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United States securities and exchange commission logo
October 22, 2021
Eric Easom
Chief Executive Officer
AN2 Therapeutics, Inc.
1800 El Camino Real, Suite D
Menlo Park, CA 94027
Re: AN2 Therapeutics,
Inc.
Draft Registration
Statement on Form S-1
Submitted September
24, 2021
CIK No. 0001880438
Dear Mr. Easom:
We have reviewed your draft registration statement and have the
following comments. In
some of our comments, we may ask you to provide us with information so
we may better
understand your disclosure.
Please respond to this letter by providing the requested
information and either submitting
an amended draft registration statement or publicly filing your
registration statement on
EDGAR. If you do not believe our comments apply to your facts and
circumstances or do not
believe an amendment is appropriate, please tell us why in your
response.
After reviewing the information you provide in response to these
comments and your
amended draft registration statement or filed registration statement, we
may have additional
comments.
Draft Registration Statement on Form S-1 Submitted September 24, 2021
Prospectus Summary
Overview, page 1
1. Please revise the
disclosure in your Summary to make clear that your clinical development
of epetraborole is
limited to the ongoing Phase 1b trial being conducted in healthy
volunteers in
Australia. Address in your revisions that you anticipate enrolling 56
volunteers, as
referenced on page 108, and include the number of volunteers enrolled to
date. Please also
expand your discussion to substantiate your statement that you believe
your planned Phase 2/3
trial will be sufficient to proceed to a marketing application for
epetraborole. In this
regard, we note your disclosure on page 17 that differences with prior
clinical trials,
including differences in patient populations, targeted indication, formulation
Eric Easom
FirstName LastNameEric
AN2 Therapeutics, Inc. Easom
Comapany
October 22,NameAN2
2021 Therapeutics, Inc.
October
Page 2 22, 2021 Page 2
FirstName LastName
and trial design will limit the use of prior clinical data for
epetraborole. Please also
balance your disclosure with discussion of the following:
Earlier clinical trials were not conducted in patients with
non-tuberculous
mycobacterial (NTM) lung disease, as referenced on page 17; and
That clinical resistance was observed in a Phase 2 clinical
trial and three other
clinical trials were terminated as a result of these
observations, as disclosed on pages
102-103.
Given the current stage of development, please revise your statement
concerning the
potential for epetraborole to become the backbone of a multi-drug
treatment regimen for
patients suffering from NTM lung disease as such statements are
premature and
speculative.
2. We note you cite a "substantial pharmacokinetic and safety data
package [that is] expected
to reduce risk in the development program" as a reason why
epetraborole is an attractive
opportunity. Please revise to remove any implication that you will
successfully mitigate
clinical development risk.
3. On page 3, when describing epetraborole, you discuss results from a
"previous Phase 1
clinical trial." Please clarify whether this clinical trial was
conducted by a third party or
whether you are referring to your ongoing Phase 1b trial.
Our Pipeline, page 1
4. Please revise your presentation to shorten the arrow corresponding to
your Phase 1 trial
for the treatment of treatment-refractory MAC to make clear the
current status. In this
regard we note that enrollment is ongoing. As written, your
presentation implies that you
are half way to completion. Your presentation should not imply that
earlier trials were
conducted in your target indications.
5. It appears your development of epetraborole for the treatment of
meliodidosis and
tuberculosis is limited to preclinical research discussed on pages
110-111 and that you
have not secured funding for these programs. Please provide us with
your analysis
supporting the materiality of these programs to your business such
that inclusion in your
pipeline table is appropriate. Alternatively, please remove these
programs from the table.
Our Solution, page 3
6. We note your statement that in previous clinical trials epetraborole
was generally safe
and well-tolerated. Please revise these and any similar statements
throughout your
registration statement that imply your product candidate is safe or
effective as such
determinations are made solely by the FDA or comparable regulatory
bodies. As a non-
exhaustive list of examples only, we note the following disclosures:
Epetraborole has demonstrated broad antimycobacterial activity
against MAC ; and
Eric Easom
FirstName LastNameEric
AN2 Therapeutics, Inc. Easom
Comapany
October 22,NameAN2
2021 Therapeutics, Inc.
October
Page 3 22, 2021 Page 3
FirstName LastName
Based on the potent in vivo efficacy seen in preclinical mouse
models .
7. We note your disclosure that you intend to conduct trials and pursue
marketing
authorizations with epetraborole in additional geographies outside of
the United States and
Europe, with an initial focus in Japan. Please discuss regulatory
approval requirements in
Europe and Japan under an appropriate heading in the Business section.
Risks Associated with our Business, page 5
8. Please add a bullet point highlighting the risks associated with your
licensing
arrangements, including that you are dependent on your license
agreement with
Anacor and that a breach by Brii Biosciences of your out-license
agreement could result in
a breach under your in-license agreement with Anacor, as referenced on
page 39.
Implications of Being an Emerging Growth Company, page 6
9. Please supplementally provide us with copies of all written
communications, as defined in
Rule 405 under the Securities Act, that you, or anyone authorized to
do so on your behalf,
present to potential investors in reliance on Section 5(d) of the
Securities Act, whether or
not they retain copies of the communications.
Risk Factors , page 12
10. Please revise this section to relocate any generic risk factors you
present to the end of the
section under the caption "General Risk Factors." Refer to Item 105(a)
of Regulation S-K.
Risks Related to Regulatory Approval of Epetraborole..., page 49
11. Please revise your discussion of the FDA s limited-population
antibacterial drug (LPAD)
pathway to remove any implication that the FDA s approval of Insmed
s Arikayce under
this pathway makes it more likely that you will secure marketing
approval for
epetraborole. Please also revise to disclose the labeling requirements
applicable under this
pathway.
Risks Related to this Offering...
Our amended and restated certificate of incorporation will provide that the
Court of Chancery...,
page 61
12. We note your disclosure on page 160 that your choice of forum
provision would not apply
to claims brought to enforce any duty or liability created by the
Securities Exchange Act.
Please revise your risk factor disclosure to so state and ensure that
the exclusive forum
provision in your governing documents states this clearly. Please also
disclose that your
forum selection provisions may increase costs for an investors to
bring a claim. Please
also revise your disclosure concerning your federal forum selection
provision to disclose
that there is uncertainty as to whether a court would enforce such
provision. In this regard,
we note that Section 22 of the Securities Act creates concurrent
jurisdiction for federal
Eric Easom
FirstName LastNameEric
AN2 Therapeutics, Inc. Easom
Comapany
October 22,NameAN2
2021 Therapeutics, Inc.
October
Page 4 22, 2021 Page 4
FirstName LastName
and state courts over all suits brought to enforce any duty or
liability created by the
Securities Act or the rules and regulations thereunder.
Management's Discussion and Analysis
Stock-Based Compensation
Common Stock Valuations, page 83
13. Please disclose the specific methodology used to determine your
enterprise value and the
nature of any significant assumptions used.
Business
Prior Clinical Experience with Epetraborole, page 102
14. We note that your disclosure that previous epetraborole studies were
discontinued in 2010
due to "clinical resistance." Please explain the term "clinical
resistance" and provide
specific examples.
15. We note your statement on page 104 that in the SAD/MAD Phase 1 study,
there were no
deaths, serious adverse events (SAEs) or any adverse events leading to
withdrawal from
the study. Throughout this section, ensure that you disclose all SAEs
and the number of
patients who experienced them for all SAEs that were determined to be
treatment related
or that the investigator could not determine were not treatment
related.
Our Global Health Initiatives, page 110
16. Please expand your disclosure to discuss the preclinical mouse model
and in vitro studies
referenced in this section, including when they were conducted. Please
revise statements
that present your conclusions regarding efficacy, such as
"Epetraborole has demonstrated
effectiveness [in] in vitro and in vivo mouse models of melioidosis."
You may present
results from your study but may not conclude that the data establishes
efficacy.
Additionally, given the early stage of development for these
indications, please revise
your disclosure concerning the potential of epetraborole to have a
significant impact on
the global health system as such statements are premature and
speculative.
Adjuvant Global Health Agreement, page 111
17. We note your disclosure that you have obligations under the Adjuvant
Global Health
Agreement to, among others, use reasonably diligent efforts to develop
epetraborole for
melioidosis and tuberculosis and to develop regulatory strategies and
pursue necessary
product registrations and actively seek funding from governmental
grants and other
granting sources. You state that if you do not maintain compliance
with these and other
program-related investment commitments, Adjuvant may be entitled to
repayment of any
portion of its investment that is not used for the purposes outlined
in the agreement. Please
revise to clearly explain the terms under which Adjuvant would be
entitled to repayment.
To the extent your activities to date pursuant to your obligations are
limited to preclinical
research referenced on pages 110-111, please revise to so state.
Alternatively, please
Eric Easom
AN2 Therapeutics, Inc.
October 22, 2021
Page 5
describe your activities to date. Additionally, please file the agreement
as an exhibit to
your registration statement. Refer to Item 601(b)(10) of Regulation S-K.
Licensing Agreements
License Agreement with Anacor Pharmaceuticals, Inc., page 112
18. Please revise this section to disclose aggregate potential milestone
payments segregated
by development, regulatory and commercial sales milestones. Where
applicable, disclose
the royalty rate or range not to exceed ten percentage points per tier.
Additionally, please
provide the number of years related to the royalty term and the
anticipated expiry of
exclusivity and the last-to-expire patent licensed under the agreement.
Please also clarify
the financial terms triggered by your out-license agreement with Brii
Biosciences Limited.
License Agreement with Brii Biosciences Limited , page 113
19. Please revise this section to disclose aggregate potential milestone
payments segregated
by development, regulatory and commercial sales milestones. Where
applicable, disclose
the royalty rate or range not to exceed ten percentage points per tier.
Additionally, please
disclose the royalty term, duration of the agreement and termination
provisions.
6. Commitments and Contingencies
Adjuvant Global Health Agreement, page F-16
20. Describe and quantify the covenants you are required to maintain
governing your
contingent obligation to repay Adjuvant for "any portion of its
investment that is not used
for purposes outlined in the Global Health Agreement." Tell us
supplementally why you
believe repayment will not be required.
You may contact Franklin Wyman at 202-551-3660 or Mary Mast at
202-551-3613 if
you have questions regarding comments on the financial statements and related
matters. Please
contact Gary Guttenberg at 202-551-6477 or Christine Westbrook at 202-551-5019
with any
other questions.
Sincerely,
FirstName LastNameEric Easom
Division of
Corporation Finance
Comapany NameAN2 Therapeutics, Inc.
Office of Life
Sciences
October 22, 2021 Page 5
cc: Josh Seidenfeld, Esq.
FirstName LastName