Document:

Eighth Amendment to Loan and Security Agreement

 Exhibit 10.1 
 EIGHTH AMENDMENT 
 TO 
 LOAN AND SECURITY AGREEMENT 
 THIS EIGHTH AMENDMENT to Loan and Security Agreement (this “Amendment”) is entered into this 5th day of June, 2008, by and
between Silicon Valley Bank (“Bank”) and Pharsight Corporation, a Delaware corporation (“Borrower”) whose address is 321 East Evelyn Avenue, 3rd Floor, Mountain View, California 94041. 
 RECITALS 
 A. Bank and Borrower have entered into that certain Amended and Restated Loan and Security Agreement dated as of May 27, 2004, as amended by
that certain Loan Modification Agreement by and between Bank and Borrower dated as of February 10, 2005, as amended by that certain Loan Modification by and between Bank and Borrower dated as of May 26, 2005, as amended by that certain
Loan Modification Agreement by and between Bank and Borrower dated as of June 20, 2005, as amended by that certain Fourth Amendment to Loan and Security Agreement by and between Bank and Borrower dated as of July 14, 2005, as amended by
that certain Fifth Amendment to Loan and Security Agreement by and between Bank and Borrower dated as of June 12, 2006, as amended by that certain Sixth Amendment to Loan and Security Agreement by and between Bank and Borrower dated as of
January 2, 2007, and as amended by that certain Seventh Amendment to Loan and Security Agreement by and between Bank and Borrower dated as of June 21, 2007 (as the same may from time to time be further amended, modified, supplemented or
restated, the “Loan Agreement”). 
 B. Bank has extended credit to Borrower for the purposes permitted in the Loan
Agreement. 
 C. Borrower has requested that Bank amend the Loan Agreement to extend the Revolving Maturity Date. 
 D. Bank has agreed to so amend certain provisions of the Loan Agreement, but only to the extent, in accordance with the terms, subject to the
conditions and in reliance upon the representations and warranties set forth below. 
 AGREEMENT 
 NOW, THEREFORE, in consideration of the foregoing recitals and other good and valuable consideration, the receipt
and adequacy of which is hereby acknowledged, and intending to be legally bound, the parties hereto agree as follows: 
 1.
Definitions. Capitalized terms used but not defined in this Amendment shall have the meanings given to them in the Loan Agreement. 
 2. Amendment to Loan Agreement. 
 2.1 Section 13 (Definitions). The following term
and its respective definition set forth in Section 13.1 is amended in its entirety and replaced with the following: 
 “Revolving Maturity Date” is July 23, 2008. 

 3. Limitation of Amendment. 
 3.1 The amendment set forth in Section 2, above, is effective for the purposes set forth herein and shall be limited
precisely as written and shall not be deemed to (a) be a consent to any amendment, waiver or modification of any other term or condition of any Loan Document, or (b) otherwise prejudice any right or remedy which Bank may now have or may
have in the future under or in connection with any Loan Document. 
 3.2 This Amendment shall be construed in
connection with and as part of the Loan Documents and all terms, conditions, representations, warranties, covenants and agreements set forth in the Loan Documents, except as herein amended, are hereby ratified and confirmed and shall remain in full
force and effect. 
 4. Representations and Warranties. To induce Bank to enter into this Amendment, Borrower hereby represents
and warrants to Bank as follows: 
 4.1 Immediately after giving effect to this Amendment (a) the representations
and warranties contained in the Loan Documents are true, accurate and complete in all material respects as of the date hereof (except to the extent such representations and warranties relate to an earlier date, in which case they are true and
correct as of such date), and (b) no Event of Default has occurred and is continuing; 
 4.2 Borrower has the
power and authority to execute and deliver this Amendment and to perform its obligations under the Loan Agreement, as amended by this Amendment; 
 4.3 The organizational documents of Borrower delivered to Bank on May 27, 2004 remain true, accurate and complete and have not been amended, supplemented or restated and are and continue to be in full
force and effect; 
 4.4 The execution and delivery by Borrower of this Amendment and the performance by Borrower of
its obligations under the Loan Agreement, as amended by this Amendment, have been duly authorized; 
 4.5 The execution
and delivery by Borrower of this Amendment and the performance by Borrower of its obligations under the Loan Agreement, as amended by this Amendment, do not and will not contravene (a) any law or regulation binding on or affecting Borrower,
(b) any contractual restriction with a Person binding on Borrower, (c) any order, judgment or decree of any court or other governmental or public body or authority, or subdivision thereof, binding on Borrower, or (d) the
organizational documents of Borrower; 
 4.6 The execution and delivery by Borrower of this Amendment and the
performance by Borrower of its obligations under the Loan Agreement, as amended by this Amendment, do not require any order, consent, approval, license, authorization or validation of, or filing, recording or registration with, or exemption by any
governmental or public body or authority, or subdivision thereof, binding on either Borrower, except as already has been obtained or made; and 

 4.7 This Amendment has been duly executed and delivered by Borrower and is the
binding obligation of Borrower, enforceable against Borrower in accordance with its terms, except as such enforceability may be limited by bankruptcy, insolvency, reorganization, liquidation, moratorium or other similar laws of general application
and equitable principles relating to or affecting creditors’ rights. 
 5. Integration. This Amendment and the Loan
Documents represent the entire agreement about this subject matter and supersede prior negotiations or agreements. All prior agreements, understandings, representations, warranties, and negotiations between the parties about the subject matter of
this Amendment and the Loan Documents merge into this Amendment and the Loan Documents. 
 6. Counterparts. This Amendment may
be executed in any number of counterparts and all of such counterparts taken together shall be deemed to constitute one and the same instrument. 
 7. Effectiveness. This Amendment shall be deemed effective as of May 24, 2008, upon the due execution and delivery to Bank of this Amendment by each party hereto. 
 IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be duly executed and delivered
as of the date first written above. 
  

									
	BANK	 		 	BORROWER
			
	Silicon Valley Bank	 		 	Pharsight Corporation
					
	By:	 	/s/ Jason Hughes	 		 	By:	 	/s/ William Frederick
					
	Name:	 	Jason Hughes	 		 	Name:	 	William Frederick
					
	Title:	 	Relationship Manager	 		 	Title:	 	Chief Financial OfficerLicense Agreement

 Exhibit 10.21 
 Portions of this exhibit marked [*] are requested to be treated confidentially. 
 

 
 PRIVATE & CONFIDENTIAL 
 This Agreement is made and effective this May 1, 2008 (the “Effective Date”) by and between: 
 Stichting
Antoni van Leeuwenhoek Ziekenhuis whose registered office is at Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands, legally represented by S. Rodenhuis (“AVL”), and Adherex Technologies Inc. with an office at 4620 Creekstone Drive, Suite
200, Durham, NC 27703 USA, legally represented by Dr. William P. Peters (“Adherex”). 
 PREAMBLE 
  

	 	A.	AVL has previously generated data in connection with the performance of a study with sodium thiosulfate (“STS”) entitled “Ototoxicity in a Randomized Phase III Trial
of Intra-Arterial Compared With Intravenous Cisplatin Chemoradiation in Patients with Locally Advanced Head and Neck Cancer” (as published by CL Zuur et al. J Clin Oncol 2007; 25(24):3759-65) (the “Published Data”);

  

	 	B.	AVL is planning further research with STS under the project identified in Schedule 1 (the “Follow-up Study”) in which related four-year ototoxicity status, disease status
and survival data from the above Phase III trial is expected to be generated (collectively with the Published Data, the “Licensed Data”); 

  

	 	C.	Adherex is desirous of obtaining a worldwide, exclusive license to the Licensed Data for purposes of submissions to regulatory agencies worldwide; 

  

	 	D.	AVL is willing to grant such an exclusive license on the terms and conditions herein specified; 

 NOW THEREFORE, in consideration of the mutual covenants and promises herein contained, AVL and Adherex agree as follows: 
 4620 Creekstone Drive, Suite 200 • Durham, North Carolina • 27703 
 Tel: (919) 484-8484 • Fax: (919) 484-8001 • www.adherex.com 

	1.	Quality Assurance Audit 

  

	1.1	AVL agrees that a Quality Assurance (“QA”) auditor to be selected by Adherex will be granted reasonable access to AVL’s facilities to conduct a QA audit at
Adherex’s sole expense to evaluate the suitability of the Published Data for submission to the U.S. Food and Drug Administration or other equivalent regulatory agencies worldwide (the “QA Audit”). 

  

	1.2	Adherex shall agree in good faith with Prof. dr A.J.M. Balm of AVL when the QA Audit will be performed. The QA Audit is not expected to last longer then three (3) working days.

  

	1.3	Adherex shall not use any confidential or proprietary AVL data, know-how, or information, or any part of it, obtained as a result of the QA Audit (the “QA Results”) for
any purpose other than the evaluation of whether Adherex wishes to obtain the exclusive license to use the Licensed Data hereunder, and Adherex agrees that it and its representatives, employees and agents will maintain in strict confidence all QA
Results and not use such QA Results for any other purpose than the QA Audit unless and until Adherex has provided the Notice and has received a confirmation thereof from AVL as set forth in Article 1.5 below. For greater certainty, this provision
will not in any way limit Adherex’s ability to refer to or use any data that have been previously published and which are in the public domain. 

  

	1.4	Adherex will ensure that the auditor selected for the QA Audit agrees to abide by the terms of confidentiality and non-use outlined in Article 1.3 above and that the QA Results will
not be copied or taken from the AVL facilities unless otherwise approved in writing by AVL. 

  

	1.5	No later than [*] weeks after the completion of the QA Audit, Adherex will give AVL written notice stating whether Adherex wishes to obtain an exclusive license in accordance with
the terms and conditions of this Agreement (the “Notice”). AVL shall confirm the receipt of such Notice without undue delay. The Notice shall be provided to: 

 NKI-AVL 
 Technology Transfer Office , Room
DC208 
 Attn. Mr. J. van der Hel, legal Adviser 
 Plesmanlaan 121 
 1066 CX Amsterdam 
 [*] Confidential treatment requested; certain information omitted and filed separately with the SEC. 

	2.	The license 

  

	2.1	Subject to receipt of the Notice under Article 1.5 above, AVL hereby grants to Adherex an exclusive, irrevocable, worldwide license, with right to transfer and sublicense, to use
the Licensed Data as part, or in support, of a New Drug Application (“NDA”) with the U.S. Food and Drug Administration (“FDA”) or any equivalent regulatory filing with agencies outside of the U.S. 

  

	2.2	Notwithstanding the above license, AVL shall retain a non-exclusive royalty-free right to use the Licensed Data for internal research, teaching, or other educational or academic
purposes and for publication in accordance with Article 6 below. 

  

	2.3	The parties will mutually agree on the manner, form, content and timelines upon which the Licensed Data will be transferred to Adherex, preferably in electronic format, at
Adherex’s sole expense. In addition, AVL agrees to reasonably support any regulatory submission of Licensed Data and provide reasonable access and assistance at Adherex’s expense as may be necessary for future regulatory agency requests or
audits. 

  

	3.	Financial consideration 

  

	3.1	In consideration for the rights granted to Adherex hereunder, Adherex agrees to pay to AVL an amount of [*] Euro as follows: 

  

	3.1.1	[*] Euro within [*] days of the Effective Date of this Agreement; 

  

	3.1.2	Subject to receipt of the Notice stating Adherex wishes to obtain an exclusive license in accordance with the terms and conditions of this Agreement: 

  

	3.1.2.1	[*] Euro within [*] days of the provision of the Notice; 

  

	3.1.2.2	[*] Euro within [*] days of the provision of the Notice; and 

  

	3.1.2.3	[*] Euro within [*] days of the provision of the Notice or within [*] days of receipt by Adherex of a final report from AVL relating to the Follow-up Study, whichever is later;

  

	3.1.3	 Subject to receipt of the Notice stating Adherex wishes to obtain an exclusive license in accordance with the terms and conditions of this Agreement, a milestone
payment of [*] Euro subject to and entirely conditional upon NDA approval by the FDA, or approval of an equivalent regulatory filing in Europe 

  

 [*] Confidential treatment requested; certain information omitted and filed separately with the SEC. 

	 	 
(i.e. an MAA by EMEA), payable within [*] days of receipt by Adherex of such an approval. 

  

	3.1.4	All amounts payable to the AVL under this Agreement are exclusive of VAT (or any similar tax) which Adherex will pay, if applicable. 

  

	3.2	The amounts set forth in this Article 3 shall be paid by wire transfer in immediately available funds to the following account: 

 ABN-AMRO Bank 
 De Entrée 99

 Postbus 90 
 1000 AB Amsterdam

 The Netherlands 
 Payee:
Stichting Antoni van Leeuwenhoek Ziekenhuis 
 Account no.: [*] 
 Iban: [*] 
 Swift code: [*] 
 Please ad reference: [*]. 
  

	3.3	If Adherex fails to pay in full any sums payable under this Agreement within the period specified for payment, the amount outstanding shall bear [*]% interest per month.

  

	4.	Confidentiality 

  

	4.1	AVL agrees that it and its representatives, employees and agents will maintain in strict confidence all information disclosed by Adherex or its representatives, employees or agents
that is identified as being confidential, including without limitation any of Adherex’s worldwide regulatory or development plans, and AVL will not disclose any such information, in whole or in part, to any third parties or use such information
for any purpose other than the performance of this Agreement. 

  

	5.	Liability and indemnification 

  

	5.1	 Any data disclosed hereunder is understood to be experimental data collected as a result of human subjects research for which informed consent was obtained and
shall be utilized by Adherex in compliance with applicable laws, including applicable privacy laws. The Licensed Data are experimental in nature and accordingly AVL makes no representation or warranty, express or implied, with 

  

 [*] Confidential treatment requested; certain information omitted and filed separately with the SEC. 

	 	 
regard to the Licensed Data as to its quality, condition, correspondence with description, or fitness for any particular purpose.

  

	5.2	Adherex will indemnify AVL, its investigators and employees (the “Indemnified Parties”) from and against any liability, loss or damage they may suffer as a result of
claims against the Indemnified Parties arising out of this Agreement, including but not limited to claims made against any of the Indemnified Parties as a result of Adherex’ use of any of the Licensed Data. The indemnity in this clause will not
apply to the extent that the claim arises as a result of the Indemnified Party’s gross negligence or willful misconduct. 

  

	6.	Publication 

  

	6.1	The parties agree that the AVL researchers, including without limitation any AVL co-authors, retain the right to publish any of the Licensed Data in accordance with accepted
scientific practices; provided, however, that AVL and AVL’s co-authors, as applicable, will submit copies to Adherex of any proposed publication or other public presentation of previously unpublished data, including without limitation data to
be generated pursuant to the Follow-up Study, at least thirty (30) days prior to the date of the proposed disclosure. Adherex may, by giving written notice to AVL, require AVL and AVL’s co-authors, as applicable, to delay the proposed
Publication for a maximum of 30 days after receipt of the written notice if, in Adherex’s reasonable opinion, that delay is necessary in order to seek patent or similar protection for any data that are to be disclosed. 

 

	7.	General 

  

	7.1	The parties acknowledge and agree that Adherex will not by reason of this Agreement have any obligation, responsibility or other role in the future conduct or monitoring of
AVL’s research activities, unless explicitly agreed in writing between the parties’ legal representatives. Adherex acknowledges that AVL may subcontract, at AVL’s sole expense, certain parts of the work to be performed under the
Follow-up Study to other, non-commercial third parties. AVL shall ensure that any such work by third parties will not in any way limit or affect the rights of Adherex or the obligations of AVL hereunder and shall obtain the acceptance of the terms
of this Agreement from such third parties as is necessary for this purpose. 

  

	7.2	 The parties represent that they are not obligated under any pre-existing arrangement or other agreement which would affect the rights or duties of the parties under
this Agreement, and the performance of this Agreement will not breach any agreement by which either party is bound, including any pre-existing 

	 	 
rights or agreement limiting the use or disclosure of the Licensed Data as contemplated hereunder. AVL agrees not to disclose or make use of any information
in the course of performing this Agreement, which AVL does not have the right to disclose. 

  

	7.3	Nothing in this Agreement will be construed to create an employer-employee relationship between any AVL representative and Adherex. Neither party will employ or use the name of the
other party in any publication or promotional material or in any public distribution without the prior written consent of the other party, except as may be required by law or regulation. 

  

	7.4	This Agreement will be binding on the each of the party’s heirs, successors, executors, legal representatives, and permitted assigns and will inure to the benefit of their
respective successors and assigns. This Agreement constitutes the entire agreement between the parties with respect to the subject matter hereof. 

  

	7.5	This Agreement may be executed in any number of counterparts, each of which shall be deemed to be an original and all of which taken together shall be deemed to constitute one and
the same instrument. Counterparts may be executed either in original or faxed form and the parties adopt any signatures received by facsimile as original signatures of the parties. 

  

	7.6	This Agreement will be effective as of the Effective date. Either party may terminate this Agreement with immediate effect by giving notice to the other party if the other party is
in breach of any provision of this Agreement and such breach has not been remedied within thirty (30) days after receipt of written notice specifying the breach and requiring its remedy. Adherex has the right to terminate the exclusive license
granted hereunder by a three (3) month prior written notice if Adherex decides not to continue with the development of STS. 

  

	7.7	Termination of this Agreement shall not affect the rights and obligations of the parties accrued prior to termination. 

 SIGNATURES START ON THE FOLLOWING PAGE 
  

 In witness thereof, AVL and Adherex have caused this Agreement to be executed in duplicate by their respective duly
authorized officers. 
  

			
	Adherex Technologies Inc.
	
	 /s/ William P. Peters

	Name:	 	William P. Peters, MD PhD
	Title:	 	Chairman & CEO
	Date:	 	05/01/2008

  

			
	Stichting Antoni van Leeuwenhoek Ziekenhuis
	
	 /s/ S. Rodenhuis

	Name:	 	Prof. dr. S. Rodenhuis
	Title:	 	Clinical Director
	Date:	 	05/13/2008

 Schedule 1 
 Description of the Follow-up Study: 
 Follow-up Study will include long-term (4-year) ototoxicity status, other treatment
related toxicity information, disease free and overall survival data from the study entitled “Ototoxicity in a Randomized Phase III Trial of Intra-Arterial Compared With Intravenous Cisplatin Chemoradiation in Patients with Locally Advanced
Head and Neck Cancer” (as published by CL Zuur et al. J Clin Oncol 2007; 25(24):3759-65).

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