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October 8, 2024
Stephen Yoder
Chief Executive Officer
Pieris Pharmaceuticals, Inc.
225 Franklin Street, 26th Floor
Boston, MA 02110
Re: Pieris Pharmaceuticals, Inc.
Amendment No. 1 to Registration Statement on Form S-4
Filed September 23, 2024
File No. 333-281459
Dear Stephen Yoder:
We have reviewed your amended registration statement and have the
following
comments.
Please respond to this letter by amending your registration statement
and providing
the requested information. If you do not believe a comment applies to your
facts and
circumstances or do not believe an amendment is appropriate, please tell us why
in your
response.
After reviewing any amendment to your registration statement and the
information
you provide in response to this letter, we may have additional comments. Unless
we note
otherwise, any references to prior comments are to comments in our September 6,
2024 letter.
Amendment No. 1 to Registration Statement on Form S-4
Prospectus Summary
The Companies
Palvella Therapeutics, Inc., page 11
1. We note your response to prior comment 7, which we reissue with respect
to the third
and fourth bullets. Please revise both the Summary and Business sections
to balance
your disclosure with respect to Palvella's QTORIN platform by stating,
if true, that
clinical trials of QTORIN rapamycin targeting other indications (i.e.,
Gorlin
Syndrome and pachyonychia congenita) failed to meet their respective
primary
endpoints, which may affect Palvella's ability to conduct clinical
programs for other
QTORIN-based product candidates and that the QTORIN platform may never
result
in the regulatory approval of any product candidate.
October 8, 2024
Page 2
2. We note your response to prior comment 8, which we reissue in part.
Please further
revise both the Summary and Business sections to highlight your
selection of "novel
endpoints or other key clinical trial design features, such as choice of
control" used or
to be used in your ongoing and planned clinical trials of QTORIN
rapamycin for
various rare disease indications. In this regard, we note your
disclosure on page 62
that such clinical trial features "could delay or prevent regulatory
approval for
Palvella's product candidates." Your revisions should:
Explain what you mean by "baseline-controlled" study and how such a
clinical
trial differs from a placebo-controlled trial;
Explain the clinical endpoints of your ongoing and planned clinical
trials; and
Explain the novelty and/or the subjective nature of your choice of
control and
selected endpoints.
Support Agreements, page 17
3. We note your response to prior comment 12; however, we are unable to
locate
responsive disclosure in the registration statement. Therefore, we
reissue the
comment.
Risk Factors
The articles of incorporation of the combined company will generally
provide..., page 58
4. We note your response to prior comment 15, which we reissue in part.
Please revise
your disclosure to expressly state whether the exclusive forum provision
in the articles
of incorporation of the combined company will apply to actions arising
under the
Securities Act or Exchange Act. If so, make conforming revisions in your
related risk
factor disclosures and disclose that risk to shareholders related to
this provision may
include increased costs to bring a claim. If not, please ensure that the
exclusive forum
provision in the governing documents states this clearly, or tell us how
you will
inform investors in future filings that the provision does not apply to
any actions
arising under the Securities Act or Exchange Act.
Certain Unaudited Projections of Palvella, page 144
5. We note your response to prior comments 21 and 24 and that the summary
financial
projections table covers a period through 2038. Please revise this
section to include
the information contained in your response letter indicating that
Palvella's expected
patent protections were tied to the length of the period projected in
the table. As
appropriate, clarify any material assumptions underlying this basis for
the presentation
period. Additionally, to the extent material, disclose the "high-level
projections" that
Palvella provided to Stifel for 2039 and 2040 for purposes of conducting
the discounted cash flow analysis.
6. We note your response to prior comment 23, which we reissue in part.
Please further
revise your discussion of the material assumptions that underlie the
financial projections table as follows:
Please revise to explain how Palvella management arrived at the
probability of
regulatory approval for QTORIN rapamycin for each indication, as
applicable.
October 8, 2024
Page 3
Clearly disclose any assumptions as to which indication(s) were
assumed to have
received approvals, the year(s) approval is received, and the
regulatory
jurisdiction(s). In this regard, we note that the bulleted list of
assumptions now
included on page 145 only appear to relate to QTORIN rapamycin for
treatment
of microcystic LM. If the probability of approval for the CVM
indication was not
assessed or was assessed to be 0 during the period presented, please
expressly
state as such, and explain the reason(s) why.
With respect to line items such as total net sales, please
specifically address the
growth rates and clearly identify the material product revenue
stream(s)
underlying the projections.
Revise to clarify what, if any, consideration the Pieris Board
gave to the separate
possibility that Palvella's product candidate may not successfully
complete
clinical trials in some or all indications.
Additionally, discuss whether the projections factored in the
possibility of FDA
approval of new competitive products
7. We note your response to prior comment 24 and reissue the first bullet
thereof. With
regard to the length of the projections, please disclose the basis for
projections beyond
year five, including whether the forecasts reflect more than simple
assumptions about
growth rates, or whether, for example, the forecasts reflect straight
line growth
assumptions.
Pieris' Business
Strategic Partnerships, page 221
8. We note your revisions in response to prior comment 28. With respect to
the Pfizer
Collaboration Agreements, please revise the description of the tiered
royalties to
disclose a royalty range within ten percentage points. Also, you
disclose that the
royalty term may terminate upon the last-to-expire patent on a
country-by-country and
product-by-product basis. Please revise to clarify when these patents
are expected to
expire.
QTORIN Rapamycin for the Treatment of Microcystic LM, page 228
9. We note your response to prior comment 31, which we reissue with respect
to the
second and third bullets. Please revise to disclose the substance of any
material FDA
comments or guidance received related to Palvella's NDA or bridging
strategy. In this
regard, we note your disclosure on page 71 that the FDA recommends that
bridging to
support an NDA for the treatment of microcystic LM be done in a relative
bioavailability study comparing the pharmacokinetics of a topical
product applied
under maximal use conditions and the approved oral drug. Notwithstanding
any FDA
recommendation(s), explain the rationale for Palvella's plans to bridge
QTORIN
rapamycin and the approved oral rapamycin product based on cross-study
comparison
between pharmacokinetic data from the prescribing information for the
approved
product rather than in a relative bioavailability study.
10. We note your response to prior comment 32, which we reissue in part.
October 8, 2024
Page 4
In light of your disclosure on page 67 that the design of a
clinical trial can
determine whether its results will support approval of a product,
please further
revise Palvella's Business section to summarize the substance of any
material
comments or guidance that the FDA provided with respect to each of
the
following Phase 3 clinical design features: proposed patient
population, choice of
control, dosing, and endpoint selection.
Notwithstanding any FDA recommendation(s), explain Palvella's
rationale for
designing a baseline-controlled study rather than a
placebo-controlled trial.
Similarly, explain Palvella's rationale for employing a dynamic
assessment that
uses a comparative rating scale as the primary and key secondary
endpoints.
Consistent with the disclosure on page 68, discuss any surrounding
uncertainty
related to Palvella's use of these approaches, explain whether, and
if so why,
Palvella's Phase 3 trial design may be susceptible to objection, and
what
additional trials or testing could be required.
Please contact Gary Newberry at 202-551-3761 or Vanessa Robertson at
202-551-
3649 if you have questions regarding comments on the financial statements and
related
matters. Please contact Lauren Sprague Hamill at 303-844-1008 or Laura Crotty
at 202-551-
7614 with any other questions.
Sincerely,
Division of
Corporation Finance
Office of Life
Sciences
cc: Joseph Walsh