Exhibit 10.1


 


Confidential Treatment has been requested for
portions of this exhibit. The copy filed herewith omits the information subject
to the confidentiality request. 
Omissions are designated as “***”. A complete version of this exhibit
has been filed separately with the Securities and Exchange Commission.


 





 


Proposal for manufacture
and supply of cGMP

Polyribonucleotide Duplex for Phase - I Clinical Trials


 


	
  F.A.O.

  	
   

  	
  Richard
  S. Dondero 

  Senesco Technologies, Inc 

  303 George St., Suite 420 

  New Brunswick, New Jersey 08901

  
	
   

  	
   

  	
   

  
	
  Prepared
  by:

  	
   

  	
  Kristy
  Bazaire 

  Commercial Development Manager

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Charles
  J Shields 

  VP, Global Business Development 

  Avecia Biotechnology

  
	
   

  	
   

  	
   

  
	
  Proposal
  Number:

  	
   

  	
  SNT071608

  
	
   

  	
   

  	
   

  
	
  Version
  Number:

  	
   

  	
  4

  
	
   

  	
   

  	
   

  
	
  Date:

  	
   

  	
  September 4,
  2008

  



 


1

















 


1.         REQUEST
FOR PROPOSAL


 


Senesco Technologies, Inc (Senesco) requested Avecia to prepare a
proposal for the supply of 3g of material for Toxicology Studies and 15g of
material for use in Phase I Clinical Trials. A stability study of the siRNA
active pharmaceutical ingredient is also included in this proposal.


 


2.         BENEFITS
AVECIA CAN BRING


 


·                  Extensive
experience in oligonucleotide manufacture, >1000 sequences prepared >700
Man-years oligonucleotide technology and manufacturing experience


·                  Available
capacity: 100’s of kg


·                  Experienced in
supply through all Phases of clinical trials


·                  Experienced in
process validation for oligonucleotides


·                  Registered and
FDA inspected USA facility (Milford, Mass)


·                  Experience in
preparation of DMF’s, CMC’s and CTD’s


·                  Intimate
knowledge and control of supply chain to ensure quality and viral safety


·                  Expertise in
process and analytical method development


·                  Industry leading
track record of compliant supply


·                  Access – via our
exclusive license – to optimum deprotection technology for RNA production


 


3.         PROJECT
SCOPE


 


3.1     Product Description:


 


	
  PRODUCT:

  	
   

  	
  RNA Duplex

  
	
   

  	
   

  	
   

  
	
  DESCRIPTION:

  	
   

  	
  Duplex of
  two 21mer single strand RNAs

  
	
   

  	
   

  	
   

  
	
  SEQUENCE

  	
   

  	
  ***

  

  SENESCO IS REQUESTED TO CONFIRM THE SEQUENCES ABOVE

  



 


3.2     Product Specifications


 


To be discussed and agreed after the limited development studies. For
Senesco’s reference, provisional specifications which reflect Avecia experience
with other siRNA compounds have been provided in Appendix A. These are for
information purposes only and should not be considered as agreed or appropriate
for this compound.


 


2

















 


3.3     Project Structure


 


Stage 1 Limited Development Studies and
Supply of Toxicology Material


 


Define from Avecia experience the most appropriate operating conditions
for synthesis, cleavage, deprotection, purification, ultra-filtration of the
RNA single strands and for duplexation and lyophilization of the RNA duplex.


 


Carry out a limited number of small scale runs to confirm process
suitability specifically for the Senesco RNA duplex and refine process as
necessary


 


Manufacture and supply *** grams of material for use in Toxicology
studies.


 


This is expected to take 8 labor weeks and includes as a deliverable a
process description to support the GMP manufacturing campaign and CMC sections
of IND submission.


 


The material produced during the experimental runs will also be used to
support an analytical method suitability assessment. A limited forced degradation
study (base and thermal exposure) will be carried out to support stability
testing. The analytical method assessment and forced degradation study are each
expected to take 2 labor weeks, for at a total of four weeks.


 


Deliverable – Technical development reports to support cGMP
manufacturing campaign, analytical methods and data summary.


 


Stage 2 cGMP Manufacture and Supply of API


 


Manufacturing  will  be  carried  out  at  a  1  x  6  mmol  synthesis  scale  for  each  single  strand,  cleavage  and  deprotection  and  purification/UF  followed  by  a  1  x  6  mmol  duplexation.  Manufacturing  scale  is  expected  to  produce  approximately  ***  g  of  cGMP  material.


 


During stage 2 Avecia will execute the following:


 


Prepare process instructions as appropriate for manufacture of a batch
suitable for use in Phase - I Clinical Trials.


 


Confirm suitability of analytical methods for raw materials, in-process
and final product analysis and equipment cleaning


 


Confirm specification for raw material, in-process and final product
Safety, Health and Environment assessment


 


Engineering Review


 


Agree primary packaging and labels and required aliquots


 


Manufacture single strand intermediates and subsequent duplexation


 


3

















 


Carry out product analysis and release


 


Deliverable – Sufficient material to satisfy requirement of testing and
regulatory retain (***), ICH stability study (***) and supply of *** cGMP API
to Senesco. QA reviewed Certificate of Analysis will also be provided.


 


Stage 3 Drug Substance ICH Derived Stability
Study


 


Under the guidance of a customer approved protocol, Avecia will perform
a stability study as described below. Should Senesco wish to extend the -209C
study beyond *** months, sufficient material will be available to accommodate
two additional time points to be detailed in a separate proposal. It is
expected that this stability study will require approximately ***g of the
material produced from stage 2.


 


***


 


Deliverable – Avecia will supply Senesco with interim stability reports
for each intermediate pull point (*** and *** months) with a final stability
report at the conclusion of the study (*** months).


 


4.      PROJECT ASSUMPTIONS


 


The following assumptions are applicable to this proposal. Changes to
these conditions and/or the scope of the project may change the project timing
and cost. All changes will be executed using a mutually agreed change order.


 


	
   

  	
   

  	
  Assumptions

  
	
  Pricing

  	
   

  	
  Prices are in US Dollar 

  Pricing includes raw materials

  
	
  Reference  Material

  	
   

  	
  If available, Senesco will supply small quantities of reference
  material

  
	
  Material Use

  	
   

  	
  The material will be used for Toxicology Studies and Phase I Clinical
  Trials 

  Senesco will conduct appropriate Toxicology
  studies in advance of any use of material in human clinical trials

  
	
  Timelines

  	
   

  	
  *** weeks for Tox material from project acceptance 

  *** months for GMP material from project acceptance 

  * Timelines dependant on Raw Material availability

  
	
  API Analysis

  	
   

  	
  Avecia will carry out product analysis and release

  
	
  Development

  	
   

  	
  Pricing assumes Avecia’s existing collection of processes for RNAi
  manufacture and methods for RNAi analyses are suitable for use with this
  compound without the requirement for substantial development.

  
	
  Stability Study  Cancellation

  	
   

  	
  Senesco retains the option to cancel the stability study at their
  sole discretion. Avecia will prorate the stability 

  



 


4

















 


	
   

  	
   

  	
  study accordingly and will include any outstanding storage fees
  incurred to date.

  
	
  Confidentiality

  	
   

  	
  All confidential information will be managed in accordance with the
  executed Mutual Confidentiality Agreement dated July 28, 2008

  
	
  Intellectual  Property

  	
   

  	
  Nothing in this Agreement shall affect the ownership by either party
  of any intellectual property or process owned by that party.

  



 


5.      PROJECT TIMELINES


 


A detailed project plan will be shared with Senesco Technologies upon
commencing.


 


6.      FACILITIES


 


Avecia will use its FDA inspected Manufacturing Facility at Milford,
Massachusetts USA


 


7.      COMPLIANCE


 


Material from Stage 1 will be non-GMP and will not be suitable for use
in human clinical trials.


 


Final API material from Stage 2 will be supplied to cGMP as interpreted
by ICH Harmonized Tripartite Guideline Q7, Good Manufacturing Practice Guide
for Active Pharmaceutical Ingredients.


 


Material is supplied under the strict understanding that Senesco
Technologies will conduct appropriate Toxicology studies to ensure material is
safe for human clinical trials before any human trials commence.


 


8.      FINANCIAL SUMMARY


 


Stage 1 Limited Development Studies and supply of *** grams duplex for
Toxicology Studies ***


 


Analytical method assessment and limited forced degradation ***


 


Stage 2 Manufacture and Supply of *** grams cGMP material, *** grams
for stability study and approximately *** grams for QC release and regulatory
retains ***.


 


Pricing assumes orders will be placed at the same time for Toxicology
and P-I material.


 


Pricing includes at no additional cost:


 


A copy of batch records


 


Reasonable assistance in regulatory submissions


 


BSE/TSE traceability documentation


 


5

















 


Access as required within project scope to analytical, technical and
validation expertise


 


Project management services


 


Stage 3 ICH Derived Stability Studies ***. Pricing assumes T0 testing
is conducted during lot release in stage 2.


 


9.      MILESTONE INVOICING


 


	
  Project Milestone

  	
   

  	
  Approximate Timing

  	
   

  	
  Payment

  	
   

  
	
  Project
  Acceptance

  	
   

  	
  August 2008

  	
   

  	
  ***

  	
   

  
	
  Start of
  cGMP Manufacture

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  
	
  Release of
  cGMP Batch

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  
	
  2009 Stability
  Activities

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  
	
  2010
  Stability Activities

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  



 


10.    EARLY TERMINATION


 


With acceptance of this proposal, Avecia is reserving equipment time
and resources in our manufacturing facility for Senesco. In the event that
Senesco terminates the project, as detailed within this proposal, a
cancellation fee will be applied. The structure of the fee will be:


 


·      If Senesco cancel the
manufacture prior to 90 days before the planned manufacturing start date, no
cancellation fee will be applied.


·      If Senesco cancel the
manufacture between 90 and 60 days before the planned manufacturing start date
40% of the total project cost will be charged as a cancellation fee, all
payments to date will be credited towards this fee.


·      If Senesco cancel the
manufacture between 60 and 30 days before the planned manufacturing start date
60% of the total project cost will be charged as a cancellation fee, all
payments to date will be credited towards this fee.


·      If Senesco cancel the
manufacture <30 days before the planned manufacturing start date 80% of the
total project cost will be charged as a cancellation fee, all payments to date
will be credited towards this fee.


 


6

















 


11.    PROPOSAL REVISION HISTORY


 


	
  Proposal Version 

  Number

  	
   

  	
  Date

  	
   

  	
  Comments/Changes

  	
   

  
	
  Version 1

  	
   

  	
  July 24,
  2008

  	
   

  	
  Original
  Version

  	
   

  
	
  Version 2

  	
   

  	
  August 5,
  2008

  	
   

  	
  stage 1
  deliverable to 3g GLP

  	
   

  
	
  Version 3

  	
   

  	
  August 27,
  2008

  	
   

  	
  Amend
  stability study

  	
   

  
	
  Version 4

  	
   

  	
  September 4,
  2008

  	
   

  	
  Correct
  name, add confidentiality and IP statement

  	
   

  



 


12.    PROPOSAL ACCEPTANCE


 


Senesco and Avecia by signing below hereby accept the scope of Proposal
SNT071608 Version 4 and the terms and conditions contained herein.


 


	
  /s/ Richard S. Dondero 

  	
   

  
	
  Name: Richard S. Dondero 

  	
   

  
	
  Title:

  	
   

  
	
  Senesco Technologies, Inc.

  	
   

  
	
   

  	
   

  
	
  /s/ CJ Shields 

  	
   

  
	
  Name: CJ Shields 

  	
   

  
	
  Title: VP Global Business Development 

  	
   

  
	
  Avecia Biotechnology, Inc.

  	
   

  



 


13.    TERMS AND CONDITIONS


 


Avecia Biotechnology Inc standard terms and conditions are outlined
below. These terms would apply in the absence of a supply agreement. We would
be happy to discuss and agree a supply agreement at Senesco Technologies
convenience.


 


This proposal is valid until September 19, 2008.


 


Avecia Biotechnology Inc standard terms and conditions are outlined
below. These terms would apply in the absence of a supply agreement. Terms of
payment are thirty (30) days net from the date of the invoice.


 


	
  Prices:

  	
   

  	
  This quotation is valid for thirty (30) days from the date issued and
  subject to satisfactory credit check. Prices are quoted in US dollars.

  
	
   

  	
   

  	
   

  
	
  Payment by Check:

  	
   

  	
  Payment should be made to: 

  Avecia Biotechnology Inc. 

  125 Fortune Blvd. 

  Milford, MA 01757

  



 


7

















 


	
  Payment by Wire Transfer:

  	
   

  	
  Payment should be made to: 

  Citizens Bank 

  Acct #: *** 

  ABA Routing #: ***

  



 


GENERAL CONDITIONS


 


This document entitled “Proposal” once signed and authorized by the
parties becomes a legally binding Agreement. The terms and conditions for sale
and purchase of Product and Services under this Agreement are as follows:


 


1.   Miscellaneous The Agreement
contains all the terms and conditions of sale and purchase of the Product and
Services listed within this Agreement. No modification of any terms and
condition, or of any aspect of the project scope, shall be effected unless
mutually agreed by the parties in writing. This Agreement and performance
hereunder shall be construed and governed by the laws of Delaware.


 


2.   Term This Agreement shall take
effect on the date of the final authorizing signature and shall remain in
effect until the later to occur of (i) completion of all Services listed
within this Agreement or (ii) 30 days following delivery of the final
shipment of Product.


 


3.   Shipments Product will be
delivered EX WORKS AVECIA’s facilities at Milford, Massachusetts. Title to and
risk in the Product shall pass to CUSTOMER at the earliest to occur of (i) the
time at which the Product is placed at CUSTOMER’s request in AVECIA storage or (ii) the
time at which the Product is delivered to CUSTOMER’s designated carrier at
AVECIA’s facilities at Milford, Massachusetts.


 


4.   Invoices and Payment AVECIA
shall issue to CUSTOMER invoices for payment for the Products and Services in
accordance with the payment milestone schedule within this Agreement. Within
thirty (30) days following the receipt of each invoice, absent a good faith
dispute, CUSTOMER shall pay the invoice. AVECIA reserves the right, among other
remedies, to suspend further work or Product deliveries in the event CUSTOMER
fails to pay any invoice when same becomes due. Unless otherwise stated in the
project assumptions within this Agreement, the invoice price for Product shall
be calculated on the weight of the Product discharged from the lyophilizer.


 


5.   Excuse of performance Neither
party shall be subject to any liability for delay in performance, or non
performance, as a result of fire, flood, natural catastrophe, strike, labor
trouble, accident, riot, act of governmental authority or compliance with
government request, act of god, or other contingencies and circumstances beyond
its reasonable control interfering with the manufacture or delivery of Product
or Services covered by this Agreement or with the supply of any raw materials
or utilities used in connection therewith, or in the event AVECIA suspends the
operation of the facility because operation thereof fails to comply with
applicable governmental law, regulation, ordinance, standard order or decree
relating to pollution, ecology, occupational safety and 


 


8

















 


health, or environmental
matters. AVECIA may, during any period of shortage due to any cause, prorate
and allocate its supply of raw materials or resources, and delivery of
contractual commitments in such manner as may be deemed fair and reasonable by
AVECIA. In no event shall AVECIA be obligated to purchase Product in the
marketplace to satisfy its obligations hereunder.


 


6.   Taxes The prices quoted exclude
any applicable sales, use, consumption, value added or excise taxes duties,
tariffs and other similar assessments which may be imposed by any governmental
authority an the sale to CUSTOMER (other than with respect to any income,
corporate or similar taxation on AVECIA); provided, however, that the Parties
shall cooperate and take any reasonable and proper steps to reduce or eliminate
taxes.


 


7.   Limited Warranty. AVECIA
warrants title and that all Product sold hereunder conforms to the agreed
specifications and where appropriate cGMP requirements. AVECIA MAKES NO OTHER
REPRESENTATION OR WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, AS TO
MERCHANTABILITY, FITNESS FOR PARTICULAR PURPOSE, OR ANY OTHER MATTER WITH
RESPECT TO THE PRODUCT OR SERVICES. Any suggestions made by AVECIA concerning
regulatory requirements, regulatory strategy, uses or applications of Product
reflect AVECIA’s opinion only, and AVECIA makes no warranty of results to be
obtained.


 


8.   Limitation of Liability. Within
fifteen days after receipt of each shipment of Product sold hereunder, CUSTOMER
shall examine such Product for any damage, defects or shortage. All claims,
including claims for alleged damaged or defective goods, shortage or
non-deliverance of goods, negligence or any other causes whatsoever, shall be
deemed waived unless made in writing and received by AVECIA within thirty days
after CUSTOMER’s receipt of the Product. Failure of CUSTOMER to give notice of
any claims within the thirty (30) day period shall be deemed an absolute and
unconditional waiver of such claim. CUSTOMER’S EXCLUSIVE REMEDY SHALL BE FOR
DAMAGES AND AVECIA’S LIABILITY FOR ANY AND ALL LOSSES OR DAMAGES RESULTING FROM
ANY CAUSE WHATSOEVER, INCLUDING ALLEGED NEGLIGENCE, SHALL IN NO EVENT EXCEED
THE PURCHASE PRICE OF THE PRODUCT OR SERVICE IN RESPECT TO WHICH THE CLAIM IS
MADE. AVECIA shall not be liable for, and CUSTOMER assumes responsibility for,
all personal injury and property damage resulting from the handling,
possession, use or resale of the Product. In no event shall AVECIA be liable
for special, incidental, or consequential damages, whether CUSTOMER’s claim is
in contract, negligence, strict liability or otherwise.


 


9.   Intellectual Property CUSTOMER
represents and warrants to AVECIA that CUSTOMER has all necessary rights to
have the Product made and that AVECIA’s manufacture of Product for CUSTOMER
will not infringe the intellectual property or other rights of any third party.
CUSTOMER shall indemnify and hold AVECIA harmless from all liability, damages,
costs and expenses relating to any claims brought by third parties for
infringement of any intellectual property rights covering the Product
manufactured to designs or specifications of CUSTOMER. Nothing in this
Agreement shall affect the ownership by either party of any intellectual
property or process owned by that party. Other than giving AVECIA the right to
manufacture the Product for the 


 


9

















 


CUSTOMER, nothing in this
Agreement shall give either party the right to use the other party’s
intellectual property. Intellectual property generated, developed, discovered
or invented in connection with work conducted under this Agreement by the
parties relating solely to the composition of the Product shall belong to
CUSTOMER. All other intellectual property generated, developed, discovered or
invented by the parties in connection with work conducted under this Agreement
shall belong to AVECIA.


 


10