Exhibit 10.3



 Exhibit 10.3 
  

	[**]	Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. 


ADDENDUM 1.1 

No. 012174-1NOHL-01.1 

TO THE PARTNERSHIP AGREEMENT No. 012174-1NOHL-OO 

This Project Addendum 1.1 (the “Project Addendum 1.1”) is made and entered into as of 1 January 2014 (the “Project
Addendum 1.1 Effective Date”), by and between GenSight Biologics SA, a corporation organized under the laws of France, registered with the Lyon Trade and Company Registry under number B 751 164 757 (SIRET: 75116475700013), with its
principal place of business at 74 rue du Faubourg Saint Antoine 75012 Paris, France (“GenSight”), and Genethon, a non-profit organization organized under the laws of France, with its principal place of business at 1bis, rue de
l’Internationale, 91002 Evry Cedex, France (SIRET: 40218752000018) (“Genethon”), (each of GenSight and Genethon a “Party” individually and collectively the “Parties”). 

BACKGROUND 

WHEREAS, the Parties entered into a partnership agreement No. 012174-1 NOHL-00 on February 1, 2013 (the “Partnership
Agreement”), and agreed on the specific conditions of the Leber’s Hereditary Optic Neuropathy (“LHON”) program (the “LHON Research Program”) in a first addendum dated 2 April 2013 (the
“Project Addendum 1”) (the Partnership Agreement and its Project Addendum 1 are hereafter referred to as the “LHON Partnership Agreement”); 

WHEREAS, the Parties agree to extend Genethon’s activities in the framework of the LHON Research Program, in particular regarding
further process development, GMP manufacturing for future commercial batches covering EU and USA territories, clinical and regulatory support activities and the provision of a project development plan. 

NOW THEREFORE, in consideration of the mutual covenants, conditions and undertakings herein contained, the Parties agree as follows:

  

	 	1.	OBJECT OF THIS PROJECT ADDENDUM 1.1 

  

	 	1.1	The Parties agree to modify the conditions of the LHON Research Program relating to clinical and regulatory support as described in Exhibit 2A of the Project Addendum 1 in particular in section 4 with the conditions set
forth in Exhibit 2B here-attached. The Parties agree to re-negotiate whether clinical support by Genethon will still be desired by GenSight and agreed by Genethon following the end of the period contracted for clinical support by
Genethon, which is October 31, 2014, and if so the amount to be paid by GenSight regarding such continued activities. 

  

	 	1.2	As mentioned in section 5 of Exhibit 2A of the Project Addendum 1, the Parties agree to further develop the manufacturing process to support the later stages of clinical development and eventual commercial sales. In
this context, Genethon has provided to GenSight a project development plan as attached in Exhibit 2C section B of this Project Addendum 1.1 with the amount to be paid by GenSight regarding such activities indicated in Exhibit 2C section A of
this Project Addendum 1.1. Such development plan and activities are also related to a quality agreement that is under discussion between both parties for defining, establishing and documenting the responsibilities of each party involved in the
contract manufacturing of LHON Research Program subject to current Good manufacturing practice (CGMP). 


  
 1 









	 	2.	STRATEGIC COMMITTEE 

 In accordance with section 3.1 of the Partnership Agreement, the
Parties agree to modify the GenSight’s authorized representatives to the Strategic Committee. Said authorized representative will be (i) the “chief operating officer” or the “directeur general” (any of them
referred to the “D” as mentioned in the Partnership Agreement) and (ii) one senior scientist (“SC Member”). 
  

	 	3.	DURATION 

 This Project Addendum 1.1 enters into force on the Project Addendum 1.1
Effective Date for the duration of the LHON Research Program. 
  

	 	4.	INTANGIBILITY OF UNMODIFIED CLAUSES 

 All the terms and conditions of the LHON
Partnership Agreement and its Project Addendum 1 that have not been modified by, and that are not in contradiction to, this Project Addendum 1.1 shall apply. Capitalized terms used in this Project Addendum 1.1 and not otherwise defined shall have
the meaning ascribed to such terms in the LHON Partnership Agreement. As of the Project Addendum 1.1 Effective Date, any reference to the Project Addendum 1.1 shall be deemed a reference to the LHON Partnership Agreement as amended by this Project
Addendum 1.1. 
 IN WITNESS WHEREOF, the Parties have caused their duly authorized representatives to execute this Project
Addendum 1.1. 
  

					
		 	GenSight Biologics SA	 	Genethon
		 	/s/ Bernard Gilly	 	/s/ Frédéric Revah
		 	Title: CEO	 	Title: CEO


  
 2 








 EXHIBIT 2B 

LHON Project Addendum 
  

[**] 
  

	[**]	Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. 


  
 3 








  EXHIBIT 2C 

LHON Project Addendum 

Amendment 
  

 
 GenSight and Genethon shall conduct the LHON Project
under the terms specified in the LHON Partnership Agreement except that the following changed provisions relating to the project development plan shall apply: 

1. Payment for the project development plan 

[**] 
 2. Project
development plan 
 [**] 

Abreviations 
 AAV: Adeno-Associated Virus 

AUC: Analytical UltraCentrifugation 
 AWD: Aerial Way Disinfection

 B LA: Biologic License Application 
 BSSS: Buffer Sterile
Saline Solution 
 CF10: Cell Factory 10 trays 
 DGAT: counting
of total aerobic germs (Dénombrement des Germes Aérobiques Totaux) 
 DM LT: counting of Total Mold and Yeast (Dénombrement des
Moisissures/Levures Totales) 
 DS: Drug substance 
 DP: Drug
Product 
 DSP: Down Stream process ER: Engineering runs 
 EOP:
End Of Production 
 EP: European Pharmacopeia FCS: Foetal Calf Serum 

GBP: Genethon Bioprod 
 GM P: Good Manufacturing Practice 

GM P-S: GM P - Source 
 GNT: Genethon 

HEK: Human Embryonic Kidney 
 ICH: International Conference on
Harmonization 
 lg: lnfectious genome 
 IPC: In Process Control

 LAL: Limulus amebocyte lysate (LAL) 
 LHON: Leber Hereditary
Optical Neuropathy 
 MCB: Master Cell Bank 
 M FT: Media Fill
Test 
 MGB: Master Glycerol Bank 
 PQ: Performance
Qualification 
 RFP: Request for Proposal 
 SOS: Sodium Dodecyl
Sulfate 
 SOP: Standard Operational Procedure 
 TBC: To be
confirmed 
 TFF: Tangential Flow Filtration 
 U FC: Unit
Forming Colony 
 USP: upstream process USP: US Pharmacopeia 

Vg: Viral genome 
 WCB: Working Cell bank 

wt: wild-type 
  

	[**]	Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. 


  
 4 








  Table of content 
   

											
	1.	  	Executive summary / GenSight requirements	  	 	5	  
	2.	  	Manufacturing process	  	 	6	  
		  	2.1.	  	Process flow chart description	  	 	6	  
		  	2.2.	  	Starting materials	  	 	7	  
		  		  	2.2.1.	  	Plasmids	  	 	7	  
		  		  	2.2.2.	  	Cell bank	  	 	7	  
		  		  	2.2.3.	  	Raw materials	  	 	11	  
		  	2.3.	  	Process parameters justification and improvements	  	 	12	  
		  		  	2.3.1.	  	UpStream Process, (USP)	  	 	12	  
		  		  	2.3.2.	  	Down Stream Process, (DSP)	  	 	13	  
		  	2.4.	  	Engineering runs	  	 	17	  
		  	2.5.	  	Drug substance	  	 	18	  
		  		  	2.5.1.	  	Storage and container	  	 	18	  
		  		  	2.5.2.	  	Stability study	  	 	18	  
		  	2.6.	  	Drug Product	  	 	19	  
		  		  	2.6.1.	  	Fill and finish operations	  	 	19	  
		  		  	        2.6.1.1.     Primary content	  	 	19	  
		  		  	        2.6.1.2.     Visual inspection	  	 	20	  
		  		  	2.6.2.	  	Packaging operations	  	 	20	  
		  		  	2.6.3.	  	Ready to use product	  	 	20	  
		  		  	2.6.4.	  	Extractables/leachables	  	 	21	  
		  		  	2.6.5.	  	Stability study	  	 	21	  
		  		  	2.6.6.	  	Clinical batches and manufacturing organization	  	 	22	  
	3.	  	Product characterization	  	 	23	  
		  		  	3.1.1.	  	Expression assay	  	 	23	  
		  		  	3.1.2.	  	Potency assay	  	 	23	  
		  		  	3.1.3.	  	Impurities	  	 	24	  
		  		  	        3.1.3.1. Residual DNA	  	 	24	  
		  		  	            3.1.3.1.1. Full length rep and cap	  	 	24	  
		  		  	            3.1.3.1.1. Full length kanamycin resistance genes	  	 	24	  
		  		  	            3.1.3.1.1. Host cell DNA	  	 	25	  
		  		  	        3.1.3.2. Proteins impurities	  	 	25	  
		  		  	3.1.4.	  	Extended characterization: aggregation	  	 	25	  
	4.	  	Validation	  	 	26	  
		  	4.1. Process validation	  	 	26	  
		  	4.2. Method validation	  	 	26	  
		  	4.3. Decontamination validation	  	 	27	  
	5.	  	Pharmaceutical establishment status	  	 	27	  
	6.	  	Project management	  	 	27	  
	7.	  	Annexes	  	 	28	  

   Figure and table content 

[**] 
  

	[**]	Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. 








  1. EXECUTIVE SUMMARY/ GENSIGHT REQUIREMENTS 

GenSight Biologics is the sponsor of a phase I/II clinical trial for the treatment of patients suffering from Leber’s hereditary optical neuropathy
disease (LHON). The pathology originates from an inherited mutation in the mitochond rial nd4 gene. 
 The treatment will consist in the intra-ocular
injection of “GS010 gene transfer product”. GS010 product is a suspension of infectious recombinant AAV2/2 viruses expressing the human wild type (wt) form of the mitochondrial nd4 gene mutated in the pathology. 

Manufacturing process developed for the supply of phase I/II clinical material is based on triple plasmid transfection into [**] cells plated in [**] followed
by vector purification based on affinity chromatography. GS010 product is presented as a [**] ([**]) of concentrated infectious viruses formulated in a [**] ([**]). 

Up to now, four batches have been produced with this manufacturing process: [**] pre- clinical batches ([**]) and [**]
clinical batches ([**]). 
 Current specification for vector titer is superior or equal to [**]vg/mL, and the mean titer obtained was [**] vg/mL. 

Next step of GS010 pharmaceutical development is to move towards pivotal phase in US and Europe with a manufacturing process compatible with commercial
registration. 
 This document is intended to present the pharmaceutical development plan to be implemented at Généthon Bioproduction (GBP)
for the supply of later clinical phase material and product registration. 
 Based on existing data and evaluation of clinical and market product needs,
Gensight and GNT have agreed to move ahead with the existing process. 
 Pharmaceutical development of production, aseptic filling, and quality control
operations will be presented as well as GBP organization. 
 Each item is presented and associated to resources, schedule, subcontracting and concerns (if
any). 
 Gensight requirements for GS010 for pivotal phase: 
  

	•	 	Specification of vg titer equal or stronger to [**] vg/mL (dose for pivotal phase up to [**] vg/dose) 

  

	•	 	Implementation of filling process [**] 

  

	•	 	Qualification of a [**] ([**]) 

  

	•	 	Release process of the Drug Substance 

  

	•	 	Drug Product presented [**] 

  

	•	 	Number of patients/dose: [**] 

 Those requirements are extended for commercial registration to: 

 

	•	 	Process and analytical methods validation 

  

	•	 	Process scale designed to support the supply of [**] units / year for commercial phase ([**] vg/year) 

  

	•	 	Genethon Bioprod approved as provider of commercial products by both EU and US regulatory agencies. 

  

	[**]	Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. 








  2. MANUFACTURING PROCESS 

 

	2.1	Process flow chart description 

 [**] 

 

	2.2	Starting materials 

 [**] 

 

	2.2.1	Plasmids 

 [**] 
  


	2.2.2	Cell Bank 

 [**] 

 

	2.2.3	Raw materials 

 [**] 

 

	2.3	Process parameters justification and improvements 

  

	2.3.1	UpStream Process, (USP) 

 [**] 

 

	2.3.2	Down Stream Process, (DSP) 

 [**] 

 

	2.4	Engineering runs 

 [**] 

 

	2.5	Drug substance 

  

	2.5.1	Storage and container 

 [**] 

 

	2.5.2	Stability study 

 [**] 

 

	2.6	Drug Product 

  

	2.6.1	Fill and finish operations. 

  

	 	2.6.1.1.	Primary content 

 [**] 

 

	 	2.6.1.2.	Visual inspection 

 [**] 

 

	 	2.6.2	Packaging operations 

 [**] 

 

	2.6.3	Ready to use product 

 [**] 

 

	[**]	Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. 


  
 7 









	2.6.4	Extractables/leachables 

 [**] 

 

	2.6.5	Stability study 

 [**] 

 

	2.6.6	Clinical batches and Manufacturing organization 

 [**] 

 

	3.	Product characterization 

 [**] 

 

	3.1	Analytical methods 

  

	3.1.1	Expression assay 

 [**] 

 

	3.1.2	Potency assay 

 [**] 

 

	3.1.3	Impurities 

  

	 	3.1.3.1	Residual DNA 

  

	 	3.1.3.1.1.	Full length rep and cap  

 [**] 

 

	 	3.1.3.1.1.	Full length kanamycin resistance genes 

 [**] 

 

	 	3.1.3.1.1.	Host cell DNA 

 [**] 

 

	 	3.1.3.2	Proteins impurities 

 [**] 

 

	3.1.4	Extended characterization : aggregation 

 [**] 

 

	4.	Validation 

  

	4.1	Process validation 

 [**] 
  

	4.2	Method validation 

 [**] 
  

	4.3	Decontamination validation 

 [**] 

 

	[**]	Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. 


  
 8 









	5.	Pharmaceutical establishment status 

 [**] 

 

	6.	Project management 

 [**] 

 

	Ø	Main time Schedule (planning) 

  

	7.	Annexes 

 [**] 
  


	[**]	Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. 


  
 9