Exhibit 10.49

Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Asterisks
denote omissions.

FIRST AMENDMENT TO LICENSE, SUPPLY AND DISTRIBUTION AGREEMENT

THIS FIRST AMENDMENT TO LICENSE, SUPPLY AND DISTRIBUTION AGREEMENT is made and entered into as of this 19th day of December, 2005 (Effective Date) by and
between F.Hoffmann-La Roche Ltd. (FHLR) having a principal office at Grenzacherstrasse 124, Basel, Switzerland and 454 Life Sciences Corporation (454) having a principal office at 20 Commercial Street, Branford, CT 06405,
USA.

RECITALS

WHEREAS, the
Parties have entered into a written License, Supply and Distribution Agreement dated May 11, 2005 (Original Agreement); and

WHEREAS, according to the last paragraph of Section 2.7 of the Original Agreement the Parties wish to change the Initial estimated ASP in Section 3.3 (b) and Exhibit 2 of the Original Agreement and the Licensed
Products Specifications in Exhibit 3 of the Original Agreement.

NOW THEREFORE, in consideration of the covenants and mutual promises set forth
herein, the receipt and sufficiency of which are hereby acknowledged, the Parties agree as follows:

1. According to Section 3.3 (b) of
the Original Agreement the Parties hereby define in detail the Licensed Products, the initial estimated ASP for the Licensed Products and the launch date by amending Exhibit 2. Exhibit 2 shall be replaced by the following new Exhibit 2:

(See attached document.)

Furthermore, the launch date for
all Licensed Products shall be September 30, 2005.

2. Exhibit 3 of the Original Agreement shall be deleted in its entirety and replaced by the
following new Exhibit 3:

(See attached document.)

3.
The Parties agree that the Accessories listed on the new Exhibit 2 shall be treated the same as the Instrument regarding the payment of royalties.

4. According to Section 3.3 (c) the Parties have to agree on the applicable estimated ASP
for the following calendar year latest by November 30th. In deviation from this Section 3.3 (c) the
Parties agree that for the calendar year 2006 the applicable estimated ASP shall be as set out in Section 1 of this First Amendment.

IN
WITNESS WHEREOF, each of the Parties has caused this First Amendment to the Original Agreement to be executed by its duly authorized representative.



---

|                               |  |                          |  |                            |  |        |  |                          
|------------------------------ |  | ------------------------ |  | -------------------------- |  | ------ |  | -------------------------
|Basel,F. Hoffmann-La Roche Ltd |  |                          |  | Branford,454 Life Sciences
|                               |  |                          |  |                           
|By:                            |  | /s/ Severin Schwan       |  |                            |  | By:    |  | /s/ Christopher K. McLeod
|Name:                          |  | Severin Schwan           |  |                            |  | Name:  |  | Christopher K. McLeod    
|Title:                         |  | CEO Division Diagnostics |  |                            |  | Title: |  | President & CEO          
|Date:                          |  | Feb. 6, 2006             |  |                            |  | Date:  |  | Jan. 9, 2006             
|                               |  |                          | 
|By:                            |  | /s/ C. J. Ruetsch        |  |                            |  |       
|Name:                          |  | C. J. Ruetsch            |  |                            |  |        |  |                          
|Title:                         |  | Legal Counsel            |  |                            |  |        |  |                          
|Date:                          |  | Feb. 2, 2006             |  |                            |  |        |  |                          



---

|          |  |             |  |                                                           |  |          |  |                        
|--------- |  | ----------- |  | --------------------------------------------------------- |  | -------- |  | -----------------------
|Reagents 
|          |  |             |  |                                                          
|          |  | Cat. No.    |  | Product                                                   |  | ASP$/Kit |  | Transfer Price$/Sub Kit
|Kit       |  | 04746694001 |  | GS 20 DNA Library Preparation Kit                         |  | [**]     |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 1 |  | 04746708001 |  | GS 20 DNA Library Preparation Kit Buffers                 |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 1 |  | 04746716001 |  | GS 20 DNA Library Preparation Kit Enzymes and Adaptors    |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 1 |  | 04746724001 |  | GS 20 DNA Library Preparation Kit Nebulizers              |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 1 |  | 04746732001 |  | GS 20 DNA Library Preparation Kit Immobilization Beads    |  |          |  | [**]                   
|          |  |             |  |                                                          
|Kit       |  | 04746503001 |  | GS 20 emPCR Kit                                           |  | [**]     |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 1 |  | 04746511001 |  | GS 20 emPCR Kit Bead Recovery Reagents                    |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 2 |  | 04746520001 |  | GS 20 emPCR Kit Clonal Amplification Reagents             |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 3 |  | 04746538001 |  | GS20 emPCR Kit Enrichment Beads                           |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 4 |  | 04746546001 |  | GS 20 emPCR Kit Emulsion Oil                              |  |          |  | [**]                   
|          |  |             |  |                                                          
|Kit       |  | 04746554001 |  | GS 20 Sequencing Kit (70 x75)                             |  | [**]     |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 1 |  | 04746562001 |  | GS 20 Sequencing Kit (70x75) Pre-wash / Post-wash Buffers |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 2 |  | 04746589001 |  | GS 20 Pre-wash Tubes                                      |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 3 |  | 04746597001 |  | GS 20 Sequencing Kit (70 x75) Wash Buffers                |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 4 |  | 04746619001 |  | GS 20 Sequencing Kit (70 x75) Sequencing Reagents         |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 5 |  | 04746627001 |  | GS 20 Sequencing Kit (70 x75) Sequencing Enzymes          |  |          |  | [**]                   
|          |  |             |  |                                                          
|Sub Kit 6 |  | 04746635001 |  | GS 20 Sipper Tubes                                        |  |          |  | [**]                   



---

|          |  |             |  |                                                           |  |      |  |     
|--------- |  | ----------- |  | --------------------------------------------------------- |  | ---- |  | ----
|Kit       |  | 04746422001 |  | GS 20 Sequencing Kit (40x75)                              |  | [**] |  | [**]
|          |  |             |  |                                                          
|Sub Kit 1 |  | 04746457001 |  | GS 20 Sequencing Kit (40x75) Pre-wash / Post-wash Buffers |  |      |  | [**]
|          |  |             |  |                                                          
|Sub Kit 2 |  | 04746589001 |  | GS 20 Pre-wash Tubes                                      |  |      |  | [**]
|          |  |             |  |                                                           |  |      |  |     
|          |  |             |  |                                                          
|Sub Kit 3 |  | 04746473001 |  | GS 20 Sequencing Kit (40x75) Wash Buffers                 |  |      |  | [**]
|          |  |             |  |                                                          
|Sub Kit 4 |  | 04746481001 |  | GS 20 Sequencing Kit (40x75) Sequencing Reagents          |  |      |  | [**]
|          |  |             |  |                                                          
|Sub Kit 5 |  | 04746490001 |  | GS 20 Sequencing Kit (40x75) Sequencing Enzymes           |  |      |  | [**]
|          |  |             |  |                                                          
|Sub Kit 6 |  | 04746635001 |  | GS 20 Sipper Tubes                                        |  |      |  | [**]
|          |  |             |  |                                                           |  |      |  |     
|          |  |             |  |                                                          
|Kit       |  | 04746759001 |  | GS 20 Maintenance Wash Kit                                |  | [**] |  | [**]
|          |  |             |  |                                                          
|Sub Kit 1 |  | 04746767001 |  | GS20 Maintenance Wash Kit Maintenance Wash Reagents       |  |      |  | [**]
|          |  |             |  |                                                          
|Sub Kit 2 |  | 04746783001 |  | GS 20 Maintenance Wash Kit Bottles                        |  |      |  | [**]
|          |  |             |  |                                                          
|Sub Kit 3 |  | 04746635001 |  | GS 20 Sipper Tubes                                        |  |      |  | [**]
|          |  |             |  |                                                           |  |      |  |     
|          |  |             |  |                                                          
|Kit       |  | 04774981001 |  | GS 20 Installation Kit                                    |  | [**] |  | [**]
|          |  |             |  |                                                          
|Sub Kit 1 |  | 04774990001 |  | GS 20 Installation Kit Control DNA Beads                  |  |      |  | [**]
|          |  |             |  |                                                          
|Sub Kit 2 |  | 04746457001 |  | GS 20 Sequencing Kit (40x75) Pre-wash / Post-wash Buffers |  |      |  | [**]
|          |  |             |  |                                                           |  |      |  |     
|          |  |             |  |                                                          
|Sub Kit 3 |  | 04746589001 |  | GS 20 Pre-wash Tubes                                      |  |      |  | [**]
|          |  |             |  |                                                           |  |      |  |     



---

|            |  |             |  |                                  |  |          |  |                        
|----------- |  | ----------- |  | -------------------------------- |  | -------- |  | -----------------------
|Disposables
|            |  |             |  |                                 
|            |  | Cat. No.    |  | Product                          |  | ASP$/Kit |  | Transfer Price$/Sub Kit
|Kit         |  | 04746821001 |  | GS 20 PicoTiterPlate Kit (70x75) |  | [**]     |  | [**]                   
|            |  |             |  |                                 
|Kit         |  | 04746813001 |  | GS 20 PicoTiterPlate Kit (40x75) |  | [**]     |  | [**]                   



---

|            |  |                                                 |  |          |  |                     
|----------- |  | ----------------------------------------------- |  | -------- |  | --------------------
|Accessories
|            |  |                                                 | 
|Cat. No.    |  | Product                                         |  | ASP$/Kit |  | Transfer Price$/ Kit
|04777034001 |  | Medium Bead Deposition Device, complete         |  | [**]     |  | [**]                
|            |  |                                                 | 
|04777042001 |  | Medium Bead Deposition Device, complete 8 lanes |  | [**]     |  | [**]                
|            |  |                                                 | 
|04777069001 |  | Large Bead Deposition Device, complete          |  | [**]     |  | [**]                
|            |  |                                                 | 
|04777115001 |  | Counterweight for the Bead Deposition Devices   |  | [**]     |  | [**]                
|            |  |                                                 | 
|04777018001 |  | Camera Faceplate Guard                          |  | [**]     |  | [**]                
|            |  |                                                 | 
|04777026001 |  | Nebulizer Holder                                |  | [**]     |  | [**]                



---

|            |  |                                                   |  |      |  |                 |  |                                                         
|----------- |  | ------------------------------------------------- |  | ---- |  | --------------- |  | --------------------------------------------------------
|Instrument 
|Cat. No.    |  | Product                                           |  | ASP$ |  | TransferPrice $ |  | Transfer Price(incl Training Kits + Installation Kits) $
|04746694001 |  | GS 20 DNA Instrument                              |  | [**] |  | [**]            |  | [**]                                                    
|            |  | including:                                        |  |      |  |                 |  |                                                         
|04777034001 |  | Medium Bead Deposition Device, complete           |  |      |  |                 |  |                                                         
|04777042001 |  | Medium Bead Deposition Device, complete 8 lanes   |  |      |  |                 |  |                                                         
|04777069001 |  | Large Bead Deposition Device, complete            |  |      |  |                 |  |                                                         
|04777115001 |  | Counterweight for the Bead Deposition Devices     |  |      |  |                 |  |                                                         
|04777018001 |  | Camera Faceplate Guard                            |  |      |  |                 |  |                                                         
|04777026001 |  | Nebulizer Holder                                  |  |      |  |                 |  |                                                         
|            |  | Medium PicoTiterPlate Cartridge; 40x75            |  |      |  |                 |  |                                                         
|            |  | Large PicoTiterPlate Cartridge; 70x75             |  |      |  |                 |  |                                                         
|            |  | Swinlock Filter Unit                              |  |      |  |                 |  |                                                         
|            |  | 5 x 16 Gauge Blunt Needles                        |  |      |  |                 |  |                                                         
|            |  | 5 x Plastic Economy Foreceps                      |  |      |  |                 |  |                                                         
|            |  | Zeiss Tissue (Box)                                |  |      |  |                 |  |                                                         
|            |  | Wash Tube Holder                                  |  |      |  |                 |  |                                                         
|            |  | Extra Fluidics Waste Tank and Bottle Support      |  |      |  |                 |  |                                                         
|            |  | GS 20 DNA Library Preparation Kit Users Manual   |  |      |  |                 |  |                                                         
|            |  | GS 20 DNA Library Preparation Kit Quick Guide     |  |      |  |                 |  |                                                         
|            |  | GS 20 emPCR Kit Users Manual                     |  |      |  |                 |  |                                                         
|            |  | GS 20 emPCR Kit Quick Guide                       |  |      |  |                 |  |                                                         
|            |  | Genome Sequencer 20 Operators Manual             |  |      |  |                 |  |                                                         
|            |  | Genome Sequencer 20 Quick Guide                   |  |      |  |                 |  |                                                         
|            |  | GS 20 Data Processing Software Manual             |  |      |  |                 |  |                                                         
|            |  | Genome Sequencer 20 Site Preparation Guide        |  |      |  |                 |  |                                                         
|            |  |                                                   |  |     
|            |  | Additional items which must be ordered seperately |  |      |  |                 |  |                                                         
|            |  |                                                   |  |     
|            |  | Training                                          |  |      |  |                 |  |                                                         
|            |  |                                                   |  |     
|04746694001 |  | GS 20 DNA Library Preparation Kit                 |  |      |  | [**]            |  | [**]                                                    
|            |  |                                                   |  |      |  |                 |  |                                                         
|04746503001 |  | GS 20 emPCR Kit (3)                               |  |      |  | [**]            |  | [**]                                                    
|            |  |                                                   |  |     
|04746554001 |  | GS 20 Sequencing Kit (70x75)                      |  |      |  | [**]            |  | [**]                                                    
|            |  |                                                   |  |      |  |                 |  |                                                         
|04746422001 |  | GS 20 Sequencing Kit (40x75) (3)                  |  |      |  | [**]            |  | [**]                                                    
|            |  |                                                   |  |     
|04746821001 |  | GS 20 PicoTiterPlate Kit (70x75)                  |  |      |  | [**]            |  | [**]                                                    
|            |  |                                                   |  |     
|04746813001 |  | GS 20 PicoTiterPlate Kit (40x75) (3)              |  |      |  | [**]            |  | [**]                                                    
|            |  |                                                   |  |     
|            |  | Installation                                      |  |      |  |                 |  |                                                         
|            |  |                                                   |  |     
|04774981001 |  | GS 20 Installation Kit                            |  |      |  | [**]            |  | [**]                                                    
|            |  |                                                   |  |     
|04746554001 |  | GS 20 Sequencing Kit (70x75)                      |  |      |  | [**]            |  | [**]                                                    
|            |  |                                                   |  |     
|04746821001 |  | GS 20 PicoTiterPlate Kit (70x75)                  |  |      |  | [**]            |  | [**]                                                    



---

Exhibit 3

Licensed Products Specifications

The following Specifications V 1.01 do not include the additional terms
that are laid down in the Original Agreement:



| |  |  | update shelf life time of reagents up to [**] after Launch
| | - |  | ----------------------------------------------------------



| |  |  | update of maintenance interval for tubings to [**] (not feasible for Version 1.01)
| | - |  | ----------------------------------------------------------------------------------



|   |  |             |  |                                                         |  |         
|-- |  | ----------- |  | ------------------------------------------------------- |  | --------
|NO |  | Document ID |  | Document Name                                           |  | PDF file
|1  |  | SPC-00028   |  | 454 Genome Sequencer Version 1.01 System Specifications |  | [**]    
|2  |  | SPC-00034   |  | Instrument: Technical Requirements Specifications       |  | [**]    
|3  |  | SPC-00036   |  | Software: Software Requirement Specifications           |  | [**]    
|4  |  | SPC-00031   |  | Specifications Library Preparation Kit                  |  | [**]    
|5  |  | SPC-00029   |  | Specification Emulsion-based Clonal Amplification Kit   |  | [**]    
|6  |  | SPC-00032   |  | Specification Sequencing Kit                            |  | [**]    
|7  |  | SPC-00033   |  | Specifications PicoTiterPlate Kits                      |  | [**]