<SEC-DOCUMENT>0000950123-24-006650.txt : 20241108
<SEC-HEADER>0000950123-24-006650.hdr.sgml : 20241108
<ACCEPTANCE-DATETIME>20240718172818
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ACCESSION NUMBER:		0000950123-24-006650
CONFORMED SUBMISSION TYPE:	DRSLTR
PUBLIC DOCUMENT COUNT:		2
FILED AS OF DATE:		20240718

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			Upstream Bio, Inc.
		CENTRAL INDEX KEY:			0002022626
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		ORGANIZATION NAME:           	03 Life Sciences
		IRS NUMBER:				000000000
		STATE OF INCORPORATION:			DE
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		DRSLTR

	BUSINESS ADDRESS:	
		STREET 1:		890 WINTER STREET, SUITE 200
		CITY:			WALTHAM
		STATE:			MA
		ZIP:			02451
		BUSINESS PHONE:		781-208-2466

	MAIL ADDRESS:	
		STREET 1:		890 WINTER STREET, SUITE 200
		CITY:			WALTHAM
		STATE:			MA
		ZIP:			02451
</SEC-HEADER>
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<TYPE>DRSLTR
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<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Goodwin Procter</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">100 Northern Avenue</P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Boston, Massachusetts 02210</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">goodwinlaw.com</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">+1 617 570 1000</P></TD></TR>
</TABLE> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">July&nbsp;18, 2024 </P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">100 F Street,
NE </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Washington, D.C. 20549 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Attention: Chris Edwards, Jimmy
McNamara, Kevin Kuhar and Franklin Wyman </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">Re:</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left">Upstream Bio, Inc. </P></TD></TR></TABLE>
<P STYLE="margin-top:0pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">Draft Registration Statement on Form <FONT STYLE="white-space:nowrap">S-1</FONT> </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">Submitted June&nbsp;12, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">CIK
No.&nbsp;0002022626 </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Dear Ladies and Gentlemen: </P>
<P STYLE="margin-top:6pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">This letter is confidentially submitted on behalf of Upstream Bio, Inc. (the &#147;Company&#148;) in response to the comments of the staff of
the Division of Corporation Finance (the &#147;Staff&#148;) of the Securities and Exchange Commission with respect to the Company&#146;s Draft Registration Statement on Form <FONT STYLE="white-space:nowrap">S-1</FONT> submitted on June&nbsp;12, 2024
(the &#147;Draft Registration Statement&#148;), as set forth in your letter dated July&nbsp;9, 2024 addressed to E. Rand Sutherland, Chief Executive Officer of the Company (the &#147;Comment Letter&#148;). The Company is concurrently confidentially
submitting Amendment No.&nbsp;1 to the Draft Registration Statement (the &#147;Amended Draft Registration Statement&#148;), which includes changes that reflect responses to the Staff&#146;s comments and other updates. </P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">For reference purposes, the text of the Comment Letter has been reproduced herein with responses below each numbered comment. For your
convenience, we have italicized the reproduced Staff comments from the Comment Letter. Unless otherwise indicated, page references in the descriptions of the Staff&#146;s comments refer to the Draft Registration Statement, and page references in the
responses refer to the Amended Draft Registration Statement. All capitalized terms used and not otherwise defined herein shall have the meanings set forth in the Amended Draft Registration Statement. </P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">The responses provided herein are based upon information provided to Goodwin Procter&nbsp;LLP by the Company. In addition to submitting this
letter via EDGAR, we are sending this letter and the Amended Draft Registration Statement (marked to show changes from the Draft Registration Statement) via email. </P>
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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange
Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">July 18, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"> Page
 2
 </P> <P STYLE="font-size:12pt; margin-top:0pt; margin-bottom:0pt">&nbsp;</P>
 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Prospectus Summary </U></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Overview, page 1 </U></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">1.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your disclosure here, and throughout the prospectus, that verekitug is a <FONT
STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">&#147;first-in-class</FONT></FONT> antagonist.&#148; This term suggests that your product candidate is effective and likely to be approved. Please revise to delete such references
throughout your registration statement.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and
directs the Staff to its response to Comment 6 below. Based on the Company&#146;s reasonable diligence to date, as described in Comment 6 below, verekitug is the only monoclonal antibody currently in clinical development that targets and inhibits
the TSLP receptor, supporting the Company&#146;s statement that verekitug is a <FONT STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">&#147;first-in-class</FONT></FONT> antagonist of the receptor for TSLP.&#148; The Company respectfully
disagrees with the Staff&#146;s comment that this term suggests effectiveness or likelihood of approval, as it simply means it is the only publicly known antagonist of the receptor for TSLP. The Company also respectfully directs the Staff to the
balancing disclosure on pages 7 and 28 that this unique mechanism of action makes it difficult to predict verekitug&#146;s likelihood of success and the timing and cost of development and obtaining regulatory approval. </P>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">2.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your disclosures relating to the regulatory approvals and commercial successes of other companies.
Please provide balancing disclosure, as you do on page 36, that such companies may have significantly greater financial resources and expertise such that they may be more successful than you in obtaining regulatory approvals and achieving widespread
market acceptance.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff
that it has revised the disclosure on page 7. </P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">3.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Please clarify, if true, that the $6 to $10</I><I></I><I>&nbsp;billion estimation refers to global annual
peak sales, or otherwise advise and please provide balancing disclosure that you do not have a COPD product in development.</I> </P></TD></TR></TABLE>
<P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and directs the Staff to the revised disclosure on pages&nbsp;1, 115
and 131, which clarifies that the $6 to $10&nbsp;billion estimation refers to annual peak sales in the United States. The Company also respectfully advises the Staff that it has revised the disclosure on pages 2, 5, 116, 119, 120, 145 and 146
regarding the initiation of development efforts in COPD and directs the Staff to its response to Comment 10 below. </P>
 <p STYLE="margin-top:0pt;margin-bottom:0pt ; font-size:8pt">&nbsp;</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">2 </P>

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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange
Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">July 18, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"> Page
 3
 </P> <P STYLE="font-size:12pt; margin-top:0pt; margin-bottom:0pt">&nbsp;</P>

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<TD WIDTH="4%" VALIGN="top" ALIGN="left">4.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your disclosures on page 2, and elsewhere, regarding comparing your product candidate to tezepelumab
and dupilumab. Please disclose here, and in the Business section, whether such observations were based on <FONT STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">head-to-head</FONT></FONT> trials. In this regard, we note your disclosure on
page 35 that &#147;[i]n most cases, [you] do not currently plan to run <FONT STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">head-to-head</FONT></FONT> clinical trials evaluating verekitug or any other potential future product candidates
against the current standards of care, which may make it more challenging for verekitug or any other potential future product candidates to compete against the current standards of care due to the lack of <FONT STYLE="white-space:nowrap"><FONT
STYLE="white-space:nowrap">head-to-head</FONT></FONT> clinical trial data.&#148;</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully
acknowledges the Staff&#146;s comment and advises the Staff that it has revised the disclosure on pages 2, 115, 132, 143 and 144. The Company further respectfully advises the Staff that it does not believe <FONT STYLE="white-space:nowrap"><FONT
STYLE="white-space:nowrap">head-to-head</FONT></FONT> clinical trials are necessary to support the development of verekitug, as regulatory authorities would not typically require such a trial to establish the safety and efficacy of a new biologic
product. </P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">5.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>With respect to the data and observations based on preclinical and clinical trials disclosed in the summary,
including those sponsored by others, please disclose whether serious adverse events were observed.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The
Company respectfully acknowledges the Staff&#146;s comment and directs the Staff to the disclosure starting on page&nbsp;134 that there was one subject in Cohort D of the Phase 1 SAD clinical trial who experienced a serious treatment-emergent
adverse event, nephrolithiasis, which was deemed not related to the study drug by the investigator. No other serious adverse events have been observed by the Company or a third party throughout verekitug&#146;s clinical development. Furthermore, the
Company respectfully advises the Staff that adverse events, by definition, are occurrences in human subjects in clinical trials, and are not observed in preclinical studies. </P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">6.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Please explain how you determined on page 2 that verekitug is the only monoclonal antibody currently in
clinical development that targets and inhibits the TSLP receptor.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges
the Staff&#146;s comment and advises the Staff that it explored numerous sources, including an industry standard market intelligence database, company press releases and clinicaltrials.gov listings, to gain an understanding of the competitive
landscape for product candidates in clinical development involving the TSLP receptor. Based on such evaluation, to our knowledge, verekitug is the only monoclonal antibody currently in clinical development that targets and inhibits the TSLP
receptor. </P>
 <p STYLE="margin-top:0pt;margin-bottom:0pt ; font-size:8pt">&nbsp;</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">3 </P>

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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange
Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">July 18, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"> Page
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">7.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note that you describe the Phase 2 trial as &#147;pivotal.&#148; Please clarify what you mean by pivotal
in this instance.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff
that it has revised the disclosure on pages 2, 5, 116, 119, 120 and 145. </P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">8.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Please define &#147;FPI&#148; in the pipeline table on page 2 and revise the footnote to the table to
explain the activities that need to be completed in order to initiate development in COPD.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company
respectfully acknowledges the Staff&#146;s comment and advises the Staff that it has revised the pipeline table appearing on pages 2 and 116 to indicate that development in COPD has been initiated. </P>
<P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>TSLP Overview, page 3 </U></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">9.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your statement that you believe </I><I>verekitug</I><I> has the potential to be an impactful
treatment due to its high potency, extended dosing interval and ability to address unmet needs in multiple diseases characterized by TSLP-driven pathobiology. Please revise to remove these and similar statements, as efficacy determinations are
within the sole jurisdiction of the FDA and other similar foreign regulators. You may include information regarding data observed in studies and trials but may not include the company&#146;s conclusions based on such data</I><I>.</I>
</P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it has revised the
disclosure on pages 3 and 117 to clarify that the Company&#146;s beliefs about the potential of verekitug are based on preclinical and clinical data observed to date, rather than determinations that have been made by the FDA or similar foreign
regulators. </P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Verekitug: Inhibiting TSLP signaling in severe asthma, CRSwNP and COPD, page 4</U> </P>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">10.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Please disclose when you plan to initiate clinical development in COPD.</I> </P></TD></TR></TABLE>
<P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it has revised the disclosure on pages 2,
5, 116, 119, 120 and 146. </P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">11.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your disclosures regarding results from preclinical and clinical trials demonstrating that verekitug
inhibited TSLP signaling, inhibited cytokine production from CD4+ T cells, and demonstrated &#147;rapid, substantial and sustained target engagement&#148; and maintained &#147;maximal inhibition of disease-related biomarkers&#148; in patients with
asthma. Please disclose whether such results are statistically significant, or otherwise advise. </I> </P></TD></TR></TABLE>
 <p STYLE="margin-top:0pt;margin-bottom:0pt ; font-size:8pt">&nbsp;</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">4 </P>

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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange
Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">July 18, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"> Page
 5
 </P> <P STYLE="font-size:12pt; margin-top:0pt; margin-bottom:0pt">&nbsp;</P>
 <P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the
Staff the goal of preclinical studies, among other things, is to assess the biological effect a drug may have in animals and pharmacology models, and thus to predict responses in human patients and identify potential toxicities. As such, these
preclinical studies were designed to model and observe these factors, rather than to achieve statistical significance. In addition, the Company respectfully advises the Staff that the Phase 1 SAD and MAD clinical trials were designed as &#147;signal
seeking&#148; trials, and not based on a formal statistical hypothesis to achieve statistical significance. The Company has revised its disclosure on pages 2, 4, 5, 116, 118, 131, 133 and 144 to clarify that its preclinical studies and clinical
trials completed to date were not designed to support formal statistical comparisons. Furthermore, the Company respectfully advises the Staff that subsequent clinical trials in humans may be designed for statistical significance and that it will
report the details of such clinical trials as applicable. </P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">12.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Please disclose the number of volunteers for the Phase 1 SAD trial and Phase 1b MAD trial.</I>
</P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it has revised the
disclosure on page 5. The Company also respectfully directs the Staff to the Phase 1 SAD and MAD clinical trial designs described on pages 134 and 137, respectively. </P>
<P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Our Team and Investors, page 5 </U></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">13.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your disclosure on page 6 that you have raised approximately $400</I><I></I><I>&nbsp;million from
&#147;premier biotechnology investors.&#148; Please provide balancing disclosure that prospective investors should not rely on such investors&#146; investment decisions, that these investors may have different risk tolerances and that the shares
purchased in the referenced financings may have been conducted at a significant discount to the IPO price, if true.</I> </P></TD></TR></TABLE>
<P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it has revised the disclosure on pages 6
and 119. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Management&#146;s Discussion and Analysis of Financial Condition and Results of Operations Critical Accounting Estimates and Significant
Judgments </U><U>Stock-based compensation, page 109</U> </P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">14.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Once you have an estimated offering price range, please explain to us the reasons for any differences
between recent valuations of your common stock leading up to the planned offering and the midpoint of your estimated offering price range. This information will facilitate our review of your accounting for stock compensation.</I>
</P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and will supplementally provide the requested
information once the estimated offering price range has been determined. </P>
 <p STYLE="margin-top:0pt;margin-bottom:0pt ; font-size:8pt">&nbsp;</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">5 </P>

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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange
Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">July 18, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"> Page
 6
 </P> <P STYLE="font-size:12pt; margin-top:0pt; margin-bottom:0pt">&nbsp;</P>
 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Business </U></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>The role of TSLP in severe asthma, CRSwNP, COPD and related inflammatory diseases, page 121</U> </P>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">15.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Please revise Figure 2 on page 122 to clarify the diseases you are planning to target with your drug
candidate.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it
has revised Figure 2 appearing on page 123. </P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Biologic therapies for severe asthma, page 124 </U></P>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">16.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your disclosure that the clinical and regulatory progress of </I><I>tezepelumab</I><I> represents a
</I><I>&#147;</I><I>significant </I><I>derisking</I><I>&#148;</I><I> for your own development program. Please remove this statement and any other statements that imply that you will be successful in mitigating risk associated with drug
development.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it
has revised the disclosure on page 125. </P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Preclinical Data </U></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Target engagement and inhibition, page 132 </U></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">17.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>With respect to the preclinical studies, please disclose, if true, that Astellas conducted such studies, or
otherwise advise. In addition, please disclose if the results were statistically significant, and any observed serious adverse events.</I> </P></TD></TR></TABLE>
<P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it has revised the disclosure on page 133.
The Company also respectfully directs the Staff to the disclosure on pages 4, 118 and 134 stating that the preclinical studies and Phase 1 SAD trial were conducted by Astellas. The Company respectfully acknowledges the Staff&#146;s request to
disclose whether the results were statistically significant and whether there were any observed serious adverse events, and directs the Staff to its above responses to Comment 11 and Comment 5, respectively. </P>
 <p STYLE="margin-top:0pt;margin-bottom:0pt ; font-size:8pt">&nbsp;</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">6 </P>

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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange
Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">July 18, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"> Page
 7
 </P> <P STYLE="font-size:12pt; margin-top:0pt; margin-bottom:0pt">&nbsp;</P>
 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Phase 1 SAD clinical trial safety and tolerability data, page 135 </U></P>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">18.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Please ensure the superscripts are legible in the graphic.</I> </P></TD></TR></TABLE>
<P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it has revised Figure 8 appearing on page
135. </P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Ongoing and planned clinical trials, page 143 </U></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">19.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Please disclose the number of patients enrolled to date in the VIBRANT and VALIANT trial.</I>
</P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and directs the Staff to the disclosure on
page&nbsp;145 stating the estimated number of patients that the Company expects to enroll in each trial. Due to the competitive landscape in which the Company is operating and other ongoing clinical trials in the indications in which the Company is
developing its product candidate, the number of patients enrolled to date is highly confidential information and subject to change over time, and as such, the Company does not plan to include this disclosure in its future public filings. The
projected timing for announcement of <FONT STYLE="white-space:nowrap">top-line</FONT> data reflects the Company&#146;s assessment of current enrollment status and the time needed for patients to complete the assessments in each trial. Accordingly,
the Company has revised the disclosure on page 145 to clarify the basis for the projected <FONT STYLE="white-space:nowrap">top-line</FONT> data readouts for the VIBRANT and VALIANT trials. </P>
<P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>COPD, page 144 </U></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">20.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>Please clarify whether the &#147;additional endpoints&#148; will be primary or secondary, or otherwise
advise.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it has
revised the disclosure on page 146. </P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Intellectual Property, page 146 </U></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">21.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your disclosures relating to your owned patent families. We also note your disclosure on page 149
regarding licensing certain intellectual property from Lonza. Please disclose, if material, whether you license any patents. To the extent you do, please disclose the type of patent protection (e.g., composition of matter, use, or process), the
patent expiration dates, and the applicable jurisdictions. In addition, please clarify what indications the Lonza license covers.</I> </P></TD></TR></TABLE>
<P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that the Lonza License Agreement does not
include a license of patents that it considers to be material to its business or pipeline and as such, the current disclosure starting on page&nbsp;147 remains accurate and complete. The material intellectual property rights licensed from Lonza
under the Lonza License Agreement relate to manufacturing <FONT STYLE="white-space:nowrap">know-how</FONT> that is not specific to an indication. </P>
 <p STYLE="margin-top:0pt;margin-bottom:0pt ; font-size:8pt">&nbsp;</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">7 </P>

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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange
Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">July 18, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"> Page
 8
 </P> <P STYLE="font-size:12pt; margin-top:0pt; margin-bottom:0pt">&nbsp;</P>
 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Asset purchase and license agreements, page 148 </U></P>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">22.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>With respect to the Maruho and Lonza license agreements, please disclose the payments received or made to
date, any expiration dates, and any potential development, regulatory and commercial milestone payments.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE:
The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that it has revised the disclosure on pages 98, 107, 150 and 151 to include all payments received or made to date under the Maruho License Agreement and Lonza
License Agreement, as applicable. The license granted to the Company under each agreement does not have a specified expiration date. In addition, the Company respectfully directs the Staff to its disclosure starting on page 149 discussing the
Company&#146;s obligation to develop the Maruho License Product for use in Japan, which will result in development and regulatory expenses to be reimbursed by Maruho, and describing the royalty payments due to Lonza under the Lonza License
Agreement. There are no other potential development, regulatory or commercial milestone payments under the Maruho License Agreement or Lonza License Agreement that are not described in the Amended Draft Registration Statement. </P>
<P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Executive Compensation </U></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Executive compensation
arrangements, page 185 </U></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">23.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your disclosure that you have entered into employment agreements with each of your named executive
officers. Please describe the material terms of such agreements with your current CEO and CFO. In addition, please file the employment or offer letter agreements with your executive officers as exhibits pursuant to Item 601(b)(10) of Regulation <FONT
STYLE="white-space:nowrap">S-K</FONT> or tell us why you believe such filing is not required.</I> </P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company
acknowledges the Staff&#146;s request to file the employment or offer letter agreements with its executive officers as exhibits, and respectfully advises the Staff that prior to effectiveness of the registration statement, the Company intends to
enter into new employment agreements with its executive officers that supersede and replace their existing offer letters in all respects. The Company undertakes to update the registration statement to include appropriate disclosure regarding these
new employment agreements in the Executive Compensation section as requested, and to file such agreements, pursuant to Item 601(b)(10), prior to the effectiveness of the registration statement. </P>
<P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>Certain relationships and related party transactions, page 195 </U></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">24.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>We note your disclosure on page 95 that Maruho, for which you have an exclusive license agreement, is a
related party. We also note on page 175 that Atsushi Sugita, who has served on your Board of Directors since 2021, is also the President and CEO of Maruho. Please disclose any related party transactions under Item 404(a) of Regulation SK or
otherwise advise. Also, please tell us whether any other officers, directors or principal shareholders are affiliated with Maruho. Finally, please provide, if material, corresponding risk factor disclosure.</I> </P></TD></TR></TABLE>
 <p STYLE="margin-top:0pt;margin-bottom:0pt ; font-size:8pt">&nbsp;</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">8 </P>

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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange
Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">July 18, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"> Page
 9
 </P> <P STYLE="font-size:12pt; margin-top:0pt; margin-bottom:0pt">&nbsp;</P>
 <P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the
Staff that it has revised page 201 to disclose the Maruho License Agreement as a related party transaction. Other than Mr. Sugita, no officers, directors or principal shareholders of the Company are affiliated with Maruho. </P>
<P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">The Company respectfully directs the Staff to the risk factors entitled &#147;<I>Our existing research and development arrangement as well as
any future collaborations with third parties for the development and commercialization of verekitug or any other potential future product candidates may not be successful, which could adversely affect our ability to advance verekitug or any other
potential future product candidates</I>&#148; starting on page 42, discussing risks associated with the Maruho License Agreement and similar potential future arrangements and collaborations, and &#147;<I>Our executive officers, directors, principal
stockholders and their respective affiliates own a significant percentage of our stock and will be able to exert significant control over matters subject to stockholder approval</I>&#148; appearing on page 74, discussing risks associated with the
influence of its directors, officers and principal stockholders. The Company respectfully advises the Staff that there are no additional material risks associated with the Maruho License Agreement due to Maruho&#146;s status as a related party or
Mr.&nbsp;Sugita&#146;s affiliation with Maruho that are not described in the Amended Draft Registration Statement. </P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><U>General </U></P>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">25.</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><I>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, present to potential investors in reliance on Section</I><I></I><I>&nbsp;5(d) of the Securities Act, whether or not they retain copies of the communications.</I>
</P></TD></TR></TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">RESPONSE: The Company respectfully acknowledges the Staff&#146;s comment and advises the Staff that the Company will
undertake to provide the Staff with any such written communications that the Company, or any authorized to do so on behalf of the Company, has presented or will present to potential investors in reliance on Section&nbsp;5(d) of the Securities Act.
</P>
 <p STYLE="margin-top:0pt;margin-bottom:0pt ; font-size:8pt">&nbsp;</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">9 </P>

</DIV></Center>


<p style="margin-top:1em; margin-bottom:0em; page-break-before:always"> </p>
<HR SIZE="3" style="COLOR:#999999" WIDTH="100%" ALIGN="CENTER">


<Center><DIV STYLE="width:8.5in" align="left">

 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Division of Corporation Finance </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Office of Life Sciences </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">United States Securities and Exchange
Commission </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">July 18, 2024 </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"> Page
 10
 </P> <P STYLE="font-size:12pt; margin-top:0pt; margin-bottom:0pt">&nbsp;</P>
 <P STYLE="margin-top:0pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">If you should have any questions concerning the enclosed matters, please contact the
undersigned at (617) <FONT STYLE="white-space:nowrap">570-1329.</FONT> </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><DIV ALIGN="right">
<TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="40%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt">


<TR>

<TD WIDTH="100%"></TD></TR>


<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top">Sincerely,</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Gabriela Morales-Rivera</TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top">Gabriela Morales-Rivera, Esq.</TD></TR>
</TABLE></DIV> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">cc:</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left">E. Rand Sutherland, M.D., M.P.H., <I>Upstream Bio, Inc.</I> </P></TD></TR></TABLE>
<P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">Michael Paul Gray, M.B.A., <I>Upstream Bio, Inc.</I> </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">William D. Collins, Esq., <I>Goodwin Procter LLP</I> </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">Kathryn W. Clerici, Esq.<I>, Goodwin Procter LLP</I> </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">Kristin VanderPas, Esq., <I>Cooley LLP</I> </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">Dave Peinsipp, Esq., <I>Cooley LLP</I> </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">Denny Won, Esq., <I>Cooley LLP</I> </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:4%; font-size:10pt; font-family:Times New Roman">Charles S. Kim, Esq., <I>Cooley LLP</I> </P>
 <p STYLE="margin-top:0pt;margin-bottom:0pt ; font-size:8pt">&nbsp;</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">10 </P>

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