IMMUNE RESPONSE CORP
424B2, 2000-01-26
BIOLOGICAL PRODUCTS, (NO DIAGNOSTIC SUBSTANCES)
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<PAGE>

                                               FILING PURSUANT TO RULE 424(b)(2)
                                            REGISTRATION STATEMENT NO. 333-94257


                              PROSPECTUS SUPPLEMENT
                      (TO PROSPECTUS DATED JANUARY 7, 2000)

                                 600,000 SHARES

                         THE IMMUNE RESPONSE CORPORATION
                                  COMMON STOCK

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

         You should read this prospectus supplement and the accompanying
prospectus carefully before you invest. Both documents contain information you
should consider carefully before making your investment decision.

         INVESTING IN OUR COMMON STOCK INVOLVES RISKS. SEE "RISK FACTORS"
BEGINNING ON PAGE 2 OF THE PROSPECTUS


                              PLAN OF DISTRIBUTION

         We entered into an Assignment Agreement dated as of December 8, 1999
with Connetics Corporation to purchase the rights to its TCR Technology in
exchange for money and shares of our common stock. We also entered into an
Agreement dated as of December 8, 1999 with XOMA (US) LLC to purchase the
rights to is TCR Technology in exchange for money and shares of our common
stock. Pursuant to both agreements, we issued 250,000 shares to Connetics
Corporation and XOMA (US) LLC, together referred to as the selling
stockholders, on December 8, 1999 and are obligated to issue to them up to an
additional 350,000 shares by June 30, 2000.

         The selling stockholders may be deemed to be "underwriters" within the
meaning of the Securities Act of 1933.

         We will not pay any compensation in conjunction with the sale of our
common stock.


                                 USE OF PROCEEDS

         We will not receive any proceeds from the sale of common stock by the
selling stockholders in the offering. See "Use of Proceeds" beginning on page 11
of our prospectus.

                       WHERE YOU CAN FIND MORE INFORMATION

         The SEC allows us to "incorporate by reference" information that we
file with them, which means that we can disclose important information to you by
referring you to those


                                      S-1
<PAGE>

documents. The information incorporated by reference is an important part of
this prospectus supplement and the accompanying prospectus. We incorporate the
documents indicated on page 10 of our prospectus.


                           MARKET FOR OUR COMMON STOCK

         On January 25, 2000 the last reported sale price of our common stock on
the Nasdaq National Market was $8.25 per share. Our common stock is
listed on the Nasdaq National Market under the symbol "IMNR." The common stock
sold under this prospectus supplement will be listed on the Nasdaq National
Market.

         As of January 20, 2000, we had 26,780,313 shares of common stock
outstanding.


                                     GENERAL

         You should rely only on the information provided or incorporated by
reference in this prospectus supplement and the prospectus. We have not
authorized anyone else to provide you with different information. You should not
assume that the information in this prospectus supplement is accurate as of any
date other than the date on the front of these documents.

         Neither The Securities And Exchange Commission Nor Any State Securities
Commission Has Approved Or Disapproved Of The Securities Or Passed Upon The
Accuracy Or Adequacy Of This Prospectus. Any Representation To The Contrary Is A
Criminal Offense.

         The date of this prospectus supplement is January 26, 2000.


                                      S-2
<PAGE>

                         THE IMMUNE RESPONSE CORPORATION
                         600,000 SHARES OF COMMON STOCK

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

         This prospectus is part of a registration statement we filed with the
Securities and Exchange Commission, which will be used by the selling
stockholders, identified on page 12, to resell the common stock.
This means:

        -      The selling stockholders may sell its shares of common stock from
               time to time.

        -      For information on the methods of sale of the common stock, you
               should refer to the section entitled "Plan of Distribution" on
               page 12. We will not receive any portion of the proceeds from the
               sale of these shares.

        -      You should read this prospectus and any prospectus supplement
               carefully before you invest.

         Our common stock is listed on the Nasdaq National Market under the
symbol "IMNR." On January 6, 2000, the last reported sale price for our common
stock on the Nasdaq National Market was $5.25 per share.

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

        INVESTING IN OUR COMMON STOCK INVOLVES RISKS. SEE "RISK FACTORS"
BEGINNING ON PAGE 2.

        NEITHER THE SECURITIES AND EXCHANGE COMMISSION NOR ANY STATE SECURITIES
COMMISSION HAS APPROVED OR DISAPPROVED THESE SECURITIES OR PASSED UPON THE
ADEQUACY OF THIS PROSPECTUS. ANY REPRESENTATION TO THE CONTRARY IS A CRIMINAL
OFFENSE.

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

                The date of this Prospectus is January 7, 2000


                                      -1-
<PAGE>

                                  RISK FACTORS

        YOU SHOULD CAREFULLY CONSIDER THE RISKS DESCRIBED BELOW BEFORE MAKING AN
INVESTMENT DECISION. THE RISKS AND UNCERTAINTIES DESCRIBED BELOW ARE NOT THE
ONLY ONES FACING US. ADDITIONAL RISKS AND UNCERTAINTIES NOT PRESENTLY KNOWN TO
US OR THAT WE CURRENTLY DEEM IMMATERIAL MAY ALSO IMPAIR OUR BUSINESS.

        IF ANY OF THE FOLLOWING RISKS ACTUALLY OCCUR, OUR BUSINESS COULD BE
ADVERSELY AFFECTED. IN THOSE CASES, THE TRADING PRICE OF OUR COMMON STOCK COULD
DECLINE, AND YOU MAY LOSE ALL OR PART OF YOUR INVESTMENT.

THE FAILURE TO SUCCESSFULLY DEVELOP AND COMMERCIALIZE PRODUCTS MAY CAUSE US TO
CEASE OPERATIONS.

        We have not completed the development of any products. A failure to
successfully develop and commercialize products may cause us to cease
operations. Our potential therapies under development will require significant
additional research and development efforts and regulatory approvals prior to
potential commercialization.

        The conclusion of the Phase III trial of REMUNE in May, 1999 due to
lack of efficacy has had a material adverse effect on us. If Agouron
Pharmaceuticals, Inc., a Warner Lambert Company, Agouron, fails to initiate
or successfully complete additional pivotal trials with REMUNE we may have to
abandon REMUNE or seek additional funding.

        Our other therapies and technologies are at earlier stages of
development than REMUNE. Some of our technologies have not yet been tested in
humans. Human testing of potential products based on these technologies may not
be permitted by regulatory authorities. Even if human testing is permitted, the
products based on these technologies may not be successfully developed or be
shown to be safe and efficacious. Potential immune-based therapies based on some
of our technologies are at an early stage of clinical testing and may not be
shown to be safe or efficacious or ever receive regulatory approval.

        The results of our preclinical studies and clinical trials may not be
indicative of future clinical trial results. A commitment of substantial
resources to conduct time-consuming research, preclinical studies and clinical
trials will be required if we are to develop any products. Delays in planned
patient enrollment in our clinical trials may result in increased costs, program
delays or both. None of our potential products may prove to be safe and
effective in clinical trials. FDA or other regulatory approvals may not be
obtained and even if successfully developed and approved, our products may not
achieve market acceptance. Any products resulting from our programs are not
expected to be successfully developed or commercially available for a number of
years, if at all.

        Unacceptable toxicities or side effects may occur at any time in the
course of human clinical trials or, if any products are successfully developed
and approved for marketing, during commercial use of our products. The
appearance of any unacceptable toxicities or side effects could interrupt,
limit, delay or abort the development of any of our products or, if previously
approved, necessitate their withdrawal from the market.


                                      -2-

<PAGE>

OUR ADDITIONAL FINANCING REQUIREMENTS AND LIMITED ACCESS TO FINANCING MAY
ADVERSELY AFFECT OUR ABILITY TO DEVELOP PRODUCTS

        We will need to raise additional funds to conduct research and
development, preclinical studies and clinical trials necessary to bring our
potential products to market and establish manufacturing and marketing
capabilities. A failure to raise additional funds would require us to scale back
or eliminate some or all of our research and development programs or license to
third parties products or technologies that we would otherwise seek to develop
ourselves. We believe that our existing resources, will enable us to maintain
our current and planned operations only into early 2001.

        Although we anticipate that the development of REMUNE will continue to
represent a significant portion of our overall expenditures, we also anticipate
that costs related to the development of REMUNE will decrease from 1999 levels
in 2000. Other anticipated costs with respect to REMUNE will depend on many
factors, in particular the continuation of our collaboration with Agouron.


        Our future capital requirements will depend on many factors, including:

        -      continued scientific progress in our research and development
               programs,

        -      the scope and results of preclinical studies and clinical trials,
               the time and costs involved in obtaining regulatory approvals,

        -      the costs involved in filing, prosecuting and enforcing patent
               claims,

        -      competing technological and market developments,

        -      the cost of manufacturing scale-up,

        -      effective commercialization activities and arrangements, and

        -      other factors not within our control.

        We intend to seek additional funding through public or private
financings, arrangements with corporate collaborators or other sources. If funds
are acquired through additional collaborations, we will likely be required to
relinquish some or all of the rights to products that we may have otherwise
developed ourselves. If adequate funds are not available when needed or on terms
acceptable to us, we may be required to scale back some or all of our research
and development programs or license to third parties products or technologies
that we would otherwise seek to develop ourselves.


                                      -3-

<PAGE>

IF AGOURON TERMINATES ITS COLLABORATION WITH US WE MAY HAVE TO ABANDON REMUNE

        Our binding Letter of Intent with Agouron is the primary
collaborative agreement that provides us with contract revenue. The
termination of our agreement with Agouron might require us to abandon REMUNE.

WE MAY NOT BE ABLE TO ENTER INTO ADDITIONAL COLLABORATIONS

         We intend to seek additional collaborative arrangements to develop and
commercialize our products. We may not be able to negotiate collaborative
arrangements on favorable terms, or at all, in the future and our current or
future collaborative arrangements may not be successful. This may cause us to
abandon some of our products under development.

OUR PATENTS AND PROPRIETARY TECHNOLOGY MAY NOT PROVIDE US WITH ANY BENEFIT AND
THE PATENTS AND PROPRIETARY TECHNOLOGY OF OTHERS MAY PREVENT US FROM
COMMERCIALIZING PRODUCTS

        A failure to obtain meaningful patent protection for our potential
products and processes would greatly diminish the value of our potential
products and processes.

        In addition, whether or not our patents are issued, or issued with
limited coverage, others may receive patents which contain claims applicable to
our products. We are aware that AstraZeneca PLC has acquired the rights to a
patent, which has been issued in Europe and other countries, that may interfere
with our ability to develop some of our technologies related to autoimmune
disease if the patent is upheld after current opposition proceedings. This
patent, and others that we are not aware of, may adversely affect our ability to
develop and commercialize products.

        The patent positions of biotechnology and pharmaceutical companies can
be highly uncertain, and involve complex legal and factual questions. Therefore,
the breadth of claims allowed in biotechnology and pharmaceutical patents cannot
be predicted. We also rely upon unpatented trade secrets and know how, and
others may independently develop substantially equivalent trade secrets or know
how.

        We also rely on protecting our proprietary technology in part through
confidentiality agreements with our corporate collaborators, employees,
consultants and certain contractors. These agreements may be breached and we may
not have adequate remedies for any breach. In addition, our trade secrets may
otherwise become known or independently discovered by our competitors.

        Our products and processes may infringe, or be found to infringe,
patents not owned or controlled by us, such as the patent owned by AstraZeneca
PLC. If relevant claims of third-party patents are upheld as valid and
enforceable, we could be prevented from practicing the subject matter claimed in
the patents, or would be required to obtain licenses to redesign our products or
processes to avoid infringement. Licenses may not be available at all or on
terms commercially reasonable to us and we may not be able to redesign our
products or processes to avoid infringement.


                                      -4-

<PAGE>

        Litigation may be necessary to defend against claims of infringement, to
enforce patents issued to us or to protect trade secrets. Litigation could
result in substantial costs and diversion of management efforts regardless of
the results of the litigation. An adverse result in litigation could subject us
to significant liabilities to third parties, require disputed rights to be
licensed or require us to cease using some technology.

OUR HISTORY OF OPERATING LOSSES AND OUR EXPECTATIONS OF CONTINUING LOSSES MAY
HURT OUR ABILITY TO CONTINUE OPERATIONS

        As of September 30, 1999, we had a consolidated accumulated deficit of
$184.4 million. We have not generated revenues from the commercialization of any
product. We expect to incur substantial net operating losses over the next
several years which may imperil our ability to continue operations. We may not
be able to generate sufficient product revenue to become profitable at all or on
a sustained basis.

THE LENGTHY APPROVAL PROCESS AND UNCERTAINTY OF GOVERNMENT REGULATORY
REQUIREMENTS MAY DELAY OR PREVENT US FROM COMMERCIALIZING PRODUCTS

        Clinical testing, manufacture, promotion and sale of our products are
subject to extensive regulation by numerous governmental authorities in the
United States, principally the FDA, and corresponding state and foreign
regulatory agencies. This regulation may delay or prevent us from
commercializing products. Noncompliance with applicable requirements can result
in, among other things, fines, injunctions, seizure of products, total or
partial suspension of product marketing, failure of the government to grant
premarket approval, withdrawal of marketing approvals and criminal prosecution.

        The regulatory process for new therapeutic drug products, including the
required preclinical studies and clinical testing, is lengthy and expensive. We
may not receive necessary FDA clearances for any of our potential products in a
timely manner, or at all. The length of the clinical trial process and the
number of patients the FDA will require to be enrolled in the clinical trials in
order to establish the safety and efficacy of our products is uncertain.

        Even if additional pivotal surrogate marker trials of REMUNE are
successfully completed, the FDA may not approve REMUNE for commercial sale. We
may encounter significant delays or excessive costs in our efforts to secure
necessary approvals. Regulatory requirements are evolving and uncertain. Future
United States or foreign legislative or administrative acts could also prevent
or delay regulatory approval of our products. We may not be able to obtain the
necessary approvals for clinical trials, manufacturing or marketing of any of
our products under development. Even if commercial regulatory approvals are
obtained, they may include significant limitations on the indicated uses for
which a product may be marketed.

        In addition, a marketed product is subject to continual FDA review.
Later discovery of previously unknown problems or failure to comply with the
applicable regulatory requirements may result in restrictions on the marketing
of a product or withdrawal of the product from the market, as well as possible
civil or criminal sanctions.


                                      -5-
<PAGE>

        Among the other requirements for regulatory approval is the requirement
that prospective manufacturers conform to the FDA's Good Manufacturing
Practices, GMP, requirements specifically for biological drugs, as well as for
other drugs. In complying with the FDA's GMP requirements, manufacturers must
continue to expend time, money and effort in production, recordkeeping and
quality control to assure that the product meets applicable specifications and
other requirements. Failure to comply with the FDA's GMP requirements subjects
the manufacturer to possible FDA regulatory action. We or our contract
manufacturers, if any, may not be able to maintain compliance with the FDA's GMP
requirements on a continuing basis. Failure to maintain compliance could have a
material adverse effect on us.

        The FDA has not designated expanded access protocols for REMUNE as
"treatment" protocols. The FDA may not determine that REMUNE meets all of the
FDA's criteria for use of an investigational drug for treatment use. Even if
REMUNE is allowed for treatment use, third party payers may not provide
reimbursement for the costs of treatment with REMUNE.

        The FDA may not consider REMUNE or any other of the Company's products
under development to be an appropriate candidate for accelerated approval,
expedited review or fast track designation.

        To market any drug products outside of the United States, we are also
subject to numerous and varying foreign regulatory requirements, implemented by
foreign health authorities, governing the design and conduct of human clinical
trials and marketing approval. The approval procedure varies among countries and
can involve additional testing, and the time required to obtain approval may
differ from that required to obtain FDA approval. The foreign regulatory
approval process includes all of the risks associated with obtaining FDA
approval set forth above, and approval by the FDA does not ensure approval by
the health authorities of any other country, nor does the approval by foreign
health authorities ensure approval be the FDA.

TECHNOLOGICAL CHANGE AND COMPETITION MAY RENDER OUR POTENTIAL PRODUCTS OBSOLETE

        The biotechnology industry continues to undergo rapid change and
competition is intense and is expected to increase. Competitors may succeed in
developing technologies and products that are more effective or affordable than
any which are being developed by us or which would render our technology and
products obsolete and noncompetitive. Many of our competitors have substantially
greater experience, financial and technical resources and production, marketing
and development capabilities than us. Accordingly, some of our competitors may
succeed in obtaining regulatory approval for products more rapidly or
effectively than us.

OUR LACK OF COMMERCIAL MANUFACTURING AND MARKETING EXPERIENCE MAY PREVENT US
FROM SUCCESSFULLY COMMERCIALIZING PRODUCTS

        We have not manufactured our product candidates in commercial
quantities. We may not successfully make the transition from manufacturing
clinical trial quantities to commercial production quantities or be able to
arrange for contract manufacturing and this could prevent us from
commercializing products. Even if REMUNE is successfully developed and receives
FDA


                                       -6-

<PAGE>

approval, we have not demonstrated the capability to manufacture REMUNE in
commercial quantities. Except for REMUNE, we have not demonstrated the ability
to manufacture our treatments in large-scale clinical or commercial quantities.

        We have no experience in the sales, marketing and distribution of
pharmaceutical products. Thus, our products may not be successfully
commercialized even if they are developed and approved for commercialization.

        The manufacture process of our products involves a number of steps and
requires compliance with stringent quality control specifications imposed by us
and by the FDA. Moreover, our products can only be manufactured in a facility
that has undergone a satisfactory inspection by the FDA. For these reasons, we
would not be able quickly to replace our manufacturing capacity if we were
unable to use our manufacturing facilities as a result of a fire, natural
disaster (including an earthquake), equipment failure or other difficulty, or if
such facilities are deemed not in compliance with the FDA's GMP requirements and
the non-compliance could not be rapidly rectified. Our inability or reduced
capacity to manufacture our products would prevent us from successfully
commercializing products.

        We may enter into arrangements with contract manufacturing companies to
expand our own production capacity in order to meet requirements for our
products, or to attempt to improve manufacturing efficiency. If we choose to
contract for manufacturing services and encounter delays or difficulties in
establishing relationships with manufacturers to produce, package and distribute
our finished products, clinical trials, market introduction and subsequent sales
of the products would be delayed. Further, contract manufacturers must also
operate in compliance with the FDA's GMP requirements; failure to do so could
result in, among other things, the disruption of product supplies. Our potential
dependence upon third parties for the manufacture of our products may adversely
affect our profit margins and our ability to develop and deliver products on a
timely and competitive basis.

ADVERSE DETERMINATIONS CONCERNING PRODUCT PRICING, REIMBURSEMENT AND RELATED
MATTERS COULD PREVENT US FROM SUCCESSFULLY COMMERCIALIZING PRODUCTS

        Our ability to earn sufficient returns on our products will depend in
part on the extent to which reimbursement for the costs of the products and
related treatments will be available from government health administration
authorities, private health coverage insurers, managed care organizations and
other organizations. Failure to obtain appropriate reimbursement could prevent
us from successfully commercializing products. Third party payors are
increasingly challenging the price of medical products and services. If
purchasers or users of our products are not able to obtain adequate
reimbursement for the cost of using the products, they may forego or reduce
their use. Significant uncertainty exists as to the reimbursement status of
newly approved health care products, and whether adequate third party coverage
will be available.

PRODUCT LIABILITY EXPOSURE MAY EXPOSE US TO SIGNIFICANT LIABILITY

        We face an inherent business risk of exposure to product liability and
other claims in the event that the development or use of our technology or
prospective products is alleged to have


                                      -7-

<PAGE>

resulted in adverse effects. We may not avoid significant liability exposure. We
may not have sufficient insurance coverage and we may not be able to obtain
sufficient coverage, at a reasonable cost. An inability to obtain product
liability insurance at acceptable cost or to otherwise protect against potential
product liability claims could prevent or inhibit the commercialization of
products developed by us. A product liability claim could hurt our financial
performance.

HAZARDOUS MATERIALS/ENVIRONMENTAL MATTERS COULD EXPOSE US TO SIGNIFICANT COSTS

        Although we do not currently manufacture commercial quantities of our
product candidates, we produce limited quantities of these products for our
clinical trials. We may be required to incur significant costs to comply with
current or future environmental laws and regulations. Our research and
development processes involve the controlled storage, use and disposal of
hazardous materials, biological hazardous materials and radioactive compounds.
We are subject to federal, state and local laws and regulations governing the
use, manufacture, storage, handling and disposal of these materials and some
waste products. Although we believe that our safety procedures for handling and
disposing of these materials comply with the standards prescribed by these laws
and regulations, the risk of accidental contamination or injury from these
materials cannot be completely eliminated. In the event of an accident, we could
be held liable for any damages that result, and any liability could exceed our
resources. Our operations, business or assets may be materially and adversely
affected by current or future environmental laws or regulations.

SUBORDINATION OF COMMON STOCK TO PREFERRED STOCK COULD HURT COMMON STOCKHOLDERS

        Our common stock is expressly subordinate to our Series F Convertible
Preferred Stock in the event of our liquidation, dissolution or winding up. If
we were to cease operations and liquidate our assets, there may not be any
remaining value available for distribution to the holders of common stock after
providing for the Series F Convertible Preferred Stock liquidation preference.

VOLATILITY OF STOCK PRICE AND ABSENCE OF DIVIDENDS MAY HURT COMMON STOCKHOLDERS

        The market price of our common stock, like that of the common stock of
many other biopharmaceutical companies, has been and is likely to be highly
volatile. Factors such as:

        -      the results of preclinical studies and clinical trials by us, our
               collaborators or our competitors,

        -      other evidence of the safety or efficacy of our products or our
               competitors,

        -      announcements of technological innovations or new products by us
               or our competitors,

        -      governmental regulatory actions,

        -      changes or announcements in reimbursement policies,

        -      developments with our collaborators,


                                      -8-

<PAGE>

        -      developments concerning patent or other proprietary rights of
               ours or our competitors (including litigation),

        -      concern as to the safety of our products,

        -      period-to-period fluctuations in our operating results,

        -      changes in estimates of our performance by securities analysts,

        -      market conditions for biopharmaceutical stocks in general, and

        -      other factors not within our control

could have a significant adverse impact on the market price of our common stock.
We have never paid cash dividends on our common stock and do not anticipate
paying any cash dividends in the foreseeable future.

EFFECT OF ANTI-TAKEOVER PROVISIONS COULD ADVERSELY AFFECT OUR COMMON
STOCKHOLDERS

        Our Certificate of Incorporation and Bylaws include provisions that
could discourage potential takeover attempts and make attempts by stockholders
to change management more difficult. The approval of 66-2/3 percent of our
voting stock is required to approve certain transactions and to take certain
stockholder actions, including the calling of special meetings of stockholders
and the amendment of any of the anti-takeover provisions contained in our
Certificate of Incorporation. Further, pursuant to the terms of our stockholder
rights plan, we have distributed a dividend of one right for each outstanding
share of common stock. These rights will cause substantial dilution to the
ownership of a person or group that attempts to acquire us on terms not approved
by the Board of Directors and may have the effect of deterring hostile takeover
attempts.


                                      -9-

<PAGE>

                       ADDITIONAL OR UPDATED RISK FACTORS

        Prior to making an investment decision with respect to the common stock
offered hereby, prospective investors should also carefully consider any
specific factors set forth under a caption "risk factors" in the applicable
prospectus supplement, if any, together with all of the other information
appearing in this prospectus or the prospectus supplement or incorporated by
reference into this prospectus.

               SPECIAL NOTE REGARDING FORWARD-LOOKING INFORMATION

        When used in this prospectus, the words "intends to," "believes,"
"anticipates," "expects" and similar expressions are intended to identify
forward-looking statements. These forward-looking statements are based largely
on our expectations and are subject to a number of risks and uncertainties, some
of which are beyond our control. For a discussion of some of these risks, see
"Risk Factors." These forward-looking statements speak only as of the date of
this prospectus. We expressly disclaim any obligation or undertaking to release
publicly any updates or revisions to any forward-looking statement contained
within this prospectus to reflect any change in our expectations with regard to
those forward-looking statements or any change in events, conditions or
circumstances on which any such statement is based.

                       WHERE YOU CAN FIND MORE INFORMATION

        We file annual, quarterly and special reports, proxy statements and
other information with the SEC. This information can be (1) read and copied at
the public reference facilities maintained by the SEC at 450 Fifth Street, N.W.,
Judiciary Plaza, Washington, D.C., and at the SEC's Chicago Regional Office, 500
West Madison Street, Chicago, Illinois; and New York Regional Office, 7 World
Trade Center, New York, New York and (2) accessed via a Web site maintained by
the SEC (http://www.sec.gov). Copies of the material can also be obtained from
the Public Reference Section of the SEC at 450 Fifth Street, N.W., Judiciary
Plaza, Washington, D.C. 20549 at prescribed rates. Please call the SEC at
1-800-SEC-0330 for further information on the public reference rooms.

        This prospectus is a part of a registration statement we filed with the
SEC. This prospectus does not contain all of the information set forth in the
registration statement. For more information about us and our common stock, you
should read the registration statement and its exhibits and schedules. Copies of
the registration statement, including its exhibits may be obtained from the
SEC's principal office in Washington, D.C. upon payment of the fees prescribed
by the SEC, or may be examined without charge at the offices of the SEC.

        The SEC allows us to "incorporate by reference" the information we file
with them, which means that we can disclose important information to you by
referring you to those documents. The information incorporated by reference is
considered to be part of this prospectus, and later information that we file
with the SEC will automatically update and supersede this information. We
incorporate by reference the documents listed below and any future filings made
by us with the SEC under Sections 13(a), 13(c), 14 or 15(d) of the Securities
Exchange Act of 1934 (File No. 0-18006):


                                      -10-

<PAGE>

        (a)    Our Annual Report on Form 10-K for the year ended December 31,
1998;

        (b)    Our Quarterly Report on Form 10-Q for the quarters ended March
31, 1999, June 30, 1999 and September 30, 1999;

        (c)    Our Current Report on Form 8-K dated May 17, 1999;

        (d)    Our Current Report on Form 8-K dated May 14, 1999;

        (e)    The description of our common stock set forth in the registration
statement on Form 8-A filed on March 30, 1990; and

        (f)    The description of the Preferred Stock Purchase rights for
Series E Participating Preferred Stock, par value $0.001, set forth in the
registration statement on Form 8-A filed on March 4, 1992.

        Upon written or oral request, we will provide without charge to each
person to whom a copy of this prospectus is delivered a copy of the documents
incorporated by reference into this prospectus (other than exhibits to these
documents unless the exhibits are specifically incorporated by reference into
those documents). Requests should be submitted in writing or by telephone at
(760) 431-7080 to The Immune Response Corporation, at our principal executive
offices, 5935 Darwin Court, Carlsbad, California 92008.

                                 USE OF PROCEEDS

        We will not receive any proceeds from the sale of common stock by the
selling stockholders in the offering.

              ISSUANCE OF COMMON STOCK TO THE SELLING STOCKHOLDERS

        We entered into an Assignment Agreement dated as of December 8, 1999
with one of the selling stockholders to purchase the rights to its TCR
Technology in exchange for money and shares of our common stock. We also entered
into an Agreement dated as of December 8, 1999 with the other selling
stockholder to purchase the rights to is TCR Technology in exchange for money
and shares of our common stock. Pursuant to both agreements, we issued 250,000
shares to the selling stockholders on December 8, 1999 and are obligated to
issue to them up to an additional 350,000 shares by June 30, 2000.

                            INCOME TAX CONSIDERATIONS

        You should consult your own tax advisor about the income tax issues and
the consequences of holding and disposing of our common stock.


                                      -11-

<PAGE>

                              SELLING STOCKHOLDERS

        As of January 7, 2000 there were two selling stockholders, as set forth
below. Share ownership information is based solely upon information furnished to
us by the selling stockholders:

<TABLE>
<CAPTION>
                                                                                                     Percentage of
                                                                                                   Common Stock to be
                                                      Shares of Common         Number of              Held After
                                                   Stock Issuable Held at    Shares Being              Sale of
          Selling Stockholders                        January  7, 2000         Offered(1)            Common Stock
- ------------------------------------------         ----------------          -----------------     ------------------
<S>                                                <C>                       <C>                   <C>
Connetics Corporation.....................         129,402                   129,402                        0
XOMA (US) LLC ............................         120,598                   120,598                        0
</TABLE>

- ----------

(1)     Does not include up to an additional 350,00 shares of common stock which
        we are obligated to issue to the selling stockholders, pursuant to the
        agreements dated as of December 8, 1999 between us and the selling
        stockholders.


        There has been no material relationship between the selling stockholders
and us in the past three years except obligations which arose out of the
agreements dated as of December 8, 1999 by and among us and the selling
stockholders.

                              PLAN OF DISTRIBUTION

        The selling stockholders (or, subject to applicable law, its pledges,
donees, distributees, transferees or other successors in interest) may sell
shares from time to time in public transactions, on or off the Nasdaq National
Market, or private transactions, at prevailing market prices or at privately
negotiated prices, including but not limited to, one or any combination of the
following types of transactions:

        -      ordinary brokers' transactions;

        -      transactions involving cross or block trades or otherwise on the
               Nasdaq National Market;

        -      purchases by brokers, dealers or underwriters as principal and
               resale by those purchasers for their own accounts pursuant to
               this prospectus;

        -      "at the market," to or through market makers, or into an existing
               market for our common stock;

        -      in other ways not involving market makers or established trading
               markets, including the direct sales to purchasers or sales
               effected through agents;

        -      through transactions in options, swaps or other derivatives
               (whether exchange-listed or otherwise); or


                                      -12-

<PAGE>

        -      in privately negotiated transactions.

        In effecting sales, brokers or dealers engaged by the selling
stockholders may arrange for other brokers or dealers to participate in the
resales. The selling stockholders also may pledge the shares to a financial
institution, broker or dealer. Upon a default, the financial institution, broker
or dealer may effect sales of the pledged shares pursuant to this prospectus.

        Brokers, dealers or agents may receive compensation in the form of
commissions, discounts or concessions from selling the stockholders in amounts
to be negotiated in connection with the sale. The selling stockholders and any
participating brokers or dealers may be deemed to be "underwriters" within the
meaning of the Securities Act in connection with such sales. In such event, any
commission, discount or concession these "underwriters" receive may be deemed to
be underwriting compensation.

                                  LEGAL MATTERS

        The validity of the issuance of the shares offered in this prospectus
was passed upon for us by Pillsbury Madison & Sutro LLP, San Francisco,
California. A partner of Pillsbury Madison & Sutro LLP owns 15,000 shares of our
common stock and an option to acquire 20,000 shares of our common stock.

                                     EXPERTS

        The consolidated financial statements of The Immune Response
Corporation as of December 31, 1997 and 1998 and for each of the three years in
the period ended December 31, 1998 included in the Company's Annual Report on
Form 10-K and incorporated herein by reference have been audited by Arthur
Andersen LLP, independent public accountants, as indicated in their reports with
respect thereto, and are incorporated herein by reference in reliance upon the
authority of said firm as experts in giving said reports.


                                      -13-

<PAGE>

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        We have not authorized any dealer, salesperson or any other person to
give any information or to represent anything not contained in this prospectus.
You must not rely on any unauthorized information. This prospectus does not
offer to sell or seek an offer to buy any shares in any jurisdiction where it is
unlawful. The information contained in this prospectus is correct only as of the
date of this prospectus, regardless of the time of the delivery of this
prospectus or any sale of the shares.

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

                                TABLE OF CONTENTS

<TABLE>
<CAPTION>
                                                                                                               PAGE

<S>                                                                                                            <C>
PROSPECTUS SUPPLEMENT
     Plan of Distribution.......................................................................................S-1
     Use of Proceeds............................................................................................S-1
     Where You Can Find More Information........................................................................S-1
     Market for Our Common Stock................................................................................S-2
     General....................................................................................................S-2

PROSPECTUS
     Prospectus Summary...........................................................................................1
     Risk Factors.................................................................................................2
     Additional or Updated Risk Factors..........................................................................10
     Special Note Regarding Forward-Looking Information..........................................................10
     Where You Can Find More Information.........................................................................10
     Use of Proceeds.............................................................................................11
     Income Tax Considerations...................................................................................11
     Selling Stockholders........................................................................................12
     Plan of Distribution........................................................................................12
     Legal Matters...............................................................................................13
     Experts.....................................................................................................13
</TABLE>



                                 600,000 Shares
                                  Common Stock






                                   THE IMMUNE
                              RESPONSE CORPORATION

                          ----------------------------
                                   PROSPECTUS

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




                                January 7, 2000



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                                      -14-




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