Document:

Exhibit
10.35

 

FIRST AMENDMENT TO LOAN AGREEMENT

 

THIS FIRST AMENDMENT TO
LOAN AGREEMENT (this “Amendment”) is made and entered into as of September 30,
2009, between ISIS PHARMACEUTICALS, INC., a
Delaware corporation (together with its successors and assigns, “Borrower”),
and RBS ASSET FINANCE, INC., a New York
corporation (together with its successors and assigns, “Lender”).

 

RECITALS

 

A.            Lender and Borrower have previously entered into a
Loan Agreement dated as of October 15, 2008 (as amended, the “Agreement”).

 

B.            Lender and Borrower wish to amend the Agreement as
provided herein.

 

NOW, THEREFORE, in
consideration of the premises and the mutual covenants and agreements herein
contained, and for other good and valuable consideration, the receipt of which is
hereby acknowledged, it is hereby agreed as follows:

 

1.             The Agreement is amended as follows:

 

(i)  The
definitions of the following terms set forth in Schedule I to the Agreement are
hereby amended to have the meanings set forth below:

 

“Financial Statements” means the audited financial statement of
Borrower and each Guarantor for their fiscal years ended December 31, 2008
and the unaudited financial statement of Borrower and each Guarantor and for
the quarter ended June 30, 2009.

 

“Maximum Principal Amount” means $18,400,000.00

 

“Scheduled Commitment
Termination Date” means July 7, 2010.

 

(ii)  ARTICLE
VI:  COVENANTS Section 6.02.
Negative Covenants of the Agreement is hereby amended to add the following
paragraph as a new subsection (f):

 

“(f) Borrower shall maintain a depository account
with RBS Citizens Bank, N.A. as with a balance of at least Two-Hundred
Fifty-Thousand Dollars and 00/100 ($250,000.00) until all Obligations of
Borrower to Lender under the Agreement are indefeasibly paid in full.”

 

(iii)  ARTICLE VII:  EVENT OF DEFAULT Section 7.01(K) is
hereby amended to read in its entirety as follows:

 

“(k)         At any time Borrower shall be a guarantor
of obligations under such Loan Agreement, an of Event of Default shall exist
under and as defined in that certain Loan Agreement dated September 30,
2009 between Lender and REGULUS THERAPEUTICS INC.”

 

2.             This Amendment may be executed in several
counterparts, each of which shall be an original and all of which shall
constitute but one and the same instrument.

 

3.             All other terms and conditions of the
Agreement not specifically amended by this Amendment shall remain in full force
and effect and are hereby ratified and confirmed by Lender and Borrower.

 

4.             This Amendment shall be governed by the
law of the State of Illinois (without regard to the conflict-of-laws principles
thereof).

 

1

 

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK;

EXECUTION PAGE FOLLOWS]

 

2

 

IN WITNESS
WHEREOF, the parties hereto have executed this Amendment in their respective
corporate names by their duly authorized officers, all as of the date first
written above.

 

	
  Lender:

  	
  RBS ASSET FINANCE, INC.,

  
	
   

  	
  a New York corporation

  
	
   

  	
   

  
	
   

  	
   

  
	
   

  	
  By

  	
  /s/ Cynthia Prince

  
	
   

  	
   

  
	
   

  	
  Name

  	
  Cynthia Prince

  
	
   

  	
   

  
	
   

  	
  Title

  	
  VP

  
	
   

  	
   

  
	
   

  	
   

  
	
  Borrower:

  	
  ISIS PHARMACEUTICALS, INC.,

  
	
   

  	
  a Delaware corporation

  
	
   

  	
   

  
	
   

  	
   

  
	
   

  	
  By

  	
  /s/ B. Lynne Parshall

  
	
   

  	
   

  
	
   

  	
  Name

  	
  B. Lynne Parshall

  
	
   

  	
   

  
	
   

  	
  Title

  	
  COO & CFO

  

 

[EXECUTION PAGE OF
AMENDMENT TO LOAN AGREEMENT]

 

3Exhibit
10.45

 

CONFIDENTIAL TREATMENT REQUESTED

UNDER 17 C.F.R. §§ 200.80(b)4, AND 240.24b-2

 

AMENDMENT
NO. 1 TO

AMENDED
AND RESTATED LICENSE AGREEMENT

 

THIS AMENDMENT NO. 1 TO AMENDED AND RESTATED LICENSE
AGREEMENT (the “Amendment”)
is made and entered into effective as of December 18, 2009 (the “Amendment
No. 1 Effective Date”), by and between ONCOGENEX TECHNOLOGIES INC., having
offices at #400 — 1001 West Broadway, Vancouver, B.C. V6H 4B1 (“OncoGenex”),
and ISIS PHARMACEUTICALS, INC., having principal offices at 1896 Rutherford
Road, Carlsbad CA 92008-7208 (“Isis”). 
OncoGenex and Isis each may be referred to herein individually as a “Party,”
or collectively as the “Parties.”

 

WHEREAS, the Parties entered into an Amended and Restated
License Agreement dated as of July 2, 2008 (the “Restated Agreement”)
under which Isis granted to OncoGenex the unilateral rights to continue the
development and commercialization of OGX-011, a second generation antisense
inhibitor of Clusterin;

 

AND WHEREAS, the Parties now wish to amend certain provisions of
the Restated Agreement, as provided herein.

 

NOW, THEREFORE, the Parties do hereby agree as follows:

 

ARTICLE 1

DEFINITIONS

 

Capitalized terms used in this Amendment and not otherwise defined
herein have the meanings ascribed to such terms as set forth in the Restated
Agreement.

 

ARTICLE 2

AMENDMENT OF RESTATED AGREEMENT

 

2.1          Amendment re Section 5.3.2.  Section 5.3.2
of the Restated Agreement is hereby amended to read in its entirety as follows:

 

“5.3.2     To the extent that [***] OncoGenex under
this Agreement collects safety and tolerability data or information
specifically regarding a Product, OncoGenex will obtain from such sublicensee (a) the
right to provide to Isis (whether through OncoGenex or its Affiliate, or directly
from such sublicensee) the [***] described in [***], and (b) the right of
Isis to [***] for the purposes described in [***].  Only sublicensees that actually provide such
[***] and grant Isis the right to use such [***] as set forth herein, will have
the right to access the results of any queries requested by OncoGenex.  If and when Isis identifies safety,
pharmacokinetic or other related issues that may be relevant to a Product [***]
Isis will promptly inform OncoGenex of such issues, and if requested, provide
the data and information supporting Isis’ conclusions regarding such
issues.  In addition, at OncoGenex’ or
its sublicensee’s (provided that such sublicensee provides the data,
information and rights described above in this Section 5.3.2) reasonable
request and at no cost to OncoGenex or its sublicensee, Isis will [***] the
Isis Database to provide OncoGenex or its sublicensee information regarding
[***] or other related issues.”

 

 

2.2          Amendment re Section 6.5. 
Cell (a) of the first column in the table set forth in Section 6.5
of the Restated Agreement is hereby amended to read in its entirety as follows:

 

“(a) Prior to the initiation [***] of a first Registration Clinical Trial
for a Product”

 

2.3          Addition of Section 6.11. 
A new Section 6.11 is hereby added to the Restated Agreement as
follows:

 

“If after the Amendment No. 1 Effective Date,
OncoGenex is the subject of a change of control with a Third Party, where the
surviving company immediately following such change of control has the right to
develop and sell the Product, then (i) a milestone payment of $20,000,000
will be due and payable to Isis 21 days following the first commercial sale of
the Product in the United States; and (ii) the royalty rate payable under Section 6.2.1
will thereafter be [***] payable under such Section; provided,
any Non-Royalty Revenue payments made to Isis under Section 6.5 prior to
the payment of the $20,000,000 milestone under this Section 6.11 will be
creditable against such milestone payment. 
If (a) OncoGenex grants a sublicense under this Agreement and the
corresponding royalty rate is established under Section 6.2.1, and (b) such
sub-licensee later acquires OncoGenex in a change of control, then
notwithstanding subsection (ii) of this Section 6.11, the royalty
rate payable under Section 6.2.1 in connection with such sublicense
immediately prior to such change of control will apply to the surviving company
after such change of control.”

 

2.4          Amendment re Section 7.2.2(b).  Section 7.2.2(b) of
the Restated Agreement is hereby amended to read in its entirety as follows:

 

“(b)         In addition, each Party will use
reasonable efforts to notify (and provide as much advance notice as possible
to) the other of any event materially related to Product (including any
regulatory approval) of which the Party becomes aware so that the Parties may
analyze the need to or desirability of publicly disclosing or reporting such
event.”

 

2.5          Addition of Section 7.2.2(c). 
A new Section 7.2.2(c) is hereby added to the Restated
Agreement as follows:

 

“(b)         Notwithstanding the foregoing, upon Isis’
written request, OncoGenex or its sublicensees will include in press releases
or oral public presentations that contain new material clinical data,
regulatory approvals or other material information regarding a Product or this
Agreement, a statement acknowledging the Parties’ joint discovery and initial
development of OGX-011, substantially in the form as OncoGenex has used
immediately prior to the Amendment #1 Effective Date, the fact that intellectual
property related to antisense technology embodied in such Product was licensed
from Isis, and Isis’ ticker symbol (e.g., Nasdaq: ISIS).”

 

2.6          Amendment re Section 8.3.1(a). 
The last sentence of Section 8.3.1(a) of the Restated
Agreement is amended to state:  “In any
case, Isis may not settle, or otherwise consent to an adverse judgment in, any
action or proceeding with respect to such infringement in a manner that
diminishes the rights or interests of OncoGenex or OncoGenex’s sublicensee, 

 

 

without the prior written
consent of both OncoGenex and OncoGenex’s sub-licensee, such consent not to be
unreasonably withheld or delayed.”

 

2.7          Amendment re Section 9.3.1.  Section 9.3.1
of the Restated Agreement is hereby amended to read in its entirety as follows:  “Upon expiration of the Term of this
Agreement in accordance with Section 9.1 and payment of all amounts owed
pursuant to this Agreement, the licenses granted by Isis to OncoGenex under
this Agreement will automatically become perpetual, irrevocable, fully-paid
non-exclusive licenses.”

 

2.8          Amendment re Section 12.2.1.  Section 12.2.1
of the Restated Agreement is hereby amended to read in its entirety as follows:

 

“12.2.1          Failure to Pay.  If OncoGenex is in material breach of
OncoGenex’ obligation to make a payment to Isis under Article 6, then Isis
may deliver written notice of such breach to OncoGenex, with a required copy of
such notice to OncoGenex’s sub-licensee. 
OncoGenex will have thirty (30) days following such notice to cure such
breach (and provided further that OncoGenex’s sub-licensee may cure such breach
by making payment to Isis of any amounts owed by OncoGenex, and Isis agrees to
accept all such payments made by OncoGenex’s sub-licensee).  If OncoGenex and its sub-licensee have
received written notice of such a payment breach from Isis, and such breach is
not cured within the 30 day period, Isis may declare an uncured material breach
hereunder upon thirty (30) days advance written notice to OncoGenex and such
notice will effectively terminate this Agreement upon expiration of such thirty
(30) day period.”

 

2.9          Amendment re Section 12.2.2.  Section 12.2.2
of the Restated Agreement is hereby amended to read in its entirety as follows:

 

“12.2.2          Discontinued
Development.

 

(a)  If OncoGenex materially
breaches its diligence obligations under Section 4.4, then Isis shall have
the right to give OncoGenex written notice of such breach describing such
material breach in reasonably specific detail, and Isis must provide at the
same time a copy of such notice to OncoGenex’s sub-licensee.  OncoGenex, or its sub-licensee, shall have
the right to cure such breach within ninety (90) days after receipt of written
notice from Isis (or longer if such breach is not reasonably curable with such
90 days), and Isis agrees to accept any performance by such sub-licensee in
seeking to cure the breach.  In the event
of a Discontinuance or if OncoGenex materially breaches its diligence
obligations under Section 4.4 and such material breach is not cured by
OncoGenex and/or its sub-licensee within ninety (90) days after receipt of
written notice from Isis (as provided above), then in any such case, as Isis’
sole and exclusive remedy therefor, Isis will have the right to terminate the
[***]under [***] upon thirty (30) days prior written notice to OncoGenex; provided that, if such breach is not
reasonably curable within such 90 days, then as long as OncoGenex and/or its
sub-licensee continues to take substantial steps toward curing such material
breach until such breach is cured, Isis may not exercise its termination rights
under this Section 12.2.2.

 

 

(b)  Upon any such termination
under subclause (a) above, OncoGenex will [***] Isis a [***], as the case
may be, to the OncoGenex Product-Specific Technology, OncoGenex Patents,
OncoGenex Technology and any Product-Specific Technology Patents assigned to
OncoGenex under Section 4.2.1 (in the case of OncoGenex Patents and
OncoGenex Technology that are the subject of one or more Third Party
agreements, such license or sublicense shall be subject to all restrictions and
obligations (including financial obligations) under such Third Party
agreements) existing as of such date solely to develop, make, have made, use,
sell, offer for sale, have sold and import Nonexclusive Clusterin ASOs (and any
products containing such Nonexclusive Clusterin ASOs).  For purposes of this Section 12.2.2, “Nonexclusive
Clusterin ASOs” means ASOs that act predominantly by [***] Clusterin [***] or
that are [***] to Clusterin [***], provided,
however that the term “Nonexclusive Clusterin ASOs” expressly
excludes:  (a) OGX-011 and any other
ASO that has the [***]; and (b) any other ASO that (i) acts to
modulate [***] Clusterin and (ii) for which, at the time of such
Discontinuance or uncured material breach, OncoGenex, its Affiliates or
sublicensees have [***].  Within ninety
(90) days following the effectiveness of any termination by Isis, pursuant to
this Section 12.2.2, of the [***], OncoGenex shall provide Isis with a
[***].

 

(c)  OncoGenex covenants and agrees
that any [***] granted by OncoGenex under the OncoGenex Product-Specific
Technology, OncoGenex Patents, OncoGenex Technology and any Product-Specific
Technology Patents assigned to OncoGenex under Section 4.2.1 will be
expressly subject to the [***] that OncoGenex [***] Isis under subclause (b) above
(if applicable) under such Patents under this Section 12.2.2, and such
[***] by OncoGenex will automatically be limited by such [***] to Isis, [***]
as above.”

 

2.10        Addition of Section 12.2.3. 
A new Section 12.2.3 is hereby added to the Restated Agreement as
follows:

 

“12.2.3  Notwithstanding the foregoing, if Isis
terminates the [***], and prior to such termination OncoGenex [***], then,
provided [***], Isis shall [***].”

 

2.11        Amendment re Section 13.15.  Section 13.15
of the Restated Agreement is hereby amended to add a new Section 13.15.7
that reads in its entirety as follows:

 

“13.15.7        All notices that may or are given by Isis
under this Section 13.15 to OncoGenex shall [***]”

 

 

2.12        Amendment re Appendix A.  The definition of “Discontinuance”
in Appendix A of the Restated Agreement is hereby amended to read in its
entirety as follows:

 

“‘Discontinuance’ means OncoGenex voluntarily elects to abandon [***] all development and
commercialization of Products, as evidenced by a written communication from an
authorized officer of OncoGenex to Isis.”

 

2.13        Amendment re Appendix A.  The definition of “Revenue” in
Appendix A of the Restated Agreement is hereby amended to read in its entirety
as follows:

 

““Revenue” means all revenues, receipts, monies, and the fair
market value of all other consideration directly or indirectly collected or
received whether by way of cash or credit or any barter, benefit, advantage, or
concession received OncoGenex relating to the sale, license or any other
commercial transaction involving OGX-011 and/or the Product, with the exception
of the following: (i) any consideration received for the reimbursement for
research and development activities and (ii) any consideration received
for the fair market portion of any sale of equity or quasi-equity securities
including, without limitation, common shares and preferred shares.”

 

2.14        Based on the fact that OncoGenex has an
obligation to disclose to Isis, under the Restated Agreement, certain
confidential information that OncoGenex may receive from its sublicensees under
the Restated Agreement, Isis agrees that, promptly after OncoGenex enters into
such a sublicense agreement, Isis, OncoGenex and such sublicensee will enter
into a mutual confidentiality agreement under which Isis will agree to protect
the confidentiality of any such information disclosed by OncoGenex or OncoGenex’s
sublicensee to Isis pursuant to the Restated Agreement or the sublicense
agreement on terms that are consistent with the confidentiality provisions of
the Restated Agreement.

 

ARTICLE 3

REPRESENTATIONS AND COVENANTS RELATING TO AMENDMENT OF RESTATED AGREEMENT

 

3.1          Representations and
Covenants Regarding Improvements and Technology.  Isis hereby
represents and warrants to OncoGenex that: 
(a) Isis has assigned to OncoGenex all rights, title, and interests
in and to the Product-Specific Technology and the Product-Specific Technology
Patents existing as of the Amendment No.1 Effective Date; and (b) to Isis’
knowledge, Isis has transferred to OncoGenex all Information and technology
required to be transferred under the first sentence of Section 4.2.2 of
the Restated Agreement.  Isis shall use
reasonable efforts to determine whether any Information and technology required
to be transferred under the first sentence of Section 4.2.2 has not been
transferred to OncoGenex and, if so, shall promptly transfer such Information
and technology to OncoGenex (such transfer to be at Isis’ expense if the [***]
set forth in Section 4.2.2 has not yet been reached, and otherwise at
OncoGenex’ expense).

 

3.2          Representations and
Covenants Regarding Agreements.  Isis hereby
represents and warrants to OncoGenex that: 
(a) as of the Amendment No.1 Effective Date, Isis 

 

 

does not believe that
OncoGenex is in breach of any of its obligations under the Restated Agreement; (b) the
Restated Agreement is in good standing and in full force and effect; and (c) Isis’
agreements with [***] are all in good standing and in full force and
effect.  Isis shall use good faith
efforts not to breach any of the terms of any such agreements.

 

ARTICLE 4

MISCELLANEOUS

 

4.1          Integration. 
This Amendment is deemed integrated into and made part of the Restated
Agreement, and is governed by all applicable terms of the Restated
Agreement.  This Amendment modifies the
applicable terms of the Restated Agreement solely as provided above.  All other terms, obligations, and conditions
of the Restated Agreement are and shall remain in full force and effect.  To the extent this Amendment is in conflict
with any terms of the Restated Agreement, this Amendment shall control.

 

4.2          This Amendment automatically terminates
upon termination of the Restated Agreement.

 

4.3          This Amendment may be executed in one or
more counterparts by the parties by signature of a person having authority to
bind the party, which may be by facsimile signature, each of which when
executed and delivered, by facsimile transmission or by mail delivery, will be
an original and all of which will constitute but one and the same Amendment.

 

*****************************

 

 

IN WITNESS
WHEREOF, the Parties hereto have caused
this Amendment to be executed by their duly authorized representatives as of
the date first above written.

 

 

	
  ONCOGENEX
  TECHNOLOGIES INC.

  	
   

  	
  ISIS
  PHARMACEUTICALS, INC.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Per:

  	
  /s/ Scott D. Cormack

  	
   

  	
  Per:

  	
  /s/ B. Lynne Parshall

  
	
   

  	
   

  	
   

  
	
  Scott D. Cormack,

  	
   

  	
  B. Lynne Parshall

  
	
  President & CEO

  	
   

  	
  COO and CFO

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