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August 8, 2019
Christian Schade
Chief Executive Officer
Aprea Therapeutics, Inc.
535 Boylston Street
Boston, MA 02116
Re: Aprea Therapeutics, Inc.
Draft Registration Statement on Form S-1
Submitted July 12, 2019
CIK No. 0001781983
Dear Mr. Schade:
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
Prospectus Summary
Aprea Therapeutics overview, page 1
1. Please delete your reference to "first-in-class" throughout your
registration statement as it
implies the product candidate will be approved by the FDA or foreign
regulatory body.
2. We note your disclosure on page 1 that your Phase 3 clinical trial is
supported by data
from an ongoing "investigator initiated" clinical trial and your
disclosure in your chart on
page 2 that indicates two "investigator initiated" trials. Please
identify the investigators in
these trials here, and expand your disclosure to explain how an
"investigator initiated
clinical trial" differs from a trial sponsored by the company. Also, on
page 4, you state
that you are "supporting" investigator initiated clinical trials. Please
describe the
Christian Schade
FirstName LastNameChristian Schade
Aprea Therapeutics, Inc.
Comapany2019
August 8, NameAprea Therapeutics, Inc.
August 8, 2019 Page 2
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material terms of your agreements with the investigators so that
investors understand the
nature of your support, and file the agreements as exhibits to your
registration statement if
required by Item 601 of Regulation S-K.
3. We note your disclosure on page 1 that you are seeking approval for
APR-246 from the
EMA as well as the FDA. Please revise your chart to indicate which
trials are being
conducted pursuant to an IND with the FDA and which are being
conducted in connection
with seeking approval from the EMA.
4. We not your disclosure on page 2 regarding results from preclinical
studies of APR-246.
As APR-246 is in clinical trials, please limit the prospectus summary
discussion of your
results to a description of the clinical trials. To the extent that
you do discuss preclinical
studies in your prospectus summary, please disclose a summary of the
number and types
of tests conducted as well as quantitative information regarding the
range of results
observed.
Implications of being an emerging growth company, page 6
5. Please 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
Risks related to the discovery, development and commercialization of our
product candidates
If serious adverse or unacceptable side effects are identified, page 16
6. We note your disclosure on page 17 that "[m]uliple patients . . . have
experienced adverse
events." Please clarify whether any of these adverse events are
serious adverse events,
and, if so, the number and percentage of patients that experienced
such serious adverse
events.
Risks related to our intellectual property
Our proprietary position for APR-246 depends upon patents that consist of
method-of-use, page
35
7. We note your disclosure on page 35 that the chemical structure of
APR-246 is in the
public domain and that you do not own or license and will not in the
future own or license
any composition of matter patents claiming the compound of APR-246.
Please revise
your prospectus summary to state that APR-246 is in the public domain
and provide a
summary of the potential effect this could have on your business.
Christian Schade
FirstName LastNameChristian Schade
Aprea Therapeutics, Inc.
Comapany2019
August 8, NameAprea Therapeutics, Inc.
August 8, 2019 Page 3
Page 3
FirstName LastName
We are an "emerging growth company," and the reduced disclosure requirements
applicable to
emerging growth companies..., page 69
8. You disclose that the JOBS Act provides for the option for emerging
growth companies
(EGCs) to delay adopting certain accounting guidance. Please revise
this section, as well
as your disclosure about being an EGC elsewhere in your document
including page 7, to
definitively confirm whether you have elected to avail yourself of
this option. If you have
elected to avail yourself of that delay, revise this risk factor to
discuss the implications.
Risks related to our common stock and this offering
Our certificate of incorporation that will become effective, page 72
9. We note your disclosure here and on page 171 that your certificate of
incorporation will
contain an exclusive forum provision. Please disclose whether this
provision applies to
actions arising under the Securities Act or Exchange Act. If these
provisions do not apply
to actions arising under the Securities Act or the Exchange Act,
please ensure that the
exclusive forum provision in the certificate of incorporation and your
disclosure regarding
the provision in the prospectus state this clearly. If the provision
does apply to actions
arising under the federal securities laws, please disclose that
investors cannot waive
compliance with the federal securities laws and the rules and
regulations thereunder. In
addition, file a copy of your certificate of incorporation with your
next amendment or tell
us when you plan to do so. Note that we may have further comment after
review of this
document and your revised disclosure.
Use of Proceeds, page 75
10. Please disclose the amount of the proceeds you intend to use for each
of the specified
purposes as well as how far in the specified clinical trials, the
research related to APR-246
and the research related to your platform and other programs the
proceeds will allow you
to reach. If you do not believe that the anticipated proceeds will be
sufficient to complete
all of the proposed purposes, please disclose an estimate of the
additional funds needed
and the sources of such funds.
Management's Discussion and Analysis of Financial Condition and Results of
Operations
Stock-based compensation, page 89
11. Once you have an estimated offering price or range, please explain to
us how you
determined the fair value of the common stock underlying your equity
issuances and the
reasons for any differences between the recent valuations of your
common stock leading
up to the initial public offering and the estimated offering price.
This information will help
facilitate our review of your accounting for equity issuances
including stock compensation
and beneficial conversion features.
Christian Schade
FirstName LastNameChristian Schade
Aprea Therapeutics, Inc.
Comapany2019
August 8, NameAprea Therapeutics, Inc.
August 8, 2019 Page 4
Page 4
FirstName LastName
Business
Our approach
Our approach to re-activating p53, page 102
12. Please remove conclusory statements regarding the results of your
preclinical studies here
and throughout the prospectus. Instead, when disclosing observed
results of your
preclinical studies, please disclose the range of results observed,
how the studies and tests
were conducted, including the number of animals tested. For example,
we note your
disclosure on page 103 that states that "[i]n vitro and in vivo
experiments have shown that
[y]our lead p53 re-activating product candidate, APR-246, via MQ,
impairs tumor cells'
capacity to respond to oxidative stress," and your disclosure on page
104 that states that
you have observed preclinical anti-tumor activity with APR-246 in a
wide variety of
hematological and solid tumors models and cell lines, including MDS,
AML, and several
solid tumors including ovarian cancer and esophageal cancer.
Similarly, include detailed
descriptions of clinical trials, including the number of patients
tested, the endpoints of the
trials, whether the results were statistically significant and the
p-valued used to determine
significance. For example, on page 115 you state that, in the CALYPSO
trial, PFS was
reported as 11.3 months and OS as 30.7 months, but you do not describe
how the study
was conducted.
Our lead product candidate, APR-246
AEs reported in > 1 patient during APR-246 monotherapy lead-in phase (n=12),
page 109
13. Please clarify which of the adverse events disclosed on page 109 are
serious adverse
events. Similarly, on page 114 identify all serious adverse events
experienced in your
Phase 1b clinical trial of APR-246 in Platinum Sensitive Ovarian
Cancer.
Clinical development in solid tumors, page 114
14. We note your disclosure that your Phase 1b trial did not indicate
"significant safety
concerns" of combining APR-246 with carboplatin and PLD. Statements
regarding safety
are a determination that only the FDA and foreign government
equivalent regulators have
the authority to make. Please revise your disclosure to eliminate any
suggestions that your
product candidates have been or will ultimately be determined safe.
Similarly, please
revise your disclosure that your "lead product candidate, APR-246,
reactivates p53 for the
treatment of various cancers" as your product has not yet been
approved by the FDA or a
foreign government equivalent regulator, and this statement suggests
that it will be
approved.
Clinical developments in solid tumors
Phase 1b/2 Clinical Trial of APR-246 in Platinum-Sensitive Ovarian Cancer, or
PiSARRO, page
114
15. Please disclose, on page 114, the number of patients evaluable for
radiological response
Christian Schade
FirstName LastNameChristian Schade
Aprea Therapeutics, Inc.
Comapany2019
August 8, NameAprea Therapeutics, Inc.
August 8, 2019 Page 5
Page 5
FirstName LastName
according to RECIST 1.1 in your Phase 1b trial and the number of
patients evaluable for
CA-125 response. In addition, explain what you mean by "stable
disease" on page 114.
Phase 2 clinical trial of APR-246 in platinum-resistant ovarian cancer, or
PiSARRO-R, page 115
16. Please disclose the observed results of the Phase 2 clinical trial,
including any serious
adverse events, the number of patients that experienced serious
adverse events and
the number of patients that received a 4500 mg/d fixed dose of APR-246
as a 6 hour
intravenous infusion as well as the number that received the same or
lower fixed dose over
3 or 4 hours for four consecutive days.
Our second product candidate, APR-548, page 116
17. We note your disclosure on page 116 that in preclinical testing you
have observed potency
with APR-548 that is superior to that of APR-246 in the cell lines
that you have tested and
that you have provided an example of one such test. Please include
disclosure regarding
the other preclinical studies, and, for all of the preclinical studies
discussed in this section,
please disclose the number of times you conducted the tests, the
number of animals
tested, the doses used in the tests, when the results were measured
and the range of results
observed. Similarly, we note your disclosure regarding your xenograft
study on page
116. Please disclose the number of mice tested in this study.
Consolidated Financial Statements
Note 2: Summary of significant accounting policies
Unaudited pro forma financial information, page F-8
18. Once the corporate reorganization described has been consummated,
revise your
disclosure in a pre-effective amendment to clearly confirm the
completed terms of the
reorganization transaction.
19. Revise your description of the pro forma amounts to more clearly
describe here the shares
exchanged in the corporate reorganization transaction as well as the
automatic conversion
in a manner that allows the reader to be able to easily recalculate
the pro forma equity
balances. More clearly identify here the triggers for the conversion,
including the specific
conversion terms of each class of the preferred shares of the
registrant that will be
outstanding after the corporate reorganization, which will be
automatically converted into
the common stock of the registrant.
General
20. Please provide us mockups of any pages that include any additional
pictures or graphics to
be presented, including any accompanying captions. Please keep in
mind, in scheduling
your printing and distribution of the preliminary prospectus, that we
may have comments
after our review of these materials.
You may contact Keira Nakada at 202-551-3659 or Kevin Vaughn at
202-551-3494 if
Christian Schade
Aprea Therapeutics, Inc.
August 8, 2019
Page 6
you have questions regarding comments on the financial statements and related
matters. Please
contact Sonia Bednarowski at 202-551-3666 or Dietrich King at 202-551-8071 with
any other
questions.
FirstName LastNameChristian Schade Sincerely,
Comapany NameAprea Therapeutics, Inc.
Division of
Corporation Finance
August 8, 2019 Page 6 Office of Healthcare
& Insurance
FirstName LastName