Amendment One to the License Agreement



 Exhibit 10.22 
 AMENDMENT ONE TO THE 
 EXCLUSIVE LICENSE 

(CMCC-10665) 
 This amendment is
made and entered into as of May 12, 2011 (the “Amendment”) by and between Children’s Medical Center Corporation, a corporation duly organized and existing under the laws of the Commonwealth of Massachusetts and having offices
located at 300 Longwood Avenue, Boston, MA (“CMCC”) and InVivo Therapeutics Corporation, a business corporation organized and existing under the laws of the State of Delaware and having its principal office at One Broadway, 14th Floor,
Cambridge, MA “Licensee”). 
 WHEREAS, CMCC and Licensee have entered into that certain Exclusive License Agreement with an effective
date of July 2, 2007 and identified as agreement number CMCC-6748 (the “Agreement”); 
 WHEREAS CMCC and Licensee wish to amend
such Agreement through this Amendment; and 
 WHEREAS the Agreement otherwise remains unchanged. 

In consideration of these premises and of the mutual promises set forth below, the parties agree to amend the Agreement as follows: 

Amendments to the Agreement: 

1. Article I. Definitions, Paragraph F of the Agreement, “Field of Use”, is hereby deleted in its entirety and replaced as follows:

  

	F.	“Field of Use” shall mean the following three subfields: i) treatment of nerve injury of the central nervous system including the brain, and spinal cord; ii)
treatment of nerve injury of the retina and the cranial nerves; and iii) treatment of the following pathologic conditions: nerve root impingement from musculoskeletal elements, demyelinated tissue, damage to neural elements exiting the spinal cord
and lumbosacral region of spinal cord by administering a Licensed Product to the peripheral nerves in the intraspinal location, foraminal and extraspinal areas, extrapyramidal regions, areas of peripheral bony impingement, and for repair or
treatment of neural elements following damage from prostate surgery; excluding the development and commercialization of tissue engineered products for human and animal therapeutics in the field of genitourinary. 


2. In consideration for expanding the Field of Use, Licensee shall pay to CMCC a license amendment fee of $75,000 within thirty (30) days of
the full execution of this Amendment in addition to any other payments due under the Agreement and/or this Amendment. 







 3. In each of the following paragraphs, the term “Development Plan” shall be replaced with
the terms “Development Plan and Commercialization Plan”: 
 Article II, Paragraph A 

Article III, Paragraphs C, F and G 
 Article V, Paragraphs C and D 
 4. Article III Due Diligence and Related Matters, Paragraph
B of the Agreement, is hereby deleted in its entirety and replaced as follows: 
  

	 	B.	The parties acknowledge that Licensee had provided to CMCC prior to the date of execution of the Agreement an initial written development plan setting forth for a
period of five (5) years beginning July 2, 2007, projections for the initial indications and markets for Licensed Products and Licensed Processes for the subfield of Spinal Cord Injury in the Field of Use. Licensee represents that Licensee
has used diligent efforts during the first three (3) years of the Agreement as described in Article III, Section D of the Agreement of having (i) raised and allocated a cumulative total of investment capital and/or research and development
funds of at least $1,000,000 during the year of September 26, 2006 and September 26, 2007 and (ii) expended at least $6 million to implement such initial development plan. The parties acknowledge that Licensee has provided to CMCC
prior to the date of execution of this Amendment a written development plan (“Development Plan”) setting forth for a period of two (2) years beginning November 16, 2010, projections for the initial indications and markets for
Licensed Products and Licensed Processes in the Field of Use, including (i) time-delimited targets for pre-clinical development, clinical trials, regulatory approval, manufacturing and marketing that represent reasonable efforts, consistent
with industry norms for similar technology and applications, to bring Licensed Products to the marketplace; and (ii) actual or projected financial resources and/or strategic alliances that will be required to implement the Development Plan and
(iii) identified project management structure calculated to meet the objectives and commitments in the Development Plan. The Development Plan is attached hereto as Appendix 2 and is hereby incorporated herein by reference. In addition, prior to
submission of the first regulatory filing relating to the first Licensed Product, but in any event no later than July 2, 2012, which is five years from the Effective Date of the Agreement, Licensee shall submit a commercialization plan
(“Commercialization Plan”) setting forth projected (i) time delimited commercialization milestones for bringing Licensed Products to the marketplace and (ii) strategic alliances (including but not limited to alliances with
Distributors) required to achieve the goals outlined in the Commercialization Plan. The Commercialization Plan shall be attached to the Agreement as Appendix 3. 








 5. Article IV Paragraph A.3 of the Agreement, is hereby deleted in its entirety and replaced as
follows: 
 3. Licensee shall make the following payments to CMCC upon the occurrence of the following events
(“Milestones”): 
  

	 	(a)	$50,000 upon the filing with the United States Food and Drug Administration (“FDA”) of the first Investigational New Drug (“IND”) application,
Investigational Device Exemption (“IDE”) application, or comparable application for the first_Licensed Product in the first subfield of the Field of Use, and $25,000 for filing such an application for the first_Licensed Products in each of
the second and third subfields of the Field of Use; 

  

	 	(b)	$75,000 upon the enrollment of the first patient in Phase II testing of the first Licensed Product in the first subfield of the Field of Use, and $37,500 for enrollment
of the first patient in phase II testing of the first_Licensed Products each of the second and third subfields of the Field of Use; 

  

	 	(c)	$100,000 upon the enrollment of the first patient in Phase III testing of the first Licensed Product in the first subfield of the Field of Use, and $50,000 for the
enrollment of the first patient in Phase III testing of the first Licensed Products each of the second and third subfields of the Field of Use; 

  

	 	(d)	$250,000 upon filing with the FDA of each first New Drug Application (“NDA”), 510(k) application, Pre-Market Approval (“PMA”) application or PMA
Supplement, or BLA, or comparable application in each of the three subfields of the Field of Use; 

  

	 	(e)	$500,000 upon approval fby the FDA of the first NDA, 510(k), PMA or PMA Supplement, BLA, or comparable application within the United States with respect to any Licensed
Product; 

  

	 	(f)	$500,000 upon first marketing approval in the first country outside of the United States; and 


 

	 	(g)	Running royalties in an amount equal to three percent (3%) of Net Sales of Licensed Products used, leased or sold by and/or for Licensee (including its
Affiliates). 

 6. Article VI Patent Prosecution, Paragraph B of the Agreement, is hereby deleted in its entirety and
replaced as follows: 
  

	 	B.	Licensee shall reimburse CMCC for all patent costs, past, present and future incurred by CMCC for the preparation, filing, prosecution and maintenance of patents
underlying the Patent Rights. Licensee shall pay 









	 	
such costs for the patents and applications in Appendix 1A within thirty (30) days after receipt of an invoice covering such costs. Upon request of CMCC, and only upon such CMCC request,
Licensee agrees to have CMCC’s patent counsel directly bill Licensee and Licensee shall directly pay such invoices in compliance with such counsel’s customary business terms, but in any event not greater than thirty (30) days from
receipt of invoice which is not disputed in good faith. If Licensee elects to no longer pay the expenses of a patent application or patent included within Patent Rights, Licensed Products or Licensed Processes, Licensee shall notify CMCC, and MIT
(at the address specified below), not less than sixty (60) days prior to such action and shall thereby surrender its rights under such patent or patent application. Such notice shall not relieve Licensee from responsibility to reimburse CMCC
for patent-related expenses incurred prior to the expiration of the (60)-day notice period (or such longer period specified in Licensee’s notice). CMCC and MIT shall each then be free to license its rights to that patent or patent application
to any other party on any other terms. Notice to MIT described herein shall be sent consistent with Article XV to: 

 Massachusetts Institute of Technology 
 Technology Licensing Office, Room NE18-501

 One Cambridge Center, Kendall Square 
 Cambridge, MA 02142-1601 
 Attention: Director 

Tel: 617-253-6966 
 Fax: 617-258-6790 
 7. Article VI Patent Prosecution, Paragraph D of the Agreement, is
hereby deleted in its entirety and replaced as follows: 
 D. MIT shall prepare, file, prosecute, and maintain all of the Patent
Rights in Appendix 1B. Licensee shall reimburse MIT, as enumerated in Articles VI(D)(i), VI(D)(ii), and VI(D)(iii) below, for patent costs, past, present and future incurred by MIT for the preparation, filing, prosecution and maintenance of patents
underlying the Patent Rights in Appendix 1B. MIT shall directly submit invoices for payment to Licensee. Licensee shall reimburse all amounts due pursuant to this Section within thirty (30) days of invoicing. Any payments by Licensee that are
not paid on or before the date such payments are due under this Article VI( D) shall bear interest, to the extent permitted by law, at two percentage points above the Prime Rate of interest as reported by the Federal Reserve Bank of St. Louis on the
date payment is due. In all instances, MIT shall pay the fees prescribed for large entities to the United States Patent and Trademark Office. 







 (i) Payment of Patent Costs Incurred by MIT from July 2, 2007
through May 12, 2011. Licensee shall be responsible for payment of Twenty Five Percent (25%) of the total patent costs incurred by MIT from the Effective Date through May 12, 2011, for the Patent Rights in Appendix 1B. 

(ii) Additional Payment of Patent Costs Incurred Prior to May 12, 2011. In addition to the amounts due in
Article VI(D)(i), Licensee shall be responsible for payment of One Hundred Percent (100%) of the total unreimbursed patent costs incurred by MIT prior to May 12, 2011, for the Patent Rights in Appendix 1B. The amount due under this section
VI(D)(ii), shall not exceed Fifty Thousand dollars ($50,000). 
 (iii) Payment of Patent Costs Incurred by
MIT on and After May 12, 2011 
 For the purpose of this section, “Co-Licensed Cases” shall mean
CMCC Case 23 (MIT Case 4973) and CMCC Case 30 (MIT Case 4279) 
  

	 	(a)	Co-Licensed Cases. Licensee shall be responsible for payment of Fifty Percent (50%) of the total unreimbursed patent costs incurred by MIT on and after
May 1, 2011, for the Patent Rights in the Co-Licensed Cases. As of May 1, 2011, there is another licensee paying Fifty Percent (50%) of the total unreimbursed patent costs incurred by MIT for the Patent Rights in the Co-Licensed Cases
(“Third Party”). In the event that the Third Party abandons its rights to the Co-Licensed Cases, Licensee shall pay One Hundred Percent (100%) of the costs of the Co-Licensed Cases from the date of abandonment of such rights by the
Third Party. 

  

	 	(b)	Patent Rights listed in Appendix 1B except for Co-Licensed Cases. Licensee shall be responsible for payment of One Hundred Percent (100%) of the total
unreimbursed patent costs incurred by MIT on and after May 1, 2011, for the Patent Rights in Appendix 1B (excluding the Co-Licensed Cases). 

 8. Article XV. Payments, Notices, And Other Communications, notice to Licensee shall be made to the following: 
 Attn: Chief Executive Officer 
 InVivo Therapeutics Corporation 

One Broadway, 14th Floor 
 Cambridge, MA 02142 







 9. The following two (2) sentences are hereby added as the last sentences to Article III,
Paragraph G of the Agreement: 
 The parties acknowledge and agree that the Field of Use is comprised of the three
(3) subfields identified as i) through iii) in the definition thereof (each a “Subfield”). If Licensee fails to meet a requirement set forth in the Development Plan and/or Commercialization Plan pertaining to a Subfield and CMCC
terminates the rights granted to Licensee in accordance with this Paragraph G, such termination of rights shall apply only to such Subfield and not to any other Subfields which license granted under such Subfields shall continue pursuant to the
terms of the Agreement. For clarity, any loss of Subfields under this section does not relieve Licensee of obligations under this agreement in any other Subfields. 
 10 Appendix 1A shall be deleted and replaced in its entirety with Appendix 1A of this Amendment One. 
 11. Appendix 1B shall be deleted and replaced in its entirety with Appendix 1B of this Amendment One. 
 IN WITNESS WHEREOF, the parties have hereunto set their hands and seals and duly executed this Amendment the day and year set forth below. 

 

									
	CHILDREN’S MEDICAL CENTER CORPORATION	 		 	INVIVO THERAPEUTICS CORPORATION
					
	By	 	/s/ Erik Halvorsen	 		 	By	 	/s/ Frank Reynolds
		 	Erik Halvorsen Ph.D.	 		 		 	Frank Reynolds
		 	Director of Technology & Business Development	 		 		 	Chief Executive Officer
		 		 		 		 	
	Date	 	5-25-11	 		 	Date	 	May 12 2011

  







 Appendix 1A: Patent Rights 

The following patents and patent applications based on CMCC case 1455 (M.I.T. Case 

Number 12084) and CMCC case 1456 (M.I.T. Case 13490Q): 
  

									
	Country	  	Serial Number	  	Filing Date	  	Status	  	Issue Date
	 U.S.
	  	60/794,986	  	4/25/2006	  	Expired	  	00/00/00
	 U.S.
	  	11/789,538	  	4/25/2007	  	Pend	  	00/00/00
	 U.S.
	  	12/186,346	  	8/5/2008	  	Pend	  	00/00/00
	 PCT
	  	PCT/US08/72226	  	8/5/2008	  	Expired	  	00/00/00
	 Australia
	  	2008360388	  	8/5/2008	  	Pend	  	00/00/00
	 Brazil
	  	TBA-BR	  	8/5/2008	  	Pend	  	00/00/00
	 Canada
	  	TBA-CA	  	8/5/2008	  	Pend	  	00/00/00
	 China
	  	TBA-CN	  	8/5/2008	  	Pend	  	00/00/00
	 India
	  	TBA-IN	  	8/5/2008	  	Pend	  	00/00/00
	 Japan
	  	TBA-JP	  	8/5/2008	  	Pend	  	00/00/00
	 Singapore
	  	TBA-SG	  	8/5/2008	  	Pend	  	00/00/00
	 South Korea
	  	10-2011-7005148	  	8/5/2008	  	Pend	  	00/00/00
	 EPO
	  	EP-TBA	  	8/5/2008	  	Pend	  	00/00/00
	 PCT
	  	PCT/US07/067403	  	4/25/2007	  	Expired	  	00/00/00
	 Australia
	  	TBA- AU	  	4/25/2007	  	Pend	  	00/00/00
	 Brazil
	  	PI 0709638-0	  	10/23/2008	  	Pend	  	00/00/00
	 Canada
	  	2650804	  	4/25/2007	  	Pend	  	00/00/00
	 China
	  	200780022752.6	  	4/25/2007	  	Pend	  	00/00/00
	 India
	  	TBA	  	10/24/2008	  	Pend	  	00/00/00
	 Japan
	  	0	  	10/23/2008	  	Pend	  	00/00/00
	 Singapore
	  	200807854-5	  	4/25/2007	  	Pend	  	00/00/00
	 South Korea
	  	10-2008-7028672	  	11/24/2008	  	Pend	  	00/00/00
	 EPO
	  	7761270.3	  	4/25/2007	  	Pend	  	00/00/00
	 Hong Kong
	  	9106081.8	  	4/25/2007	  	Pend	  	00/00/00








 Appendix 1B: Additional Patent Rights 

 

	I.	United States Patents and Applications 


CMCC Case No. 23 (M.I.T. Case No. 4973) 
 United States of America Patent No. 5804178, Issued September 8,1998 
 “IMPLANTATION
OF CELL-MATRIX STRUCTURE ADJACENT MESENTERY, OMENTUM OR PERITONEUM TISSUE” 
 by Linda G. Griffith, Lynt Johnson, Robert S. Langer and
Joseph P. Vacanti 
 CMCC Case No. 25 (M.I.T. Case No. 5573) 
 United States of America Patent No. 5514378, Issued May 7, 1996 
 “BIOCOMPATIBLE
POLYMER MEMBRANES AND METHODS OF PREPARATION OF THREE DIMENSIONAL MEMBRANE STRUCTURES” 
 by Linda G. Griffith, Robert S. Langer, Antonios
G. Mikos, Georgios Sarakinos and Joseph P. Vacanti 
 CMCC Case Nos. 20 and 30 (M.I.T. Case No. 4279) 

United States of America Patent No. 5759830, Issued June 2, 1998 
 United States of America Patent No. 5770417, Issued June 23,1998 

“THREE-DIMENSIONAL FIBROUS SCAFFOLD CONTAINING 
 ATTACHED CELLS FOR PRODUCING VASCULARIZED TISSUE IN VIVO” 
 by Robert S. Langer and Joseph P.
Vacanti 
 United States of America Patent No. 5770193, Issued June 23, 1998 “PREPARATION OF THREE-DIMENSIONAL FIBROUS SCAFFOLD
CONTAINING ATTACHED CELLS FOR PRODUCING VASCULARIZED TISSUE IN VIVO” 
 by Robert S. Langer and Joseph P. Vacanti 

CMCC Case No. 26 (M.I.T. Case No. 5729) 
 United States of America Patent No. 6309635, Issued October 30, 2011 

“PREVASCULARIZED POLYMERIC IMPLANTS FOR ORGAN TRANSPLANTATION” 
 by James C. Gilbert, Donald E. Ingber, Robert S. Langer, James E. Stein and Joseph P. Vacanti 

CMCC Case No. 389 (M.I.T. Case No. 6560) 
 United States of America Patent No. 7462471, Issued December 9, 2008 







 “POROUS BIODEGRADABLE POLYMERIC MATERIALS FOR CELL TRANSPLANTATION” 

by Linda G. Griffith, Robert S. Langer, Antonios G. Mikos, Georgios Sarakinos and Joseph P. Vacanti 

CMCC Case No. 415 (M.I.T. Case No. 6798) 
 United States of America Patent No. 6281015, Issued August 28, 2001 
 “LOCALIZED
DELIVERY OF FACTORS ENHANCING SURVIVAL OF TRANSPLANTED CELLS” 
 by Robert S. Langer, David J. Mooney and Joseph P. Vacanti 

CMCC Case No. 505 (M.I.T. Case No. 7138) 
 United States of America Patent No. 6095148, Issued August 1, 2000 
 “NEURONAL
STIMULATION USING ELECTRICALLY CONDUCTING POLYMERS” 
 by Robert S. Langer, Christine E. Schmidt, Venkatiam P. Shastri and Joseph P. Vacanti

 M.I.T. Case No. 6984 

United States of America Patent No. 5654381, Issued August 5, 1997 
 “FUNCTIONALIZED POLYESTER GRAFT COPOLYMERS” 
 by Jeffrey S. Hrkach, Robert S. Langer and
Noah Lotan 
 M.I.T. Case No. 13525 (CMCC Case No. 26) 
 United States of America Patent No. 6689608, Issued February 10, 2004 
 United States of
America Serial No. 12/218448, Filed July 15, 2008 
 “POROUS BIODEGRADABLE POLYMERIC MATERIALS FOR CELL TRANSPLANTATION”

 by Linda G. Griffith, Robert S. Langer, Antonios G. Mikos, Georgios Sarakinos and Joseph P. Vacanti 

 

	II.	International (non-U.S.) Patents and Applications 

 CMCC Case No. 26 (M.I.T. Case No. 5729) 
 European Patent Convention Patent
No. 0610423, Issued May 7, 1997 
 Japan Patent No. 3524919, Issued February 20, 2004 

Austria Patent No. 0610423, Issued May 7, 1997 
 Belgium Patent No. 0610423, Issued May 7, 1997 
 France Patent No. 0610423, Issued
May 7, 1997 
 Germany Patent No. 69219613, Issued May 7, 1997 
 Italy Patent No. 0610423, Issued May 7, 1997 







 Luxembourg Patent No. 0610423, Issued May 7,1997 

Netherlands Patent No. 0610423, Issued May 7, 1997 
 Sweden Patent No. 0610423, Issued May 7, 1997 
 United Kingdom Patent No. 0610423,
Issued May 7, 1997 
 “PREVASCULARIZED POLYMERIC IMPLANTS FOR ORGAN TRANSPLANTATION” 

by James C. Gilbert, Donald E. Ingber, Robert S. Langer, James E. Stein and Joseph P. Vacanti 
 CMCC Case No. 30 (M.I.T. Case No. 4279) 
 Canada Patent No. 1340581, Issued
June 8, 1999 
 “CHIMERIC NEOMORPHOGENESIS OF ORGANS BY CONTROLLED CELLULAR IMPLANTATION USING ARTIFICIAL MATRICES” 

by Robert S. Langer and Joseph P. Vacanti 

CMCC Case No. 415 (M.I.T. Case No. 6798) 
 European Patent Convention Patent No. 0794790, Issued April 17, 2002 
 Japan Patent
No. 4361134, Issued August 21, 2009 
 Canada Patent No. 2207286, Issued October 7, 2003 

Ireland Patent No. 0794790, Issued April 17, 2002 
 Belgium Patent No. 0794790, Issued April 17, 2002 
 Switzerland Patent No. 0794790,
Issued April 17, 2002 
 Germany Patent No. 0794790, Issued April 17, 2002 

Denmark Patent No. 0794790, Issued April 17, 2002 
 Spain Patent No. 0794790, Issued April 17, 2002 
 France Patent No. 0794790, Issued
April 17, 2002 
 Austria Patent No. 0794790, Issued April 17, 2002 
 Greece Patent No. 3039884, Issued April 17, 2002 
 Sweden Patent No. 0794790, Issued
April 17, 2002 
 Italy Patent No. 0794790, Issued April 17, 2002 
 Luxembourg Patent No. 0794790, Issued April 17, 2002 
 Monaco Patent No. 0794790,
Issued April 17, 2002 
 Netherlands Patent No. 0794790, Issued April 17, 2002 

Portugal Patent No. 0794790, Issued April 17, 2002 
 United Kingdom Patent No. 0794790, Issued April 17, 2002 
 “LOCALIZED DELIVERY OF
FACTORS ENHANCING SURVIVAL OF TRANSPLANTED CELLS” 
 by Robert S. Langer, David J. Mooney and Joseph P. Vacanti 

CMCC Case No. 505 (M.I.T. Case No. 7138) 
 New Zealand Patent No. 321886, Issued June 8, 2000 
 Japan Patent No. 4451929,
Issued February 5,2010 
 South Korea Serial No. 98-703320, Filed October 31, 1996 







 Australia Patent No. 720275, Issued September 11, 2000 

Canada Serial No. 2236749, Filed October 31, 1996 
 Japan Serial No. 2008-287194, Filed October 31, 1996 
 Japan Serial No. 2009-244981,
Filed October 31, 1996 
 “NEURONAL STIMULATION USING ELECTRICALLY CONDUCTING POLYMERS” 

by Robert S. Langer, Christine E. Schmidt, Venkatram P. Shastri and Joseph P. Vacanti 







 Appendix 2 
 Development Plan 
 May 12, 2011 

Children’s Hospital Boston 
 300 Longwood
Avenue 
 Boston, MA 02115 
 To Whom it
May Concern: 
 Licensee shall use good faith and diligent efforts to accomplish the milestones set forth in this Development Plan and to
manufacture and distribute Licensed Products. 
 Our Development Plan for the patents licensed from CMCC is as follows. 

Licensee agrees to achieve the following specific requirements: 
 Spinal Cord Injury 
  

	 	1.	Rodent Study for scaffold implantation optimization (2010 through no later than November 2, 2012) 


 

	 	a.	Understanding the lesion volume associated with a contusion spinal cord injury 


 

	 	b.	Understanding the technique for implantation of a scaffold into an acute spinal cord contusion injury 


 

	 	c.	Understanding the safety and efficacy of scaffold implantation into a contusion injury in a rat 


 

	 	2.	Primate studies in acute SCI (2010 through no later than November 2, 2012) 


 

	 	a.	Further electromyographic, kinematic and histologic studies on the safety and efficacy of scaffold implantation in a spinal cord injury in a non-human primate


 Brain 
 Motor
pathways in mammals generally consist of two neuron systems where an upper motor neuron originates in the motor cortex and travels downwards and synapses in the spinal cord to the lower motor neuron that then exits the spinal cord. There are
occasions where study of the motor neurons and spinal cord will require brain/cerebral applications to assess for effects of any plasticity, sprouting, regeneration, or on the converse side, atrophy or dieback. Consequently, there may be occasions
where biotinylated dextran 







 amines (BDA) will be injected in the motor cortex with assessments conducted at the levels of the brain,
brain stem, and spinal cord. 
  

	1.	Rodent study using BDA tracing (2011 through no later than November 2, 2012) 


 

	 	a.	Study will label motor neurons with emphasis on the spinal cord and components of neurons originating from the motor cortex in the brain 


Peripheral Nervous System 
 Applications
related to acute, subacute, and chronic neurologic conditions and syndromes of the peripheral nerves to include those caused by trauma, impingement, inflammation, complex regional pain syndrome, and causalgia that can be treated using using these
patents. Pathologic conditions appropriate for treatment would include nerve root impingement from musculoskeletal elements, demyelinated tissue, damage to neural elements exiting the spinal cord and lumbosacral region of spinal cord. Target areas
include any part of the peripheral nerves in the intraspinal location, foraminal and extraspinal areas, extrapyramidal regions, and all locations of entrapment and impingement to include peripheral bony impingement, and repair or treatment of
cavernous nerves following damage from prostate surgery. Graft site support following primary peripheral nerve repair may also be appropriate for application of these technologies. 
 Currently the majority of compressive peripheral nerves injuries (such as disc herniation with nerve root impingement) are treated with injections of naked steroids and/or local anesthesia. One well-known
shortcoming in this area is the ability to maintain a consistent presence of the drug near the nerve for any sustained period beyond 1-3 days. We will perform pilot exploratory studies on the use of drug releasing hydrogel in the treatment of
compressive peripheral nerve injuries in the rodent. These studies will consist of the use of well-established compressive peripheral nerve injury models, likely of the rodent sciatic nerve, with application of injected hydrogel around the nerve and
possibly directly into the nerve depending on treatment arm. There are well-established models for assessing behavioral improvement after these experimental treatments and relatively well-established histological methodologies for assessing repair,
plasticity, and regeneration in peripheral nerve. 
  

	1.	Rodent pilot study for peripheral nerve regeneration (2011 through no later than November 2, 2012) 


 

	 	a.	The utility of drug-releasing hydrogels to protect and repair peripheral nerves will be assessed in a model injury in a rat. 


Retina 
 Primary sources of vision loss
are due to loss of: 








	 	•	 	 Photoreceptors: age-related macular degeneration, retinitis pigmentosa and retinal detachment. 



 

	 	•	 	 Retinal ganglion degeneration: glaucoma 


  

	1.	Porcine model of photoreceptor transplantation using biomaterials (2009 through 2011) 


 

	 	a.	Scaffold and stem cells will be transplanted subretinally in a porcine model to assess photoreceptor replacement using histological evaluation.


  

	2.	Nerve regeneration model in rodents using neural cell transplantation (2011 through no later than November 2, 2012) 


 

	 	a.	An optic nerve crush model will be used and scaffold and stem cells transplanted subretinally to assess regeneration of retinal ganglion cells histologically.


 Cranial Nerves 

Cranial nerves 2, 5, 7 and 8 (optic, trigeminal, facial, vestibulecochlear) are targets for regenerative therapies using biomaterials for cell delivery.

  

	1.	Cranial nerve regeneration pilot study in a rodent model (using optic nerve results to guide) (2011 through no later than November 2, 2012)


  

	 	a.	Intracranial injection of drug-releasing hydrogel to assess nerve regeneration in one or more rodent cranial nerve injury models with an initial emphasis on cranial
nerve 2 

 The actual or projected financial resources and/or strategic alliances that will be required to implement the
Development Plan beginning May 12, 2011 are: 
  

	 	1)	Licensee shall expend at least $3,000,000 in the aggregate during each calendar year 2011 and 2012 to implement the Development Plan and pay salaries and payroll
expenses. 

 Our future Research and Development plans will support our regulatory efforts to gain FDA approval for our range of
neurological devices. Therefore, the details of our research for 2011 and beyond will be determined through our meetings with the FDA and outlined in our Commercialization Plan. 
 Since we will be treating the same tissue for multiple central nervous system conditions, we are concurrently developing all of the technologies. As a result, we are cutting costs and development time,
for example by using tissue analysis results from spinal cord injuries to support human studies for retina repair, peripheral nerve repair, and the brain. 







 Please let me know if you have any questions. 

 

	
	Best Regards,
	
	/s/ Frank Reynolds
	 Frank Reynolds, CEO
 InVivo
Therapeutics Corporation