable Property Officer.

   

  The physical inventory
  report shall identify the Contractor’s Point of Contact with telephone number
  and signature and the following data elements at a minimum: Accountable
  Contract/Task Order Number, Original Manufacturer’s Name,
  Description/Commercial Use, Original Manufacturer’s Part-Number, Model Number, Serial Number, DTRA Asset ID #,
  Equipment Identification Number, Quantity, Task Order to which equipment is
  assigned, Work Breakdown Schedule (WBS) Project Number, Item Unique
  Identifier or equivalent, Project Descriptor, Equipment Location, Date Placed
  in Service, Condition of Property, Status (active, stored, in-transit or
  waiting disposal), Government Property Type [Government Furnished Equipment
  (GFE), Government Furnished Material (GFM), Government Furnished Property
  (GFP), Contractor Acquired Property (CAP) ], Unit Acquisition Cost (From
  Accounting System), and Remarks.

   

  The physical inventory
  report shall be documented ih writing and validated/confirmed, via signature,
  by both the Contractor’s Property Administrator and the DTRA’s Government
  Representative. Inventory discrepancies must be reported immediately to the
  Contracting Officer, Contracting Officer Representative/Program Manager or DTRA
  Accountable Property Officer. The report shall contain original signatures
  with spreadsheet attachments and be delivered electronically in a spreadsheet
  using Microsoft Office Excel. Abbreviations are not allowed.

   

  Ninety (90) days prior
  to Contract expiration, the Contractor shall submit a final property
  identification listing suitable for close-out purposes containing
  use/disposition recommendations. The report must be reviewed,approved and
  signed by the DTRA Accountable Property Officer prior to contract close out.

   

  	
  DTRA/BE-BL

  	
   

  	
   

  	
   

  
	
  DTRA/BE-BF

  	
   

  	
   

  	
   

  
	
  DTRA/BE-BI

  	
   

  	
   

  	
   

  
	
  DTRA/BE-BC

  	
   

  	
   

  	
   

  
	
  DTRA/COR

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  15.
  Total

  	
   

  	
   

  	
   

  
	
  G.
  PREPARED BY

  	
  H. DATE

  	
  I.
  APPROVED BY

  	
  J. DATE

  
														



 


	
  17. PRICE GROUP

  
	
  18. ESTIMATED TOTAL PRICE

  



 


DD FORM 1423-1, JUN 90 (EG)                     Previous
editions are obsolete         Page       1              of            1              Pages


 


BE-BC SOP 09-03 Enclosure 1


 


3






 












 


Statement of Work


 


A New Antiviral (AntiSense) Platform Targeting
Hemorrhagic Fever Viruses


 


November 21, 2006


 


1.0          Objective:


 


The objective is to show a new capability of identifying
potential target countermeasures to specific Category A and B threat agents
rapidly (weeks to months), then producing and testing them in animals. The
compounds have broad spectrum capability against the threat agents, whether
naturally occurring or genetically engineered. AVI BioPharma proposes advanced
applied research with its unique Phosphorodiamidate Morpholino Oligomers
(PMOs), to demonstrate their safety and efficacy, as well as their
unprecedented agility for rapid development and production of countermeasures
for a broad spectrum of extant and emergent biothreat agents.


 


2.0          Scope:


 


This proposal builds on two key elements of AVI BioPharma’s
third generation antisense compounds designed against hemorrhagic threat
agents, specifically the filoviruses Ebola and Marburg, as well as arenavirus.
The Scripps Research Institute, within the last month, reported dramatic
success against arenaviruses, specifically the Junin virus vaccine strain, in
cell culture with AVI’s PMOs. This Phase has two Parts, each with a number of
tasks and subtasks.


 


First, the PMOs are targeted against highly conserved
nucleotide sequences of the viral genomes (RNA). Once species and strain and
genomic makeup of a virus are known, AVI scientists are able to categorize a
series of potential treatment compounds within several weeks or months. This correlates
well with the concept of developing countermeasures very rapidly against
unknown genetically engineered threats. Properly designed PMOs can be targeted
against a family of related viruses (multiple strains), empowering them as a
broad spectrum countermeasure for a particular threat category.


 


The second aspect of the proposal brings AVI’s already
successful work with USAMRIID on Ebola and Marburg viruses through IND and
Phase 1 safety trials. It also prepares, with the Department of Defense,
establishment of Emergency Use Authorizations for therapeutic use of these
compounds. The proposal will include a roadmap for the capability to ramp up
production to 20,000 doses of selected compound(s), should the government
desire to do so. The proposal builds this methodology for production and will
provide the initial capability to begin with a small run of 1000 doses.


 


AVI acknowledges existence of export control laws related
to export of, and foreign access to, USG-funded technology development and will
take measures to comply with same upon contract execution.


 


1

















 


A detailed spreadsheet of AVI Direct Labor Costs is
submitted in Excel file format along with this SOW, in a file called “BAA I
revised budget shell detail071906 for submission”. Discussion of subcontractor
efforts in the areas of fill/finish, USAMRIID, TSRI, NHP tox/pk, and Tessarae
appear as Appendix A.


 


3.0          Background


 


AVI’s PMOs have been extensively tested against a variety
of infectious disease agents and against other common illnesses. These
compounds have successfully been utilized in animals and humans with
exceptional safety results, which portends well for future success when applied
broadly to human disease. AVI has nearly 12 years of experience in the area of
developing antisense compounds and an impressive array of successes. AVI has
moved well beyond the current siRNAs target gene interference work being
accomplished at many university and commercial entities. Significant toxicity
problems occur when using siRNA. AVI’s patented third generation PMOs have
overcome these problems.


 


AVI’s proprietary chemistry has significantly improved the
stability, function, and bioavailability of antisense complexes. The improved
characteristics of AVI PMOs compared to conventional antisense oligonucleotides
include:


 


·                  resistance
to proteases and nucleases,


·                  enhanced
stereochemical base stacking,


·                  inherent
stability for steric blockade of ribosomal assembly and translation arrest,


·                  reliable
aqueous solubility, and


·                  no
diminished hybridization to mRNA targets.


 


The biological effects of PMOs are evident after
intravenous, intraperitoneal, subcutaneous, transdermal, and oral
administrations, because of intrinsic biodistribution and bioavailability
characteristics of these compounds.


 


The theoretical biological advantages of PMO are based on
the lack of net charge and a non-enzymatic mechanism of action. The PMO include
fewer “off-target” effects and do not result in:


 


·                  immune modulation through CpG motifs (Art Krieg personal communication),


·                  altered blood coagulation times (preliminary data),


·                  metal chelation because there is no net charge for binding,


·                  complement activation (based on clinical trial observations),


·                  off-target alteration of gene expression through O-quartets (Hudziak et
al., 2000; and E. Wickstrom personal communication)


·                  RNAse H or other enzymatic RNA cleavage (Stein et al, 1997),


·                  induction of cytokine release, or


·                  induction of interferon responses.


 


Most importantly, compared to conventional antisense
oligonucleotides, PMOs are highly resistant to degradation (Hudziak et al.,
1996).


 


2

















 


4.0          Tasks/Technical Requirements:


 


The following Gantt Chart delineates AVI’s tasks under
this contract. Tasks for subcontractors are shown in Appendix A:


 


	
   

  	
   

  	
   

  	
   

  	
  Quarter

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  2 mo.

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Ended

  	
   

  
	
  Milestone

  	
   

  	
  Description

  	
   

  	
  12/06

  	
   

  	
  07Q1

  	
   

  	
  07Q2

  	
   

  	
  07Q3

  	
   

  	
  07Q4

  	
   

  	
  08Q1

  	
   

  	
  08Q23

  	
   

  	
  08Q3

  	
   

  	
  11/30/08

  	
   

  
	
  1 

  	
   

  	
  Efficacy Evaluation of PMO/PPMOs

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  1.1

  	
   

  	
  Evaluate cellular toxicity of EBOV and MARV

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  1.2

  	
   

  	
  Evaluate cellular toxicity of Arenavirus

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2

  	
   

  	
  Mechanism of Action and Cell Culture Studies

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2.1

  	
   

  	
  Cell culture efficacy and mechanism EBOV and MARV

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2.2

  	
   

  	
  Cell culture efficacy and mechanism Junin

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3

  	
   

  	
  Efficacy Testing in Murine and Guinea Pig Models

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  3.1

  	
   

  	
  Optimal PPMO EBOV lethal challenge studies in mouse

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.2

  	
   

  	
  Optimal PPMO MARV lethal challenge in guinea pig

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.3

  	
   

  	
  Optimal PPMO Junin challenge in mouse

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4

  	
   

  	
  Pharmacokinetic and toxicology

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  4.1

  	
   

  	
  Develop analytical methods to detect PPMOs in
  tissues

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.2

  	
   

  	
  Pharmacokinetics and toxicity in rodents

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.2.1

  	
   

  	
  PK PPMOs for
  EBOV and MARV

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.2.2

  	
   

  	
  PK PPMOs for
  Junin

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.3

  	
   

  	
  PK and toxicology studies in non-human primates;

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.3.1

  	
   

  	
  PPMOs for EBOV
  and MARV

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.3.2

  	
   

  	
  PPMOs for Junin

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  5

  	
   

  	
  Efficacy Testing in second species

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  5.1

  	
   

  	
  PPMOs for EBOV
  and MARV

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  5.2

  	
   

  	
  PPMOs for Junin

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  6

  	
   

  	
  Manufacturing

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  6.1

  	
   

  	
  Manufacturing scale up and establish QC procedures

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  6.2

  	
   

  	
  Subunit preparation and PMO development

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  6.3

  	
   

  	
  Peptide development and production

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  6.4

  	
   

  	
  Conjugation production

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  6.5

  	
   

  	
  Fill and Finish

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  7

  	
   

  	
  Prepare and file IND with FDA

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  7.1

  	
   

  	
  EBOV

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  7.2

  	
   

  	
  MARV

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  7.3

  	
   

  	
  Junin

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  



 


3

















 


5.0          CDRLs/Other Deliverables:


 


	
  Document
  Type

  	
   

  	
  Description

  	
   

  	
  Pages

  	
   

  	
  Date

  
	
  Exhibit A001

  	
   

  	
  Quarterly Status
  Reports

  	
   

  	
  1

  	
   

  	
  15-NOV-2006

  
	
  Exhibit A002

  	
   

  	
  Annual Report

  	
   

  	
  1

  	
   

  	
  15-NOV-2006

  
	
  Exhibit A003

  	
   

  	
  Quarterly Financial
  Status Reports

  	
   

  	
  1

  	
   

  	
  15-NOV-2006

  
	
  Exhibit A004

  	
   

  	
  Miscellaneous Data Submission

  	
   

  	
  1

  	
   

  	
  15-NOV-2006

  
	
  Exhibit A005

  	
   

  	
  Final Report

  	
   

  	
  1

  	
   

  	
  15-NOV-2006

  
	
  Exhibit A006

  	
   

  	
  Interim Reports

  	
   

  	
  1

  	
   

  	
  15-NOV-2006

  
	
  Exhibit A007

  	
   

  	
  Investigational New
  Drug (IND) Submission Report

  	
   

  	
  1

  	
   

  	
  15-NOV-2006

  



 


Appendix A: Subcontractor Efforts


 


Fill/Finish
Tasks:


 


Fill/finish
refers to the manufacturing efforts required to convert bulk drug into a final
dosage form suitable for injection into humans. The overriding goal of assuring
patient safety requires that the final dosage form be filled in an aseptic
operation, which necessitates a sterile environment, process controls, trained
personnel, validated procedures, and validated test methods in order to ensure
a very low probability of microorganism contamination. The equipment necessary
to perform aseptic filling activities is of special design and construction and
must undergo extensive qualification and validation activities since the
failure of one control aspect could lead to lot contamination. Specialized
manufacturers provide contract filling services for smaller companies that may
require only a few filling runs per year, and which do not have the resources
to acquire and maintain the facilities, equipment, and the personnel needed. We
have successfully subcontracted for this type of effort several times in the past
with multiple vendors, and would anticipate doing the same under this contract,
in the most cost effective and quality assured manner available at the time.


 


USAMRIID
Tasks:


 


Scientific
Director: Dr. Sina Bavari


Technical
Director: Dr. Kelly Warfield


CDC
Registration: C20060223-0428, effective Feb. 23, 2006, expires Jan. 20,
2009


 


USAMRIID
will conduct studies related to Part A-1 of the proposal involving
Filovirus infection. Regular communication with investigators at USAMRIID will
be required to discuss goals, experimental protocols, observations and
preparation of reports. USAMRIID will evaluate the training of individuals
involved in studies conducted in theBSL-4 and will prepare applications to the
ethical care and use of animals. USAMRIID will utilize multiple isolates for
the different strains Ebola and Marburg. The laboratory tasks will initially
involve screening studies in Ebola and Marburg infection in cell culture.
Mechanism of action studies


 


4

















 


will
be conducted by USAMRIID using mini-genome systems in cell culture. Finally,
the USAMRIID tasks include efficacy studies involving Ebola and Marburg lethal
challenge in murine, guinea pig and nonhuman primate models. The mechanism of
action studies with mini-genome systems will be conducted in BSL-2 facilities
but infected cell culture and animal challenge studies will require BSL-4
containment. USAMRIID will prepare final reports in collaboration with AVI for
Ebola and Marburg studies. Specific tasks include:


 


TASK
1: Complete efficacy and toxicology evaluation of P-PMOs targeting highly
conserved regions of Ebola and Marburg in cell culture.


 


TASK
2: Complete mechanism of action studies with replicons and mini-genome systems
in cell culture.


 


TASK
3: Complete evaluation of lead candidates in mouse lethal challenge model.


 


TASK
4: Complete evaluation of lead candidates in guinea pig lethal challenge model.


 


TASK
5: Perform initial studies in non-human primate lethal challenge model.


 


TASK
6: Perform second round of non-human primate lethal challenge studies.


 


TASK
7: Complete lethal challenge studies in non-human primates.


 


The
Scripps Research Institute (TSRI) Tasks:


 


Scientific
Director: Dr. Michael Buchmeier


Technical
Director: Dr. Benjamin Neuman


CDC
Registration: neither Junin Candid#1 nor LCMV are select agents, so
registration is not required.


 


TSRI
will conduct studies related to Part A-2 of the proposal involving
Arenavirus infection. Regular communication with investigators at USAMRIID will
be required to discuss goals, experimental protocols, observations and
preparation of reports. TSRI will evaluate the training of individuals involved
in studies conducted in the BSL-2 and will prepare applications to the ethical
care and use of animals. TSRI will utilize lymphotropic choriiomeningitis virus
(LCMV), a pathogenic Old World arenaviru3, and the Candid#1 vaccine strain of
Junin virus, the agent of Argentine hemorrhagic fever (neither are select
agents). The laboratory tasks will initially involve screening studies in
infection in cell culture monitoring plaque assays to measure viral entry,
multiplication and spread. Further measures will include measures of viral
protein synthesis, viral RNA synthesis, and viral induced cytopathic effects.
These in vitro studies will provide information about efficacy, mechanism of
action and the resistance profile for effective agents. Finally, TSRI will
conduct acute infection studies in mouse challenge models measuring virus titer
in blood, liver, kidneys, lungs, and the central nervous system to determine
antiviral effects of test agents. TSRI will prepare final reports in
collaboration with AVI. Specific tasks include:


 


TASK
1:  Complete efficacy studies with Junin
Candid#1 in cell culture.


 


TASK
2:  Complete efficacy studies with LCMV
in cell culture.


 


5

















 


TASK
3:  Complete mechanism of action studies
in cell culture.


 


TASK
4:  Initiate acute infection model
studies of Junin in mouse.


 


TASK
5:  Complete acute infection model
studies of Junin in mouse.


 


TASK
6:  Initiate chronic infection studies in
mouse and initiate guinea pig infection studies.


 


TASK
7:  Repeat studies in mouse and guinea
pig.


 


TASK
8:  Complete Junin Candid#1 infection
studies.


 


TASK
9:  Complete LCMV infection studies.


 


NHP
Toxicology Pharmacokinetic Tasks:


 


CDC
Registration: there will be no use of selected agents in animals. 


 


Potential
Subcontractors:


 


	
  Conventional
  Toxicology Rat Studies

  	
  CTBR

  
	
  Conventional
  Toxicology Non-Human Primate

  	
  MPIR

  
	
  Non-Human
  Primate Pharmacokinetic Studies

  	
  MPIR

  
	
  Safety
  Pharmacology Studies

  	
  MDSP

  
	
  Genotoxicity

  	
  BioReliance

  



 


Conventional
Safety Pharmacology Studies:


 


Single
dose exposure for each agent in preparation of IND filing, (3
months duration per agent) will require three dosage levels [i.e., anticipated
subtherapeutic dosage {low}, therapeutic dosage {intermediate}, and 10X the
therapeutic dosage {high} all studies).


 


Cardiovascular
Study to assure no clinically significant change in temperature, blood
pressure, heart rate, or conduction problems.


 


Pulmonary
Function Study to assure no clinically significant
bronchoconstricting or bronchodilating effects occur.


 


Renal
Function Study to assure no clinically significant reduction
occurs in. renal function (viz., drop in creatinine clearance and rise in serum
creatinine) after single dose administration.


 


Central
Nervous System to assure no excitatory or inhibitory activity
occurs in central or peripheral nervous systems after single dose
administration in accordance with Irwin test.


 


Pharmacokinetic
studies:


 


15
monkeys per agent, after single dose and serial dosing at low, intermediate,
and high dosing


 


Conventional
Toxicology:


 


28
Day Daily Dosing Rat Study (estimated total of 96 rats
to be tested).


 


6

















 


28
Day Daily Rat Study at the highest dosing level
with a 14-day washout (estimated total of 24 rats to be tested).


 


28
Day Daily Dosing Monkey Study
(estimated total of 50 monkeys to be tested).


 


28
Day Daily Monkey Study at the highest dosing
level with 14-day washout (estimated total of 12 monkeys to be tested).


 


Conventional genotoxicity studies:


 


Two assays; 2 months duration to complete per
agent.


 


Specific tasks include:


 


TASK 1: Initiate Conventional tox, Safety Pharm, NHP PK
and Genotoxicity for Filovirus therapeutic agent.


 


TASK 2: Complete Conventional tox, Safety Pharm and
Genotoxicity for Filovirus therapeutic agent.


 


TASK 3: Complete NHP PK for Filovirus agent and Initiate
Conventional tox, Safety Pharm, NHP PK and Genotoxicity for Arenavirus
therapeutic agent.


 


TASK 4: Complete Conventional tox, Safety Pharm, Genotox
and NHP PK for Arenavirus therapeutic agent.


 


Tessarae Tasks:


 


Tessarae LLC will provide pharmacogenomic endpoint
modeling services and reports to AVI BioPharma, related to evaluations of
clinical safety and efficacy of next generation antivirals targeting
hemorrhagic fever viruses. Tessarae will analyze 30 archived blood specimens
tested with either placebo or fixed dosages of antiviral PMO compounds to be
selected by AVI BioPharma. Archived blood specimens will be subjected to
standard preparation of total RNA for microarray-based analysis of gene
expression profiles, including reduction of abundant globin mRNA. Global gene
expression analysis will be performed on the Affymetrix U 133 2.0 Plus
microarray platform. Aliquots of purified total RNA preparations will also be
analyzed Eppendorf DualChip microarrays, representing four palettes of gene
sets related to processes of aging, inflammation, cancer and response to siRNA
treatments. A portion of original blood specimens will also be archived for
future retrospective analysis.


 


Specific tasks include:


 


TASK 1: Receive and archive inventory of blood specimens,
each specimen representing three PreAnalytix PAXgene RNA tubes and one Whatman
4-spot FTA card.


 


TASK 2: Subject 60 PAXgene RNA specimens (180 tubes) to
total RNA purification, including globin mRNA reduction protocol.


 


TASK 3: Perform gene expression profiling (GXP) assay
using 50% of each of the 60 RNA samples on 60 Affymetrix U 133 microarrays.


 


TASK 4: Perform gene expression profiling assay using 50%
of each of the 60 RNA samples on 120 Eppendorf DualChip microarrays.


 


7

















 


TASK 5: Perform bioinformatics analysis to determine if
significant clusters of gene expression changes are observed among the
before/after and placebo/antiviral specimen cohorts.


 


TASK 6: Compare specific gene set associations and
statistical significance of differences using results from the two analytical
platforms (Affymetrix and Eppendorf).


 


TASK 7: Deliver summary report on technical efficacy and
cost-value analysis of pilot gene expression profiling for ongoing
pharmacogenomic endpoint tracking in trials of PMO antivirals.


 


Addendum to Original Statement of Work

AVI-6002 and AVI-6003 Bridge Funding Proposal


 


A.    INTRODUCTION:


 


AVI BioPharma is focused on the discovery and development
of RNA-based drugs utilizing an extensive proprietary technology platform with
applications to a range of diseases and genetic disorders. The current funding
mechanism supported a discovery process, based upon antisense oligomers, to
identify lead antiviral candidates for Ebola Zaire (AVI-6002) and Marburg
Musoke (AVI-6003). These compounds are effective in multiple animal models of
viral infection. AVI BioPharma has prepared and submitted INDs for AVI-6002 and
AVI6003 for immediate treatment of patients following documented or suspected
exposure to Ebola Zaire or Marburg Musoke, respectively. In order to continue
the science and prepare for NDA submittals, AVI BioPharrna is submitting this
bridge funding proposal to TMTI to perform tasks that are required to be
performed prior to AVI BioPharma’s performance of the Advanced funding. These
tasks include Program Management, Dose titration studies, Preparation of
Clinical Materials, Development of Analytical Methods, Development &  Implementation, as well
as Incorporation and Resolution of FDA comments from initial IND filing. The
specific Statement of Work for these tasks is outlined below:


 


B.    TASKS:


 


1.              Program
Management: The overall administration of
the Ebola/Marburg program includes coordination of items of a technical nature,
working with the government to facilitate the proper approvals, as well as
ensuring that the program is on task and on budget the program management task
is made up of the following:


 


1.1  Program Management Team for coordination of effort, evaluation of progress and communication
with TMTI.


 


1.2  Antiviral Project Team meets bi-weekly to ensure timelines are met, reviews decisions and
communicates with internal departments.


 


8

















 


2.              Dose Titration Studies:


 


AVI-6002 Dose Titration Study:
Dose ranging studies with AVI-6002 in the Ebola lethal challenge model in
Rhesus monkeys.


 


Objective: Establish a
dose versus survival relationship for AVI-6002 following infection of rhesus
macaques with EBOV Zaire critical to the dose refinement for advanced
development and human safety studies.


 


AVI-6003 Dose Titration Study:
Dose ranging studies with AVI-6003 in the Marburg lethal challenge model in
Cynomolgus monkeys.


 


Objective: Establish a
dose versus survival relationship for AVI-6003 following infection of
cynomolgus macaques with MARV Musoke critical to the dose refinement for
advanced development and human safety studies.


 


3.              Clinical Study Preparations: In preparation for the first
human volunteer safety study, two major work streams prior to the study site
activation are required:


 


3.1  Clinical Study
Start-up Activities. Conducting the various activities required to
open a clinical study site usually takes a minimum of 12 weeks after the key contracts
are awarded.


 


3.2  Clinical Supply Preparations. The Active
Pharmaceutical Ingredients (API), AVI-6002 and AVI-6003 will be dispensed into
sterile vials for future clinical use.


 


4.              Analytical Methods Development and Implementation: The improvement
of analytical methods to be used in the first in man pharmacokinetic studies
represents ongoing studies that will require support. Transfer of methods to
contract research organizations will be required prior to initiating GLP
pharmacokinetic studies.


 


5.              Incorporation and Resolution of FDA Comments: We propose to
schedule a face- to-face strategy meeting regarding our proposed development
plan, prior to providing responses to the questions and comments received upon
IND approval. The next steps would be to provide three separate category
responses: clinical, nonclinical and CMC (chemistry, manufacturing, and
control). The clinical submission includes the revised protocol, a revised DSMB
charter, and the ICF template, as well as responses to FDA questions, and a
development plan outlining what additional clinical studies might be needed
prior to approval. The nonclinical responses will be sent with the initial
animal study protocols, as requested, and will include efficacy studies as well
as PK/PD work. The CMC response will be provided after clinical supply
manufacture is complete.


 


9

















 


Addendum  to Original Statement of Work


AVI-7012 (Junin) Extension Proposal


 


TASK 1: Establish and maintain a
project management team


 


1.1 Program Management Team


1.2
Junin Project Team


 


TASK 2: Conduct efficacy studies in animal models of Junin
arenavirus infection.


 


2.1
Efficacy studies in mice (LCMV).


2.2
Efficacy studies in guinea pigs (Junin) at UTMB.


2.3
Efficacy studies in NHP (Junin) at USAMRIID.


2.4
Efficacy studies in NHP (Junin)
at USAMRIID. 


 


TASK 3: Expanded arenavirus efficacy studies.


 


TASK 4: Evaluate the mechanism of action of AVI-7012.


 


TASK 5: Conduct pharmacokinetic and pilot toxicology studies
with AVI-7012.


 


TASK 6: Conduct GLP Safety
Pharmacology and Toxicology Studies. 


 


6.1
Fill for GLP Studies.


6.2
GLP Toxicology Studies in rat.


6.3
GLP Toxicology Studies in monkey.


6.4
GLP Safety Pharmacology studies.


6.5
GLP Genotoxicity evaluation.


 


TASK 7: Chemistry & Manufacturing Support.


 


7.1
GMP synthesis (1 x 120 g) at Johnson Matthey Pharma Services (includes tech
transfer) 


7.2
GMP synthesis (1 x 120 g) at Johnson Matthey Pharma Services


7.3
Drug substance stability


7.4
Analytical – subunit, PMO and bioanalytical development


7.5
Subunit chemistry/process development 


 


TASK 8: Clinical Study Preparations.


 


8.1
Phase I Single Dose NHV Clinical Study Preparations. 


8.2
HPLC asay qualification.


8.3
Clinical Supply Preparations.


8.4
Drug Product Stability.


 


TASK 9: Prepare pre-IND for AVI-7012 (Junin).


 


TASK 10: Prepare and submit the IND
for AVI-7012 (Junin). 


 


10.1 Prepare and submit IND.


10.2
Respond to FDA questions regarding IND.


 


10