SEC Company Response from Annovis Bio, Inc. (ANVS) (CIK 0001477845) (ANVS) — Jul 2, 2019
Annovis Bio, Inc. (ANVS) (CIK 0001477845)
Date: July 2, 2019 · CIK: 0001477845 · Accession: 0001104659-19-039166
AI Filing Summary & Sentiment
Reasoning
Referenced dates: June 21, 2019
Letter
NEW YORK
BALTIMORE
LONDON
WILMINGTON
SINGAPORE
MIAMI
PHILADELPHIA
FIRM and AFFILIATE OFFICES
BOCA RATON
CHICAGO
PITTSBURGH
WASHINGTON, DC
NEWARK
SAN FRANCISCO
LAS VEGAS
SILICON VALLEY
CHERRY HILL
SAN DIEGO
www.duanemorris.com
LAKE TAHOE
BOSTON
MYANMAR
HOUSTON
OMAN
LOS ANGELES
A GCC REPRESENTATIVE OFFICE
HANOI
OF DUANE MORRIS
HO CHI MINH CITY
ATLANTA
MEXICO CITY
ALLIANCE WITH
MIRANDA & ESTAVILLO
July 2, 2019
VIA EDGAR AND FEDEX
Division of Corporation Finance
Securities and Exchange Commission
100 F Street, N.E.
Washington, D.C. 20549
Re
Annovis Bio, Inc.
Amendment No. 1 Draft Registration Statement on Form S-1
Submitted May 24, 2019
CIK No. 0001477845
On behalf of our client, Annovis Bio, Inc. (the “Company”), we are responding to the comments of the staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”) contained in its letter dated June 21, 2019 (the “Comment Letter”) relating to the above referenced Amendment No. 1 to Confidential Draft Registration Statement (the “DRS”).
Set forth below are the Company’s responses to the Staff’s comments. The numbering of the paragraphs below corresponds to the numbering of the Staff’s comments, which for your convenience we have incorporated into this response letter. Page references in the text of this response letter correspond to the page numbers of the Registration Statement on Form S-1 filed today (the “Registration Statement”). We also describe below the changes the Company has made in response to the Staff’s comments in the Registration Statement and the prospectus included therein.
For the Staff’s convenience, we will send a copy of this letter, a clean copy of the Registration Statement and a copy of the Registration Statement marked to show all changes from the DRS via Federal Express.
Amendment No. 1 to Draft Registration Statement on Form S-1
Prospectus Summary, page 1
1. We note your disclosure on page 1 that you have a “ready program” to conduct a second Phase 2a study in PD patients. Please explain what you mean.
Response: The Company has revised the sentence on page 1 to remove these words and explain that it has planned to commence the Phase 2a study in PD patients.
2. We note your disclosure that you expect your lead compound to be efficacious and that you showed in studies that ANVS-401 was safe on page 1, that you expect to obtain FDA approval in 2024 on page 2 and that clinical studies and preclinical data have established and/or proven the safety or efficacy of ANVS-401 on page 3. As your product candidate has not received FDA approval, it is premature to suggest or imply that it is safe or effective. Also, there can be no certainty as to when or if you will receive FDA approval. Please revise your disclosure here and all similar statements throughout the prospectus accordingly. We will not object to statements that your product candidate was well-tolerated or to presentation in the Business section of the trial endpoints, the extent to which the end points were met or were not met, or the aggregate or summary data collected from your trials.
Response: The Company has modified its disclosure throughout the document to conform to this comment to remove suggestions or implications that ANVS-401 is safe or effective.
3. We note your disclosure on page 2 that successful termination of the Alzheimer’s disease and Parkinson’s disease study will “de-risk” ANVS-401 for use in neurodegenerative diseases and will validate the target and pathway. Please remove this statement and any other statements that imply that you will be successful in mitigating risk associated with drug development. Please also tell us what you mean by stating that termination of the study will validate the target and pathway.
Response: The Company has deleted this statement on page 2 and inserted a statement it intends as more descriptive regarding its plans for a Phase 3 study.
4. We note statements throughout that imply efficacy, such as “lowering their high levels of APP will restore axonal transport and homeostasis...and normalize their memory loss and dementia,” and “ANVS-401 treatment restores normal axonal transport and prevents or restores all those events all the way to preserving nerve cell health.” In addition, we note that your description of ANVS-401 under “Pathway Engagement” includes numerous statements claiming efficacy, such as “full recovery of memory, learning and brain function,” “normalizes all the functions that are negatively affected by disturbances of the transport,” and “normalizes the affected function in all diseases that we tested it in.” These are just examples. Please substantially revise your disclosure throughout your prospectus to remove these statements as determinations of efficacy are solely within the authority of the FDA.
Response: The Company has modified these statements throughout the document to remove and modify these statements so as not to imply efficacy. The Company has expressly referred to completed preclinical and clinical studies and the
results that have occurred in those studies in the past tense, with inclusion of data point information in a summary manner, so as not to imply efficacy in any present or future context. The Company has added a brief discussion of data points under “Our Company — Axonal Transport and Pathway Engagement — Pathway Engagement” on page 5 in the Summary and page 87 in the Business Section.
5. We note your statement here and in the Business section that you have an ongoing Phase 2a proof-of-concept study in AD patients. Please tell us the status of the study, including the number of patients enrolled and whether you have started the study. Please add similar disclosure in the Business section.
Response: The Company has added disclosure on page 2 and page 81 describing the status of the study, its commencement and the number of patients enrolled.
6. You state that you have conducted clinical trials with 125 humans and these trials have shown promising clinical signals, including normalized levels of neurotoxic proteins. However, it appears that these results were only observed in your proof of concept study in five patients with mild cognitive impairment. Please revise to remove the implication that the clinical signals you list were observed in 125 humans and clarify that the AD patients had only mild cognitive impairment.
Response: The Company has added disclosure to page 1 and page 81 to clarify the clinical signals were observed in five patients who had only mild cognitive impairment.
7. Please provide us with support for your statement that AD and PD are the two largest medical needs for the aging U.S. population and two potentially largest markets.
Response: The Company has modified this sentence on page 2 and page 82 to state that AD and PD are two of the largest medical needs for the aging U.S. population and two potentially large markets.
8. Please revise your statement that focusing on AD in the DS population “perfectly represents AD” as this statement suggests that your studies in this population will translate to approval in the AD population generally.
Response: The Company has revised this statement to indicate that DS population is substantially similar to AD population.
9. Please explain your references to Parexel and Posiphen, as there is no explanation in the prospectus as to the relevance of these terms.
Response: The Company has explained that Parexel as a clinical research organization on page 1. The Company has removed references to Posiphen, a prior informal name for ANVS-401, that was included in certain imbedded graphics in the DRS.
10. We note your disclosure on page 5 that you have a Scientific Advisory Board. Please describe the role or function of the Scientific Advisory Board and whether there are any
rules or procedures governing such board. Please also provide us with support for your statement that the board is composed of “world-renowned scientists.”
Response: The Company has described the role of the Scientific Advisory Board and stated that it has no rules or procedures governing the board, except for restrictions place on the members by their universities on page 7. We have also removed the term “world-renowned” with respect to the board members.
11. We note that you intend to conduct chronic toxicology studies in rats and dogs with the funds from the offering. Given that you are already testing ANVS-401 in humans, please explain the relevance of the animal toxicology study and whether it is necessary for you to continue studies in humans.
Response: The Company has added explanation on page 8 that the toxicology studies are needed in order to then test for extended periods in humans.
Implications of Being an Emerging Growth Company, page 7
12. 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 5(d) of the Securities Act, whether or not they retain copies of the communications.
Response: The Company or anyone authorized on its behalf, has not made any written communications to potential investors in reliance on Section 5(d) of the Securities Act.
Risk Factors We have concentrated our research and development efforts on the treatment of AD and PD..., page 18
13. Please revise this risk factor to provide detail regarding the particular challenges in obtaining FDA approval for AD and PD. For example, we note your statement on page 80 that since 2003, there have been over 500 clinical studies and no compound has shown efficacy.
Response: The Company has revised the risk factor on page 19 to add references to challenges in obtaining FDA approval for AD and PD.
If we fail to comply with our obligations under our existing intellectual property license, page 37
14. Please expand this risk factor to disclose the term of the license agreement and under what circumstances Horizon would be able to terminate your license.
Response: The Company added disclosure on page 38 regarding the term of the license agreement and under what circumstances the licensor would be able to terminate the license.
Industry and Other Data, page 55
15. Please revise to clarify your liability for statements included in the prospectus, regardless of the fact that you did not verify them and cannot guarantee their accuracy.
Response: The Company has clarified this section on page 57 to remove statements that may be considered limitation on liability.
Use of Proceeds, page 57
16. We note your disclosure on page 6 that you intend to complete both Phase 2a studies with the funds raised in this offering. Please revise this section to make it clear that you expect the proceeds to be sufficient to fund both Phase 2a studies through completion, if accurate. In addition, we note your statement that the Phase 2a trial in AD patients is presently run and paid for by the Alzheimer’s Disease Cooperative Study. Please tell us what obligations you have, if any, to fund this trial and whether you will have to reimburse ADCS. Please also tell us whether you have any agreement with ADCS relating to this study. If so, please provide materially complete disclosure of the agreement and file it as an exhibit to the registration statement, or tell us why you believe you are not required to do so.
Response: The Company has revised the disclosure on page 59 in response to the staff’s comment. The Company has also added a description of the ADCS agreement on page 81 and filed it as Exhibit 10.7 to the registration statement.
17. Please revise to clarify what you mean by the remaining proceeds will be used to “provide runway” while raising money for the Phase 3 studies in AD-DS and PD.
Response: The Company has revised the disclosure on page 60 to explain that it anticipates the offering will provide sufficient liquidity until the Company is able raise additional capital for the Phase 3 studies in AD-DS and PD
Founders’ Vision, page 78
18. Please revise this section to provide a balanced discussion of your business. Please also remove your statements that you have engineered medicines that normalize brain homeostasis and that you have been able to “stop every step leading to destruction up to the last step that is nerve cell death.” We note that your company is a clinical stage company and you have not yet established, and may never establish, the safety or efficacy of your product candidate. Please also remove the suggestion that investing in your company will help “patients [who] are desperately waiting for a solution to their problems” and will “solve neurodegeneration and protect nerve cells from dying.” Your disclosure in this section should be appropriately balanced to account for the risks of drug development. Please also provide the basis for your statement that “neurodegenerative diseases represent the biggest challenge facing us today.”
Response: The Company has modified this section on page 80 to remove certain statements and provide a balanced discussion of its business.
Business Target Engagement, page 82
19. Please revise the two tables on this page to make them more legible. Please make similar revisions to the tables on page 89.
Response: The Company has revised the two tables on pages 85-86 and pages 91-92 to make them more legible.
Reproducible Results Across Species, page 92
20. Please remove your statement that it is rare to see “perfect reproducibility” across species or tell us why you believe this is an appropriate statements. Categorizing the observation of similar effects in various species as “perfect reproducibility” suggests that success in animal models guarantees success in humans. In addition, given your limited observations in humans, it is not appropriate to make this conclusion.
Response: The Company has removed this term on page 2 and in the Business section on page 82 and replaced it with the term “substantially similar,” as it believes this is more indicative of the relationship.
Intellectual Property, page 100
21. We note your disclosure that your patent portfolio includes patents licensed from the NIH. Please clarify whether this is referencing the patents that are licensed from Horizon. If not, please file the license agreement with the NIH as an exhibit and provide a summary of the material terms in the Material Agreements section on page 102.
Response: The patents licensed from the NIH are the same patents licensed from Horizon. The Company has modified the disclosure here and elsewhere in the document to clarify that the patents are co-owned by Horizon and the Public Health Service (PHS), of which the NIH is a component.
22. We note that certain of your patents in 2021 or 2022. Please revise your disclosure to explain the material impact, if any, of the patent expirations on your business and on the success of ANVS-401. Please add risk factor disclosure to the extent appropriate.
Response: The Company has added disclosure on page 105 and in the risk factor on page 39 regarding t
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CORRESP 1 filename1.htm NEW YORK BALTIMORE LONDON WILMINGTON SINGAPORE MIAMI PHILADELPHIA FIRM and AFFILIATE OFFICES BOCA RATON CHICAGO PITTSBURGH WASHINGTON, DC NEWARK SAN FRANCISCO LAS VEGAS SILICON VALLEY CHERRY HILL SAN DIEGO www.duanemorris.com LAKE TAHOE BOSTON MYANMAR HOUSTON OMAN LOS ANGELES A GCC REPRESENTATIVE OFFICE HANOI OF DUANE MORRIS HO CHI MINH CITY ATLANTA MEXICO CITY ALLIANCE WITH MIRANDA & ESTAVILLO July 2, 2019 VIA EDGAR AND FEDEX Division of Corporation Finance Securities and Exchange Commission 100 F Street, N.E. Washington, D.C. 20549 Re Annovis Bio, Inc. Amendment No. 1 Draft Registration Statement on Form S-1 Submitted May 24, 2019 CIK No. 0001477845 On behalf of our client, Annovis Bio, Inc. (the “Company”), we are responding to the comments of the staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”) contained in its letter dated June 21, 2019 (the “Comment Letter”) relating to the above referenced Amendment No. 1 to Confidential Draft Registration Statement (the “DRS”). Set forth below are the Company’s responses to the Staff’s comments. The numbering of the paragraphs below corresponds to the numbering of the Staff’s comments, which for your convenience we have incorporated into this response letter. Page references in the text of this response letter correspond to the page numbers of the Registration Statement on Form S-1 filed today (the “Registration Statement”). We also describe below the changes the Company has made in response to the Staff’s comments in the Registration Statement and the prospectus included therein. For the Staff’s convenience, we will send a copy of this letter, a clean copy of the Registration Statement and a copy of the Registration Statement marked to show all changes from the DRS via Federal Express. Amendment No. 1 to Draft Registration Statement on Form S-1 Prospectus Summary, page 1 1. We note your disclosure on page 1 that you have a “ready program” to conduct a second Phase 2a study in PD patients. Please explain what you mean. Response: The Company has revised the sentence on page 1 to remove these words and explain that it has planned to commence the Phase 2a study in PD patients. 2. We note your disclosure that you expect your lead compound to be efficacious and that you showed in studies that ANVS-401 was safe on page 1, that you expect to obtain FDA approval in 2024 on page 2 and that clinical studies and preclinical data have established and/or proven the safety or efficacy of ANVS-401 on page 3. As your product candidate has not received FDA approval, it is premature to suggest or imply that it is safe or effective. Also, there can be no certainty as to when or if you will receive FDA approval. Please revise your disclosure here and all similar statements throughout the prospectus accordingly. We will not object to statements that your product candidate was well-tolerated or to presentation in the Business section of the trial endpoints, the extent to which the end points were met or were not met, or the aggregate or summary data collected from your trials. Response: The Company has modified its disclosure throughout the document to conform to this comment to remove suggestions or implications that ANVS-401 is safe or effective. 3. We note your disclosure on page 2 that successful termination of the Alzheimer’s disease and Parkinson’s disease study will “de-risk” ANVS-401 for use in neurodegenerative diseases and will validate the target and pathway. Please remove this statement and any other statements that imply that you will be successful in mitigating risk associated with drug development. Please also tell us what you mean by stating that termination of the study will validate the target and pathway. Response: The Company has deleted this statement on page 2 and inserted a statement it intends as more descriptive regarding its plans for a Phase 3 study. 4. We note statements throughout that imply efficacy, such as “lowering their high levels of APP will restore axonal transport and homeostasis...and normalize their memory loss and dementia,” and “ANVS-401 treatment restores normal axonal transport and prevents or restores all those events all the way to preserving nerve cell health.” In addition, we note that your description of ANVS-401 under “Pathway Engagement” includes numerous statements claiming efficacy, such as “full recovery of memory, learning and brain function,” “normalizes all the functions that are negatively affected by disturbances of the transport,” and “normalizes the affected function in all diseases that we tested it in.” These are just examples. Please substantially revise your disclosure throughout your prospectus to remove these statements as determinations of efficacy are solely within the authority of the FDA. Response: The Company has modified these statements throughout the document to remove and modify these statements so as not to imply efficacy. The Company has expressly referred to completed preclinical and clinical studies and the 2 results that have occurred in those studies in the past tense, with inclusion of data point information in a summary manner, so as not to imply efficacy in any present or future context. The Company has added a brief discussion of data points under “Our Company — Axonal Transport and Pathway Engagement — Pathway Engagement” on page 5 in the Summary and page 87 in the Business Section. 5. We note your statement here and in the Business section that you have an ongoing Phase 2a proof-of-concept study in AD patients. Please tell us the status of the study, including the number of patients enrolled and whether you have started the study. Please add similar disclosure in the Business section. Response: The Company has added disclosure on page 2 and page 81 describing the status of the study, its commencement and the number of patients enrolled. 6. You state that you have conducted clinical trials with 125 humans and these trials have shown promising clinical signals, including normalized levels of neurotoxic proteins. However, it appears that these results were only observed in your proof of concept study in five patients with mild cognitive impairment. Please revise to remove the implication that the clinical signals you list were observed in 125 humans and clarify that the AD patients had only mild cognitive impairment. Response: The Company has added disclosure to page 1 and page 81 to clarify the clinical signals were observed in five patients who had only mild cognitive impairment. 7. Please provide us with support for your statement that AD and PD are the two largest medical needs for the aging U.S. population and two potentially largest markets. Response: The Company has modified this sentence on page 2 and page 82 to state that AD and PD are two of the largest medical needs for the aging U.S. population and two potentially large markets. 8. Please revise your statement that focusing on AD in the DS population “perfectly represents AD” as this statement suggests that your studies in this population will translate to approval in the AD population generally. Response: The Company has revised this statement to indicate that DS population is substantially similar to AD population. 9. Please explain your references to Parexel and Posiphen, as there is no explanation in the prospectus as to the relevance of these terms. Response: The Company has explained that Parexel as a clinical research organization on page 1. The Company has removed references to Posiphen, a prior informal name for ANVS-401, that was included in certain imbedded graphics in the DRS. 10. We note your disclosure on page 5 that you have a Scientific Advisory Board. Please describe the role or function of the Scientific Advisory Board and whether there are any 3 rules or procedures governing such board. Please also provide us with support for your statement that the board is composed of “world-renowned scientists.” Response: The Company has described the role of the Scientific Advisory Board and stated that it has no rules or procedures governing the board, except for restrictions place on the members by their universities on page 7. We have also removed the term “world-renowned” with respect to the board members. 11. We note that you intend to conduct chronic toxicology studies in rats and dogs with the funds from the offering. Given that you are already testing ANVS-401 in humans, please explain the relevance of the animal toxicology study and whether it is necessary for you to continue studies in humans. Response: The Company has added explanation on page 8 that the toxicology studies are needed in order to then test for extended periods in humans. Implications of Being an Emerging Growth Company, page 7 12. 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 5(d) of the Securities Act, whether or not they retain copies of the communications. Response: The Company or anyone authorized on its behalf, has not made any written communications to potential investors in reliance on Section 5(d) of the Securities Act. Risk Factors We have concentrated our research and development efforts on the treatment of AD and PD..., page 18 13. Please revise this risk factor to provide detail regarding the particular challenges in obtaining FDA approval for AD and PD. For example, we note your statement on page 80 that since 2003, there have been over 500 clinical studies and no compound has shown efficacy. Response: The Company has revised the risk factor on page 19 to add references to challenges in obtaining FDA approval for AD and PD. If we fail to comply with our obligations under our existing intellectual property license, page 37 14. Please expand this risk factor to disclose the term of the license agreement and under what circumstances Horizon would be able to terminate your license. Response: The Company added disclosure on page 38 regarding the term of the license agreement and under what circumstances the licensor would be able to terminate the license. 4 Industry and Other Data, page 55 15. Please revise to clarify your liability for statements included in the prospectus, regardless of the fact that you did not verify them and cannot guarantee their accuracy. Response: The Company has clarified this section on page 57 to remove statements that may be considered limitation on liability. Use of Proceeds, page 57 16. We note your disclosure on page 6 that you intend to complete both Phase 2a studies with the funds raised in this offering. Please revise this section to make it clear that you expect the proceeds to be sufficient to fund both Phase 2a studies through completion, if accurate. In addition, we note your statement that the Phase 2a trial in AD patients is presently run and paid for by the Alzheimer’s Disease Cooperative Study. Please tell us what obligations you have, if any, to fund this trial and whether you will have to reimburse ADCS. Please also tell us whether you have any agreement with ADCS relating to this study. If so, please provide materially complete disclosure of the agreement and file it as an exhibit to the registration statement, or tell us why you believe you are not required to do so. Response: The Company has revised the disclosure on page 59 in response to the staff’s comment. The Company has also added a description of the ADCS agreement on page 81 and filed it as Exhibit 10.7 to the registration statement. 17. Please revise to clarify what you mean by the remaining proceeds will be used to “provide runway” while raising money for the Phase 3 studies in AD-DS and PD. Response: The Company has revised the disclosure on page 60 to explain that it anticipates the offering will provide sufficient liquidity until the Company is able raise additional capital for the Phase 3 studies in AD-DS and PD Founders’ Vision, page 78 18. Please revise this section to provide a balanced discussion of your business. Please also remove your statements that you have engineered medicines that normalize brain homeostasis and that you have been able to “stop every step leading to destruction up to the last step that is nerve cell death.” We note that your company is a clinical stage company and you have not yet established, and may never establish, the safety or efficacy of your product candidate. Please also remove the suggestion that investing in your company will help “patients [who] are desperately waiting for a solution to their problems” and will “solve neurodegeneration and protect nerve cells from dying.” Your disclosure in this section should be appropriately balanced to account for the risks of drug development. Please also provide the basis for your statement that “neurodegenerative diseases represent the biggest challenge facing us today.” Response: The Company has modified this section on page 80 to remove certain statements and provide a balanced discussion of its business. 5 Business Target Engagement, page 82 19. Please revise the two tables on this page to make them more legible. Please make similar revisions to the tables on page 89. Response: The Company has revised the two tables on pages 85-86 and pages 91-92 to make them more legible. Reproducible Results Across Species, page 92 20. Please remove your statement that it is rare to see “perfect reproducibility” across species or tell us why you believe this is an appropriate statements. Categorizing the observation of similar effects in various species as “perfect reproducibility” suggests that success in animal models guarantees success in humans. In addition, given your limited observations in humans, it is not appropriate to make this conclusion. Response: The Company has removed this term on page 2 and in the Business section on page 82 and replaced it with the term “substantially similar,” as it believes this is more indicative of the relationship. Intellectual Property, page 100 21. We note your disclosure that your patent portfolio includes patents licensed from the NIH. Please clarify whether this is referencing the patents that are licensed from Horizon. If not, please file the license agreement with the NIH as an exhibit and provide a summary of the material terms in the Material Agreements section on page 102. Response: The patents licensed from the NIH are the same patents licensed from Horizon. The Company has modified the disclosure here and elsewhere in the document to clarify that the patents are co-owned by Horizon and the Public Health Service (PHS), of which the NIH is a component. 22. We note that certain of your patents in 2021 or 2022. Please revise your disclosure to explain the material impact, if any, of the patent expirations on your business and on the success of ANVS-401. Please add risk factor disclosure to the extent appropriate. Response: The Company has added disclosure on page 105 and in the risk factor on page 39 regarding t