LYNX THERAPEUTICS INC
S-3/A, 1997-12-31
MEDICINAL CHEMICALS & BOTANICAL PRODUCTS
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       As filed with the Securities and Exchange Commission on December 31, 1997
                                                      Registration No. 333-39171
================================================================================
                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549
    

                                   -----------
   
                               Amendment No. 1 To
    
                                    FORM S-3
                             REGISTRATION STATEMENT
                                      Under
                           THE SECURITIES ACT OF 1933

                                   -----------

                             Lynx Therapeutics, Inc.
             (Exact name of registrant as specified in its charter)

           Delaware                                   94-3161073
(State or other jurisdiction of          (I.R.S. Employer Identification Number)
incorporation or organization)

                                   -----------

                              3832 Bay Center Place
                            Hayward, California 94545
                                 (510) 670-9300
    (Address, including zip code, and telephone number, including area code,
                  of registrant's principal executive offices)

                                   -----------

                                Edward C. Albini
                             Chief Financial Officer
                             Lynx Therapeutics, Inc.
                              3832 Bay Center Place
                            Hayward, California 94545
                                 (510) 670-9300
                               Fax: (510) 670-9302
            (Name, address, including zip code, and telephone number,
                   including area code, of agent for service)

                                   -----------

                                   Copies to:
                              James C. Kitch, Esq.
                               COOLEY GODWARD LLP
                              Five Palo Alto Square
                               3000 El Camino Real
                        Palo Alto, California 94306-2155
                                 (650) 843-5000
                               Fax (650) 857-0663

                                   -----------

        Approximate date of commencement of proposed sale to the public:
                        As soon as practicable after the
                 effective date of this Registration Statement.
                                   -----------
If the only securities  being registered on this Form are being offered pursuant
to dividend or interest reinvestment plans, please check the following box. [ ]

If any of the  securities  being  registered on this Form are to be offered on a
delayed or continuous  basis  pursuant to Rule 415 under the  Securities  Act of
1933, other than securities offered only in connection with dividend or interest
reinvestment plans, check the following box. [X]

If this form is filed to register additional securities for an offering pursuant
to Rule 462(b) under the Securities Act, please check the following box and list
the  Securities  Act  registration  statement  number of the  earlier  effective
registration statement for the same offering. [ ]

If this form is a  post-effective  amendment filed pursuant to Rule 462(c) under
the  Securities  Act,  check  the  following  box and  list the  Securities  Act
registration  statement number of the earlier effective  registration  statement
for the same offering. [ ]

If delivery  of the  prospectus  is  expected  to be made  pursuant to Rule 434,
please check the following box. [ ]

   
    
                                   -----------

     The Registrant  hereby amends this  Registration  Statement on such date or
dates as may be necessary to delay its effective date until the Registrant shall
file a  further  amendment  that  specifically  states  that  this  Registration
Statement shall  thereafter  become effective in accordance with Section 8(a) of
the  Securities  Act of 1933 or until the  Registration  Statement  shall become
effective on such date as the Commission,  acting pursuant to said Section 8(a),
may determine.

<PAGE>

INFORMATION   CONTAINED  HEREIN  IS  SUBJECT  TO  COMPLETION  OR  AMENDMENT.   A
REGISTRATION  STATEMENT  RELATING  TO THESE  SECURITIES  HAS BEEN FILED WITH THE
SECURITIES  AND EXCHANGE  COMMISSION.  THESE  SECURITIES MAY NOT BE SOLD NOR MAY
OFFERS TO BUY BE ACCEPTED PRIOR TO THE TIME THE REGISTRATION  STATEMENT  BECOMES
EFFECTIVE.  THIS  PROSPECTUS  SHALL  NOT  CONSTITUTE  AN  OFFER  TO  SELL OR THE
SOLICITATION OF AN OFFER TO BUY NOR SHALL THERE BE ANY SALE OF THESE  SECURITIES
IN ANY STATE IN WHICH SUCH OFFER,  SOLICITATION  OR SALE WOULD BE UNLAWFUL PRIOR
TO REGISTRATION OR QUALIFICATION UNDER THE SECURITIES LAWS OF ANY SUCH STATE.


   
                 SUBJECT TO COMPLETION, DATED DECEMBER 31, 1997
    

PROSPECTUS


                                2,675,500 Shares


                             LYNX THERAPEUTICS, INC.


                                  Common Stock

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

   
         All of the shares of Common Stock,  par value $0.01 per share,  of Lynx
Therapeutics,  Inc. ("Lynx" or the "Company")  offered hereby (the "Shares") are
being  offered  and  sold  by  certain  persons  listed  herein  under  "Selling
Stockholders"  (collectively,  the  "Selling  Stockholders").  The  Shares  were
purchased by the Selling Stockholders from the Company in a private placement in
1997.  All of the Shares are being offered  hereby by the Selling  Stockholders,
and the Company will not receive any of the proceeds from the sale of the Shares
by the Selling Stockholders.  The Company's Common Stock is quoted on the Nasdaq
National Market under the symbol "LYNX". On December 30, 1997, the last reported
sales price of the Company's Common Stock was $12.875 per share.
    

         The Selling Stockholders, directly or through agents, broker-dealers or
underwriters,  may sell the Shares  offered hereby from time to time on terms to
be determined at the time of sale, in transactions on the Nasdaq National Market
or in privately negotiated transactions. The Selling Stockholder and any agents,
broker-dealers  or  underwriters  that  participate in the  distribution  of the
Common  Stock may be deemed  to be  "underwriters"  within  the  meaning  of the
Securities Act of 1933, as amended (the  "Securities  Act"),  and any commission
received by them and any profit on the resale of the Common  Stock  purchased by
them may be  deemed  to be  underwriting  discounts  or  commissions  under  the
Securities Act. See "Selling Stockholders" and "Plan of Distribution."

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

       THE COMMON STOCK OFFERED HEREBY INVOLVES A HIGH DEGREE OF RISK. SEE
                   "RISK FACTORS" COMMENCING ON PAGE 3 HEREOF.

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

    THESE SECURITIES HAVE NOT BEEN APPROVED OR DISAPPROVED BY THE SECURITIES
     AND EXCHANGE COMMISSION OR ANY STATE SECURITIES COMMISSION NOR HAS THE
      SECURITIES AND EXCHANGE COMMISSION OR ANY STATE SECURITIES COMMISSION
          PASSED UPON THE ACCURACY OR ADEQUACY OF THIS PROSPECTUS. ANY
              REPRESENTATION TO THE CONTRARY IS A CRIMINAL OFFENSE.

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

         No underwriting commissions or discounts will be paid by the Company in
connection  with this  offering.  Estimated  expenses  payable by the Company in
connection with this offering are $60,000. The aggregate proceeds to the Selling
Stockholders  from  the sale of the  Shares  will be the  purchase  price of the
Shares sold less the aggregate agents' commissions and underwriters'  discounts,
if any,  and  other  expenses  of  issuance  and  distribution  not borne by the
Company. See "Plan of Distribution."

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

   
                The date of this Prospectus is ___________, 1997.
    

<PAGE>

                              AVAILABLE INFORMATION

         The Company is subject to the information reporting requirements of the
Securities  Exchange  Act of 1934,  as  amended  (the  "Exchange  Act"),  and in
accordance  therewith file reports,  proxy statements and other information with
the  Securities  and  Exchange  Commission  (the  "SEC").  Such  reports,  proxy
statements  and other  information  may be  inspected  and  copied at the public
reference  facilities  maintained by the SEC at Room 1024,  Judiciary Plaza, 450
Fifth Street,  N.W.,  Washington,  D.C. 20549, and at the SEC's regional offices
located at Seven World Trade Center,  Suite 1300, New York, New York 10048,  and
at Citicorp  Center,  500 West Madison  Street,  Suite 1400,  Chicago,  Illinois
60661-2511.  Copies of such  material  may be  obtained  by mail from the Public
Reference  Section  of the SEC at  Judiciary  Plaza,  450  Fifth  Street,  N.W.,
Washington,  D.C. 20549, at prescribed  rates. The SEC also maintains a Web site
that contains  reports,  proxy and information  statements and other information
regarding  registrants  that  file  electronically  with the SEC at the  address
http://www.sec.gov.   The  Company's   reports,   proxy   statements  and  other
information  can also be inspected and copied at the offices of The Nasdaq Stock
Market, 1735 K Street, N.W., Washington DC 20006.

         The Company has filed with the SEC a registration statement on Form S-3
(herein  referred  to,  together  with  all  amendments  and  exhibits,  as  the
"Registration  Statement")  under the  Securities  Act of 1933,  as amended (the
"Securities  Act").  This Prospectus does not contain all of the information set
forth in the  Registration  Statement,  certain  parts of which are  omitted  in
accordance with the rules and  regulations of the SEC. For further  information,
reference  is  hereby  made  to  the  Registration  Statement.   Copies  of  the
Registration Statement and the exhibits and schedules are available as described
above.

                 INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE

         The following documents, filed or to be filed with the Commission under
the Exchange Act are hereby incorporated by reference into this Prospectus:

         (a) The Company's  Annual Report on Form 10-K for the fiscal year ended
December 31, 1996;

   
         (b) The Company's  Quarterly Reports on Form 10-Q, as amended,  for the
quarterly periods ended March 31, June 30, and September 30, 1997; 

         (c) The  Company's  Current  Report on Form 8-K filed on  December  18,
1997; and

         (d) The  description  of the Common Stock  contained  in the  Company's
Registration Statement on Form 10 (No. 0-22570), as amended,  initially filed on
October 5, 1993.
    

         All documents filed by the Company  pursuant to Sections 13(a),  13(c),
14 or 15(d) of the Exchange Act after the date of this  Prospectus  and prior to
the  termination of the offering shall be deemed to be incorporated by reference
herein and to be a part  hereof from the date of filing of such  documents.  Any
statement  contained in this Prospectus or in a document  incorporated or deemed
to be  incorporated  by  reference  herein  shall be  deemed to be  modified  or
superseded  for  purposes  of this  Prospectus  to the extent  that a  statement
contained  herein  or in any  subsequently-filed  document  which  also is or is
deemed to be  incorporated  by  reference  herein  modifies or  supersedes  such
statement.  Any such  statement so modified or  superseded  shall not be deemed,
except as so modified or superseded, to constitute a part of this Prospectus.

         The Company will provide  without charge to each person,  including any
beneficial  owner,  to whom this  Prospectus is delivered,  upon written or oral
request of such person,  a copy of any and all of the  documents  that have been
incorporated  by  reference  herein (not  including  exhibits to such  documents
unless such exhibits are  specifically  incorporated by reference herein or into
such  documents).  Such  request  may be directed  to Lynx  Therapeutics,  Inc.,
Attention:  Chief Financial Officer, 3832 Bay Center Place, Hayward,  California
94545, telephone (510) 670-9300.

                           FORWARD LOOKING STATEMENTS

         This Prospectus contains forward-looking  statements within the meaning
of Section 27A of the  Securities  Act and Section 21E of the Exchange Act which
are subject to the "safe harbor"  created by those  sections.  When used in this
Prospectus,  the words  "anticipate,"  "believe,"  "estimate,"  and "expect" and
similar expressions as they relate to the Company or its management are intended
to identify  such  forward-looking  statements.  The Company's  actual  results,
performance,  or achievements could differ materially from the results expressed
in, or  implied  by,  these  forward-looking  statements  as a result of certain
factors,  including  those set forth in "Risk  Factors"  and  elsewhere  in this
Prospectus.

                                        2

<PAGE>

                                   THE COMPANY

         Lynx Therapeutics, Inc. (the "Company") was incorporated in Delaware in
February  1992. The Company's  executive  offices are located at 3832 Bay Center
Place, Hayward, California 94545, and its telephone number is (510) 670-9300.

                                  RISK FACTORS

         This Prospectus contains forward-looking  statements that involve risks
and  uncertainties.  Actual results could differ materially from those discussed
in the  forward-looking  statements  as a result of certain  factors,  including
those set forth below and  elsewhere  in this  Prospectus.  The  following  risk
factors should be considered  carefully in addition to the other  information in
this Prospectus before purchasing the shares of Common Stock offered hereby.

Unproven Business Strategy; Uncertainty of Product Success or Market Acceptance

         The  Company's  strategy  of using  its  massively  parallel  signature
sequencing   technologies  for  gene  sequencing  for  the  purpose  of  rapidly
identifying  genes,  defining and  characterizing  gene  function,  and enabling
high-resolution genomic mapping is unproven.  While certain other companies have
similar technology or have adopted a similar strategy,  the application of these
technologies and strategies is in too early a stage to determine  whether it can
be successfully implemented.

         The Company's genomic database subscription business and the use of its
products  to  assist in and  improve  the  efficiency  of the  traditional  drug
discovery  process  is in too  early  a stage  to  determine  whether  it can be
successful.  There can be no assurance that companies will accept the usefulness
of the Company's  products and related  services.  In addition,  the Company has
limited  experience in providing  software-based  database products or services.
The Company's ability to achieve  profitability  depends on attracting customers
for its  database  and  sequencing  products  and  services.  The  nature of the
Company's products and services are such that there is a limited number of large
pharmaceutical  companies  that are  potential  customers  for such products and
services,  two of which have signed  agreements with the Company to date.  There
can be no assurance that any of the Company's product  development  efforts will
be  successfully  completed  or that the  Company's  products  will gain  market
acceptance.

Early Stage of Development; Technological Uncertainty

         Lynx is at an early stage of development and must be evaluated in light
of the uncertainties and complications  present in an early stage  biotechnology
company. All of Lynx's products and services are in research or development, and
have not generated  significant  revenues.  To date, most of Lynx's efforts have
been dedicated to the development of its original  oligodeoxynucleotide  ("ODN")
chemistry technology and recently developed  technologies for massively parallel
signature sequencing of cloned cDNA. The massively parallel signature sequencing
program  is in the  development  stage  and is  dependent  upon  the  successful
integration of independent  technologies,  each of which has its own development
risks.  There can be no assurance that these  technologies  will be successfully
developed  or, if they are,  that they can be  integrated  successfully.  Lynx's
research in molecular biology and medicinal  chemistry and its assessment of the
potential  pharmaceutical  effectiveness  of ODN compounds  have, to date,  been
entirely  dependent on collaborative  efforts.  While Lynx and its collaborators
have demonstrated that some of Lynx's antisense compounds are active in cellular
in vitro  systems and in animal  models,  there can be no  assurance  that these
results  are  indicative  of results  that will be  obtained  in human  clinical
testing.  Pharmaceutical or biotechnology based products, if any, resulting from
Lynx's  research and  development  programs are not expected to be  commercially
available  for a number of years  even if they are  successfully  developed  and
proven to be safe and effective.

Competition

         There  are a  finite  number  of genes in the  human  genome.  The race
amongst competitors in the genomics field is not just to identify these genes by
their sequences, but also to determine gene function, particularly gene function
in disease. Even when all genes are known, and their sequences  determined,  the
hunt for  functional  information  in the wide  variety of diseases  and disease
conditions will continue,  and characterization of genes (by their sequences) in
various samples will still be needed.  While Lynx believes that it contributes a
uniquely  efficient gene analysis  technique to that hunt,  other companies have
substantially   greater  research  and  product  development   capabilities  and
financial, scientific, and marketing resources than the Company.

                                        3

<PAGE>

         In its gene  analysis  programs,  Lynx will be  competing in some sense
with both  purveyors and users of current DNA analysis  technology.  Competition
from   fully   integrated   pharmaceutical   companies   and  more   established
biotechnology  companies  also is intense and is expected to increase.  Academic
institutions,  governmental  agencies  and other  public  and  private  research
organizations  also  conduct  research,  seek patent  protection  and  establish
collaborative arrangements for products and data access. While Lynx at this time
is not aware of a technology  that is  equivalent  or superior to its  massively
parallel  signature  sequencing,  there are other companies that provide data or
access to data  similar  to that which  Lynx  intends to offer.  There can be no
assurance that research and development efforts by others will not render any of
the Company's potential products and services noncompetitive.

Patents and Proprietary Rights

         Lynx's  success  will depend on its  ability to obtain  patents for its
technologies and products, maintain trade secrets and operate without infringing
on the  proprietary  rights of others,  both in the  United  States and in other
countries.  Patent  matters in  biotechnology  are highly  uncertain and involve
complex  legal and  factual  questions.  Accordingly,  the  availability  of and
breadth of claims allowed in biotechnology and pharmaceutical  patents cannot be
predicted.   Lynx  has  filed  and  will  continue  to  file  applications,   as
appropriate,  for patents  covering  both its  products  and  processes  and has
licensed a number of patents  and patent  applications  covering  certain of its
technologies,  processes and  compounds.  No assurance can be given that patents
will issue from any of the pending  applications  or that,  if patents do issue,
the claims allowed will be sufficiently broad to protect Lynx's  technology.  In
addition,  no assurance  can be given that any patents  issued to or licensed by
Lynx will not be challenged,  invalidated, infringed or circumvented or that the
rights  granted  thereunder  will  provide   competitive   advantages  to  Lynx.
Competitors  may have been issued  patents,  may have filed  applications or may
obtain  additional  patents  and  proprietary  rights  relating  to  products or
processes  competitive  with  those of the  Company  or which  could  block  the
Company's efforts to obtain patents.

         The  commercial  success  of Lynx will also  depend in part on Lynx not
infringing  patents  issued to  competitors  and on  others  not  breaching  the
technology  licenses upon which Lynx's products might be based.  There can be no
assurance  that  Lynx  will be able to  obtain  a  license  to any  third  party
technology  that it may require to conduct its business or that, if  obtainable,
such technology can be licensed at a reasonable cost.  Failure by Lynx to obtain
a  license  to  any  technology  that  it  may  require  to  commercialize   its
technologies or products may have a material adverse effect on Lynx.

         Litigation,  which could result in substantial  costs to Lynx, may also
be necessary  to enforce any patents  issued or licensed to Lynx or to determine
the  scope and  validity  of third  party  proprietary  rights.  There can be no
assurance  that the Company's  issued  patents would be held valid by a court of
competent jurisdiction. Even if the outcome of such litigation is favorable, the
cost of such litigation and the diversion of the Company's resources during such
litigation  could  have a material  adverse  effect on the  Company.  An adverse
outcome could subject the Company to  significant  liabilities to third parties,
require disputed rights to be licensed from third parties or require the Company
to cease  using such  technology,  any of which  could  have a material  adverse
effect on the Company.  If  competitors  of the Company  prepare and file patent
applications  in the United  States that claim  technology  also  claimed by the
Company,  the  Company  may  have to  participate  in  interference  proceedings
declared by the Patent and Trademark Office to determine  priority of invention,
which could  result in  substantial  cost to the  Company,  even if the eventual
outcome is favorable to Lynx.

         Lynx also relies on trade secrets and  proprietary  know-how,  which it
seeks to protect in part by  confidentiality  agreements with its collaborators,
employees and consultants.  There can be no assurance that these agreements will
not be breached,  that Lynx would have adequate  remedies for any breach or that
its trade secrets will not otherwise become known or be independently  developed
by  competitors.  To the extent that the Company or its  consultants or research
collaborators  use  intellectual  property owned by others in their work for the
Company,  disputes  may also  arise as to the  rights in  related  or  resulting
know-how and inventions.

Need to Establish Collaborative Relationships; Dependence on Partners

         Lynx's   business   strategy   includes   entering  into   subscription
arrangements,  strategic  alliances or  licensing  arrangements  with  corporate
partners, primarily pharmaceutical and biotechnology companies,  relating to the
development and commercialization of certain of its potential technologies, data
bases and products. There can be

                                        4

<PAGE>

no  assurance  that  Lynx  will be able to  negotiate  attractive  collaborative
arrangements or that such collaborations will be available to Lynx on acceptable
terms so that any such relationships,  once established,  will be scientifically
or commercially successful.  Lynx currently has two corporate agreements for its
massively parallel signature sequencing technology,  with Hoechst AG and Hoechst
Marion Roussel (collectively  referred to as "Hoechst") and BASF AG ("BASF"). In
exchange for access to the  technology  and for a specified  number of massively
parallel signature sequencing analyses per year, Lynx has received signing fees,
and  may  receive  milestone  payments  (upon  demonstration  by Lynx  that  the
technology  can  substantially   reproduce  data  obtained  by  other  means  in
well-studied  systems) and subscription  fees.  Additionally,  under the Hoechst
agreement,  Lynx  received  an initial  equity  investment  and will  receive an
additional equity investment, subject to achievement of a milestone.

         There can be no  assurance  that  Hoechst  or BASF or any other  future
collaborator  will not pursue  their  existing or  alternative  technologies  in
preference  to  those  being  developed  in  collaboration   with  the  Company.
Furthermore,  there  can be no  assurance  that  the  Company  will  be  able to
negotiate additional collaborative  arrangements on acceptable terms, if at all,
or that such collaborations  will be successful.  To the extent that the Company
chooses not to or is unable to establish  such  arrangements,  it would  require
substantially  greater capital to undertake  research and development of certain
of its potential technologies, data bases and products at its own expense.

         Lynx will be dependent on  collaborative  arrangements  relating to the
development  of LR 3280 for the  treatment  of  restenosis  and other  potential
antisense  compounds.  Although LR 3280 is in Phase II clinical trials in Europe
for the prevention of restenosis following balloon angioplasty and is the object
of  development  and   commercialization   agreements  with  two  pharmaceutical
companies,  there can be no assurance  that the Company's  clinical  trials will
demonstrate  sufficient  safety and efficacy  necessary to obtain the  requisite
regulatory  approvals  or will result in  marketable  products.  While Lynx will
depend on partners for funding and development  expertise in connection with the
Company's antisense  research,  the amount and timing of resources to be devoted
to these  activities  by such  corporate  partners,  if any,  are not within the
control of the Company. In addition,  there can be no assurance that the Company
will be able to negotiate such  collaborative  arrangements on acceptable terms,
if at all, or that such collaborations will be successful.

Absence of Sales and Marketing Experience

         Lynx has no  experience  in the sales,  marketing  or  distribution  of
pharmaceutical  products or services.  To market the products or services of its
massively  parallel  signature  sequencing  technologies,  Lynx must  define the
particular  products  and  services  that it will offer and  develop a sales and
marketing group with the appropriate technical expertise.  Lynx does not plan to
market  any of its  future  pharmaceutical  products  directly.  There can be no
assurance  that Lynx will be able to build such a sales force or that its direct
sales and marketing efforts will be successful.

History of Operating Losses

         The Company has a limited  history of  operations  and has  experienced
significant  operating  losses since its  inception in 1992.  The Company had an
accumulated  deficit of approximately  $39.0 million through September 30, 1997.
To achieve and sustain profitable operations, the Company, alone or with others,
must  develop   successfully,   obtain  regulatory  approval  for,  manufacture,
introduce,  market and sell its  products.  The time frame  necessary to achieve
market  success is  uncertain.  There can be no assurance  that the Company will
ever generate  sufficient  product  revenues to become  profitable or to sustain
profitability.

Use of Hazardous Materials

         Lynx's  research  and  development  may involve the  controlled  use of
hazardous  materials,  chemicals,  viruses  and various  radioactive  compounds.
Although Lynx believes that its safety  procedures for handling and disposing of
such materials will comply with the standards  prescribed by state,  federal and
local  regulations,  the risk of accidental  contamination  or injury from these
materials  cannot be  completely  eliminated.  In the event of such an accident,
Lynx could be held liable for any damages  that result,  and any such  liability
could exceed the resources of Lynx.

                                       5
<PAGE>

Dependence Upon Key Personnel

         Lynx is highly dependent on the principal members of its management and
scientific  staff,  the  loss of whose  services  could  significantly  delay or
prevent the achievement of research,  development and business objectives,  thus
having a material adverse effect on Lynx. Furthermore,  recruiting and retaining
qualified  scientific  personnel to perform research and development work in the
future will be critical to Lynx's  success.  Although  Lynx  believes it will be
successful  in  attracting  and  retaining  skilled and  experienced  scientific
personnel,  there can be no  assurance  that Lynx  will be able to  attract  and
retain such personnel on acceptable terms,  given the competition among numerous
pharmaceutical and health care companies,  universities and non-profit  research
institutions  for  experienced  scientists.  The  Company  is  dependent  on its
Chairman  and Chief  Executive  Officer,  Sam  Eletr,  Ph.D.,  the loss of whose
services would have a material  adverse  effect on the Company.  The Company has
recently  applied for key-man life  insurance on Dr. Eletr.  The Company has not
entered into an employment agreement with him.

Potential Volatility of Stock Price; Limited Market for Stock

   
         The Company  qualified its Common Stock to trade on the Nasdaq National
Market  ("Nasdaq")  on  December  30,  1997.  There can be no  assurance  that a
sufficient trading market will develop. In addition, the securities markets have
from time to time experienced significant price and volume fluctuations that may
be unrelated to the operating  performance of particular  companies.  The market
prices of the common  stock of many  publicly  held,  early stage  biotechnology
companies  have in the past  been,  and can in the  future  be  expected  to be,
especially  volatile.  Factors such as fluctuations  in the Company's  operating
results,  announcements of technological  innovations or new commercial products
by the Company or its  competitors,  release of reports by securities  analysts,
developments or disputes concerning patent or proprietary  rights,  developments
in the Company's relationships with current or future collaborative partners, if
any, and general market  conditions may have a significant and adverse impact on
the market price of the Common Stock.
    

Control by Officers, Directors and Principal Stockholders

         As of September 30, 1997,  directors,  executive officers and principal
stockholders  of the Company  will  beneficially  own  approximately  31% of the
outstanding   shares  of  the  Company's  capital  stock.   Accordingly,   these
stockholders,  individually  and as a group,  may be able to control the Company
and direct its affairs and business, including any determination with respect to
a change in control of the  Company,  future  issuances of Common Stock or other
securities by the Company,  declaration of dividends on the Common Stock and the
election of directors.


Shares Eligible for Future Sale

         On March 31, 1998, the outstanding  shares of Series B Preferred Stock,
Series C Preferred Stock and Series D Preferred Stock will automatically convert
into shares of Common Stock on a  ten-for-one  basis.  Sales of shares of Common
Stock,  including  shares  issued  upon  conversion  of  outstanding  shares  of
Preferred Stock and shares issued upon the exercise of outstanding  options,  in
the public market could  adversely  affect the market price of the Common Stock.
Such  sales also might make it more  difficult  for the  Company to sell  equity
securities or  equity-related  securities in the future at a time and price that
the Company deems appropriate.

                                        6

<PAGE>

<TABLE>
                              SELLING STOCKHOLDERS

         The following  table sets forth the names of the Selling  Stockholders,
the  number  of  shares  of  Common  Stock,  on  an  as-converted  basis,  owned
beneficially by each Selling  Stockholder prior to this offering,  the number of
shares of Common Stock being offered for the account of each Selling Stockholder
and the number of shares of Common Stock, on an as-converted  basis, to be owned
by each Selling Stockholder after completion of this offering.  This information
is based upon  information  provided  by the Selling  Stockholders.  Because the
Selling  Stockholders  may  offer  all,  some or none of its  Common  Stock,  no
definitive  estimate as to the number of shares thereof that will be held by the
Selling Stockholders after such offering can be provided.

<CAPTION>
                                                    Shares Beneficially          Shares             Shares Beneficially
                                                       Owned Prior to            Being                  Owned After
                                                        Offering (1)             Offered              Offering (1)(2)
                                                  ------------------------       --------            ----------------
            Selling Stockholder                    Number            Percent%                       Number        Percent%
            -------------------                    ------            --------                       ------        --------
<S>                                                       <C>           <C>      <C>                  <C>            <C>
WPG-Farber, Weber Fund, L.P...............                459,000       7.8      459,000              0              -
WPG-Farber, Weber Overseas, L.P...........                 22,500        *        22,500              0              -
Star Creation Ltd.........................                 18,500        *        18,500              0              -
Lombard Odier Zuerich Ltd.................                400,000       6.8      400,000              0              -
Four Partners.............................                360,000       6.1      360,000              0              -
FBB Associates............................                 40,000        *        40,000              0              -
INVESCO Global Health Sciences Fund.......                350,000       5.9      350,000              0              -
H&Q Healthcare Investors..................                150,000       2.5      150,000              0              -
H&Q Life Sciences Investors...............                100,000       1.7      100,000              0              -
BioCentive Limited........................                150,000       2.5      150,000              0              -
PHARMA/wHealth............................                150,000       2.5      150,000              0              -
Caduceus Capital, Ltd.....................                110,000       1.9      110,000              0              -
Caduceus Capital, L.P.....................                 40,000        *        40,000              0              -
Axa U.S. Growth Fund LLC..................                 57,500        *        57,500              0              -
Parvest U.S. Partners II C.V..............                120,000(3)    2.0       20,000            100,000          1.7
U.S. Growth Fund Partners C.V.............                210,000(4)    3.5       20,000            190,000          3.1
Double Black Diamond II LLC...............                 10,000        *        10,000              0              -
Almanori Limited..........................                  2,200        *         2,200              0              -
David Sherry..............................                  2,500        *         2,500              0              -
Multinvest Limited........................                  4,300(5)     *         1,300              3,000          *
Partech International Salary Deferral
  Plan U/A Dated 1/1/92
  FBO: Thomas G. McKinley.................                  3,000(6)     *         1,000              2,000          *
Partech International Salary Deferral
  Plan U/A Dated 1/1/92
  FBO: Scott Matson.......................                    500        *           500              0              -
CDC - Valeurs de Croissance...............                 75,000       1.3       75,000              0              -
Punk, Ziegel & Knoell Investors LLC.......                 28,000        *        28,000              0              -
William J. Punk, Jr.......................                  5,000        *         5,000              0              -
Julia P. Gregory..........................                  3,000        *         3,000              0              -
European Medical Ventures Fund SCA........                163,000(7)    2.7       30,000            133,000          2.2
David Bellet..............................                 10,000        *        10,000              0              -
The Pidwell Family Living Trust                                                                                      -
  Dated 6/25/87...........................                  5,000        *         5,000              0
Tony Di Bona..............................                  1,000        *         1,000              0              -
Douglas E. Kelly SEP-IRA..................                  1,000        *         1,000              0              -
Mark Platshon.............................                  2,500        *         2,500              0              -
Sam Eletr, Ph.D. (8)......................                463,759       7.5       50,000            413,759          6.8
<FN>
- -------------------
 *       Represents beneficial ownership of less than 1%.

(1)      Percentage  of ownership  is based on 5,886,253  shares of Common Stock
         outstanding  as of  October  1, 1997 and the number of shares of Common
         Stock, on an as-converted basis, owned as of such date. The

                                        7

<PAGE>

         number of shares of Series B Preferred Stock,  Series C Preferred Stock
         and  Series D  Preferred  Stock  outstanding  as of October 1, 1997 was
         332,288, 123,299 and 40,000,  respectively.  The Series B, Series C and
         Series  D  Preferred  Stock  are  convertible  into  Common  Stock on a
         ten-for-one  basis.  Beneficial  ownership is  determined in accordance
         with the rules of the Securities  and Exchange  Commission and includes
         sole or shared voting or investment  power with respect to shares shown
         as beneficially owned.

(2)      Assumes the sale of all Shares offered  hereby.  The Company has agreed
         to pay all  reasonable  fees and  expenses  incident  to the  filing of
         offering. See "Plan of Distribution."

(3)      Represents  10,000 shares of Series C Preferred Stock and 20,000 shares
         of Common Stock.

(4)      Represents  15,000 shares of Series B Preferred Stock,  4,000 shares of
         Series C Preferred Stock and 20,000 shares of Common Stock.

(5)      Represents  300 shares of Series C Preferred  Stock and 1,300 shares of
         Common Stock.

(6)      Represents  200 shares of Series C Preferred  Stock and 1,000 shares of
         Common Stock.

(7)      Represents  13,300 shares of Series C Preferred Stock and 30,000 shares
         of Common Stock.

(8)      Includes 217,500 shares of Common Stock issuable upon exercise of stock
         options  held by Dr.  Eletr that are  exercisable  within 60 days.  Dr.
         Eletr is  Chairman  of the  Board and Chief  Executive  Officer  of the
         Company.
</FN>
</TABLE>

                                        8

<PAGE>

                              PLAN OF DISTRIBUTION

   
         The Shares may be offered by the Selling Stockholders from time to time
on the OTC  market and the  Nasdaq  National  Market,  in  privately  negotiated
transactions  or a combination of such methods of sale, at fixed prices that may
be changed,  at market prices  prevailing at the time of sale, at prices related
to  such  prevailing  market  prices  or  at  negotiated   prices.  The  Selling
Stockholders  may effect such  transactions by selling the Shares directly or by
or through agents or broker-dealers who may receive  compensation in the form of
discounts,  concessions  or  commissions  from the Selling  Stockholders  or the
purchasers  of the  Shares for whom such  broker-dealers  may act as agent or to
whom  they  sell  as  principal  or both  (which  compensation  to a  particular
broker-dealer might be in excess of customary commissions).
    

         The Selling  Stockholders and any underwriters,  dealers or agents that
participate in the distribution of the Shares may be deemed to be "underwriters"
within the meaning of the  Securities  Act, and any  discounts,  commissions  or
concessions received by them and any provided pursuant to the sale of the Shares
by them might be deemed to be underwriting  discounts and commissions  under the
Securities  Act. In order to comply with the securities  laws of certain states,
if  applicable,  the  Shares  will be sold in such  jurisdictions  only  through
registered or licensed  brokers or dealers.  In addition,  in certain states the
Shares may not be sold unless they have been registered or qualified for sale or
an exemption from the registration or qualification requirement is available and
is complied with.

         Pursuant to an  agreement  with the Selling  Stockholders,  the Company
will pay  substantially all of the expenses incident to the offering and sale to
the public of the Shares offered hereby, other than commissions, concessions and
discounts of  underwriters,  dealers or agents.  Such expenses  (excluding  such
commissions  and  discounts)  are estimated to be  approximately  $60,000.  Such
agreement provides for the cross-indemnification of the Selling Stockholders and
the  Company  to the extent  permitted  by law,  for  losses,  claims,  damages,
liabilities  and  expenses  arising,  under  certain  circumstances,  out of any
registration of the Shares.

                                  LEGAL MATTERS

         The  validity  of the  issuance of the shares of Common  Stock  offered
hereby  will be passed upon for the Company by Cooley  Godward  LLP,  Palo Alto,
California ("Cooley Godward"). As of the date of this Prospectus, Cooley Godward
beneficially owns 700 shares of Series B Preferred Stock, 300 shares of Series C
Preferred  Stock and 10,000  shares of Common Stock  issuable  upon  exercise of
stock options held by James C. Kitch, a partner of Cooley Godward,  on behalf of
Cooley Godward. In addition, Mr. Kitch is a director of the Company.

                                     EXPERTS

         The  consolidated  financial  statements  of  Lynx  Therapeutics,  Inc.
appearing in the Company's  Annual Report on Form 10-K for the fiscal year ended
December 31, 1996, have been audited by Ernst & Young LLP, independent auditors,
as set forth in their report thereon included therein and incorporated herein by
reference.  Such consolidated  financial  statements are incorporated  herein by
reference in reliance  upon such report given upon the authority of such firm as
experts in accounting and auditing.

                                        9

<PAGE>
================================================================================

         NO DEALER,  SALESPERSON OR OTHER PERSON HAS BEEN AUTHORIZED TO GIVE ANY
INFORMATION OR TO MAKE ANY  REPRESENTATIONS  OTHER THAN THOSE  CONTAINED IN THIS
PROSPECTUS AND, IF GIVEN OR MADE, SUCH INFORMATION OR  REPRESENTATIONS  MUST NOT
BE  RELIED  UPON  AS  HAVING  BEEN  AUTHORIZED  BY  THE  COMPANY,   ANY  SELLING
STOCKHOLDERS  OR BY ANY OTHER PERSON.  THIS  PROSPECTUS  DOES NOT  CONSTITUTE AN
OFFER TO SELL OR A SOLICITATION OF AN OFFER TO BUY ANY SECURITIES OTHER THAN THE
SHARES OF COMMON STOCK OFFERED  HEREBY,  NOR DOES IT CONSTITUTE AN OFFER TO SELL
OR A  SOLICITATION  TO BUY ANY OF THE SHARES OFFERED HEREBY TO ANY PERSON IN ANY
JURISDICTION  IN WHICH SUCH OFFER OR  SOLICITATION  WOULD BE  UNLAWFUL OR TO ANY
PERSON TO WHOM IT IS UNLAWFUL.  NEITHER THE DELIVERY OF THIS  PROSPECTUS NOR ANY
OFFER  OR SALE  MADE  HEREUNDER  SHALL,  UNDER  ANY  CIRCUMSTANCES,  CREATE  ANY
IMPLICATION  THAT THERE HAS BEEN NO CHANGE IN THE AFFAIRS OF THE COMPANY OR THAT
THE  INFORMATION  CONTAINED  HEREIN IS CORRECT AS OF ANY TIME  SUBSEQUENT TO THE
DATE HEREOF.

                                   ----------

                                TABLE OF CONTENTS
                                                                            Page
                                                                            ----
                                                                         
Available Information........................................................  2
Incorporation of Certain Documents by                                    
  Reference..................................................................  2
Forward Looking Statements...................................................  2
The Company..................................................................  3
Risk Factors.................................................................  3
Selling Stockholders.........................................................  7
Plan of Distribution.........................................................  9
Legal Matters................................................................  9
Experts......................................................................  9

================================================================================


                                2,675,500 Shares


                             Lynx Therapeutics, Inc.


                                  Common Stock


                                   ----------


                                   PROSPECTUS


                                   ----------


   
                                December __, 1997
    


================================================================================

                                       10

<PAGE>

                                     PART II

                     INFORMATION NOT REQUIRED IN PROSPECTUS

Item 14.  Other Expenses of Issuance and Distribution

         The following  table sets forth all expenses  payable by the Registrant
in  connection  with the sale of the  Common  Stock  being  registered.  All the
amounts  shown are  estimates  except  for the  registration  fee and the Nasdaq
Listing Fee.

                  Registration fee........................    $11,351
                  Nasdaq listing fee......................     18,500
                  Printing expenses.......................      1,500
                  Legal fees and expenses.................     25,000
                  Accounting fees and expenses............      2,000
                  Miscellaneous...........................      1,649
                                                              -------
                          TOTAL...........................    $60,000

Item 15.  Indemnification of Officers and Directors.

         Under  Section  145  of  the  Delaware  General  Corporation  Law,  the
Registrant  has broad powers to indemnify  its  directors  and officers  against
liabilities they may incur in such capacities,  including  liabilities under the
Securities  Act of 1933, as amended (the  "Securities  Act").  The  Registrant's
Bylaws also  provide  that the  Registrant  will  indemnify  its  directors  and
executive officers and may indemnify its other officers, employees and agents to
the fullest extent permitted by Delaware law.

         The  Registrant's   Certificate  of  Incorporation   provides  for  the
elimination  of  liability  for  monetary  damages for breach of the  directors'
fiduciary duty of care to the Registrant and its stockholders.  These provisions
do not eliminate the directors' duty of care and, in appropriate  circumstances,
equitable remedies such an injunctive or other forms of non-monetary relief will
remain available under Delaware law. In addition, each director will continue to
be subject to  liability  for  breach of the  director's  duty of loyalty to the
Registrant,  for acts or omissions  not in good faith or  involving  intentional
misconduct,  for knowing  violations of law, for any transaction  from which the
director derived an improper personal  benefit,  and for payment of dividends or
approval of stock  repurchases or  redemptions  that are unlawful under Delaware
law. The provision does not affect a director's responsibilities under any other
laws,  such as the  federal  securities  laws or state or federal  environmental
laws.


Item 16. Exhibits and Financial Statement Schedules

         (a)  Exhibits

   
         Exhibit
         Number      Description of Document
         ------      -----------------------
         4.1         Form of Common Stock Purchase Agreement, dated as of 
                     September 28, 1997, by and between the Company and the
                     investors listed therein.(+)
         5.1         Opinion of Cooley Godward LLP.(+)
         23.1        Consent of Ernst & Young LLP, Independent Auditors.(+)
         23.2        Consent of Cooley Godward LLP.  Reference is made to
                     Exhibit 5.1.
         24.1        Power of Attorney.  Reference is made to page II-3.

- --------------------
(+) Previously filed.
    

                                      II-1
<PAGE>

Item 17.  Undertakings.

         The undersigned registrant hereby undertakes:

         (1) To file, during any period in which offers or sales are being made,
a  post-effective  amendment  to this  Registration  Statement  to  include  any
material  information  with respect to the plan of  distribution  not previously
disclosed  in  the  registration  statement  or  any  material  change  to  such
information in the registration statement.

         (2) That,  for the  purpose  of  determining  any  liability  under the
Securities Act of 1933, each such post-effective amendment shall be deemed to be
a new registration statement relating to the securities offered therein, and the
offering of such  securities at that time shall be deemed to be the initial bona
fide offering thereof; and

         (3) To remove from registration by means of a post-effective  amendment
any of the securities being registered which remain unsold at the termination of
the offering.

         The  undersigned  registrant  hereby  undertakes  that, for purposes of
determining  any liability  under the Securities Act of 1933, each filing of the
registrant's  annual report pursuant to Section 13(a) or 15(d) of the Securities
Exchange  Act of 1934 that is  incorporated  by  reference  in the  registration
statement  shall be deemed to be a new  registration  statement  relating to the
securities  offered  therein,  and the offering of such  securities at that time
shall be deemed to be the initial bona fide offering thereof.

         Insofar as indemnification for liabilities arising under the Securities
Act may be  permitted to  directors,  officers  and  controlling  persons of the
registrant  pursuant  to  provisions  described  in Item 15, or  otherwise,  the
registrant  has been advised that in the opinion of the  Securities and Exchange
Commission  such  indemnification  is against  public policy as expressed in the
Securities Act and is, therefore,  unenforceable.  In the event that a claim for
indemnification  against  such  liabilities  (other  than  the  payment  by  the
registrant of expenses  incurred or paid by a director,  officer or  controlling
person of the  registrant  in the  successful  defense  of any  action,  suit or
proceeding)  is  asserted by such  director,  officer or  controlling  person in
connection with the securities being registered,  the registrant will, unless in
the opinion of its counsel the matter has been settled by controlling precedent,
submit  to a  court  of  appropriate  jurisdiction  the  question  whether  such
indemnification  by it is against  public policy as expressed in the  Securities
Act and will be governed by the final adjudication of such issue.

                                      II-2

<PAGE>

                                   SIGNATURES

   
         Pursuant  to the  requirements  of the  Securities  Act  of  1933,  the
Registrant certifies that it has reasonable grounds to believe that it meets all
of the  requirements  for filing on Form S-3 and has duly caused this  Amendment
No. 1 to Registration  Statement to be signed on its behalf by the  undersigned,
thereunto duly authorized,  in the City of Hayward, State of California,  on the
31st day of December, 1997.
    

                              LYNX THERAPEUTICS, INC.

   
                              By:      Sam Eletr*
                                 -----------------------------------------------
                                       Sam Eletr, Ph.D.
                                       Chairman and Chief Executive Officer
                                       (Principal Executive Officer)
    

                                POWER OF ATTORNEY

   
    

<TABLE>
   
         Pursuant  to the  requirements  of the  Securities  Act of  1933,  this
Amendment No. 1 to Registration Statement has been signed below by the following
persons in the capabilities and on the dates indicated.
<CAPTION>
                    Signature                                         Title                              Date
                    ---------                                         -----                              ----
<S>                                                  <C>                                           <C> 
    Sam Eletr*                                       Chairman and Chief Executive                  December 31, 1997
- ---------------------------------------              Officer
                Sam Eletr                              (Principal Executive Officer)
                                          

/s/ Edward C. Albini                                 Chief Financial Officer                       December 31, 1997
- ---------------------------------------                (Principal Financial and
            Edward C. Albini                            Accounting Officer)

    William K. Bowes, Jr.*                           Director                                      December 31, 1997
- ---------------------------------------
          William K. Bowes, Jr.

    Craig C. Taylor*                                 Director                                      December 31, 1997
- ---------------------------------------
             Craig C. Taylor

    Sydney Brenner*                                  Director                                      December 31, 1997
- ---------------------------------------
             Sydney Brenner

                                                     Director                                      ___________, 1997
- ---------------------------------------
          Kathleen D. La Porte

    James C. Kitch*                                  Director                                      December 31, 1997
- ---------------------------------------
             James C. Kitch

*  By: /s/ Edward C. Albini
       --------------------------
           Edward C. Albini
           ATTORNEY-IN-FACT
    
</TABLE>

                                      II-3

<PAGE>

                                INDEX TO EXHIBITS

Exhibit
Number     Description of Document
- ------     -----------------------

   
4.1        Form of Common Stock Purchase Agreement, dated as of 
           September 28, 1997, by and between the Company and
           the investors listed therein.(+)
5.1        Opinion of Cooley Godward LLP.(+)
23.1       Consent of Ernst & Young LLP, Independent Auditors.(+)
23.2       Consent of Cooley Godward LLP.  Reference is made to Exhibit 5.1.
24.1       Power of Attorney.  Reference is made to page II-3.

- ----------------
(+) Previously filed.
    



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