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CORRESP
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filename1.htm

APTORUM
GROUP LIMITED

17th
Floor, Guangdong Investment Tower

148
Connaught Road Central

Hong
Kong

October
5, 2018

VIA
EDGAR

Keira
Nakada

U.S.
Securities and Exchange Commission

Division
of Corporation Finance

Office
of Consumer Products

100
F Street, N.E.

Mail
Stop 4631

Washington,
DC 20549

    Re:
    Aptorum Group Limited

Registration
Statement on Form F-1

September
5, 2018

File
No. 333-227198

Dear
Ms. Nakada:

Aptorum
Group Limited (the “Company,” “Aptorum,” “we,” “us” or “our”)
hereby transmits its response to the letter received from the staff (the “Staff”) of the Securities and Exchange Commission
(the “Commission”), dated September 20, 2018 regarding our Registration Statement on Form F-1 (the “Registration
Statement”) previously submitted on September 5, 2018. For ease of reference, we have repeated the Commission’s comments
in this response and numbered them accordingly. An amended F-1 submitted publicly accompanying this Response Letter is referred
to as Form F-1.

Please
note that new language we are including in Form F-1 pursuant to your comments, is indicated in this letter in bold, italicized
font; any deletions from the initial Registration Statement are indicated in this letter as strikethrough
font.

Registration
Statement on Form F-1 filed September 5, 2018

Cover
page

 1. We
                                         note your response to comment 1, which we reissue in part. You continue to reference
                                         a minimum and maximum dollar amount of offered securities. Please amend your prospectus
                                         cover page to state the volume of securities being offered on a minimum and maximum offering
                                         basis. Refer to Item 501(b)(2) of Regulation S-K.

Response:
In response to the Staff’s comment, we updated the information on the prospectus cover page to state the volume of securities
being offered on a minimum and maximum offering basis.

 2. Please
                                         expand your revisions in response to prior comment 3 to disclose what the selling shareholders'
                                         fixed price will be. If it will be the same as the primary offering price, please revise
                                         to so state.

Response:
In response to the Staff’s comment, we disclosed that the selling shareholders’ fixed price is
equal to the Offering Price until the Class A Ordinary Shares are listed on NASDAQ and thereafter, the Selling Shareholders
will be able to sell their Class A Ordinary Shares at prevailing market prices or privately negotiated prices.

    1

Prospectus
Summary

Aptorum's
Lead Projects

ALS-1:
Small molecule intended for the treatment of viral infections caused by Influenza virus A, page 3

 3. We
                                         note your response to comment 10 and your revised disclosure stating your belief that
                                         “it is unlikely that ALS-1 will experience the resistance developed by the viruses
                                         against  the existing anti-viral therapy.” As you have not yet conducted any
                                         clinical studies, it is premature for you imply that ALS-1 will be effective. Please
                                         remove this statement. Similarly, please remove the disclosure on page 4 stating your
                                         belief that ALS-4 is “less likely to be susceptible to antibiotic resistance.”

Response:
Pursuant to the Staff’s comment, we removed the noted language.

NLS-1:
A Derivative of Epigallocatechin-3-Gallate (“Pro-EGCG”) for the treatment of Endometriosis, page
5

 4. We
                                         note your response to comment 11, which we reissue in part. Please remove your conclusion
                                         that studies of EGCG for the treatment of endometriosis have produced “encouraging
                                         results.” Additionally, please move the discussion of p-values observed to the
                                         Business section and expand your disclosure to explain how p-values are used to measure
                                         statistical significance and how they relate to the U.S. Food and Drug Administration’s
                                         evidentiary standards of efficacy. Additionally, please revise your discussion of preclinical
                                         studies of NLS-1 stating that it “prevents the progression of fibrosis” and
                                         “reduced lesion size significantly better that EGCG and other hormone- based therapy”
                                         to remove these conclusions regarding the efficacy of NLS-1. We will not object to a
                                         discussion of objective data points in the Business section.

Response:
In response to the Staff’s comment, we removed and revised the noted language. With regards to p-values, we added the
following section to the Business section of the amendment:

P.
82

“Statistical
Significance

The
term statistical significance is to define the probability that a measured difference between two groups (e.g. two treatment groups,
treatment versus control groups) is the result of a real difference in the tested variations and not the result of chance. It
means that the result of a test does not appear randomly or by chance, but because of a specific change that is tested, so it
can be attributed to a specific cause.

The
confidence level indicates to what percentage the test results will not commit a type 1 error, the false positive. A false
positive occurs when a change in the result is due to randomness (or other noise) and not the change in variations. At a 95%
confidence level (p = 0.05), there is a 5% chance that the test results are due to a type 1 error. 95% has become the
standard and usually be the minimum confidence level for the tests. To make the test more stringent, a 99% confidence level
(p = 0.01) is also commonly employed, which means that there is a 5% chance that the test results are due to a type 1
error.

    2

In
other words, a p value represents the confidence level. For example, if the p-value for a test is < 0.05, it means that there
is less than 5% chance the difference between two groups is due to random error or by chance. If the p-value is < 0.01, it
means that there is less than 1% chance the difference between two groups is due to random error or by chance.

We
employed statistical testing to compare different treatment groups in animal studies simply for proof of concept and to aid further
development. We do not intend to use this standard for any regulatory submission. The US FDA or other regulatory agencies may
not necessarily employ the same statistical standard to assess the efficacy in clinical trials, the results of which would be
submitted for regulatory approval. The US FDA or other regulatory agencies may also individualize their efficacy standard for
different clinical programs based on the indications, the purpose of a clinical trial, among others.”

Capitalization,
page 54

 5. We
                                         reissue our prior comment 18 since it does not appear that you have revised your capitalization
                                         table.

Response:
In response to the Staff’s comment, we revised our capitalization table to include a column reflecting our capitalization
on a pro forma basis to give effect to the issuance of 22,437,754 Class A Ordinary Shares issuable upon conversion of the Class
B Ordinary Shares.

The
revised capitalization section is provided below for your convenience.

“The
following table presents our capitalization as of June 30, 2018:

    ●
    on
    an actual basis (column 1);

    ●
    on
    a pro forma basis, to give effect to the issuance of 22,437,754 Class A Ordinary Shares issuable upon conversion
    of the Class B Ordinary Shares; (See “Transactions with Related Persons”) (column 2); and

    ●
    on
a pro forma as-adjusted basis, to give effect and the issuance of 1,290,323 Class A Ordinary Shares in this Offering
and the issuance of 234,648 Class A Ordinary Shares1 as a result of the automatic conversion of the Notes
issued in the Series A Note Offering, each at an assumed price to the public of $15.5 per share, the midpoint of
the price range set forth on the cover page of this prospectus after deducting underwriting discounts and commissions and estimated
offering expenses, and the issuance of 125,681 Class A Ordinary Shares as a result of the automatic partial conversion
of the Bond (columns 3 and 4).

1
Pursuant to the terms of the Note,
no fractional shares or securities shall be issued upon conversion of the Note; in lieu thereof, the Company shall pay an amount
equal to the product obtained by multiplying the applicable Conversion Price in such conversion, by the fraction of a share or
such other security not issued pursuant to the previous sentence. Accordingly, full conversion of the Notes would result in the
issuance of an aggregate of 234,648 Class A Ordinary Shares and $100.64, based on a conversion price of $6.82 per share.

    3

This
table should be read in conjunction with “Management’s Discussion and Analysis of Financial Condition and Results
of Operations” and our financial statements, consolidated financial statements and related notes included elsewhere in this
prospectus.

    June
    30, 2018

    1
    2
    3
    4

    Actual
    Pro
    Forma
    As
    adjusted
 (Minimum
 offering amount)
    As
    adjusted
 (Maximum
 offering amount)

    US$
    US$
    US$
    US$

    Equity

    Class
    A Ordinary Shares
      5,426,381
      27,864,135
      28,869,625
      30,159,948

    Class
    B Ordinary Shares
      22,437,754
      -
      -
      -

    Additional
    paid-in capital(1)
      5,346,129
      5,346,129
      16,440,941
      33,150,618

    Accumulated
    other comprehensive loss
      (545,642 )
      (545,642 )
      (545,642 )
      (545,642 )

    Accumulated
    deficit
      (8,035,834 )
      (8,035,834 )
      (8,035,834 )
      (8,035,834 )

    Non-controlling
    interests
      (113,341 )
      (113,341 )
      (113,341 )
      (113,341 )

    Total
    equity
      24,515,447
      24,515,447
      36,615,749
      54,615,749

    Total
    capitalization
      24,515,447
      24,515,447
      36,615,749
      54,615,749

 (1) Pro
forma additional paid-in capital reflects the net proceeds we expect to receive, after deducting underwriting fee, underwriters
expense allowance and other expenses. We expect to receive net proceeds of (a) approximately $9,000,000 if minimum
offering is raised or (b) approximately $27,000,000 if maximum offering is raised).

The
information above is illustrative only and our capitalization following the completion of this Offering and the Series A Note
Offering will be adjusted based on the actual initial public offering price and other terms of this Offering determined at pricing.

A
$1.00 increase (decrease) in the assumed initial public offering price of $15.5 per Class A Ordinary Share, the
midpoint of the estimated price range shown on the cover page of this prospectus, would increase (decrease) the amount of cash
and cash equivalents, additional paid-in capital, total (deficit) equity and total capitalization on a pro forma as adjusted basis
by approximately $1.16 million, assuming the number of Class A Ordinary Shares offered by us, as set forth on the
cover page of this prospectus, remains the same and after deducting underwriting discounts and commissions and estimated offering
expenses payable by us. Similarly, each increase (decrease) of 100,000 Class A Ordinary Shares offered by us would
increase (decrease) cash and cash equivalents, total (deficit) equity and total capitalization on a pro forma as adjusted basis
by approximately $1.40 million, assuming the assumed initial public offering price remains the same, and after deducting
underwriting discounts and commissions and estimated offering expenses payable by us.

    4

Business

Lead
Projects

ALS-1:
Small molecule intended for the treatment of viral infections caused by Influenza virus A, page 70

 6. We
                                         note your response to comment 22. Please expand your disclosure to briefly explain EC50.
                                         Additionally, please remove your conclusion that the “animal study results strongly
                                         suggest that ALS-1 protected mice against hypervirulent influenza A H5N1 virus in vivo.”
                                         Please also expand your disclosure on page 72 to briefly explain IC50.

Response:
We revised the disclosure in the Amendment as per the Staff’s comment. In addition to removing the noted language, we
included the following regarding IC50 on the pages noted; reference to EC50 was a typo and reference to
same has been revised to IC50.

Page
73:

“It
is our hypothesis that Influenza A NP is an essential protein for the proliferation of the influenza virus. ALS-1 targets NP and
triggers the aggregation of NP and this prevents the aggregated NP from entering the nucleus. In a paper published by the inventor,
Prof. Richard Kao, in Nature Biotechnology (28 (6): 600, 2010), ALS-1 inhibited infection of MDCK cells by the Influenza A/WSN/33,
H3N2 (clinical isolate) and Vietnam/1194/04 (H5N1) viruses with an ECIC50 (IC50
is defined as the concentration of a drug which inhibits half of the maximal response of a biochemical process. In
this case, inhibition of the growth of PFU = plaque-forming units is the response) of 0.069 ± 0.003 μM, 0.16
± 0.01 μM and 0.33 ± 0.04 μM in plaque reduction assay (PRA), respectively (Figure 1A). In this study, oseltamivir
(sold under the brand name Tamiflu®) was also included as a control. In this cell culture, ALS-1 outperformed oseltamivir
with a lower IC50 (Figure 1A). ALS-1 inhibited viral growth even when added within 6 hours after infection of the MDCK
cells with the virus (Figure 1B), indicating that the antiviral activities of ALS-1 arise from post-entry and post-nuclear events,
suggesting that multiple processes involving NP may be affected, although only the nuclear import process of NP can be readily
observed.”

Page
75:

“In a recent
publication by the inventor, Prof. Richard Kao, in mBio (8(5): e01224, 2017), ALS-4 demonstrates potent activity against Staphylococcus
aureus pigment formation in vitro, as indicated in Figure 2A, with an IC50 equal to 300 nM (Figure 2B).(IC50
is defined as the concentration of a drug which inhibits half of the maximal response of a biochemical process. In
this case, inhibition of the formation of the golden pigment is the response) equal to 300 nM (Figure 2B). In addition,
ALS-4 exhibits low cytotoxicity in MDCK, Vero, A549, Huh-7, or 293T cells, with 50% toxic concentrations higher than 500 µM.”

Patent
License, page 71

 7. We
                                         note your response to comment 24, which we reissue in part as it does not appear that
                                         you have disclosed the aggregate regulatory development and aggregate sales milestones
                                         payable under the license agreement. Please revise here and make similar revisions concerning
                                         the license agreement related to each of ALS-4 discussed on page 74 and NLS-1 discussed
                                         on page 79.

Response: In response
to the Staff’s comment, we disclosed the aggregate regulatory development and aggregate sales milestones payable under the
license agreements. Examples of this disclosu