SecProbe.io

July 18, 2024
Gregory J. Flesher
President and Chief Executive Officer
Reneo Pharmaceuticals, Inc.
18575 Jamboree Road, Suite 275-S
Irvine, CA 92612
Re:Reneo Pharmaceuticals, Inc.
Registration Statement on Form S-4
Filed June 21, 2024
File No. 333-280369
Dear Gregory J. Flesher:
            We have reviewed your 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.
Registration Statement on Form S-4
Following the Mergers, will Reneo's securities be traded on a stock exchange?, page 12
1.We note your disclosure that it is expected that the NewCo Class A Common Stock will
trade on the Nasdaq Global Market after completion of the Proposed Transactions. Please
revise to disclose if the terms of the merger agreement permit that the Nasdaq listing
closing condition could be waived without recirculation or resolicitation. If so, please
revise your risk factors to reflect the risks associated with any such waiver and revise to
indicate that shareholders may not have certainty at the time of the vote that the shares of
NewCo will be listed on Nasdaq following the merger or revise your disclosure in a pre-
effective amendment as appropriate if and when there is more certainty regarding the
Nasdaq listing of the NewCo Class A Common Stock.

July 18, 2024
Page 2
Prospectus Summary
OnKure, Inc., page 20
2.We note your disclosure here that OnKure is focused on developing "best-in-
class" precision medicines. Please revise this and similar statements throughout the proxy
statement/prospectus that OnKure's product candidates may be "best-in-class" as these
statements appear to be speculative given the current development status of those product
candidates and the noted length and uncertainty of the drug approval and
commercialization processes.
3.Please tell us your basis for your statement asserting that OnKure's design platform is
"proven" given that OnKure has no products approved for commercial sale.
Risk Factors, page 34
4.We note from Section 10.1 of the Merger Agreement that, in general, the representations
and warranties of the parties contained in the Merger Agreement do not survive the
Closing and that there are no indemnification rights. Please include appropriate risk factor
disclosure.
OnKure contracts with third parties for the manufacture of its product candidates for preclinical
studies..., page 80
5.Please revise this risk factor to name the single-source supplier OnKure currently relies
upon and clarify if OnKure has entered into any supply agreements with them.
The Amended Bylaws will provide that, unless NewCo consents in writing to the selection of an
alternative forum..., page 91
6.We note that your forum selection provision identifies the Court of Chancery of the State
of Delaware as the exclusive forum for certain litigation, including any "derivative
action." Please disclose whether this provision applies to actions arising under
the Exchange Act. In that regard, we note that Section 27 of the Exchange Act creates
exclusive federal jurisdiction over all suits brought to enforce any duty or liability created
by the Exchange Act or the rules and regulations thereunder. If this provision does not
apply to actions arising under the Exchange Act, please also 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 Exchange Act.
The Mergers
Background of the Mergers, page 104
7.Please revise this section to provide a more fulsome description of the negotiations related
to the Concurrent PIPE Investments.
8.Please revise to explain why the board of Reneo found the proposal from OnKure "more
attractive" than the proposal from Party B. Please also clearly disclose when Reneo's
board decided to stop considering the proposal from Party B.
9.Please briefly explain why the Reneo board decided to also retain Cooley LLP in
connection with this transaction. In your revisions, provide a more fulsome discussion of
the role Cooley played in negotiating the merger agreement with OnKure.

July 18, 2024
Page 3
10.Please specify which terms remained under negotiation on April 26, 2024.
Opinion of Leerink Partners LLC
Certain Unaudited Financial Projections of OnKure, page 130
11.Please revise to disclose the material assumptions underlying the Reneo-prepared OnKure
financial projections that were made available to Leerink Partners.
12.We note the disclaimers throughout this section that readers are cautioned not to rely on
the prospective financial projections. While it is acceptable to include qualifying language
concerning subjective analyses, it is inappropriate to indicate that investors cannot rely on
disclosure. Please revise accordingly.
13.We see in the OnKure Forecasts on page 132 the significant variances among the amounts
shown as projected net sales, adjusted net sales and adjusted net revenue for the years
presented. Briefly indicate how these terms were defined for purposes of the forecasts and
the reasons for the material differences.
OnKure Business, page 212
14.Please revise your disclosure to remove any implication that OnKure's product candidates
will be safe or effective, as such conclusions are within the sole authority of the FDA
and comparable foreign regulators. By way of example only, on page 216 you state that
OKI-219 causes "tumor regression" and has a "favorable safety profile." We also note
statements throughout OnKure's business section claiming your product candidates are
"more effective" than approved products or can "minimize known side effects" observed
in other PI3K α inhibitors. Please remove these statements, and any others like them, or
revise these statements to instead present the objective data resulting from your
clinical trials.
15.Please indicate if the data presented in figure 1 (page 216), figure 7 (page 223) and
figure 8 (page 224) was statistically significant, and include p-values if appropriate.
OnKure's Clinical Pipeline, page 214
16.Please revise your pipeline table to present all phases of clinical development.
OnKure's Preclinical Pipeline, page 214
17.We note the inclusion of OnKure's preclinical pipeline in this section. Given the limited
disclosure related to the programs contained in this pipeline table throughout OnKure's
Business section, please explain why they are sufficiently material to OnKure's business
to warrant inclusion here. If they are material, please expand the disclosure in the
Business section related to these candidates to provide a more fulsome discussion of any
development activities conducted. Alternatively, remove this pipeline table.
OKI-219, a Targeted Inhibitor of PI3K α, page 216
18.We note your disclosure in the last paragraph on page 215 that both alpelisib and
capivasertib are ATP-competitive kinase inhibitors. Please indicate if OKI-219 is also an
ATP-competitive kinase inhibitor or works by some other mechanism of action.

July 18, 2024
Page 4
19.We note your disclosure that OnKure has shown preclinical data supporting the selectivity
of OKI-219 and that OKI-219 targets the H1047R mutated PI3K α with approximately 80-
fold selectivity over the wild-type PI3K α. Please disclose the material data underlying
this disclosure and indicate if such data was statistically significant, providing p-values, if
appropriate.
Commercial Opportunity in Breast Cancer, page 217
20.Please revise this section to clearly state that you will need to receive FDA approval prior
to commercialization of any of your product candidates.
Limitations of Currently Approved PI3K Inhibitors, page 218
21.Please identify the parties that conducted the clinical studies referenced in this section that
targeted mutated PI3K α. Please also clarify, if true, that OnKure did not conduct any of
the studies referenced here.
Phase 1 PIKture-01 Trial, page 224
22.Please disclose the planned endpoints for all three parts of your Phase 1 PIKture-
01 trial. Please also explain how this trial will be powered to assess efficacy.
Figure 9. PIKture-01 trial design and timeline, page 225
23.Please revise this graphic to ensure that all text is legible without magnification.
Intellectual Property, page 228
24.We note your statement here that OnKure's owned and licensed patent portfolio consists
of 128 patents and patent applications, including two licensed issued patents. Please revise
to clarify if any of the licensed patents are material to OnKure's business. To the extent
they are, please revise wherever appropriate to disclose the name of the party or parties
these patents are licensed from and discuss the material terms of the licensing agreements
related to these patents. Please also file these agreements as exhibits to your registration
statement. Refer to Item 601 of Regulation S-K for guidance.
PI3K Platform, page 228
25.Please revise this section to the disclose the type of patent protection and potential
expiration dates, if granted, for each of the eleven patent families relating to your PI3K
platform. Please also discuss what a provisional patent application is and what rights flow
from this type of application.
Principal Stockholders of the Combined Company, page 326
26.Please revise the footnotes to the table on page 327 to identify the natural person(s) with
voting and/or dispositive control over the shares in the combined company that will
be held by Acorn Bioventures, L.P., Cormorant Asset Management LP, Perceptive Life
Sciences Master Fund, Ltd. and Samsara BioCapital, L.P.
Exhibits
We note you intend to file the form of preliminary proxy card as Exhibit 99.1. Please note
that the form of proxy card should be filed as an appendix rather than as an exhibit to the 27.

July 18, 2024
Page 5
registration statement. Refer to the Note to paragraph (a)(3) of Exchange Act Rule 14a-4.
General
28.Please provide us your analysis as to whether Reneo Pharmaceuticals, Inc. is a shell
company as defined in Rule 12b-2 of the Exchange Act or whether it could become one
prior to the closing of the merger. For guidance, see Special Purpose Acquisition
Companies, Shell Companies, and Projections, Release No. 33-11265 (January 24, 2024)
at nt. 943.
            We remind you that the company and its management are responsible for the accuracy
and adequacy of their disclosures, notwithstanding any review, comments, action or absence of
action by the staff.
            Refer to Rules 460 and 461 regarding requests for acceleration. Please allow adequate
time for us to review any amendment prior to the requested effective date of the registration
statement.
            Please contact Gary Newberry at 202-551-3761 or Lynn Dicker at 202-551-3616 if you
have questions regarding comments on the financial statements and related matters. Please
contact Tyler Howes at 202-551-3370 or Tim Buchmiller at 202-551-3635 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:Jonn R. Beeson, Esq.