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July 14, 2024
Josh Mandel-Brehm
Chief Executive Officer
Camp4 Therapeutics Corp
One Kendall Square, Building 1400 West, 3rd Floor
Cambridge, MA 02139
Re: Camp4 Therapeutics Corp
Draft Registration Statement on Form S-1
Submitted June 14, 2024
CIK No. 0001736730
Dear Josh Mandel-Brehm:
We have reviewed your draft registration statement and have the
following comments.
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 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 the information you provide in response to this letter
and your amended
draft registration statement or filed registration statement, we may have
additional comments.
Draft Registration Statement on Form S-1 submitted June 14, 2024
Overview, page 1
1. We refer to your July 20, 2022 press release concerning your Series B
financing. We note
that your press release indicates that your lead product candidate was
designed to treat
Dravet syndrome and that you expected to commence clinical trials for
this program by
mid-2023. We also note that your prospectus disclosure does not mention
this program or
indicate whether it was one of the legacy programs that you out-licensed
in July 2023.
Given that this program was recently your lead candidate and given that
it appears that
your RAP platform was used to develop this candidate, please revise the
prospectus (e.g.,
Summary, Risk Factor, MD&A and Business sections) to address your
experience with
this program.
2. With reference to your risk factor disclosures on pages 15, 21 and 25,
please revise the
opening paragraph to provide balance and context to the first sentence
as well as to the
subsequent performance claims concerning your RAP platform in the same
paragraph and
July 14, 2024
Page 2
on pages 2-3. In particular, it should be clear that you are in the
early stages of
development, that you do not have clinical data to support your beliefs
and that your
approach is unproven and may not lead to successful efforts to identify,
discover and
develop potential product candidates.
3. You state on pages 1, 4, and throughout the Business section that your
lead candidate
CMP-CPS-001 has the potential to be the "first disease-modifying
therapy" to market for
the treatment of the most prevalent UCDs. Please provide context and
balance to the
statement by clarifying that your belief is based on preclinical
studies.
4. Please revise to explain briefly the term "upregulate."
Our RAP platform, page 2
5. As safety and efficacy determinations are solely within the authority of
the FDA and
comparable foreign regulators and are continually assessed through all
phases of clinical
trials, please remove or revise any statements that state or imply that
your product
candidates are safe or effective. By way of example only, we note the
statements on pages
2 and 107 regarding your proprietary technology enabling you to design
RNA Actuators
that "optimize for specificity and safety."
6. With reference to your risk factor disclosure on page 27, please revise
to disclose that
regulatory authorities to date have not approved any ASOs that are
directed towards
regulatory RNAs and the resulting uncertainty as to the safety profile
of your product
candidates.
Our Pipeline, page 3
7. You state that you are advancing a pipeline of programs initially
focused on metabolic
and CNS disorders with validated disease biology, significant unmet
needs and large
potential market opportunities. In light of your disclosures on page 29
and elsewhere
regarding the "small number of patients" who have the rare diseases on
which you are
initially focused, please clarify what you mean by "large potential
market opportunities."
CMP-CPS-001: Potential treatment for urea cycle disorders, page 4
8. You state that you have designed CMP-CPS-001 to overcome the limitations
of
other programs in development for the treatment of late onset UCDs by
"targeting more
than 85% of patients with UCD." Please revise to describe the relevant
patient
subpopulation(s) you are targeting. In this regard, we note your
disclosure on page 123
that assuming the successful completion of your ongoing Phase 1 clinical
trial in health
adult volunteers, you anticipate conducting a Phase 2/3 clinical trial
to enroll patients, two
years of age or older, who have been diagnosed with OTC deficiency. As
applicable, please revise, where appropriate, to discuss risks or
challenges associated
with pediatric trials.
9. With reference to the risk disclosure on page 25, please provide balance
to your page 4
discussion of the NHP studies by disclosing that ureagenesis is not an
established clinical
endpoint, and that this is one reason why these results should not be
interpreted as
evidence of efficacy.
July 14, 2024
Page 3
CMP-FH: Program for the treatment for heterozygous familial
hypercholesterolemia, page 5
10. We note your disclosure that you expect to initiate final GLP
toxicology studies to enable
the filing of a clinical trial application for your CMP-FH program.
Please revise to
disclose the jurisdiction(s) where you plan to file such application(s)
or clarify that such
determinations remain pending. Make similar revisions in the sections
throughout the
prospectus discussing your CMP-SYNGAP program.
11. You disclose that Heterozygous FH is a common genetic disorder
affecting over 3 million
patients in the United States and Europe, in the aggregate. To the
extent that this genetic
disorder is materially less prevalent in other large geographic markets
that you might
target, please briefly discuss.
Risk Factors
We currently depend on third-party suppliers for the manufacture of our product
candidates., page
45
12. We note your disclosure that you rely on third-party suppliers for the
manufacture of your
product candidates, and that "certain" Chinese biotechnology companies
and CMOs
supply you with product candidate components.
Please tell us whether any Chinese companies you do business with
have been named
as "companies of concern" in the amended version of the U.S. House
of
Representatives' draft of the BIOSECURE Act approved on May 15,
2024, or are a
subsidiary or affiliate of a named company of concern.
Revise your disclosure to include an updated discussion of the
pending BIOSECURE
legislation that would result in trade restrictions, sanctions, or
other regulatory
requirements by the U.S. government, which could restrict or even
prohibit your
ability to work with your contractual counterparties.
To the extent you are unable to replace any supply or contract
manufacturing
agreement(s) with any Chinese counterparty, please consider whether
you are
substantially dependent on such agreement(s) and whether such
agreement(s) are
required to be filed pursuant to Item 601(b)(10)(ii)(B) of
Regulation S-K.
If we or our licensors are unable to obtain..., page 51
13. Please revise to explain the significance of composition of matter
patents. Also, add a
Summary risk factor to highlight the risks of not having this type of
patent coverage for
your product candidates.
Management's Discussion and Analysis of Financial Condition and Results of
Operations
Components of our Results of Operations
Revenue, page 94
14. You state that through the year ended December 31, 2023 you have
recognized $17.4
million in research collaboration and license revenue through your
collaboration and
license agreements. Since you recognized $350,000 and none in the years
ended
December 31, 2023 and 2022, respectively, please clarify in this
discussion of the
collaboration and licensing agreements to which the $17.4 million
revenue was derived
and whether the agreement(s) is ongoing.
July 14, 2024
Page 4
Business
The role of regRNA in controlling transcription, page 113
15. We note your disclosure that modest increases in protein expression can
lead to clinically
meaningful therapeutic benefits in many of the more than 1,200
haploinsufficient or
recessive partial loss-of-function indications. Please revise to explain
your support for this
statement and provide disclosure that explains what is depicted in each
of the three
columns in the graph. Also revise to explain the term "many" in
quantitative terms.
Our solution for UCDs: CMP-CPS-001, page 118
16. Please revise to provide descriptive text to explain in greater detail
what the table on page
118 shows and how you interpret those results. Also explain the
references to analogs and
explain why CMP-CPS-001 could not be used in what appear to be in vitro
studies of
healthy human donor cells.
17. Please revise to explain when you commenced work on this program,
including when you
identified the target gene and generated the ASO candidate.
Our preclinical studies, page 119
18. Please expand your discussion of your preclinical animal studies as
follows:
Briefly describe the scope and size of the animal studies and the
number of tests
conducted. Also, with respect to your discussion of the evaluation
of CPS1
upregulation in a mouse Otc deficiency model on page 119, disclose
the three
different dose levels.
Wherever you disclose you observed study results that were
statistically significant,
such as the statistically significant decrease in ammonia levels
observed in
the preclinical evaluation of CMP-CPS-001 in mice with humanized
livers, please
revise to provide p-values. At first use of the term p-value, please
provide a brief
explanation regarding how p-values are used to measure statistical
significance and
the p-value that you have to achieve to conclude a statistically
significant result.
Our ongoing Phase 1 clinical trial, page 123
19. Please revise to explain the reason(s) for conducting your clinical
trial in Australia as
opposed to the United States, particularly in light of the risks
discussed on page 64. With
reference to the risk factors on pages 19 and 25, please also tell us
whether the utilization
of the URT test impacted the decision to conduct the trials in
Australia.
20. Please revise to discuss here, and as applicable, on page 25, to explain
why URT is not an
established clinical endpoint even though it has experienced expanded
use in clinical
studies.
21. With reference to your disclosure on page 122, please revise your
disclosure to discuss the
use of sodium acetate as a surrogate biomarker. Explain the basis for
concluding that
sodium acetate is a valid surrogate for ammonia in humans and discuss
whether there are
risks that sodium acetate could act differently or measure differently
than ammonia.
July 14, 2024
Page 5
License and collaboration agreements
Whitehead Institute patent license agreement, page 128
22. Please revise your disclosure regarding the license agreement with the
Whitehead Institute
to include a discussion of all material payment terms, including
quantification of the past
patent expenses paid in addition to the upfront fee, and aggregate
potential milestone
payments segregated by development and commercial milestone payments.
23. You state that your royalty obligations will terminate on a
product-by-product and
country-by-country basis upon either the last-to-expire valid claim of a
Whitehead
Institute patent covering the product, which such patent you state is
expected to expire in
2043, or "a specified duration after the first commercial sale." Please
disclose
this specified duration.
Program-related intellectual property, page 131
24. Please disclose the dates when provisional patent applications were
filed and/or when the
applications expire.
Exhibits
25. With reference to your disclosures on pages 170-171, please file the
employment
agreements and indemnification agreements with each of your directors
and executive
officers.
General
26. 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,
have presented or expect to present to potential investors in reliance
on Section 5(d) of the
Securities Act, whether or not they retain copies of the communications.
Please contact Gary Newberry at 202-551-3761 or Mary Mast at
202-551-3613 if you
have questions regarding comments on the financial statements and related
matters. Please
contact Lauren Sprague Hamill at 303-844-1008 or Joe McCann at 202-551-6262
with any other
questions.
Sincerely,
Division of
Corporation Finance
Office of Life
Sciences
cc: Thomas Danielski