As filed with the Securities and Exchange Commission on November 21, 2001.
Registration No. 333-
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SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

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FORM S-3
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933

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ESSENTIAL THERAPEUTICS, INC.
(formerly known as Microcide Pharmaceuticals, Inc.)
(Exact name of registrant as specified in its charter)

DELAWARE 94-3186021
(State or other jurisdiction of (I.R.S. Employer Identification No.)
incorporation or organization)

1365 Main Street
Waltham, MA 02451
(781) 647-5554
(Address, including zip code, and telephone number, including area code, of
registrant's principal executive offices)

Mark Skaletsky
President and Chief Executive Officer
Essential Therapeutics, Inc.
1365 Main Street
Waltham, MA 02451
(781) 647-5554
(Name, address, including zip code, and telephone number, including area code,
of agent for service)

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with copies to:
Julio E. Vega, Esq.
Bingham Dana LLP
150 Federal Street
Boston, MA 02110
(617) 951-8000

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Approximate date of commencement of proposed sale to the public:
As soon as practicable after this Registration Statement becomes effective.

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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. [_]

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CALCULATION OF REGISTRATION FEE
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Proposed Maximum Proposed Maximum
Title of Each Class of Securities Amount to be Offering Price Aggregate Amount of
to be Registered Registered(1) Per Share(2) Offering Price(2) Registration Fee
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Common Stock, $0.001 par value
per share..................... 24,854,687 $3.15 $78,292,264.05 $19,574

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(1) Pursuant to Rule 416, this Registration Statement covers such indeterminate
number of additional shares of common stock as may become issuable upon
conversion of the Series B convertible redeemable preferred stock of the
Company in accordance with the terms of the preferred stock as a result of
stock splits, stock dividends or similar transactions. In addition, the
number of shares being registered includes such indeterminate number of
additional shares of common stock as may become issuable upon conversion of
the preferred stock as a result of the conversion price adjustments
provided in the terms of the preferred stock.
(2) Estimated solely for the purpose of calculating the amount of the
registration fee, based on the average of the high and low prices for the
Company's common stock as reported on the Nasdaq National Market on
November 15, 2001 in accordance with Rule 457(c) under the Securities Act
of 1933.

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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 WHICH 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 SECTION 8(a), MAY
DETERMINE.

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The information contained in this prospectus is not complete and may be
changed. We may not sell these securities until the registration statement
filed with the Securities and Exchange Commission is effective. This prospectus
is not an offer to sell securities, and we are not soliciting offers to buy
these securities in any state where the offer or sale is not permitted.

SUBJECT TO COMPLETION, DATED NOVEMBER 21, 2001

PROSPECTUS

24,854,687 Shares

Essential Therapeutics, Inc.

Common Stock

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Selling stockholders identified in this prospectus may sell up to 24,854,687
shares of common stock of Essential Therapeutics, Inc. Essential will not
receive any of the proceeds from the sale of shares by the selling
stockholders. Essential's common stock is listed on the Nasdaq National Market
under the symbol "ETRX". When used in this prospectus, the term "selling
stockholder" includes donees, transferees, pledgees and other successors in
interest.

On November 19, 2001 the last sale price of the common stock, as reported on
the Nasdaq National Market, was $3.74 per share.

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Investing in the common stock of Essential involves a high degree of risk.
See "Risk Factors," beginning on page 3.

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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.

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The selling stockholders may sell the shares of common stock described in
this prospectus in public or private transactions, including underwritten
transactions, on or off the National Market System of the Nasdaq Stock Market,
at prevailing market prices, or at privately negotiated prices. The selling
stockholders may sell shares directly to purchasers or through brokers or
dealers or an underwritten offering. Brokers, dealers or underwriters may
receive compensation in the form of discounts, concessions or commissions from
the selling stockholders. More information is provided in the section titled
"Plan of Distribution."

The date of this Prospectus is , 2001.

ESSENTIAL THERAPEUTICS

Company Overview

Essential Therapeutics, Inc. (formerly known as Microcide Pharmaceuticals,
Inc.) is a biopharmaceutical company committed to the discovery, development
and commercialization of new classes of pharmaceutical products. Essential has
discovery programs for inhibitors of bacterial cell wall biosynthesis (both
cephalosporins and novel agents) and for inhibitors of efflux pumps in both
bacteria and fungi. Essential's target validation and drug discovery programs
comprise a broad-based program, including Essential's proprietary VALID
Microbial Genomics technologies and its target validation system, known as
ACTT. Essential's structure-based drug design, or SBDD, and related
technologies guide the optimization of drug candidates prior to entry into more
advanced pre-clinical testing and preparation for clinical testing.

On October 24, 2001, Essential acquired The Althexis Company, Inc. and
simultaneously with that acquisition closed an equity financing that raised an
aggregate of $60.0 million through a private placement of Series B convertible
redeemable preferred stock to a group of venture capital investors. This recent
acquisition is expected to increase opportunities for clinical candidate
development through our structure-based drug design.

Our objective is to focus on the discovery and development of pharmaceutical
products through VALID Microbial Genomics technologies, our discovery platform,
and ACTT, our proprietary target validation system. We believe that these
combined platforms will accelerate target validation efforts and new compound
discovery.

Our recent preferred stock financing has provided us with resources to
pursue these research and development goals. We believe that we can maximize
the value of our drug discoveries by advancing them into later stages of
development, including clinical development. We plan to acquire additional
resources necessary to move product candidates from discovery stage through
clinical development to regulatory approval. We may collaborate with other
companies to commercialize our future products or market future products
directly. We are also considering in-licensing later stage development
compounds that reflect our development focus.

INFORMATION WE ARE INCORPORATING BY REFERENCE

We incorporate by reference the following documents and any future filings
we will make with the SEC under Section 13(a), 13(c), 14 or 15(d) of the
Securities Exchange Act of 1934 prior to the termination of the offering
described under "Plan of Distribution":

. Our Annual Report on Form 10-K for our fiscal year ended December 31,
2000, filed on March 1, 2001 and Amendment No. 1 on Form 10-K/A for our
fiscal year ended December 31, 2000, filed on March 21, 2001;

. Our Current Reports on Form 8-K, filed with the SEC on March 23, 2001,
August 6, 2001 and November 8, 2001;

. Our Quarterly Reports on Form 10-Q for our fiscal quarters ended March 31,
2001, June 30, 2001 and September 30, 2001, filed on May 15, 2001, August
14, 2001 and November 14, 2001, respectively; and

. The description of our common stock contained in our Registration
Statement filed with the SEC under Section 12(g) of the Securities
Exchange Act including any amendment or report filed for the purpose of
updating such description.

You may request a copy of these filings at no cost, by writing, telephoning
or emailing us at the following address:

ESSENTIAL THERAPEUTICS, INC.
850 Maude Avenue
Mountain View, CA 94043
(650) 428-1550
Attn.: Investor Relations

This prospectus is part of a registration statement we filed with the SEC.
You should rely only on the information incorporated by reference or provided
in this prospectus. No one else is authorized to provide you with different
information. No offer of these securities is being made in any state where the
offer is not permitted. You should not assume that the information in this
prospectus is accurate as of any date other than the date on the front of this
document.

RISK FACTORS

Any investment in our shares of common stock involves a high degree of risk.
You should carefully consider the risks listed below, which we believe state
the material risks to our business, together with the information contained
elsewhere in the prospectus, before you make a decision to purchase shares of
our common stock.

If our research and development efforts do not result in potential drug
candidates and/or we cannot advance potential products through clinical trials,
we may fail to develop pharmaceutical products.

Our first potential pharmaceutical product, a compound in the cephalosporin
class of antibacterials, commenced Phase I Clinical Trials under the direction
of our partner, The R.W. Johnson Pharmaceutical Research Institute (RWJPRI), an
affiliate of Johnson & Johnson, in November 1999. The cephalosporin class of
antibacterial drugs is the largest class of antibiotics in terms of global
sales. The purpose of these Phase I studies is to assess the compound's safety,
tolerability and pharmacokinetics. Safety and tolerability are measures of the
body's ability to assimilate a compound at various dose levels without adverse
reactions or side effects. Pharmacokinetics is an analysis of the absorption,
distribution, metabolism and excretion of the compound in the body. Based upon
the observation of irritation at the injection site in some subjects in these
trials, we announced in May 2001 that RWJPRI had decided to focus current
efforts on the advancement of RWJ-442831, an Essential Therapeutics-developed
prodrug form of the collaboration's lead parenteral cephalosporin product
(RWJ-54428), into pre-clinical toxicology studies which, if successful, would
allow the compound to advance into Phase I clinical trials. A prodrug is a
modified form of a drug that is readily converted to the active drug in the
body. Preliminary studies of RWJ-442831 in animals, conducted by Essential,
demonstrated reduced venous irritation at the injection site compared to
RWJ-54428. The Phase I clinical trials for such cephalosporin compound may not
be completed. There are two other Essential cephalosporin compounds in the
Johnson & Johnson collaboration: another parenteral compound which is in
pre-clinical development and a cephalosporin intended for oral administration,
in the research stage. Our other potential products are in the pre-clinical or
research stage. Our potential products will require significant additional
research and development efforts before we can sell them. These efforts include
extensive pre-clinical and clinical testing prior to submission to the Food and
Drug Administration (FDA) or other regulatory authority. Pre-clinical and
clinical testing will likely take several years. After submission, these
potential products will be subject to lengthy regulatory review. We cannot
predict with accuracy the time required to commercialize new pharmaceutical
products.

The development of new pharmaceutical products is highly uncertain and
subject to a number of significant risks. We do not expect any of our potential
products to be commercially available for a number of years, if at all.
Pharmaceuticals that appear to be promising at early stages of development may
not reach the market for a number of reasons including the following:

. we or our collaborators may not successfully complete our research and
development efforts;

. any pharmaceuticals we or our collaborators develop may be found to be
ineffective or to cause harmful side effects during pre-clinical testing
or clinical trials;

. we may fail to obtain required regulatory approvals for any products we
develop;

. we may be unable to manufacture enough of any potential products at an
acceptable cost and with appropriate quality;

. our products may not be competitive with other existing or future
products; and

. proprietary rights of third parties may prevent us from commercializing
our products.

If we are unable to maintain our current corporate collaborations or enter into
new collaborations, development of our potential products could be delayed.

Our strategy for enhancing our research and development capability and
funding, in part, our capital requirements involves entering into collaboration
agreements with major pharmaceutical companies. We have

entered into such collaboration agreements with Johnson & Johnson, Daiichi
Pharmaceutical Co., Ltd., Pfizer Inc.'s animal health group, PLIVA and
Schering-Plough Animal Health Corporation. Under these agreements, our
collaborative partners are responsible for:

. selecting which compounds discovered in the collaboration will proceed
into subsequent development, if any;

. conducting pre-clinical testing, clinical trials and obtaining required
approvals for such potential products; and

. manufacturing and commercializing any such approved products.

We cannot control the timing of such actions or the amount of resources
devoted to these activities by our partners. In addition, these agreements are
subject to cancellation or the election not to extend by our partners. As a
result, our receipt of revenue, whether in the form of continued research
funding, product development milestones, or royalties on sales, depends upon
the decisions made and the actions taken by our partners. Our collaborative
partners may view compounds that we may discover as competitive with their own
products or potential products, and therefore any partner may elect not to
proceed with the development of our potential product. Our partners are free to
pursue their own existing or alternative technologies to develop products in
preference to our potential products. We cannot be certain that our interests
will continue to coincide with those of our partners, or that disagreements
concerning our rights, technology, or other proprietary interests will not
arise with our partners.

Substantially all of our revenues to date have resulted from our
collaborations. We intend to continue to rely on our collaborations to fund a
substantial portion of our research and development activities over the next
several years. If our existing partners do not extend our collaborations or if
we are unable to enter into new collaborations, the development and
commercialization of our potential products may be delayed. In addition, we may
be forced to seek alternative sources of financing for such product development
and commercialization activities.

We have incurred substantial losses in the past, expect to continue to incur
losses for the next several years and may never achieve profitability.

We have incurred substantial net losses in every year since our inception in
December 1992. We had net losses of $4.6 million in 1997, $9.8 million in 1998,
$10.7 million in 1999, and $13.9 million in 2000. We had an accumulated deficit
of $61.5 million through September 30, 2001. We expect to continue to incur
operating losses over the next several years.

Substantially all of our revenues to date have resulted from license fees,
research support and milestone payments under our collaborative agreements. We
will not receive revenues or royalties from drug sales until we or our
collaborative partners successfully complete clinical trials with regard to a
drug candidate, obtain regulatory approval for this drug candidate, and
successfully commercialize the drug. We do not expect to receive revenues or
royalties from sales of drugs for a number of years, if at all. If we fail to
achieve sufficient revenues to become profitable or sustain profitability, we
may be unable to continue operations.

Our approach to drug discovery is unproven and we may not succeed in
identifying any drug candidates with clinical benefits.

We are developing a gene function-based technology platform and other
proprietary technology to attempt to identify and commercialize novel
antibiotics, antifungals and antiviral agents. To date these technologies have
identified a small number of compounds that have demonstrated potential
clinical benefits. We cannot be certain that these or any other technology we
may develop will allow us to identify drug candidates that may have clinical
benefits. The failure to identify and develop new drug candidates will have a
material adverse effect on our business.

If we fail to satisfy safety and efficacy requirements or meet regulatory
requirements in our clinical trials, we will not be able to commercialize our
drug candidates.

Either we or our collaborators must show through pre-clinical studies and
clinical trials that each of our pharmaceutical products is safe and effective
in humans for each indication before obtaining regulatory clearance from the
FDA for the commercial sale of that pharmaceutical. If we fail to adequately
show the safety and effectiveness of a pharmaceutical, regulatory approval
could be delayed or denied. The results from pre-clinical studies and early
clinical trials are often different than the results that are obtained in
large-scale testing. We cannot be certain that we will show sufficient safety
and effectiveness in our clinical trials that would allow us to obtain the
needed regulatory approval. A number of companies in the pharmaceutical
industry, including biotechnology companies, have suffered significant setbacks
in advanced clinical trials, even after promising results in earlier trials.

Any drug is likely to produce some level of toxicity or undesirable side
effects in animals and in humans when administered at sufficiently high doses
and/or for a long period of time. Unacceptable toxicities or side effects may
occur in the course of toxicity studies or clinical trials. We have observed
local irritation at the injection site in some subjects receiving RWJ-54428,
one of our potential cephalosporin products, in Phase I clinical trials
conducted by our collaborator, RWJPRI. In addressing this problem, we announced
in May 2001 that RWJPRI had decided to focus current efforts on the advancement
of RWJ-442831, an Essential Therapeutics-developed prodrug form of the
cephalosporin compound RWJ-54428, into pre-clinical toxicology studies which,
if successful, would allow the compound to advance into Phase I clinical
trials. Preliminary studies of RWJ-442831 in animals, conducted by Essential,
demonstrated reduced venous irritation at the injection site as compared to
RWJ-54428. If we observe further unacceptable toxicities or other side effects,
we, our collaborators or regulatory authorities may interrupt, limit, delay or
halt the development of the drug. In addition, unacceptable toxicities or side
effects could prevent approval by the FDA or foreign regulatory authorities for
any or all indications.

We must obtain regulatory approval before marketing or selling our future
drug products. In the United States, we must obtain FDA approval for each drug
that we intend to commercialize. The FDA approval process is lengthy and
expensive, and approval is never certain. Products distributed abroad are also
subject to foreign government regulation. The process of obtaining FDA and
other required regulatory approvals can vary a great deal based upon the type,
complexity and novelty of the products involved. Delays or rejections may be
encountered based upon additional government regulation from future legislation
or administrative action or changes in FDA policy during the period of clinical
trials and FDA regulatory review. Similar delays also may be encountered in
foreign countries.

None of our drug candidates have received regulatory approval. If we fail to
obtain this approval, we will be unable to manufacture and sell our drug
products commercially. Even if we obtain regulatory approval, we may be
required to continue clinical studies even after we have started selling a
pharmaceutical. In addition, identification of certain side effects after a
drug is on the market or the occurrence of manufacturing problems could cause
subsequent withdrawal of approval, reformulation of the drug, additional
pre-clinical testing or clinical trials and changes in labeling of the product.
This could delay or prevent us from generating revenues from the sale of that
drug or cause our revenues to decline.

If we obtain regulatory approval, we will also be subject to ongoing
existing and future FDA regulations and guidelines and continued regulatory
review. In particular, we, our collaborators, or any third party that we use to
manufacture the drug will be required to adhere to regulations setting forth
current good manufacturing practices. The regulations require that we
manufacture our products and maintain our records in a particular way with
respect to manufacturing, testing and quality control activities. Furthermore,
we, our collaborators, or our third-party manufacturers must pass a
pre-approval inspection of manufacturing facilities by the FDA before obtaining
marketing approval.

Failure to comply with the FDA or other relevant regulatory requirements may
subject us to administrative or legally imposed restrictions. These include:
warning letters, civil penalties, injunctions, product seizure or detention,
product recalls, total or partial suspension of production and FDA refusal to
approve pending New Drug Applications, or NDAs, or supplements to approved NDAs.

If we are unable to protect our intellectual property, we may lose the
competitive advantage inherent in our proprietary technologies.

Our success depends in part on our ability to establish, protect and enforce
our proprietary rights relating to our lead compounds, gene discoveries,
screening technology and certain other proprietary technology. We have filed
approximately 80 patent applications in the United States, in addition to
applications filed in other countries, in order to protect lead compounds, gene
discoveries and screening technology, and more than 20 United States patents
have been issued to date on such applications. We cannot be certain that
patents will be granted with respect to any of our patent applications
currently pending in the United States or in other countries, or with respect
to applications filed in the future. For example, although in 2000 a patent was
granted in the U.S. covering our cephalosporin compounds now in development,
prosecution has not yet begun on more recently filed patent applications
related to prodrugs of our earlier inventions, as well as on our new compounds
having potential for oral administration. Our failure to obtain patents
pursuant to our current or future applications could have a material adverse
effect on our business. Furthermore, we cannot be certain that any patents
issued to us will not be infringed, challenged, invalidated or circumvented by
others, or that the rights granted thereunder will provide competitive
advantages to us. In particular, it is difficult to enforce patents covering
methods of use of screening and other similar technologies. Litigation to
establish the validity of patents, to defend against patent infringement claims
and to assert infringement claims against others can be expensive and
time-consuming, even if the outcome is favorable to us. If the outcome of
patent prosecution or litigation is not favorable to us, our business could be
materially adversely affected.

Our commercial success also depends on our ability to operate without
infringing patents and proprietary rights of third parties. We cannot assure
you that our products will not infringe on the patents or proprietary rights of
others. For example, many companies are active in the field of genomics, and
some have filed patents on essential genes in bacteria. While we are not
currently aware of any patents encumbering our ability to practice the
technologies we have discovered, it is possible that a patent of this nature
may issue in the future. We may be required to obtain licenses to patents or
other proprietary rights of others. Any licenses may not be available on terms
acceptable to us, if at all. The failure to obtain these licenses could delay
or prevent our collaborative partners' activities, including the development,
manufacture or sale of drugs requiring such licenses.

In addition to patent protection, we rely on trade secrets, proprietary
know-how and technological advances which we seek to protect, in part, by
confidentiality agreements with our collaborative partners, employees and
consultants. We cannot assure you that these agreements will not be breached,
that we would have adequate remedies for any such breach, or that our trade
secrets, proprietary know-how and technological advances will not otherwise
become known or be independently discovered by others.

If other companies develop better products than ours or market similar products
sooner, our products may be rendered obsolete or noncompetitive.

We operate in a field in which new developments are occurring at an
increasing pace. Competition from biotechnology and pharmaceutical companies,
joint ventures, academic and other research institutions and others is intense
and is expected to increase. Many of our competitors have substantially greater
financial, technical and personnel resources than we have. Although we believe
that we have identified new and distinct approaches to drug discovery, there
are other companies with drug discovery programs, at least some of the
objectives of which are the same as or similar to ours. For example, there are
other companies that have recently described cephalosporins in early stages of
development that are designed for treatment of resistant Gram-positive

infections in hospitals, the same objective as our lead cephalosporin compound.
Similarly, several other companies are seeking to capitalize on the expanding
body of knowledge of efflux pumps in microorganisms.

Competing technologies may be developed which would render our technologies
obsolete or non-competitive. We are aware of many pharmaceutical and
biotechnology companies that are engaged in efforts to treat each of the
infectious diseases for which we are seeking to develop therapeutic products.
We cannot assure you that our competitors will not develop competing drugs that
are more effective than those developed by us and our collaborative partners or
obtain regulatory approvals of their drugs more rapidly than we and our
collaborative partners, thereby rendering our and our collaborative partners'
drugs obsolete or noncompetitive. Moreover, we cannot assure you that our
competitors will not obtain patent protection or other intellectual property
rights that would limit our and our collaborative partners' ability to use our
technology or commercialize our or their drugs.

Our potential products may not be acceptable in the market or eligible for
third party reimbursement, resulting in a negative impact on our future
financial results.

Any products successfully developed by us or our collaborative partners may
not achieve market acceptance. The antibiotic products that we are attempting
to develop will compete with a number of well-established traditional
antibiotic drugs manufactured and marketed by major pharmaceutical companies.
The degree of market acceptance of any of our products will depend on a number
of factors, including:

. the establishment and demonstration in the medical community of the
clinical efficacy and safety of our products;

. the potential advantage of our products over existing treatment methods;
and

. reimbursement policies of government and third-party payors.

Physicians, patients or the medical community in general may not accept or
use any products that may be developed by us or our collaborative partners. Our
ability to receive revenues and income with respect to drugs, if any, developed
through the use of our technology will depend, in part, upon the extent to
which reimbursement for the cost of these drugs will be available from
third-party payors, such as government health administration authorities,
private health care insurers, health maintenance organizations, pharmacy
benefits management companies and other organizations. Third-party payors are
increasingly challenging the prices charged for pharmaceutical products. If
third-party reimbursement was not available or sufficient to allow profitable
price levels to be maintained for drugs developed by us or our collaborative
partners, it could adversely affect our business.

We have no manufacturing, marketing or sales experience, and if we are unable
to enter into manufacturing agreements or maintain collaborations with
marketing partners or if we are unable to develop our own manufacturing, sales
and marketing capability, we may not be successful in commercializing our
products.

We do not have any experience in the manufacture of commercial quantities of
drugs, and our current facilities and staff are inadequate for the commercial
production or distribution of drugs. We intend to rely on our collaborative
partners for the manufacturing, marketing and sales of any products that result
from these collaborations. The current third-party manufacturer of our
potential cephalosporin product has in the past encountered difficulties with
the manufacture of related compounds in sufficient quantities for clinical
trial purposes. Manufacturers often encounter difficulties in scaling up to
manufacture commercial quantities of pharmaceutical products. We cannot be
certain that our current or any other manufacturer will not encounter similar
delays in the scale-up to manufacture this or any other compound in commercial
quantities in the future.

We will be required to contract with third parties for the manufacture of
our products or to acquire or build production facilities before we can
manufacture any of our products. We cannot assure you that we will be able

to enter into contractual manufacturing arrangements with third parties on
acceptable terms, if at all, or acquire or build such production facilities
ourselves.

To date we have no experience with sales, marketing or distribution. In
order to market any of our products, we will be required to develop marketing
and sales capabilities, either on our own or in conjunction with others. We
cannot be certain that we will be able to develop any of these capabilities.

Health care reform measures or cost control initiatives may negatively impact
pharmaceutical pricing.

The levels of revenue and profitability of pharmaceutical companies may be
affected by continuing governmental efforts to contain or reduce the costs of
health care through various means. For example, in some foreign markets pricing
or profitability of prescription pharmaceuticals is already subject to
governmental control. In the United States, there have been, and we expect that
there will continue to be, a number of federal and state proposals to implement
similar governmental control. Cost control initiatives could decrease the price
that we or our collaborative partners receive for any products which we or they
may develop in the future which would adversely affect our business. Further,
to the extent that these proposals or initiatives have a material adverse
effect on our collaborative partners or potential collaborative partners, our
ability to commercialize our potential products may be materially adversely
affected.

If our products harm people, we may experience product liability claims that
may not be covered by insurance.

We face an inherent business risk of exposure to potential product liability
claims in the event that drugs, if any, developed through the use of our
technology are alleged to have caused adverse effects on patients. This risk
exists for products being tested in human clinical trials, as well as products
that receive regulatory approval for commercial sale. We will, if appropriate,
seek to obtain product liability insurance with respect to drugs developed by
us and our collaborative partners. We may, however, not be able to obtain
insurance. Even if insurance is obtainable, it may not be available at a
reasonable cost or in a sufficient amount to protect us against liability.

If we cannot attract and retain management and scientific staff, we may not be
able to proceed with our drug discovery and development programs.

We are highly dependent on management and scientific staff, including Mark
Skaletsky, our Chairman and Chief Executive Officer, George H. Miller, Ph.D.,
our Executive Vice President--Research and Development, Paul Mellett, our
Senior Vice President and Chief Financial Officer and on our other officers.
Considering the time necessary to recruit replacements, if we lose the services
of any of the named individuals or other senior management and key scientific
staff, we may incur delays in our product development and commercialization
efforts or experience difficulties in raising additional funds. We may also
lose a significant amount of revenues without the senior staff necessary to
adequately maintain existing corporate collaborations or to enter into new
collaborations. We do not carry key-man life insurance on any of our
executives. We believe that our future success will depend, in part, on our
ability to attract and retain highly talented managerial and scientific
personnel and consultants. We face intense competition for such personnel from,
among others, biotechnology and pharmaceutical companies, as well as academic
and other research institutions. We cannot be certain that we will be able to
attract and retain the personnel we require on acceptable terms.

Our operations involve hazardous materials, which could subject us to
significant liability.

As with many biotechnology and pharmaceutical companies, our activities
involve the use of radioactive compounds and hazardous materials. As a
consequence, we are subject to numerous environmental and safety laws and
regulations. Any violation of, and the cost of compliance with, these
regulations could materially adversely affect our operations. We are subject to
periodic inspections for possible violations of any environmental or safety law
or regulation.

Anti-takeover provisions in our charter and bylaws and Delaware law, together
with our stockholder rights plan, could make the acquisition of our company by
another company more difficult.

Some provisions of our Restated Certificate of Incorporation and Bylaws may
have the effect of making it more difficult for a third party to acquire, or
discouraging a third party from attempting to acquire, control of our company.
These provisions could limit the price that investors might be willing to pay
in the future for shares of our common stock. These provisions allow us to
issue preferred stock without a vote or further action by our stockholders,
provide for staggered elections of our Board of Directors and specify
procedures for director nominations by stockholders and submission of other
proposals for consideration at stockholder meetings. None of these provisions
provides for cumulative voting in the election of directors. Some provisions of
Delaware law applicable to us could also delay or make more difficult a merger,
tender offer or proxy contest involving us, including Section 203 of the
Delaware General Corporation Law, or DGCL, which prohibits a Delaware
corporation from engaging in any business combination with any stockholder
owning fifteen percent or more of our outstanding voting stock for a period of
three years from the date such person became a 15% stockholder unless certain
conditions are met.

We adopted a stockholder rights plan, dated as of February 2, 1999, pursuant
to which our Board of Directors declared a dividend of one right for each share
of the common stock outstanding, which right entitles the holder to purchase
for $30.00 a fraction of a share of our Series A preferred stock with economic
terms similar to that of one share of the common stock. In the event that an
acquiror obtains 20% or more of our outstanding common stock, each right, other
than rights owned by the acquiror or its affiliates, will thereafter entitle
the holder thereof to purchase, for the exercise price, a number of shares of
the common stock having a then current market value equal to twice the exercise
price. If, after an acquiring person obtains 20% or more of our outstanding
common stock, we merge into another entity, an acquiring entity merges into our
company, or we sell more than 50% of our assets or earning power, then each
right, other than rights owned by the acquiring person or its affiliates, will
entitle the holder thereof to purchase for the exercise price, a number of
shares of common stock of the person engaging in the transaction having a then
current market value equal to twice the exercise price.

The possible issuance of preferred stock, the procedures required for
director nominations and stockholder proposals and Delaware law could have the
effect of delaying, deferring or preventing a change in control of Essential,
including without limitation, discouraging a proxy contest or making more
difficult the acquisition of a substantial block of our common stock. These
provisions could also limit the price that investors might be willing to pay in
the future for shares of our common stock.

If we cannot obtain substantial additional funding for future operations, we
may not be able to proceed with our drug discovery and development programs.

The development of our potential pharmaceutical products will require
substantially more money than we currently have. We intend to seek to raise
such additional funding from sources including other collaborative partners and
through public or private financings involving the sale of equity or debt
securities. We cannot be certain that any financings will be available when
needed, or if available will be on acceptable terms. Funding from collaborative
partners could limit our ability to control the research, development and
commercialization of potential products, and could limit our revenues and
profits from such products, if any. Collaborative agreements may also require
us to give up rights to products or technologies that we would otherwise seek
to develop or commercialize ourselves. Any additional equity financing will
result in dilution to our current stockholders. If we fail to secure sufficient
additional funding we will have to delay or terminate some or all of our drug
discovery and development programs.

Market conditions and changes in operating results may continue to cause
volatility in the market price of our stock, making future equity financings
more difficult.

The market price of the common stock, like that of the securities of many
other biopharmaceutical companies, has been and is likely to continue to be
highly volatile. The stock market has experienced significant

price and volume fluctuations that are often unrelated to the operating
performance of particular companies. Factors contributing to volatility in the
market price of our common stock include:

. results of pre-clinical studies and clinical trials by us or our
competitors;

. announcements of new collaborations;

. announcements of our technological innovations or new therapeutic products
or that of our competitors;

. developments in our patent or other proprietary rights or that of our
competitors, including litigation;

. governmental regulation; and

. healthcare legislation.

Fluctuations in our operating results and market conditions for
biotechnology stocks in general could have a significant impact on the
volatility of the market price for our common stock and on the future price of
our common stock.

We expect to retain all future earnings and have no intention to pay dividends.

We have never paid any cash dividends on Essential common stock. We
currently intend to retain all future earnings, if any, for use in our business
and do not expect to pay any dividends in the foreseeable future.

We may not realize any of the anticipated benefits from our acquisition of
Althexis.

On October 24, 2001, we concluded our acquisition of Althexis. We
consummated the transaction with the expectation that it will result in mutual
benefits including benefits relating to expanded and complementary product
offerings, increased market opportunity, new technology and the addition of
research and development personnel. Achieving the benefits of the acquisition
will depend in part on the integration of our technology, operations and
personnel in a timely and efficient manner so as to minimize the risk that the
acquisition will result in the loss of market opportunity or key employees or
the diversion of the attention of management. We cannot assure you that,
following the transaction, our businesses will achieve revenues, specific net
income or loss levels, efficiencies or synergies that justify the acquisition
or that the acquisition will result in increased earnings, or reduced losses,
for the combined company in any future period.

We may not be able to effectively and efficiently integrate the operations of
Essential Therapeutics and Althexis.

Integrating the operations and management of Essential and Althexis will be
a complex process, and we cannot assure you that this integration will be
completed rapidly or will achieve all of the anticipated synergies and other
benefits expected from the merger. The integration of the two companies will
require significant management attention, which may temporarily distract
management from its usual focus on the daily operations of the combined
company. Moreover, as a result of the change of Essential's corporate
headquarters from California to Massachusetts and the operation of offices on
both coasts, management will face new challenges not previously encountered.
Management's inability to integrate successfully the operations of Essential
and Althexis, or any significant delay in achieving this integration, could
cause our business to suffer.

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

Some of the statements contained in this prospectus constitute
"forward-looking statements", within the meaning of Section 27A of the
Securities Act and Section 21E of the Exchange Act, that involve substantial
risks and uncertainties. In some cases, you can identify these statements by
forward-looking words such as "may", "will", "should", "expect", "plan",
"anticipate", "believe", "estimate" or "continue" and variations of these words
or comparable words. In addition, any statements which refer to expectations,
projections or other characterizations of future events or circumstances are
forward-looking statements. These forward-looking statements involve known and
unknown risks, uncertainties and situations that may cause our or our
industry's actual results, level of activity, performance or achievements to be
materially different from any future results, levels of activity, performance
or achievements expressed or implied by these statements. The risk factors
contained in this prospectus, as well as any other cautionary language in this
prospectus, provide examples of risks, uncertainties and events that may cause
our actual results to differ from the expectations described or implied in our
forward-looking statements.

Although we believe that the expectations reflected in the forward-looking
statements are reasonable, we cannot guarantee future results, levels of
activity, performance or achievements. You should not place undue reliance on
these forward-looking statements, which apply only as of the date of this
prospectus. Except as required by law, we do not undertake to update or revise
any forward-looking statement, whether as a result of new information, future
events or otherwise.

USE OF PROCEEDS

We will not receive any proceeds from the sale of the shares of common stock
offered pursuant to this registration statement by the selling stockholders.

SELLING STOCKHOLDERS

The shares of common stock being offered by the selling stockholders were
either received by the selling stockholders in connection with our acquisition
of the capital stock of The Althexis Company, Inc. or are issuable upon
conversion of outstanding shares of our Series B convertible redeemable stock.

Approximately 14.2 million shares of common stock are subject to various
lock-up arrangements entered into by some of the selling stockholders and
Essential for the periods set forth below:

. approximately 9.8 million shares are subject to lock-up arrangements for a
period of 270 days after October 24, 2001;

. approximately 2.7 million shares are subject to lock-up arrangements
pursuant to which 40% of such shares may be sold beginning on October 24,
2002 and the remaining shares may be sold on October 24, 2003; and

. approximately 1.7 million shares are subject to lock-up arrangements until
October 24, 2002.

The table below includes information regarding the beneficial ownership of
our common stock by each of the selling stockholders as of the date hereof. The
information provided in the table below assumes that each selling stockholder
will sell all of such stockholder's Essential common stock. Our registration of
the shares of common stock covered by this prospectus does not necessarily mean
that the selling stockholders will sell all or any of the shares. The
information provided in the table below with respect to each selling
stockholder has been obtained from such selling stockholder. Except as
otherwise disclosed below, none of the selling stockholders has, or within the
past three years has had, any position, office or other material relationship
with Essential or any of its predecessors or affiliates. Because the selling
stockholders may sell all or some portion of the shares of common stock
beneficially owned by them, only an estimate, assuming each selling stockholder

sells all of their shares offered hereby, can be given as to the number of
shares of common stock that will be beneficially owned by the selling
stockholders after this offering. In addition, the selling stockholders may
have sold, transferred or otherwise disposed of, or may sell, transfer or
otherwise dispose of, at any time or from time to time since the date on which
they last provided to Essential any information regarding the shares of common
stock beneficially owned by them, all or a portion of the shares of common
stock beneficially owned by them in transactions exempt from the registration
requirements of the Securities Act of 1933. The applicable percentages of
ownership are based on an aggregate of 16,707,339 shares of common stock issued
and outstanding as of October 30, 2001.

Shares Beneficially
Shares Number of Owned After Offering(1)
Beneficially Owned Shares Being ----------------------
Name of Beneficial Owner Prior to Offering(1) Offered Number Percent
- ------------------------ -------------------- ------------ ------- -------

Delta Opportunity Fund (Institutional), LLC.......... 253,333 253,333 0 1.5%
Delta Opportunity Fund, Ltd.......................... 413,333 413,333 0 2.4%
Acorn Investment Partners, L.P....................... 166,666 166,666 0 *
SV (Nominees) Limited as nominee for Schroder
Ventures Investments Limited....................... 180,333 180,333 0 1.1%
SITCO Nominees Limited--VC 01903 as nominee for
Schroder Ventures International Life Sciences Fund
Group Co-Investment Scheme......................... 42,000 42,000 0 *
Schroder Ventures International Life Sciences Fund II
Strategic Partners L.P............................. 22,666 22,666 0 *
Schroder Ventures International Life Sciences
Fund II LP3........................................ 166,333 166,333 0 *
Schroder Ventures International Life Sciences
Fund II LP2........................................ 624,000 624,000 0 3.6%
Schroder Ventures International Life Sciences
Fund II LP1........................................ 1,464,666 1,464,666 0 8.1%
International Biotechnology Trust(2)................. 2,500,000 2,500,000 0 13.0%
Montagu Newhall Global Partners L.P.................. 166,666 166,666 0 *
HFM Charitable Remainder Trust....................... 333,333 333,333 0 2.0%
New Enterprise Associates 10(3)...................... 6,643,333 6,643,333 0 28.5%
NEA Ventures 2001 Limited Partnership................ 23,333 23,333 0 *
Prospect Venture Partners L.P.(4).................... 1,666,666 1,666,666 0 9.1%
Prospect Venture Partners II, L.P.(4)................ 5,000,000 5,000,000 0 23.0%
Manuel Navia......................................... 1,233,900 1,233,900 0 6.9%
Patrick Connelly..................................... 822,600 822,600 0 4.7%
Mass Ventures LLC.................................... 991,690 991,690 0 5.6%
Michael Dailey....................................... 744,910 744,910 0 4.3%
Frank Marcinowski.................................... 36,560 36,560 0 *
Peter Finnican....................................... 205,650 205,650 0 1.2%
Jeffrey Arnstein..................................... 41,130 41,130 0 *
Judy Cannon.......................................... 36,560 36,560 0 *
Mark Skaletsky(5).................................... 503,185 502,685 500 2.9%
Paul Mellett(6)...................................... 155,469 155,469 0 *
John Burns........................................... 3,427 3,427 0 *
Aloka Roy............................................ 2,285 2,285 0 *
James P. Schadt...................................... 58,739 58,739 0 *
Peter M. Finnican.................................... 183,739 58,739 125,000 *
Andrew Offit......................................... 59,054 44,054 15,000 *
William H. Waltrip................................... 29,369 29,369 0 *
Montgomery Fund Ltd. Partnership..................... 29,369 29,369 0 *

Shares Beneficially
Shares Number of Owned After Offering(1)
Beneficially Owned Shares Being -----------------------
Name of Beneficial Owner Prior to Offering(1) Offered Number Percent
- ------------------------ -------------------- ------------ ------ -------

Michael Dailey................. 29,369 29,369 0 *
John Peace..................... 29,369 29,369 0 *
Ralph Parks.................... 29,369 29,369 0 *
1976 Philip Lehner Family Trust 14,684 14,684 0 *
1975 Philip Lehner Family Trust 14,684 14,684 0 *
1976 Peter Lehner Family Trust. 14,684 14,684 0 *
1975 Peter Lehner Family Trust. 14,684 14,684 0 *
Lillian Montgomery............. 7,341 7,341 0 *
Walter S. Montgomery IV........ 7,341 7,341 0 *
William J. Montgomery.......... 7,341 7,341 0 *
John D. Montgomery............. 7,341 7,341 0 *
Patricia Carroll............... 7,341 7,341 0 *
DeVer Warner................... 7,342 7,342 0 *

- --------
* Less than 1% of the outstanding shares of Common Stock.
(1) Beneficial ownership is determined in accordance with Rule 13d-3(d)
promulgated by the Commission under the Securities and Exchange Act of
1934, as amended. Shares of Common Stock issuable pursuant to options,
warrants and convertible securities are treated as outstanding for
computing the percentage of the person holding such securities but are not
treated as outstanding for computing the percentage of any other person.
Unless otherwise noted, each person or group identified possesses sole
voting and investment power with respect to shares, subject to community
property laws where applicable. Shares not outstanding but deemed
beneficially owned by virtue of the right of a person or group to acquire
them within 60 days are treated as outstanding only for purposes of
determining the number of and percent owned by such person or group.
(2) Schroder Ventures Life Sciences (UK) Limited advises Schroder Investment
Management Limited, which is engaged to be the discretionary investment
manager of International Biotechnology Trust. Kate Bingham, a director of
Essential, is a member of the investment committee of Schroder Ventures
Life Sciences (UK) Limited and has the shared ability to direct the voting
of securities held by International Biotechnology Trust. Ms. Bingham
disclaims beneficial ownership of such shares.
(3) NEA Partners 10, Limited Partnership is the sole general partner of New
Enterprise Associates 10. Charles W. Newhall III, a director of Essential,
is a general partner of NEA Partners 10, Limited Partnership and may be
deemed to beneficially own the shares of common stock of Essential held by
New Enterprise Associates 10. Mr. Newhall disclaims beneficial ownership of
such shares.
(4) David Schnell, a director of Essential, is a managing member of Prospect
Venture Partners, L.P. and Prospect Venture Partners II, L.P. and may be
deemed to beneficially own the shares of common stock of Essential held by
Prospect Venture Partners, L.P. and Prospect Venture Partners II, L.P. Mr.
Schnell disclaims beneficial ownership of such shares.
(5) Mark Skaletsky is the Chairman of the Board of Directors, President and
Chief Executive Officer of Essential.
(6) Paul Mellett is the Chief Financial Officer and Treasurer of Essential.

PLAN OF DISTRIBUTION

The shares of common stock may be sold from time to time by the selling
stockholders or their donees, pledgees, transferees and other successors in
interest in one or more transactions at fixed prices, at market prices at the
time of sale, at varying prices determined at the time of sale or at negotiated
prices. When used herein, the term "selling stockholders" refers to all of
their donees, pledgees, transferees and other successors in interest. The
shares of common stock may be sold in one or more of the following transactions:

. on any national securities exchange or quotation service on which the
common stock may be listed or quoted at the time of sale, including the
Nasdaq National Stock Market,

. in the over-the-counter market,

. in private transactions, block sales, short sales or other similar types
of transactions,

. through options,

. in an underwritten offering, or

. a combination of any of the above transactions.

If required, we will distribute a supplement to this prospectus to describe
material changes in the terms of the offering. The supplement will set forth
the aggregate number of shares of common stock being offered and the terms of
such offering, including the name or names of the broker/dealers or agents, any
discounts, commissions and other terms constituting compensation from the
selling stockholders and any discounts, commissions or concessions allowed or
reallowed to be paid to broker/dealers.

The shares of common stock described in this prospectus may be sold from
time to time directly by the selling stockholders. Alternatively, the selling
stockholders may from time to time offer shares of common stock to or through
broker/dealers or agents. The selling stockholders and any broker/dealers or
agents that participate in the distribution of the shares of common stock may
be deemed to be "underwriters" within the meaning of the Securities Act of
1933. Any profits on the resale of shares of common stock and any compensation
received by any broker/dealer or agent may be deemed to be underwriting
discounts and commissions under the Securities Act of 1933.

The selling stockholders, alternatively, may sell all or any part of the
shares offered hereby through an underwriter. No selling stockholder has
entered into any agreement with a prospective underwriter and there is no
assurance that any such agreement will be entered into. If a selling
stockholder enters into such an agreement or agreements, the relevant details
will be set forth in a supplement or revisions to this prospectus.

Any shares covered by this prospectus which qualify for sale pursuant to
Rule 144 under the Securities Act of 1933 may be sold under Rule 144 rather
than pursuant to this prospectus. The selling stockholders may decide not to
sell all of their shares. The selling stockholders may transfer, devise or gift
such shares by other means not described in this prospectus.

To comply with the securities laws of certain jurisdictions, if applicable,
the common stock must be offered or sold only through registered or licensed
brokers or dealers. In addition, in certain jurisdictions, the common stock may
not be offered or sold unless registered or qualified for sale or an exemption
is available and complied with.

Under applicable rules and regulations under the Securities Exchange Act of
1934, any person engaged in a distribution of the common stock offered hereby
may not simultaneously engage in market-making activities with respect to our
common stock for a specified period prior to the start of the distribution. In
addition, each selling stockholder and any other person participating in a
distribution will be subject to the Securities Exchange Act and the rules and
regulations promulgated under the Exchange Act, including Regulation M, which
may limit the timing of purchases and sales of common stock by the selling
stockholders or any such other person. These factors may affect the
marketability of the common stock and the ability of brokers or dealers to
engage in market-making activities.

All expenses of this registration will be paid by Essential. These expenses
include the SEC's filing fees and fees under state securities or "blue sky"
laws. The selling stockholders will pay all underwriting discounts and selling
commissions, if any.

LEGAL MATTERS

Bingham Dana LLP, Boston, Massachusetts has given its opinion that the
shares offered in this prospectus have been duly authorized and upon issuance
will be validly issued, fully paid and non-assessable.

EXPERTS

Ernst & Young LLP, independent auditors, have audited our financial
statements included in our Annual Report on Form 10-K/A for the year ended
December 31, 2000, as set forth in their report, which is incorporated by
reference in this prospectus and elsewhere in the registration statement. Our
financial statements are incorporated by reference in reliance on Ernst & Young
LLP's report, given on their authority as experts in accounting and auditing.

WHERE YOU CAN GET MORE INFORMATION

Essential is subject to the reporting requirements of the Securities
Exchange Act of 1934 and files annual, quarterly and current reports, proxy
statements and other information with the SEC. You may read and copy these
reports, proxy statements and other information at the SEC's public reference
facilities at Judiciary Plaza, 450 Fifth Street, N.W., Washington, D.C. 20549,
and at Northwest Atrium Center, 500 W. Madison Street, Suite 1400, Chicago,
Illinois 60661-2511. You can request copies of these documents by writing to
the SEC and paying a fee for the copying cost. Please call the SEC at
1-800-SEC-0330 for more information about the operation of the public reference
facilities. SEC filings are also available at the SEC's Web site at
http://www.sec.gov. Essential's common stock is listed on the Nasdaq National
Market, and you can read and inspect our filings at the offices of the National
Association of Securities Dealers, Inc. at 1735 K Street, Washington, D.C.
20006.

The SEC allows us to "incorporate by reference" information that we file
with them. Incorporation by reference allows us to disclose important
information to you by referring you to those other documents. The information
incorporated by reference is an important part of this prospectus, and
information that we file later with the SEC will automatically update and
supersede this information. Essential has filed a registration statement on
Form S-3 under the Securities Act of 1933 with the SEC with respect to the
common stock being offered pursuant to this prospectus. This prospectus omits
certain information contained in the Registration Statement on Form S-3, as
permitted by the SEC. Refer to the registration statement on Form S-3,
including the exhibits, for further information about Essential and the common
stock being offered pursuant to this prospectus. Statements in this prospectus
regarding the provisions of certain documents filed with, or incorporated by
reference in, the registration statement are not necessarily complete and each
statement is qualified in all respects by that reference. Copies of all or any
part of the Registration Statement, including the documents incorporated by
reference or the exhibits, may be obtained upon payment of the prescribed rates
at the offices of the SEC listed above.

Upon request, Essential will provide without charge to each person to whom a
copy of this prospectus has been delivered a copy of any information that was
incorporated by reference in the prospectus, other than exhibits to documents,
unless the exhibits are specifically incorporated by reference into the
prospectus. Essential will also provide upon request, without charge to each
person to whom a copy of this prospectus has been delivered, a copy of all
documents filed from time to time by Essential with the SEC pursuant to the
Securities Exchange Act of 1934. Requests for copies should be directed to
Investor Relations, Essential Therapeutics, Inc., 850 Maude Avenue, Mountain
View, CA 94043. Telephone requests may be directed to (650) 428-1550.

================================================================================
We have not authorized any dealer, salesperson or other person to give any
information or to make any representations not contained in this Prospectus or
any Prospectus Supplement. You must not rely on any unauthorized information.
Neither this Prospectus nor any Prospectus Supplement is an offer to sell or a
solicitation of an offer to buy any of these securities in any jurisdiction
where an offer or solicitation is not permitted. No sale made pursuant to this
Prospectus shall, under any circumstances, create any implication that there
has not been any change in the affairs of Essential since the date of this
Prospectus.

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

24,854,687 Shares

Essential Therapeutics, Inc.

Common Stock

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

PROSPECTUS

, 2001

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

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

PART II

INFORMATION NOT REQUIRED IN PROSPECTUS

Item 14. Other Expenses of Issuance and Distribution

Expenses of the Registrant in connection with the issuance and distribution
of the securities being registered are estimated as follows:

Total
----------

SEC Registration Fee........... $ 19,574
Printing and Engraving Expenses 200,000
Legal Fees and Expenses........ 750,000
Accountants' Fees and Expenses. 200,000
Miscellaneous Costs............ 550,000
----------
Total....................... $1,719,574

Item 15. Indemnification of Directors, Officers and Employees

Section 145 of the General Corporation Law of Delaware permits a corporation
to indemnify any person who was or is, or is threatened to be made a party to
any threatened, pending or completed suit or proceeding, whether civil,
criminal, administrative or investigative, by reason of the fact that he or she
is or was a director, officer, employee or agent of the Registrant or is or was
serving at the request of the Registrant as director, officer, employee or
agent of another corporation, partnership, joint venture, trust or other
enterprise, against expenses, judgments, fines and amounts paid in settlement
actually and reasonably incurred by him in connection with such action.

A corporation may indemnify against expenses (including attorney's fees)
and, except for an action by or in the name of the corporation, against
judgements, fines and amounts paid in settlement as part of such suit or
proceeding. This applies only if the person indemnified acted in good faith and
in a manner he or she reasonably believed to be in the best interest of the
corporation. In addition, with respect to any criminal action or proceeding,
the person had no reasonable cause to believe his or her conduct was unlawful.

In the case of an action by or in the name of the corporation, no
indemnification of expenses may be made for any claim, as to which the person
has been found to be liable to the corporation. The exception is if the court
in which such action was brought determines that the person is reasonably
entitled to indemnity for expenses.

Section 145 of the General Corporation Law of Delaware further provides that
if a director, officer, employee or agent of the corporation has been
successful in the defense of any suit, claim or proceeding described above, he
or she will be indemnified for expenses (including attorney's fees) actually
and reasonably incurred by him or her.

Article VII of the Registrant's Restated Certificate of Incorporation, as
amended, provides that to the fullest extent permitted by the General
Corporation Law of Delaware, a director of the Registrant shall not be
personally liable to the Registrant or its stockholders for monetary damages
for breach of fiduciary duty as a director. In addition, Article VII provides
that the Registrant may indemnify to the fullest extent permitted by law any
person made or threatened to be made a party to an action or proceeding,
whether criminal, civil, administrative or investigative, by reason of the fact
that such person or his or her testator or intestate is or was a director,
officer or employee of the Registrant, or any predecessor of the of the
Registrant, or serves or served at any other enterprise as a director, officer
or employee at the request of the Registrant or any predecessor to the
Registrant.

II-1

Article VI of the Registrant's Bylaws provides for the indemnification of
directors, officers, employees and other agents acting on behalf on the
Registrant to the fullest extent permissible under the General Corporation Law
of Delaware. Article VI of the Registrant's Bylaws also permits the Registrant
to secure insurance on behalf of any officer, director, employee or other agent
against any liability asserted against him or her and incurred by him or her in
any such capacity, or arising out of his or her status as such, whether or not
the corporation would have the power to indemnify him or her against such
liability under the provisions of the General Corporation Law of Delaware.

The Registrant has entered, and expects to enter, into indemnification
agreements with its directors.

Item 16. Exhibits

The following is a list of exhibits filed as a part of this registration
statement:

Exhibit
Number Description
- ------ -----------

3.1. Restated Certificate of Incorporation of Essential Therapeutics, Inc. (incorporated by reference to
Exhibit No. 3.3 to the Registrant's Registration Statement on Form S-1 (file No. 333-02400) filed on
May 14, 1996).

3.2. Certificate of Designations to Essential Therapeutics, Inc.'s Certificate of Incorporation filed with the
Secretary of the State of the State of Delaware on October 24, 2001 (incorporated by reference to
Exhibit No. 3.2 to the Registrant's Current Report on Form 8-K filed on November 8, 2001).

3.3. Amendment to the Company's Certificate of Incorporation filed with the Secretary of the State of the
State of Delaware on October 24, 2001 (incorporated by reference to Exhibit No. 3.3 to the Registrant's
Current Report on Form 8-K filed on November 8, 2001).

4.1. Specimen Certificate for shares of the Registrant's common stock.

4.2. Specimen Certificate for shares of the Registrant's Series B preferred stock.

5.1. Opinion of Bingham Dana LLP, counsel to the Registrant, regarding the legality of the shares of
common stock registered hereunder.*

23.1. Consent of Ernst & Young LLP, independent auditors.*

23.2. Consent of Bingham Dana LLP, counsel to the Registrant (included in Exhibit 5.1).*

24.1. Power of Attorney (included on the signature page of this Registration Statement).

- --------
* To be filed by amendment.

Item 17. Undertakings

The undersigned Registrant hereby undertakes:

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

(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.

II-2

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 (and, where applicable, each filing of an employee benefit
plan's annual report pursuant to Section 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
of 1933 may be permitted to directors, officers and controlling persons of the
Registrant pursuant to the foregoing provisions described in Item X above, 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-3

SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, as amended, 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
Registration Statement on Form S-3 to be signed on its behalf by the
undersigned, thereunto duly authorized, in the Town of Waltham, Massachusetts
on this 21st day of November, 2001.

ESSENTIAL THERAPEUTICS, INC.

By: /S/ MARK SKALETSKY
----------------------------------------
Mark Skaletsky
President and Chief Executive Officer

POWER OF ATTORNEY

Each person whose signature appears below hereby appoints Mark Skaletsky and
Paul J. Mellett, and each of them severally, acting alone and without the
other, his/her true and lawful attorney-in-fact with full power of substitution
or resubstitution, for such person and in such person's name, place and stead,
in any and all capacities, to sign on such person's behalf, individually and in
each capacity stated below, any and all amendments, including post-effective
amendments to this Registration Statement, and to sign any and all additional
registration statements relating to the same offering of securities of the
Registration Statement that are filed pursuant to Rule 462(b) of the Securities
Act of 1933, and to file the same, with all exhibits thereto, and other
documents in connection therewith, with the Securities and Exchange Commission,
granting unto said attorneys-in-fact, full power and authority to do and
perform each and every act and thing requisite or necessary to be done in and
about the premises, as fully to all intents and purposes as such person might
or could do in person, hereby ratifying and confirming all that said
attorneys-in-fact, or their substitute or substitutes, may lawfully do or cause
to be done by virtue hereof.

Pursuant to the requirements of the Securities Act of 1933, as amended, this
Registration Statement has been signed by the following persons in the
capacities indicated as of the 21st day of November, 2001.

Signature Title Date
--------- ----- ----

/S/ MARK SKALETSKY Chairman of the Board of Directors, November 21, 2001
---------------------- President, Chief Executive
Mark Skaletsky Officer and a Director (Principal
Executive Officer)

/S/ PAUL J. MELLETT Chief Financial Officer and November 21, 2001
---------------------- Treasurer (Principal Financial
Paul J. Mellett Officer)

/S/ RICHARD ALDRICH Director November 21, 2001
----------------------
Richard Aldrich

/S/ KATE BINGHAM Director November 21, 2001
----------------------
Kate Bingham

---------------------- Director November , 2001
Charles W. Newhall III

/S/ JAMES. E. RURKA Director November 21, 2001
----------------------
James E. Rurka

---------------------- Director November , 2001
David Schnell

/S/ JOHN P. WALKER Director November 21, 2001
----------------------
John P. Walker

II-4

EXHIBIT INDEX

Exhibit
Number Description
- ------ -----------

2.1. Agreement and Plan of Merger, dated July 27, 2001, by and among Essential Therapeutics, Inc. and
The Althexis Company, Inc. (incorporated by reference to Exhibit No. 2.1 to the Registrant's Current
Report on Form 8-K filed on November 8, 2001).
3.1. Restated Certificate of Incorporation of Essential Therapeutics, Inc. (incorporated by reference to
Exhibit No. 3.3 to the Registrant's Registration Statement on Form S-1 (file No. 333-02400) filed on
May 14, 1996).
3.2. Certificate of Designations to Essential Therapeutics, Inc.'s Certificate of Incorporation filed with the
Secretary of the State of the State of Delaware on October 24, 2001 (incorporated by reference to
Exhibit No. 3.2 to the Registrant's Current Report on Form 8-K filed on November 8, 2001).
3.3. Amendment to the Company's Certificate of Incorporation filed with the Secretary of the State of the
State of Delaware on October 24, 2001 (incorporated by reference to Exhibit No. 3.3 to the Registrant's
Current Report on Form 8-K filed on November 8, 2001).
4.1. Specimen Certificate for shares of the Registrant's common stock.
4.2. Specimen Certificate for shares of the Registrant's Series B preferred stock.
5.1. Opinion of Bingham Dana LLP, counsel to the Registrant, regarding the legality of the shares of
common stock registered hereunder.*
23.1. Consent of Ernst & Young LLP, independent auditors.*
23.2. Consent of Bingham Dana LLP, counsel to the Registrant (included in Exhibit 5.1).*
24.1. Power of Attorney (included on the signature page of this Registration Statement).

- --------
* To be filed by amendment.