View:
United States securities and exchange commission logo
July 27, 2020
Preston Klassen, M.D.
President and Chief Executive Officer
Metacrine, Inc.
3985 Sorrento Valley Blvd., Suite C
San Diego, CA 92121
Re: Metacrine, Inc.
Amendment No. 2 to
Draft Registration
Statement on Form S-1
Submitted July 2,
2020
CIK No. 0001634379
Dear Mr. Klassen:
We have reviewed your amended 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
Overview, page 1
1. Please balance your
Summary with disclosure that doctors recommend weight loss to treat
nonalcoholic fatty
liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
because weight loss can
reduce fat in the liver, inflammation, and fibrosis, or scarring.
We note your Risk
Factor disclosure that the current standard of care is likely to present a
major challenge to the
market penetration of MET409 and MET642 for the treatment of
NASH, if ever
commercialized, please include this in your Summary.
2. We note your disclosure
that you "believe FXR agonists will become first-line
Preston Klassen, M.D.
FirstName
Metacrine, LastNamePreston Klassen, M.D.
Inc.
Comapany
July NameMetacrine, Inc.
27, 2020
July 27,
Page 2 2020 Page 2
FirstName LastName
monotherapy, as well as the backbone of combination therapy (emphasis
added), for
patients with NASH." Please provide your basis for this statement
given that diabetes,
obesity and metabolic syndrome appear to be the diseases with which
NASH is associated
and it appears that the current standard of care includes antidiabetic
therapies, which
would appear to be the principal therapy in any potential combination
with a therapy for
NASH.
3. Please revise here and throughout your prospectus to balance and
provide the basis
for your disclosure that "with our program, we believe we can be the
leader [emphasis
added] in developing best-in-class FXR agonist therapies for NASH and
other GI
diseases." We note your disclosure that other companies are in later
stages of clinical
trials for their FXR agonists than you and that "MET409 and MET 642
are FXR agonists,
a class of drugs from which there are no approved therapies in the
diseases for which we
are currently pursuing clinical trials, and our initial target
indication is NASH, for which
there are no approved therapies." Further, please remove
"best-in-class" and "first-in-
class" therapy references (and similar phrases) found throughout your
registration
statement since these terms suggest that the product candidates are
effective and likely to
be approved.
4. We note your disclosure that "targeting FXR has demonstrated
improvements in NASH in
large-scale clinical trials, including reversal of fibrosis, which we
believe makes this a
well-established target (emphasis added) for the treatment of NASH
patients." Please
revise your disclosure to provide the basis for this belief given your
disclosure that
"MET409 and MET 642 are FXR agonists, a class of drugs from which
there are no
approved therapies in the diseases for which we are currently pursuing
clinical trials, and
our initial target indication is NASH, for which there are no approved
therapies." We
further note your disclosure on page 13 that the FDA recently denied
accelerated approval
for a competitor's product candidate based on the surrogate histologic
endpoint of
improvement of fibrosis as shown by liver biopsy with no worsening of
NASH in lieu of
clinical outcomes such as overall survival and time to transplant."
5. As safety and efficacy determinations are solely within the Food and
Drug
Administration's authority and they continue to be evaluated
throughout all phases of
clinical trials, please remove references to these terms, along with
references to "potency,"
and any similar references in your prospectus.
6. We note your Summary disclosure on page 2 that you intend to pursue
development of
your FXR agonist product candidates for the treatment of Inflammatory
Bowel Disease, or
IBD, including Ulcerative Colitis, or UC, and Crohn s disease.
Please provide us with
your analysis as to why it is appropriate to include the lengthy
Summary discussion of
these indications and emphasis on the $9 billion annual market
opportunity for IBD given
it appears your product candidates are preclinical for such
indication. We note your
disclosure that you plan to submit an IND for an undisclosed product
candidate in 2022.
Preston Klassen, M.D.
FirstName
Metacrine, LastNamePreston Klassen, M.D.
Inc.
Comapany
July NameMetacrine, Inc.
27, 2020
July 27,
Page 3 2020 Page 3
FirstName LastName
7. We note your disclosure that "[i]n preclinical studies of our FXR
agonists, we have
observed improvement in colon inflammation on a level similar to that
of biologics
currently used for treatment. We believe an oral, once-daily therapy
with FXR agonists,
such as those in our FXR program, could be an attractive treatment
option for IBD
patients." Efficacy is a determination that is solely within the
authority of the FDA or
similar foreign regulators. Additionally, comparisons to other
available treatments
require head-to-head trials. Please delete the statements indicating
that your FXR agonists,
which haven't been clinically tested for this indication are effective
at treating IBD and
remove any comparisons with third party treatments, including your
perceived similarity
to existing therapies currently used for treatment.
8. We note that the status arrows in your pipeline chart on pages 4 and
86 end at different
locations within the columns. Please include a narrative that
describes what the chart is
depicting.
9. We note that your pipeline table includes the "MET409 or MET642" for
IBD
Monotherapy, as preclinical programs that you are exploring, but it
appears you don't plan
to file an IND for either of these candidates for such indication
until 2022. As your
narrative disclosure only briefly discusses these programs for any
indication within the
class of IBD, an IND is not planned until two years from now and you
have not allocated
any proceeds for their development in your use of proceeds section,
please explain to us
why you believe these programs are sufficiently material to your
business to be included
in your pipeline table. Your analysis should address specific product
candidates and
indications within IBD.
10. We note that your pipeline table includes "MET409 or MET642" for
"other indications"
as preclinical programs that you are exploring. As you only discuss
these programs in
general terms very briefly in the prospectus and you have not
allocated any proceeds for
their development in your use of proceeds section, please provide us
your analysis
supporting your determination to include a specific product candidate
for a specific
indication in this category in your pipeline table.
11. Please remove the last row of your pipeline table that generically
references
"inflammation and fibrosis targets" and then "NASH," neither of which
are a summary of
your research and development programs.
12. We note your disclosure that your lead candidate, MET409, completed
Phase 1b clinical
trial as a monotherapy in the Netherlands and that you plan to
initiate a Phase 2a
combination trial in the first half of 2021 of MET409 with an
antidiabetic agent in patients
with type 2 diabetes and NASH, and expect to report topline data in
the first half of 2022.
Please revise your disclosure to indicate whether you are conducting
the Phase 2a trial in
the United States and if so, whether you have submitted an IND to FDA.
To the extent
that you have submitted an IND, disclose when you submitted it and
identify
the IND sponsor(s) and the specific indications listed therein. Please
disclose whether you
believe that clinical data generated in the Netherlands will be
accepted by the FDA and its
Preston Klassen, M.D.
FirstName
Metacrine, LastNamePreston Klassen, M.D.
Inc.
Comapany
July NameMetacrine, Inc.
27, 2020
July 27,
Page 4 2020 Page 4
FirstName LastName
foreign equivalents and therefore enable you to commence your planned
Phase 2a trials in
the United States, without the need to repeat your Phase 1 clinical
trial in the United
States.
13. Please state when you plan to submit an IND in advance of your plans
to initiate a Phase
2a, randomized, placebo-controlled trial of MET642 in patients with
NASH in the first
half of 2021.
14. We note your intent to expand the development of your FXR program into
IBD. Please
identify the product candidate and specific IBD indication referenced
and state with more
specificity when you plan to submit an IND and when you intend to
initiate a Phase 2a
clinical trial in IBD patients in 2022.
15. We note your Risk Factor disclosure that "...some of our competitors
may have ongoing
clinical trials for product candidates that would treat the same
indications as our product
candidates, and patients who would otherwise be eligible for our
clinical trials may
instead enroll in clinical trials of our competitors product
candidates. This is acutely
relevant (emphasis added) for our development of MET409 and MET642 for
the
treatment of patients with NASH and IBD, diseases for which there are
significant
competition (emphasis added) for clinical trial subjects." Please
consider whether this is
material to your business and as such should be included on page 5,
Risks Associated with
Our Business.
We are an early stage biopharmaceutical company with a very limited operating
history., page 12
16. We note that you disclose your results for the fiscal years ended
December 31, 2018 and
December 31, 2019, and for the six months ended June 30, 2020. Please
expand your
disclosure here and throughout your registration statement, where
appropriate, to includes
results for the six months ended June 30, 2019.
Risk Factors
We are very early in our development efforts and we have limited experience
conducting clinical
trials in humans., page 15
17. We note your disclosure that "[t]o date, MET409 and MET642 have only
been evaluated
for safety and toxicology in animals for up to 13 weeks and 16 weeks,
respectively, and
their longer term toxicity is unknown." Please confirm that this is
current information, as
it appears to be inconsistent with your clinical development
disclosures.
We rely, and intend to rely, on third parties to conduct our clinical trials
and perform some of our
research and preclinical studies., page 30
18. We note that you rely, and intend to rely, on third parties to conduct
your clinical trials
and perform certain other tasks. To the extent material, attach any
agreements covering
such relationships.
Use of Proceeds, page 64
Preston Klassen, M.D.
Metacrine, Inc.
July 27, 2020
Page 5
19. Please disclose how far into development (e.g., phase of clinical
study) for each product
candidate with a specific indication you anticipate the proceeds of
this offering will allow.
Expedited development and review programs, page 106
20. Please expand your disclosure to explicitly state that fast track
designation does not
guarantee an accelerated review by the Food and Drug Administration.
Amended and Restated Certificate of Incorporation and Amended and Restated
Bylaws, page
151
21. Please provide amended bylaws that reflect your disclosures regarding
the applicability of
your exclusive forum provision to Exchange Act and Securities claims
or revise your
disclosure here and your risk factor to clarify that your bylaws do
not explicitly address
the Exchange Act or Securities Act.
You may contact Tracie Mariner at (202) 551-3744 or Kevin Vaughn at
(202) 551-3494
if you have questions regarding comments on the financial statements and
related
matters. Please contact Courtney Lindsay at (202) 551-7237 or Celeste Murphy at
(202) 551-
3257 with any other questions.
FirstName LastNamePreston Klassen, M.D. Sincerely,
Comapany NameMetacrine, Inc.
Division of
Corporation Finance
July 27, 2020 Page 5 Office of Life
Sciences
FirstName LastName