Blueprint
As filed with the Securities and Exchange Commission on April 2,
2018
Registration No. 333-223452
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
AMENDMENT NO. 1
to
FORM S-3
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933
Cellular Biomedicine Group, Inc.
(Exact name of registrant as specified in its charter)
Delaware
|
86-1032927
|
(State or other jurisdiction of
incorporation or organization)
|
(I.R.S. Employer
Identification Number)
|
19925 Stevens Creek Blvd., Suite 100
Cupertino, CA 95014
(408) 973-7884
(Address, including zip code, and telephone number, including area
code, of registrant’s principal executive
offices)
Tony Liu, Chief Executive Officer
19925 Stevens Creek Blvd., Suite 100
Cupertino, CA 95014
(408) 973-7884
(Name, address, including zip code, and telephone number, including
area code, of agent for service)
Copies to:
Barry I. Grossman, Esq.
Sarah E. Williams, Esq.
Ellenoff Grossman & Schole LLP
1345 Avenue of Americas
New York, NY 10105
(212) 370-1300
Fax: (212) 370-7889
Approximate date of commencement of proposed
sale to the public: From time to time after the effective
date of this Registration Statement.
If the
only securities being registered on this Form are being offered
pursuant to dividend or interest reinvestment plans, please check
the following box: ☐
If any
of the securities being registered on this Form are to be offered
on a delayed or continuous basis pursuant to Rule 415 under the
Securities Act of 1933, as amended, other than securities offered
only in connection with dividend or interest reinvestment plans,
check the following box: ☒
If this
Form is filed to register additional securities for an offering
pursuant to Rule 462(b) under the Securities Act, please check the
following box and list the Securities Act registration statement
number of the earlier effective registration statement for the same
offering: ☐
If this
Form is a post-effective amendment filed pursuant to Rule 462(c)
under the Securities Act, check the following box and list the
Securities Act registration statement number of the earlier
effective registration statement for the same offering.
☐
If this
Form is a registration statement pursuant to General Instruction
I.D. or a post-effective amendment thereto that shall become
effective upon filing with the Commission pursuant to Rule 462(e)
under the Securities Act, check the following box. ☐
If this
Form is a post-effective amendment to a registration statement
filed pursuant to General Instruction I.D. filed to register
additional securities or additional classes of securities pursuant
to Rule 413(b) under the Securities Act, check the following box.
☐
Indicate by check
mark whether the Registrant is a large accelerated filer, an
accelerated filer, a non-accelerated filer, or a smaller reporting
company. See the definitions of “large accelerated
filer,” “accelerated filer” and “smaller
reporting company” in Rule 12b-2 of the Exchange
Act.
Large
accelerated filer
|
☐
|
Accelerated
filer
|
☒
|
Non-accelerated
filer
|
☐ (Do not check if a smaller reporting
company)
|
Smaller
reporting company
|
☐
|
|
|
Emerging
Growth Company
|
☐
|
If an
emerging growth company, indicate by check mark if the registrant
has elected not to use the extended transition period for complying
with any new or revised financial accounting standards provided
pursuant to Section 7(a)(2)(B) of Securities Act. ☐
CALCULATION OF REGISTRATION FEE
Title of Each
Class of
Securities to
be Registered
|
Amount
to
be
Registered(1)(2)
|
Proposed
Maximum
Aggregate
Offering
Price
per
Security(1)(2)
|
Proposed
Maximum
Aggregate
Offering
Price(2)
|
Amount
of
Registration
Fee(3)
|
Common Stock,
par value $0.001 per share
|
2,927,658
|
$16.20
|
$47,428,059.60
|
$5,904.80
|
(1)
Pursuant to Rule
416 of the Securities Act of 1933, as amended (the
“Securities Act”), the shares of common stock offered
hereby also include such presently indeterminate number of shares
of the registrant’s common stock as a result of stock splits,
stock dividends or similar transactions.
(2)
Estimated solely
for the purpose of calculating the registration fee for the
secondary offering, pursuant to Rule 457(c) under the Securities
Act, based on the average of the high and low prices of the
Registrant’s Common Stock on The NASDAQ Global Market on
March 1, 2018.
The Registrant hereby amends this Registration Statement on such
date or dates as may be necessary to delay its effective date until
the Registrant shall file a further amendment which specifically
states that this Registration Statement shall thereafter become
effective in accordance with Section 8(a) of the Securities Act of
1933, as emended, or until this Registration Statement shall become
effective on such date as the Commission, acting pursuant to said
Section 8(a), may determine.
The information in this prospectus is not complete and may be
changed. We may not sell the securities until the Registration
Statement filed with the Securities and Exchange Commission, of
which this prospectus is a part, is effective. This prospectus is
not an offer to sell these securities and is not soliciting an
offer to buy these securities in any state where the offer or sale
is not permitted.
SUBJECT TO COMPLETION, DATED APRIL 2, 2018
PROSPECTUS
Up to
2,927,658 Shares of Common Stock
This
prospectus relates to the resale of up to 2,927,658 shares (the
“Shares”) of our common stock, par value $.001 per
share of Cellular Biomedicine Group, Inc. a Delaware corporation,
for sale by the selling stockholders named herein (the
“Selling Stockholders”) for their own accounts. The
shares to be sold by the Selling Stockholders include: (i) up to
41,667 shares of our common stock issued in connection with a $0.5
million closing on a private placement financing on December 22,
2017 (the “Management Tranche”), (ii) up to 1,166,667
shares of our common stock issued in connection with a $14.0
million closing on a private placement financing on December 28,
2017 (the “Investor Tranche”), and (iii) up to
1,719,324 shares of our common stock issued in connection with a
$30.6 million closing on a private placement financing on February
5, 2018 (the “February PIPE”).
To the
extent the Selling Stockholders wish to sell their shares of our
common stock as provided for herein, they may offer and sell such
shares on a continuous or delayed basis in the future. These sales
may be conducted in the open market or in privately negotiated
transactions and at market prices, fixed prices or negotiated
prices. We will not receive any of the proceeds from the sale of
the Shares. See “Use of Proceeds” on page 19. We have
agreed to pay the expenses in connection with the registration of
the Shares.
Our
common stock is listed on The NASDAQ Global Market under the symbol
“CBMG.” The last reported sale price of our common
stock on March 28, 2018 was $18.25.
Investing
in our securities involves a high degree of risk. You should review
carefully the risks and uncertainties described under the heading
“Risk Factors” beginning on page 18, and under similar
headings in the other documents that are incorporated by reference
into this prospectus or any prospectus supplement before making a
decision to purchase our securities.
Neither
the Securities and Exchange Commission nor any state securities
commission has approved or disapproved of these securities or
determined if this prospectus is truthful or complete. Any
representation to the contrary is a criminal offense.
The date of this prospectus
is ,
2018.
TABLE OF CONTENTS
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Page
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Cautionary
Note Regarding Forward-Looking Statements
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ii
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Prospectus
Summary
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1
|
The
Offering
|
17
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Risk
Factors
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18
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Use of
Proceeds
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19
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Determination
of Offering Price
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19
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Selling
Stockholders
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20
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Plan of
Distribution
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21
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Description
of Securities to be Registered
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23
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Legal
Matters
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24
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Experts
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24
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Where
You Can Find Additional Information
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24
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Incorporation
of Documents by Reference
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25
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Disclosure
of Commission Position of Indemnification For Securities Law
Violations
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26
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You
should rely only on the information we have provided or
incorporated by reference in this prospectus or in any prospectus
supplement. We have not authorized anyone to provide you with
information different from that contained or incorporated by
reference in this prospectus or in any prospectus
supplement.
You
should assume that the information contained in this prospectus and
in any prospectus supplement is accurate only as of their
respective dates and that any information we have incorporated by
reference is accurate only as of the date of the document
incorporated by reference, regardless of the time of delivery of
this prospectus or any prospective supplement or any sale of
securities.
In
this prospectus, we rely on and refer to information and statistics
regarding our industry. We obtained this statistical, market and
other industry data and forecasts from publicly available
information. While we believe that the statistical data, market
data and other industry data and forecasts are reliable, we have
not independently verified the data.
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
This
prospectus and any accompanying prospectus supplement and the
documents we have filed or will file with the SEC that are or will
be incorporated by reference into this prospectus and the
accompanying prospectus supplement contain forward-looking
statements, within the meaning of Section 27A of the Securities Act
and Section 21E of the Securities Exchange Act of 1934, as amended
(the "Exchange Act"), that involve risks and uncertainties. Any
statements contained, or incorporated by reference, in this
prospectus and any accompanying prospectus that are not statements
of historical fact may be forward-looking statements. When we use
the words “anticipate,” “believe,”
“could,” “estimate,” “expect,”
“intend,” “may,” “plan,”
“predict,” “project,” “will”
and other similar terms and phrases, including references to
assumptions, we are identifying forward-looking statements.
Forward-looking statements involve risks and uncertainties which
may cause our actual results, performance or achievements to be
materially different from those expressed or implied by
forward-looking statements.
A
variety of factors, some of which are outside our control, may
cause our operating results to fluctuate significantly. They
include:
●
our
plans and expectations regarding the timing and outcome of our
research, development, manufacturing, distribution and
commercialization efforts, whether with partners or on our own,
with primary research and manufacturing facilities in China,
relating to our therapies derived from two major cell platforms:
(i) Immune Cell therapy for treatment of a broad range of cancers
using vaccine, T Central Memory (“Tcm”) Cell, T Cells
Receptor (“TCR”) clonality, Chimeric Antigen Receptor T
cell (“CAR-T”) and anti-PD-1 technologies for various
liquid and solid cancerous diseases, and (ii) human adipose-derived
mesenchymal progenitor cells (“haMPC”) for treatment of
joint and autoimmune diseases comprised of Knee Osteoarthritis
(“KOA”), and Cartilage Defect (“CD”)
Asthma, and Chronic Obstructive Pulmonary Disease ("COPD")
autologous and allogeneic therapies and any other proposed
products, product candidates or approved products;
●
the
domestic and international regulatory process and related laws,
rules and regulations governing our technologies and our approved
and proposed products and formulations, including: (i) the timing,
status and results of our or our commercial partners’ filings
with the U.S. Food and Drug Administration (“FDA”),
Ministry of Health (“MOH”) and the China Food and Drug
Administration (“CFDA”) or their f equivalents in other
jurisdictions, (ii) the timing, status and results of non-clinical
work and clinical studies, including regulatory review thereof and
(ii) the heavily regulated industry in which we operate our
business generally;
●
the
significant challenges our newly acquired technology platform
presents;
●
our
ability to enter into strategic partnerships for the development,
commercialization, manufacturing and distribution of our products
and product candidates;
●
Our
reliance in significant part on outside scientists and their
third-party research institutions for research and development and
early clinical testing of our product candidates;
●
our
ability, or the ability of our commercial partners to actually
develop, commercialize, manufacture or distribute our products and
product candidates;
●
our
ability to generate commercially viable products and the market
acceptance of our cell therapy and cell banking technologies and
our proposed products and product candidates;
●
our
ability to finance our operations on acceptable terms, either
through the raising of capital, the incurrence of convertible or
other indebtedness or through strategic financing or
commercialization partnerships;
●
the
protection and control afforded by our patents or other
intellectual property, and any interest patents or other
intellectual property that we license, or our or our
partners’ ability to enforce our rights under such owned or
licensed patents or other intellectual property;
●
our
ability to maintain our licenses, patents or other intellectual
property;
●
the
outcome of ongoing or potential future litigation or other claims
or disputes relating to our business, technologies, products or
processes;
●
the
ability of our manufacturing partners to supply us or our
commercial partners with clinical or commercial supplies of our
products in a safe, timely and regulatory compliant manner and the
ability of such partners to address any regulatory issues that have
arisen or may in the future arise;
●
competition
existing today or that will likely arise in the future;
and
●
regulatory
oversight of our company by the Securities and Exchange Commission
(“SEC”), FDA, CFDA, the NASDAQ Stock Market and other
regulatory agencies.
The
foregoing does not represent an exhaustive list of risks that may
impact upon the forward-looking statements used herein or in the
documents incorporated by reference herein. Please see “Risk
Factors” in our reports filed with the SEC or in a prospectus
supplement related to this prospectus for additional risks which
could adversely impact our business and financial performance.
Moreover, new risks regularly emerge and it is not possible for our
management to predict all risks, nor can we assess the impact of
all risks on our business or the extent to which any risk, or
combination of risks, may cause actual results to differ from those
contained in any forward-looking statements. All forward-looking
statements included in this prospectus and any accompanying
prospectus supplement are based on information available to us on
the date hereof or thereof. Except to the extent required by
applicable laws or rules, we undertake no obligation to publicly
update or revise any forward-looking statement, whether as a result
of new information, future events or otherwise. All subsequent
written and oral forward-looking statements attributable to us or
persons acting on our behalf are expressly qualified in their
entirety by the cautionary statements contained throughout (or
incorporated by reference in) this prospectus, any accompanying
prospectus and the documents we have filed with the
SEC.
PROSPECTUS SUMMARY
The following summary highlights selected information contained or
incorporated by reference in this prospectus. This summary does not
contain all of the information you should consider before investing
in the securities. Before making an investment decision, you should
read the entire prospectus and any supplement hereto carefully,
including the risk factors section as well as the financial
statements and the notes to the financial statements incorporated
herein by reference.
In this prospectus and any amendment or supplement hereto, unless
otherwise indicated, the terms “Cellular Biomedicine Group,
Inc.,” “CBMG,” the “Company,”
“we,” “us,” and “our” refer and
relate to Cellular Biomedicine Group, Inc. and its consolidated
subsidiaries.
Our Company
Cellular
Biomedicine Group, Inc. is a clinical stage biopharmaceutical
company, principally engaged in the development of novel therapies
for cancer and degenerative diseases utilizing proprietary
cell-based technologies. Our technology includes two major
platforms: (i) immune cell therapy for treatment of a broad range
of cancer indications comprised of technologies in Chimeric Antigen
Receptor modified T cells (CAR-T), T-Cell Receptor(TCR), cancer
vaccine, and ex vivo expanded autologous Central Memory T Cells
(Tcm), and (ii) human adipose-derived mesenchymal progenitor cells
(haMPC) for treatment of joint and autoimmune diseases. Our
research & development facilities and manufacturing facilities
are based in China in the cities of Shanghai, Wuxi and
Beijing.
We are
focused on developing and marketing safe and effective cell-based
therapies based on our cellular platforms, to treat cancer,
orthopedic diseases and metabolic diseases. We have developed
proprietary technologies and know-hows for our cell therapy
platforms. Our primary target market is Greater China. We believe
that our cell-based therapies will be able to help patients with
high unmet needs. We expect to carry out clinical studies leading
to the eventual CFDA approval of our products through Biologics
License Application (“BLA”) filings and authorized
clinical centers throughout Greater China.
We have
launched multiple clinical trials using our CAR-T products in
multiple indications such as Diffuse Large B-cell Lymphoma (DLBCL)
and Acute Lymphoblastic leukemia (ALL). We may also establish
partnerships with other companies for co-development of CAR-T,
TCR-T and stem cell based therapies. We are striving to build a
highly competitive research and development function, a
translational medicine unit, along with a well-established cellular
manufacturing capability and ample capacity, to support the
development of multiple assets in multiple indications. These
efforts will allow us to boost the Company's immuno-oncology
presence and pave the way for additional future
partnerships.
Recent Developments
In
January 2016, we launched a Phase I clinical trial of an
off-the-shelf allogeneic haMPC AlloJoin™ therapy for KOA (the
“Allogenic KOA Phase I Trial”) to evaluate the safety
and efficacy of AlloJoin™, an off-the-shelf allogeneic
adipose derived progenitor cell (haMPC) therapy for the treatment
of KOA.
On
March 23, 2016, we filed a Form S-3 Registration Statement (the
“S-3 Registration Statement”) with the SEC, which was
declared effective on June 17, 2016. The S-3 Registration Statement
contained three prospectuses:
●
Offering Prospectus. A base prospectus which covers the offering,
issuance and sale by us of up to $150,000,000 of our common stock,
preferred stock, debt securities, warrants, rights and/or
units;
●
Resale Prospectus. A prospectus to be used for the resale by the
selling stockholders of up to 3,824,395 shares of the Common Stock;
and
●
Sales Agreement Prospectus. A sales agreement prospectus covering
the offering, issuance and sale by the registrant of up to a
maximum aggregate offering price of $50,000,000 of the Common Stock
that may be issued and sold under a sales agreement with Cantor
Fitzgerald & Co.
On
August 5, 2016, we completed patient treatment for the Allogenic
KOA Phase I Trial. On December 9, 2016, we announced interim
3-month safety data from the Allogenic KOA Phase I Trial in China.
Preliminary results from interim analysis have demonstrated a
safety and tolerability profile of AlloJoinTM in the three doses tested, and no
serious adverse events (SAE) have been observed. The trial has been
completed and we are analyzing the results on cartilage
regeneration as well as recent development in the competitive
landscape.
On
November 29, 2016, we announced the approval and commencement of
patient enrollment in China for our CARD-1 (CAR-T Against DLBCL)
Phase I clinical trial of CD19 CAR-T therapy utilizing our
optimized proprietary C-CAR011 construct for the treatment of
patients with refractory DLBCL. The CARD-1 trial has begun
enrollment with more data expected to be available in the first
half of 2018.
On
December 9, 2016, we announced interim 3-month safety data from our
Phase I clinical trial in China for AlloJoin™ off-the-shelf
allogeneic stem cell therapy for KOA. The preliminary data was
presented in December 2016 at the World Stem Cell Summit in West
Palm Beach, Florida. The interim analysis of the trial has
preliminarily demonstrated a safety and tolerability profile of
AlloJoin™ in the three doses tested, and adverse events (AE)
are similar to that of our prior autologous trials. No serious
adverse events (SAE) have been observed.
On
January 3, 2017, we announced the signing of a ten-year lease of an
113,038-square foot building located in the “Pharma
Valley” in Shanghai Zhangjiang High-Tech Park. The new
facility designed and built to GMP standards will consist of 40,000
square feet dedicated to advanced cell manufacturing. We plan to
invest an aggregate of approximately $35 million into the
Zhangjiang facility, of which $10 million will be spent on to bring
the facility into compliance with current GMP standards and around
25 million will be spent on lease of this real estate. By the end
of 2017, the combination of new Zhangjiang facility, an expanded
Wuxi, and Beijing facilities, all meeting international GMP
standards, of the Company had provided 70,000 square feet for cell
manufacturing. The Company expects that it will be capable of
supporting clinical trials for five different CART and stem cell
products simultaneously, or the ability to produce products to
treat approximately 10,000 cancer patients and 10,000 KOA patients
per year. To reach this capacity, we plan to hire an additional 60
R&D and Manufacturing personnel by end of 2018.
On
January 9, 2017, we announced the commencement of patient
enrollment in China for our CALL-1 (CAR-T against Acute
Lymphoblastic Leukemia) Phase I clinical trial of CD19 CAR-T
therapy utilizing its optimized proprietary C-CAR011 construct for
the treatment of patients with relapsed or refractory (r/r) CD19+
B-cell ALL. The CALL-1 trial began enrollment with more data
expected to be available in the first half of 2018. Depending on
the Phase I CALL-1 results, CBMG expects to initiate a larger Phase
II clinical trial as soon as possible.
On
February 27, 2017 we announced the Company received a $2.29 million
grant from California Institute of Regenerative Medicine (CIRM) to
fund our off-the-shelf AlloJoin™ Allogeneic Stem Cell Therapy
for KOA in the United States. On May 4, 2017, the Company received
$1.2 million from the CIRM grant, the first of four disbursements
totaling $2.29 million grant.
On
March 30, 2017 we announced the completion of our newly expanded
30,000-square foot facility in Huishan High Tech Park in Wuxi,
China. 20,000 square feet of the Wuxi facility will be dedicated to
advanced stem cell culturing, centralized plasmid and viral vector
production, cell banking and development of reagents.
On
April 10, 2017, we announced a strategic research collaboration to
co-develop certain high-quality industrial control processes in
CAR-T and stem cell manufacturing with GE Healthcare Life Science.
In connection with the collaboration, a joint laboratory within
CBMG’s new Shanghai Zhangjiang facility designed and built to
GMP standards will be established and dedicated to the joint
research and development of a functionally integrated and automated
immunotherapy cell manufacturing system.
On May
15, 2017, we announced the addition of a new independent Phase I
clinical trial of the Company’s ongoing CARD-1 study in
patients with chemorefractory or refractory B cell Non-Hodgkin
Lymphoma (NHL). The Company and Shanghai Tongji Hospital are
conducting a single arm, non-randomized study to evaluate the
safety and efficacy of C-CAR011 (Anti-CD19 single-chain variable
fragment (scFv) (41BB-CD3f)) therapy in relapsed or refractory B
cell NHL patients. The trial will enroll 15 patients comprised of
DLBCL, Primary Mediastinal Large B-Cell Lymphoma (PMBCL) and
Follicular Lymphoma (FL).
On June
1, 2017, we announced our Board of Directors has approved a new
stock repurchase program granting the company authority to
repurchase up to $10 million in common shares (the “2017
Stock Repurchase Program”) through open market purchases
pursuant to a plan adopted in accordance with Rule 10b5-1 of the
Securities Exchange Act of 1934, as amended (the “Exchange
Act”) and in accordance with Rule 10b-18 of the Exchange Act.
The 2017 Stock Repurchase Program contemplates repurchase shares of
our common stock in the open market in accordance with all
applicable securities laws and regulations. From June to December
2017, we repurchased a total of 426,794 shares at a total cost of
$3,977,929, or an average of $9.32 per share.
On June
20, 2017, we announced the establishment of an External Advisory
Board and the appointment of Michael A. Caligiuri, MD, as Chair of
the External Advisory Board to bring together experts from diverse
disciplines to provide knowledge and insight to help CBMG fulfill
its mission and build a network for development opportunities. On
November 28, 2017, Dr. Caligiuri was appointed as President and
physician-in-chief of City of Hope National Medical
Center.
On
November 4, 2017, we announced the grand opening of our Zhangjiang
facility. On the same day, we announced the signing of a strategic
partnership with Thermo Fisher Scientific (China) Ltd. to build a
joint Cell Therapy Technology Innovation and Application Center
(Center) at CBMG’s newly opened Shanghai Zhangjiang GMP
facility.
In
December 2017, we announced the closing of two private placement
transactions pursuant to which we sold an aggregate of 1,208,333
shares of our common stock to certain key executives and private
investors at $12.00 per share, for total aggregate gross proceeds
of approximately $14.5 Million.
On
January 30, 2018 and February 5, 2018, we entered into securities
purchase agreements with certain investors pursuant to which we
agreed to sell, and the investors agreed to purchase from the
Company, an aggregate of 1,719,324 shares of our common stock at
$17.80 per share for total gross proceeds of approximately $30.6
million (the “February 2018 Private Placement”). The
transaction closed on February 5, 2018. Pursuant to the purchase
agreements, the investors have the right to nominate one director
to the board of directors of the Company to stand for election at
the 2018 Annual Meeting of Stockholders. Effective as of the
closing of the February 2018 Private Placement, Bosun S. Hau was
elected as a non-executive Class III director of the
Company.
In
March 2018, we announced 48-week clinical data from our Phase I
clinical trial in China for AlloJoin™ for KOA. The 48-week analysis of study data
of 22 patients demonstrated AlloJoin™ off-the-shelf
allogeneic stem cell therapy for KOA to have good safety tolerance
and early signs of efficacy in preventing cartilage deterioration.
Effective March 14,
2018, our CIRM project in the United States also
terminated. The two AlloJoin™ cell
banks created in the United States will be stored in the
Company’s Maryland facility for future
use.
Biopharmaceutical Business
Our
biopharmaceutical business was founded in 2009 as a newly formed
specialty biomedicine company by a team of seasoned
Chinese-American executives, scientists and doctors. In 2010, we
established a facility designed and built to GMP standards in Wuxi,
and in 2012 we established a FDA GMP standard protocol-compliant
manufacturing facility in Shanghai. In October 2015, we opened a
facility designed and built to GMP standards in Beijing. In
November 2017, we announced the grand opening of our Zhangjiang
facility in Shanghai, of which 40,000 square feet was designed and
built to GMP standards and dedicated to advanced cell
manufacturing. Our focus has been to serve the rapidly growing
health care market in China by marketing and commercializing stem
cell and immune cell therapeutics, related tools and products from
our patent-protected homegrown and acquired cell technology, as
well as by utilizing exclusively in-licensed and other acquired
intellectual properties.
Our
current treatment focal points are cancer and other degenerative
diseases such as KOA.
Cancer. In the cancer field, with the
recent build-up of multiple cancer therapeutic technologies, we
have prioritized our clinical efforts on CAR-T. We are not actively
pursuing the fragmented Tcm technical services opportunities. On
November 29, 2016, we announced the approval and commencement of
patient enrollment in China for its CARD-1 Phase I clinical trial
utilizing its optimized proprietary C-CAR011 construct of CD19
CAR-T therapy for the treatment of patients with refractory DLBCL.
The CARD-1 trial has begun enrollment with final data expected to
be available in the second half of 2018. On January 9, 2017 we
announced the approval and commencement of patient enrollment in
China for its CALL-1 Phase I clinical trial utilizing its optimized
proprietary C-CAR011 construct of CD19 CAR-T therapy for the
treatment of patients with relapsed or refractory (r/r) CD19+
B-cell ALL. The CALL-1 trial has begun enrollment with final data
expected to be available in the second half of 2018. Depending on
the Phase I CARD-1 and CALL-1 results, we expect to initiate larger
trials to confirm the safety and efficacy profile and support BLA
submission as soon as practicable.
On May
15, 2017, we announced the addition of a new independent Phase I
clinical trial of the Company’s ongoing CARD-1 study in
patients with chemorefractory and aggressive DLBCL. Recruitment has
started on patients comprised of DLBCL, PMBCL and FL. Final data
for this single arm, non-randomized study to evaluate the safety
and efficacy of C-CAR011 41BB-CD3f therapy in relapsed or
refractory B cell NHL is expected in the first half of
2019.
KOA. In 2013, we completed a Phase
I/IIa clinical study in China for our KOA therapy named
Re-Join®. The trial tested the safety and efficacy of
intra-articular injections of autologous haMPCs in order to reduce
inflammation and repair damaged joint cartilage. The 6-month
follow-up clinical data showed Re-Join® therapy to be both
safe and effective.
In Q2
of 2014, we completed patient enrollment for the Phase IIb clinical
trial of Re-Join® for KOA. The multi-center study enrolled 53
patients to participate in a randomized, single blind trial. We
published 48 weeks follow-up data of Phase I/IIa on December 5,
2014. The 48 week data indicated that patients have reported a
decrease in pain and a significant improvement in mobility and
flexibility, while the clinical data shows our Re-Join®
regenerative medicine treatment to be safe. We announced the
interim 24 week results for Re-Join® on March 25, 2015 and
released positive Phase IIb 48 week follow-up data in January 2016,
which shows the primary and secondary endpoints of Re-Join®
therapy group having all improved significantly compared to their
baseline, which has confirmed some of the Company’s Phase
I/IIa results. Our Re-Join® haMPC therapy for KOA is an
interventional therapy using proprietary device, process, culture
and medium:
●
Obtain adipose
(fat) tissue from the patient using our CFDA approved medical
device, the A-Stromal™ Kit;
●
Expand haMPCs
using our proprietary culture medium (serum-free and
antibiotics-free); and
●
Formulated for
ReJoin therapy using our proprietary formulation.
Our
process is distinguishable from sole Stromal Vascular Fraction
(SVF) therapy. The immunophenotype of our haMPCs exhibited multiple
biomarkers such as CD29+, CD73+, CD90+, CD49d+, HLA-I+, HLA-DR-,
Actin-, CD14-, CD34-, and CD45-. In contrast, SVF is merely a
heterogeneous fraction including preadipocytes, endothelial cells,
smooth muscle cells, pericytes, macrophages, fibroblasts, and
adipose-derived stem cells (ASCs).
In
January 2016, we launched the Allogeneic KOA Phase I Trial in China
to evaluate the safety and efficacy of AlloJoin™, an off-the
shelf allogeneic haMPC therapy for the treatment of KOA. On August
5, 2016 we completed patient treatment for the Allogeneic KOA Phase
I trial, and on December 9, 2016 we announced interim 3-month
safety data from the Allogenic KOA Phase I Trial in China. The
interim analysis of the trial has preliminarily demonstrated a
safety and tolerability profile of AlloJoin™ in the three
doses tested, and no SAE have been observed. In March 2018, we
announced 48-week clinical data from our Phase I clinical trial in
China for AlloJoin™ for KOA. The 48-week analysis of study
data of 22 patients demonstrated AlloJoin™ off-the-shelf
allogeneic stem cell therapy for KOA to have good safety tolerance
and early signs of efficacy in preventing cartilage deterioration.
The total WOMAC scores (consisting of pain, stiffness and function
scores of joints) as a primary end point showed a significant
improvement at 12 weeks post AlloJoin™ cell therapy and
continued improvement at 48 weeks. The secondary evaluation end
point, the data of 3D spoiled gradient-recalled echo (SPGR)
quantitative magnetic resonance imaging (MRI) for whole knee
cartilage volume at 48 weeks, showed an increased tendency when
compared with that at baseline 0 weeks, and as compared with normal
cartilage deterioration as a result of aging.
In
January 2015, we initiated patient recruitment in a phase II
clinical study, in China, of ReJoin haMPC in Cartilage Damaged
patients resulting from osteoarthritis or sports injury, in further
support of KOA indication. The study is based on the same
technology that has shown significant efficacy in the treatment of
KOA but requires two arthroscopic examinations and the use of
magnetic resonance imaging (“MRI”) to further
demonstrate the regenerative efficacy of ReJoin. Upon further
review of the protocol and the difficulty of getting patients back
for a second arthroscopic examination, we determined to terminate
the study.
The
unique lines of adult adipose-derived stem cells and the immune
cell therapies enable us to create multiple cell formulations in
treating specific medical conditions and diseases, as well as
applying single cell types in a specific treatment protocol. The
quality management systems of CBMG Shanghai and CBMG Wuxi were
issued a Certificate of ISO-9001:2008 by SGS /ANAB (ANSI-ASQ
National Accreditation Board). Our facility in Shanghai was issued
a Certificate of Compliance by ENV Services, Inc., and ISO
Inspection Service Provider that (i) its rooms 1-7, 10 are
certified to ISO Class 7 per ISO-14644 in accordance with cGMP;
(ii) its biological safety cabinets are certified per NSF/ANSI 49
and to ISO Class 5;and (iii) its instrumentation calibration has
been certified to perform in accordance with ANSI/NCSL Z-540-1 and
document in accordance with 10CFR21. Our facility in Shanghai was
issued a Testing Report concluding that certain testing items of
our Shanghai facility’s cleanrooms are in compliance with the
Good Manufacturing Practice for Drugs (2010 Revision) of China. The
cleanrooms in our Beijing facility are certified to meet the
standard of CNAS L1669 and the cleanrooms of our Wuxi facility have
been certified to meet the SHPMCC standard.
In
addition to standard protocols, we use proprietary processes and
procedures for manufacturing our cell lines, comprised
of:
●
Banking
processes that ensure cell preservation and viability;
●
DNA
identification for stem cell ownership; and
●
Bio-safety
testing at independently certified laboratories.
Regenerative Medicine and Cell Therapy
Regenerative
medicine is the “process of replacing or regenerating human
cells, tissues or organs to restore or establish normal
function”. Cell therapy as applied to regenerative medicine
holds the promise of regenerating damaged tissues and organs in the
body by rejuvenating damaged tissue and by stimulating the
body’s own repair mechanisms to heal previously irreparable
tissues and organs. Medical cell therapies are classified into two
types: allogeneic (cells from a third-party donor) or autologous
(cells from one’s own body), with each offering its own
distinct advantages. Allogeneic cells are beneficial when the
patient’s own cells, whether due to disease or degeneration,
are not as viable as those from a healthy donor. Similarly, in
cases such as cancer, where the disease is so unique to the
individual, autologous cells can offer true personalized
medicine.
Regenerative
medicine can be categorized into major subfields as
follows:
●
Cell
Therapy. Cell therapy involves the use of cells, whether derived
from adults, third party donors or patients, from various parts of
the body, for the treatment of diseases or injuries. Therapeutic
applications may include cancer vaccines, cell based
immuno-therapy, arthritis, heart disease, diabetes,
Parkinson’s and Alzheimer’s diseases, vision
impairments, orthopedic diseases and brain or spinal cord injuries.
This subfield also includes the development of growth factors,
serums and natural reagents that promote and guide cell
development.
●
Tissue
Engineering. This subfield involves using a combination of cells
with biomaterials (also called “scaffolds”) to generate
partially or fully functional tissues and organs, or using a
mixture of technology in a bioprinting process. Some natural
materials, like collagen, can be used as biomaterial, but advances
in materials science have resulted in a variety of synthetic
polymers with attributes that would make them uniquely attractive
for certain applications. Therapeutic applications may include
heart patch, bone re-growth, wound repair, replacement neo-urinary
conduits, saphenous arterial grafts, inter-vertebral disc and
spinal cord repair.
●
Diagnostics and
Lab Services. This subfield involves the production and derivation
of cell lines that may be used for the development of drugs and
treatments for diseases or genetic defects. This sector also
includes companies developing devices that are designed and
optimized for regenerative medicine techniques, such as specialized
catheters for the delivery of cells, tools for the extraction of
stem cells and cell-based diagnostic tools.
All
living complex organisms start as a single cell that replicates,
differentiates (matures) and perpetuates in an adult through its
lifetime. Cell therapy is aimed at tapping into the power of cells
to prevent and treat disease, regenerate damaged or aged tissue and
provide cosmetic applications. The most common type of cell therapy
has been the replacement of mature, functioning cells such as
through blood and platelet transfusions. Since the 1970s, bone
marrow and then blood and umbilical cord-derived stem cells have
been used to restore bone marrow and blood and immune system cells
damaged by chemotherapy and radiation used to treat many cancers.
These types of cell therapies have been approved for use world-wide
and are typically reimbursed by insurance.
Over
the past number of years, cell therapies have been in clinical
development to attempt to treat an array of human diseases. The use
of autologous (self-derived) cells to create vaccines directed
against tumor cells in the body has been demonstrated to be
effective and safe in clinical trials. Researchers around the globe
are evaluating the effectiveness of cell therapy as a form of
replacement or regeneration of cells for the treatment of numerous
organ diseases or injuries, including those of the brain and spinal
cord. Cell therapies are also being evaluated for safety and
effectiveness to treat heart disease, autoimmune diseases such as
diabetes, inflammatory bowel disease, joint diseases and cancerous
diseases. While no assurances can be given regarding future medical
developments, we believe that the field of cell therapy is a subset
of biotechnology that holds promise to improve human health, help
eliminate disease and minimize or ameliorate the pain and suffering
from many common degenerative diseases relating to
aging.
Recent Developments in Cancer Cell Therapy
According to the
U.S. National Cancer Institute’s 2013 cancer topics research
update on CAR-T-Cells, excitement is growing for
immunotherapy—therapies that harness the power of a
patient’s immune system to combat their disease, or what some
in the research community are calling the “fifth
pillar” of cancer treatment.
One
approach to immunotherapy involves engineering patients’ own
immune cells to recognize and attack their tumors. And although
this approach, called adoptive cell transfer ("ACT"), has been
restricted to small clinical trials so far, treatments using these
engineered immune cells have generated some remarkable responses in
patients with advanced cancer. For example, in several early-stage
trials testing ACT in patients with ALL who had few if any
remaining treatment options, many patients’ cancers have
disappeared entirely. Several of these patients have remained
cancer free for extended periods.
Equally
promising results have been reported in several small clinical
trials involving patients with lymphoma. Although the lead
investigators cautioned that much more research is needed, the
results from the trials performed thus far indicate that
researchers can successfully alter patients’ T cells so that
they attack their cancer cells. As an example, we look to Spectrum
Pharmaceutical’s Folotyn approved in September 2009 for
treatment of R/R peripheral T-cell lymphoma with approval supported
by a single arm trial observing an overall response rate of 27% and
median duration of response of 9.4 months. In addition, CTI
Therapeutics Pixuvri received a complete response letter in April
2010 in R/R aggressive NHL in which a 37% overall response rate and
5.5 month duration of response was observed.
ACT’s
building blocks are T cells, a type of immune cell collected from
the patient’s own blood. After collection, the T cells are
genetically engineered to produce special receptors on their
surface called chimeric antigen receptors ("CARs"). CARs are
proteins that allow the T cells to recognize a specific protein
(antigen) on tumor cells. These engineered CAR T cells are then
grown in the laboratory until they number in the billions. The
expanded population of CAR T cells is then infused into the
patient. After the infusion, if all goes as planned, the T cells
multiply in the patient’s body and, with guidance from their
engineered receptor, recognize and kill cancer cells that harbor
the antigen on their surfaces. This process builds on a similar
form of ACT pioneered from NCI’s Surgery Branch for patients
with advanced melanoma. According to www.cancer.gov, in 2013,
NCI’s Pediatric Oncology Branch commented that the CAR T
cells are much more potent than anything they can achieve with
other immune-based treatments being studied. Although investigators
working in this field caution that there is still much to learn
about CAR T-cell therapy, the early results from trials like these
have generated considerable optimism. Researchers opined that CAR
T-cell therapy eventually may become a standard therapy for some
B-cell malignancies like ALL and chronic lymphocytic
leukemia.
So
far, chimeric antigen receptor T cell therapy such as CD19 CAR-T,
have been tested in several hematological indications on patients
that are refractory/relapsing to chemotherapy, and many of them
have relapsed after stem cell transplantation. All of these
patients had very limited treatment option prior to CAR-T therapy.
CAR-T has shown positive clinical efficacy in many of these
patients. Some of have them lived for years post CAR-T treatment.
Management believes the remaining risk in monetizing cancer immune
cell therapies is concentrated in late stage clinical studies,
speed-to-approval, manufacturing and process
optimization.
On July
2016, Juno Therapeutics, Inc. reported the death of patients
enrolled in the U.S. Phase II clinical trial of JCAR015 for the
treatment of relapsed or refractory B cell acute lymphoblastic
leukemia (B-ALL). The US FDA put the trial on hold and lifted the
hold within a week after Juno provided satisfactory explanation and
solution. Juno believes that the patient deaths were caused by the
use of Fludarabine preconditioning and they will use only
cyclophosphamide pre-conditioning in the future enrollment. The
trial was halted in November of 2016 after two more deaths occurred
after the trial resumed. The Company believes that its product and
study are distinguishable from Juno Therapeutics and plans to
continue to monitor any toxicities associated with the
study.
In
August 2017, the FDA approved Novartis’ CAR-T therapy on
relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL),
the most common cancer in Children. Current treatments show a rate
of 80% remission using intensive chemotherapy. However, there are
almost no conventional treatments to help patients who have
relapsed. Novartis’ Tisagenlecleucel (Kymriah), a
CD19-targeted CAR-T therapy for children and adolescents with r/r
ALL has shown results of complete and long lasting remission, which
led the FDA to approve the drug funded by Novartis and the first
CAR-T therapy.
In
October 2017, the FDA approved Kite Pharmaceuticals’ (Gilead)
CAR-T therapy for DLBCL, the most common type of NHL in adults. The
initial results of axicabtagene ciloleucel (Yescarta), Kite
Pharma’s drug for NHL, shows four out of seven patients
treated achieved complete remission, which continued after 12
months. The prognosis of high-grade chemo refractory NHL is dismal
with a medium survival time of a few weeks. Yescarta is a therapy
for patients who have not responded to or who have relapsed after
at least two other kinds of treatment.
In
December 2017, the Chinese government issued trial guidelines
concerning the development of cell therapy products in China.
Although these trial guidelines are not yet codified as mandatory
regulations, we believe they provide a measure of clarity and a
preliminary regulatory pathway for our cell therapy operations in a
still uncertain regulatory environment.
Market for Cell-Based Therapies
In
2013, U.S. sales of products which contain stem cells or progenitor
cells or which are used to concentrate autologous blood, bone
marrow or adipose tissues to yield concentrations of stem cells for
therapeutic use were, conservatively, valued at $236 million at the
hospital level. It is estimated that the orthopedics industry used
approximately 92% of the stem cell products.
The
forecast is that in the United States, shipments of treatments with
stem cells or instruments which concentrate stem cell preparations
for injection into painful joints will fuel an overall increase in
the use of stem cell based treatments and an increase to $5.7
billion in 2020, with key growth areas being Spinal Fusion, Sports
Medicine and Osteoarthritis of the joints. According to Centers for
Disease Control and Prevention. Prevalence of doctor-diagnosed
arthritis and arthritis-attributable activity limitation United
States. 2010-2012, Osteoarthritis (OA) is a chronic disease that is
characterized by degeneration of the articular cartilage,
hyperosteogeny, and ultimately, joint destruction that can affect
all of the joints. According to Dillon CF, Rasch EK, Gu Q et al.
Prevalence of knee osteoarthritis in the United States: Arthritis
Data from the Third National Health and Nutrition Examination
Survey 1991-94. J Rheumatol. 2006, the incidence of OA is 50% among
people over age 60 and 90% among people over age 65. KOA accounts
for the majority of total OA conditions and in adults, OA is the
second leading cause of work disability and the disability
incidence is high (53%). The costs of OA management have grown
exponentially over recent decades, accounting for up to 1% to 2.5%
of the gross national product of countries with aging populations,
including the U.S., Canada, the UK, France, and Australia.
According to the American Academy of Orthopedic Surgeons (AAOS),
the only pharmacologic therapies recommended for OA symptom
management are non-steroidal anti-inflammatory drugs (NSAIDs) and
tramadol (for patients with symptomatic osteoarthritis). Moreover,
there is no approved disease modification therapy for OA in the
world. Disease progression is a leading cause of hospitalization
and ultimately requires joint replacement surgery. In 2009, the
U.S. spent over $42 billion on replacement surgery for hip and knee
joints alone. International regulatory guidelines on clinical
investigation of medicinal products used in the treatment of OA
were updated in 2015, and clinical benefits (or trial outcomes) of
a disease modification therapy for KOA has been well defined and
recommended. Medicinal products used in the treatment of
osteoarthritis need to provide both a symptom relief effect for at
least 6 months and a structure modification effect to slow
cartilage degradation by at least 12 months. Symptom relief is
generally measured by a composite questionnaire Western Ontario and
McMaster Universities Osteoarthritis Index (WOMAC) score, and
structure modification is measured by MRI, or radiographic image as
accepted by international communities. The Company uses the WOMAC
as primary end point to demonstrate symptom relief, and MRI to
assess structure and regeneration benefits as a secondary
endpoint.
According to the
Foundation for the National Institutes of Health, there are 27
million Americans with OA, and symptomatic KOA occurs in 13% of
persons aged 60 and older. The International Journal of Rheumatic
Diseases, 2011 reports that approximately 57 million people in
China suffer from KOA. Currently no treatment exists that can
effectively preserve knee joint cartilage or slow the progression
of KOA. Current common drug-based methods of management, including
anti-inflammatory medications (NSAIDs), only relieve symptoms and
carry the risk of side effects. Patients with KOA suffer from
compromised mobility, leading to sedentary lifestyles; doubling the
risk of cardiovascular diseases, diabetes, and obesity; and
increasing the risk of all causes of mortality, colon cancer, high
blood pressure, osteoporosis, lipid disorders, depression and
anxiety. According to the Epidemiology of Rheumatic Disease (Silman
AJ, Hochberg MC. Oxford Univ. Press, 1993:257), 53% of patients
with KOA will eventually become disabled.
The
number of cell therapy companies that are currently in Phase 2 and
Phase 3 trials has been gathering momentum, and we anticipate that
new cellular therapy products will appear on the market within the
next several years.
Our Targeted Indications and Potential Therapies
Knee Osteoarthritis (KOA)
We are
currently pursuing two primary therapies for the treatment of KOA:
our Re-Join ® therapy and our AlloJoinTM therapy.
We
completed the Phase I/IIa clinical trial for the treatment of KOA.
The trial tested the safety and efficacy of intra-articular
injections of autologous haMPCs in order to reduce inflammation and
repair damaged joint cartilage. The 6-month follow-up clinical data
showed Re-JoinTM therapy to be
both safe and effective.
In the
second quarter of 2014, we completed patient enrollment for the
Phase IIb clinical trial of Re-Join® for KOA. The multi-center
study has enrolled 53 patients to participate in a randomized,
single blind trial. We published 48 weeks follow-up data of Phase
I/IIa on December 5, 2014. The 48 weeks data indicated that
patients have reported a decrease in pain and a significant
improvement in mobility and flexibility, while the clinical data
shows our Re-Join® regenerative medicine treatment to be safe.
We announced positive Phase IIb 48-week follow-up data in January
2016, with statistical significant evidence that Re-Join®
enhanced cartilage regeneration, which concluded the planned phase
IIb trial.
In January 2016, we launched the Allogeneic KOA Phase I Trial in
China to evaluate the safety
and efficacy of AlloJoin™, an off-the haMPC therapy for the
treatment of KOA. On August 5, 2016 we completed patient treatment
for the Allogeneic KOA Phase I
trial. On August 5, 2016 we completed patient treatment for
the Allogenic KOA Phase I Trial, and on December 9, 2016, we
announced interim 3-month safety data from the Allogenic KOA Phase
I Trial in China. The interim analysis of the trial has
preliminarily demonstrated a safety and tolerability profile of
AlloJoin™ in the three doses tested, and no serious adverse
events (SAE) have been observed. In March 2018, we announced
48-week clinical data from our Phase I clinical trial in China for
AlloJoin™ for KOA. The 48-week analysis of study data of 22
patients demonstrated AlloJoin™ off-the-shelf allogeneic stem
cell therapy for KOA to have good safety tolerance and early signs
of efficacy in preventing cartilage deterioration. The total WOMAC
scores (consisting of pain, stiffness and function scores of
joints) as a primary end point showed a significant improvement at
12 weeks post AlloJoin™ cell therapy and continued
improvement at 48 weeks. The secondary evaluation end point, the
data of 3D spoiled gradient-recalled echo (SPGR) quantitative
magnetic resonance imaging (MRI) for whole knee cartilage volume at
48 weeks, showed an increased tendency when compared with that at
baseline 0 weeks, and as compared with normal cartilage
deterioration as a result of aging.
Osteoarthritis is a
degenerative disease of the joints. KOA is one of the most common
types of osteoarthritis. Pathological manifestation of
osteoarthritis is primarily local inflammation caused by immune
response and subsequent damage of joints. Restoration of immune
response and joint tissues are the objective of
therapies.
According to
International Journal of Rheumatic
Diseases, 2011, 53% of KOA patients will degenerate to the
point of disability. Conventional treatment usually involves
invasive surgery with painful recovery and physical therapy. As
drug-based methods of management are ineffective, the same journal
estimates that some 1.5 million patients with this disability will
degenerate to the point of requiring artificial joint replacement
surgery every year. However, only 40,000 patients will actually be
able to undergo replacement surgery, leaving the majority of
patients to suffer from a life-long disability due to lack of
effective treatment.
haMPCs
are currently being considered as a new and effective treatment for
osteoarthritis, with a huge potential market. Osteoarthritis is one
of the ten most disabling diseases in developed countries.
Worldwide estimates are that 9.6% of men and 18.0% of women aged
over 60 years have symptomatic osteoarthritis. It is estimated that
the global OA therapeutics market was worth $4.4 billion in 2010
and is forecast to grow at a compound annual growth rate
(“CAGR”) of 3.8% to reach $5.9 billion by
2018.
In
order to bring haMPC-based KOA therapy to market, our market
strategy is to: (a) establish regional laboratories that comply
with cGMP standards in Shanghai and Beijing that meet Chinese
regulatory approval; and (b) file joint applications with Class AAA
hospitals to use haMPCs to treat KOA in a clinical trial
setting.
Our
competitors are pursuing treatments for osteoarthritis with knee
cartilage implants. However, unlike their approach, our KOA therapy
is not surgically invasive. It uses a small amount (30ml) of
adipose tissue obtained via liposuction from patients, which is
cultured and re-injected into the patient. The injections are
designed to induce the body’s secretion of growth factors
promoting immune response and regulation, and regrowth of
cartilage. The down-regulation of the patient’s immune
response is aimed at reducing and controlling inflammation which is
a central cause of KOA.
We
believe our proprietary method, subsequent haMPC proliferation and
processing know-how will enable haMPC therapy to be a low cost and
relatively safe and effective treatment for KOA. Additionally,
banked haMPCs can continue to be stored for additional use in the
future.
Immuno-oncology (I/o)
We
continue to fortify our cancer breakthrough technology platform
with I/o, programmed cell death and vaccine
technology.
Our
CAR-T platform is built on lenti-virial vector and
second-generation CAR design, which is used by most of the current
trials and studies. We rigorously select the patient population for
each asset and indication to allow the optimal path forward for
regulatory approval. We also fully integrate the state of art
translational medicine effort into each clinical study to aid in
dose selection, to confirm the mechanism of action and proof of
concept, and to identify the optimal targeting patient population
whenever appropriate. We plan to continue to grow our translational
medicine team and engage key opinion leaders to meet the
demand.
Solid
tumors pose more challenges than hematological cancers. The
patients are more heterogeneous, making it difficult to have one
drug to work effectively in the majority of the patients in any
cancer indication. The duration of response is most likely shorter
and patients are likely to relapse even after initial positive
clinical response. We will continue our efforts in developing cell
based therapies to target both hematological cancers and solid
tumors.
Human Adipose-Derived Mesenchymal Progenitor Cells
(haMPC)
Adult
mesenchymal stem cells can currently be isolated from a variety of
adult human sources, such as liver, bone marrow, and adipose (fat)
tissue. We believe the advantages in using adipose tissue (as
opposed to bone marrow or blood) are that it is one of the richest
sources of pluripotent cells in the body, the easy and repeatable
access to fat via liposuction, and the simple cell isolation
procedures that can begin to take place even on-site with minor
equipment needs. The procedure we are testing for KOA involves
extracting a very small amount of fat using a minimally invasive
extraction process which takes up to 20 minutes, and leaves no
scarring. The haMPC cells are then processed and isolated on site,
and injected intra articularly into the knee joint with ultrasound
guidance.
These
haMPC cells are capable of differentiating into bone, cartilage,
tendon, skeletal muscle, and fat under the right conditions. As
such, haMPCs are an attractive focus for medical research and
clinical development. Importantly, we believe both allogeneic and
autologously sourced haMPCs may be used in the treatment of
disease. Numerous studies have provided preclinical data that
support the safety and efficacy of allogeneic and autologously
derived haMPC, offering a choice for those where factors such as
donor age and health are an issue.
Additionally,
certain disease treatment plans call for an initial infusion of
these cells in the form of SVF, an initial form of cell isolation
that can be completed and injected within ninety minutes of
receiving lipoaspirate. The therapeutic potential conferred by the
cocktail of ingredients present in the SVF is also evident, as it
is a rich source for preadipocytes, mesenchymal stem cells,
endothelial progenitor cells, T regulatory cells and
anti-inflammatory macrophages.
Tumor Cell Specific Dendritic Cells (TC-DC)
Recent
scientific findings indicate the presence of special cells in
tumors that are responsible for cancer metastases and relapse.
Referred to as “cancer stem cells”, these cells make up
only a small portion of the tumor mass. The central concept behind
TC-DC therapy is to immunize against these cells. TC-DC therapy
takes a sample of the patient’s own purified and irradiated
cancer cells and combines them with specialized immune cells,
thereby ‘educating’ the immune cells to destroy the
cancer stem cells from which tumors arise. We believe the selective
targeting of cells that drive tumor growth would allow for
effective cancer treatment without the risks and side effects of
current therapies that also destroy healthy cells in the
body.
Our Strategy
The
majority of our biopharmaceutical business is in the development
stage. We intend to concentrate our business on cell therapies and
in the near-term, carrying our KOA stem cell therapy and cancer
immune cell therapies to commercialization.
We are
developing our business in cell therapeutics and capitalizing on
the increasing importance and promise that adult stem cells have in
regenerative medicine. Our most advanced candidate involves
adipose-derived mesenchymal stem cells to treat KOA. Based on
current estimates, we expect our biopharmaceutical business to
generate revenues primarily through the development of therapies
for the treatment of KOA within the next three to four
years.
Presently we have
two completed KOA cell therapy clinical studies in China, a Phase
IIb autologous study and a Phase I allogeneic study. If and when
either therapy obtains regulatory approval in the PRC, we will be
able to market and offer the therapy for clinical use in
China.
Our
strategy is to develop safe and effective cellular medicine
therapies for indications that represent a large unmet need in
China, based on technologies developed both in-house and obtained
through acquisition, licensing and collaboration arrangements with
other companies. Our near term objective is to pursue successful
clinical trials in China for our KOA application. We intend to
utilize our comprehensive cell platform to support multiple cell
lines to pursue multiple therapies, both allogeneic and autologous.
We intend to apply U.S. Standard Operating Procedures ("SOPs") and
protocols while complying with Chinese regulations, while owning,
developing and executing our own clinical trial protocols. We plan
to establish domestic and international joint ventures or
partnerships to set up cell laboratories and/or research
facilities, acquire technology or in-license technology from
outside of China, and build affiliations with hospitals, to develop
a commercialization path for our therapies, once approved. We
intend to use our first-mover advantage in China, against a
backdrop of enhanced regulation by the central government, to
differentiate ourselves from the competition and establish a
leading position in the China cell therapeutic market. We also
intend to out-license our technologies to interested
parties.
With
the AG acquisition we intend to monetize AG’s U.S. and
Chinese intellectual property for immune cell therapy preparation
methodologies and patient immunity assessment by engaging with
prominent hospitals to conduct pre-clinical and clinical studies in
specific cancer indications. The T Cell clonality analysis
technology patent, together with AG’s other know-hows for
immunity analysis, will enable us to establish an immunoassay
platform that is crucial for immunity evaluation of patients with
immune disorders as well as cancerous diseases that are undergoing
therapy. We will continue to seek to empower hospitals’
immune cell cancer development programs that help patients improve
their quality of life and survival rate.
We
believe that few competitors in China are as well-equipped as we
are in the clinical trial development, diversified FDA protocol
compliant manufacturing facilities, regulatory compliance and
policy making participation, as well as a long-term presence in the
U.S. with U.S.-based management and investor base.
We
intend to continue our business development efforts by adding other
proven domestic and international biotechnology partners to
monetize the China health care market.
In
order to expedite fulfillment of patient treatment, we have been
actively developing technologies and products with a strong
intellectual properties protection, including haMPC, derived from
fat tissue, for the treatment of KOA and other indications. Our
acquisition of AG provides an enlarged opportunity to expand the
application of its cancer therapy-enabling technologies and to
initiate clinical trials with leading cancer
hospitals.
Our
proprietary and patent-protected production processes and clinical
protocols enable us to produce raw material, manufacture cells, and
conduct cell banking and distribution. These protocols include
medical assessment to qualify each patient for treatment,
evaluation of each patient before and after a specific therapy,
cell transplantation methodologies including dosage, frequency and
the use of adjunct therapies, potential adverse effects and their
proper management. Applying our proprietary intellectual property,
we will be able to customize specialize formulations to address
complex diseases and debilitating conditions.
We have
been developing disease-specific clinical treatment protocols.
These protocols are designed for each of these proprietary cell
lines to address patient-specific medical conditions. These
protocols include medical assessment to qualify each patient for
treatment, evaluation of each patient before and after a specific
therapy, cell transplantation methodologies including dosage,
frequency and the use of adjunct therapies, potential adverse
effects and their proper management.
The
protocol of allogeneic haMPC therapy for KOA has been approved by
Shanghai Renji Hospital’s Institutional Review Board for
clinical studies. Once the studies are completed, the clinical data
will be analyzed by qualified third party statisticians and reports
will be published.
We
operate our manufacturing facilities under the design of GMP
conditions in the ISO accredited laboratories standard. We employ
an institutionalized and proprietary process and quality management
system to optimize reproducibility and to hone our efficiency.
Three facilities designed and built to GMP in Beijing, Shanghai and
Wuxi, China meet international standards. With our integrated
Plasmid, Viral Vectors, and CART cells Chemistry,
Manufacturing, and Controls processes as well as planned capacity
expansion, we are highly distinguishable with other companies in
the cellular medicine space.
In
total, our cGMP facilities have approximately 70,000 sq. ft. of
space and are expected to have a capacity to treat approximately
10,000 cancer patients and 10,000 patients per year.
Most
importantly, our most experienced team members have more than 20
years of relevant experience in China, European Union, and the
United States. All of these factors make CBMG a high quality cell
products manufacturer in China.
In the
next 12 months, we aim to accomplish the following, though there
can be no assurances that we will be able to accomplish any of
these goals:
●
Bolster R&D resources to fortify our
intellectual properties portfolio and scientific development.
Continue to develop a competitive Immuno-oncology pipeline for
CBMG. Seek opportunities
to file new patents in China and potentially the rest of the
world;
●
Continue to identify and evaluate advanced technologies and seek
partnerships to bolster our competitive edge in the cell therapy
field in China;
●
Submit to the CFDA an IND package for C-CAR011 in treating patients
with CD19+ B-cell malignancies.
●
Confirm the safety and efficacy profile of C-CAR011 in China in
refractory aggressive DLBCL and to initiate a larger Phase II
clinical trial whenever feasible.
●
Confirm the safety and efficacy of C-CAR011 in relapsed and
refractory (r/r) CD19+ B-cell Acute Lymphoblastic Leukemia (ALL) in
China, and / to prepare for a follow up multicenter phase IIb
trial.
●
Initiate an investigator sponsored phase I trial of anti-BCMA CART
in adults with relapsed/refractory multiple myeloma;
●
Implement our GE Joint Technology Laboratory to develop control
processes for the manufacturing of CAR-T and Stem Cell
Therapies;
●
Implement steps to advance our Thermo Fisher joint Cell Therapy
Technology Innovation and Application Center;
●
Initiate a clinical study to support the biological license
application (BLA) for autologous and allogeneic KOA study in
China;
●
Complete Chemistry, Manufacturing and Controls (CMC), non-clinical
and preclinical study data package to prepare for Allogeneic KOA
IND filing in the United States;
●
Initiate clinical study to support the BLA for allogeneic KOA study
in the United States;
●
Evaluate new regenerative medicine technology platform for other
indications and review recent development in the competitive
landscape;
●
Evaluate our corporate development strategy on maintaining the
CAR-T and regenerative medicine dual technology
platform;
●
Evaluate the feasibility and opportunities of novel Alpha
Fetoprotein Specific TCR to redirect T Cells for a Hepatocellular
Carcinoma (HCC) Immunotherapy;
●
Evaluate the addition of cancer diagnostics to our business;
and
●
Improve liquidity and fortify our balance sheet by courting
institutional investors.
Manufacturing
We
manufacture cells for our own research, testing and clinical
trials. We are scaling up and expanding our manufacturing capacity
to treat up to 10,000 CAR-T and 10,000 KOA patients per year when
our facilities are fully operational by the end of 2018. Our
facilities are operated by a manufacturing and technology team with
decades of relevant experience in China, the EU and the United
States.
In any
precision setting, it is vital that all controlled environment
equipment meet certain design standards. We operate our
manufacturing facilities under GMP conditions in the ISO accredited
laboratories standard. We employ an institutionalized and
proprietary process and quality management system to optimize
reproducibility and to hone our efficiency. Three of our facilities
designed and built to GMP in Beijing, Shanghai and Wuxi, China meet
international standards. Specifically, our Shanghai cleanroom
facility underwent rigorous cleanroom certification since 2013. Our
facility in Shanghai was issued a Certificate of Compliance by ENV
Services, Inc., an ISO Inspection Service Provider, that (i) its
rooms 1-7, 10 are certified to ISO Class 7 per ISO-14644 in
accordance with cGMP. (ii) its biological safety cabinets are
certified per NSF/ANSI 49 and to ISO Class 5. and (iii) its
instrumentation calibration has been certified to perform in
accordance with ANSI/NCSL Z540-1 and document in accordance with
10CFR21. The cleanrooms in Beijing are certified to meet the
standard of CNAS L1669 and our Wuxi facility has been certified to
meet the CNAS SHPMCC standard. With our integrated Plasmid, Viral
Vectors, and CAR-T cells Chemistry, Manufacturing, and Controls
processes as well as planned capacity expansion, we believe that
are highly distinguishable with other companies in the cellular
medicine space.
In
January 2017, we leased a 113,038-square foot building located in
the “Pharma Valley” of Shanghai, the People’s
Republic of China. We are establishing 43,000 square foot GMP
facilities there with 25 clean-rooms and equipped with 12
independent production lines to support clinical batch production
and commercial scale manufacturing. With above expansion, the
Company could support up to 10,000 patients with CAR-T therapy and
10,000 KOA patients with the stem cell therapy per
annum.
We have
built cell preparation and inspection laboratories that enable the
following mode of human body immune cell in-vitro culture service
to be provided: make cell preparation for human body venous blood
samples, after completion of the cell preparation, deliver the
immune cell agents to the customer; and provide immune function
evaluation for the patients in Jilin and several other hospitals in
China.
Competition
Many
companies operate in the cellular biopharmaceutical field. In 2010,
the FDA approved the first cell therapy for Dendreon Corporation to
apply an autologous cellular immunotherapy for the treatment of a
certain type of prostate cancer. In May 2012, the Canadian
authorities approved the first stem cell drug and granted Osiris
Therapeutics’ manufactured stem cell product for use in the
pediatric graft-versus-host disease. To date, there are over 30
publicly listed and several private cellular biopharmaceutical
focused companies outside of China with varying phases of clinical
trials addressing a variety of diseases. We compete with these
companies in bringing cellular therapies to the market. However,
our focus is to develop a core business in the China market. This
difference in focus places us in a different competitive
environment from other western companies with respect to fund
raising, clinical trials, collaborative partnerships, and the
markets in which we compete.
The PRC
central government has a focused strategy to enable China to
compete effectively in certain designated areas of biotechnology
and the health sciences. Because of the aging population in China,
China’s Ministry of Science and Technology
(“MOST”) has targeted stem cell development as high
priority field, and development in this field has been intense in
the agencies under MOST. For example, the 973 Program has funded a
number of stem cell research projects such as differentiation of
human embryonic germ cells and the plasticity of adult stem cells.
Notwithstanding such government support, China has had a highly
fragmented cellular medicine landscape. Shenzhen Beike
Biotechnology Co. Ltd. (“Beike”) and Union Stem Cell
& Gene Engineering Co., Ltd. (“Union Stem Cell”)
are two large stem cell companies in China. To the best of our
knowledge, none of the Chinese companies are utilizing our proposed
international manufacturing protocol and our unique technologies in
conducting what we believe will be fully compliant CFDA-sanctioned
clinical trials to commercialize cell therapies in China. Our
management believes that it is difficult for most of these Chinese
companies to turn their results into translational stem cell
science or commercially successful therapeutic products using
internationally acceptable standards.
We
compete globally with respect to the discovery and development of
new cell based therapies, and we also compete within China to bring
new therapies to market. The biotechnology industry, namely in the
areas of cell processing and manufacturing, clinical development of
cellular therapies and cell collection, processing and storage, are
characterized by rapidly evolving technology and intense
competition. Our competitors worldwide include pharmaceutical,
biopharmaceutical and biotechnology companies, as well as numerous
academic and research institutions and government agencies engaged
in drug discovery activities or funding, in the U.S., Europe and
Asia. Many of these companies are well-established and possess
technical, research and development, financial, and sales and
marketing resources significantly greater than ours. In addition,
many of our smaller potential competitors have formed strategic
collaborations, partnerships and other types of joint ventures with
larger, well established industry competitors that afford these
companies potential research and development and commercialization
advantages in the technology and therapeutic areas currently being
pursued by us. Academic institutions, governmental agencies and
other public and private research organizations are also conducting
and financing research activities which may produce products
directly competitive to those being commercialized by us. Moreover,
many of these competitors may be able to obtain patent protection,
obtain government (e.g. FDA) and other regulatory approvals and
begin commercial sales of their products before us.
Our
primary competitors in the field of stem cell therapy for
osteoarthritis, and other indications include Beike, Cytori
Therapeutics Inc.(“Cytori”), Caladrius Biosciences,
Inc. and others. Among our competitors, to our knowledge, the only
ones based in and operating in Greater China are Beike, Lorem
Vascular and Olife Bio. Lorem Vascular has partnered with Cytori to
commercialize Cytori Cell Therapy for the cardiovascular, renal and
diabetes markets in China and Hong Kong. Olife Bio, a Medi-Post
joint venture with JingYuan Bio in Taian, Shandong Province, plans
to initiate clinical trial in China in 2016. Our primary
competitors in the field of cancer immune cell therapies include
pharmaceutical, biotechnology companies such as Northwest
Biotherapeutics, Inc., Juno Therapeutics, Inc., Kite Pharma, Inc.,
CARSgen, Sorrento Therapeutics, Inc. and others. Among our
competitors, the ones based in and operating in Greater China are
BeiGene, Limited, CARsgen and China Oncology Focus Limited, which
has licensed Sorrento’s anti-PD-L1 monoclonal antibody for
Greater China. Other western big pharma and biotech companies in
the cancer immune cell therapies space are starting to make inroads
into China by partnering or seeking to partner with local
companies. For example, in April, 2016, Seattle-based Juno
Therapeutics, Inc. started a new company with WuXi AppTec in China
named JW Biotechnology (Shanghai) Co., Ltd. Its mission is to build
China's leading cell therapy company by leveraging Juno's chimeric
antigen receptor (CAR) and T cell receptor (TCR) technologies
together with WuXi AppTec's R&D and manufacturing platform and
local expertise to develop novel cell-based immunotherapies for
patients with hematologic and solid organ cancers. In January 2017,
Shanghai Fosun Pharmaceutical created a joint venture with Santa
Monica-based Kite Pharma Inc. to develop, manufacture and
commercialize axicabtagene ciloleucel in China with the option to
include additional products, including two T cell receptor (TCR)
product candidates from Kite. Axicabtagene ciloleucel is Kite's
lead product candidate and is an investigational chimeric antigen
receptor (CAR) T-cell therapy under development for the treatment
of B-cell lymphomas and leukemias. In late 2017 Gilead acquired
Kite Pharma for $11.9 billion. On January 22, 2018 Celgene
announced that it had agreed to buy Juno Therapeutics for
approximately $9 billion.
The
CFDA has received six applications for CD19 chimeric antigen
receptor T cells cancer therapies from different companies. The
applicants are Nanjing Legend biotechnology, Chengdu Yinhe
Biological Medicine, Shanghai HRAIN Biotechnology, Carsgene
Biomedicine (Shanghai), Biogene ANKE Cell Technology and Shanghai
Mingju Biotechnology.
Additionally, in
the general area of cell-based therapies for knee osteoarthritis
ailments, we potentially compete with a variety of companies, from
large pharmaceutical companies to specialty medical products or
biotechnology companies. Some of these, such as Abbvie, Merck KGaA,
Sanofi, Teva, GlaxosmithKline, Baxter, Johnson & Johnson,
Medtronic and Miltenyi Biotec, are well-established and have
substantial technical and financial resources compared to ours.
However, as cell-based products are only just emerging as viable
medical therapies, many of our more direct competitors are smaller
biotechnology and specialty medical products companies. These
include Vericel Corporation, Regeneus Ltd., Advanced Cell
Technology, Inc., Nuo Therapeutics, Inc., Arteriocyte Medical
Systems, Inc., Athersys, Inc., Bioheart, Inc., Cytori, Harvest
Technologies Corporation, Mesoblast, Pluristem, Inc., TissueGene,
Inc., Medipost Co., Ltd. and others. There are also several non
cell-based, small molecule and peptide clinical trials targeting
knee osteoarthritis and several other FDA approved treatment for
knee pain.
Some of
our competitors also work with adipose-derived stem cells. To our
knowledge, none of these companies are currently utilizing the same
technologies as ours to treat KOA, nor to our knowledge are any of
these companies conducting government-approved clinical trials in
China.
We
believe we have a strategic advantage over our competitors based on
our ability to meet cGMP regulatory requirements, a capability
which we believe is possessed by few to none of our competitors in
China, in an industry in which meeting exacting standards and
achieving extremely high purity levels is crucial to success. In
addition, in comparison to the broader range of cellar
biopharmaceutical firms, we believe we have the advantages of cost
and expediency, and a first mover advantage with respect to
commercialization of cell therapy products and treatments in the
Greater China market.
Corporate Structure, Subsidiaries and Affiliates
Our
current corporate structure is illustrated in the following
diagram:
We
conduct our business operations through the following subsidiaries
(including a controlled various interest entity
(“VIE”):
Cellular
Biomedicine Group HK Limited is a Hong Kong company limited by
shares, a holding company and wholly owned subsidiary of the
Company.
Cellular
Biomedicine Group Ltd. (Wuxi), license number 320200400034410 (the
“WFOE”), is a wholly foreign-owned entity that is 100%
owned by Cellular Biomedicine Group HK Limited. This entity’s
legal name in China translates to “Xi Biman Biological
Technology (Wuxi) Co. Ltd.” WFOE controls and holds ownership
rights in the business, assets and operations of Cellular
Biomedicine Group Ltd. (Shanghai) (“CBMG Shanghai”)
through variable interest entity (VIE) agreements. We conduct
certain biopharmaceutical business activities through WFOE,
including lab kit production and research.
Cellular
Biomedicine Group Ltd. (Shanghai) license number 310104000501869
(“CBMG Shanghai”), is a PRC domestic corporation, which
we control and hold ownership rights in, through WFOE and the
above-mentioned VIE agreements. This entity’s legal name in
China translates to “Xi Biman Biotech (Shanghai) Co.,
Ltd.” We conduct certain biopharmaceutical business
activities through our controlled VIE entity and CBMG Shanghai,
including clinical trials and certain other activities requiring a
domestic license in the PRC. Mr. Chen Mingzhe and Mr. Lu Junfeng
together are the record holders of all of the outstanding
registered capital of CBMG Shanghai. Mr. Chen and Mr. Lu are also
directors of CBMG Shanghai constituting the entire management of
the same. Mr. Chen and Mr. Lu receive no compensation for their
roles as managers of CBMG Shanghai.
Beijing
Agreen Biotechnology Co., Ltd. (“AG”) is a PRC domestic
corporation and a wholly owned subsidiary of CBMG
Shanghai.
Wuxi
Cellular Biopharmaceutical Group Ltd. is a PRC domestic corporation
and a wholly owned subsidiary of CBMG Shanghai.
Shanghai Cellular
Biopharmaceutical Group Ltd. was established on January 18, 2017.
It is a PRC domestic corporation and wholly owned subsidiary of
CBMG Shanghai.
Eastbridge
Investment Corporation, a Delaware corporation, is a wholly owned
subsidiary of the Company.
Cellular
Biomedicine Group VAX, Inc., a California corporation, is a wholly
owned subsidiary of the Company.
Additional Information
Since
inception and through December 31, 2017, we have recorded
accumulated losses totaling approximately $111 million. Our
historical operating losses have resulted principally from our
research and development activities, including clinical trial
activities for our product candidates and general and
administrative expenses. Ultimately, if we secure additional
approvals from the MOH, CFDA and other regulatory bodies throughout
the world for our product candidates, our goal will be to augment
our current sources of revenue and, as applicable, deferred revenue
(principally licensing fees), with sales of such products or
royalties from such sales, on which we may pay royalties or other
fees to our licensors and/or third-party collaborators as
applicable.
We have
based our estimates of development costs, market size estimates,
peak annual sales projections and similar matters described or
incorporated by reference in this prospectus on our market
research, third party reports and publicly available information
which we consider reliable. However, readers are advised that the
projected dates for filing and approval of our drug applications
with the MOH, CFDA or other regulatory authorities, our estimates
of development costs, our projected sales and similar metrics
regarding our KOA and
CD therapies or any
other product candidates discussed elsewhere (or incorporated by
reference) in this prospectus are merely estimates and subject to
many factors, many of which may be beyond our control, which will
likely cause us to revise such estimates. Readers are also advised
that our projected sales figures do not take into account the
royalties and other payments we will need to make to our licensors
and strategic partners. Our estimates are based upon our
management’s reasonable judgments given the information
available and their previous experiences, although such estimates
may not prove to be accurate.
Corporate Information
Our
principal executive offices are located at 19925 Stevens Creek
Blvd., Suite 100 Cupertino, CA 95014. Our telephone number is:
(408) 973-7884.
The Offering
Common stock outstanding prior to the offering
|
17,453,623
and 16,991,367 shares of common stock issued and outstanding as of
March 28, 2018.
|
Common stock offered by the Selling Stockholders
|
Up to
2,927,658 shares of common stock for sale by the Selling
Stockholders for their own account. These shares
include:
(i) Up
to 41,667 shares of our common stock issued in connection with the
Management Tranche;
(ii) up
to 1,166,667 shares of our common stock issued in connection with
the Investor Tranche;
(iii)
up to 1,719,324 shares of our common stock issued in connection
with the February PIPE.
|
Proceeds
|
We will
not receive any proceeds from the sale of our common stock by the
Selling Stockholders.
|
Risk Factors
|
The
securities offered hereby involve a high degree of risk. See
“Risk Factors.”
|
NASDAQ Global Market Symbol
|
CBMG
|
The
number of shares of our common stock that will be outstanding
immediately prior this offering as shown above is based on
17,453,623 shares outstanding as of March 28, 2018. The number of
shares outstanding as of the date of this prospectus, as used
throughout this prospectus, unless otherwise indicated, excludes
the following, all as of March 28, 2018:
●
273,847 shares
of our common stock issuable upon exercise of stock options
outstanding under our 2011 Incentive Stock Option Plan, which had a
weighted average exercise price of $5.77 per share;
●
648,378 shares
of our common stock issuable upon exercise of stock options
outstanding under our 2013 Stock Incentive Plan, which had a
weighted average exercise price of $ 9.19 per share;
and
●
891,727 shares
of our common stock issuable upon exercise of stock options
outstanding under our 2014 Stock Incentive Plan, which had a
weighted average exercise price of $15.74 per share, and 856,481
shares of our common stock outstanding under our 2014 Stock
Incentive Plan subject to vest before March 27, 2022.
RISK FACTORS
We have
included discussions of the risks, uncertainties and assumptions
under the heading “Risk Factors” included in our Annual
Report on Form 10-K for the year ended December 31, 2017, which
risk factors are incorporated by reference into this prospectus.
See “Where You Can Find More Information” for an
explanation of how to get a copy of this report. Additional risks
related to our securities may also be described in a prospectus
supplement and in any related free writing prospectus that we may
authorize to be provided to you.
Investing in our securities involves a high
degree of risk. Before deciding whether to invest in our
securities, you should carefully consider the risk factors we
describe in any prospectus supplement and in any related free
writing prospectus that we may authorize to be provided to you or
in any report incorporated by reference into this prospectus or
such prospectus supplement, including our Annual Report on Form
10-K for the year ended December 31, 2017, or any Annual Report on
Form 10-K or Quarterly Report on Form 10-Q that is incorporated by
reference into this prospectus or such prospectus supplement after
the date of this prospectus. Although we discuss key risks in those
risk factor descriptions, additional risks not currently known to
us or that we currently deem immaterial also may impair our
business. Our subsequent filings with the SEC may contain amended
and updated discussions of significant risks. We cannot predict
future risks or estimate the extent to which they may affect our
financial performance.
Please
also read carefully the section above entitled “Cautionary
Note Regarding Forward-Looking Statements.”
USE OF PROCEEDS
We will
not receive any proceeds from the sale of shares registered
hereunder by the selling stockholders.
DETERMINATION OF OFFERING PRICE
The
selling stockholders will offer common stock at the prevailing
market prices or privately negotiated price as they may determine
from time to time.
The
offering price of our common stock to be sold by the selling
stockholders does not necessarily bear any relationship to our book
value, assets, past operating results, financial condition or any
other established criteria of value. The facts considered in
determining the offering price were our financial condition and
prospects, our limited operating history and the general condition
of the securities market.
In
addition, there is no assurance that our common stock will trade at
market prices in excess of the offering price as prices for common
stock in any public market will be determined in the marketplace
and may be influenced by many factors, including the depth and
liquidity.
SELLING STOCKHOLDERS
The
following table sets forth certain information as of March 28, 2018
regarding the selling stockholders and the shares offered by them
in this prospectus. In computing the number of shares owned by a
person and the percentage ownership of that person in the table
below, securities that are currently convertible or exercisable
into shares of our common stock that are being offered in this
prospectus are deemed outstanding. Such shares, however, are not
deemed outstanding for the purposes of computing the percentage
ownership of any other person. Except as indicated in the footnotes
to the following table, each stockholder named in the table has
sole voting and investment power with respect to the shares set
forth opposite such stockholder’s name. The percentage of
ownership of each selling stockholder in the following table is
based upon 17,453,623 shares of common stock issued as of March 28,
2018 plus shares the selling stockholders will receive upon
exercise of warrants or conversion of debt which are being offered
in this offering.
Except
as set forth below, no selling stockholder has held a position as
an officer or director of the Company, nor has any material
relationship of any kind with us or any of our affiliates. All
information with respect to share ownership has been furnished by
the selling stockholders. The common stock being offered is being
registered to permit secondary trading of the shares and the
selling stockholders may offer all or part of the common stock
owned for resale from time to time. Except as set forth below, none
of the selling stockholders have any family relationships with our
officers, directors or controlling stockholders. Furthermore, none
of the selling stockholders are a registered broker-dealer or an
affiliate of a registered broker-dealer.
The
term “selling stockholder” also includes any
transferees, pledges, donees, or other successors in interest to
the selling stockholder named in the table below. To our knowledge,
subject to applicable community property laws, each person named in
the table has sole voting and investment power with respect to the
common stock set forth opposite such person’s name. We will
file a supplement to this prospectus (or a post-effective amendment
hereto, if necessary) to name successors to any named selling
stockholder who is able to use this prospectus to resell the
securities registered hereby.
* Less
than 1%
(1)
James Xiao Dong Liu is the sole director of Wealth Map Holdings
Limited. The investment committee of Sailing Capital Overseas
Investments Fund, L.P. has decision making power over voting and
disposition of the CBMG securities owned by Wealth Map Holdings
Limited.
(2)
James Xiao Dong Liu, as the sole director of Earls Mill Limited,
has voting and dispositive power over the CBMG securities owned by
Earls Mill Limited.
(3)
RTSing Raffles Limited and RTSing Marina Limited, as the MapleBrook
Limited’s corporate directors, can act jointly to dispose of
and vote on the securities in accordance with the Memorandum of
Association of MapleBrook Limited. Britta Pfister, Patricia Tan and
Chue Chee Chen, individual directors of both RTSing Raffles Limited
and RTSing Marina Limited, have voting and dispositive power over
the shares owned by MapleBrook Limited.
(4)
Bizuo (Tony) Liu’s total number of shares owned prior to the
offering and after the offering include 35,300 options issued under
the 2011 Plan, 255,000 options issued under 2013 Plan and 325,800
options issued under 2014 Plan, of which an aggregate of 500,600
are currently vested and exercisable as of March 28,
2018.
(5)
Andrew Chan’s total number of shares owned prior to the
offering and after the offering include 53,880 options issued under
the 2011 Plan, 37,904 options issued under 2013 Plan and 38,000
options issued under 2014 Plan, of which an aggregate of 107,011
are currently vested and exercisable as of March 28,
2018.
(6)
Yihong Yao’s total number of shares owned prior to the
offering and after the offering include 61,500 options issued under
2014 Plan, of which an aggregate of 25,176 are currently vested and
exercisable as of March 28, 2018.
(7)
Ming Li, as a director of
Winsor Capital Limited, has voting and dispositive power over the
CBMG securities owned by Winsor Capital Limited .
PLAN OF DISTRIBUTION
Selling Stockholders
The
common stock held by the selling stockholders may be sold or
distributed from time to time by the selling stockholders directly
to one or more purchasers or through brokers, dealers, or
underwriters who may act solely as agents at market prices
prevailing at the time of sale, at prices related to the prevailing
market prices, at negotiated prices, or at fixed prices, which may
be changed on any stock exchange, market or trading facility on
which the shares are traded or in private transactions. The sale of
the selling stockholders’ common stock offered by this
prospectus may be effected in one or more of the following
methods:
●
ordinary brokerage transactions and transactions in which the
broker-dealer solicits purchasers;
●
transactions involving cross or block trades;
●
purchases by a broker-dealer as principal and resale by the
broker-dealer for its account;
●
an exchange distribution in accordance with the rules of the
applicable exchange;
●
in privately negotiated transactions;
●
short sales after the registration statement, of which this
prospectus forms a part, becomes effective;
●
broker-dealers may agree with the selling stockholders to sell a
specified number of such shares at a stipulated price per
share;
●
“at the market” into an existing market for the common
stock;
●
through the writing of options on the shares;
●
a combination of any such methods of sale; and
●
any other method permitted pursuant to applicable law.
In
order to comply with the securities laws of certain states, if
applicable, the shares of each of the selling stockholders may be
sold only through registered or licensed brokers or dealers. In
addition, in certain states, such shares may not be sold unless
they have been registered or qualified for sale in the state or an
exemption from the registration or qualification requirement is
available and complied with.
The
selling stockholders may also sell shares of common stock under
Rule 144 promulgated under the Securities Act, if available, rather
than under this prospectus. In addition, the selling stockholders
may transfer the shares of common stock by other means not
described in this prospectus.
The
selling stockholders may also sell the shares directly to market
makers acting as principals and/or broker-dealers acting as agents
for themselves or their customers. Such broker-dealers may receive
compensation in the form of discounts, concessions or commissions
from the selling stockholders and/or the purchasers of shares for
whom such broker-dealers may act as agents or to whom they sell as
principal or both, which compensation as to a particular
broker-dealer might be in excess of customary commissions. Market
makers and block purchasers purchasing the shares will do so for
their own account and at their own risk. It is possible that a
selling stockholder will attempt to sell shares of common stock in
block transactions to market makers or other purchasers at a price
per share which may be below the then market price. The selling
stockholders cannot assure that all or any of the shares offered in
this prospectus will be issued to, or sold by, such selling
stockholder.
Brokers,
dealers, underwriters, or agents participating in the distribution
of the shares held by the selling stockholders as agents may
receive compensation in the form of commissions, discounts, or
concessions from the selling stockholders and/or purchasers of the
common stock for whom the broker-dealers may act as agent. The
selling stockholders may agree to indemnify any agent, dealer or
broker-dealer that participates in transactions involving sales of
the shares if liabilities are imposed on that person under the
Securities Act.
Each
of the selling stockholders acquired the securities offered hereby
in the ordinary course of business and has advised us that they
have not entered into any agreements, understandings or
arrangements with any underwriters or broker-dealers regarding the
sale of their shares of common stock, nor is there an underwriter
or coordinating broker acting in connection with a proposed sale of
shares of common stock by any selling stockholder. If we are
notified by any selling stockholder that any material arrangement
has been entered into with a broker-dealer for the sale of shares
of common stock, if required, we will file a supplement to this
prospectus.
With
regard only to the shares it sells for its own behalf, each selling
stockholder may be deemed an “underwriter” within the
meaning of the Securities Act. This offering as it relates to each
selling stockholder will terminate on the date that all shares
issued to and issuable to such selling stockholder that are offered
by this prospectus have been sold by such selling
stockholder.
We
may suspend the sale of shares by the selling stockholders pursuant
to this prospectus for certain periods of time for certain reasons,
including if the prospectus is required to be supplemented or
amended to include additional material information.
If
any of the selling stockholders use this prospectus for any sale of
the shares of common stock, such selling stockholder will be
subject to the prospectus delivery requirements of the Securities
Act.
Regulation M
The
anti-manipulation rules of Regulation M under the Exchange Act of
1934, as amended (the “Exchange Act”) may apply to
sales of our common stock and activities of the selling
stockholder.
We
have advised the selling stockholders that while it is engaged in a
distribution of the shares included in this prospectus it is
required to comply with Regulation M promulgated under the Exchange
Act. With certain exceptions, Regulation M precludes the selling
stockholder, any affiliated purchasers, and any broker-dealer or
other person who participates in the distribution from bidding for
or purchasing, or attempting to induce any person to bid for or
purchase any security which is the subject of the distribution
until the entire distribution is complete. Regulation M also
prohibits any bids or purchases made in order to stabilize the
price of a security in connection with the distribution of that
security. All of the foregoing may affect the marketability of the
shares offered hereby this prospectus.
DESCRIPTION OF SECURITIES TO BE REGISTERED
General
Our
authorized capital stock consists of 300,000,000 shares of common
stock and 50,000,000 shares of preferred stock. As of the date of
this prospectus, our outstanding capital stock consists of
17,453,623 shares of common stock, $0.001 par value, and no shares
of preferred stock. These figures do not include securities that
may be issued: (i) pursuant to our Amended and Restated 2011
Incentive Plan; (ii) pursuant to our 2013 Stock Incentive Plan; or
(iii) pursuant to our 2014 Stock Incentive Plan, as
amended.
We are
a Delaware corporation and our affairs are governed by our
Certificate of Incorporation and By-laws. The following are
summaries of material provisions of our Certificate of
Incorporation and By-laws insofar as they relate to the material
terms of our common shares. Complete copies of our Certificate of
Incorporation and By-laws are filed as exhibits to our public
filings.
Common Stock
Our
common stock is listed on the Nasdaq Global Market under the symbol
“CBMG.”
All outstanding shares of common stock are of the
same class and have equal rights and attributes. The holders of
common stock are entitled to one vote per share on all matters
submitted to a vote of stockholders of the Company. All
stockholders are entitled to share equally in dividends, if any, as
may be declared from time to time by the Board of Directors out of
funds legally available. In the event of liquidation, the holders
of common stock are entitled to share ratably in all assets
remaining after payment of all liabilities. The stockholders do not
have cumulative or preemptive rights.
Dividend
Rights
Holders
of the common stock may receive dividends when, as and if declared
by our Board of Directors out of the assets legally available for
that purpose and subject to the preferential dividend rights of any
other classes or series of stock of our Company. We have never
paid, and have no plans to pay, any dividends on our shares of
common stock.
Voting
Rights
Holders
of the common stock are entitled to one vote per share in all
matters as to which holders of common stock are entitled to vote.
Holders of not less than a majority of the outstanding shares of
common stock entitled to vote at any meeting of stockholders
constitute a quorum unless otherwise required by law.
Election of Directors
Directors
hold office until the next annual meeting of stockholders and are
eligible for reelection at such meeting. Directors are elected by a
plurality of the shares present in person or represented by proxy
at the meeting and entitled to vote on the election of directors.
There is no cumulative voting for directors.
Liquidation
In
the event of any liquidation, dissolution or winding up of the
Company, holders of the common stock have the right to receive
ratably and equally all of the assets remaining after payment of
liabilities and liquidation preferences of any preferred stock then
outstanding.
Redemption
The
common stock is not redeemable or convertible and does not have any
sinking fund provisions.
Preemptive Rights
Holders
of the common stock do not have preemptive rights.
Other Rights
Our
common stock is not liable to calls or to assessment or for
liabilities imposed on our stockholders under state
statutes.
Our
board is divided into three classes, each of which will generally
serve for a term of three years with only one class of directors
being elected in each year. The common stock has no cumulative
voting rights, including with respect to the election of
directors.
LEGAL MATTERS
The
validity of the securities offered by this prospectus, and any
supplement thereto, will be passed upon for us by Ellenoff Grossman
& Schole LLP, New York, NY.
EXPERTS
The
financial statements for the years ended December 31, 2017, 2016
and 2015 incorporated in this prospectus by reference to the Annual
Report on Form 10-K for the year ended December 31, 2017 has been
so incorporated in reliance on the report of BDO China Shu Lun Pan
Certified Public Accountants LLP, an independent registered public
accounting firm, given on the authority of such firm as an expert
in auditing and accounting.
WHERE YOU CAN FIND MORE INFORMATION
We have
filed a registration statement with the Securities and Exchange
Commission under the Securities Act with respect to the shares of
our common stock offered by this prospectus. This prospectus is
part of that registration statement and does not contain all the
information included in the registration statement.
For
further information with respect to our common stock and us, you
should refer to the registration statement, its exhibits and the
material incorporated by reference therein. Portions of the
exhibits have been omitted as permitted by the rules and
regulations of the Securities and Exchange Commission. Statements
made in this prospectus as to the contents of any contract,
agreement or other document referred to are not necessarily
complete. In each instance, we refer you to the copy of the
contracts or other documents filed as an exhibit to the
registration statement, and these statements are hereby qualified
in their entirety by reference to the contract or document. The
registration statement may be inspected and copied at the public
reference facilities maintained by the Securities and Exchange
Commission at Room 1024, Judiciary Plaza, 100 F Street, N.E.,
Washington, D.C. 20549 and the Regional Offices at the Commission
located in the Citicorp Center, 500 West Madison Street, Suite
1400, Chicago, Illinois 60661, and at 233 Broadway, New York, NY
10279. Copies of those filings can be obtained from the
Commission’s Public Reference Section, Judiciary Plaza, 100 F
Fifth Street, N.E., Washington, D.C. 20549 at prescribed rates and
may also be obtained from the web site that the Securities and
Exchange Commission maintains at http://www.sec.gov. You may also
call the Commission at 1-800-SEC-0330 for more information. We file
annual, quarterly and current reports and other information with
the Securities and Exchange Commission. You may read and copy any
reports, statements or other information on file at the
Commission’s public reference room in Washington, D.C. You
can request copies of those documents upon payment of a duplicating
fee, by writing to the Securities and Exchange
Commission.
INCORPORATION OF CERTAIN INFORMATION BY REFERENCE
We are
“incorporating by reference” certain documents we file
with the SEC, which means that we can disclose important
information to you by referring you to those documents. The
information in the documents incorporated by reference is
considered to be part of this prospectus. Statements contained in
documents that we file with the SEC and that are incorporated by
reference in this prospectus will automatically update and
supersede information contained in this prospectus supplement,
including information in previously filed documents or reports that
have been incorporated by reference in this prospectus, to the
extent the new information differs from or is inconsistent with the
old information. We have filed or may file the following documents
with the SEC and they are incorporated herein by reference as of
their respective dates of filing:
●
our Annual Report on Form 10-K for the year
ended December 31, 2017 as filed with the SEC on March 5,
2018;
●
our Current Reports on Form 8-K and/or their amendments as filed
with the SEC on January 31, 2018, February 7, 2018 , February 12,
2018 and February 15, 2018;
●
the information specifically incorporated by reference into our
Annual Report on Form 10-K for the year ended December 31, 2017
from our definitive proxy statement on Schedule 14A related to our
2018 annual meeting of stockholders, which was filed with the SEC
on March 12, 2018;
●
the description of our Common Stock contained in our Form 8-A filed
with the SEC on June 13, 2014, and as it may be further amended
from time to time, under the caption “Item 1. Description of
Registrant’s Securities to be Registered.”
All
reports and definitive proxy or information statements filed
pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act
subsequent to the filing of this Registration Statement and prior
to the filing of a post-effective amendment which indicates that
all securities offered hereby have been sold or which de-registers
all securities then remaining unsold shall be deemed to be
incorporated by reference into this Registration Statement and to
be a part hereof from the date of filing such documents, except as
to specific sections of such statements as set forth therein. Any
statement contained in a document incorporated or deemed to be
incorporated by reference herein shall be deemed to be modified or
superseded for purposes of this Registration Statement to the
extent that a statement contained in any subsequently filed
document which also is deemed to be incorporated by reference
herein modifies or supersedes such statement.
You may
request a copy of these filings at no cost (other than exhibits
unless such exhibits are specifically incorporated by reference) by
writing or telephoning us at the following address and telephone
number:
Cellular
Biomedicine Group, Inc.
19925
Stevens Creek Blvd., Suite 100
Cupertino,
CA 95014
Telephone:
(408) 973-7884
Attention:
Tony Liu
DISCLOSURE OF COMMISSION POSITION ON
INDEMNIFICATION FOR SECURITIES LAW VIOLATIONS
Our
directors and officers are indemnified to the fullest extent
permitted under Delaware law. We may also purchase and maintain
insurance which protects our officers and directors against any
liabilities incurred in connection with their service in such a
capacity, and such a policy may be obtained by us in the
future.
Insofar
as indemnification for liabilities arising under the Securities Act
may be permitted to our directors, officers and controlling persons
pursuant to the foregoing, or otherwise, we have been advised that
in the opinion of the SEC such indemnification is against public
policy as expressed in the Securities Act and is, therefore,
unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by us of expenses
incurred or paid by a director, officer or controlling person of
ours in the successful defense of any action, suit or proceeding)
is asserted by such director, officer or controlling person in
connection with the securities being registered, we will, unless in
the opinion of our counsel the matter has been settled by
controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is
against public policy as expressed in the Securities Act and will
be governed by the final adjudication of such issue.
You should rely only on the information contained in this document.
We have not authorized anyone to provide you with information that
is different. This document may only be used where it is legal to
sell these securities. The information in this document may only be
accurate on the date of this document.
Additional risks and uncertainties not presently known or that are
currently deemed immaterial may also impair our business
operations. The risks and uncertainties described in this document
and other risks and uncertainties which we may face in the future
will have a greater impact on those who purchase our common stock.
These purchasers will purchase our common stock at the market price
or at a privately negotiated price and will run the risk of losing
their entire investment.
Up to 2,927,658 Shares of
Common Stock
Prospectus
, 2018
You should rely only on the information contained in this
prospectus. We have not authorized anyone to provide you with
information different from that contained in this prospectus or any
prospectus supplement. This prospectus is not an offer of these
securities in any jurisdiction where an offer and sale is not
permitted. The information contained in this prospectus is accurate
only as of the date of this prospectus, regardless of the time of
delivery of this prospectus or any sale of our common
stock.
PART II
INFORMATION NOT REQUIRED IN THE PROSPECTUS
Item 14. Other Expenses of Issuance and Distribution
The
following table sets forth an estimate of the fees and expenses,
other than the underwriting discounts and commissions, payable by
the Registrant in connection with the issuance and distribution of
the securities being registered. All the amounts shown are
estimates, except for the SEC registration fee.
SEC
Registration Fee
|
$5,904.8
|
Accounting
Fees and Expenses
|
$11,017.3
|
Legal
Fees and Expenses
|
$75,000.0
|
Total
|
$91,922.1
|
(1) These fees are
calculated based on the securities offered and the number of
issuance and accordingly cannot be estimated at this
time.
Item 15. Indemnification of Directors and Officers
Our
certificate of incorporation provides that all our directors,
officers, employees and agents shall be entitled to be indemnified
by us to the fullest extent permitted under the Delaware General
Corporation Law, provided that they acted in good faith and that
they reasoned their conduct or action was in, or not opposed to,
the best interest of our company.
Our
bylaws provide for indemnification of our officers, directors and
others who become a party to an action on our behalf by us to the
fullest extent not prohibited under the Delaware General
Corporation Law. Further, we maintain officer and director
liability insurance.
The
underwriting agreement(s) that we may enter into in connection with
the securities being offered under this registration statement may
provide for indemnification by any underwriters used by us, our
directors, our officers who sign the registration statement and our
controlling persons for some liabilities, including liabilities
arising under the Securities Act.
Insofar
as indemnification for liabilities arising under the Securities Act
may be permitted to directors, officers and controlling persons of
the Company pursuant to the foregoing provisions, or otherwise, we
have been advised that in the opinion of the Securities and
Exchange Commission such indemnification is against public policy
as expressed in the Securities Act and is, therefore,
unenforceable.
Item 16. Exhibits
The
following exhibits are filed with this Registration
statement.
ITEM 15. EXHIBITS AND
FINANCIAL STATEMENT SCHEDULES.
Exhibit Number
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Description
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*
Previously filed.
1.
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Incorporated
by reference filed with the Registration Statement on Form 10-SB
filed with the Securities and Exchange Commission on October 30,
2006 (File No. 000-52282)
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2.
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Incorporated
by reference filed with the Registration Statement on Form 10-SB/A
filed with the Securities and Exchange Commission on February 27,
2007 (File No. 000-52282)
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3.
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Incorporated
by reference filed with the Registration Statement on Form S-8
filed with the Securities and Exchange Commission on June 19, 2007
(File No. 333-143878)
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4.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on July 20, 2007 (File No.
000-52282)
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5.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on September 25, 2007 (File No.
000-52282)
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6.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on October 1, 2007 (File No.
000-52282)
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7.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on October 9, 2007 (File No.
000-52282)
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8.
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Incorporated
by reference filed with the Registration Statement on Form S-8
filed with the Securities and Exchange Commission on August 22,
2008 (File No. 333-153129)
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9.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on October 22, 2008 (File No.
000-52282)
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10.
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Incorporated
by reference filed with the Registration Statement on Form S-8
filed with the Securities and Exchange Commission on April 15, 2009
(File No. 333-158583)
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11.
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Incorporated
by reference filed with the Form 8-K/A filed with the Securities
and Exchange Commission on December 12, 2013 (File No.
000-52282)
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12.
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Incorporated
by reference filed with the Form 10-K filed with the Securities and
Exchange Commission on April 15, 2010 (File No.
000-52282)
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13.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on July 14, 2010 (File No.
000-52282)
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14.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on November 12, 2010 (File No.
000-52282
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15.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on December 7, 2010 (File No.
000-52282)
|
16.
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Incorporated
by reference filed with the Form 10-K filed with the Securities and
Exchange Commission on June 18, 2013 (File No.
000-52282)
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17.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on November 20, 2012 (File No.
000-52282)
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18.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on January 22, 2013 (File No.
000-52282)
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19.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on February 4, 2013 (File No.
000-52282)
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20.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on February 12, 2013 (File No.
000-52282)
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21.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on January 3, 2012 (File No.
000-52282)
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22.
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Incorporated
by reference filed with the Registration Statement on Form S-8
filed with the Securities and Exchange Commission on March 7, 2012
(File No. 333-179974)
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23.
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Incorporated
by reference filed with the Form 10-K filed with the Securities and
Exchange Commission on April 4, 2013 (File No.
000-52282)
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24.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on December 16, 2013 (File No.
000-52282)
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25.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on January 3, 2014 (File No.
000-52282)
|
26.
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on October 2, 2014 (File No.
001-36498)
|
27.
|
Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on July 2, 2015 (File No.
001-36498)
|
28.
|
Incorporated
by reference filed with Schedule 14A filed with the Securities and
Exchange Commission on November 21, 2013 (File No.
000-52282)
|
29.
|
Incorporated
by reference filed with Schedule 14A filed with the Securities and
Exchange Commission on September 23, 2014 (File No.
001-36498)
|
30
|
Incorporated
by reference filed with the Form 10-K filed with the Securities and
Exchange Commission on April 15, 2014 (File No.
000-52282).
|
31
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Incorporated
by reference filed with the Form 10-K filed with the Securities and
Exchange Commission on March 31, 2015 (File No.
001-36498).
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32
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Incorporated
by reference filed with the Form 10-K filed with the Securities and
Exchange Commission on March 14, 2016 (File No.
001-36498).
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33
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Incorporated
by reference filed with the Form 10-Q filed with the Securities and
Exchange Commission on May 9, 2016 (File No.
001-36498).
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34
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Incorporated
by reference filed with the Form 10-Q filed with the Securities and
Exchange Commission on August 8, 2016 (File No.
001-36498).
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35
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on February 4, 2016 (File No. 000-
36498).
|
36
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on April 15, 2016 (File No. 000-
36498).
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37
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on November 15, 2016 (File No. 000-
36498).
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38
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Incorporated
by reference filed with Schedule 14A/A filed with the Securities
and Exchange Commission on March 23, 2017 (File No.
001-36498)
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39
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Incorporated
by reference filed with the Form 10-K filed with the Securities and
Exchange Commission on March 13, 2017 (File No.
001-36498).
|
40
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on January 25, 2013 (File No.
000-52282)
|
41
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on September 21, 2016 (File No.
000-36498).
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42
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on December 21, 2017 (File No.
000-36498).
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43
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on December 28, 2017 (File No.
000-36498).
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44
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on January 31, 2018 (File No.
000-36498).
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45
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Incorporated
by reference filed with the Form 8-K filed with the Securities and
Exchange Commission on February 7, 2018 (File No.
000-36498).
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46
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Incorporated
by reference filed with the Form 10-K filed with the Securities and
Exchange Commission on March 5, 2018 (File No.
001-36498).
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Item 17. Undertakings
(a) The
undersigned registrant hereby undertakes:
(1) To
file, during any period in which offers or sales are being made, a
post-effective amendment to this registration
statement:
(i) To
include any prospectus required by Section 10(a)(3) of the
Securities Act of 1933;
(ii) To
reflect in the prospectus any facts or events arising after the
effective date of the registration statement (or the most recent
post-effective amendment thereof) which, individually or in the
aggregate, represent a fundamental change in the information set
forth in the registration statement. Notwithstanding the foregoing,
any increase or decrease in volume of securities offered (if the
total dollar value of securities offered would not exceed that
which was registered) and any deviation from the low or high end of
the estimated maximum offering range may be reflected in the form
of prospectus filed with the Commission pursuant to Rule 424(b) if,
in the aggregate, the changes in volume and price represent no more
than 20 percent change in the maximum aggregate offering price set
forth in the “Calculation of Registration Fee” table in
the effective registration statement;
(iii)
To include any material information with respect to the plan of
distribution not previously disclosed in the registration statement
or any material change to such information in the registration
statement.
Provided, however, that the
undertakings set forth in paragraphs (a)(1)(i), (a)(1)(ii) and
(a)(1)(iii) above do not apply if the registration statement is on
Form S-3 or Form F-3 and the information required to be included in
a post-effective amendment by those paragraphs is contained in
reports filed with or furnished to the Commission by the registrant
pursuant to Section 13 or Section 15(d) of the Securities Exchange
Act that are incorporated by reference in the registration
statements or is contained in a form of prospectus filed pursuant
to Rule 424(b) that is a part of the registration
statement.
(2)
That, for the purpose of determining any liability under the
Securities Act of 1933, each such post-effective amendment shall
deemed to be a new registration statement relating to the
securities offered therein, and the offering of such securities at
that time shall be deemed to be the initial bona fide offering
thereof.
(3) To
remove from registration by means of a post-effective amendment any
of the securities being registered which remain unsold at the
termination of the offering.
(5)
That, for the purpose of determining liability under the Securities
Act of 1933 to any purchaser:
(1) (i)
Each prospectus filed by the registrant pursuant to Rule 424(b)(3)
shall be deemed to be part of the registration statement as of the
date the filed prospectus was deemed part of and included in the
registration statement; and
(B)
Each prospectus required to be filed pursuant to Rule 424(b)(2),
(b)(5), or (b)(7) as part of a registration statement in reliance
on Rule 430B relating to an offering made pursuant to Rule
415(a)(1)(i), (vii), or (x) for the purpose of providing the
information required by section 10(a) of the Securities Act of 1933
shall be deemed to be part of and included in the registration
statement as of the earlier of the date such form of prospectus is
first used after effectiveness or the date of the first contract of
sale of securities in the offering described in the prospectus. As
provided in Rule 430B, for liability purposes of the issuer and any
person that is at that date an underwriter, such date shall be
deemed to be a new effective date of the registration statement
relating to the securities in the registration statement to which
that prospectus relates, and the offering of such securities at
that time shall be deemed to be the initial bona fide offering
thereof. Provided, however, that no statement made in a
registration statement or prospectus that is part of the
registration statement or made in a document incorporated or deemed
incorporated by reference into the registration statement or
prospectus that is part of the registration statement will, as to a
purchaser with a time of contract of sale prior to such effective
date, supersede or modify any statement that was made in the
registration statement or prospectus that was part of the
registration statement or made in any such document immediately
prior to such effective date.
(ii) If
the registrant is subject to Rule 430C, each prospectus filed
pursuant to Rule 424(b) as part of a registration statement
relating to an offering, other than registration statements relying
on Rule 430B or other than prospectuses filed in reliance on Rule
430A ( § 230.430A of this chapter), shall be deemed to be part
of and included in the registration statement as of the date it is
first used after effectiveness. Provided, however, that no
statement made in a registration statement or prospectus that is
part of the registration statement or made in a document
incorporated or deemed incorporated by reference into the
registration statement or prospectus that is part of the
registration statement will, as to a purchaser with a time of
contract of sale prior to such first use, supersede or modify any
statement that was made in the registration statement or prospectus
that was part of the registration statement or made in any such
document immediately prior to such date of first use.
(b) The
undersigned registrant hereby undertakes that, for purposes of
determining any liability under the Securities Act of 1933, as
amended, each filing of the registrant’s annual report
pursuant to Section 13(a) or Section 15(d) of the Securities
Exchange Act that is incorporated by reference in this registration
statement shall be deemed to be a new registration statement
relating to the securities offered therein, and the offering of
such securities at that time shall be deemed to be the initial bona
fide offering thereof.
(h)
Insofar as indemnification for liabilities arising under the
Securities Act of 1933 may be permitted to directors, officers and
controlling persons of the registrant pursuant to the foregoing
provisions or otherwise, the registrant has been advised that in
the opinion of the Securities and Exchange Commission such
indemnification is against public policy as expressed in the
Securities Act of 1933 and is therefore unenforceable. In the event
that a claim for indemnification against such liabilities (other
than the payment by the registrant of expenses incurred or paid by
a director, officer or controlling person of the registrant in the
successful defense of any action, suit or proceeding) is asserted
by such director, officer or controlling person in connection with
the securities being registered, the registrant will, unless in the
opinion of its counsel the matter has been settled by controlling
precedent, submit to a court of appropriate jurisdiction the
question whether such indemnification by it is against public
policy as expressed in the Securities Act of 1933, and will be
governed by the final adjudication of such issue.
SIGNATURES
Pursuant to the
requirements of the Securities Act of 1933, as amended, the
registrant certifies that it has reasonable grounds to believe that
it meets all of the requirements for filing on Form S-3 and has
duly caused this registration statement to be signed on its behalf
by the undersigned, thereunto duly authorized, in the City of
Cupertino, California, on April 2, 2018.
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CELLULAR BIOMEDICINE GROUP, INC.
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By:
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/s/
Bizuo (Tony) Liu
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Name:
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Bizuo
(Tony) Liu
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Title:
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Chief
Executive Officer
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Pursuant to the
requirements of the Securities Act of 1933, as amended, this
Registration Statement has been signed by the following persons on
behalf of the Registrant in the capacities and on the dates
indicated.
Signature
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Title
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Date
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*
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Chairman
of the Board
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April
2, 2018
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Terry
Belmont
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/s/
Bizuo (Tony) Liu
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Chief
Executive Officer, Chief Financial Officer, Director
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April
2, 2018
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Bizuo
(Tony) Liu
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(Principal
Executive, Financial, and Accounting Officer)
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*
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Director
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April
2, 2018
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Alan
Au
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*
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Director
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April
2, 2018
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Hansheng
Zhou
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*
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Director
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April
2, 2018
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Gang
Ji
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*
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Director
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April
2, 2018
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Wen Tao
(Steve) Liu
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*
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Director
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April
2, 2018
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Nadir
Patel
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*
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Director
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April
2, 2018
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Bosun
Hau
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By: /s/
Bizuo (Tony) Liu
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Bizuo
(Tony) Liu
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Attorney-in-fact
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