Exhibit 10.50

Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Asterisks denote omissions.

SECOND AMENDMENT TO LICENSE, SUPPLY AND DISTRIBUTION AGREEMENT

THIS SECOND AMENDMENT TO LICENSE, SUPPLY AND DISTRIBUTION AGREEMENT is made and
entered into as of this 24th day of October, 2006 (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, as amended by the First Amendment to
License, Supply and Distribution Agreement dated December 19, 2005 (“Original
Agreement”); and

WHEREAS, the Parties intend to launch Rev. 1.1 (under the product name GS FLX)
now a Proposed Licensed Product listed under Exhibit 5 of the Original
Agreement. Customers who bought the Rev. 1.0 (the product name being GS 20) will
have the choice to upgrade their Rev 1.0 instrument to a Rev. 1.1 instrument.
Hereby, the Parties wish to agree on the sharing of costs for such an upgrade.

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. The following new Section 3.3 (e) shall be added to the Original Agreement:

“454 shall charge FHLR, and FHLR will purchase from 454 an upgrade for the Rev.
1.0 (“Upgrade”) at a transfer price of [**] percent ([**] %) for each of the
Upgrades based on the estimated Average Unit Upgrade Price (“AUUP”). The AUUP
shall be the total amount invoiced to customers for Upgrades divided by the
total number of Upgrades. The initial estimated AUUP for the Upgrade shall be
[**] US Dollars (US $ [**]). The value of the estimated AUUP shall be subject to
adjustment based on the actual AUUP. The calculation of the actual AUUP shall be
done in the same way as for the ASP in Section 3.3 (c) of the Original
Agreement.

Furthermore, FHLR will pay 454 a fixed amount of [**] percent ([**] %) of the
material costs for every upgrade of a Rev. 1.0 which consists of the delivery
according to Specifications of a Rev. 1.1 instrument [**]. The material costs
for an Upgrade are currently [**] US Dollars (US $ [**]). In the event 454 does
the Upgrade, FHLR shall also reimburse 454’s actual costs for (i) travel of 454
personnel to upgrade Rev. 1.0 instruments (ii) personnel costs for the
installation in the amount of $[**] per day of installation. These costs are the
total costs of 454 for upgrading a Rev. 1.0 to a Rev. 1.1 at the customer’s
site. If FHLR does the Upgrade with its own technical service personnel, FHLR
shall not be obligated to pay 454 costs for travel and installation.

Based on its 2006 forecast, FHLR has so far failed to order [**] Rev. 1.0
instruments from 454. Instead of purchasing those remaining Rev. 1.0
instruments, FHLR shall have the option to pay 454 a compensation of [**] US
Dollars (US $ [**]) per Rev. 1.0 instrument by December 31,

--------------------------------------------------------------------------------

2006. This shall be 454’s sole remedy for FHLR not taking delivery of the
instruments. FHLR will inform 454 the latest by October 31, 2006 about the
number of Rev 1.0 instruments (if any) which it will order before December 31,
2006, with any unordered balance of the 2006 forecast subject to the above
payment.

If FHLR has by the end of the calendar year 2006 any Rev. 1.0 instruments in
stock and FHLR chooses to upgrade those instruments, FHLR shall only pay the
material costs of [**] US Dollars (US $ [**]) for such Upgrade without further
payments. Such payment will not be deducted from any customer receipts for
calculation of the ASP (Section 3.3) or royalties (Section 3.4) for the Rev. 1.1
instrument.”

2. The following new Section 3.4 (a)(vii) shall be added to the Original
Agreement:

“[**] percent ([**] %) on Net Sales of Upgrades.”

3. The Upgrade will be done on the basis of the following specifications
(Exhibit 16):

(See attached document.)

4. Exhibit 3 shall be complemented according to Section 2.7 of the Original
Agreement by addition of the Specifications for the Rev. 1.1 instrument as
follows:

[**]

5. According to Section 3.3 (b) of the Original Agreement the Parties hereby
amend Exhibit 2 by adding the following for the additional Licensed Products
Rev. 1.1, emPCR Kits II, III and paired end adaptor kit:

(See attached documents.)

6. The Parties agree to amend the Original Agreement such that the text of
Exhibit 5, “Proposed Licensed Products, Launch Dates and Initial Estimated ASP”
shall be deleted in its entirety and replaced with the following:

(See attached document.)

7. Both new GS FLX instruments and upgraded Rev. 1.0 (GS20) instruments are
warranted by 454 to FHLR for [**] starting with installation of the GS FLX
instruments at the customer and with completion and installation at the customer
of the upgrade for the Rev. 1.0 (GS20) instruments. This warranty is extended by
FHLR or its Affiliates to the customer.

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

 

Basel,     Branford, F. Hoffmann-La Roche Ltd     454 Life Sciences By:   /s/ P.
Saladin     By:   /s/ Christopher K. McLeod Name:   P. Saladin     Name:  
Christopher K. McLeod Title:   Head of Diag. Licensing     Title:   President &
CEO Date:   11/21/2006     Date:   Nov. 28, 2006

 

    By:   /s/ C. J. Ruetsch       Name:   Dr. C. J. Ruetsch       Title:   Head
of Legal Diagnostics       Date:   November 21, 2006      

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The GS-20 to GS-100 upgrade

Manufacturing an Upgrade Performance overview

454 will produce 2 identical types of GS-100 instruments, whereas the
instruments dedicated for upgrades [**]. During the upgrade at the customer site
the [**] of the GS-20 instrument already owned by the customer will be switched
to the GS-100.

The upgrade at the customer site will take [**] days. The upgrade will be
performed preferentially by trained* Roche service engineers. Where necessary
Roche and 454 agree that Roche could contract the 454 engineer to perform the
upgrade. Approximately [**] hours will be needed to switch the [**] and to
install/QC the upgraded instrument. Test fragment run will be performed [**],
followed by data analysis, filling the installation form and packing the old
GS-20 instrument. The customer confirms the successful installation by signing
the installation report.

Supply Chain Logistics Overview

The upgrade process follows already established supply chain mechanisms already
in place for the GS-20. This is valid for entering the Purchase Order (PO_ as
well as for shipping of instrument and reagents to the customer.

In detail:

What parts will be sent to a customer upon ordering an upgrade?

 

  •  

[**]

What has to happen to send the new instrument ?

 

  •  

[**]

What happens at the customer site (Instrument, engineering)?

 

  •  

[**]

Training concept

 

  •  

Instrument: [**]

 

  •  

Kits & Protocols: [**]

How it will be confirmed that the upgrade has been successful?

[**]

Warranty

 

  •  

Both, GS-100 system and [**] are warranteed by 454 to Roche for [**]. This
warranty is extended by Roche to the customer

 

* Training of Roche staff by 454

1. Service engineers

454 ([**]) will provide a common training for 2-3 service engineers from Roche
Global System Support (GSS) and 2-3 service engineers from Roche U.S. Technical
Services. Training will take place at 454 as soon as a GS-100 instrument will be
available (GS-20 instrument in the 454 Sequencing Centre owned by Roche U.S.
will be used to train the [**] switch). Training contains entire procedure
(hands-on) of all steps done by the service engineers during the upgrade.

2. Roche training staff

Roche Global Customer Support (one person) will need one week training at 454 in
October to update the training guide and to become familiar with the instrument.
This person will then train rest of Roche staff. Training needs for the U.S.
colleagues will be similar.

To be organized by [**].

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Kit    04891384001    GS emPCR Kit II (Amplicon A, Paired End)    [**]    [**]
Sub Kit 1    04891406001    GS emPCR Kit II (Amplicon A, Paired End) Bead
Recovery Reagents       [**] Sub Kit 2    04891414001    GS emPCR Kit II
(Amplicon A, Paired End) Clonal Amplification Reagents       [**] Sub Kit 3   
04746538001    GS emPCR Kit Enrichment Beads       [**] Sub Kit 4    04746546001
   GS emPCR Kit Emulsion Oil       [**] Kit    04891392001    GS 20 emPCR Kit
III (Amplicon B)    [**]    [**] Sub Kit 1    04891422001    GS emPCR Kit III
(Amplicon B) Bead Recovery Reagents       [**] Sub Kit 2    04891449001    GS
emPCR Kit III (Amplicon B) Clonal Amplification Reagents       [**] Sub Kit 3   
04746538001    GS emPCR Kit Enrichment Beads       [**] Sub Kit 4    04746546001
   GS emPCR Kit Emulsion Oil       [**] Kit    04891457001    GS Paired End
Adaptor Kit    [**]    [**]

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GS FLX Product Line

  

Catalog No

  

Initial Average Selling Price
Per Kit (USD)

  

Transfer Price

GS FLX LR20 Sequencing Kit

   04 852 419 001    [**]    [**]

PicoTiterPlate Kit (20 x 25)

   04 746 813 001    [**]    [**]

GS FLX LR70 Sequencing Kit

   04 853 342 001    [**]    [**]

GS FLX System

      [**]    [**]

GS20 Upgrade to GS FLX

      [**]    [**]

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EXHIBIT 5

Proposed Licensed Products, Launch Dates and Initial estimated ASP

Version 2.0

 

System Components

   Launch Date   

Initial Estimated

ASP

Sequencer Instrument V 2.0

   2008    tbd

Software V 2.0

     

DNA Library Preparation Kit

      tbd

Emulsion-based Clonal Amplification Kit

     

PicoTiter Sequencing Kits

     

PicoTiterPlate Kits

      tbd

 

Other Components as well as details tbd at the Steering Committee