SecProbe.io

CORRESP
1
filename1.htm

      March 19, 2024

    Page 1

    March 19, 2024

    VIA EDGAR

    U.S. Securities and Exchange Commission

    Division of Corporation Finance

    Office of Life Sciences

    100 F Street, N.E.

    Washington, D.C. 20549

          Attn:

            Mr. Eric Atallah
              Ms. Lynn Dicker

              Mr. Daniel Crawford

              Mr. Alan Campbell

          Re:

            APRINOIA Therapeutics Inc.
              Amendment No. 1 to Registration Statement on Form F-1

              Filed February 26, 2024

              File No. 333-276696

    Ladies and Gentlemen:

    On behalf of our client, APRINOIA Therapeutics Inc. (the “Company”), we are responding to the comments of the staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”) contained in the letter dated March 5, 2024 (the “Comment Letter”) in relation to the above-captioned Amendment No. 1 to Registration Statement on Form F-1 (the “Amendment No. 1”).

    Set forth below are the Company’s responses to the Comments. The Staff’s comments are repeated below in bold and are followed by the Company’s responses. Page references in the text of this response
      letter correspond to the page numbers of the Amendment No. 1. Capitalized terms used but not defined herein are used herein as defined in Amendment No. 1.

    As certain of the Staff’s comments may result in further changes to the Company’s disclosure, the Company intends to file Amendment No. 2 to the Company’s Registration Statement on Form F-1 after it
      receives the Staff’s further comments to the Company’s responses herein.

    55 Hudson Yards, New York, New York 10001-2157

    t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

    March 19, 2024

    Page 2

    Amendment No. 1 to Registration Statement on Form F-1

    Prospectus Summary

    Overview, page 1

              1.

              We note your revised disclosure in response to prior comment 1 and reissue in part. Please revise to describe the ADDF’s “rigorous scientific review process.”

    In response to the Staff’s comment, the Company proposes to revise the disclosure in relation to the ADDF’s “rigorous scientific review process” on pages 3 and 88 of Amendment No. 1 as follows (with
      changes marked in italics, deletions a strike-through and additions underlined):

    “Our tau degrader program is supported by Alzheimer’s Drug Discovery Foundation (“ADDF”) following their rigorous scientific review of the program which included an independent review by external scientists from academia and industry, who are members of the foundation’s Scientific Review Board in addition to a review by members of the
      foundation’s process Business Review Board.”

    Our Pipeline, page 4

              2.

              We note your revised disclosure indicating that you plan to submit an NDA for APN-1607 in the fourth quarter of 2026. Given that you have yet to commence or complete the Phase 3 trial for
                this product candidate, please revise here and throughout to remove this statement. You may state when you anticipate commencing the pivotal trial for APN-1607.

    In response to the Staff’s comment, the Company proposes to revise the disclosure in relation to the NDA submission for APN-1607 on pages 5, 90, 95 and 102 of Amendment No. 1 as follows (with changes
      marked in italics, deletions a strike-through and additions underlined):

    Pages 5, 90 and 95 of Amendment No. 1:

    “We plan to implement this trial in the fourth quarter of 2024 in the United States, Europe, the United Kingdom, Japan and Taiwan and submit results from
          this trial, if positive, in an NDA as a basis for regulatory approval in the United States in the fourth quarter of 2026, and subsequently seek marketing authorization in Europe and Asia.”

    Page 102 of Amendment No. 1:

    “We plan to implement this trial in the fourth quarter of 2024 in the United States, Europe, the United Kingdom, Japan and Taiwan and submit results from
          this trial, if positive, in an NDA as a basis for regulatory approval in the United States in the fourth quarter of 2026, and subsequently seek marketing authorization in Europe and Asia. We plan to implement the trial in the United States,
          Europe, the United Kingdom, Japan and Taiwan and submit results from this trial, if positive, as a basis for regulatory approval in the United States, with the eventual goal of gaining marketing authorization in Europe and Asia.”

      55 Hudson Yards, New York, New York 10001-2157

      t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

    March 19, 2024

    Page 3

    Risk Factors

    General Risk Factors

    An active trading market for our ordinary shares may not be available…., page 53

              3.

              Please revise this risk factor to clearly state that stock price volatility, including any stock-run up, may be unrelated to your actual or expected operating performance and financial
                condition or prospects, making it difficult for prospective investors to assess the rapidly changing value of your stock.

    In response to the Staff’s comment, the Company proposes to revise the disclosure to include the following paragraph to the end of this risk factor on page 54 of Amendment No. 1:

    “Further, the stock market in general has experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating
        performance of companies. The stock price volatility, including any stock run up, may be unrelated to our actual or expected operating performance and financial condition or prospects. As a result, potential investors may find it difficult to
        assess the rapidly changing value of our securities.”

    Capitalization, page 64

              4.

              Please revise your filing to clearly describe the nature of the transaction that resulted in a $4.45 million increase to your cash on a pro forma basis.

    In response to the Staff’s comment, the Company proposes to revise the disclosure to include the following note to describe the nature of the $4.45 million increase to the Company’s cash on a pro
      forma basis on page 64 of Amendment No. 1:

    “(3)    Cash as of June 30, 2023 on a pro forma basis increases by $4.45 million compared to our cash as of June 30, 2023 on an actual basis, reflecting, subsequent
        to June 30, 2023 and up to the date of this prospectus, (i) the issuance of four new convertible promissory notes for an aggregate of cash proceeds of $4.50 million, and (ii) the repayment of one convertible promissory note for $0.05 million. See
        “Management’s Discussion and Analysis of Financial Condition and Results of Operations — Subsequent Events — Issuance and Renewal of Convertible Promissory Notes” for more details.”

    Management’s Discussion and Analysis of Financial Condition and Results of Operations

    Share-Based Compensation, page 83

              5.

              We note that you have updated your filing with an estimated price range. As previously requested in comment 15 of our December 8, 2023 comment letter, 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. Please discuss with the staff how to submit your response.

    The Company respectfully advises the Staff that it has submitted the response through confidential submission system.

      55 Hudson Yards, New York, New York 10001-2157

      t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

    March 19, 2024

    Page 4

    Business

    Summary of Safety for APN-1607, page 94

              6.

              We note your revised disclosure in response to prior comment 3. Please revise to remove your statement that APN-1607 “was demonstrated to have a favorable safety profile.” You may describe
                the data supporting your conclusion.

    In response to the Staff’s comment, the Company proposes to revise the disclosure on page 94 of Amendment No. 1 as follows (with changes marked in italics and deletions a strike-through):

    “As of May 31, 2023, between investigator initiated and our studies, APN-1607 had been administered to approximately 2,853 healthy adults and patients with a broad range of primary and secondary
      tauopathies, including PSP, as well as other disorders associated with tau aggregation, such as AD, FTD, CBS, and traumatic brain injury. A total of 67 AEs and one SAE had been reported by 43 subjects. The SAE was not attributed to APN-1607 and all
      AEs were mild or moderate in severity, resolved without intervention and, importantly, were also not considered to be related to APN-1607. Across all sponsor- and investigator-initiated studies, APN-1607 was well tolerated, and was demonstrated to have a favorable safety profile.”

    Preclinical Results, page 105

              7.

              We note your revised disclosure providing data from preclinical tests for APNmAb005. Please revise to state whether any of these tests were powered for statistical significance. If so,
                revise to provide the p-values and state whether the results were statistically significant.

    In response to the Staff’s comment, the Company proposes to revise relevant disclosure in relation to preclinical results on pages 106, 107, 110 and 111 of Amendment No. 1 as follows (with changes
      marked in italics, deletions a strike-through and additions underlined):

    Pages 106 and 107 of Amendment No. 1:

    “One of the lessons learned from the development of anti-amyloid antibody in the past 20 years is the importance of selective binding to disease relevant proteins, which reduces side effects but also
      allows for more effective treatment. As shown in the figure below, APNmAB005 shows selectivity for selective binding to pathological forms of
      tau in AD brains but not normal tau. The data is a representative of at least three independent dot blot binding assays and error bars are the standard deviations
          of three replicates in the experiment.

        55 Hudson Yards, New York, New York 10001-2157

        t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

    March 19, 2024

    Page 5

    Evidence for a pharmacodynamic effect for APNmAb005 is shown in the figure below, where APNmAB005 is shown to dose dependently block tau seeding in a
      cellular assay. It is believed that pathological tau released to extracellular space entering normal cells can act as seeds to promote tau aggregate development and contribute to disease progression.  In this
          experiment incubation of tau from brain lysates led to the development of tau aggregates as detected by antibody staining (green spots in upper panels) while co-incubation with APNmAb005 reduced tau aggregates by approximately 60%. The graph on
          the right is representative of more than three independent runs of quantification of tau aggregates by high content imaging analysis.  Error bars represent standard deviation of images from n=9 replicate wells in a 96-well plate dose
          dependent manner in a well-established in vitro model of tau seeding, a phenomenon that is believed to occur in the AD brain and contributes to disease progression.

    “In addition, as shown in the figure below, chronic administration of APNmAb005 significantly ameliorates the neuronal loss in CA1 region in rTg4510
      mice, an animal model that genetically overexpresses human tau mutant P301L protein. A high dose of APNmAb-005

          can neutralize APNmAb005 neutralizes the secreted tau and reduce reduces
      the synaptic loss. The figure on the left shows representative immunostaining of the hippocampal formation with NeuN antibody and the figure on the right is the image quantification. The group size n=15 was
          designed to achieve 80% power of the study and the statistics was using One-Way ANOVA in GraphPad software.

    ”

      55 Hudson Yards, New York, New York 10001-2157

      t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

    March 19, 2024

    Page 6

    Page 110 of Amendment No. 1:

    “Preclinical Results and Plans

    Using our cellular tau degrader assay we have identified compounds that may selectively degrade the pathological tau aggregates while sparing the native (healthy) tau. As shown below, these results
      were confirmed in a rat primary neuron assay. Our lead compound (TPD-3) has demonstrated in vivo degradation activity in a mouse tauopathy model. Our current effort is focusing on further screening and optimizing the physicochemical properties of tau
      degraders with the goal to identify lead candidates for IND-enabling preclinical studies and eventual clinical development. The cellular assays in A and B are representatives of more than three independent runs
          and error bars are SD of n=3 replicates in one experiment. The graph in C is the preliminary study of a single intravenous dose at 25 mg/kg.

    ”

    Page 111 of Amendment No. 1:

    “Preclinical Results

    We have developed a human dopaminergic neuronal model to test α-Syn soluble oligomer degradation with our compounds. Upon screening with our proprietary degrader library, we have identified several
      α-Syn degraders as shown in A and B below, which demonstrate characteristics of a PROTAC-based mechanism resulting in proteasome-mediated degradation (see
          figures below as shown in C). The cellular data here are representative of more than three independent runs and error bars are
          standard deviation from three replicate wells in a 96-well plate. Our lead Compound (TPD-2) has also shown degradation of α-Syn in a transgenic mouse model expressing human wild-type α-Syn after
          given a single intravenous dose at 25 mg/kg. Our current effort, including toxicology studies, is focusing on optimizing the drug properties of our degrader for preclinical candidate selection and eventual clinical development.

    ”

      55 Hudson Yards, New York, New York 10001-2157

      t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

    March 19, 2024

    Page 7

    License Agreements and Collaborations

    Research Collaboration Agreement with Lundbeck and Abbvie, page 112

              8.

              We note your response to prior comment 4 and reissue in part. Please revise to describe the material terms of your agreement with Lundbeck and AbbVie, including the obligations of all
                parties to the agreement, the aggregate payments made and/or received to date, the aggregate amounts of all potential milestone payments, quantify any royalty rates or provide a reasonable range, disclose who will own rights to technologies
                arising from the collaboration, who will have commercialization rights and disclose term and termination provisions. To the extent that any of these terms have not been negotiated pursuant to the existing collaboration agreement, please
                advise.

    In response to the Staff’s comment, the Company respectfully advises the Staff that (i) no milestone payments, royalty rates or range, or other monetary obligations have been negotiated pursuant to
      the existing collaboration agreements, (ii) as such, no payments have been made or received to date, and (iii) no commercialization rights have been negotiated pursuant to the existing collaboration agreements. The Company further proposes to revise
      the disclosure in relation to the research collaboration agreement with Lundbeck and Abbvie on page 112 of Amendment No. 1 as follows to add more description of the obligations of all