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United States securities and exchange commission logo
March 15, 2023
Shao-Lee Lin, MD
Chief Executive Officer
ACELYRIN, Inc.
4149 Liberty Canyon Road
Agoura Hills, CA 91301
Re: ACELYRIN, Inc.
Draft Registration
Statement on Form S-1
Submitted on
February 10, 2023
CIK 0001962918
Dear Shao-Lee Lin:
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 on February 10, 2023
Overview, page 1
1. Throughout your filing
you make statements and predictions regarding the safety and
efficacy of your
product candidates. Safety and efficacy are conclusions that are within
the sole authority of
the FDA and are assessed throughout the entire development
process. Given that
none of your candidates have received FDA approval, it is not
appropriate to state,
imply or predict that they are effective or safe. Please remove all
statements related to
the safety and efficacy of your product candidates. For example:
"Lonigutamab has
been shown to be markedly more potent than the currently
marketed therapy
for thyroid eye disease (TED)."
"izokibep
demonstrated clinically meaningful and differentiated benefits..."
Shao-Lee Lin, MD
FirstName LastNameShao-Lee Lin, MD
ACELYRIN, Inc.
Comapany
March NameACELYRIN, Inc.
15, 2023
March2 15, 2023 Page 2
Page
FirstName LastName
"Izokibep...with a safety profile consistent with that of the
anti-IL-17A class as a
whole."
"Izokibep has demonstrated higher orders of clinical response in
Part A of our Phase
2b/3 trial in HS, which we believe supports the potential to
offer
clinically meaningful, differentiated benefit to participants in
this severe autoimmune
condition..."
"Clinical responses in this open label portion of our ongoing
Phase 2b/3 trial in HS
were demonstrated at higher orders of Hidradenitis Suppuativa
Clinical Response
(HiSCR)..."
"These results from our trials in HS and PsA offer two independent
sets of clinical
data supporting our hypothesis that izokibep could offer
clinically meaningful
differentiated outcomes due to its high potency and small size,
and therefore the
potential to provide greater benefit to patients.
Please note, this is not an inclusive list of the safety and efficacy
claims you have included
in your filing. You should include a description of your clinical
trials, include a
comparison of the objective data from your trials to the trial
endpoints, discuss the
statistical significance of such results and indicate whether a
candidate was well tolerated
in the Business section where the information can be discussed in
proper context, without
describing the results as "positive" or validating the therapeutic
potential. To the extent
that your product candidates have been well tolerated, you may
indicate that this is the
case. If there have been any serious adverse events, describe the
events and indicate how
many instances have occurred. It is only appropriate to compare the
results of your
candidate's trials to another product or product candidate if head to
head trials were
conducted.
Our Pipeline, page 1
2. Please clarify if your global rights to izokibep apply to all
indications or are limited to
psoriatic arthritis.
Summary Overview of Izokibep, page 3
3. Please revise your reference to orphan drug designation to clarify
that such a designation
neither shortens the development time or regulatory review time of a
drug, nor does it
provide any approval in the regulatory review or approval process and
if your expected
plans will change if you do not obtain orphan drug designation.
4. Clarify that the FDA has not consented to your plans to conduct only
one Phase 3 clinical
trial, rather than the generally required two Phase 3 clinical trials.
Izokibep for the Treatment of Moderate-to-Severe HS, page 4
5. We note that the market research was conducted on our behalf by
Skysis. Please file its
consent as an exhibit to your registration statement.
Our Strategy, page 8
Shao-Lee Lin, MD
FirstName LastNameShao-Lee Lin, MD
ACELYRIN, Inc.
Comapany
March NameACELYRIN, Inc.
15, 2023
March3 15, 2023 Page 3
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FirstName LastName
6. Explain what "pipeline-in-a-program" means and its impact on your
strategy.
We are a clinical stage biopharma company with a limited history and no
products approved for
commercial sale., page 16
7. Revise your risk factor heading to indicate you have a history of
losses and highlight the
explanatory paragraph in your audit opinion raising substantial doubt
about your ability to
continue as a going concern. Additionally, disclose the potential
effect the going concern
opinion may have on your ability to raise additional funds through
equity or debt
financing.
Our product candidates licensed from various third parties may be subject to
retained rights.,
page 50
8. Revise your discussion to identify licenses that provide that the
licensors retain certain
rights, and describe the rights that the licensors have retained.
Additionally, identify the
licenses that are subject to "march-in rights."
Use of Proceeds, page 83
9. Please enhance your disclosure to quantify the amount of proceeds you
intend to use for
each stated purpose and indicate the stage of development you expect
to achieve for each
proposed use for izokibep.
Affibody Agreement, page 100
10. Please explain what priority review vouchers are and how the fair
market value will be
determined in accordance with the Affibody Agreement.
Management's Discussion and Analysis of Financial Condition and Results of
Operations
Critical Accounting Policies and Significant Judgments and Estimates
Stock-Based Compensation Expense, page 109
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 IPO and the estimated offering price. This information will
help facilitate our
review of your accounting for equity issuances. Please discuss with
the staff how to
submit your response.
Targeting IL-17A in the Treatment of HS, page 123
12. Clarify that secukinumab and bimekizumab are being developed by a
third party and
indicate whether they have received FDA approval. If they have not
received FDA
approval, clearly state that they have not been determined to be safe
or effective.
Shao-Lee Lin, MD
FirstName LastNameShao-Lee Lin, MD
ACELYRIN, Inc.
Comapany
March NameACELYRIN, Inc.
15, 2023
March4 15, 2023 Page 4
Page
FirstName LastName
Our Ongoing Phase 2b/3 Trial of Izokibep, page 126
13. Please describe the relevant preclinical and clinical trials and
objective results of such
trials supporting the INDs for your planned trial for AxSpa and
ongoing trials for HS, PsA
and uvetisis. Your discussion should identify the trial endpoints, the
objective results, the
p-values and statistical significance of the results.
14. Please Include a textual discussion of the table included on page 126.
Your table should
not not be included in lieu of a thorough descripting of your ongoing
trial. Similarly,
describe the table depicting your ongoing Phase 2b/3 Trial in PsA on
page 132 and your
ongoing Phase 2b/3 Trial in Uveitis on page 136.
Current Treatments for PsA, page 127
15. Please include a textual discussion explaining Figure 10 on page 128.
Your discussion
should explain the terms ACR50, PAS175 and enthesitis. Additionally,
explain which
therapies are the standard of care for each each manifestation
depicted.
Summary of the Completed Phase 2 Trial of Izokibep in PsA, page 128
16. Please revise to include a textual description of your Phase 2 trial
for PsA, rather than, or
in addition to, a table. Your description should explain the acronyms
and industry jargon
included in your table so that a reader without specialized medical
knowledge can
understand who can participate in the trial, what the safety and
efficacy endpoints are and
the meaning of the terms Q2W, 16W, 24W and the significance of the
axis along the
bottom of the table. Please note, industry terms should be explained
in the context of the
discussion.
17. Revise the statement preceding Figure 12 on page 129 to remove the
statement that you
believe the results demonstrate izokobep has the potential to provide
clinically
meaningful, differentiated benefits in the treatment of PsA over
existing therapies.
18. Explain what Figure 12 is attempting to depict. How are improvements
measured?
Explain what the percentages represent and how the information was
gathered. Disclose
the applicable p-vales and explain their meaning or indicate that the
results were not
statistically meaningful.
Pharmacokinetic-pharmacodynamic (PK-PD) Modeling Supports Higher Doses, page
131
19. Revise our disclosure to provide the objective data that led you to
conclude there was a
lack of plateau without providing your conclusion. Additionally,
revise the discussion to
ensure that it is understandable for a person without specialized
medical knowledge.
Izokibep for the treatment of AxSpA, page 133
20. Please clarify whether the FDA has approved your Phase 3 clinical
trials in AxSpA. If it
has not, please explain the basis for your strategy for going directly
to Phase 3 trials and
Shao-Lee Lin, MD
ACELYRIN, Inc.
March 15, 2023
Page 5
discuss the possibility that the FDA may require a Phase 2 trial.
21. Please disclose the known aspects of your trials, such as the meaning
of radiographic and
non-radiographic, the clinical trial endpoints, and the number of
participants.
Evidence for the Role of IL-17A Inhibitors in the Treatment if Non-Infectious
Uveitis, page 135
22. Unless secukinumab was approved for the treatment of uveitis, delete
the statements that
it demonstrated clinical benefits. You may present objective
information from the trial
providing the conclusion that it provided a clinical benefit.
Our Lonigutamab (IGF-1R Monoclonal Antibody) Program, page 137
23. Please describe the preclinical trials related to Lonigutamab for the
treatment of TED.
Clinical Development, page 142
24. Describe the early proof-of-concept data your Phase 1 trial is
designed to generate.
Our XLRN-517 (c-KIT Monoclonal Antibody) Program, page 142
25. Please provide a textual description of Figure 23, including the
relevance of the
information in the column on the right of the table.
26. Your pipeline table appearing on pages 2 and 117 indicates you have
completed
preclinical trials for chronic urticaria. Revise to describe the
preclinical trials.
General
27. 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.
You may contact Ibolya Ignat at 202-551-3636 or Vanessa Robertson at
202-551-3649 if
you have questions regarding comments on the financial statements and related
matters. Please
contact Cindy Polynice at 202-551-8707 or Suzanne Hayes at 202-551-3675 with
any other
questions.
FirstName LastNameShao-Lee Lin, MD Sincerely,
Comapany NameACELYRIN, Inc.
Division of
Corporation Finance
March 15, 2023 Page 5 Office of Life
Sciences
FirstName LastName