Table of Contents
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 10-K
(Mark One)
☒ ANNUAL REPORT PURSUANT TO SECTION 13
OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended April 30, 2023
or
☐ TRANSITION REPORT PURSUANT TO SECTION
13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from __________ to __________
Commission File Number 001-40699
PHARMACYTE BIOTECH, INC.
(Exact name of registrant as specified in its charter)
Securities registered pursuant to Section 12(b)
of the Act:
Title of each class Trading symbol(s) Name of each exchange on which registered
Securities registered pursuant to Section 12(g)
of the Act: None
Indicate by check mark if the registrant is a
well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒
Indicate by check mark if the registrant is not
required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒
Indicate by check mark whether the registrant
(1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months
(or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements
for the past 90 days. Yes ☒ No ☐
Indicate by check mark whether the registrant
has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405
of this chapter) during the precedent 12 months (or for such shorter period that the registrant was required to submit such files). Yes
☒ No ☐
Indicate by check mark whether the registrant
is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company.
See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,”
and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ 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 13(a) of the Exchange Act. ☐
Indicate by check mark whether the
registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control
over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm
that prepared or issued its audit report. ☐
If securities are registered pursuant to
Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect
the correction of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error
corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s
executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the registrant
is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
State the aggregate market value of the voting
and non-voting common equity held by non-affiliates computed by reference to the price at which the common equity was last sold, or the
average bid and asked price of such common equity, as of October 31, 2022: $54,212,148.
As of July 31, 2023, the registrant had 8,778,101
outstanding shares of common stock.
DOCUMENTS INCORPORATED BY REFERENCE
None.
TABLE OF CONTENTS
ITEM 1. BUSINESS 1
ITEM 1A. RISK FACTORS 29
ITEM 1B. UNRESOLVED STAFF COMMENTS 72
ITEM 2. PROPERTIES 72
ITEM 3. LEGAL PROCEEDINGS 72
ITEM 4. MINE SAFETY DISCLOSURES 72
ITEM 6. [RESERVED] 75
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 80
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 81
ITEM 9A. CONTROLS AND PROCEDURES 81
ITEM 9B. OTHER INFORMATION 82
ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 82
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 83
ITEM 11. EXECUTIVE COMPENSATION 89
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 98
i
Cautionary Note Regarding Forward-Looking Statements
This Annual Report on Form 10-K (“Report”)
includes “forward-looking statements” within the meaning of the federal securities laws. Forward-looking statements are inherently
subject to risks, uncertainties and assumptions. Generally, statements other than statements of historical fact are “forward-looking
statements” for purposes of this Report, including any projections of earnings, revenue or other financial items, any statements
regarding the plans and objectives of management for future operations, any statements concerning proposed new products or services, any
statements regarding future economic conditions or performance, any statements regarding expected benefits from any transactions and any
statements of assumptions underlying any of the foregoing. In some cases, forward-looking statements can be identified by use of terminology
such as “may,” “will,” “should,” “believes,” “intends,” “expects,”
“plans,” “anticipates,” “estimates,” “goal,” “aim,” “potential”
or “continue,” or the negative thereof or other comparable terminology. Although we believe that the expectations reflected
in the forward-looking statements contained in this Report are reasonable, there can be no assurance that such expectations or any of
the forward-looking statements will prove to be correct, and actual results could differ materially from those projected or assumed in
the forward-looking statements. Thus, investors should refer to and carefully review information in future documents we file with the
U.S. Securities and Exchange Commission (“Commission”). Our future financial condition and results of operations, as well
as any forward-looking statements, are subject to inherent risk and uncertainties, including, but not limited to, the risk factors set
forth in “Part I, Item 1A – Risk Factors” set forth in this Report and for the reasons described elsewhere in this Report.
Among others, these include:
· the success and timing of our preclinical studies and clinical trials;
All forward- looking statements and reasons why
results may differ included in this Report are made as of the date hereof, and we do not intend to update any forward-looking statements
except as required by law or applicable regulations. New risk factors emerge from time to time, and it is not possible to predict all
such risk factors, nor can we assess the impact of all such risk factors on our business or the extent to which any factor or combination
of factors may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements
are not guarantees of performance. All forward-looking statements attributable to us or persons acting on our behalf are expressly qualified
in their entirety by the foregoing cautionary statements.
Except where the context otherwise requires, in
this Report, the “Company,” “we,” “us” and “our” refer to PharmaCyte Biotech, Inc., a
Nevada corporation, and, where appropriate, its subsidiaries.
ii
PART I
ITEM 1. BUSINESS.
We are a biotechnology company focused on developing
cellular therapies for cancer, diabetes, and malignant ascites based upon a proprietary cellulose-based live cell encapsulation technology
known as “Cell-in-a-Box®.” The Cell-in-a-Box® technology is intended to be used as a platform upon which therapies
for several types of cancer, including LAPC, will be developed. The current generation of our product candidate is referred to as “CypCapsTM.”
On August 15, 2022, we entered into a Cooperation
Agreement (the “Cooperation Agreement”) with Iroquois Master Fund Ltd. and its affiliates, pursuant to which we elected a
reconstituted board of directors (the “Board”). The Board then formed a Business Review Committee to evaluate, investigate
and review our business, affairs, strategy, management and operations and in its sole discretion, to make recommendations to our management
and Board with respect thereto. The Business Review Committee is also reviewing many of the risks relative to our business. In addition,
the Board is reviewing risks associated with our development programs and our relationship with SG Austria Pte. Ltd (“SG Austria”),
including that all licensed patents have expired, that know-how relating to our Cell-in-a-Box® technology solely resides with SG Austria,
and that the incentives of SG Austria and its management may not be currently aligned with ours. The Board has curtailed spending on our
programs, including pre-clinical and clinical activities, until the review by the Business Review Committee and the Board is complete
and the Board has determined the actions and plans to be implemented. The Business Review Committee’s recommendations will include
potentially seeking a new framework for our relationship with SG Austria and its subsidiaries. If we are unsuccessful in seeking an acceptable
new framework, we will reevaluate whether we should continue those programs which are dependent on SG Austria, including our development
programs for locally advanced, inoperable, non-metastatic pancreatic cancer (“LAPC”), diabetes and malignant ascites. The
issues involving SG Austria have delayed our timeline for addressing the FDA clinical hold for its planned clinical trial in LAPC and
could result in other delays or termination of the development activities. In addition, the curtailment of spending on our programs pending
the review by the Business Review Committee and the Board may cause additional delays.
The Cell-in-a-Box® encapsulation technology
potentially enables genetically engineered live human cells to be used as a means to produce various biologically active molecules. The
technology is intended to result in the formation of pinhead-sized cellulose-based porous capsules in which genetically modified live
human cells can be encapsulated and maintained. In a laboratory setting, this proprietary live cell encapsulation technology has been
shown to create a micro-environment in which encapsulated cells survive and flourish. They are protected from environmental challenges,
such as the sheer forces associated with bioreactors and passage through catheters and needles, which we believe enables greater cell
growth and production of the active molecules. The capsules are largely composed of cellulose (cotton) and are bioinert.
We have been developing therapies for pancreatic
and other solid cancerous tumors by using genetically engineered live human cells that we believe are capable of converting a cancer prodrug
into its cancer-killing form. We encapsulate those cells using the Cell-in-a-Box® technology and place those capsules in the body
as close as possible to the tumor. In this way, we believe that when a cancer prodrug is administered to a patient with a particular type
of cancer that may be affected by the prodrug, the killing of the patient’s cancerous tumor may be optimized.
We have also been developing a way to delay the
production and accumulation of malignant ascites that results from many types of abdominal cancerous tumors. Our potential therapy for
malignant ascites involves using the same encapsulated cells we employ for pancreatic cancer but placing the encapsulated cells in the
peritoneal cavity of a patient and administering ifosfamide intravenously.
We have also been developing a potential therapy
for Type 1 diabetes and insulin-dependent Type 2 diabetes. Our product candidate for the treatment of diabetes consists of encapsulated
genetically modified insulin-producing cells. The encapsulation will be done using the Cell-in-a-Box® technology. Implanting these
encapsulated cells in the body is designed to have them function as a bio-artificial pancreas for purposes of insulin production.
In addition to the two cancer programs discussed
above, we have been working on ways to exploit the benefits of the Cell-in-a-Box® technology to develop therapies for cancer that
involve prodrugs based upon certain constituents of the Cannabis plant. However, until the FDA allows us to commence our clinical trial
in LAPC and we are able to validate our Cell-in-a-Box® encapsulation technology in a clinical trial, we are not spending any further
resources developing our Cannabis Program.
Finally, we have been developing a potential therapy
for Type 1 diabetes and insulin-dependent Type 2 diabetes. Our product candidate for the treatment of diabetes consists of encapsulated
genetically modified insulin-producing cells. The encapsulation will be done using the Cell-in-a-Box® technology. Implanting these
encapsulated cells in the body is designed to have them function as a bio-artificial pancreas for purposes of insulin production.
Until the Business Review Committee completes
its evaluation of our programs and we enter into a new framework for its relationship with SG Austria, spending on our development programs
has been curtailed.
Investigational New Drug Application and Clinical
Hold
On September 1, 2020, we submitted an IND to the
FDA for a planned clinical trial in LAPC. On October 1, 2020, we received notice from the FDA that it had placed our IND on clinical hold.
On October 30, 2020, the FDA sent us a letter setting forth the reasons for the clinical hold and providing specific guidance on what
we must do to have the clinical hold lifted.
In order to address the clinical hold, the FDA
has requested that we:
· Provide additional sequencing data and genetic stability studies;
· Provide additional product release specifications for our encapsulated cells;
· Conduct a biocompatibility assessment using the capsules material;
The FDA also requested that we address the following
issues as an amendment to our IND:
We assembled a scientific and regulatory team
of experts to address the FDA requests. That team has been working diligently to complete the items requested by the FDA. We are in the
latter stages of conducting the studies and providing the information requested by the FDA. We have completed the pilot study of two pigs
and are evaluating the preliminary data before it commences the larger study of 90 pigs.
The following provides a detailed summary of our
activities to have the clinical hold lifted:
History of the Business
In 2013, we restructured
our operations to focus on biotechnology. On January 6, 2015, we changed our name from “Nuvilex, Inc.” to “PharmaCyte
Biotech, Inc.” to reflect the nature of our business.
We are a biotechnology
company focused on developing and preparing to commercialize cellular therapies for cancer, diabetes, and malignant ascites using our
live cell encapsulation technology. This resulted from entering into the following agreements.
Commencing in May 2011,
we entered into a series of agreements and amendments with SG Austria Pte. Ltd. (“SG Austria”) to acquire certain assets from
SG Austria as well as an exclusive, worldwide license to use, with a right to sublicense, the Cell-in-a-Box® technology and trademark
for the development of therapies for cancer (“SG Austria APA”).
In June 2013, we and
SG Austria entered a Third Addendum to the SG Austria APA (“Third Addendum”). The Third Addendum materially changed the transaction
contemplated by the SG Austria APA. Under the Third Addendum, we acquired 100% of the equity interests in Bio Blue Bird and received a
14.5% equity interest in SG Austria. We paid: (i) $500,000 to retire all outstanding debt of Bio Blue Bird; and (ii) $1.0 million to SG
Austria. We also paid SG Austria $1,572,193 in exchange for a 14.5% equity interest of SG Austria. The transaction required SG Austria
to return to us the 66,667 shares of our common stock held by SG Austria and for us to return to SG Austria the 67 shares of common stock
of Austrianova we held.
Effective as of the same
date we entered the Third Addendum, we and SG Austria also entered a Clarification Agreement to the Third Addendum (“Clarification
Agreement”) to clarify and include certain language that was inadvertently left out of the Third Addendum. Among other things, the
Clarification Agreement confirmed that the Third Addendum granted us an exclusive, worldwide license to use, with a right to sublicense,
the Cell-in-a-Box® technology and trademark for the development of therapies for cancer.
With respect to Bio Blue
Bird, Bavarian Nordic A/S (“Bavarian Nordic”) and GSF-Forschungszentrum für Umwelt u. Gesundheit GmbH (collectively,
“Bavarian Nordic/GSF”) and Bio Blue Bird entered into a non-exclusive License Agreement (“Bavarian Nordic/GSF License
Agreement”) in July 2005, whereby Bio Blue Bird was granted a non-exclusive license to further develop, make, have made (including
services under contract for Bio Blue Bird or a sub-licensee, by Contract Manufacturing Organizations, Contract Research Organizations,
Consultants, Logistics Companies or others), obtain marketing approval, sell and offer for sale the clinical data generated from the pancreatic
cancer clinical trials that used the cells and capsules developed by Bavarian Nordic/GSF (then known as “CapCellsTM”)
or otherwise use the licensed patent rights related thereto in the countries in which patents had been granted. Bio Blue Bird was required
to pay Bavarian Nordic a royalty of 3% of the net sales value of each licensed product sold by Bio Blue Bird and/or its Affiliates and/or
its sub-licensees to a buyer. The term of the Bavarian Nordic/GSF License Agreement continued on a country-by-country basis until the
expiration of the last valid claim of the licensed patent rights.
Bavarian Nordic/GSF and
Bio Blue Bird amended the Bavarian Nordic License Agreement in December 2006 (“First Amendment to Bavarian Nordic/GSF License Agreement”)
to reflect that: (i) the license granted was exclusive; (ii) a royalty rate increased from 3% to 4.5%; (iii) Bio Blue Bird assumed the
patent prosecution expenses for the existing patents; and (iv) to make clear that the license will survive as a license granted by one
of the licensors if the other licensor rejects performance under the Bavarian Nordic License Agreement due to any actions or declarations
of insolvency.
In June 2013, we acquired
from Austrianova an exclusive, worldwide license to use the Cell-in-a-Box® technology and trademark for the development of a
therapy for Type 1 and insulin-dependent Type 2 diabetes (“Diabetes Licensing Agreement”). This allows us to develop a therapy
to treat diabetes through encapsulation of a human cell line that has been genetically modified to produce, store and release insulin
in response to the levels of blood sugar in the human body.
In October 2014, we entered
into an exclusive, worldwide license agreement with the UTS (“Melligen Cell License Agreement”) in Australia to use insulin-producing
genetically engineered human liver cells developed by UTS to treat Type 1 diabetes and insulin-dependent Type 2 diabetes. These cells,
named “Melligen,” were tested by UTS in mice and shown to produce insulin in direct proportion to the amount of glucose in
their surroundings. In those studies, when Melligen cells were transplanted into immunosuppressed diabetic mice, the blood glucose levels
of the mice became normal. In other words, the Melligen cells reportedly reversed the diabetic condition.
In December 2014, we
acquired from Austrianova an exclusive, worldwide license to use the Cell-in-a-Box® technology and trademark in combination with
genetically modified non-stem cell lines which are designed to activate cannabinoid prodrug molecules for development of therapies for
diseases and their related symptoms using of the Cell-in-a-Box® technology and trademark (“Cannabis Licensing Agreement”).
This allows us to develop a therapy to treat cancer and other diseases and symptoms through encapsulation of genetically modified cells
designed to convert cannabinoids to their active form using the Cell-in-a-Box® technology and trademark.
In July 2016, we entered
into a Binding Memorandum of Understanding with Austrianova (“Austrianova MOU”). Pursuant to the Austrianova MOU, Austrianova
will actively work with us to seek an investment partner or partners who will finance clinical trials and further develop products for
our therapy for cancer, in exchange for which we, Austrianova and any future investment partner will each receive a portion of the net
revenue from the sale of cancer products.
In October 2016, Bavarian
Nordic/GSF and Bio Blue Bird further amended the Bavarian Nordic License Agreement (“Second Amendment to Bavarian Nordic/GSF License
Agreement”) in order to: (i) include the right to import in the scope of the license; (ii) reflect ownership and notification of
improvements; (iii) clarify which provisions survive expiration or termination of the Bavarian Nordic License Agreement; (iv) provide
rights to Bio Blue Bird to the clinical data after the expiration of the licensed patent rights; and (v) change the notice address and
recipients of Bio Blue Bird.
In May 2018, we entered
into a series of binding term sheet amendments (“Binding Term Sheet Amendments”). The Binding Term Sheet Amendments provide
that our obligation to make milestone payments to Austrianova is eliminated in their entirety under the: (i) Cannabis License Agreement;
and (ii) the Diabetes License Agreement, as amended. The Binding Term Sheet Amendments also provide that our obligation to make milestone
payments to SG Austria for therapies for cancer be eliminated in their entirety. In addition, the Binding Term Sheet Amendments also provides
that the scope of the Diabetes License Agreement is expanded to include all cell types and cell lines of any kind or description now or
later identified, including, but not limited to, primary cells, mortal cells, immortal cells and stem cells at all stages of differentiation
and from any source specifically designed to produce insulin for the treatment of diabetes.
In addition, one of the
Binding Term Sheet Amendments provides that we will have a 5-year right of first refusal from August 30, 2017 in the event that Austrianova
chooses to sell, transfer or assign at any time during this period the Cell-in-a-Box® technology, tradename and Associated Technologies
(defined below), intellectual property, trade secrets and know-how, which includes the right to purchase any manufacturing facility used
for the Cell-in-a-Box® encapsulation process and a non-exclusive license to use the special cellulose sulfate utilized with the
Cell-in-a-Box® encapsulation process (collectively, “Associated Technologies”); provided, however, that the Associated
Technologies subject to the right of first refusal do not include Bac-in-a-Box® (which is used to encapsulate bacteria). Additionally,
for a period of one year from August 30, 2017 one of the Binding Term Sheet Amendments provides that Austrianova will not solicit, negotiate
or entertain any inquiry regarding the potential acquisition of the Cell-in-a-Box® and its Associated Technologies.
The Binding Term Sheet
Amendments further provide that: (i) the royalty payments on gross sales as specified in the SG Austria APA, the Cannabis License Agreement
and the Diabetes License Agreement are changed to 4%; and (ii) the royalty payments on amounts received by us from sublicensees on sublicensees’
gross sales under the same agreements are changed to 20% of the amount received us from our sublicensees, provided, however, that
in the event the amounts received by us from sublicensees is 4% or less of sublicensees’ gross sales, Austrianova will receive 50%
of what we receive (up to 2%) and then additionally 20% of any amount we receive over that 4%.
One of the Binding Term
Sheet Amendments requires that we pay $900,000 to Austrianova ratably over a nine-month period in the amount of two $50,000 payments each
month during the nine-month period on the days of the month to be agreed upon between the parties, with a cure period of 20 calendar days
after receipt by us of written notice from Austrianova that we have failed to pay timely a monthly payment. As of April 30, 2020, the
$900,000 amount has been paid in full. The Binding Term Sheet Amendments also provide that Austrianova receives 50% of any other financial
and non-financial consideration received from our sublicensees of the Cell-in-a-Box® technology.
Impact of the COVID-19 Pandemic on Operations
In March 2020, the World
Health Organization declared an outbreak of COVID-19 as a pandemic, and the world’s economies have experienced pronounced effects.
Despite the multiple COVID-19 vaccines globally, there remains uncertainty around the extent and duration of disruption and any future
related financial impact cannot reasonably be estimated at this time. COVID-19 has caused and may continue to cause significant, industry-wide
delays in clinical trials. Although we are not yet in a clinical trial, we have filed an IND with the FDA to commence a clinical trial
in LAPC, and this clinical trial may experience delays relating to COVID-19 once commenced, including but not limited to: (i) delays or
difficulties in enrolling patients in our clinical trial if the FDA allows us to go forward with the trial; (ii) delays or difficulties
in clinical site activation, including difficulties in recruiting clinical site investigators and clinical site personnel; (iii) delays
in clinical sites receiving the supplies and materials needed to conduct the clinical trial, including interruption in global shipping
that may affect the transport of our clinical trial product; (iv) changes in local regulations as part of a response to COVID-19 which
may require us to change the ways in which its clinical trial is to be conducted, which may result in unexpected costs, or to discontinue
the clinical trial altogether; (v) diversion of healthcare resources away from the conduct of clinical trials, including the diversion
of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trial; (vi) interruption of key
clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal or state
governments, employers and others, or interruption of clinical trial subject visits and study procedures, the occurrence of which could
affect the integrity of clinical trial data; (vii) risk that participants enrolled in our clinical trials will acquire COVID-19 while
the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse
events; (viii) delays in necessary interactions with local regulators, ethics committees, and other important agencies and contractors
due to limitations in employee resources or forced furlough of government employees; (ix) limitations in employee resources that would
otherwise be focused on the conduct of our clinical trial because of sickness of employees or their families or the desire of employees
to avoid contact with large groups of people; (x) refusal of the FDA to accept data from clinical trials in affected geographies; and
(xi) interruption or delays to our clinical trial activities. Many of these potential delays may be exacerbated by the impact of COVID-19
in foreign countries where we are conducting these preclinical studies, including India, Europe, Singapore and Thailand.
Further, the various
precautionary measures taken by many governmental authorities around the world in order to limit the spread of COVID-19 has had and may
continue to have an adverse effect on the global markets and global economy, including on the availability and pricing of employees, resources,
materials, manufacturing and delivery efforts and other aspects of the global economy. COVID-19 could materially disrupt our business
and operations, hamper its ability to raise additional funds or sell securities, continue to slow down the overall economy, curtail consumer
spending, interrupt our supply chain, and make it hard to adequately staff our operations.
Market Opportunity
and Competitive Landscape
The three areas we are
developing for live cell encapsulation-based therapies are cancer, diabetes and malignant ascites.
The Cell-in-a-Box® capsules
are comprised of cotton’s natural component – cellulose. Other materials used by competitors include alginate, collagen, chitosan,
gelatin and agarose. Alginate appears to be the most widely used of these. We believe the inherent strength and durability of our cellulose-based
capsules provides us with advantages over the competition. They do so with no evidence of rupture, damage, degradation, fibrous overgrowth
or immune system response. The cells within the capsules also remained alive and functioning during these studies. Other encapsulating
materials degrade in the human body over time, leaving the encapsulated cells open to immune system attack. Damage to surrounding tissues
has also been reported to occur over time when other types of encapsulation materials begin to degrade.
The cells encapsulated
using the Cell-in-a-Box® technology can be frozen for extended periods of time. When thawed, the cells are recovered
with approximately 85% viability. We are unaware of any other cell encapsulation material that is capable of protecting their encapsulated
cells to this degree. The implications of this property of the Cell-in-a-Box® technology are obvious – long-term
storage of encapsulated cells and shipment of encapsulated cells over long distances.
We believe our live cell
encapsulation technology may have significant new advantages and opportunities for us in numerous and developing ways. For example:
Pancreatic cancer is
increasing in most industrialized countries. The American Cancer Society estimates that in 2022 there will be 62,210 people in the U.S.
diagnosed with pancreatic cancer. It also estimates 48,830 patients with pancreatic cancer will die in 2022. Pancreatic cancer accounts
for about 3% of all cancers in the U.S. and about 7% of all cancer deaths.
Our goal is to satisfy
a clear unmet medical need for patients with LAPC whose tumors no longer respond after 4-6 months of treatment with the chemotherapy combination
of Abraxane® plus gemcitabine or the four-drug combination known as FOLFIRINOX. For these patients, there is currently
no effective therapy. We believe there will be no therapy comparable to our Cell-in-a-Box® plus low dose of ifosfamide
combination therapy when it is used in these patients.
We face intense competition
in the field of treating pancreatic cancer. There are dozens of startups, smaller biotech companies, big pharma, and several academic
institutions and cancer centers all trying to improve the outcome for pancreatic cancer patients. For example, in a single patient case
report published June 2022 in the New England Journal of Medicine, a study funded by the Providence Portland Medical Foundation in conjunction
with the Earle A. Chiles Research Institute reported objective regression of metastatic pancreatic cancer using genetically-engineered
autologous T cells. There are several drugs already available and in the pipelines of pharmaceutical companies worldwide, not the least
of which is the combination of the drugs of Abraxane® and gemcitabine. This is the primary FDA-approved combination
of drugs for treating advanced pancreatic cancer. In Europe and in the U.S., the 4-drug combination FOLFIRINOX has also found use as a
first-line treatment for advanced pancreatic cancer. Some of our competitive strengths include the Orphan Drug Designation we have been
granted by the FDA and the European Medicines Agency for our pancreatic cancer therapy, our trade secrets, the patents we are seeking
and the licensing agreements we have that are described in this Report. Yet many of our competitors have substantially greater financial
and marketing resources than we do. They also have stronger name recognition, better brand loyalty and long-standing relationships with
customers and suppliers. Our future success will be dependent upon our ability to compete.
We believe our product
candidate for pancreatic cancer has already shown promise through the completion of a Phase 1/2 and a Phase 2 clinical trial in advanced,
inoperable pancreatic cancer carried out in Europe by Bavarian Nordic in 1998 – 1999 and 2000, respectively.
We have a number of competitors
developing Cannabis-based treatments for cancer. In February 2021, Jazz Pharmaceuticals Public Limited Company (“Jazz”),
a neuroscience and oncology focused company, acquired GW Pharmaceuticals, PLC for $7.2 billion. Jazz now has two approved cannabinoid
extract-based products: Epidiolex® (CBD) oral solution for the treatment of seizures associated with Lennox-Gastaut
syndrome, Dravet syndrome or tuberous sclerosis complex, and Sativex® (THC/CBD) oromucosal spray for the treatment
of severe multiple sclerosis spasticity. Sativex® is currently being studied in conjunction with the Brain Tumour
Charity and the UK National Health Service to examine effectiveness in the treatment of recurrent glioblastoma brain tumor when used alongside
the chemotherapeutic agent temozolomide. Jazz’s pipeline indications include: neonatal hypoxic-ischemic encephalopathy, neuropsychiatry
targets, autism spectrum disorders, epilepsy, spasticity and undisclosed targets. Cannabis Science, Inc. (“CBIS”) has a number
of indications in its product development pipeline, all pre-clinical, the most advanced being for the treatment of oxidative stress, psychosis/anxiety,
PTSD, and sleep deprivation. CBIS also has plans to develop treatments for Stage 4 lung cancer and pancreatic cancer. CNBX Pharmaceuticals
Inc. (previously Cannabics Pharmaceuticals, Inc.) (“CNBX”) has a primary research focus on the development of cannabinoid
therapies for the treatment of cancer, mainly cancers of the gastrointestinal tract, skin, breast and prostate. CNBX’s other Cannabis-based
areas of research include Alzheimer’s disease, mental health conditions, and auto-immune diseases. Cannabotech Ltd. (“Cannabotech”),
an Israeli company, in collaboration with Haifa University, is studying an improved method for killing pancreatic and colon cancer cells
using a botanical drug based on an extract of the Cyathus striatus fungus and a cannabinoid extract. Cannabotech is also
developing therapies for breast, lung and prostate cancers.
In contrast to the work
being done by these companies, we plan to focus on developing specific therapies based on chosen molecules rather than using Cannabis extracts.
We intend to use the Cell-in-a-Box® technology in combination with genetically-modified cell lines designed to activate
cannabinoid molecules for the targeted treatment of diseases and their related symptoms.
The Centers for Disease
Control and Prevention estimates that in 2022 a total of 37.3 million people in the U.S. have been diagnosed with diabetes (11.3% of the
U.S. population) and another 8.5 million people (23.0% of adults) are undiagnosed. The diabetes market is estimated in the tens of billions
of dollars, and it continues to grow.
The field of diabetes cell therapy development
is very competitive. There are numerous companies developing cell-based therapies for diabetes. These competitors include companies such
as ViaCyte, Inc. which has two stem cell-based product candidates in Phase 1/2 clinical trials for type 1 diabetes: PEC-Direct, which
is a pouch that is “open” to the surrounding vasculature and requires the use of immunosuppressive drugs, and PEC-Encap, which
is a pouch that contains the implanted cells and prevents contact with the vasculature and immune cells but still allows passage of nutrients
and proteins to travel between the cells inside the device and blood vessels which grow along the outside of the device. PEC-Encap is
reported to generally prevent immune rejection and immune sensitization. Conceptually, PEC-Encap has similarities with Cell-in-a-Box®.
Other companies developing some form of encapsulation-based diabetes therapy include Vertex Pharmaceuticals Inc., Defymed, Diatranz Otsuka
Limited, Seraxis, Inc., Unicyte AG, Sernova Corp., Betalin Therapeutics Ltd., Novo Nordisk, Beta-O2 Technologies Ltd., Eli Lilly &
Co. in collaboration with Sigilon Therapeutics, Inc. and the Diabetes Research Institute Foundation.
Although such competition exists in the diabetes
space, we believe these other companies are developing encapsulation-based therapies using materials and methodologies that produce capsules
or devices that are far less robust than ours or that are associated with other problems, such as extremely short shelf-life of the product
and/or fibrotic overgrowth of their encapsulation products when implanted in the body. We believe these properties are not characteristic
of the Cell-in-a-Box® capsules. Our product candidate for diabetes has shown promise. Completed research studies have resulted
in positive responses in animal models using the Melligen cells. We believe we are in a strong competitive position considering our unique
encapsulation technology and the genetically modified cells that we have the exclusive worldwide license to use in most industrialized
countries.
Malignant ascites occurs when cancer cells irritate
the peritoneum causing an overproduction of ascitic fluid which causes the abdomen to swell as fluid accumulates. It is more likely to
develop in patients who have ovarian, uterine, cervical, colorectal, stomach, pancreatic, breast and liver cancers. In most patients,
development of malignant ascites is a sign of advanced disease and poor prognosis. Malignant ascites can result in impairment to the quality
of life of a cancer patient. In addition to abdominal distention, pain and difficulty breathing, it may also cause nausea, vomiting, early
satiety, lower extremity edema, weight gain and reduced mobility. These symptoms can interfere with a patient’s ability to eat,
to walk and to perform daily activities. They also reduce a patient’s ability to withstand anti-cancer therapies, potentially reducing
survival.
We are developing a therapy to delay the production
and accumulation of malignant ascites using our cancer therapy (i.e., ifosfamide converting encapsulated live cells). Preclinical studies
are underway in Germany, and, if successful, we plan to seek FDA approval to conduct a Phase 1 study. Typical treatments for malignant
ascites include paracentesis, percutaneously implanted catheters, peritoneal ports and peritoneovenous shunts. These treatments can be
painful, ineffective and expensive. There is currently no available treatment that delays the production and accumulation of malignant
ascites fluid, and we know of no competitors in this area.
Material Agreements
Third Addendum to
the SG Austria APA
In June 2013, we and SG Austria entered the Third
Addendum and the Clarification Agreement. The Third Addendum requires us to make the following payments for the purchased assets; these
payments were timely made in full under the payment deadlines set forth in the Third Addendum:
· A $60,000 payment due under the SG Austria APA;
· $500,000 to be used to pay off the existing debt of Bio Blue Bird; and
Pursuant to the Third Addendum, we agreed to and
have entered a manufacturing agreement with SG Austria for the manufacture of the pancreatic cancer clinical trial product to treat LAPC.
The Manufacturing Framework Agreement requires us to pay Austrianova a one-time manufacturing setup fee in the amount of $647,000, of
which 50% is required to be paid on the effective date of the Manufacturing Framework Agreement and 50% is required to be paid three months
later. We have paid the full amount of the manufacturing setup fee.
The Manufacturing Framework Agreement also requires
us to pay a fee for producing the final encapsulated cell product of $647 per vial of 300 capsules after production, with a minimum purchased
batch size of 400 vials of any Cell-in-a-Box® product. The fees under the Manufacturing Framework Agreement are subject to annual
increases according to the annual inflation rate in the country in which the encapsulated cell products are manufactured. We placed and
have received an order to produce 400 vials for our clinical trial to treat LAPC. Austrianova has been paid the full amount for the order.
The Third Addendum also requires us to make future
royalty and milestone payments as follows:
· Two percent royalty on all gross sales received by us or our affiliates;
On May 14, 2018, we entered into amendments to
the Third Addendum. For a full description of these amendments, see Item 1. “History of the Business.”
Diabetes Licensing
Agreement
Under the Diabetes Licensing Agreement, we are
required to make a payment of $2,000,000 in two equal payments of $1,000,000 each. We made our first $1,000,000 payment on October 30,
2013. Our second payment of $1,000,000 was made on February 25, 2014.
The Diabetes Licensing Agreement requires us to
pay Austrianova, pursuant to a manufacturing agreement to be entered between the parties, a one-time manufacturing setup fee in the amount
of approximately $600,000, of which 50% is required to be paid on the signing of a manufacturing agreement for a product and 50% is required
to be paid three months later. In addition, the Diabetes Licensing Agreement requires us to pay a manufacturing production fee, which
is to be defined in the manufacturing agreement, for producing the final encapsulated cell product of approximately $600.00 per vial of
300 capsules after production, with a minimum purchased batch size of 400 vials of any Cell-in-a-Box® encapsulation-based product.
All costs for encapsulated cell products will be subject to an annual increase equal to the published rate of inflation in the country
of manufacture of the vials.
The Diabetes Licensing Agreement requires us to
make future royalty and milestone payments as follows:
· Ten percent royalty of gross sales of all products we sell;
The license under the Diabetes Licensing Agreement,
as amended, may be terminated and all rights will revert to Austrianova if any of the following milestone events do not occur within the
following timeframes, subject to all the necessary and required research having been successful and the relevant product being sufficiently
prepared to enter a clinical trial:
In May 2018, we entered into amendments to the
Diabetes Licensing Agreement. For a full description of these amendments, see Item 1. “History of the Business.”
Cannabis Licensing
Agreement
Pursuant to the Cannabis Licensing Agreement,
we acquired from Austrianova an exclusive worldwide license to use the Cell-in-a-Box® trademark and its associated technology
with genetically modified non-stem cell lines which are designed to activate cannabinoids to develop therapies involving Cannabis with
a right to sublicense.
Under the Cannabis Licensing Agreement, we are
required to pay Austrianova an initial upfront payment of $2,000,000 (“Upfront Payment”). We have the right to make periodic
monthly partial payments of the Upfront Payment in amounts to be agreed upon between the parties prior to each such payment being made.
Under the Cannabis Licensing Agreement, the Upfront Payment must be paid in full by no later than June 30, 2015. The parties amended the
Cannabis Licensing Agreement twice pursuant to which the balance of the Upfront Payment is to be paid by June 30, 2016. We have paid the
Upfront Payment of $2,000,000 in full.
The Cannabis Licensing Agreement requires us to
pay Austrianova, pursuant to a manufacturing agreement to be entered between the parties, a one-time manufacturing setup fee in the amount
of $800,000, of which 50% is required to be paid on the signing of a manufacturing agreement for a product and 50% is required to be paid
three months later. In addition, the Cannabis Licensing Agreement requires us to pay a manufacturing production fee, which is to be defined
in the manufacturing agreement, for producing the final encapsulated cell product of $800 per vial of 300 capsules after production with
a minimum purchased batch size of 400 vials of any Cell-in-a-Box® product. All costs for encapsulated cell products, the manufacturing
setup fee and the manufacturing production fee will be subject to annual increases, in accordance with the inflation rate in the country
in which the encapsulated cell products are manufactured.
The Cannabis Licensing Agreement requires us to
make future royalty and milestone payments as follows:
· Ten percent royalty of the gross sale of all products sold by us;
The license under the Cannabis Licensing Agreement,
as amended, may be terminated and all rights will revert to Austrianova if any of the following milestone events do not occur within the
following timeframes:
In May 2018, we entered into amendments to the
Cannabis Licensing Agreement. For a full description of these amendments, see Item 1. “History of the Business.”
Melligen Cell License
Agreement
The Melligen Cell License Agreement requires that
we pay royalty, milestone and patent costs to UTS as follows:
· Six percent of gross exploitation revenue on product sales;
· Twenty-five percent of gross revenues if the product is sublicensed by us;
In the event of a default under the Melligen Cell
License Agreement, the non-defaulting party may immediately terminate the agreement by notice in writing to the defaulting party if: (i)
the default has continued for not less than 14 days or occurred more than 14 days earlier and has not been remedied; (ii) the non-defaulting
party serves upon the defaulting party notice in writing requiring the default to be remedied within 30 days of such notice, or such greater
number of days as the non-defaulting party may in its discretion allow, and (iii) the defaulting party has failed to comply with the notice
referred to in (ii) above.
The Melligen Cell License Agreement was amended
in April 2016 to change the name of the licensee to our current name and clarify certain ambiguities in the agreement. We are required
to pay the Melligen cell patent prosecution costs and to pay to UTS a patent administration fee equal to 15% of all amounts paid by UTS
to prosecute and maintain patents related to the Melligen cells.
In August 2017, we entered into the Binding Term
Sheet pursuant to which the parties reached an agreement to amend certain provisions in the SG Austria APA, the Diabetes Licensing Agreement
and the Cannabis Licensing Agreement.
In May 2018, we entered into agreements with SG
Austria and Austrianova to amend certain provisions of the SG Austria APA, the Diabetes Licensing Agreement and the Cannabis Licensing
Agreement pursuant to the Binding Term Sheet. For a full description of these amendments, see Item 1. “History of the Business.”
Sources and Availability
of Raw Materials
The entire encapsulation
process relating to the encapsulation of the cells for the oncology and diabetes-based therapies we are developing is to be carried out
by Austrianova. Austrianova is the sole source of our product candidates. Austrianova is responsible for acquiring all of the necessary
raw materials used in this process, including the cellulose sulfate necessary for encapsulating the live cells, a process proprietary
to Austrianova. Austrianova from time to time has experienced significant supply chain delays, and we believe Austrinova may also be experiencing
liquidity issues as well. If Austrianova is unwilling or unable to perform such manufacturing for us, we may not be able to locate a replacement
manufacturer for our product candidates.
Patents, Intellectual Property and Trade Secrets
Intellectual property and patent protection are
of paramount importance to our business, as are the trade secrets and other strategies we have employed with Austrianova to protect the
proprietary Cell-in-a-Box® technology. Although we believe we take reasonable measures to protect our intellectual property and trade
secrets and those of Austrianova, we cannot guarantee we will be able to protect and enforce our IP or obtain patent protection for our
product candidates as needed. We license technology and trademarks relating to three areas: (i) live cell encapsulation with cells that
express cytochrome P450 where the capsule is permeable to prodrug molecules and the cells are retained within the capsules; (ii) treatment
of solid cancerous tumors and (ii) encapsulation of cells for producing retroviral particles for gene therapy. We also have exclusive
licensing rights to patents, trademarks and know-how using Cell-in-a-Box® technology in the diabetes field and in the treatment of
diseases and related conditions using cannabinoids.
Litigation may be required to protect our product
candidates, intellectual property rights or to determine the validity and scope of the proprietary rights of others. Establishment, maintenance
and enforcement of our intellectual property utilizes financial and operational resources. In addition, the possibility exists that our
intellectual property could be discovered to be owned by others, be invalid or be unenforceable – potentially bringing unforeseen
challenges to us.
Human Capital
As of April 30, 2023, we had two full-time employees
and several consultants who devote substantial time to us. The consultants are physicians, scientists, regulatory experts, clinical operation
experts and cGMP experts. All of our research and development (“R&D”) work is handled by our consultants.
Reverse Stock Split
Effective July 12, 2021, we filed a Certificate
of Change with the Nevada Secretary of State that authorized a 1:1500 reverse stock split of our common stock. The reverse stock split
resulted in reducing the authorized number of shares of our common stock from 50 billion to 33,333,334 with a par value of $0.0001 per
share. Any fractional shares resulting from the reverse stock split were rounded up to the next whole share. All warrants, option, share
and per share information in this Quarterly Report gives retroactive effect to such 1:1500 reverse stock split.
Our Corporate Information
We are a Nevada corporation incorporated in 1996.
In 2013, we restructured our operations to focus on biotechnology. The restructuring resulted in us focusing our efforts developing a
novel, effective and safe way to treat cancer and diabetes. In January 2015, we changed our name from Nuvilex, Inc. to PharmaCyte Biotech,
Inc. to reflect the nature of our current business.
Our corporate headquarters are located at 3960
Howard Hughes Parkway, Suite 500, Las Vegas, Nevada 89169. Our telephone number is (917) 595-2850. We maintain a website at www.pharmacyte.com
to which we post copies of our press releases as well as additional information about us. Our filings with the SEC are available free
of charge through our website as soon as reasonably practicable after being electronically filed with or furnished to the SEC. Information
contained in our website is not a part of, nor incorporated by reference into, this Report or our other filings with the SEC, and should
not be relied upon.
Government Regulation and Product Approval
As a development-stage biotechnology company that
operates in the U.S., we are subject to extensive regulation by the FDA and other federal, state, and local regulatory agencies. The federal
Food, Drug, and Cosmetic Act (“FDCA”) and its implementing regulations set forth, among other things, requirements for the
research, testing, development, manufacture, quality control, safety, effectiveness, approval, labeling, storage, record keeping, reporting,
distribution, import, export, advertising, promotion, marketing and sale of our product candidates. Although the discussion below focuses
on regulation in the U.S., we anticipate seeking approval for, and marketing of, our product candidates in other countries. Our activities
in other countries will also be the subject of extensive regulation, although there can be important differences with the U.S. The process
of obtaining regulatory marketing approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes
and regulations will require the expenditure of substantial time and financial resources and may not be successful.
Regulatory approval, when obtained, may be limited
in scope which may significantly limit the uses for which a product may be placed in the market. Further, approved drugs or biologic products,
as well as their manufacturers, are subject to ongoing post-marketing review, inspection and discovery of previously unknown issues regarding
the safety and efficacy of such products or the manufacturing or quality control procedures used in their production. These may result
in restrictions on their manufacture, sale or use or in their withdrawal from the market. Any failure or delay by us, our suppliers of
manufactured drug product, collaborators or licensees in obtaining regulatory approvals could adversely affect the marketing of our product
candidates and our ability to receive product revenue, license revenue or profit-sharing payments. For more information, see Item 1A.
“Risk Factors.”
U.S. Government Regulation
The FDA is the main regulatory body that controls
pharmaceuticals and biologics in the U.S. Its regulatory authority is based in the FDCA and the Public Health Service Act. Pharmaceutical
products and biologics are also subject to other federal, state and local statutes and regulations. A failure to comply with any requirements
during the product development, approval, or post-approval periods, may lead to administrative or judicial sanctions. These sanctions
could include the imposition by the FDA or by an Institutional Review Board (“IRB”) of a hold on clinical trials, refusal
to approve pending marketing applications or supplements, withdrawal of approval, warning letters, product recalls, product seizures,
total or partial suspension of production or distribution, injunctions, fines, civil penalties or criminal prosecution.
The steps required before a new drug or biologic
may be marketed in the U.S. generally include:
· submission to the FDA of an IND to support human clinical testing in the U.S.;
· FDA review and approval of the NDA or BLA.
Clinical Development
Before a drug or biologic product may be given
to humans, it must undergo preclinical testing. Preclinical tests include laboratory evaluation of a product candidate’s chemical
and biological activities and animal studies to assess potential safety and efficacy in humans. The results of these studies must be submitted
to the FDA as part of an IND which must be reviewed by the FDA for safety and other considerations before testing can begin in humans.
An IND is a request for authorization from the
FDA to administer an investigational product candidate to humans. This authorization is required before interstate shipping and administration
can commence of any new drug or biologic product destined for use in humans in the U.S. A 30-day waiting period after the submission of
each IND is required before commencement of clinical testing in humans. If the FDA has neither commented on nor questioned the IND within
this 30-day period after submission of the IND, the clinical trial proposed in the IND may begin. A clinical trial involves the administration
of the investigational product candidate to patients under the supervision of qualified investigators following GCP standards. These international
standards are meant to protect the rights and health of patients and to define the roles of clinical trial sponsors, administrators and
monitors. A clinical trial is conducted under protocols that detail the parameters to be used in monitoring safety, and the efficacy criteria
to be evaluated. Each protocol involving testing on U.S. patients and subsequent protocol amendments must be submitted to the FDA as part
of the IND.
The product candidates in our pipeline are at
various stages of preclinical development. The path to regulatory approval includes three phases of clinical trials in which we collect
data to support an application to regulatory agencies to allow us to ultimately market a product for treatment of a specified disease.
There are many difficulties and uncertainties inherent in research and development of new products, and these can conceivably result in
a high rate of failure. To bring a drug or biologic from the discovery phase to regulatory approval, and ultimately to market, takes years
and the costs to do so are significant. Failure can occur at any point in the process, including after the product is approved, based