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July 5, 2024
Claire Mazumdar
Chief Executive Officer
Bicara Therapeutics Inc.
116 Huntington Avenue, Suite 703
Boston, MA 02116
Re: Bicara Therapeutics Inc.
Draft Registration Statement on Form S-1
Submitted June 10, 2024
CIK No. 0002023658
Dear Claire Mazumdar:
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
Cover Page
1. Please revise your cover page to clarify whether the offering is
contingent upon final
approval of your Nasdaq listing. Please ensure that the disclosure is
consistent with your
underwriting agreement.
BCA101 Clinical results, page 3
2. We note your disclosure here and elsewhere throughout your Prospectus
comparing data
from your clinical trials with other therapeutics. To the extent that
these comparisons were
not the result of head-to-head clinical trials, revise to remove the
comparisons. As a non-
exhaustive list, we note the following:
"The CR rate we observed in this cohort appears to be significantly
higher compared
to those previously reported in investigator-sponsored trials, or
ISTs, of cetuximab in
combination with pembrolizumab or nivolumab, as well as the
KEYNOTE-048 study
July 5, 2024
Page 2
with pembrolizumab, of approximately 3%" on pages 3 and 113;
"the mPFS in HPV-negative subjects was 9.8 months, a threefold
increase in PFS
benefit when compared to published historical data for pembrolizumab
monotherapy,
and superior to the data published for cetuximab and anti-PD-1
combination ISTs" on
page 113; and
"treatment-related adverse events, or TRAEs, leading to
discontinuation of BCA101
and/or pembrolizumab was 12%, markedly lower than historical
pembrolizumab
combinations, including lenvatinib or chemotherapy, which showed
TRAEs leading
to discontinuation rates of 28% and 33%, respectively" on page 114.
3. Revise page 4 and where else you state you believe you may use the
accelerated approval
pathway for BCA101 to briefly describe the feedback received from the
FDA that
supports your belief. Please also revise to include balancing disclosure
that an accelerated
approval pathway may not lead to a faster development or regulatory
review or approval
process and does not increase the likelihood that your product candidate
will receive
marketing approval.
4. Please revise to remove the statements appearing on pages 4 and 113 that
you "believe
BCA101 in combination with pembrolizumab could be established as the new
chemotherapy-free standard of care for HPV-negative first-line R/M
HNSCC" as it is
speculative given your current stage of development.
5. Please revise pages 4, 112 and 113 to state what "PD" abbreviates in the
graphics.
6. Discuss whether the results presented in this section were statistically
significant. Include
the associated p-values, if appropriate.
Our Team, page 6
7. We note you disclose the names of your investors on pages 6 and 101.
Please limit the
disclosure of specific investors to those identified in the Principal
Stockholders table on
page 174. Additionally, indicate that prospective investors should not
rely on the named
investors investment decision, that these investors may have
different risk tolerances and
that the shares purchased in the referenced financings were conducted at
a significant
discount to the IPO price, if true.
Summary of Material Risks Associated with our Business, page 6
8. Please expand your summary of material risks to further provide
balancing disclosure by
discussing if you are substantially dependent on any license agreements
for BCA101, that
you have never generated revenue and never commercialized a product.
The Offering, page 9
9. Please revise pages 9 and 78 to clearly state for your Phase 2/3 trial
whether proceeds are
intended to fund some but not all of the clinical trial work that would
be necessary for you
to file a Biologics License Application. Disclose the additional head
and neck squamous
cell carcinoma patient populations you plan to expand your BCA101
program to using
proceeds from this offering.
July 5, 2024
Page 3
Risk Factors
The operations of our suppliers, many of which are located outside of the
United States, are
subject to additional risks . . ., page 37
10. Please revise to state why "[i]f approved, the BIOSECURE Act in its
current form would
not prevent [you] from sourcing drug product from WuXi Bio for clinical
use."
Management's Discussion and Analysis of Financial Condition and Results of
Operations
Results of Operations
Research and Development Expenses (including Research and Development (Related
Party),
page 90
11. We note your disclosure that you have not reported program costs since
your inception
because you have not historically tracked or recorded your research and
development
expenses on a program-by-program basis. Please break out your external
research and
development costs separately and clarify if they relate to more than the
BCA101 program.
Critical Accounting Policies and Estimates
Common Stock Valuation, page 95
12. 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. Please discuss with the staff how to submit your response.
Business
Overview, page 98
13. We note your disclosure on page 28 that you are currently conducting a
clinical trial in
Canada. Please revise your Business section where appropriate to
disclose all the
jurisdictions where you are currently conducting clinical trials.
Our Solution: BCA101, a Novel Bifunctional Antibody, page 105
14. Please revise your graphic on page 105 to remove "[i]mproved efficacy"
as efficacy
determinations are within the sole discretion of the FDA or similar
foreign regulators.
BCA101 synergizes with anti-PD-1 therapies, with anti-tumor activity superior
to other anti-
EGFR therapies in preclinical models, page 108
15. Please revise to disclose the design, data and results of the two
preclinical cancer mouse
models whose data were published in Cancer Research.
Preclinical in vivo models demonstrate BCA101 may have an enhanced ability to
prevent tumor
relapse compared to cetuximab, page 108
16. Please revise to state whether your preclinical experiments in patient
derived xenograft
models of EGFR-expressing treatment-na ve HNSCC tumors were powered for
statistical
significance and if so, provide the p-values.
July 5, 2024
Page 4
Ongoing Phase 1/1b Trial, page 111
17. Please revise your graphic on page 111 so all of the text is legible.
18. Please revise page 111 to state the number of patients you expect to
enroll in the multiple
dose expansion cohorts.
BCA101 has been generally well-tolerated with a favorable tolerability profile,
page 114
19. Please disclose the number of patients that experienced
treatment-related severe adverse
events due to dermatitis acneiform and the number of patients with
treatment-related
adverse events that discontinued BCA101 and/or pembrolizumab. Also
revise to clarify if
the Grade 3 or 4 adverse events were considered treatment-related severe
adverse events.
20. We note your disclosure in the second paragraph of this section of the
EGFR-related
adverse events and note that your first paragraph indicates that there
may also be adverse
events associated with TGF-B inhibition. Please revise to clarify if you
have observed any
adverse events related to TGF-B inhibition in your trials of BCA101 to
date.
Contract Transfer And License Agreement with Biocon, page 117
21. Please revise to clarify how you use the technology licensed from
Biocon. Revise to state
how each party may terminate the Biocon Agreement, the aggregate amount
paid to date,
the aggregate amount of any future milestone payments, whether there is
a royalty term
and if so, disclose the royalty rate. Please also file the Assumed
Contracts as exhibits, or
tell us why they are not required to be filed, and disclose when the
ownership of
the Assumed Contracts will be transferred to you.
Intellectual Property, page 118
22. Please revise to disclose the jurisdictions for each patent family where
you have pending
patents. Revise to describe the patent family with "pending patent
applications that, if
issued, may provide additional intellectual property protection for
BCA101."
Manufacturing, page 120
23. Please disclose the names of your principal suppliers. Refer to Item
101(h)(4)(v) of
Regulation S-K.
Certain Relations and Related Party Transactions
Policies for approval of related party transactions, page 173
24. Please disclose the standards to be applied in deciding whether to
approve or ratify any
related party transaction. Refer to Regulation S-K Item 404(b)(1)(ii).
Exhibits
25. Please file the Director Engagement Letters, Scientific Advisory Board
Letter with Dr.
Hodi, Ivan Hyep Promissory Note, Syngene Master Manufacturing Services
Agreement,
and Syngene Master Contract Services Agreement as exhibits or otherwise
advise.
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,
July 5, 2024
Page 5
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 Tara Harkins at 202-551-3639 or Vanessa Robertson at
202-551-3649 if
you have questions regarding comments on the financial statements and related
matters. Please
contact Daniel Crawford at 202-551-7767 or Tim Buchmiller at 202-551-3635 with
any other
questions.
Sincerely,
Division of
Corporation Finance
Office of Life
Sciences
cc: Gabriela Morales-Rivera, Esq.