As filed with the Securities and Exchange Commission on March 5,
2018
Registration
No. 333-
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM S-8
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 No.)
|
19925 Stevens Creek Blvd., Suite 100
Cupertino, Ca 95014
(Address
of Principal Executive Offices) (Zip Code)
2014 Stock Incentive Plan, as amended
(Full
Title of the Plan)
______________________
Bizuo (Tony) Liu
Chief Executive Officer
Cellular Biomedicine Group, Inc.
19925 Stevens Creek Blvd., Suite 100
Cupertino, CA 95014
(Name
and Address of Agent for
Service)
(408) 973-7884
(Telephone
Number, including area code, of agent for
service)
______________________
Copies
to:
Barry I. Grossman, Esq.
Sarah Williams, Esq.
Ellenoff Grossman & Schole LLP
1345 Avenue of Americas, 11th Floor
New York, New York 10105
(212) 370-1300
Fax: (212) 370-7889
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 definitions of “large
accelerated filer,” “accelerated filer,” and
“smaller reporting company” in Rule 12b-2 of the
Exchange Act. (Check one):
|
Large
accelerated filer ☐
|
Accelerated
filer ☒
|
|
Non-accelerated
filer ☐
|
Smaller
reporting company ☐
|
|
(Do not
check if a 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 the Securities Act.
☐
CALCULATION OF REGISTRATION FEE
|
Title of
Securities To Be Registered
|
Amount To
Be
Registered
(1)
|
Proposed
Maximum Offering Price
Per Share
(2)
|
Proposed
Maximum Aggregate Offering Price
|
Amount of
Registration Fee
|
|
|
|
|
|
|
|
Common Stock,
$0.001 par value per share
|
1,000,000
|
$16.20
|
$16,200,000
|
$2,016.90
|
|
(1)
|
This
Registration Statement shall also cover any additional shares of
the Registrant's common stock that become issuable in respect of
the securities identified in the above table by reason of any stock
dividend, stock split, recapitalization or other similar
transaction effected without the Registrant's receipt of
consideration which results in an increase in the number of the
outstanding shares of the Registrant's common stock.
|
|
(2)
|
Calculated
solely for the purposes of this offering under Rule 457(c), the
average of the high and low prices reported in the consolidated
reporting system within 5 business days prior to the date of filing
the registration statement.
|
Explanatory Note
This
registration statement on Form S-8 of Cellular Biomedicine Group,
Inc. (this “Registration Statement”) has been prepared
in accordance with the requirements of Form S-8 under the
Securities Act of 1933, as amended (the “Securities
Act”) to:
●
Register an
additional 1,000,000 shares of our common stock, par value $0.001
per share, issuable pursuant to our 2014 Equity Incentive Plan (as
amended and approved by our stockholders on April 28, 2017, and
which we refer to herein as the Plan or the 2014 Plan). Shares of
our common stock underlying options or restricted stock units
granted pursuant to the Plan were previously registered Form S-8
(No. 333-211679, filed on May 27, 2016, and which we refer to as
the 2016 S-8); and
●
Update the reoffer
prospectus included in the 2016 S-8 and that forms a part of this
Registration Statement relating to the resale of “control
securities” and/or “restricted securities” that
have been or will be acquired under the Plan by certain of our
officers and directors, who are the selling stockholders identified
in the reoffer prospectus.
The
reoffer prospectus contained herein has been prepared in accordance
with the requirements of General Instruction C of Form S-8 and Part
I of Form S-3. The 1,016,307 shares included in the reoffer
prospectus are the number of shares of our common stock underlying
options or restricted stock units that have been or may be acquired
by the selling stockholders under the Plan.
Accordingly:
(i) the reoffer prospectus included herein is a combined prospectus
with the reoffer prospectus included as part of the 2016 S-8
pursuant to Rule 429(a) under the Securities Act, and (ii) this
Registration Statement, which is a new registration statement, also
constitutes a post-effective amendment to the 2016 S-8 pursuant to
Rule 429(b) under the Securities Act.
PART I
INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS
|
Item 1.
|
Plan Information.*
|
|
|
|
|
Item 2.
|
Registrant Information and Employee Plan Annual
Information.*
|
__________
|
*
|
Information
required by Part I to be contained in the Section 10(a) Prospectus
is omitted from the Registration Statement in accordance with Rule
428 under the Securities Act. The documents containing
the information specified in Part I will be delivered to the
participants in the Plan covered by this Registration Statement as
required by Rule 428(b)(1).
|
Reoffer Prospectus
Cellular Biomedicine Group, Inc.
1,016,307 Shares
Common Stock
This
prospectus is being used in connection with the offering from time
to time by certain selling stockholders of our company (which
include certain of our prior, current and future officers and
directors or their successors in interest of shares of our common
stock, par value $0.001 (“Common Stock”) issued or to
be issued, or which may be acquired upon the exercise of stock
options or restricted stock units issued or to be issued, pursuant
to our 2014 Stock Incentive Plan, as amended, which we refer to
herein as the Plan.
The
common stock offered hereby may be sold from time to time by the
selling stockholders (which include certain of our prior, current
and future officers and directors or by their pledgees, donees,
transferees or other successors in interest. Such sales may be made
in the over-the-counter market or otherwise at prices and at terms
then prevailing or at prices related to the then current market
price, or in negotiated transactions. The Common Stock may be sold
by one or more of the following: (a) block trades in which the
broker or dealer so engaged will attempt to sell the shares as
agent but may position and resell portions of the block as
principal to facilitate the transaction; (b) purchases by a broker
or dealer as principal and resale by such broker or dealer for its
account pursuant to this prospectus; (c) an exchange distribution
in accordance with the rules of such exchange; and (d) ordinary
brokerage transactions and transactions in which the broker
solicits purchases. In effecting sales, brokers or dealers engaged
by the selling stockholders may arrange for other brokers or
dealers to participate. Brokers or dealers will receive commissions
or discounts from selling stockholders in amounts to be negotiated
immediately prior to the sale. Such brokers or dealers and any
other participating brokers or dealers may be deemed to be
“underwriters” within the meaning of the Securities
Act, in connection with such sales. In addition, any securities
covered by this prospectus which qualify for sale pursuant to Rule
144 may be sold under Rule 144 rather than pursuant to this
prospectus. We will not receive any of the proceeds from the sale
of these shares, although we have paid the expenses of preparing
this prospectus and the related registration statement. The
proceeds from the exercise of any options issued or issuable under
the plan will be used by us for our operations.
Our
Common Stock is listed on the Nasdaq Global Market, under the
symbol “CBMG.” On March 1, 2018, the closing sales
price for our Common Stock on the Nasdaq Global Market was
$16.90 per share.
Our
principal executive offices are located in the 19925 Stevens Creek
Blvd., Suite 100, Cupertino, California 95104. Our telephone number
is: (408) 973-7884.
Investing in our Common Stock involves a high degree of risk. See
the section entitled "Risk Factors" beginning on page 18 and in the
documents incorporated by reference herein before you decide to buy
our Common Stock.
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 March 5, 2018.
TABLE OF CONTENTS
|
|
Page
No.
|
|
Cautionary
Note on Forward Looking Statements
|
ii
|
|
Prospectus
Summary
|
1
|
|
The
Offering
|
17
|
|
Risk
Factors
|
18
|
|
Use of
Proceeds
|
18
|
|
Selling
Stockholders
|
18
|
|
Plan of
Distribution
|
21
|
|
Legal
Matters
|
22
|
|
Experts
|
22
|
|
Incorporation
of Certain Documents By Reference
|
22
|
|
Where
You Can Find More Information
|
23
|
|
Disclosure
of Commission Position on Indemnification for Securities Law
Violations
|
23
|
You
should rely only upon the information contained in this prospectus
and the registration statement of which this prospectus is a part.
We have not authorized any other person to provide you with
different information. If anyone provides you with different or
inconsistent information, you should not rely on it. We are not
making an offer to sell these securities in any jurisdiction where
the offer or sale is not permitted. You should assume the
information appearing in this prospectus is accurate only as of the
date on the front cover of this prospectus. Our business, financial
condition, results of operations and prospects may have changed
since that date. This prospectus is based on information provided
by us and other sources that we believe are reliable. We have
summarized certain documents and other information in a manner we
believe to be accurate, but we refer you to the actual documents
for a more complete understanding of what we discuss in this
prospectus. In making an investment decision, you must rely on your
own examination of our business and the terms of the offering,
including the merits and risks involved.
We
obtained statistical data, market data and other industry data and
forecasts used throughout, or incorporated by reference in, this
prospectus from market research, publicly available information and
industry publications. Industry publications generally state that
they obtain their information from sources that they believe to be
reliable, but they do not guarantee the accuracy and completeness
of the information. Similarly, while we believe that the
statistical data, industry data and forecasts and market research
are reliable, we have not independently verified the data, and we
do not make any representation as to the accuracy of the
information. We have not sought the consent of the sources to refer
to their reports appearing or incorporated by reference in this
prospectus.
i
CAUTIONARY NOTE ON FORWARD LOOKING STATEMENTS
Certain
statements contained or incorporated by reference in this
prospectus constitute “forward-looking statements.” The
words “believe,” “expect,”
“anticipate,” “intend,”
“estimate,” “plan,” “project”
and other expressions which are predictions of or indicate future
events and trends and which do not relate to historical matters
identify forward-looking statements. Reliance should not be placed
on forward-looking statements because they involve known and
unknown risks, uncertainties and other factors, which may cause our
actual results, performance or achievements to differ materially
from anticipated future results, performance or achievements
expressed or implied by such forward-looking
statements.
Factors
that might affect our forward-looking statements include, among
other things:
|
●
|
overall economic and business conditions;
|
|
●
|
results of our clinical research and development;
|
|
|
|
|
●
|
the demand for our products and services;
|
|
●
|
competitive factors in the industries in which we
compete;
|
|
●
|
the emergence of new technologies which compete with our product
and service offerings;
|
|
●
|
our cash position and cash burn rate;
|
|
●
|
other capital market conditions, including availability of funding
sources;
|
|
●
|
the strength of our intellectual property portfolio;
and
|
|
●
|
changes in government regulations in China and the
U.S. related to our industries.
|
Please
see “Risk Factors” for additional risks which could
adversely impact our business and financial performance. Moreover,
new risks emerge from time to time 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 are based on information
available to us on the date of this prospectus. 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 this prospectus.
ii
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 approval by the China Food and Drug Administration
(“CFDA”) 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.
1
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 AlloJoinTM Allogeneic Stem
Cell Therapy for KOA in the United States. We are performing
pre-clinical studies at Children’s Hospital Los Angeles
(CHLA) and plan to file an AlloJoinTM Phase I
clinical trial in the United States. On May 4, 2017, the Company
received $1.2 million from the CIRM grant, the first of four
disbursement totaling $2.29 million to fund our off-the-shelf
AlloJoin™ Allogeneic Stem Cell Therapy for KOA in the United
States.
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.
2
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.
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 U.S. Food and Drug Administration
(“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.
3
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. The trial has been
completed in 2017.
4
In
January 2015, we initiated patient recruitment in a phase II
clinical study, in China, of 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.
5
●
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.
6
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.
7
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.
8
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. The trial
has been completed in 2017. We plan to release the data in the
second quarter of 2018.
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.
9
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.
10
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 and are exploring the
feasibility of a U.S. allogeneic KOA clinical study with the
FDA.
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.
11
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.
12
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.
13
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.
14
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.
15
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 Ministry of Health (“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.
16
THE OFFERING
|
Outstanding Common Stock
|
As of
February 11, 2018, there were 17,430,762 shares of Common
Stock, par value $0.001 per share issued and
outstanding.
|
|
|
|
|
Common Stock Offered
|
Up to
1,016,307 shares of Common Stock for sale by the selling
stockholders (which include our executive officers and directors)
for their own account, which shares were received pursuant to a
grant of shares, restricted stock units or options to purchase
shares under the Plan.
|
|
|
|
|
Selling Stockholders
|
The
selling stockholders are set forth in the Section entitled "Selling
Stockholders" of this prospectus on page 18.
|
|
|
|
|
Proceeds
|
We will
not receive any proceeds from the sale of our Common Stock by the
selling stockholders. Any proceeds received by the Company upon the
exercise of options issued or issuable pursuant to the Plan
will be used for operations.
|
|
|
|
|
Risk Factors
|
The
securities offered hereby involve a high degree of risk. See
“Risk Factors.”
|
|
|
|
|
Nasdaq Symbol
|
CBMG.
|
17
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 (as updated in our subsequently filed Quarterly Reports on
Form 10-Q), which risk factors are incorporated by reference into
this reoffer prospectus. See “Where You Can Find More
Information” for an explanation of how to get a copy of this
report.
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 herein and in any document
incorporated herein by reference, including our Annual Report on
Form 10-K for the year ended December 31, 2017, or any Current
Report on Form 8-K or Quarterly Report on Form 10-Q that is
incorporated by reference into this reoffer prospectus after the
date of this reoffer 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 of the proceeds from the sale of Common Stock
registered hereunder. The proceeds from the exercise of any options
issued or issuable under the plan will be used by the company for
its operations. All expenses of the registration of the shares will
be paid by the Company.
SELLING STOCKHOLDERS
This
prospectus relates to the shares of our Common Stock that are being
registered for reoffers and resale by selling stockholders who have
acquired or may acquire shares pursuant to the Plan. Offers and
sales by selling stockholders who are our employees, consultants
and "affiliates" (as such term is defined in Rule 405 under the
Securities Act) are also covered by this prospectus.
The
selling stockholders are our current directors, officers and
affiliates who have acquired or may acquire in the future shares of
our Common Stock under the Plan. The selling stockholders may, from
time to time, resell all, a portion or none of the shares of our
Common Stock covered by this prospectus. The following table sets
forth information as of February 11, 2018 with respect
to ownership of our Common Stock by each selling stockholder
whose identity is known as of the date of this prospectus. There is
no assurance that any of the selling stockholders will sell any or
all of the shares offered by them under this registration
statement. The address for each selling stockholders listed below
is c/o Cellular Biomedicine Group, Inc., 19925 Stevens Creek Blvd.,
Suite 100, Cupertino, California 95014.
Any
changed information will be set forth in an amendment to the
registration statement or supplement to this prospectus, to the
extent required by law.
18
* Less
than 1%
(1)
Shares of Common Stock that a selling stockholder has a right to
acquire pursuant to the exercise of options under the 2014 Plan are
deemed to be outstanding for the purpose of computing the number
and percentage of shares of Common Stock owned by such selling
stockholder, but are not deemed to be outstanding for computing the
percentage ownership of any other selling stockholder.
(2)
Includes 22,444 options issued under the 2014 Plan which are being
registered for reoffer and resale herein. Does not include 146,667
options to purchase Common Stock granted pursuant to the Company's
2011 Incentive Stock Option Plan (the “2011
Plan”).
(3)
Represents 22,444 options to purchase Common Stock under the 2014
Plan, of which 22,444 are currently vested as of February 11,
2018.
(4)
Includes 38,000 options and 5,269 restricted common stock issued
under the 2014 Plan which are being registered for reoffer and
resale herein. Does not include 53,880 options to purchase Common
Stock granted pursuant to the 2011 Plan and 37,904 options to
purchase Common Stock granted pursuant to the 2013 Stock Incentive
Plan (the “2013 Plan”), which are all currently vested
as of February 11, 2018.
(5)
Represents 38,000 options and 5,269 restricted common stock issued
under the 2014 Plan, of which 14,269 options are currently vested
as of February 11, 2018.
(6)
Includes 325,800 options and 26,525 restricted common stock issued
under the 2014 Plan which are being registered for reoffer and
resale herein. Does not include 35,300 options to purchase Common
Stock granted pursuant to the 2011 Plan and 255,000 options to
purchase Common Stock granted pursuant to the 2013 Plan, which are
all currently vested as of February 11, 2018.
(7)
Represents 325,800 options and 26,525 restricted common stock
issued under the 2014 Plan, of which 205,300 options are currently
vested as of February 11, 2018.
(8)
Includes 28,961 options issued under the 2014 Plan which are being
registered for reoffer and resale herein. Does not include 4,000
options to purchase Common Stock under the 2013 Plan, which are all
currently vested as of February 11, 2018.
(9)
Represents 28,961 options to purchase Common Stock under the 2014
Plan, of which 16,905 are currently vested as of February 11,
2018.
(10)
Includes 35,304 options issued under the 2014 Plan which are being
registered for reoffer and resale herein. Does not include 7,000
options to purchase Common Stock under the 2013 Plan, which are all
currently vested as of February 11, 2018.
(11)
Represents 35,304 options to purchase Common Stock under the 2014
Plan, of which 20,656 are currently vested as of February 11,
2018.
19
(12)
Includes 21,549 options issued under the 2014 Plan which are being
registered for reoffer and resale herein. Does not include 12,000
options to purchase Common Stock under the 2013 Plan, which are all
currently vested as of February 11, 2018.
(13)
Represents 21,549 options to purchase Common Stock under the 2014
Plan, of which 12,938 are currently vested as of February 11,
2018.
(14)
Includes 17,356 options issued under the 2014 Plan which are being
registered for reoffer and resale herein. Also includes 2,270,000
shares of common stock held by Dangdai
International Group Co., Limited. Wuhan Dangdai Technology &
Industries Group Inc. has voting and dispositive power over the
shares of Dangdai International Group Co., Limited in Hong Kong.
Wuhan Dangdai Technology & Industries Group Inc. is controlled
by Hansheng Zhou, Xiaodong Zhang, Luming Ai, Xuehai Wang, Lei Yu,
Xiaoling Du and Haichun Chen. Such individuals share voting and
dispositive power over the shares held by Dangdai International
Group Co., Limited.
(15)
Represents 17,356 options to purchase Common Stock under the 2014
Plan, of which 5,300 are currently vested as of February 11,
2018.
(16)
Includes 8,546 options issued under the 2014 Plan which are being
registered for reoffer and resale herein.
(17)
Represents 8,546 options to purchase Common Stock under the 2014
Plan, of which 3,620 are currently vested as of February 11,
2018.
(18)
Includes 285 options issued under the 2014 Plan which are being
registered for reoffer and resale herein.
(19)
Represents 285 options to purchase Common Stock under the 2014
Plan, which is not vested as of February 11, 2018.
(20)
Includes 61,500 options and 21,373 restricted common stock issued
under the 2014 Plan which are being registered for reoffer and
resale herein.
(21)
Represents 61,500 options and 21,373 restricted common stock issued
under the 2014 Plan, of which 24,072 options are currently vested
as of February 11, 2018.
20
PLAN OF DISTRIBUTION
In this
section of the prospectus, the term “selling
stockholder” means and includes:
●
the
persons identified in the table above as the selling
stockholders;
●
those persons
whose identities are not known as of the date hereof but may in the
future be eligible to receive options under the Plan;
and
●
any
of the donees, pledgees, distributees, transferees or other
successors in interest of those persons referenced above who may:
(a) receive any of the shares of our Common Stock offered hereby
after the date of this prospectus and (b) offer or sell those
shares hereunder.
The
shares of our Common Stock offered by this prospectus may be sold
from time to time directly by the selling stockholders.
Alternatively, the selling stockholders may from time to time offer
such shares through underwriters, brokers, dealers, agents or other
intermediaries. The selling stockholders as of the date of this
prospectus have advised us that there were no underwriting or
distribution arrangements entered into with respect to the Common
Stock offered hereby. The distribution of the Common Stock by the
selling stockholders may be effected: in one or more transactions
that may take place on the NASDAQ or any other stock exchange
(including one or more block transaction) through customary
brokerage channels, either through brokers acting as agents for the
selling stockholders, or through market makers, dealers or
underwriters acting as principals who may resell these shares on
the Nasdaq or any other stock exchange; in
privately-negotiated sales; by a combination of such methods; or by
other means. These transactions may be effected at market prices
prevailing at the time of sale, at prices related to such
prevailing market prices or at other negotiated prices. Usual and
customary or specifically negotiated brokerage fees or commissions
may be paid by the selling stockholders in connection with sales of
our Common Stock.
The
selling stockholders may enter into hedging transactions with
broker-dealers in connection with distributions of the shares or
otherwise. In such transactions, broker-dealers may engage in short
sales of the shares of our Common Stock in the course of hedging
the positions they assume with the selling stockholders. The
selling stockholders also may sell shares short and redeliver the
shares to close out such short positions. The selling stockholders
may enter into option or other transactions with broker-dealers
which require the delivery to the broker-dealer of shares of our
Common Stock. The broker-dealer may then resell or otherwise
transfer such shares of Common Stock pursuant to this
prospectus.
The
selling stockholders also may lend or pledge shares of our Common
Stock to a broker-dealer. The broker-dealer may sell the shares of
Common Stock so lent, or upon a default the broker-dealer may sell
the pledged shares of Common Stock pursuant to this prospectus. Any
securities covered by this prospectus which qualify for sale
pursuant to Rule 144 may be sold under Rule 144 rather than
pursuant to this prospectus.
The
selling stockholders have advised us that they have not entered
into any agreements, understandings or arrangements with any
underwriters or broker-dealers regarding the sale of their
securities. There is no underwriter or coordinating broker acting
in connection with the proposed sale of shares of Common Stock the
selling stockholders.
Although
the shares of Common Stock covered by this prospectus are not
currently being underwritten, the selling stockholders or their
underwriters, brokers, dealers or other agents or other
intermediaries, if any, that may participate with the selling
security holders in any offering or distribution of Common Stock
may be deemed “underwriters” within the meaning of the
Securities Act and any profits realized or commissions received by
them may be deemed underwriting compensation there
under.
21
Under
applicable rules and regulations under the Exchange Act, any person
engaged in a distribution of shares of the Common Stock offered
hereby may not simultaneously engage in market making activities
with respect to the Common Stock for a period of up to five days
preceding such distribution. The selling stockholders will be
subject to the applicable provisions of the Exchange Act and the
rules and regulations promulgated there under, including without
limitation Regulation M, which provisions may limit the timing of
purchases and sales by the selling stockholders.
In
order to comply with certain state securities or blue sky laws and
regulations, if applicable, the Common Stock offered hereby will be
sold in such jurisdictions only through registered or licensed
brokers or dealers. In certain states, the Common Stock may not be
sold unless they are registered or qualified for sale in such
state, or unless an exemption from registration or qualification is
available and is obtained.
We will
bear all costs, expenses and fees in connection with the
registration of the Common Stock offered hereby. However, the
selling stockholders will bear any brokerage or underwriting
commissions and similar selling expenses, if any, attributable to
the sale of the shares of Common Stock offered pursuant to this
prospectus. We have agreed to indemnify certain of the selling
security holders against certain liabilities, including liabilities
under the Securities Act, or to contribute to payments to which any
of those security holders may be required to make in respect
thereof.
There
can be no assurance that the selling stockholders will sell any or
all of the securities offered by them hereby.
LEGAL MATTERS
The
validity of the securities being offered herein has been passed
upon for us by Ellenoff Grossman & Schole LLP, New York,
New York.
EXPERTS
The consolidated financial statements for the years ended December
31, 2017, 2016 and 2015 appearing in our Annual Report on Form 10-K
for the fiscal year ended December 31, 2017 have been incorporated
by reference in this prospectus 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.
INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE
The
following documents are incorporated by reference into this
prospectus:
●
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 and February 12,
2018; and
●
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.
22
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 materials
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 exhibits 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, New York 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.
DISCLOSURE OF COMMISSION POSITION ON
INDEMNIFICATION FOR SECURITIES LAW VIOLATIONS
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. Our Amended and Restated 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.
However,
insofar as indemnification for liabilities arising under the
Securities Act may be permitted to our directors, officers, and
controlling persons pursuant to the foregoing provisions 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 of expenses incurred or paid by a director, officer or
controlling person in a 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 the 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.
23
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 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.
Cellular Biomedicine Group, Inc.
1,016,307 shares
Common Stock
_______________
PROSPECTUS
________________
March 5, 2018
PART II
INFORMATION NOT REQUIRED IN PROSPECTUS
Item 3.
Incorporation of Documents by Reference.
Cellular
Biomedicine Group, Inc. (the “Registrant”) hereby
incorporates by reference into this Registration Statement the
following documents previously filed with the Securities and
Exchange Commission (the “Commission”):
●
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 and February 12,
2018; and
●
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.
Item 4.
Description of Securities.
Not
applicable.
Item 5.
Interests of Named Experts and Counsel.
The
validity of the shares of Common Stock offered hereby will be
passed upon by Ellenoff Grossman & Schole LLP, counsel to the
Registrant.
Item 6.
Indemnification of Officers and Directors.
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. 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.
Insofar
as indemnification for liabilities arising under the Securities Act
may be permitted to our directors, officers, and controlling
persons pursuant to the foregoing provisions 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 of
expenses incurred or paid by a director, officer or controlling
person in a 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 the 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.
II-1
Item 7.
Exemption from Registration Claimed.
All
shares of Common Stock registered hereunder for reoffer or resale
have been or will be issued to our employees and consultants
pursuant to the Plan and a restrictive legend is placed on the
certificates for the shares of Common Stock purchased and transfer
stops are placed against such certificates. Such shares may only be
reoffered and sold pursuant to registration under the Securities
Act or pursuant to an applicable exemption under the Securities
Act. As a result, such offers and sales are exempt from the
registration requirements of the Securities Act pursuant to the
provisions of Section 4(a)(2) of the Securities
Act.
Item 8.
Exhibits.
|
Number
|
|
Description
|
|
5.1
|
|
Opinion
of Ellenoff Grossman & Schole LLP (1)
|
|
5.2
|
|
Opinion
of Ellenoff Grossman & Schole LLP (*)
|
|
23.1
|
|
Consent
of Ellenoff Grossman & Schole LLP (contained in Exhibit 5.1)
(*)
|
|
23.2
|
|
Consent
of BDO China Shu Lun Pan Certified Public Accountants
LLP
(*)
|
|
24.1
|
|
Power
of Attorney (included in the signature page to this Registration
Statement)
|
|
99.1
|
|
Cellular
Biomedicine Group, Inc. 2014 Stock Incentive Plan, as amended
(2)
|
__________
|
*
|
Filed
herewith
|
|
(1)
|
Incorporated
by reference filed with the Registration Statement on Form S-8
filed with the SEC on May 27, 2016 (File No.
333-211679).
|
|
(2)
|
Incorporated
by reference filed with the Schedule 14A filed with the SEC on
September 23, 2014 (File No. 001-36498) and the Schedule 14A filed
with the SEC on March 23, 2017 (File No. 001-36498).
|
Item 9.
Undertakings.
(a)
The 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;
(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 SEC 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 paragraphs
(a)(1)(a) and (a)(1)(b) do not apply if the Registration
Statement is on Form S-8 and the information required to be
included in a post-effective amendment by those paragraphs is
contained in periodic reports filed with or furnished to the SEC by
the Registrant pursuant to Section 13 or 15(d) of the
Exchange Act that are incorporated by reference in the Registration
Statement.
II-2
(2) That,
for the purpose of determining any liability under the Securities
Act, each such post-effective amendment 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.
(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.
(b) The
Registrant hereby undertakes that, for purposes of determining any
liability under the Securities Act, each filing of the
Registrant’s annual report pursuant to
Section 13(a) or 15(d) of the Exchange Act (and,
where applicable, each filing of an employee benefit plan’s
annual report pursuant to Section 15(d) of the Exchange
Act) that is incorporated by reference in the 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.
(c) Insofar
as indemnification for liabilities arising under the Securities Act
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 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 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 and will be governed by
the final adjudication of such issue.
II-3
SIGNATURES
Pursuant to the
requirements of the Securities Act of 1933, the registrant
certifies that it has reasonable grounds to believe that it meets
all of the requirements for filing on Form S-8 and has duly caused
this registration statement to be signed on its behalf by the
undersigned, thereunto duly authorized, in the City of Cupertino,
State of California, on March 5, 2018.
|
|
Cellular Biomedicine Group, Inc.
|
|
|
|
|
|
|
|
|
|
By:
|
/s/ Bizuo
(Tony) Liu
|
|
|
|
|
Name:
Bizuo (Tony) Liu
|
|
|
|
|
Title:
Chief Executive Officer and Chief Financial Officer
|
|
POWER OF ATTORNEY
KNOW ALL PERSONS BY THESE PRESENTS, that
each person whose signature appears below does hereby constitute
and appoint Terry Belmont and Bizuo (Tony) Liu, and each of them,
with full power of substitution, such person’s true and
lawful attorneys-in-fact and agents for such person, with full
power and authority to do any and all acts and things and to
execute any and all instruments which said attorneys and agents,
and any one of them, determine may be necessary or advisable or
required to enable said corporation to comply with the Securities
Act of 1933, as amended, and any rules or regulations or
requirements of the Securities and Exchange Commission in
connection with this Registration Statement. Without limiting the
generality of the foregoing power and authority, the powers granted
include the power and authority to sign the names of the
undersigned officers and directors in the capacities indicated
below to this Registration Statement, to any and all amendments,
both pre-effective and post-effective, and supplements to this
Registration Statement, and to any and all instruments or documents
filed as part of or in conjunction with this Registration Statement
or amendments or supplements thereof, and each of the undersigned
hereby ratifies and confirms that all said attorneys and agents, or
any one of them, shall do or cause to be done by virtue hereof.
This Power of Attorney may be signed in several
counterparts.
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
|
Title
|
Date
|
|
|
|
|
|
/s/
Terry Belmont
|
Chairman
of the Board
|
March
5, 2018
|
|
Terry
Belmont
|
|
|
|
|
|
|
|
/s/
Bizuo (Tony) Liu
|
Chief
Executive Officer, Chief Financial Officer and
Director
|
March
5, 2018.
|
|
Bizuo
(Tony) Liu
|
(Principal
Executive and Financial Officer)
|
|
|
|
|
|
|
/s/
Alan Au
|
Director
|
March
5, 2018.
|
|
Alan
Au
|
|
|
|
|
|
|
|
/s/
Gang Ji
|
Director
|
March
5, 2018.
|
|
Gang
Ji
|
|
|
|
|
|
|
|
/s/
Hansheng Zhou
|
Director
|
March
5, 2018.
|
|
Hansheng
Zhou
|
|
|
|
|
|
|
|
/s/ Wen
Tao (Steve) Liu
|
Director
|
March
5, 2018.
|
|
Wen Tao
(Steve) Liu
|
|
|
|
|
|
|
|
/s/
Nadir Patel
|
Director
|
March
5, 2018.
|
|
Nadir
Patel
|
|
|
|
|
|
|
|
/s/
Bosun Hau
|
Director
|
March
5, 2018.
|
|
Bosun
Hau
|
|
|
II-4
INDEX TO EXHIBITS
|
Number
|
|
Description
|
|
|
||
|
|
||
|
|
||
|
|
||
|
|
||
|
|
__________
|
*
|
Filed
herewith
|
|
(1)
|
Incorporated
by reference filed with the Registration Statement on Form S-8
filed with the SEC on May 27, 2016 (File No.
333-211679).
|
|
(2)
|
Incorporated
by reference filed with the Schedule 14A filed with the SEC on
September 23, 2014 (File No. 001-36498) and the Schedule 14A filed
with the SEC on March 23, 2017 (File No. 001-36498).
|
II-5