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
$    Transfer
Price $    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

   [**]