<PAGE>
Exhibit 99.1
RISK FACTORS
This Quarterly Report on Form 10-Q contains "forward-looking
statements." These statements include descriptions of Millennium's operational
plans, expectations about future earnings and other results of operations, views
of future industry or market conditions, and other statements that include words
like "may," "expects," "believes," and "intends," and that describe opinions
about future events. Known and unknown risks may cause Millennium's actual
results and performances to be materially different from those expressed or
implied by these statements. Factors that could cause or contribute to such
differences include those discussed below, as well as those discussed elsewhere
in this Form 10-Q.
REGULATORY RISKS
WE HAVE NOT YET RECEIVED MARKETING APPROVAL FOR ANY PRODUCT OR SERVICE RESULTING
FROM OUR DEVELOPMENT EFFORTS AND MAY NOT BE ABLE TO OBTAIN ANY SUCH APPROVAL
We have completed development of only one product candidate,
CAMPATH-Registered Trademark-monoclonal antibody, which we developed in our
partnership with Ilex Oncology, Inc. This partnership only recently applied
to the U.S. Food and Drug Administration for approval to market this product.
It is possible that the FDA will not grant this marketing approval. As of
July 21, 2000, we and our alliance partners were conducting clinical trials
of six product candidates resulting from our research and development
programs, including clinical trials of CAMPATH-Registered Trademark-
monoclonal antibody, and preclinical testing of approximately ten product
candidates resulting from these programs.
All of the products that we are developing will require additional
research and development, extensive preclinical studies and clinical trials and
regulatory approval prior to any commercial sales. This process is lengthy,
often taking a number of years, and expensive. In some cases, the length of time
that it takes for us to achieve various regulatory approval milestones affects
the payments that we are eligible to receive under our strategic alliance
agreements.
We may need to successfully address a number of technological
challenges in order to complete development of our products. Moreover, these
products may not be effective in treating any disease or may prove to have
undesirable or unintended side effects, toxicities or other characteristics that
may preclude our obtaining regulatory approval or prevent or limit commercial
use.
WE HAVE ONLY LIMITED EXPERIENCE IN REGULATORY AFFAIRS, AND SOME OF OUR PRODUCTS
MAY BE BASED ON NEW TECHNOLOGIES; THESE FACTORS MAY AFFECT OUR ABILITY OR THE
TIME WE REQUIRE TO OBTAIN NECESSARY REGULATORY APPROVALS
We have only limited experience in filing and prosecuting applications
necessary to gain regulatory approvals which may affect our ability to obtain
these approvals. Moreover, certain of the products that are likely to result
from our research and development programs may be based on new technologies and
new therapeutic approaches that have not been extensively tested
<PAGE>
in humans. The regulatory requirements governing these types of products may be
more rigorous than for conventional products. As a result, we may experience a
longer regulatory process in connection with any products that we develop based
on these new technologies or new therapeutic approaches.
RISKS RELATING TO OUR INDUSTRY, BUSINESS AND STRATEGY
BECAUSE THE GENOMICS INDUSTRY IS NEW, IT IS POSSIBLE THAT THE DISCOVERIES AND
TECHNOLOGY ON WHICH THIS INDUSTRY IS BASED WILL NOT RESULT IN COMMERCIAL
PRODUCTS OR SERVICES
The genomics industry is new and evolving rapidly. We focus our
genomics research primarily on diseases that may be linked to several or many
genes working in combination. Both we and the general scientific and medical
communities have only a limited understanding relating to the role of genes and
their products in these diseases. To date, we have not commercialized any
products or services, and we may not be successful in doing so in the future. In
addition, relatively few products based on gene discoveries have been developed
and commercialized by others. Rapid technological development by us or others
may result in compounds, products or processes becoming obsolete before we
recover our development expenses.
OUR PLAN TO GROW THROUGH ACQUISITIONS OF OTHER COMPANIES WILL NOT BE SUCCESSFUL
IF WE ARE UNABLE TO INTEGRATE ACQUIRED COMPANIES WITH OUR OTHER OPERATIONS OR IF
THE TECHNOLOGY OR PERSONNEL OF ACQUIRED COMPANIES DO NOT MEET OUR EXPECTATIONS
We completed our merger with LeukoSite, Inc. on December 22, 1999. In
addition, we recently have announced our plans to acquire Cambridge Discovery
Chemistry, a wholly-owned subsidiary of Oxford Molecular Group. We may not be
able to successfully integrate or profitably manage these businesses. In
addition, the combination of our business with these businesses may not achieve
revenues, net income or loss levels, efficiencies or synergies that justify the
merger. The combined company may experience slower rates of growth as compared
to the historical rates of growth of Millennium and these businesses
independently. We plan to make additional acquisitions in the future, which will
entail similar risks.
COMPETITION FOR SCIENTIFIC AND MANAGERIAL PERSONNEL IN OUR INDUSTRY IS INTENSE;
WE WILL NOT BE ABLE TO SUSTAIN OUR OPERATIONS AND GROW IF WE ARE NOT ABLE TO
ATTRACT AND RETAIN KEY PERSONNEL
Our success substantially depends on the ability, experience and
performance of our senior management and other key personnel. If we lose one or
more of the members of our senior management or other key employees, our
business and operating results could be seriously harmed.
In addition, our future success will depend heavily on our ability to
continue to hire, train, retain and motivate additional skilled managerial and
scientific personnel. The pool of personnel with the skills that we require is
limited. Competition to hire from this limited pool is intense.
<PAGE>
The stock options held by LeukoSite employees became fully vested upon
the closing of our acquisition of LeukoSite. This acceleration may adversely
affect our ability to retain former LeukoSite employees.
WE FACE SUBSTANTIAL COMPETITION, WHICH MAY RESULT IN OTHERS DISCOVERING,
DEVELOPING OR COMMERCIALIZING PRODUCTS AND SERVICES BEFORE OR MORE SUCCESSFULLY
THAN WE DO
The fields of genomics, biotechnology and pharmaceuticals are highly
competitive. Many of our competitors are substantially larger than we are and
have substantially greater capital resources, research and development staffs
and facilities than we have. Furthermore, many of our competitors are more
experienced than we are in drug discovery, development and commercialization,
obtaining regulatory approvals and product manufacturing and marketing. As a
result, our competitors may identify genes associated with diseases or discover,
develop and commercialize products or services based on such genes before we do.
In addition, our competitors may discover, develop and commercialize products or
services which render non-competitive or obsolete the products or services that
we or our strategic alliance partners are seeking to develop and commercialize.
WE MAY NOT BE ABLE TO OBTAIN BIOLOGICAL MATERIAL, INCLUDING HUMAN AND ANIMAL DNA
SAMPLES, REQUIRED FOR OUR GENETIC STUDIES, WHICH COULD DELAY OR IMPEDE OUR DRUG
DISCOVERY EFFORTS
Our gene identification strategy includes genetic studies of families
and populations prone to particular diseases. These studies require the
collection of large numbers of DNA samples from affected individuals, their
families and other suitable populations as well as animal models. The
availability of DNA samples and other biological material is important to our
ability to discover the genes responsible for human diseases through human
genetic approaches and other studies. Competition for these resources is
intense. Access to suitable populations, materials and samples could be limited
by forces beyond our control, including governmental actions. Some of our
competitors may have obtained access to significantly more family and population
resources and biological materials than we have obtained. As a result, we may
not be able to obtain access to DNA samples necessary to support our human gene
discovery programs.
RISKS RELATING TO OUR FINANCIAL RESULTS AND STRUCTURE AND NEED FOR FINANCING
WE HAVE INCURRED SUBSTANTIAL LOSSES, WE EXPECT TO CONTINUE TO INCUR LOSSES AND
WE WILL NOT BE SUCCESSFUL UNLESS WE REVERSE THIS TREND
We have incurred losses in four of the last six years, including the
year ended December 31, 1999. We expect to continue to incur substantial
operating losses in future periods. To date, substantially all of our revenues
have resulted from payments from strategic alliance partners. We have not
received any revenues from the sale of products or clinical or diagnostic
services.
We expect to increase our spending significantly as we continue to
expand our infrastructure, research and development programs and
commercialization activities. As a result, we will need to generate significant
revenues to pay these costs and achieve profitability. We cannot be certain
whether or when we will become profitable because of the significant
<PAGE>
uncertainties with respect to our ability to generate revenues from the sale of
products and services and from existing and potential future strategic
alliances.
OUR SUBSTANTIAL INDEBTEDNESS MAY ADVERSELY AFFECT OUR CASH FLOW AND OPERATIONS
AND BE DIFFICULT FOR US TO REPAY, WHICH COULD ADVERSELY AFFECT THE VALUE OF YOUR
INVESTMENT IN US
We have substantial amounts of outstanding indebtedness, primarily our
5.50% convertible subordinated notes due January 15, 2007. We also may obtain
additional long term debt and working capital lines of credit. As a result of
this indebtedness, we have substantial principal and interest payment
obligations. There is the possibility that we may be unable to generate cash
sufficient to pay the principal of, interest on and other amounts due in respect
of our indebtedness when due.
Our substantial leverage could have significant negative consequences,
including:
- Increasing our vulnerability to general adverse economic and industry
conditions.
- Limiting our ability to obtain additional financing;
- Requiring the dedication of a substantial portion of our cash from
operations to service our indebtedness, thereby reducing the amount of
our cash available for other purposes, including capital expenditures;
- Limiting our flexibility in planning for, or reacting to, changes in
our business and the industry in which we compete; and
- Placing us at a possible competitive disadvantage vis-a-vis less
leveraged competitors and competitors that have better access to
capital resources.
WE MAY NEED ADDITIONAL FINANCING, WHICH MAY BE DIFFICULT TO OBTAIN; OUR FAILURE
TO OBTAIN NECESSARY FINANCING OR DOING SO ON UNATTRACTIVE TERMS COULD AVERSELY
AFFECT OUR DISCOVERY AND DEVELOPMENT PROGRAMS AND OTHER OPERATIONS
We will require substantial funds to conduct research and development,
including preclinical testing and clinical trials of our potential products,
meet our obligations to our strategic alliance partners, manufacture and market
any products and services that are approved for commercial sale and meet our
debt service obligations. Additional financing may not be available when we need
it or may not be available on terms that are favorable to us.
If we are unable to obtain adequate funding on a timely basis, we may
be required to significantly curtail one or more of our discovery or development
programs. We could be required to seek funds through arrangements with
collaborative partners or others that may require us to relinquish rights to
certain of our technologies, product candidates or products which we would
otherwise pursue on our own.
<PAGE>
RISKS RELATING TO STRATEGIC ALLIANCE PARTNERS
WE DEPEND SIGNIFICANTLY ON OUR STRATEGIC ALLIANCE PARTNERS TO DEVELOP AND
COMMERCIALIZE PRODUCTS AND SERVICES BASED ON OUR WORK; OUR BUSINESS MAY SUFFER
IF ANY OF OUR STRATEGIC ALLIANCE PARTNERS BREACHES THEIR AGREEMENT OR FAILS TO
SUPPORT OR TERMINATES THEIR ALLIANCE WITH US
We conduct most of our discovery and development activities through
strategic alliances. The success of these programs depends heavily on the
efforts and activities of our strategic alliance partners. Each of our alliance
partners has significant discretion in determining the efforts and resources
that they will apply to the alliance. Our existing and any future alliances may
not be scientifically or commercially successful.
The risks that we face in connection with these alliances include:
- All of our strategic alliance agreements are subject to termination
under various circumstances, including in many cases on short notice
without cause.
- In our strategic alliance agreements, we generally agree not to
conduct specified types of research and development in the field that
is the subject of the alliance. These agreements may have the effect
of limiting the areas of research and development we may pursue,
either alone or in collaboration with third parties.
- Our alliance partners may develop and commercialize, either alone or
with others, products and services that are similar to or competitive
with the products and services that are the subject of the alliance
with us.
- Our alliance partners may change the focus of their development and
commercialization efforts. Pharmaceutical and biotechnology companies
historically have re-evaluated their priorities following mergers and
consolidations, which have been common in recent years in these
industries.
- We will rely on our alliance partners to manufacture most products
covered by our alliances. For example, Becton Dickinson has the sole
right to manufacture our Melastatin(TM) gene detection product.
WE MAY NOT BE SUCCESSFUL IN ESTABLISHING ADDITIONAL STRATEGIC ALLIANCES, WHICH
COULD ADVERSELY AFFECT OUR ABILITY TO DEVELOP AND COMMERCIALIZE PRODUCTS
An important element of our business strategy is entering into
strategic alliances for the development and commercialization of products and
services based on our discoveries. We face significant competition in seeking
appropriate alliance partners. Moreover, these alliance arrangements are complex
to negotiate and time-consuming to document. We may not be successful in our
efforts to establish additional strategic alliances or other alternative
arrangements. The terms of any additional strategic alliances or other
arrangements that we establish may not be favorable to us. Moreover, such
strategic alliances or other arrangements may not be successful.
<PAGE>
RISKS RELATING TO INTELLECTUAL PROPERTY
IF WE ARE UNABLE TO OBTAIN PATENT PROTECTION FOR OUR DISCOVERIES, THE VALUE OF
OUR TECHNOLOGY AND PRODUCTS WILL BE ADVERSELY AFFECTED; IF WE INFRINGE PATENT OR
OTHER INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES, WE MAY NOT BE ABLE TO
DEVELOP AND COMMERCIALIZE OUR PRODUCTS AND SERVICES OR THE COST OF DOING SO MAY
INCREASE
Our patent positions, and those of other pharmaceutical and
biotechnology companies, are generally uncertain and involve complex legal,
scientific and factual questions.
Our ability to develop and commercialize products and services depends
in significant part on our ability to:
- Obtain patents;
- Obtain licenses to the proprietary rights of others on commercially
reasonable terms;
- Operate without infringing upon the proprietary rights of others;
- Prevent others from infringing on our proprietary rights; and
- Protect trade secrets.
THERE IS SIGNIFICANT UNCERTAINTY ABOUT THE VALIDITY AND PERMISSIBLE SCOPE OF
GENOMICS PATENTS IN OUR INDUSTRY, WHICH MAY MAKE IT DIFFICULT FOR US TO OBTAIN
PATENT PROTECTION FOR OUR DISCOVERIES
The validity and permissible scope of patent claims in the
pharmaceutical and biotechnology fields, including the genomics field, involve
important unresolved legal principles and are the subject of public policy
debate in the United States and abroad. For example, there is significant
uncertainty both in the United States and abroad regarding the patentability of
gene sequences in the absence of functional data and the scope of patent
protection available for full-length genes and partial gene sequences. Moreover,
certain groups have made certain gene sequences available in publicly accessible
databases. These and other disclosures may adversely affect our ability to
obtain patent protection for gene sequences claimed by us in patent applications
that we file subsequent to such disclosures. There is also some uncertainty as
to whether human clinical data will be required for issuance of patents for
human therapeutics. If such data are required, our ability to obtain patent
protection could be delayed or otherwise adversely affected.
THIRD PARTIES MAY OWN OR CONTROL PATENTS OR PATENT APPLICATIONS AND REQUIRE US
TO SEEK LICENSES, WHICH COULD INCREASE OUR DEVELOPMENT AND COMMERCIALIZATION
COSTS, OR PREVENT US FROM DEVELOPING OR MARKETING PRODUCT OR SERVICE CANDIDATES
We may not have rights under some patents or patent applications
related to our proposed products, processes or services. Third parties may own
or control these patents and patent applications in the United States and
abroad. Therefore, in some cases, such as those described below, to develop,
manufacture, sell or import certain of our proposed products, processes or
<PAGE>
services, we or our alliance partners may choose to seek, or be required to
seek, licenses under third party patents issued in the United States and abroad
or those which might issue from United States and foreign patent applications.
In such event, we would be required to pay license fees or royalties or both to
the licensor. If licenses are not available to us on acceptable terms, we or our
alliance partners may not be able to develop, manufacture, sell or import these
products, processes or services.
With respect to our product candidate LDP-01, we are aware of third
party patents and patent applications which relate to certain anti-CD18
antibodies and their use in various methods of treatment including methods of
reperfusion therapy and methods of treating focal ischemic stroke. In
addition, our LDP-01, LDP-02, and CAMPATH-Registered Trademark- product
candidates are humanized monoclonal antibodies. We are aware of third party
patents and patent applications which relate to certain humanized or modified
antibodies, products useful for making humanized or modified antibodies, and
processes for making and using humanized or modified antibodies. We are also
aware of third party patents and patent applications relating to certain
manufacturing processes, products thereof and materials useful in such
processes.
Our product candidates LDP-977, LDP-341, and LDP-519 are all small
molecule drug candidates. With respect to LDP-341, we are aware of third party
patents or patent applications which relate to either intermediates or synthetic
processes used in the synthesis of these compounds. Additionally, for the use of
LDP-341 and LDP-519 in the treatment of infarctions we are aware of the
existence of a potentially interfering patent application filed by one of our
former consultants.
WE MAY BECOME INVOLVED IN EXPENSIVE PATENT LITIGATION OR OTHER PROCEEDINGS,
WHICH COULD RESULT IN OUR INCURRING SUBSTANTIAL COSTS AND EXPENSES OR
SUBSTANTIAL LIABILITY FOR DAMAGES OR REQUIRE US TO STOP OUR DEVELOPMENT AND
COMMERCIALIZATION EFFORTS
There has been substantial litigation and other proceedings regarding
the patent and other intellectual property rights in the pharmaceutical and
biotechnology industries. We may become a party to patent litigation or other
proceedings regarding intellectual property rights. For example, we believe that
we hold patent applications that cover genes that are also claimed in patent
applications filed by others. Interference proceedings before the United States
Patent and Trademark Office may be necessary to establish which party was the
first to invent these genes.
The cost to us of any patent litigation or other proceeding, even if
resolved in our favor, could be substantial. Some of our competitors may be able
to sustain the cost of such litigation or proceedings more effectively than we
can because of their substantially greater financial resources. If a patent
litigation or other proceeding is resolved against us, we or our alliance
partners may be enjoined from developing, manufacturing, selling or importing
our products, processes or services without a license from the other party and
we may be held liable for significant damages. We may not be able to obtain any
required license on commercially acceptable terms or at all.
Uncertainties resulting from the initiation and continuation of patent
litigation or other proceedings could have a material adverse effect on our
ability to compete in the marketplace. Patent litigation and other proceedings
may also absorb significant management time.
<PAGE>
RISKS RELATING TO PRODUCT MANUFACTURING, MARKETING AND SALES
BECAUSE MANY OF THE PRODUCTS AND SERVICES THAT WE DEVELOP WILL BE BASED ON NEW
TECHNOLOGIES AND THERAPEUTIC APPROACHES, THE MARKET MAY NOT BE RECEPTIVE TO
THESE PRODUCTS AND SERVICES UPON THEIR INTRODUCTION
The commercial success of our products and services that are approved
for marketing will depend upon their acceptance by the medical community and
third party payors as clinically useful, cost effective and safe. Many of the
products and services that we are developing are based upon new technologies or
therapeutic approaches. As a result, it may be more difficult for us to achieve
market acceptance of our products and services, particularly the first products
and services that we introduce to the market based on new technologies and
therapeutic approaches.
BECAUSE WE HAVE NO SALES, MARKETING OR DISTRIBUTION EXPERIENCE AND CAPABILITIES,
WE WILL BE DEPENDENT ON THIRD PARTIES TO SUCCESSFULLY PERFORM THESE FUNCTIONS OR
WILL BE REQUIRED TO INCUR SIGNIFICANT COSTS AND DEVOTE SIGNIFICANT EFFORTS TO
DEVELOP THESE CAPABILITIES
We have no sales, marketing or distribution experience and
capabilities. We plan to rely significantly on sales, marketing and
distribution arrangements with our strategic alliance partners and other
third parties for the products and services that we are developing. For
example, our partnership that holds CAMPATH-Registered Trademark- monoclonal
antibody will rely solely upon Schering AG and its U.S. affiliate, Berlex
Laboratories, for the marketing, distribution and sale of the
CAMPATH-Registered Trademark- product throughout the world other than the Far
East. If in the future we determine to perform sales, marketing and
distribution functions ourselves, we would face a number of additional risks,
including the need to recruit experienced marketing and sales personnel.
BECAUSE WE HAVE LIMITED MANUFACTURING CAPABILITIES, WE WILL BE DEPENDENT ON
THIRD PARTY MANUFACTURERS TO MANUFACTURE PRODUCTS FOR US OR WILL BE REQUIRED TO
INCUR SIGNIFICANT COSTS AND DEVOTE SIGNIFICANT EFFORTS TO ESTABLISH OUR OWN
MANUFACTURING FACILITIES AND CAPABILITIES
We have limited manufacturing experience and no commercial scale
manufacturing capabilities. In order to continue to develop products and
services, apply for regulatory approvals and, ultimately, commercialize any
products and services, we will need to develop, contract for or otherwise
arrange for the necessary manufacturing capabilities.
We currently rely upon third parties to produce material for
preclinical testing purposes and expect to continue to do so in the future.
We also expect to rely upon other third parties, including our strategic
alliance partners, to produce materials required for clinical trials and for
the commercial production of certain of our products if we succeed in
obtaining necessary regulatory approvals. Our partnership with ILEX Oncology
relies on Boehringer Ingleheim as the sole source manufacturer of
CAMPATH-Registered Trademark- monoclonal antibody.
There are a limited number of manufacturers that operate under the
FDA's good manufacturing practices regulations capable of manufacturing for us.
As a result, we have experienced some difficulty finding manufacturers for our
products with adequate capacity for our anticipated future needs. If we are
unable to arrange for third party manufacturing of our
<PAGE>
products, or to do so on commercially reasonable terms, we may not be able to
complete development of our products or market them.
Reliance on third party manufacturers entails risks to which we would
not be subject if we manufactured products ourselves, including reliance on the
third party for regulatory compliance and quality assurance, the possibility of
breach of the manufacturing agreement by the third party because of factors
beyond our control and the possibility of termination or nonrenewal of the
agreement by the third party, based on its own business priorities, at a time
that is costly or inconvenient for us.
We may in the future determine to manufacture certain of our products
in our own manufacturing facilities. We will require substantial additional
funds and need to recruit qualified personnel in order to build or lease and
operate any manufacturing facilities.
IF WE FAIL TO OBTAIN AN ADEQUATE LEVEL OF REIMBURSEMENT FOR OUR FUTURE PRODUCTS
OR SERVICES BY THIRD PARTY PAYORS, THERE MAY BE NO COMMERCIALLY VIABLE MARKETS
FOR OUR PRODUCTS OR SERVICES
The availability and levels of reimbursement by governmental and other
third party payors affects the market for any pharmaceutical product or
healthcare service. These third party payors continually attempt to contain or
reduce the costs of healthcare by challenging the prices charged for medical
products and services. In certain foreign countries, particularly the countries
of the European Union, the pricing of prescription pharmaceuticals is subject to
governmental control. We may not be able to sell our products and services
profitably if reimbursement is unavailable or limited in scope or amount.
In both the United States and certain foreign jurisdictions, there have
been a number of legislative and regulatory proposals to change the healthcare
system. Further proposals are likely. The potential for adoption of these
proposals affects or will affect our ability to raise capital, obtain additional
collaborative partners and market our products.
If we or our alliance partners obtain marketing approvals for our
products and services, we expect to experience pricing pressure due to the trend
toward managed health care, the increasing influence of health maintenance
organizations and additional legislative proposals.
ETHICAL, LEGAL AND SOCIAL ISSUES RELATED TO GENETIC TESTING MAY CAUSE OUR
DIAGNOSTIC PRODUCTS TO BE REJECTED BY CUSTOMERS OR PROHIBITED OR CURTAILED BY
GOVERNMENTAL AUTHORITIES
Diagnostic tests that evaluate genetic predisposition to disease raise
issues regarding the use and confidentiality of the information provided by such
tests. Insurance carriers and employers might discriminate on the basis of such
information, resulting in a significant barrier to the acceptance of such tests
by customers. This type of discrimination could cause governmental authorities
to prohibit or limit the use of such tests.
