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Item 1. Business

2021-09-28 compared with 2020-10-01 · 863 added, 1278 removed, 82 unchanged (96% of the section changed)

used in this Annual Report, references to the “Company,”

“Propanc,”

“we,”

“our,”

and “us”

refer to Propanc Biopharma, Inc.

used in this Annual Report, references to the “Company,” “Propanc,” “we,” “our,” and

“us” refer to Propanc Biopharma, Inc.

and its consolidated subsidiary, unless otherwise indicated.

references to our “financial statements”

are to our consolidated financial statements included elsewhere in this Annual

Report except as the context otherwise requires.

prepare our consolidated financial statements in United States dollars and in accordance with generally accepted accounting

principles as applied in the United States, (“U.S.

GAAP”).

In this Annual Report, references to “$”

“dollars”

In addition, references

to our “financial statements” are to our consolidated financial statements included elsewhere in this Annual Report except

as the context otherwise requires.

prepare our consolidated financial statements in United States dollars and in accordance with generally accepted accounting principles

as applied in the United States, (“U.S.

In this Annual Report, references to “$” and “dollars”

are to United States dollars.

are a development-stage healthcare company that is currently focused on developing new cancer treatments for patients suffering

from pancreatic, ovarian and colorectal cancer.

Utilizing our scientific and oncology consultants, we have developed a rational,

composite formulation of anti-cancer compounds, which together exert a number of effects designed to control or prevent tumors

from recurring and spreading through the body.

Our lead product candidate, PRP, is a variation upon our novel formulation and

involves proenzymes, the inactive precursors of enzymes.

As a result of positive early indications of the anti-cancer effects

of our technology, over the last year we have conducted successful pre-clinical studies on PRP and subject to us receiving adequate

financing, hope to submit a clinical trial application in the first half of 2021.

We intend to develop our PRP to treat early-stage

cancer and pre-cancerous diseases and as a preventative measure for patients at risk of developing cancer based on genetic screening.

Research and Development Highlights:

cancer treatment :

We are developing PRP, an intravenous once-daily proenzyme treatment as a therapeutic option in cancer

treatment and prevention.

PRP is a combination of the pancreatic proenzymes trypsinogen and chymotrypsinogen.

mechanisms of action on cancerous or carcinogenic cells :

PRP produces multiple effects on cancerous cells intended to

inhibit tumor growth and potentially stop a tumor from spreading through the body.

This is in contrast to current cancer treatments

that lack sufficient efficacy to achieve a durable clinical response.

As our research progresses, we intend to explore further

these multiple mechanisms of action in order to identify opportunities to expand our intellectual property portfolio.

we hope to uncover the molecular targets of the proenzymes to identify their potential for developing new compounds.

data from patient treatment :

We began our development efforts by analyzing scientific research undertaken over the last

15 years, including clinical data from patients in the UK and Australia.

We concluded that there is at least indirect evidence

that a formulation such as PRP may be an effective treatment against cancer and warranted further development.

Efficacy Studies :

In November 2015, we completed animal efficacy studies in mice through our contract research partner,

vivoPharm, demonstrating proof of concept in vivo .

During the course of these studies, we discovered a new target therapeutic

dose range using proenzymes for treating cancer.

That month, we filed a patent application in support of this discovery, as

described further herein.

Toxicology Studies :

In October 2016, we completed an animal study for PRP, in which we evaluated its toxicokinetic parameters

as well as its distribution and bioavailability, both before and after repeat dosages.

We then initiated a second such study

in December 2016.

That study escalated the dosage levels in different phases and was completed in April 2017.

no major toxicological findings after PRP was administered by intravenous injection once daily throughout the study period.

Clinical Trial Application :

With the successful completion of the studies described above, we believe we have accumulated

sufficient data to establish a safe and effective dosage level for PRP and advance our product development to the clinical

We are currently working with our manufacturer to create the finished product that will be part of our Investigational

Medicinal Product Dossier to be submitted in connection with our anticipated first clinical trial for PRP, which we expect

will be conducted in Australia.

Drug Designation :

In June 2017, we received notification from the U.S.

Food and Drug Administration (FDA) that PRP had

been conferred Orphan Drug Designation.

This special status is granted when a rare disease or condition is implicated and

a potential treatment qualifies under the Orphan Drug Act and applicable FDA regulations.

Orphan Drug status qualifies us

for various development incentives, including protocol assistance, the potential for research grants, the waiver of future

application fees, and tax credits for clinical testing if we choose to host future clinical trials in the U.S.

intellectual property :

In addition to our pre-clinical studies, we have also focused on building a significant portfolio

of intellectual property around the use of proenzymes in the treatment of cancer, identifying new formulations, alternative

routes of administration and potential new therapeutic targets.

We have filed numerous patent applications relating to PRP,

several of which have been granted while others remain pending.

In the U.S., we have been issued two patents to date

9,636,359 and 10,350,239).

A further application has been filed and an Examiner’s first report expected by May

Our patent protection extends to both PRP’s mechanism of action and the new compositions of proenzymes.

and development expenses:

During the fiscal years ended June 30, 2020 and 2019, we have spent $179,987 and $260,335, respectively,

on research and development expenses.

Historically, we have assumed all of the costs associated with research and development.

In September 2018, the Company entered into a two-year collaboration agreement with the University of Jaén (the “University”)

to provide certain research services to the Company.

In consideration of such services, the Company agreed to pay the University

approximately 52,000 Euros ($59,508 USD) in year one of which 31,754 Euros ($36,117 USD) was paid in fiscal 2019

and 15,410 Euros ($17,331 USD) was accrued in fiscal 2020;

and a maximum of 40,000 Euros ($45,775 USD) in year two.

Additionally, in exchange for full ownership of the intellectual property the Company agreed to pay royalties of 2% of net

revenues to the University.

In August 2019, we announced that we have

developed a method to quantify the active ingredients of our lead product candidate, PRP, in preparation for the

company’s First-In-Human (“FIH”) study, planned for the second half of 2021 calendar year.

was conducted by Propanc’s research partner based in Berlin, Germany, who has extensive experience in the development

of functional assays for unique bio-therapeutics.

This bioanalytical method development and validation plays a significant

role in evaluation and interpretation of the systemic absorption of PRP in clinical studies including its distribution, and

clinical effects throughout the body.

The development of the bioanalytical assay is also an important step for the clinical

development of PRP, as Propanc evaluates sites to conduct the FIH study in advanced cancer patients, such as the Peter Mac

Center, Australia’s largest cancer hospital, which has significant experience in early stage clinical development.

Validation of the bioanalytical method will be undertaken in 2021.

November 2019, we announced today that our POP1 research and drug discovery program has made significant advancements towards

producing synthetic versions of the two proenzymes, trypsinogen and chymotrypsinogen.

With the aim of producing large quantities

of trypsinogen and chymotrypsinogen for commercial use, exhibiting minimal variation between lots and without sourcing the proenzymes

from animals, the Company is undertaking a challenging research project in collaboration with the universities of Jaén

The two active ingredients are currently naturally derived from animal sources, which combine to form our lead product

candidate, PRP.

Our vision is to produce a backup product candidate to PRP which can further stabilize and enhance the effects

of the proenzymes when administered to patients.

At the research laboratories at the universities of Jaén and Granada,

scientific researchers are in the process of optimizing conditions to achieve high titers of recombinant trypsinogen and chymotrypsinogen

with this expression system.

January 2020, we announced that a Certificate for Advance Overseas Finding was received from the Board of Innovation and Science

Australia to receive up to a 43.5% “cash back”

benefit from overseas R&D expenses.

The finding relates to the

planned Phase 1 clinical trial –

Multiple Ascending Dose Studies of proteolytic proenzymes for the treatment of pancreatic

Overseas activities to be undertaken include the development of an analytical assay for the quantification of active pharmaceutical

ingredients in the Company’s lead product candidate, PRP, and its manufacture of the finished product for the Phase 1 clinical

were originally incorporated in Melbourne, Victoria Australia on October 15, 2007 as Propanc PTY LTD and continue to be based

in Camberwell, Victoria Australia.

Since our inception, substantially all of our operations have been focused on the development

of new cancer treatments targeting high-risk patients, particularly cancer survivors, who need a follow-up, non-toxic, long-term

therapy designed to prevent the cancer from returning and spreading.

We anticipate establishing global markets for our products.

November 23, 2010, our Company was incorporated in the state of Delaware as Propanc Health Group Corporation.

In January 2011,

to reorganize our Company, we acquired all of the outstanding shares of Propanc PTY LTD on a one-for-one basis and Propanc PPY

LTD became our wholly-owned subsidiary.

Effective April 20, 2017, we changed our name to “Propanc Biopharma, Inc.”

to better reflect our stage of operations and development.

On the same date, we also effected a 1-for-250 reverse stock split

whereby we (i) decreased the number of authorized shares of our common stock to 100,000,000 (ii) decreased the number of authorized

shares of our preferred stock to 1,500,005 and (iii) decreased, by a ratio of 1-for-250 the number of retroactively issued and

outstanding shares of our common stock.

January 23, 2018, we filed a Certificate of Amendment to our Certificate of Incorporation to increase the number of authorized

shares of our common stock from 100,000,000 to 400,000,000.

On September 21, 2018, we filed a Certificate of Amendment to our

Certificate of Incorporation to increase the number of authorized shares of our common stock from 400,000,000 to 4,000,000,000.

On June 11, 2019, we filed a Certificate of Amendment, as amended, to our Certificate of Incorporation to decrease the number

of authorized shares of our common stock from 4,000,000,000 to 100,000,000 in connection with the 1-for-500 reverse stock split

that occurred on June 24, 2019.

February 4, 2020, we filed a Certificate of Amendment to our Certificate of Incorporation to increase the number of

authorized shares of our common stock from 100,000,000 to 1,000,000,000 which was effected on March 13,

Milestones for Propanc

the late 1990s, work from other scientists and clinicians, including Dr.

Josef Novak in the U.S., and a since retired oncologist

from the Czech Republic, Dr.

Frantisek Trnka, shed new light on the therapeutic potential of Professor John Beard’s

Extensive laboratory work undertaken over a number of years by Novak and Trnka was reported in the journal Anticancer

Research in 2005 in the paper entitled Proenzyme Therapy of Cancer .

The conclusion of Novak and Trnka from this

work was the discovery “that proenzyme therapy mandated first by John Beard nearly one hundred years ago, shows remarkable

selective effects that result in growth inhibition of tumor cells with metastatic potential.”

Today, these important

scientific observations support our view that proenzymes are selective and effective in targeting malignant tumor cells and

could become an effective tool in the fight against metastatic cancer.

Julian Kenyon, Medical Director of the Dove Clinic in the UK, and Dr.

Douglas Mitchell further developed the therapeutic

concepts of Beard and identified strategies that could improve upon the therapeutic potential of Beard’s original ground-breaking

A suppository formulation was developed by Mandeville Medicines in Buckinghamshire, UK, at the request of, and in consultation

Kenyon and Mitchell, in an effort to improve on results reported in the literature pertaining to the potential

therapeutic use of proenzymes in cancer treatment.

Patients were first treated with the suppository formulation in April 2007

at The Dove Clinic in the UK, and in July 2007 at the Opal Clinic in Australia.

Kenyon and Mitchell, through The Dove

Clinic and Opal Clinic respectively, treated cancer patients in the United Kingdom and Australia with a suppository formulation

of proenzymes.

The treatment was undertaken under special UK and Australian regulatory provisions.

In the UK it was undertaken

under the regulations of the Medicines and Healthcare Products Regulatory Agency (the “MHRA”), designed for patients

who have special clinical needs that cannot be met by licensed medicinal products, and in Australia under the Therapeutic

Goods Administration (“TGA”) Special Access Scheme, a mechanism that provides for the import and/or supply of

an unapproved therapeutic good for a single patient, on a case by case basis.

In both jurisdictions, patients are permitted

to receive treatment on an individual basis for compassionate use as long it is supplied by a recognized, licensed manufacturer

who is able to meet certain guidelines for unapproved products, and individual case files are maintained for patients should

the regulatory authorities require this information.

No prior approval was required by either the MHRA or TGA prior to the

commencement of treatment.

No suppository formulation of the proenzymes was available and it was necessary for a novel suppository

formulation to be manufactured specifically for these patients by a suitably licensed manufacturer.

late stage cancer patients suffering from a range of malignancies in the UK and Australia received treatment with the proenzyme

suppositories over periods of time ranging from one month to in excess of 17 months.

Inspired by their observations in clinical

practice, Drs.

Kenyon and Mitchell resolved to develop proenzyme therapy for cancer patients worldwide.

late 2007, Drs.

Kenyon and Mitchell and Mr.

James Nathanielsz, our Chief Executive Officer and Chief Financial Officer, developed

a strategy to commercialize the newly developed proenzyme formulation, now designated PRP.

Propanc PTY LTD.

was established

in Australia as a vehicle to refine, develop and commercialize novel, patented proenzyme therapeutics for the treatment of

2008, our Scientific Advisory Board (the “Scientific Advisory Board”) comprising Professor John Smyth (Edinburgh

University), Professor Klaus Kutz (Bonn University) and Professor Karrar Khan (De Montfort University) was established.

the expertise of the Scientific Advisory Board in oncology research and development will be relied upon as we initiate patient

trials and advance our products down the requisite regulatory pathways to commercialize our proenzyme therapies.

2009, a retrospective review of the patient notes from the 46 patients treated in the UK and Australia with the proenzymes

suppositories (as described above) was undertaken by Dr.

This report was subject to analysis by Professor Klaus Kutz

who, at the time of the review, was an independent consultant in clinical pharmacology and safety, specializing in oncology.

Professor Kutz observed that no patients were reported as living for a period less than that predicted by the treating clinician

and a number of terminally ill patients lived marginally longer than predicted, particularly those suffering from pancreatic,

colorectal, ovarian and gastro-intestinal cancers.

As a result of the observations made by Dr.

Kenyon and Professor Kutz,

we are targeting the development of proenzyme therapy for the treatment of colorectal and pancreatic cancers for clinical

trials, and in the future targeting other cancer types as our product candidate progresses to commercialization.

In early 2008, a research collaborative partnership

was established with Professor David Tosh at the Center for Regenerative Medicine, Department of Biology and Biochemistry

at Bath University, to investigate the molecular mechanisms by which the proenzyme formulation is acting, which resulted in

us filing two provisional patents a year later.

We undertook additional scientific research with Professor Tosh, Dr.

Perán, Department of Health Sciences at Jaén University, and Dr.

Juan Antonio Marchal, Biopathology and Regenerative

Medicine Institute at Granada University.

Important anti-cancer effects of the proenzymes were discovered, including triggering

cell necrosis (cell death) and apoptosis (programmed cell death) and significantly, the induction of cell differentiation

inducing cancer cells to exhibit normal cell behavior).

This led to us increasing our intellectual property base and

patent new pharmaceutical compositions designed to enhance the effects of proenzymes.

Subsequently, two provisional patents

were combined into one Patent Cooperation Treaty (“PCT”) Application, filed on October 22, 2010 (PCT Application),

and then a year later, we completed a 30 month national phase filing deadline for an international patent and commenced entering

the national phase in countries around the world.

Thus far, we have received grant status in Australia, China, Japan, Indonesia,

Israel, New Zealand, Singapore and South Africa and our application remains under examination in Brazil, Canada, the European

Union, Malaysia, Mexico and the Republic of Korea.

In the United States, two patents have been issued

to date by the United States Patent and Trademark Office (No.

9,636,359 and No.

10,350,239) while another remains pending.

We also have another 3 PCT applications for proenzyme compositions that have entered national phase in major global jurisdictions.

late 2010, we made important discoveries and scientific observations, resulting in additional composition claims, which were

included in the original PCT Application, further protecting the company’s proenzyme formulation.

Collaboration with

vivoPharm Pty Ltd.

(“vivoPharm”), located in Melbourne, Australia, with research facilities in Hershey, Pennsylvania,

United States, identified a highly synergistic ratio of the proenzymes when combined together, resulting in increased anti-cancer

effects in several tumor cell lines.

Furthermore, although α-Amylase was previously included in the early days of enzyme

therapy and in the suppository formulation developed by Dr.

Kenyon and Dr.

Mitchell, after evaluating the synergistic interaction

between the two proenzymes and α-Amylase, we concluded that α-Amylase did not contribute to the anti-tumor activity

of the formulation, and so it was removed.

By 2011, further work completed by vivoPharm confirmed the anti-metastatic effects

of the newly combined ratio of the proenzymes in various cell line assays, and anti-angiogenic (inhibition of blood vessel

formation) properties of the proenzyme treatment in mice.

this time, we decided to access the U.S.

markets in order to raise the capital needed

to finance the Company’s proenzyme treatment for future preclinical testing and

clinical trials.

We incorporated as Propanc Health Group Corporation in the state of

Delaware in November 2010 and in January 2011, we acquired all of the outstanding shares

of Propanc PTY LTD on a one-for-one basis making and Propanc PTY LTD became our wholly-owned

In mid-2012, our common stock began trading on the Over-the-Counter Bulletin

Board and it currently trades on OTCQB.

May 2013, it was observed that proenzymes enforce the re-entry of cancer cells back into normal cellular pathways and this

may represent a novel approach to the treatment of cancer.

These findings were published in Cellular Oncology , a peer

reviewed journal of the International Society for Cellular Oncology.

2014, after conducting a detailed strategic review of our scientific and preclinical research, our development team determined

that parenteral drug administration is the preferred route for the Company’s lead product, PRP.

This approach is expected

to maximize results in future patient trials, by ensuring maximum exposure of the drug to the tumor site.

mid-2015, Dr.

Joseph Chalil joined our Scientific Advisory Board as an independent expert to provide advice on the Company’s

drug development programs, in particular, our lead product, PRP.

Chalil is a physician and executive at Boehringer Ingelheim,

one of the world’s largest privately held pharmaceutical companies.

July 2015 and February 2016, several scientific research findings were announced demonstrating significant anti-tumor efficacy

in several animal models, including pancreatic and ovarian cancers at higher doses when administering proenzymes by intravenous

injection, dramatic suppression of cancer stems cells in cell culture by altering several key pathways involved with invasion

and metastasis, and identification of a synergistic response in a broad range of cancer types including kidney, melanoma,

brain, prostate, liver, uterine and lung cancers.

2016, we added additional members from our partner universities and hospital to our Scientific Advisory Board, including Dr.

Macarena Perán, who is currently Reader in Anatomy at the University of Jaén in Spain, Professor Juan Antonio

Marchal Corrales, Professor of Anatomy and Embryology at the Faculty of Medicine at the University of Granada, and Dr.

García, Head of Translational Research at the University Hospital of Granada.

August 2016, we entered into a Manufacturing Services Agreement and Quality Assurance Agreement with Amatsigroup NV, formally

known as Q-Biologicals NV, a contract manufacturing organization located in Belgium.

Pursuant to the Manufacturing Services

Agreement, Amatsigroup produces for us certain drug substances and product containing certain enzymes at its facility in Belgium.

We use these substances and products for development purposes, including but not limited to future clinical trials.

October 2016, we completed an animal study for PRP, in which we evaluated its toxicokinetic parameters as well as its distribution

and bioavailability, both before and after repeat dosages.

We then initiated a second such study in December 2016.

escalated the dosage levels in different phases and was completed in April 2017.

We observed no major toxicological findings

after PRP was administered by intravenous injection once daily throughout the study period.

April 20, 2017, we changed our corporate name to “Propanc Biopharma, Inc.”

to better reflect our stage of operations

and development.

June 2017, we received notification from the FDA that PRP had been granted Orphan Drug Designation, a special status that

will enable us to qualify for tax credits for our future clinical trials, among other benefits.

October 2017, we published key findings relating to a combination of two proenzymes trypsinogen and chymotrypsinogen A with

potent in vitro and in vivo anti-tumor efficacy in Scientific Reports , a peer reviewed scientific journal

covering all areas of the natural sciences.

It was concluded that PRP could have relevant oncological clinical applications

for the treatment of advanced or metastatic adenocarcinoma and advanced epithelial ovarian cancer.

February 2018, we announced allowance of our key patent application from the European Patent Office (EPO) covering a pharmaceutical

composition for treating cancer comprising trypsinogen and chymotrypsinogen within the European Union.

The allowed patent

application is the first approval for the Company in the EU, which protects the Company’s lead product candidate, PRP,

a solution for once-daily intravenous administration of a combination of two pancreatic proenzymes trypsinogen and chymotrypsinogen.

March 2018, we completed the successful reproduction run of the manufacturing process for the Company’s two drug substances

trypsinogen and chymotrypsinogen.

The successful reproduction run demonstrated scalability of our proprietary manufacturing

process to enable routine production of the two active substances for PRP.

The process was developed in collaboration with

a European Contract Manufacturing Organization (CMO) experienced in the production of biopharmaceuticals.

July 2018, we entered national phase for two of our key patent applications from our intellectual property portfolio.

first patent application, which entered national phase in July 2018, describes a method to eradicate cancer stem cells, and

a second patent application, covering proenzyme compositions for the treatment of solid tumors, completed national phase entry

mid-July 2018.

National phase is a process whereby applicants file a patent application in each individual jurisdiction or

country, according to where intellectual property protection is sought.

September 2018, we entered into a two-year collaboration agreement with the University

of Jaén to provide certain research services to us.

In consideration of such services,

we agreed to pay the university approximately 52,000 Euros ($59,508 USD) in year

one and a maximum of 40,000 Euros ($45,775 USD) in year two.

Additionally, in

exchange for full ownership of the intellectual property we agreed to pay royalties of

2% of net revenues to the University.

December 2018, we announced that our foundation patent application has been granted by the Office of the Controller General

of Patents, Design and Trademarks, India.

The foundation patent, which covers our lead product candidate, PRP, pioneers the

discovery of a pharmaceutical composition for treating cancer via a combination of trypsinogen and/or chymotrypsinogen pancreatic

As of June 30, 2020, the foundation patent has been granted in the United States, Belgium, Czech Republic,

Denmark, France, Germany, Ireland, Italy, Netherlands, Portugal, Spain, Sweden, Switzerland, Liechtenstein, Turkey, United

Kingdom, Australia, China, Japan, Indonesia, Israel, New Zealand, Singapore, Malaysia, South Africa, Mexico, Republic of Korea

It is presently under examination in Brazil and Canada.

January 2019, we announced that a cooperation agreement has been entered into between the University of Jaén and our

Company to commence the POP1 joint drug discovery program to be co-funded by both parties.

The agreement coincides with the

appointment of research scientist, Mr.

Aitor González, to lead the drug discovery and research activities over the

next 3 to 4 years.

The objective of the program is to identify and develop suitable backup compounds to our lead product candidate,

As part of the agreement, Macarena Perán, Ph.D.

and Julian Kenyon, M.D.

have been appointed as joint supervisors,

representing the University and our Company, respectively.

The program involves advancing new compounds through a drug screening

process, followed by preclinical and early stage clinical development.

As the drug candidate progresses along the development

pathway, the collaboration will also involve the Universities of Granada and Jaén, as well as Granada and Almeria Hospitals,

which are members of FIBAO, a Public Health Foundation, based in Granada, Spain, committed to assisting commercial partners

with the development and commercialization of innovative technologies designed to benefit humankind.

March 2019, we announced that we received a notification of allowance from the United States Patent and Trademark Office (“USPTO”)

confirming both methods of treatment and composition of matter claims involving trypsinogen and chymotrypsinogen for our foundation

patent in the U.S.

that covers PRP.

The notification of allowance from the USPTO signifies that a USPTO examiner has determined

that PRP’s patent application is complete and meets all relevant statutory requirements.

March 2019, we announced that we have initiated development of a bio-analytical assay

intended to quantify the active ingredients of RPR in preparation for human trails.

necessary work performed in connection with this development will be conducted by a specialist

Contract Research Organization with extensive knowledge in the development of functional

assays for different bio-therapeutics.

July 2019, we appointed Mr.

Carlo Campiciano as Chief Financial Officer.

Campiciano brings significant experience

to the Company across a broad range of financial disciplines in the healthcare sector, including taxation, finance, operations,

planning and financial strategy.

Campiciano will assist with the transformational stage into a clinical development company,

along with the goal of up-listing to a U.S.

national stock exchange.

November 2019, we announced that the POP1 research and drug discovery program has made significant advancements towards

producing synthetic versions of the two proenzymes, trypsinogen and chymotrypsinogen.

With the aim of producing large quantities

of trypsinogen and chymotrypsinogen for commercial use, exhibiting minimal variation between lots and without sourcing the

proenzymes from animals, the Company is undertaking a challenging research project in collaboration with the universities

of Jaén and Granada.

So far, the Company’s scientific researchers have developed a novel expression system.

the research laboratories at the universities of Jaén and Granada, scientific researchers are in the process of optimizing

conditions to achieve high titers of recombinant trypsinogen and chymotrypsinogen with this expression system.

January 2020, we announced that a Certificate for Advance Overseas Finding was received from the Board of Innovation and Science

Australia to receive up to a 43.5% “cash back”

benefit from overseas R&D expenses.

The finding relates to

the planned Phase 1 clinical trial –

Multiple Ascending Dose Studies of proteolytic proenzymes for the treatment of

pancreatic cancer, for 2018/19 and the two following financial years.

Overseas activities to be undertaken include the development

of an analytical assay for the quantification of active pharmaceutical ingredients in the Company’s lead product candidate,

PRP, and its manufacture of the finished product for the Phase 1 clinical trial.

The finding from the Board agreed there is

a significant link between the two supporting activities and the planned Phase 1 clinical trial, and the two activities cannot

be conducted solely in Australia.

The Phase 1 clinical trial is planned to be conducted at the Peter Mac Center, one of the

world’s leading cancer research, education and treatment centers, globally and is Australia’s only public hospital

solely dedicated to caring for people affected by cancer.

after deepening our scientific knowledge of the anti-cancer effects of proenzymes through

our ongoing efforts with our research partners and strengthening our intellectual property

portfolio by filing our patents in countries around the world, we believe we are ready

to undertake human clinical trials and subject to receiving adequate financing, we hope

to submit a clinical trial application in the second quarter of 2021 calendar

the early phases of tumor progression, cancer cells multiply near the site where their predecessors first began uncontrolled proliferation.

The result, usually over a long period of time, is a primary tumor mass.

Tumors often need to reach a large size before they make

themselves apparent to the individual concerned, or the clinician screening for them.

tumors of substantial size may begin to compromise the functioning of organs in which they have arisen and begin to evoke symptoms.

In many cases, the effects on normal tissue function come from the physical pressure exerted by the expanding tumor masses.

example, large tumors in the colon may obstruct digestion products through the lumen, or in the lungs, airways may be compromised.

dangerous and threatening as these primary tumors are, they are ultimately responsible for only about 10% of deaths.

A far greater

threat often arises for the patient, even after a primary tumor has been identified and removed.

This threat involves cancerous

growths that are discovered at sites far removed from the locations in their bodies where their primary tumors first appeared.

These cancerous growths, called metastases, are responsible for approximately 90% of patient deaths from cancer.

Metastases are

formed by cancer cells that have left the primary tumor mass and traveled by the body’s blood and lymphatic vessels (a vein-like

vessel carrying lymph, or white blood cells, from the tissues) to seek new sites and form new colonies.

For example, breast cancers

often spawn metastatic colonies in many tissues throughout the body including the brain, liver, bones, and lungs.

primary tumors that have not yet metastasized, current treatments for cancer can be effective in initially reducing tumor burden.

However, for many forms of cancer, current treatments lack sufficient efficacy to achieve a long lasting clinical response.

a vast majority of patients who succumb to cancer are killed by tumors that have metastasized.

According to the National Cancer

Institute’s SEER Cancer Statistics Review (2001 –

2007), of the patients diagnosed with late stage metastatic breast

cancer, only 23% are expected to live longer than five years.

This is compared to a 98% five-year survival rate for an early stage

breast cancer patient when the cancer is confined to the primary site.

invasion-metastasis cascade

great majority of life-threatening cancers occur in epithelial tissues, yielding carcinomas.

Epithelial cells generally have a

multi-sided, uniform shape.

They have well defined contact points with neighboring cells and a strong attachment to the underlying

connective tissue, or stroma, which creates a framework for solid tumors in the body.

Separating the two is the specialized type

of extracellular matrix, known as the basement membrane.

definition, carcinomas that originate on the epithelial side of the basement membrane are considered to be benign ;

as the cells forming them remain on the same side.

However, many carcinomas acquire the ability to penetrate the basement membrane,

and individual cancer cells or groups of cancer cells begin to invade the stroma.

This mass of cells is now reclassified as malignant .

Often, many pathologists and surgeons reserve the label “cancer”

for those epithelial tumors that have acquired this

invasive ability.

carcinoma cells may invade into lymphatic or blood micro vessels.

The latter may then transport these cancer cells to distant

sites in the body where they may be trapped and subsequently form new metastases.

is important to note, that even before cells penetrate the basement membrane, they often stimulate angiogenesis (blood

vessel formation) on the stromal side of the membrane, by expressing angiogenic proteins through the porous barrier.

does this enhance the ability of malignant cells to circulate into the blood, but also provides an important feedback loop for

the cancer cell to maintain its invasiveness.

Understanding

the mechanism by which benign cells change to a malignant state is therefore pivotal to developing anti-cancer treatments that

have sufficient efficacy to achieve a long lasting clinical response.

epithelial-mesenchymal transition and associated loss of E-cadherin expression enable carcinoma cells to become invasive.

cells can undergo a transformation to a different cell type, called mesenchymal cells, through a process called the epithelial-to-mesenchymal

transition (“EMT”).

Mesenchymal cells have an elongated spindle shape, lack orderly contacts with neighboring cells

and can survive without contact with a surface or connective tissue.

The EMT process is a series of events that normally occur

during the development of tissues and organs prior to birth, and also apply to normal wound healing processes.

However, the same

EMT process can also be applied to epithelial cancer cells, or carcinomas.

When epithelial carcinoma cells residing in a solid

tumor undergo the EMT process, the resulting mesenchymal cancer cells can invade through local barriers and metastasize to other

parts of the body.

addition to becoming invasive and motile after undergoing the EMT process, the resulting mesenchymal cells have significantly

increased resistance to current cancer treatments.

For example, in Cancer Research in 2005, it was reported that lung cancer

cells expressing mesenchymal biomarkers appeared to be resistant to Tarceva and other targeted anti-cancer agents when transplanted

the center of this critical process for transforming benign cells into carcinomas, is the protein Epithelial Cadherin (“E-Cadherin”).

In normal cells, E-cadherin is located in the membrane and involved in maintaining cell to cell contact, which is critical to

normal function and structure of epithelial tissues.

The individual E-Cadherin molecules are attached to the actin (scaffolding,

or cytoskeleton structure) within the cell, anchored by β-catenin, a protein which helps form the junction between epithelial

As well as forming an anchor between epithelial cells, β-catenin is also involved in gene transcription, a process

by which DNA (deoxyribose nucleic acid) is converted into RNA (ribose nucleic acid) within the nucleus of a cell for the purpose

of producing new proteins normally associated with routine cell function.

the case of tumors, when cells become invasive, E-Cadherin expression decreases substantially, and β-catenin becomes free

within the cell, which may then migrate to the nucleus and induce expression of the EMT program.

Furthermore, once cells undergo

an EMT, they begin to produce their own cytokines (cell signaling molecules), such as Transforming Growth Factor β, (“TGF-β”).

This protein plays a critical multi-functional role in promoting angiogenesis, immunosuppression (suppressing the immune system

from recognizing and attacking cancer cells), and maintaining their mesenchymal cell structure for prolonged periods via a feedback

Studies also suggest that TGF-β

works with β-catenin to cause epithelial cancer cells to undergo an EMT.

study in the British Journal of Cancer in 2011 demonstrated that in cholangiocarcinoma (bile duct cancer) cell lines, treatment

of TGF-β

increased cell migration, invasion and mesenchymal changes.

Furthermore, expression of E-cadherin and N-cadherin

was measured from resected (cut out) specimens from extra-hepatic (outside the liver) cholangiocarcinoma patients.

Patients with

low E-cadherin expression had a significantly lower survival rate than patients with high E-cadherin expression.

They concluded

the cadherin switch via TGF-β

induced EMT in extra-hepatic cholangiocarcinoma leads to cancer progression.

in studies of several types of carcinoma cells that had lost E-cadherin expression, re-expression of this protein strongly suppressed

the invasiveness and motility of these cancer cells.

these observations indicate that E-Cadherin levels is a key determinant of the biological behavior of epithelial cancer cells

and that the cell to cell contact constructed by E-cadherin molecules impede invasiveness and hence metastasis.

solution is to develop and commercialize a long-term therapy to prevent tumor recurrence and metastases, the main cause of patient

death from cancer.

We believe this problem can be addressed by developing a proenzyme formulation specifically targeting malignant

carcinoma cells to create a long-lasting clinical benefit to the patient.

Propanc’s

Theory Proenzymes Regulate Cell Proliferation

than 100 years ago, Professor John Beard, a comparative embryologist, made an observation that the pancreas develops in most vertebrates

at the time when the placenta begins to slow its rate of growth.

He hypothesized that enzymes produced by the developing pancreatic

gland curtail trophoblastic invasion (a rare condition in which abnormal cells grow inside the uterus from tissue that forms after

conception) and suggested that pancreatic extracts should have a similar inhibitory effect on invasive tumors.

in the late 1990s, after following Professor Beard’s recommendations, Drs.

Novak and Trnka hypothesized that administration

of proenzymes, rather than the enzymes, was of crucial importance to the clinical effectiveness of the treatment approach first

developed by Professor Beard, and that the precursor nature of the active enzymes may offer protection against numerous serpins

(proteins which can inhibit proenzymes) in the blood.

knowledge of tumor cell and molecular cell biology has increased over the years, our scientists and research partners have made

important scientific discoveries identifying that proenzymes suppress the EMT program and induce cell differentiation, i.e., return

cancerous cells towards normal cell behavior, or a benign state.

more than 100 years, the initial observations made by Professor Beard may have a potential common link between embryogenesis and

cancer, by which cells are able to become motile and invasive, via the EMT program, where the administration of proenzymes may

regulate cell proliferation as a means to controlling carcinomas.

lead product, PRP, is a novel, patented formulation consisting of two proenzymes, trypsinogen and chymotrypsinogen, combined at

a ratio of one-to-six (1:6), to be administered intravenously.

After establishing proof of concept in vivo as described

earlier, supplemented by laboratory research at the Universities of Jaén and Granada on the mechanism of action of the

proenzyme mixture, evidence suggests PRP may be effective against a range of solid tumors.

published by Novak and Trnka in Anticancer Research (2005) suggests that the proenzymes in our product, trypsinogen and chymotrypsinogen,

exhibit specificity for tumor cells and not normal cells.

Once activated, they in turn activate Protease Activated Receptors Type

2 (“PAR2”), which are located on the cell membrane and involved with cancer cell proliferation.

Activation of PAR2

results in a cascade of intracellular activities, including activation of a major component of the cell which controls its structure

and architecture, the actin cytoskeleton.

In a cancer cell, proenzymes have the effect of converting globular actin into filamentous

actin, which causes the cell structure to collapse and induce cell death.

This reduces tumor volume and is often seen in clinical

Effects and Mechanism of Action

consists of proenzymes which are known to influence a number of pathways critical for cancer cells to invade, grow and metastasize.

Research published in collaboration with our research partners at Jaén and Granada Universities in the Journal of Cellular

Oncology in 2013 shows the clinical benefits of PRP appear to result from enhanced differentiation of tumor cells, which inhibits

proliferation and consequently reduces their ability to invade and metastasize.

Specifically,

the research showed that proenzymes:

a dose-dependent inhibition of cell growth, triggering apoptosis and cell necrosis;

expression of epithelial markers, such as E-cadherin and β-catenin;

expression of EMT transcription factors responsible for coding specific gene sequences from DNA, associated with TGF-β

cell signaling pathways;

malignant cells to differentiate to benign forms.

activated, proenzymes influence the micro-immune environment around the cell, altering a number of pathways critical for supporting

cancer cell growth, invasion and metastasis.

This includes interacting with proteinases and cell signaling pathways in the extracellular

matrix, whilst also interacting directly with cell surface proteins that effect the internal pathways of the cancer cell, triggering

re-expression of epithelial markers, reducing important EMT markers, and inducing a series of cellular activities which alters

the cancer cell’s morphology (structure) from a malignant to a benign state.

Up to four pathways related to cancer spread

and metastasis, including TGFΒ, Hippo, Wnt and Notch pathways were regulated by proenzymes.

Clinical Development

recently completed preclinical development.

A First-In-Human (FIH), Phase Ib study in patients with advanced solid tumors, evaluating

the safety, pharmacokinetics and anti-tumor efficacy of PRP is planned to commence in the second half of 2021 calendar year in

a jurisdiction to be selected by us, subject to us receiving adequate financing, and is hoped to be completed within twelve months.

The study will be an open-label, multicenter, non-comparative study of PRP administered at increasing dose levels, with once daily

intravenous injections over a 28-day cycle, with at least 20 and up to 40 patients enrolled.

Phase Ib study is planned to be followed by two open Phase IIa studies evaluating the safety, pharmacokinetics and anti-tumor

efficacy of PRP administered intravenously to patients with locally advanced or metastatic pancreatic adenocarcinoma, or to patients

with advanced epithelial ovarian cancer who have failed prior anti-cancer therapy regimen.

These studies are envisioned to start

in parallel, shortly after the FIH Phase IIa study, and are hoped to be finalized in 2022.

Both studies will be open, multicenter

phase II studies measuring overall survival of patients having received once daily intravenous administrations of PRP.

have extensive in vitro and in vivo studies demonstrating the anti-tumor efficacy of a novel proenzyme formulation consisting

of a combination of trypsinogen and chymotrypsinogen in a synergistic ratio.

The preclinical work was undertaken in collaboration

with our contract research organization, vivoPharm, in both Melbourne, Australia and Hummelstown, PA, United States, together

with universities we partnered with, including the Biopathology and Regenerative Medicine Institute, Center for Biomedical Research,

at the University of Granada in Granada, Spain, and the Department of Health Sciences at the University of Jaén in Jaén,

We funded both vivoPharm and the universities to carry out this research and retained the intellectual property rights

within the field relating to any discoveries based on the mechanism of action and anti-tumor effects of the proenzymes.

following preclinical development activities have been undertaken to date:

tested the anti-proliferative effects of trypsinogen and chymotrypsinogen in 24 cancer cell lines and determined a synergistic

ratio of 1:6, which we used to formulate PRP;

evaluated the in vitro anti-angiogenic effects of PRP, by soft-agar formation assay, and in vivo using the AngioChamber ™

assay, which is based on the normal physiological process of wound healing, to promote fibrous capsule formation around

an implanted growth factor-releasing Teflon chamber;

analyze the anti-metastatic effects of proenzymes, we studied the effects of PRP in cell invasion, cell migration, and in

the modulation of EMT related genes in pancreatic and ovarian cancer cells;

also performed in vivo a pharmacokinetic study and assessed the anti-tumor efficacy of PRP in murine cancer models.

To accomplish this, we treated mice that were orthotopically inoculated with A2780 human ovarian cancer cells, or with Pan02

mouse pancreatic tumor cells, with PRP.

Determination

of Optimal Proenzyme Ratio

this study, we determined first the half-maximal inhibitory concentrations (IC 50 ) trypsinogen and chymotrypsinogen

to measure their effect as single test articles in an extended panel of 24 human cancer cell lines.

The IC 50 values

of trypsinogen ranged from 2.5 to 17.5 mg/ml and from 1.4 to 25.2 mg/ml for chymotrypsinogen.

The IC 50 values of trypsinogen

were the basis for the calculation of concentration ratios for the combination of trypsinogen and chymotrypsinogen at 1:1, 1:2,

1:4, 1:6, 1:8, and 1:10.

At these ratios, the growth inhibitory properties of the combination were evaluated in 24 cancer cell

Based on the coefficient of drug interaction (CDI) values, the combination of trypsinogen and chymotrypsinogen demonstrated

greater growth inhibition at ratios of 1:4, 1:6, and 1:8, compared to the 1:1 ratio in most cell lines tested.

Finally, a ratio

of trypsinogen to chymotrypsinogen of 1:6 was determined to be the optimal formulation and used for later experiments.

Determination

of the Coefficient of Drug Interaction

representative graphs show an optimal pro-enzyme synergistic ratio of the Trypsinogen to Chymotrypsinogen as 1:6

Anti-angiogenic

efficacy of pancreatic proenzyme formulation

determine whether PRP affects angiogenesis, we used a soft-agar tube formation assay.

Dispersed human umbilical vein endothelial

cells (HUVEC) organized into clusters after three hours and began to form tube-like structures after five hours that were clearly

evident after 24 hours.

In contrast, PRP treated HUVECs presented a marked reduction in the number and length of closed capillary

tubes in a concentration dependent manner, with a total disappearance of the structures after treatment with trypsinogen to chymotrypsinogen

(T/C) 0.07/0.42 mg/ml.

assess if the inhibition of the tubule-like structures formation could be due to cell death caused by PRP treatment, CellTracker

Green/CMFDA staining was used to identify viable cells.

Both control and PRP treated cells showed green staining, indicating that

the inhibition of cellular cords was independent from cell viability.

quantification of the number of capillary-like structures at different areas of the cell revealed a dramatic and significant difference

between the number of structures formed by non-treated cells when compared with PRP-treated cells (p <0.01 vs.

anti-angiogenic effect of PRP was additionally investigated in vivo using the AngioChamber™

assay, a model used to

assess the efficacy of anti-angiogenic treatments by measuring fibrous capsule formation in mice.

In this assay the inclusion

of basic fibroblast growth factor (bFGF) in the chamber supports the induction of blood vessels development and formation of a

fibrous capsule.

AngioChamber™

were excised from all post-mortem mice on the termination day, 24 hours following final treatment

results show that fibrous capsule formation was significantly greater in the vehicle control group with bFGF captured in the chamber

(Group 2, Induction Control) than in the vehicle control group without bFGF loaded into the chamber (Group 1, Baseline Control)

(p<0.05) indicating that bFGF adequately and significantly stimulated capsule formation.

Furthermore, treatment with PRP (Group

3) resulted in a significant reduction in angiogenesis compared to the induction control (Group 2), as indicated by the difference

in capsule weight (p < 0.05) with a 57% of fibrous capsule formation inhibition.

Thus, PRP inhibits fibrous capsule formation

showing significant in vivo anti-angiogenic effects.

Anti-invasion,

anti-migration and anti-EMT effect of PRP

analyze the in vitro anti-metastatic effect of the proenzyme treatment, we studied the effect of PRP in cell invasion,

cell migration and the modulation of EMT related genes in cancer cells.

First, to evaluate the effect of PRP on cell migration,

a key event in carcinogenesis, we performed a wound-healing assay on human pancreatic BxPC3 and human ovarian A2780 cells.

is defined as the directed movement of cells on a substrate such as plastic plates occurring on 2D surfaces.

show that non-treated cells migrated faster to close the gap of a scratch in the cell monolayer than PRP treated cells.

PRP significantly

reduced cell migration of pancreatic BxPC3 cells and compared with control cells even enhanced the width of the wound.

the A2780 ovarian tumor cell line does not grow forming a homogeneous monolayer like BxPC3, it can be observed that PRP treatment

significantly reduces the ability of the ovarian cells to migrate.

Data showed significant cell migration inhibition after 24

hours and 48 hours of treatment with PRP compared to control cells.

we tested the inhibitory effect of the proenzyme formulation on cell invasion of colon and pancreatic tumor cells.

defined as cell movement through an extracellular 3D matrix.

The principle of this assay is based on two medium containing chambers

separated by a porous membrane through which cells transmigrate.

Here, we tested different concentrations of PRP on MIA PaCa-2

pancreatic and HCT-15 colon human cancer cell lines.

PRP showed a marked and significantly dose-dependent inhibition of invasion

in both cell lines.

Total inhibition of cell migration was achieved from PRP concentrations of T/C 0.015/0.093 mg/ml and so on

with the other increasing concentrations tested.

to investigate whether the exposure of PRP has a potential regulation in the transcriptional machinery that drives EMT in cancer

cells, expression of EMT genes were studied in BxPC3 pancreatic and A2780 ovarian human cancer cells.

EMT markers in both BxPC3

and A2780 cells were affected by PRP treatment at T/C 0.07/0.42 mg/ml.

Results show that PRP treatment increased the expression

of E-Cadherin (0.4 fold) (p < 0.05), whilst reduced the expressions of N-cadherin, Slug and vimentin (0.9, 0.5 and 0.6 fold,

respectively) (p < 0.01) in BxPC3 cells.

addition, PRP significantly up-regulated the expression of E-Cadherin (0.9 fold) (p < 0.01) and significantly down-regulated

the expression of N-cadherin and Slug (0.4 and 0.6 fold, respectively) (p < 0.01) and induced a slight, but not significant,

decrease of vimentin expression in A2780 cells.

pharmacokinetic study

evaluate the pharmacokinetics and organ distribution of trypsinogen and chymotrypsinogen, non-tumor bearing female athymic Nude-Foxn1nu

mice were treated with IRDye®

800CW labeled trypsinogen (5 mg/kg) plus unlabeled trypsinogen (50 mg/kg), or IRDye®

CW labeled chymotrypsinogen (7 mg/kg) plus unlabeled Chymotrypsinogen (300 mg/kg).

Animals were euthanized at specified time-points

post-dose and plasma along with organ homogenates was prepared, then imaged via IVIS imaging system.

was measured in organ homogenates.

Mice treated with labeled T, presented a fluorescence peak in all organs between 15 minutes

and 2 hours post-dose.

While mice treated with labeled C showed the maximum fluorescent emission between 15 minutes and 6 hours

For both highest readings were observed in the kidneys and liver.

Maximum levels of both IRDye®800CW labeled trypsinogen

and chymotrypsinogen A in mouse plasma occurred at 15 minutes post dose (7.5 and 72.2 ìg/ml, respectively).

Levels of both

800CW labeled proenzymes decreased rapidly after this time.

efficacy of PRP in orthotropic mice models

effect of the proenzyme formulation PRP at different doses on tumor weight in orthotopically implanted pancreatic and ovary tumors

was assessed.

In the pancreatic tumor control group, there was significant (*P < 0.05) reduction in mean tumor weight in animals

treated for 26 days with trypsinogen/chymotrypsinogen at 83.3/500 mg/kg (30.2 mg;

Biopharma is a biopharmaceutical company developing a novel approach to prevent recurrence and metastasis from solid tumors by using

pancreatic proenzymes that target and eradicate cancer stem cells in patients suffering from pancreatic, ovarian and colorectal cancers.

Our novel proenzyme therapy is based on the science that enzymes stimulate biological reactions in the body, especially enzymes secreted

by the pancreas.

These pancreatic enzymes could represent the body’s primary defense against cancer.

lead product candidate, PRP, is a variation upon our novel formulation and involves proenzymes, the inactive precursors of enzymes.

a result of positive early indications of the anti-cancer effects of our technology, we have conducted successful pre-clinical studies

on PRP and also commenced preparation for a clinical study in advanced cancer patients.

Subject to us receiving sufficient financing,

we plan to begin our Investigational Medicinal Product Dossier, study proposal and Investigator’s Brochure in the 2021 calendar

Our plan is to then commence our study preparation process with the contract research organization, analytical lab and trial site(s)

selection and to begin our clinical trial application for PRP (“CTA”) compilation in the first calendar quarter of 2022 and

complete the CTA compilation and submit the CTA in the first half of 2022.

In the second quarter of 2022, we plan to begin the preparation

of logistics and trial site initiation visits.

Subject to raising additional sufficient capital, we subsequently plan to commence a First-In-Human

(FIH), Phase Ib study in patients with advanced solid tumors, evaluating the safety, pharmacokinetics and anti-tumor efficacy of PRP

in the second half of 2022 calendar year, which study we hope to complete within twelve months thereafter.

We intend to develop our PRP

to treat early-stage cancer and pre-cancerous diseases and as a preventative measure for patients at risk of developing cancer based

on genetic screening.

is an intravenous injection proenzyme treatment designed as a therapeutic option in cancer treatment and prevention.

PRP is a combination

of the pancreatic proenzymes, trypsinogen and chymotrypsinogen.

PRP produces multiple effects on cancerous cells intended to inhibit

tumor growth and potentially stop a tumor from spreading through the body.

received notification from the U.S.

Food and Drug Administration (FDA) that PRP had been conferred Orphan Drug Designation for the treatment

of pancreatic cancer.

This special status is granted when a rare disease or condition is implicated and a potential treatment qualifies

under the Orphan Drug Act and applicable FDA regulations.

Certificate for Advance Overseas Finding was received from the Board of Innovation and Science Australia to receive up to a 43.5% “cash

back” benefit from overseas R&D expenses.

The finding relates to the planned Phase 1 clinical trial – Multiple Ascending

Dose Studies of proteolytic proenzymes for the treatment of advanced cancer patients suffering from solid tumors planned to be conducted

at the Peter MacCallum Center, Melbourne, Australia.

Overseas activities to be undertaken include the development of an analytical assay

for the quantification of active pharmaceutical ingredients in the Company’s lead product candidate, PRP, and its manufacture of

the finished product for the Phase 1 clinical trial.

POP1 joint research and drug discovery program is designed to produce a backup clinical compound to the lead product candidate, PRP.

With the aim of producing large quantities of trypsinogen and chymotrypsinogen for commercial use, exhibiting minimal variation between

lots and without sourcing the proenzymes from animals, Propanc Biopharma is undertaking a challenging research project in collaboration

with the Universities of Jaén and Granada.

We entered into a second two-year joint research and collaboration agreement with the

University of Jaén who are undertaking the research activities for the POP1 program.

occurs when cells in the body start to divide quickly and uncontrollably with an ability to migrate from one location and spread to distant

A cell becomes cancerous when it becomes undifferentiated.

The cell forgets to do its job and invests all its energy to proliferating.

Unlike normal cells, cancer cells multiply, but do not differentiate.

cancer therapies take advantage of the uncontrolled proliferation of the cancer cells and kill these cells by targeting the cell division machinery.

These therapies are effective but affect healthy cells as well, particularly those with a high rate of cell

turnover, inducing undesirable side effects.

goal is to stop cancer not by targeting tumor cell death, but inducing cell differentiation.

This is known as differentiation therapy.

The key focus is to convince the malignant cells to stop proliferating and return to do their work as a specific cell type.

Differentiation

therapy does not target cell death, so healthy cells within the patient will not be compromised, unlike chemotherapeutic drugs or gamma

Differentiation

therapy induces the cancer cells into the pathway of terminal differentiation and eventual senescence (i.e., a non-proliferative state).

Differentiation therapy acts not only against cancer cells, but interestingly can turn cancer stem cells (undifferentiated cells) towards

completely differentiated (i.e., normal) cells.

are natural elements within our body that could help us fight against cancer.

Enzymes are natural proteins that stimulate and accelerate

biological reactions in the body.

Particularly enzymes secreted by the exocrine pancreas that are essential for the digestion of proteins

More than one hundred years ago, Professor John Beard first proposed that pancreatic enzymes represent the body’s primary

defense against cancer and would be useful as a cancer treatment.

Since then, several scientists have endorsed Beard´s hypothesis

with encouraging data from patient treatment.

are developing a long-term therapy based on a pancreatic proenzyme formulation to prevent tumor recurrence and metastasis, the main cause

of patient death from cancer.

PRP is a novel, patented, formulation consisting of two proenzymes mixed in a synergetic ratio.

extensive laboratory research and a limited amount of human data, we have evidence that PRP:

cancer cell growth via promotion of cell differentiation;

cell adhesion and may suppress metastasis progression;

no observable serious side effects and improves patient survival.

is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection.

A synergistic

ratio of 1:6 inhibits growth of most tumor cells.

Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung liver,

uterine and skin cancers.

occurs because a program inside the cell, called the Epithelial-Mesenchymal Transition (EMT) is activated, which causes epithelial cancer

cells to become invasive and stem cell-like, features which then allow these cancer cells to spread and metastasize.

PRP reverses the

conversion from an epithelial to a mesenchymal phenotype and, as such, may reduce the metastatic potential of the tumor cells.

promotes the acquisition of a less malignant phenotype, in addition to a decrease in proliferation due to lineage (i.e., direct descent)

specific cellular differentiation.

treatment affects the TGFβ pathway, a significant tumor promoter in late-stage cancer.

The likely molecular targets are proteinase-activated-receptors

(PARs) type 1 and 2, which are over frequently overexpressed in many types of cancers.

Trypsinogen and chymotrypsinogen are activated

by proteases in the extracellular matrix of tumor cells.

In turn, trypsin (activated trypsinogen) has a preference to activate PAR-2,

whilst Chymotrypsin (activated chymotrypsinogen) mainly activates PAR-1.

Against Cancer Stem Cells

Stem Cells are resistant to standard treatments because they remain dormant for long periods, then migrate to other organs, and trigger

explosive tumor growth, causing the patient to relapse.

Approximately eighty percent of cancers are from solid tumors and metastasis

is the main cause of patient death.

Our unique patented approach is designed to target and eradicate cancer stem cells not killed by

radiation or chemotherapy.

is designed to target and eradicate cancer stem cells not killed by radiation or chemotherapy.

Traditional cancer therapies act on tumor

replicating cells, but not cancer stem cells, so they can rebuild the tumor mass and can migrate to start a new tumor in another organ.

PRP stops cancer stem cells so that a tumor loses the ability to generate new cells and therefore the tumor disappears with no option

to form a metastatic tumor elsewhere.

treatment regulates up to four relevant pathways related to cancer spread and metastasis of cancer stem cells.

PRP acts on TGFβ,

Hippo, Wnt and Notch pathways.

It promotes the up-regulation of RAC1b which avoids the hyper-activation of the p38 pathway induced by

the TGFβ pathway, leading to the phosphorylation of YAP, which sequesters B-catenin in the cytoplasm, blocking the canonical Wnt

pathway and inhibiting the Notch pathway.

That cascade of reactions implies the disruption of the cancer stem cell phenotype and the

reversal of the malignant epithelial to mesenchymal transition process that leads to tumor invasion.

Impairs Niche Formation and Tumor Initiation

proenzyme treatment inhibits the expression of genes related to the cancer stem cell phenotype, changing these malignant cells toward

a more differentiated and less dangerous cellular condition.

PRP interferes with the signals that the primary tumor sends to other tissues

to prepare the pre-metastatic niche.

Vivo Efficacy of PRP In Pancreatic and Ovarian Tumors

effect of the pro-enzyme formulation PRP at different doses on tumor weight in orthotopically implanted pancreatic and ovary tumors was

In the pancreatic tumor model, there was significant (*P < 0.05) reduction in mean tumor weight in animals treated for

26 days with trypsinogen/chymotrypsinogen at 83.3/500 mg/kg (30.2 mg;

85.9% inhibition) compared with control (PBS;

214.8 mg), but not between trypsinogen/chymotrypsinogen at 27.5/165 mg/kg (196.5 mg;

8.5% inhibition) and the control (as shown

in the figure below).

ovary tumor-bearing mice (as shown in the figure below) showed a significant (p < 0.05) reduction in mean tumor weight in animals

treated for 21 days with two different doses of trypsinogen/chymotrypsinogen, 9.1/54 mg/kg and 27.5/165 mg/kg, compared with control

The mean weight of control group tumors was 2062.2 mg while the treated groups presented a mean tumor weight of 1074.2

mg and 957.3 respectively, ranging in a 50% tumor inhibition (52% - 46%).

pancreatic enzymes have been administered previously in a variety of circumstances and are in current clinical use in conditions

where the pancreas is unable to produce sufficient enzymes for the digestion of food.

A number of oral pancreatic enzyme products

are presently approved in the U.S.

for use in patients who do not produce enough pancreatic enzymes.

Approved pancreatic enzyme

products include Pancreaze™

from Johnson & Johnson, CREON®

from Abbott Laboratories, and ULTRASE®

is a combination of two proenzymes, trypsinogen and chymotrypsinogen, specifically formulated within a specific ratio (1:6, as

described above) designed to synergistically enhance their anti-cancer effects based on the mechanism of action.

Patent protection

for PRP has been secured in multiple jurisdictions, including the United States, and continues to be sought for similar compositions

and mechanisms of action.

enzymes have also been investigated previously for the treatment of cancer and, while generating encouraging results, their widespread

use has been hampered by the very large quantities that have been considered necessary for effective treatment –

more tablets per day.

The high dose used with oral delivery is considered necessary due to the oral enzymes being broken down

in the stomach and duodenum, the first part of the small intestine and very little actually being absorbed into the general circulation.

By administering a proenzyme parenterally, and using a specific proenzyme formulation, the normal breakdown of the enzymes when

taken orally is avoided and the drug can potentially be absorbed into the general circulation intact.

It is also suggested that

proenzymes are resistant to inactivation by numerous protein digesting enzymes, like serpins, which are circulating in the blood.

Together with our scientific consultants, we believe that the development of a parenteral proenzyme formulation will lead to improved

efficacy in the treatment of cancer compared with oral enzyme preparations, and will substantially reduce the dose in comparison

to that used previously for oral enzyme therapy for the treatment of cancer.

ovary tumor-bearing mice showed a significant (*P < 0.05) reduction in mean tumor weight in animals treated for 21 days with two different

doses of trypsinogen/chymotrypsinogen, 9.1/54 mg/kg and 27.5/165 mg/kg, compared with control (PBS).

The mean weight of control group

tumors was 2062.2 mg while the treated groups presented a mean tumor weight of 1074.2 mg and 957.3 respectively, ranging in a 50% tumor

inhibition (52–46%).

Of Clinical Studies

clinical efficacy of a suppository formulation containing bovine pancreatic pro-enzymes trypsinogen and chymotrypsinogen was evaluated

in the context of a UK Pharmaceuticals Special Scheme and the results were published in a peer reviewed journal, Scientific Reports .

Clinical effects were studied in 46 patients with advanced metastatic cancers of different origin (prostate, breast, ovarian, pancreatic,

colorectal, stomach, non-small cell lung, bowel cancer and melanoma) after treatment with a rectal formulation of both pancreatic pro-enzymes.

severe or serious adverse events related to the rectal administration were observed.

Patients did not experience any hematological side

effects as typically seen with classical chemotherapy regimens.

No allergic reactions after rectal administration of suppositories were

order to assess the therapeutic activity of rectal administration, overall survival of patients under treatment was compared to the life

expectancy assigned to a patient prior to treatment start.

Nineteen from 46 patients (41.3%) with advanced malignant diseases, most of

them suffering from metastases, had a survival time significantly longer than their expected, in fact, for the whole set of cancer types,

mean survival (9.0 months) was significantly higher than mean life expectation (5.6 months).

Although the number of patients per cancer

indication is naturally quite low, 3 out of 8 patients with prostate cancer and 5 out of 11 patients with gastrointestinal cancers appear

to particularly benefit from the treatment with the proenzyme suppositories.

proves to be an in vivo effective and non-toxic anti-tumor treatment, able to inhibit angiogenesis and tumor growth, cancer cell migration

and invasiveness.

Furthermore, a suppository formulation containing both pancreatic proenzymes increased the life expectancy of advanced

cancer patients.

Consequently, PRP could have relevant oncological clinical applications for the treatment of solid tumors like advanced

pancreatic adenocarcinoma and advanced epithelial ovarian cancer.

carcinoma (n = 4)

Cancer (n = 7)

Cancer (n = 6)

Rectal Cancer (n = 5)

Cancer (n = 2)

Cancer (n = 8)

Lymphoma (n = 1)

Neuro-endocrine

Tumor (n = 1)

Cell Carcinoma (n = 1)

Cancer (n = 1)

unknown primary (n = 1)

of clinical studies.

Patients who met prognosis of life expectation (*).

For the whole set of cancer types, mean survival (9.0 months)

was statistically significantly higher than mean life expectation (5.6 months).

One way ANOVA (α = 0.05, P < 0.05).

JOINT RESEARCH AND DRUG DISCOVERY PROGRAM

date, both proenzymes were synthesized and purified in the laboratory.

Once purified, the proenzymes were lyophilized (freeze dried)

and each formed a stable, dry white powder.

The sequence of proteins of each proenzyme were then determined by mass spectrometry.

quantities of the proenzymes were produced with the objective of establishing their combined anti-cancer effects against pancreatic and

colorectal cancers.

In addition, research activities were transferred to the MEDINA Foundation Research Center to investigate the potential

to scale up production of the recombinant proenzymes from the expression of the novel expression system, which is currently ongoing.

MEDINA is a Non-Profit Research Organization established in 2008 through a public-private alliance between the Regional Government of

Andalusia, Spain, the pharmaceutical company Merck Sharp & Dohme de España S.A.

(MSD), and the University of Granada.

scientific platforms support the development of multidisciplinary research programs in Microbiology, Natural Product Chemistry and Screening

& Target Validation.

are elucidating the molecular pathways involved in the proenzymes anti-tumor efficacy and study how proenzymes interact with the pre-metastatic

tumor niche, focusing on the interaction and suppression of tumor associated cells, like cancer-associated fibroblasts and macrophages.

A pre-metastatic tumor niche is an environment in a secondary organ conducive to the metastasis of a primary tumor.

Such a niche provides

favorable conditions for growth, and eventually metastasis, in an otherwise foreign and hostile environment for the primary tumor cells.

Metastasis remains the main cause of patient death from solid tumors for cancer sufferers.

achieve this, we are using integrated tumor models in a microfluidics chip by obtaining 3-dimensional bio-impression samples from patients

with advanced solid tumors, developed at the Centre for Biomedical Research, University of Granada, Granada, Spain.

As well as explaining

the mechanism of action by which proenzymes exert their anti-cancer effects, it also confirms whether proenzymes penetrate into the tumor

microenvironment and exert their effects.

At the same time, it confirms the selectivity of the drug on solid tumors, by targeting cancer

cells and leaving healthy cells alone.

date, our investigation has confirmed that proenzyme therapy is effective against cancer stem cells, which are the cells responsible

for the formation of secondary tumors through metastasis.

They were also observed to be effective against cancer cells within the primary

tumor, whilst also leaving non-tumor cells alone.

The final part of the investigation is to determine the effects of the proenzymes against

both these cancerous cell types within the tumor microenvironment.

Joint Research Team successfully published data confirming the anti-tumor potential of a mixture of trypsinogen and chymotrypsinogen.

Treatment with proenzymes sensitizes cancer stem cells, which may allow standard treatment approaches like chemotherapy and radiotherapy

to be more effective.

vision is to produce a backup product candidate to PRP which can further stabilize and enhance the effects of the proenzymes when administered

Our scientific researchers are in the process of optimizing conditions to achieve high titers of recombinant trypsinogen

and chymotrypsinogen with this expression system.

TARGET INDICATIONS

management of cancer differs widely, with a multitude of factors impacting the choice of treatment strategy.

Some of those factors

Some of those factors include:

type of tumor, usually defined by the tissue in the body from which it originated;

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the primary tumor is amenable to surgery, either as a potentially curative procedure, or as a palliative one;

balance between potential risks and potential benefits from the various treatments and, probably most importantly, the patient’s

many patients with solid cancers, such as breast, ovarian, colorectal, lung and pancreatic cancer, surgery is frequently the first

treatment option, often followed by first line chemotherapy with or without radiotherapy.

While hopefully such procedures are

curative, in many instances the tumor returns, and second line treatment strategies are chosen in an effort to achieve a degree

of control over the tumor.

In most instances, the benefit is temporary, and eventually the point is reached where the patient’s

tumor either fails to adequately respond to treatment, or the treatment has unacceptable toxicity which severely limits its usefulness.

the planned Phase I, II and III clinical trials confirm the efficacy of PRP, along with the favorable safety and tolerability

profile suggested by pre-clinical studies conducted to date, we believe our product will have utility in a number of clinical

situations including:

the early stage management of solid tumors, most likely as part of a multi-pronged treatment strategy in combination with

existing therapeutic interventions;

balance between potential risks and potential benefits from the various treatments and, probably most importantly, the patient’s

many patients with solid cancers, such as breast, ovarian, colorectal, lung and pancreatic cancer, surgery is frequently the first treatment

option, often followed by first line chemotherapy with or without radiotherapy.

While hopefully such procedures are curative, in many

instances the tumor returns, and second line treatment strategies are chosen in an effort to achieve a degree of control over the tumor.

In most instances, the benefit is temporary, and eventually the point is reached where the patient’s tumor either fails to adequately

respond to treatment, or the treatment has unacceptable toxicity which severely limits its usefulness.

the planned Phase I, II and III clinical trials confirm the efficacy of PRP, along with the favorable safety and tolerability profile

suggested by pre-clinical studies conducted to date, we believe our product will have utility in a number of clinical situations including:

the early-stage management of solid tumors, most likely as part of a multi-pronged treatment strategy in combination with existing

therapeutic interventions;

a product that can be administered long term for patients following standard treatment approaches, such as surgery, or chemotherapy,

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a preventative measure for patients at risk of developing cancer based on genetic screening.

the near term as part of our planned Phase I, II and III clinical trials, we plan to target patients with solid tumors, most likely

ovarian and pancreatic, for whom other treatment options have been exhausted.

This is a common approach by which most new drugs

for cancer are initially tested.

Once efficacy and safety has been demonstrated in this patient population, exploration of the

potential utility of the drug in earlier stage disease can be undertaken, together with investigation of the drug’s utility

in other types of cancers, such as gastro-esophageal tumors, colon or rectal carcinoma might be conducted.

A Phase II study in

a back-up indication, such as advanced therapy refractant prostate cancer will also be considered.

This indication is based on

positive preclinical pharmacology studies.

goal is to undertake early stage clinical development of PRP through to a significant value inflection point, where the commercial

attractiveness of a drug in development, together with a greater likelihood of achieving market authorization, may attract potential

interest from licensees seeking to acquire new products.

Such value inflection points in the context of cancer drugs are typically

at the point where formal, controlled clinical trials have demonstrated either ‘efficacy’

or ‘proof of concept’

typically meaning that there is controlled clinical trial evidence that the drug is effective in the proposed target patient

population, has an acceptable safety profile, and is suitable for further development.

From a ‘big picture’

it is our intention to progress the development of our technology through the completion of our planned Phase IIa clinical trials

and then to seek a licensee for further development beyond that point.

the near term as part of our planned Phase I, II and III clinical trials, we plan to target patients with solid tumors, most likely ovarian

and pancreatic, for whom other treatment options have been exhausted.

This is a common approach by which most new drugs for cancer are

initially tested.

Once efficacy and safety has been demonstrated in this patient population, exploration of the potential utility of

the drug in earlier stage disease can be undertaken, together with investigation of the drug’s utility in other types of cancers,

such as gastro-esophageal tumors, colon or rectal carcinoma might be conducted.

A Phase II study in a back-up indication, such as advanced

therapy refractant prostate cancer will also be considered.

This indication is based on positive preclinical pharmacology studies.

cancer is one of the most lethal malignancies with a median survival of less than 6 months and a 5-year survival rate of less than 5%.

The lethal nature of this disease stems from its propensity to rapidly disseminate to the lymphatic system and distant organs.

This aggressive

biology and resistance to conventional and targeted therapeutic agents leads to a typical clinical presentation of incurable disease

at the time of diagnosis.

cancer has claimed notoriety over the last decades by proving to be one of the most recalcitrant solid tumors.

As an indicator of its

lethality, pancreatic cancer accounts for less than 3% of new cancers diagnosed annually in developed countries, yet it is the third

leading cause of cancer related mortality.

pancreatic cancer is an essentially fatal condition, disease duration is roughly equivalent with survival time.

The median time of survival

of patients with pancreatic cancer depends on the extend of disease at the time of diagnosis and ranges from 11-20 months for patients

who qualified for surgical resection (Stage I/II), to 6-11 months for patients with locally advanced disease (Stage III), and only 2-6

months for patients with metastatic disease (Stage IV) (Amikura 1995, Richter 2003).

Taking these low survival times into consideration,

the yearly incidence rates for pancreatic cancer are considered the more relevant measure for this disease.

year the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current

year and compiles the most recent data on cancer incidence, mortality, and survival.

Incidence data are collected by the National Cancer

Institute (NCI), the Centers for Disease Control and Prevention (CDC), and the North American Association of Central Cancer Registries

In 2015, a total of more than 1,500,000 new cancer cases and more than 500,000 cancer deaths will occur in the United States.

Amongst these, a total of almost 50.000 new cases of pancreatic cancer (3.33% of new cancer cases) have been estimated, which will result

in more than 40,000 deaths (8% of cancer deaths).

This means only 20% survival rate of patients diagnosed with pancreatic cancer.

cancer is a generic term that can be used for any cancer involving the ovaries, arising from one of the several different cell types

of ovaries, including germ cells, specialized gonadal stromal cells and epithelial cells.

Epithelial ovarian cancer accounts for 90 percent

of ovarian cancers and is responsible for most ovarian cancer related deaths.

Furthermore, several subtypes of ovarian cancer have been

described according to different risk factors, different genetic mutations, different biological behaviors and different prognoses.

heterogeneity of the disease has impeded progress in the prevention, early detection, treatment and management of ovarian cancer.

cancer is the seventh most commonly diagnosed cancer among women in the world and accounts for an estimated 239,000 new cases and 152,000

deaths worldwide annually, of which 21,290 new cases and 14,180 related deaths are estimated to occur in the USA alone.

The disease typically

presents at late stage when the 5-year relative survival rate is only 29%.

Few cases (15%) are diagnosed with localized tumor (stage

1), when the 5-year survival rate is 92%.

Strikingly, the overall 5-year relative survival rate generally ranges between 30%–40%

across the globe and has seen only very modest increases since 1995.

DEVELOPMENT STRATEGY

goal is to undertake early-stage clinical development of PRP through to a significant value inflection point, where the commercial attractiveness

of a drug in development, together with a greater likelihood of achieving market authorization, may attract potential interest from licensees

seeking to acquire new products.

Such value inflection points in the context of cancer drugs are typically at the point where formal,

controlled clinical trials have demonstrated either ‘efficacy’ or ‘proof of concept’ – typically meaning

that there is controlled clinical trial evidence that the drug is effective in the proposed target patient population, has an acceptable

safety profile, and is suitable for further development.

From a ‘big picture’ perspective, it is our intention to progress

the development of our technology through the completion of our planned Phase IIa clinical trials and then to seek a licensee for further

development beyond that point.

part of that commercial strategy, we will:

research and development to build our existing intellectual property portfolio, and to seek new, patentable discoveries;

to ensure all product development is undertaken in a manner that makes its products approvable in the major pharmaceutical

markets, including the U.S., Europe, the UK, Australia and Japan;

to ensure all product development is undertaken in a manner that makes its products approvable in the major pharmaceutical markets,

including the U.S., Europe, the UK, Australia and Japan;

pursue the protection of our technology through all means possible, including patents in all major jurisdictions, and potentially

trade secrets;

strategic acquisitions to acquire new companies that have products or services that complement our future goals.

Plan and Milestones

strategic acquisitions to acquire new companies that have intellectual property or products that complement our future goals.

DEVELOPMENT PLAN AND MILESTONES

plan to progress PRP down a conventional early-stage clinical development pathway for:

and/or ethics approval to conduct a Phase Ib study, and submit it with the applicable government agency for approval;

and/or ethics approval to conduct a Phase Ib study;

IIa multiple escalating dose studies to investigate the safety, tolerability, and pharmacokinetics of PRP administered intravenously

are currently evaluating Australia, UK and Europe as the potential destination where we may commence the Phase Ib trial.

In particular,

we are closely evaluating Australia because of its research and development tax incentives, as well as a simplified regulatory

As part of such incentives, eligible companies conducting clinical trials in Australia receive up to 43.5% “cash-back”

benefit in the form of a refund of their qualified research and development costs and expenses.

The Company received a refund

of $199,834 AUD ($134,728 USD) and $161,383 AUD ($115,437 USD) in the years ended June 30, 2020 and 2019 respectively.

are continuing to evaluate all options to conduct our planned clinical trials in the most cost-efficient manner, while

striving to minimize dilution to our stockholders.

anticipate reaching the Phase IIa proof of concept milestone in approximately three to four years, subject to regulatory approval

in Europe, and the results from our research and development and licensing activities.

development has been completed, including pharmacology and safety toxicology studies, process development activities and bioanalytical

method development.

The full-scale GMP (Good Manufacturing Practice) finished product manufacture of PRP will be completed in preparation

for the FIH Phase Ib study.

Validation of the bioanalytical method will also be completed prior to lodging our first clinical trial application

(CTA) which we plan to undertake at the Peter Mac Cancer Center in Melbourne, Victoria, Australia’s biggest cancer hospital.

Biopharma is collaborating with contract research organizations, manufacturing partners and consultants to complete activities prior

to preparing the CTA for the Phase Ib study.

Company has received expressions of interest to evaluate proenzyme therapy as a method to prevent recurrence and metastasis of solid

tumors in pancreatic and ovarian cancers.

The letters of interest were confirmed by medical oncologists specializing in pancreatic and

ovarian cancers, from the University Hospital of Jaén, in Granada, Spain.

The evaluation will most likely be conducted as separate

Phase IIa proof of concept (POC), multi-trial center studies for each target indication.

The expressions of interest were confirmed after

their evaluation of Propanc’s scientific literature supporting the use of proenzymes in pancreatic and ovarian cancers.

IIa POC studies will be conducted after the Phase Ib dose escalation study investigating the tolerability and activity of proenzyme therapy

in patients with advanced solid tumors is completed at the Peter Mac Cancer Center.

Australia, we receive up to 43.5% “cash-back” benefit in the form of a refund of their qualified research and development

costs and expenses.

The Company received a refund of $151,767 AUD ($113,415 USD) and $199,834 AUD ($134,728 USD) for the

years ended June 30, 2021 and 2020 respectively.

We are continuing to evaluate all options to conduct our planned clinical

trials in the most cost-efficient manner, while striving to minimize dilution to our stockholders.

anticipate reaching the Phase IIa proof of concept milestone in approximately three to four years, subject to regulatory approval in

Europe, and the results from our research and development and licensing activities.

overhead and expenses are likely to increase from its current level as PRP progresses down the development pathway.

This increase

will be driven by the need to increase our internal resources in order to effectively manage our research and development activities.

is the timeline and a detailed discussion of our anticipated milestones and steps that we plan to take in preparation for our

planned Phase Ib clinical trial.

first quarter of 2021 calendar year, we anticipate the submission of the Clinical Trial Application for PRP in a jurisdiction

to be determined by us that would suit the best interests of the trial and our Company.

We anticipate receiving approval of such

application in the first half of 2021.

Following the clinical trial application, we plan to commence our Study Preparation, including

CRO Selection and Contracts, Analytical Lab Selection Contracts and Trial Sites Selection and Contracts.

In connection with the

Clinical Trial Application, this product will be part of our Investigation Medicinal Product Dossier, Study Protocol and Investigator’s

In the first half of 2021 calendar year, we hope to complete the Study Preparation with the Preparation of Logistics

This increase will

be driven by the need to increase our internal resources in order to effectively manage our research and development activities.

second quarter of 2022 calendar year, we anticipate the submission of the Clinical Trial Application for PRP.

We anticipate receiving

approval of such application in the first half of 2022.

Following the clinical trial application, we plan to commence our Study Preparation,

including CRO Selection and Contracts, Analytical Lab Selection Contracts and Trial Sites Selection and Contracts.

In connection with

the Clinical Trial Application, this product will be part of our Investigation Medicinal Product Dossier, Study Protocol and Investigator’s

In the second half of 2022 calendar year, we hope to complete the Study Preparation together with the Preparation of Logistics

and Trial Sites Initiation Visits and complete our clinical trial application review.

in the second half of 2021 calendar year, we intend to initiate a Phase Ib study in advanced cancer patients with solid tumors

and the anticipated costs will be approximately $6.5 million.

We will need to raise additional financing to fund our planned Phase

I, II and III clinical trials and for working capital.

factors, many of which are outside of our control, can impact our ability to achieve our target objectives within the planned

time and budgetary constraints.

Subject to these caveats, our objective is to complete our planned Phase IIa study for PRP within

the proposed budget.

Commencing in the second half of 2022 calendar

year, we intend to initiate a Phase Ib study in advanced cancer patients with solid tumors and the anticipated costs will be approximately

$6.5 million.

We will need to raise additional financing to fund our planned Phase I, II and III clinical trials and for working capital.

Trial Application (CTA)

‘21 - Apr ‘22

Investigational

Medicinal Product Dossier

Ib Clinical Study Protocol

Investigator’s

‘22 – Jul ‘22

Research Organization & Contracts

Laboratory Selection & Contracts

Site Selection & Contracts

Site Initiation Visits

Patient/First Visit

JOINT RESEARCH AND DRUG DISCOVERY PROGRAM

outlined previously, a joint research and drug discovery program has been established with our collaborators at the Universities of Jaén

and Granada to investigate the changes in genetic and protein expression that occur in cancer cells as a consequence of being exposed

to our proenzyme formulation.

The objective of this work is to understand at the molecular level the targets of our proenzyme formulation,

thereby providing the opportunity for new, patentable drugs which can be developed further.

We plan to commence a targeted drug discovery

program utilizing the identified molecular target to search for novel anticancer agents.

specific objective of the project is to synthesize both proenzymes by an in vivo system to produce crystalized proteins that could be

maintained for long periods without suffering degradation, even in absence of refrigeration.

This will be particularly useful for a longer

shelf life as well as global distribution of the drug product, particularly in warmer climates and developing regions where refrigeration

may not be available.

POP1 joint research and drug discovery program has produced synthetic recombinant versions of the two proenzymes, trypsinogen and chymotrypsinogen.

Propanc Biopharma’s joint scientific researchers are developing a novel expression system and are also in the process of optimizing

conditions to achieve high titers of recombinant trypsinogen and chymotrypsinogen.

Further, the anticancer effects of the synthetic versions

will be tested against the naturally derived proenzymes from bovine origin.

factors, many of which are outside of our control, can impact our ability to achieve our target objectives within the planned time and

budgetary constraints.

Subject to these caveats, our objective is to complete our planned Phase IIa study for PRP within the proposed

primarily outsource services, skills and expertise to third parties as required to achieve our scientific and corporate objectives.

As the business grows and gains more personnel, outsourcing will continue to be the preferred model, where fixed and variable

costs are carefully managed on a project-by-project basis.

This means our research and development activities are carried out

by third parties.

Additional third parties with specific expertise in research, compound screening and manufacturing (including

raw material suppliers) have been contracted as required.

the business grows and gains more personnel, outsourcing will continue to be the preferred model, where fixed and variable costs are

carefully managed on a project-by-project basis.

This means our research and development activities are carried out by third parties.

Additional third parties with specific expertise in research, compound screening and manufacturing (including raw material suppliers)

have been contracted as required.

initial focus is to organize, coordinate and finance the various parts of our drug development pipeline.

New personnel will be

carefully introduced into our Company over a period of time as our research and development activities expand.

They will have

specific expertise in product development, manufacture and formulation, regulatory affairs, toxicology, clinical operations and

business development (including intellectual property management, licensing and other corporate activities).

the first instance, additional clinical management and development expertise is likely to be required for our lead product.

we anticipate an increase in employees in order to effectively manage our contractors as the projects progress down the development

New personnel will be carefully

introduced into our Company over a period of time as our research and development activities expand.

They will have specific expertise

in product development, manufacture and formulation, regulatory affairs, toxicology, clinical operations and business development (including

intellectual property management, licensing and other corporate activities).

In the first instance, additional clinical management and

development expertise is likely to be required for our lead product.

Therefore, we anticipate an increase in employees in order to effectively

manage our contractors as the projects progress down the development pathway.

outsourcing strategy is common in the biotechnology sector, and is an efficient way to obtain access to the necessary skills required

to progress a project, in particular as the required skills change as the project progresses from discovery, through manufacturing

and non-clinical development and into clinical trials.

We anticipate that we will continue to use this model, thereby retaining

the flexibility to contract in the appropriate resource as and when required.

to progress a project, in particular as the required skills change as the project progresses from discovery, through manufacturing and

non-clinical development and into clinical trials.

We anticipate that we will continue to use this model, thereby retaining the flexibility

to contract in the appropriate resource as and when required.

intend to seek and identify potential licensing partners for our product candidates as they progress through the various development

stages, reaching certain milestones and value inflection points.

If a suitable licensee is identified, a potential licensing deal

could consist of payments for certain milestones, plus royalties from future sales if the product is able to receive approval

from the relevant regulatory authorities where future product sales are targeted.

We intend to seek and identify potential licensees

based on the initial efficacy data from Phase II clinical trials.

To accomplish this objective, we have commenced discussions

with potential partners in our current preclinical phase of development.

part of our overall expansion strategy, from time to time, we investigate potential intellectual property acquisition opportunities

to expand our product portfolio.

While our initial focus is on the development of PRP as the lead product candidate, potential

product candidates may also be considered for future preclinical and clinical development.

These potential opportunities have

arisen from other research and development organizations, which either own existing intellectual property or are currently developing

new intellectual property, which may be of interest to us.

These opportunities are possible new cancer treatments that are potentially

less toxic than existing treatment approaches and are able to fill an existing gap in the treatment process, such as a systemic

de-bulking method which could reduce the size and threat of metastases to a more manageable level for late stage cancer patients.

We believe these potential treatment approaches will be complementary to existing treatment regimens and our existing product

candidate, PRP.

No formal approaches have been made at this stage and it is unknown whether we will engage in this discussion

in the near future.

However, we remain hopeful that as PRP progresses further down the development pathway, future opportunities

may arise to use the expertise of our management and scientific personnel for future prospective research and development projects.

If a suitable licensee is identified, a potential licensing deal could

consist of payments for certain milestones, plus royalties from future sales if the product is able to receive approval from the relevant

regulatory authorities where future product sales are targeted.

We intend to seek and identify potential licensees based on the initial

efficacy data from Phase II clinical trials.

To accomplish this objective, we have commenced discussions with potential partners in our

current preclinical phase of development.

part of our overall expansion strategy, from time to time, we investigate potential intellectual property acquisition opportunities to

expand our product portfolio.

While our initial focus is on the development of PRP as the lead product candidate, potential product candidates

may also be considered for future preclinical and clinical development.

These potential opportunities have arisen from other research

and development organizations, which either own existing intellectual property or are currently developing new intellectual property,

which may be of interest to us.

These opportunities are possible new cancer treatments that are potentially less toxic than existing

treatment approaches and are able to fill an existing gap in the treatment process, such as a systemic de-bulking method which could

reduce the size and threat of metastases to a more manageable level for late-stage cancer patients.

believe these potential treatment approaches will be complementary to existing treatment regimens and our existing product candidate,

No formal approaches have been made at this stage and it is unknown whether we will engage in this discussion in the near future.

However, as PRP progresses further down the development pathway, we intend to assess future opportunities that may arise to use the expertise

of our management and scientific personnel for future prospective research and development projects.

are at a pre-revenue stage.

We do not know when, if ever, we will be able to commercialize our products and begin generating revenue.

We are focusing our efforts on organizing, coordinating and financing the various aspects of the drug research and development

program outlined earlier in this document.

In order to commercialize our products, we must complete preclinical development, Phase

Ib, IIa and IIb clinical trials in Europe, the U.S., United Kingdom, Australia or elsewhere, and satisfy the applicable regulatory

authority that PRP is safe and effective.

If the results from the Phase II trials are convincing, we will seek conditional approval

from the regulatory authorities sooner.

Therefore, from the time we commence clinical trials, we estimate that this will take

approximately three to four years if we seek conditional approval upon completion of Phase II trials, or up to seven years if

we determine that Phase III trials are needed.

As described previously, when we advance our development projects sufficiently

down the development pathway and achieve a major increase in value, such as obtaining interim efficacy data from Phase II clinical

trials, we will seek a suitable licensing partner to complete the remaining development activities, obtain regulatory approval

We are focusing our efforts on organizing, coordinating and financing the various aspects of the drug research and development program

outlined earlier in this document.

In order to commercialize our products, we must complete preclinical development, Phase Ib, IIa and

IIb clinical trials in Europe, the U.S., United Kingdom, Australia or elsewhere, and satisfy the applicable regulatory authority that

PRP is safe and effective.

If the results from the Phase II trials are convincing, we will seek conditional approval from the regulatory

authorities sooner.

Therefore, from the time we commence clinical trials, we estimate that this will take approximately three to four

years if we seek conditional approval upon completion of Phase II trials.

As described previously, when we advance our development projects

sufficiently down the development pathway and achieve a major increase in value, such as obtaining interim efficacy data from Phase II

clinical trials, we will seek a suitable licensing partner to complete the remaining development activities, obtain regulatory approval

and market the product.

are developing a therapeutic solution for the treatment of patients with advanced stages of cancer targeting solid tumors, which

is cancer that originates in organs or tissues other than bone marrow or the lymph system.

Common cancer types classified as solid

tumors include lung, colorectal, ovarian cancer, pancreatic cancer and liver cancers.

In each of these indications, there is a

large market opportunity to capitalize on the limitations of current therapies.

are developing a therapeutic solution for the treatment of patients with advanced stages of cancer targeting solid tumors, which is cancer

that originates in organs or tissues other than bone marrow or the lymph system.

Common cancer types classified as solid tumors include

lung, colorectal, ovarian cancer, pancreatic cancer and liver cancers.

In each of these indications, there is a large market opportunity

to capitalize on the limitations of current therapies.

therapeutic options for the treatment of cancer offer, at most, a few months of extra life or tumor stabilization.

believe that drugs that kill most tumor cells do not affect cancer stem cells, which can regenerate the tumor (e.g.

chemotherapy).

Studies are revealing the genetic changes in cells that cause cancer and spur its growth.

This research is providing scientific

researchers with many potential targets for drugs.

Some experts believe

that drugs that kill most tumor cells do not affect cancer stem cells, which can regenerate the tumor (e.g., chemotherapy).

revealing the genetic changes in cells that cause cancer and spur its growth.

This research is providing scientific researchers with

many potential targets for drugs.

Tumor cells, however, can develop resistance to drugs.

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cancer which are more effective than current therapies, and which have a substantially reduced side effect profile.

progress has been made within the oncology sector in developing new treatments, the overall cancer death rate has only improved

by 7% over the last 30 years.

Most of these new treatments have some limitations, such as:

progress has been made within the oncology sector in developing new treatments, the overall cancer death rate has only improved by 7%

over the last 30 years.

of these new treatments have some limitations, such as:

toxic effects;

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Chemotherapeutics:

Side effects from chemotherapy can include pain, diarrhea, constipation, mouth sores, hair loss, nausea and vomiting, as well

as blood-related side effects, which may include a low cell count of infection fighting white blood cells (neutropenia), low

red blood cell count (anemia), and low platelet count (thrombocytopenia).

Our goal is to demonstrate that our treatment will

be more effective than chemotherapeutic and hormonal therapies with fewer side effects.

The most common type is multi-targeted kinase inhibitors (molecules which inhibit a specific class of enzymes

called kinases).

Common side effects include fatigue, rash, hand–foot reaction, diarrhea, hypertension and dyspnoea

(shortness of breath).

Furthermore, tyrosine kinases inhibited by these drugs appear to develop resistance to inhibitors.

While the clinical findings with PRP are early and subject to confirmation in future clinical trials, no evidence has yet

been observed of the development of resistance by the cancer to PRP.

Side effects from chemotherapy can include pain, diarrhea, constipation, mouth sores, hair loss, nausea and vomiting, as well as

blood-related side effects, which may include a low cell count of infection fighting white blood cells (neutropenia), low red blood

cell count (anemia), and low platelet count (thrombocytopenia).

Our goal is to demonstrate that our treatment will be more effective

than chemotherapeutic and hormonal therapies with fewer side effects.

The most common type is multi-targeted kinase inhibitors (molecules which inhibit a specific class of enzymes called kinases).

Common side effects include fatigue, rash, hand–foot reaction, diarrhea, hypertension and dyspnoea (shortness of breath).

tyrosine kinases inhibited by these drugs appear to develop resistance to inhibitors.

While the clinical findings with PRP are early

and subject to confirmation in future clinical trials, no evidence has yet been observed of the development of resistance by the

cancer to PRP.

Development of monoclonal antibodies is often difficult due to safety concerns.

Side effects that are most

common include skin and gastro-intestinal toxicities.

For example, several serious side effects from Avastin, an anti-angiogenic

cancer drug, include gastrointestinal perforation and dehiscence (e.g.

rupture of the bowel), severe hypertension (often requiring

emergency treatment) and nephrotic syndrome (protein leakage into the urine).

Antibody therapy can be applied to various cancer

types, but can also be limited to certain genetic sub populations in many instances.

Side effects that are most common include

skin and gastro-intestinal toxicities.

For example, several serious side effects from Avastin, an anti-angiogenic cancer drug, include

gastrointestinal perforation and dehiscence (e.g., rupture of the bowel), severe hypertension (often requiring emergency treatment)

and nephrotic syndrome (protein leakage into the urine).

Antibody therapy can be applied to various cancer types, but can also be

limited to certain genetic sub populations in many instances.

Immunotherapy:

There is a long history of attempts to develop therapeutic cancer vaccines to stimulate the body’s own immune system

to attack cancer cells.

While these products generally do not have the poor safety profile of standard therapeutic approaches,

only a relatively small number of them are FDA-approved and available as compared to the number of patients diagnosed with

Furthermore, only a relatively small number of the patient population is eligible to receive and subsequently respond

to treatment, as defined by preventing tumor growth.

previously sponsored a collaborative research project at Bath University to investigate the cellular and molecular mechanisms

underlying the potential clinical approach of our proprietary proenzyme formulation.

As a result of this undertaking, we entered

into a Commercialization Agreement with University of Bath (UK), dated November 12, 2009 (the “Commercialization Agreement”),

where, initially, we held an exclusive license with Bath University, and where we and Bath University co-owned the intellectual

property relating to our proenzyme formulations.

The Commercialization Agreement originally provided for Bath University to assign

the Patents (as defined therein) to Propanc in certain specified circumstances, such as successful completion of a clinical trial

and commencement of a Phase II (Proof of Concept) clinical trial.

June 14, 2012, Propanc and Bath University agreed to an earlier assignment to us of the patents pursuant to an Assignment and

Amendment Deed, on the proviso that Bath University retains certain rights arising from the Commercialization Agreement, as follows:

University reserves for itself (and its employees and students and permitted academic sub-licensees with respect to research

use) the non-exclusive, irrevocable, worldwide, royalty free right to use the patents for research use;

publication rights of Bath University specified in the contract relating to the original research made between the parties

with an effective date of July 18, 2008 shall continue in force;

shall pay to Bath University a royalty of two percent of any and all net revenues;

shall use all reasonable endeavors to develop and commercially exploit the patents for the mutual benefit of Bath University

and Propanc to the maximum extent throughout the covered territory and in any additional territory and to obtain, maintain

and/or renew any licenses or authorizations that are necessary to enable such development and commercial exploitation.

prejudice to the generality of the foregoing, Propanc shall comply with all relevant regulatory requirements in respect of

its sponsoring and/or performing clinical trials in humans involving the administration of a product or materials within a

claim of the patents;

There is a long history of attempts to develop therapeutic cancer vaccines to stimulate the body’s own immune system to attack

cancer cells.

While these products generally do not have the poor safety profile of standard therapeutic approaches, only a small

number of them are FDA-approved and available compared to the number of patients diagnosed with cancer.

Furthermore, only a relatively

small number of the patient population is eligible to receive and subsequently respond to treatment, as defined by preventing tumor

global metastatic cancer treatment market is predicted to reach $111 Billion by 2027 by Emergen Research.

Demand for new cancer

products can largely be attributed to a combination of a rapidly aging population in western countries and changing environmental factors,

which together are resulting in rising cancer incidence rates.

Worldwide, the World Health Organization estimated 19.3 million

new cancer cases and almost 10.0 million cancer deaths occurred in 2020.

As such, global demand for new cancer treatments which are effective,

safe and easy to administer is rapidly increasing.

Our treatment will potentially target many aggressive tumor types for which little

or few treatment options exist.

plan to target patients with solid tumors, most likely pancreatic and ovarian tumors, for whom other treatment options have been exhausted.

Globally these cancers resulted in over 673,255 deaths in 2020, according to the World Health Organization.

With such a high mortality

rate, a substantial unmet medical need exists for new treatments.

Once the efficacy and safety of PRP has been demonstrated in late-stage

patient populations, we plan to undertake exploration of the utility of the drug in earlier stage disease, together with investigation

of the drug’s utility in other types of cancer.

Market Potential

is difficult to estimate the size of the market opportunity for this specific type of product as a clinically proven, pro-enzyme formulated

suppository marketed to oncologists across global territories for specific cancer indications, to the best of management’s knowledge,

has not been previously available.

However, the markets for potential market for pancreatic and ovarian cancers may be characterized

world market for pancreatic cancer drugs is projected to grow to $4.2 billion by the year 2025, according to Grandview Research.

Major players operating in the pancreatic cancer therapy market include Eli Lilly and Company, F.

Hoffmann-La Roche AG, Celgene

Corporation, Amgen Inc., Novartis AG, Pharmacyte Biotech Inc., Clovis Oncology, Teva Pharmaceutical Industries Ltd., Pfizer Inc.,

Merck & Co., Inc.

among others.

For instance, in May 2018, Eli Lilly and Company acquired AMRO BioSciences.

AMRO BioSciences

is engaged into number of drugs for cancer.

The clinical trial explores a drug (pegilodecakin) which is ongoing for the pancreatic

The developments performed by the companies are helping the market to grow in the coming years.

global market for ovarian cancer drugs expected to reach $10.1 billion by 2027, according to iHealthcareAnalyst.

be driven by continued uptake and expected launches of the approved PARP (poly adenosine diphosphate-ribose polymerase) inhibitors.

Major competitors operating in the global ovarian cancer treatment market include AbbVie, Inc., AstraZeneca plc (Acerta Pharma),

Boehringer Ingelheim GmbH, Chugai Pharmaceutical Co., Ltd., Clovis Oncology, Five Prime Therapeutics, Inc., GlaxoSmithKline plc (Tesaro),

Gradalis, Inc., Incyte Corporation, MacroGenics, Inc., Mateon Therapeutics, Inc., Merck & Co., Inc., Novartis AG, Novogen Limited,

Oasmia Pharmaceuticals, Inc., Pfizer, Inc., PharmaMar S.A, and Roche Holding AG.

products can be defined as addition-in-class, advance-in-class, or first-in-class, depending on their degree of innovation.

Addition-in-class

products, defined as new Active Pharmaceutical Ingredients (API) with established mechanisms of action, are often clinically important

and highly commercially successful.

Advance-in-class product innovation, defined as significantly differentiated and innovative new APIs,

albeit with established mechanisms of action, remains a highly attractive strategy.

However, first-in-class innovation, defined as products

with a molecular target and/or mechanism of action not found in any approved products globally, remains the key product development strategy

in terms of providing the greatest degree of differentiation, extending to a first-mover advantage and potentially the capture of significant

market share.

on the current situation for these two markets, we believe there is an attractive opportunity in both the pancreatic and ovarian cancer

market sectors for the introduction of a first-in-class, clinically proven product which can achieve new benefits for patients in terms

of survival and quality of life.

The current concentration of products suggests oncologists may be willing to try newly approved products,

particularly if they can exhibit a favorable safety profile, although substantive R&D activities will be necessary to both obtain

regulatory approval, and to generate the clinical safety and efficacy data needed to convince clinicians to use a new product.

previously sponsored a collaborative research project at University of Bath to investigate the cellular and molecular mechanisms underlying

the potential clinical approach of our proprietary proenzyme formulation.

As a result of this undertaking, we entered into a Commercialization

Agreement with University of Bath (UK), dated November 12, 2009 (the “Commercialization Agreement”), where, initially, we

held an exclusive license with Bath University, and where we and University of Bath co-owned the intellectual property relating to our

proenzyme formulations.

The Commercialization Agreement originally provided for University of Bath to assign the Patents (as defined

therein) to Propanc in certain specified circumstances, such as successful completion of a clinical trial and commencement of a Phase

II (Proof of Concept) clinical trial.

June 14, 2012, Propanc and University of Bath agreed to an earlier assignment to us of the patents pursuant to an Assignment and Amendment

Deed, on the provision that Bath University retains certain rights arising from the Commercialization Agreement, as follows:

of Bath reserves for itself (and its employees and students and permitted academic sub-licensees with respect to research use) the

non-exclusive, irrevocable, worldwide, royalty free right to use the patents for research use;

publication rights of University of Bath specified in the contract relating to the original research made between the parties with

an effective date of July 18, 2008 shall continue in force;

shall pay to University of Bath a royalty of two percent of any and all net revenues;

shall use all reasonable endeavors to develop and commercially exploit the patents for the mutual benefit of University of Bath and

Propanc to the maximum extent throughout the covered territory and in any additional territory and to obtain, maintain and/or renew

any licenses or authorizations that are necessary to enable such development and commercial exploitation.

Without prejudice to the

generality of the foregoing, Propanc shall comply with all relevant regulatory requirements in respect of its sponsoring and/or performing

clinical trials in humans involving the administration of a product or materials within a claim of the patents;

shall take out with a reputable insurance company and maintain liability insurance coverage prior to the first human trials.

consideration of such assignment, we agreed to pay royalties of 2% of net revenues to Bath University.

Additionally, we agreed

to pay 5% of each and every license agreement subscribed for.

consideration of such assignment, we agreed to pay royalties of 2% of net revenues to University of Bath.

Additionally, we agreed to

pay 5% of each and every license agreement subscribed for.

The contract is cancellable at any time by either party.

no amounts are owed under the agreement.

To date, no amounts

are owed under the agreement.

have established a collaboration with the University of Jaén to carry out a Research Project aimed at the synthetic development

of PRP and its subsequent validation.

The University of Jaén is providing scientific research activities the Department of Health

Sciences, which provides the necessary technical and human resources in order to carry out the programmed works.

A Collaboration Agreement

(the “Collaboration Agreement”) according was established, dated October 1, 2020, with the main objective for the synthetic

development of PRP and its subsequent validation.

To that end, there shall be established a pre-clinical protocol of safety evaluation

and antitumor efficacy on cancer stem cells and in orthotopic xenotransplantations derived from cancer stem cells isolated from tumor

cell lines, of a newly developed synthetic formulation based on the two pancreatic zymogens.

ownership of potential intellectual property rights that may arise as a result of the knowledge obtained through the project will belong

In consideration for payment of the compensation, the University of Jaén hereby assigns and agrees to do all things

reasonably required to assign to the contracting entity all industrial property rights arising from the Project.

return for ownership of the entire right and title in all industrial property rights arising from the Project, Propanc agrees to pay

the University of Jaén two percent (2%) of the net sales of any products sold by the contracting entity which fall within the

scope of the protection of such industrial property rights.

continue to learn the properties of proenzymes with the long-term aim of screening new compounds for development.

We anticipate

engaging in future discussions with several technology companies who are progressing new developments in the oncology field as

potential additions to our product line.

Initially targeting the oncology sector, our focus is to identify and develop novel treatments

that are highly effective targeted therapies, with few side effects as a result of toxicity to healthy cells.

have filed multiple patent applications relating to our lead product, PRP.

The first application was filed in October 2010 in

each of the countries listed in the table below.

This patent has been granted and remains in force in the United States,

Belgium, Czech Republic, Denmark, France, Germany, Ireland, Italy, Netherlands, Portugal, Spain, Sweden, Switzerland, Liechtenstein,

Turkey, United Kingdom, Australia, China, Japan, Indonesia, Israel, New Zealand, Singapore, Malaysia, South Africa, Mexico, Republic

of Korea and India.

In Brazil and Canada, the patent application remains under examination.

2016 and 2017 we filed other patent applications, as indicated below.

Three applications were filed under the PCT.

The PCT assists

applicants in seeking patent protection by filing one international patent application under the PCT, which allows the applicants

to seek protection for an invention in over 150 countries.

Once national or regional applications are filed, the application is

placed under the control of the national or regional patent offices, as applicable, in what is called the national or regional

One PCT application, filed in November 2016, entered the national phase in July 2018 in each of the countries listed in

the table below.

A second application filed in January 2017 entered the national phase commencing July 2018.

A third application

filed in April 2017 entered the national phase in October 2018.

pharmaceutical composition for treating cancer comprising trypsinogen and/or chymotrypsinogen and an active agent selected

from a selenium compound, a vanilloid compound and a cytoplasmic reduction agent.

Belgium, Czech Republic, Denmark, France, Germany, Ireland, Italy, Netherlands, Portugal, Spain, Sweden, Switzerland, Liechtenstein,

Turkey, United Kingdom, Australia, China, Japan, Indonesia, Israel, New Zealand, Malaysia, Singapore, Malaysia, South Africa,

Mexico, Republic of Korea and India

divisional applications granted and also under examination in Mexico and China

China, Europe, Hong Kong, India, Indonesia, Israel, Japan, Malaysia, New Zealand, Singapore, South Africa and USA

filed and pending

China, Europe, Hong Kong, Israel, Japan, Malaysia, New Zealand, Singapore and USA

filed and pending

of proenzymes for cancer treatment

China, Europe, Japan, and USA

filed and pending

patent applications are expected to be filed to capture and protect additional patentable subject matter based on our field of

technology relating to pharmaceutical compositions of proenzymes for treating cancer.

basis of our intellectual property protection will be built around the following elements:

Understanding the mechanism of action of the PRP proenzyme formulations, enabling the identification of new molecular

targets, potential new therapeutic compounds and identification of new formulations that are adapted to enhance activity.

Formulation :

We have developed an enhanced formulation containing the proenzyme trypsinogen in combination with at least one of two types

of identified compounds considered effective for providing synergistic enhancement of the proenzyme-based formulations.

patentability assessment, based on an international prior art search, has indicated that strong potential exists for successfully

obtaining patent claims covering the formulation.

Synthetic recombinant proteins designed to improve the quality, safety and performance of proenzymes used in

the proposed formulations form part of the research and development program.

We anticipate engaging

in future discussions with several technology companies who are progressing new developments in the oncology field as potential additions

to our product line.

Initially targeting the oncology sector, our focus is to identify and develop novel treatments that are highly effective

targeted therapies, with few side effects as a result of toxicity to healthy cells.

Company has filed multiple patent applications relating to its lead product, PRP.

The Company’s lead patent application has been

granted and remains in force in the United States, Belgium, Czech Republic, Denmark, France, Germany, Ireland, Italy, Netherlands, Portugal,

Spain, Sweden, Switzerland, Liechtenstein, Turkey, United Kingdom, Australia, China, Japan, Indonesia, Israel, New Zealand, Singapore,

Malaysia, South Africa, Mexico, Republic of Korea, India and Brazil.

In Canada, the patent application remains

under examination.

2016 and early 2017, we filed other patent applications.

Three applications were filed under the Patent Cooperation Treaty (the “PCT”).

The PCT assists applicants in seeking patent protection by filing one international patent application under the PCT, applicants can

simultaneously seek protection for an invention in over 150 countries.

Once filed, the application is placed under the control of the

national or regional patent offices, as applicable, in what is called the national phase.

One of the PCT applications filed in November

2016, entered national phase in July 2018 and another PCT application entered national phase in August 2018.

A third PCT application

entered national phase in October 2018.

Presently, there are 31 granted patents and 34

patents under examination in key global jurisdictions relating to the use of proenzymes against solid tumors, covering the lead product

candidate PRP.

patent applications are expected to be filed to capture and protect additional patentable subject matter based on the Company’s

field of technology relating to pharmaceutical compositions of proenzymes for treating cancer.

oversight of the pharmaceutical industry is usually classified into pre-approval and post-approval categories.

Most of the therapeutically

significant innovative products marketed today are the subject of New Drug Applications (“NDA”).

Preapproval activities,

based on these detailed applications, are used to assure the product is safe and effective before marketing.

In the United States,

The Center for Drug Evaluation and Research (“CDER”), is the FDA organization responsible for over-the-counter and

prescription drugs, including most biological therapeutics, and generic drugs.

approval, the FDA may inspect and audit the development facilities, planned production facilities, clinical trials, institutional

review boards and laboratory facilities in which the product was tested in animals.

After the product is approved and marketed,

the FDA uses different mechanisms for assuring that firms adhere to the terms and conditions of approval described in the application

and that the product is manufactured in a consistent and controlled manner.

This is done by periodic unannounced inspections of

production and quality control facilities by FDA’s field investigators and analysts.

In the United States, The

Center for Drug Evaluation and Research (“CDER”), is the FDA organization responsible for over-the- counter and prescription

drugs, including most biological therapeutics, and generic drugs.

approval, the FDA may inspect and audit the development facilities, planned production facilities, clinical trials, institutional review

boards and laboratory facilities in which the product was tested in animals.

After the product is approved and marketed, the FDA uses

different mechanisms for assuring that firms adhere to the terms and conditions of approval described in the application and that the

product is manufactured in a consistent and controlled manner.

This is done by periodic unannounced inspections of production and quality

control facilities by FDA’s field investigators and analysts.

Food, Drug and Cosmetic Act and Public Health Service Act

drug and biologic products are subject to extensive pre- and post-market regulation by the FDA, including regulations that govern

the testing, manufacturing, safety, efficacy, labelling, storage, record keeping, advertising and promotion of such products under

the Federal Food, Drug and Cosmetic Act, the Public Health Service Act, and their implementing regulations.

The process of obtaining

FDA approval and achieving and maintaining compliance with applicable laws and regulations requires the expenditure of substantial

time and financial resources.

Failure to comply with applicable FDA or other requirements may result in refusal to approve pending

applications, a clinical hold, warning letters, civil or criminal penalties, recall or seizure of products, partial or total suspension

of production or withdrawal of the product from the market.

FDA approval is required before any new drug or biologic, including

a new use of a previously approved drug, can be marketed in the United States.

All applications for FDA approval must contain,

among other things, information relating to safety and efficacy, stability, manufacturing, processing, packaging, labelling and

quality control.

Drug Applications (“NDAs”)

FDA’s NDA approval process generally involves:

of preclinical laboratory and animal testing in compliance with the FDA’s good laboratory practice, or GLP, regulations;

to the FDA of an investigational new drug (“IND”) application for human clinical testing, which must become effective

drug and biologic products are subject to extensive pre- and post-market regulation by the FDA, including regulations that govern the

testing, manufacturing, safety, efficacy, labelling, storage, record keeping, advertising and promotion of such products under the Federal

Food, Drug and Cosmetic Act, the Public Health Service Act, and their implementing regulations.

The process of obtaining FDA approval

and achieving and maintaining compliance with applicable laws and regulations requires the expenditure of substantial time and financial

Failure to comply with applicable FDA or other requirements may result in refusal to approve pending applications, a clinical

hold, warning letters, civil or criminal penalties, recall or seizure of products, partial or total suspension of production or withdrawal

of the product from the market.

FDA approval is required before any new drug or biologic, including a new use of a previously approved

drug, can be marketed in the United States.

All applications for FDA approval must contain, among other things, information relating

to safety and efficacy, stability, manufacturing, processing, packaging, labelling and quality control.

Drug Applications (“NDAs”)

FDA’s NDA approval process generally involves:

of preclinical laboratory and animal testing in compliance with the FDA’s good laboratory practice, or GLP, regulations;

to the FDA of an investigational new drug (“IND”) application for human clinical testing, which must become effective

before human clinical trials may begin in the United States;

of adequate and well-controlled human clinical trials to establish the safety, purity and potency of the proposed product

for each intended use;

completion of an FDA pre-approval inspection of the facility or facilities at which the product is manufactured to assess

compliance with the FDA’s “current good manufacturing practice”

(“CGMP”) regulations;

to and approval by the FDA of a NDA.

preclinical and clinical testing and approval process requires substantial time, effort and financial resources, and we cannot

guarantee that any approvals for our product candidates will be granted on a timely basis, if at all.

Preclinical tests include

laboratory evaluation of toxicity and immunogenicity in animals.

The results of preclinical tests, together with manufacturing

information and analytical data, are submitted as part of an IND application to the FDA.

The IND automatically becomes effective

30 days after receipt by the FDA, unless the FDA raises concerns or questions about the conduct of the clinical trial, including

concerns that human research subjects will be exposed to unreasonable health risks.

In such a case, the IND sponsor and the FDA

must resolve any outstanding concerns before clinical trials can begin.

Our submission of an IND may not result in FDA authorization

to commence clinical trials.

A separate submission to an existing IND must also be made for each successive clinical trial conducted

during product development.

Further, an independent institutional review board (“IRB”) covering each medical center

proposing to conduct clinical trials must review and approve the plan for any clinical trial before it commences at that center

and it must monitor the study until completed.

The FDA, the IRB or the sponsor may suspend a clinical trial at any time on various

grounds, including a finding that the subjects or patients are being exposed to an unacceptable health risk.

Clinical testing

also must satisfy extensive “good clinical practice”

(“GCP”) regulations, which include requirements that

all research subjects provide informed consent and that all clinical studies be conducted under the supervision of one or more

qualified investigators.

purposes of an NDA submission and approval, human clinical trials are typically conducted in the following sequential phases,

which may overlap:

of adequate and well-controlled human clinical trials to establish the safety, purity and potency of the proposed product for each

intended use;

completion of an FDA pre-approval inspection of the facility or facilities at which the product is manufactured to assess compliance

with the FDA’s “current good manufacturing practice” (“CGMP”) regulations;

to and approval by the FDA of an NDA.

preclinical and clinical testing and approval process requires substantial time, effort and financial resources, and we cannot guarantee

that any approvals for our product candidates will be granted on a timely basis, if at all.

Preclinical tests include laboratory evaluation

of toxicity and immunogenicity in animals.

The results of preclinical tests, together with manufacturing information and analytical data,

are submitted as part of an IND application to the FDA.

The IND automatically becomes effective 30 days after receipt by the FDA, unless

the FDA raises concerns or questions about the conduct of the clinical trial, including concerns that human research subjects will be

exposed to unreasonable health risks.

In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before clinical

trials can begin.

Our submission of an IND may not result in FDA authorization to commence clinical trials.

A separate submission to

an existing IND must also be made for each successive clinical trial conducted during product development.

Further, an independent institutional

review board (“IRB”) covering each medical center proposing to conduct clinical trials must review and approve the plan for

any clinical trial before it commences at that center and it must monitor the study until completed.

The FDA, the IRB or the sponsor

may suspend a clinical trial at any time on various grounds, including a finding that the subjects or patients are being exposed to an

unacceptable health risk.

Clinical testing also must satisfy extensive “good clinical practice” (“GCP”) regulations,

which include requirements that all research subjects provide informed consent and that all clinical studies be conducted under the supervision

of one or more qualified investigators.

purposes of an NDA submission and approval, human clinical trials are typically conducted in the following sequential phases, which may

Initially conducted in a limited population to test the product candidate for safety and dose tolerance;

Generally conducted in a limited patient population to identify possible adverse effects and safety risks, to determine

the initial efficacy of the product for specific targeted indications and to determine optimal dosage.

A Phase IIa trial is

a non-pivotal, exploratory study that assesses biological activity as its primary endpoint.

A Phase IIb trial is designed

as a definite dose finding study with efficacy as the primary endpoint.

Multiple Phase II clinical trials may be conducted

by the sponsor to obtain information prior to beginning larger and more extensive Phase III clinical trials;

Generally conducted in a limited patient population to identify possible adverse effects and safety risks, to determine the initial

efficacy of the product for specific targeted indications and to determine optimal dosage.

A Phase IIa trial is a non-pivotal, exploratory

study that assesses biological activity as its primary endpoint.

A Phase IIb trial is designed as a definite dose finding study with

efficacy as the primary endpoint.

Multiple Phase II clinical trials may be conducted by the sponsor to obtain information prior to

beginning larger and more extensive Phase III clinical trials;

Commonly referred to as pivotal studies.

When Phase II evaluations demonstrate that a dose range of the product is effective

and has an acceptable safety profile, Phase III clinical trials are undertaken in large patient populations to further evaluate

dosage, to provide substantial evidence of clinical efficacy and to further test for safety in an expanded and diverse patient

population at multiple, geographically-dispersed clinical trial sites.

Generally, replicate evidence of safety and effectiveness

needs to be demonstrated in two adequate and well-controlled Phase III clinical trials of a product candidate for a specific

These studies are intended to establish the overall risk/benefit ratio of the product and provide adequate basis

for product labelling;

In some cases, the FDA may condition approval of a NDA on the sponsor’s agreement to conduct additional clinical

trials to further assess the product’s safety, purity and potency after NDA approval.

Such post-approval trials are

typically referred to as Phase IV clinical trials.

reports detailing the results of the clinical studies must be submitted at least annually to the FDA and safety reports must be

submitted to the FDA and the investigators for serious and unexpected adverse events.

Concurrent with clinical studies, sponsors

usually complete additional animal studies and must also develop additional information about the product and finalize a process

for manufacturing the product in commercial quantities in accordance with CGMP requirements.

The manufacturing process must be

capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop

methods for testing the identity, strength, quality and purity of the final product.

Moreover, appropriate packaging must be selected

and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration

over its shelf life.

results of product development, preclinical studies and clinical trials, along with the aforementioned manufacturing information,

are submitted to the FDA as part of a NDA.

NDA’s must also contain extensive manufacturing information.

Under the Prescription

Drug User Fee Act (“PDUFA”), the FDA agrees to specific goals for NDA review time through a two-tiered classification

system, Standard Review and Priority Review.

Standard Review is applied to products that offer at most, only minor improvement

over existing marketed therapies.

Standard Review NDAs have a goal of being completed within a ten-month timeframe, although a

review can take significantly longer.

A Priority Review designation is given to products that offer major advances in treatment,

or provide a treatment where no adequate therapy exists.

and has an acceptable safety profile, Phase III clinical trials are undertaken in large patient populations to further evaluate dosage,

to provide substantial evidence of clinical efficacy and to further test for safety in an expanded and diverse patient population

at multiple, geographically-dispersed clinical trial sites.

Generally, replicate evidence of safety and effectiveness needs to be

demonstrated in two adequate and well-controlled Phase III clinical trials of a product candidate for a specific indication.

studies are intended to establish the overall risk/benefit ratio of the product and provide adequate basis for product labelling;

In some cases, the FDA may condition approval of a NDA on the sponsor’s agreement to conduct additional clinical trials

to further assess the product’s safety, purity and potency after NDA approval.

Such post-approval trials are typically referred

to as Phase IV clinical trials.

reports detailing the results of the clinical studies must be submitted at least annually to the FDA and safety reports must be submitted

to the FDA and the investigators for serious and unexpected adverse events.

Concurrent with clinical studies, sponsors usually complete

additional animal studies and must also develop additional information about the product and finalize a process for manufacturing the

product in commercial quantities in accordance with CGMP requirements.

The manufacturing process must be capable of consistently producing

quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength,

quality and purity of the final product.

Moreover, appropriate packaging must be selected and tested and stability studies must be conducted

to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

results of product development, preclinical studies and clinical trials, along with the aforementioned manufacturing information, are

submitted to the FDA as part of a NDA.

NDA’s must also contain extensive manufacturing information.

Under the Prescription Drug

User Fee Act (“PDUFA”), the FDA agrees to specific goals for NDA review time through a two-tiered classification system,

Standard Review and Priority Review.

Standard Review is applied to products that offer at most, only minor improvement over existing

marketed therapies.

Standard Review NDAs have a goal of being completed within a ten-month timeframe, although a review can take significantly

A Priority Review designation is given to products that offer major advances in treatment, or provide a treatment where no adequate

therapy exists.

A Priority Review takes the FDA six months to review a NDA.

that our product candidates will be granted Standard Reviews.

The review process is often significantly extended by FDA requests

for additional information or clarification.

The FDA may refer the application to an advisory committee for review, evaluation

and recommendation as to whether the application should be approved.

The FDA is not bound by the recommendation of an advisory

committee, but it generally follows such recommendations.

FDA may deny approval of a NDA if the applicable regulatory criteria are not satisfied, or it may require additional clinical

data or additional pivotal Phase III clinical trials.

Even if such data is submitted, the FDA may ultimately decide that the NDA

does not satisfy the criteria for approval.

Data from clinical trials is not always conclusive and the FDA may interpret data

differently than Propanc.

Once issued, product approval may be withdrawn by the FDA if ongoing regulatory requirements are not

met or if safety problems occur after the product reaches the market.

In addition, the FDA may require testing, including Phase

IV clinical trials, Risk Evaluation and Mitigation Strategies (“REMS”), and surveillance programs to monitor the effect

of approved products that have been commercialized, and the FDA has the power to prevent or limit further marketing of a product

based on the results of these post-marketing programs.

Products may be marketed only for the approved indications and in accordance

with the provisions of the approved label.

Further, if there are any modifications to the drug, including changes in indications,

labelling or manufacturing processes or facilities, approval of a new or supplemental NDA may be required, which may involve conducting

additional preclinical studies and clinical trials.

It is likely that our product candidates will be granted

Standard Reviews.

The review process is often significantly extended by FDA requests for additional information or clarification.

FDA may refer the application to an advisory committee for review, evaluation and recommendation as to whether the application should

The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations.

FDA may deny approval of a NDA if the applicable regulatory criteria are not satisfied, or it may require additional clinical data or

additional pivotal Phase III clinical trials.

Even if such data is submitted, the FDA may ultimately decide that the NDA does not satisfy

the criteria for approval.

Data from clinical trials is not always conclusive and the FDA may interpret data differently than Propanc.

Once issued, product approval may be withdrawn by the FDA if ongoing regulatory requirements are not met or if safety problems occur

after the product reaches the market.

In addition, the FDA may require testing, including Phase IV clinical trials, Risk Evaluation and

Mitigation Strategies (“REMS”), and surveillance programs to monitor the effect of approved products that have been commercialized,

and the FDA has the power to prevent or limit further marketing of a product based on the results of these post-marketing programs.

may be marketed only for the approved indications and in accordance with the provisions of the approved label.

Further, if there are

any modifications to the drug, including changes in indications, labelling or manufacturing processes or facilities, approval of a new

or supplemental NDA may be required, which may involve conducting additional preclinical studies and clinical trials.

Regulatory Requirements

approval, products are subject to extensive continuing regulation by the FDA, which include company obligations to manufacture

products in accordance with GMP, maintain and provide to the FDA updated safety and efficacy information, report adverse experiences

with the product, keep certain records, submit periodic reports, obtain FDA approval of certain manufacturing or labeling changes

and comply with FDA promotion and advertising requirements and restrictions.

Failure to meet these obligations can result in various

adverse consequences, both voluntary and FDA-imposed, including product recalls, withdrawal of approval, restrictions on marketing

and the imposition of civil fines and criminal penalties.

In addition, later discovery of previously unknown safety or efficacy

issues may result in restrictions on the product, manufacturer or NDA holder.

and any manufacturers of our products, are required to comply with applicable FDA manufacturing requirements contained in the

FDA’s GMP regulations.

GMP regulations require, among other things, quality control and quality assurance as well as the

corresponding maintenance of records and documentation.

The manufacturing facilities for our products must meet GMP requirements

to the satisfaction of the FDA pursuant to a pre-approval inspection before Propanc can use them to manufacture products.

and any third-party manufacturers are also subject to periodic inspections of facilities by the FDA and other authorities, including

procedures and operations used in the testing and manufacture of our products to assess our compliance with applicable regulations.

approval, products are subject to extensive continuing regulation by the FDA, which include company obligations to manufacture products

in accordance with GMP, maintain and provide to the FDA updated safety and efficacy information, report adverse experiences with the

product, keep certain records, submit periodic reports, obtain FDA approval of certain manufacturing or labeling changes and comply with

FDA promotion and advertising requirements and restrictions.

Failure to meet these obligations can result in various adverse consequences,

both voluntary and FDA-imposed, including product recalls, withdrawal of approval, restrictions on marketing and the imposition of civil

fines and criminal penalties.

In addition, later discovery of previously unknown safety or efficacy issues may result in restrictions

on the product, manufacturer or NDA holder.

and any manufacturers of our products, are required to comply with applicable FDA manufacturing requirements contained in the FDA’s

GMP regulations.

GMP regulations require, among other things, quality control and quality assurance as well as the corresponding maintenance

of records and documentation.

The manufacturing facilities for our products must meet GMP requirements to the satisfaction of the FDA

pursuant to a pre-approval inspection before Propanc can use them to manufacture products.

Propanc and any third-party manufacturers

are also subject to periodic inspections of facilities by the FDA and other authorities, including procedures and operations used in

the testing and manufacture of our products to assess our compliance with applicable regulations.

respect to post-market product advertising and promotion, the FDA imposes complex regulations on entities that advertise and promote

pharmaceuticals, which include, among others, standards for direct-to-consumer advertising, promoting products for uses or in

patient populations that are not described in the product’s approved labeling (known as “off-label use”), industry-sponsored

pharmaceuticals, which include, among others, standards for direct-to-consumer advertising, promoting products for uses or in patient

populations that are not described in the product’s approved labeling (known as “off-label use”), industry-sponsored

scientific and educational activities and promotional activities involving the Internet.

Failure to comply with FDA requirements

can have negative consequences, including adverse publicity, enforcement letters from the FDA, mandated corrective advertising

or communications with doctors and civil or criminal penalties.

Although physicians may prescribe legally available drugs for

off-label uses, manufacturers may not market or promote such off-label uses.

to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing

processes or facilities, require submission and FDA approval of a new NDA or NDA supplement before the change can be implemented.

A NDA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA

uses the same procedures and actions in reviewing NDA supplements as it does in reviewing a NDA.

Failure to comply with FDA requirements can

have negative consequences, including adverse publicity, enforcement letters from the FDA, mandated corrective advertising or communications

with doctors and civil or criminal penalties.

Although physicians may prescribe legally available drugs for off-label uses, manufacturers

may not market or promote such off-label uses.

to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes

or facilities, require submission and FDA approval of a new NDA or NDA supplement before the change can be implemented.

A NDA supplement

for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures

and actions in reviewing NDA supplements as it does in reviewing a NDA.

event reporting and submission of periodic reports is required following FDA approval of a NDA.

The FDA also may require post-marketing

testing, known as Phase IV testing, risk mitigation strategies and surveillance to monitor the effects of an approved product

or to place conditions on an approval that could restrict the distribution or use of the product.

Drug Designation

testing, known as Phase IV testing, risk mitigation strategies and surveillance to monitor the effects of an approved product or to place

conditions on an approval that could restrict the distribution or use of the product.

June 2017, we were notified by the FDA that PRP had been granted orphan drug designation for the treatment of pancreatic cancer.

Orphan drug designation may be granted by the FDA when a rare disease or condition is implicated and a potential treatment qualifies

under the Orphan Drug Act and applicable FDA regulations.

This qualifies us for various developmental incentives, including protocol

assistance, the potential for research grants, the waiver of future application fees, and tax credits for clinical testing if

we choose to host future clinical trials in the United States.

drug designation may be granted by the FDA when a rare disease or condition is implicated and a potential treatment qualifies under the

Orphan Drug Act and applicable FDA regulations.

This qualifies us for various developmental incentives, including protocol assistance,

the potential for research grants, the waiver of future application fees, and tax credits for clinical testing if we choose to host future

clinical trials in the United States.

October 2017, we submitted a request for a second orphan drug designation for PRP, this time for ovarian cancer.

November 2, 2017, we were notified by the FDA that our request was not granted.

The Office of Orphan Products Development (“OOPD”)

stated that complete prevalence is used as a measure of disease in ovarian cancer, as this reflects the number of women who have

been diagnosed with disease and may be eligible for treatment with the proposed therapy.

Therefore, on the date of the submission

of our application, the OOPD estimated that the prevalence of ovarian cancer was 228,110 cases.

Since the prevalence exceeds the

threshold of 200,000 to qualify for orphan drug designation, they could not grant our request.

We may consider resubmitting our

application if we can identify a suitable sub population in ovarian cancer, which may meet the target threshold.

addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials,

commercial sales and distribution of our products.

Whether or not we obtain FDA approval for a product, we must obtain approval

of a product by the comparable regulatory authorities of foreign countries before we can commence clinical trials or market our

product in those countries.

The approval process varies from country to country and the time may differ than that required for

FDA approval.

The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly

from country to country.

Despite these differences, the clinical trials will be conducted according to international standards

such as Good Clinical Practice (GCP), Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP), which is recognized

by each foreign country under the International Conference of Harmonization (ICH) Guidelines.

We will conduct our trials in each

foreign jurisdiction according to these standards, undertaking a First-In-Human (FIH) Phase I study in patients with advanced

solid tumors, evaluating the safety, pharmacokinetics, and anti-tumor efficacy of PRP.

This will be followed by two Phase II studies

evaluating the efficacy and safety of PRP.

To ensure harmonization between the jurisdictions, we intend to conduct regulatory

meetings in the country where trials are conducted, as well as the FDA and European Medicines Agency.

A pre-IND (Investigational

New Drug) meeting will be held with the FDA once initial patient data has been collected from the FIH study to ensure acceptability

of future planned Phase II trials.

European Union regulatory systems, we must submit and obtain authorization for a clinical trial application in each member state

in which we intend to conduct a clinical trial.

After we have completed clinical trials, we must obtain marketing authorization

before it can market its product.

We must submit applications for marketing authorizations for oncology products under a centralized

The centralized procedure provides for the grant of a single marketing authorization that is valid for all European

Union member states.

The European Medicines Agency (the “EMA”) is the agency responsible for the scientific evaluation

of medicines that are to be assessed via the centralized procedure.

On June 23, 2016, the

UK government held a referendum to gauge voters’

support to remain or leave the European Union.

The referendum resulted

in 51.9% of UK voters in favor of leaving the European Union, commonly referred to as “Brexit.”

On March 29, 2017,

the UK invoked Article 50 of Lisbon Treaty to initiate complete withdrawal from the European Union, which was effected on January

The center for the EMA was based in London but the European Union has relocated the center

to The Netherlands.

impact of Brexit on the drug approval process in the UK is uncertain, which could significantly impact Propanc as we may elect

to conduct our clinical trials for PRP in the UK.

Companies based in the UK and operating in the drug industry are urging the

European Union and the UK to reach an agreement to harmonize the regulatory process once the UK officially exits the European

We hope to commence our Phase IIa trials in 2021, and we are hopeful that there will be greater clarity on the regulatory

process for drug approvals in UK in the near future.

Australia, the relevant regulatory body responsible for the pharmaceutical industry is the Therapeutics Goods Administration (the

“TGA”).

The Office of Orphan Products Development (“OOPD”)

stated that complete prevalence is used as a measure of disease in ovarian cancer, as this reflects the number of women who have been

diagnosed with disease and may be eligible for treatment with the proposed therapy.

Therefore, on the date of the submission of our application,

the OOPD estimated that the prevalence of ovarian cancer was 228,110 cases.

Since the prevalence exceeds the threshold of 200,000 to

qualify for orphan drug designation, they could not grant our request.

We may consider resubmitting our application if we can identify

a suitable sub population in ovarian cancer, which may meet the target threshold.

addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials, commercial

sales and distribution of our products.

Whether or not we obtain FDA approval for a product, we must obtain approval of a product by

the comparable regulatory authorities of foreign countries before we can commence clinical trials or market our product in those countries.

The approval process varies from country to country and the time may differ than that required for FDA approval.

The requirements governing

the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country.

Despite these differences,

the clinical trials will be conducted according to international standards such as Good Clinical Practice (GCP), Good Manufacturing Practice

(GMP) and Good Laboratory Practice (GLP), which is recognized by each foreign country under the International Conference of Harmonization

(ICH) Guidelines.

We will conduct our trials in each foreign jurisdiction according to these standards, undertaking a First-In-Human

(FIH) Phase I study in patients with advanced solid tumors, evaluating the safety, pharmacokinetics, and anti-tumor efficacy of PRP.

This will be followed by two Phase II studies evaluating the efficacy and safety of PRP.

To ensure harmonization between the jurisdictions,

we intend to conduct regulatory meetings in the country where trials are conducted, as well as the FDA and European Medicines Agency.

A pre-IND (Investigational New Drug) meeting will be held with the FDA once initial patient data has been collected from the FIH study

to ensure acceptability of future planned Phase II trials.

European Union regulatory systems, we must submit and obtain authorization for a clinical trial application in each member state in which

we intend to conduct a clinical trial.

After we have completed clinical trials, we must obtain marketing authorization before it can

market its product.

We must submit applications for marketing authorizations for oncology products under a centralized procedure.

centralized procedure provides for the grant of a single marketing authorization that is valid for all European Union member states.

The European Medicines Agency (the “EMA”) is the agency responsible for the scientific evaluation of medicines that are to

be assessed via the centralized procedure.

June 23, 2016, the UK government held a referendum to gauge voters’ support to remain or leave the European Union.

The referendum

resulted in 51.9% of UK voters in favor of leaving the European Union, commonly referred to as “Brexit.” On March 29, 2017,

the UK invoked Article 50 of Lisbon Treaty to initiate complete withdrawal from the European Union, which was effectuated on January

The center for the EMA was based in London but the European Union has relocated the center to The Netherlands.

The impact of Brexit on the drug approval process

in the UK is uncertain.

Companies based in the UK and operating in the drug industry are urging the European Union and the UK to reach

an agreement to harmonize the regulatory process once the UK officially exits the European Union.

Australia, the relevant regulatory body responsible for the pharmaceutical industry is the Therapeutics Goods Administration (the “TGA”).

Prescription medicines are regulated under the Therapeutic Goods Act 1989.

Under the Therapeutic Goods Act,

the Therapeutic Goods Administration evaluates new products for quality, safety and efficacy before being approved for market

authorization, according to similar standards employed by the FDA and EMA in the United States and European Union, respectively.

However, receiving market authorization in one or two regions does not guarantee approval in another.

Under the Therapeutic Goods Act, the Therapeutic Goods Administration

evaluates new products for quality, safety and efficacy before being approved for market authorization, according to similar standards

employed by the FDA and EMA in the United States and European Union, respectively.

However, receiving market authorization in one or

two regions does not guarantee approval in another.

Payor Coverage and Reimbursement

none of our product candidates have been commercialized for any indication, if they are approved for marketing, commercial success

of our product candidates will depend, in part, upon the availability of coverage and reimbursement from third-party payors at

the federal, state and private levels.

In addition, in many countries outside the United States, a drug must be approved for reimbursement

before it can be approved for sale in that country.

none of our product candidates have been commercialized for any indication, if they are approved for marketing, commercial success of

our product candidates will depend, in part, upon the availability of coverage and reimbursement from third-party payors at the federal,

state and private levels.

In addition, in many countries outside the United States, a drug must be approved for reimbursement before

it can be approved for sale in that country.

for reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including research,

3 unchanged sentences

Reimbursement rates may vary according to the use of the drug and the clinical setting

in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing

payments for other services.

Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare

programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where

they may be sold at lower prices than in the United States.

Third-party payors often rely upon Medicare coverage policy and payment

limitations in setting their own reimbursement policies.

many countries outside the United States, a drug must be approved for reimbursement before it can be approved for sale in that

Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval

by one foreign regulatory authority does not ensure approval by regulatory authorities in other foreign countries or by the FDA.

The foreign regulatory approval process may include all of the risks associated with obtaining FDA approval.

We may not obtain

foreign regulatory approvals on a timely basis, if at all.

We may not be able to file for regulatory approvals and may not receive

necessary approvals to commercialize our products in any foreign market.

Approvals, Pricing and Reimbursement Regulations

in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments

for other services.

Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs

or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold

at lower prices than in the United States.

Third-party payors often rely upon Medicare coverage policy and payment limitations in setting

their own reimbursement policies.

many countries outside the United States, a drug must be approved for reimbursement before it can be approved for sale in that country.

Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one foreign

regulatory authority does not ensure approval by regulatory authorities in other foreign countries or by the FDA.

The foreign regulatory

approval process may include all of the risks associated with obtaining FDA approval.

We may not obtain foreign regulatory approvals

on a timely basis, if at all.

We may not be able to file for regulatory approvals and may not receive necessary approvals to commercialize

our products in any foreign market.

regulations that govern marketing approvals, pricing and reimbursement for new drug products vary widely from country to country.

In the United States, recently passed legislation may significantly change the approval requirements in ways that could involve

additional costs and cause delays in obtaining approvals.

Some countries require approval of the sale price of a drug before it

can be marketed.

the United States, recently passed legislation may significantly change the approval requirements in ways that could involve additional

costs and cause delays in obtaining approvals.

Some countries require approval of the sale price of a drug before it can be marketed.

In many countries, the pricing review period begins after marketing or product licensing approval is granted.

In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial

approval is granted.

authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications

they will pay for and establish reimbursement levels.

In some foreign markets,

prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted.

authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications they

will pay for and establish reimbursement levels.

A primary trend in the U.S.

healthcare industry and elsewhere is cost containment.

Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement

for particular medications.

Increasingly, third-party payors are requiring that drug companies provide them with predetermined

discounts from list prices and are challenging the prices charged for medical products.

are also subject to numerous federal, state and local laws relating to such matters as safe working conditions, manufacturing

practices, environmental protection, fire hazard control, and disposal of hazardous or potentially hazardous substances.

incur significant costs to comply with such laws and regulations now or in the future.

authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular

Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices

and are challenging the prices charged for medical products.

are also subject to numerous federal, state and local laws relating to such matters as safe working conditions, manufacturing practices,

environmental protection, fire hazard control, and disposal of hazardous or potentially hazardous substances.

We may incur significant

costs to comply with such laws and regulations now or in the future.

biotechnology and pharmaceutical industries are characterized by continuing technological advancement and significant competition.

While we believe that our technology platforms, product candidates, know-how, experience and scientific resources provide us with

competitive advantages, we face competition from major pharmaceutical and biotechnology companies, academic institutions, governmental

agencies and public and private research institutions, among others.

Any product candidates that we successfully develop and commercialize

will compete with existing therapies and new therapies that may become available in the future.

Key product features that would

affect our ability to effectively compete with other therapeutics include the efficacy, safety and convenience of our products.

The level of generic competition and the availability of reimbursement from government and other third-party payers will also

significantly impact the pricing and competitiveness of our products.

Our competitors also may obtain FDA or other regulatory

approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing

a strong market position before we are able to enter the market.

we believe that our technology platforms, product candidates, know-how, experience and scientific resources provide us with competitive

advantages, we face competition from major pharmaceutical and biotechnology companies, academic institutions, governmental agencies and

public and private research institutions, among others.

Any product candidates that we successfully develop and commercialize will compete

with existing therapies and new therapies that may become available in the future.

Key product features that would affect our ability

to effectively compete with other therapeutics include the efficacy, safety and convenience of our products.

The level of generic competition

and the availability of reimbursement from government and other third-party payers will also significantly impact the pricing and competitiveness

of our products.

Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain

approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical

1 unchanged sentence

Smaller or early-stage

companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established

These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and

establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary

to, or necessary for, our programs.

of September 14, 2020, we have one full-time employee and two part-time employees.

In addition to our employees, we engage

key consultants and utilize the services of independent contractors to perform various services on our behalf.

Some of our executive

officers and directors are engaged in outside business activities that we do not believe conflict with our business.

we may be required to hire additional employees or engage independent contractors to execute various projects that are necessary

to grow and develop our business.

These decisions will be made by our officers and directors, if and when appropriate.

Corporate Information

companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical

trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our

of September 28, 2021, we have one full-time and one part-time employee.

In addition to our employees, we engage key consultants and

utilize the services of independent contractors to perform various services on our behalf.

Some of our executive officers and directors

are engaged in outside business activities that we do not believe conflict with our business.

Over time, we may be required to hire additional

employees or engage independent contractors to execute various projects that are necessary to grow and develop our business.

These decisions

will be made by our officers and directors, if and when appropriate.

principal executive office is located at 302, 6 Butler Street, Camberwell, VIC, 3124 Australia.

of our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other documents that we will

file with or furnish to the SEC will be available free of charge by sending a written request to our Corporate Secretary at our

corporate headquarters.

Additionally, the documents we file with the SEC are or will be available free of charge at the SEC’s

Public Reference Room at 100 F Street, N.E., Washington, D.C.

Other information on the operation of the Public Reference

Room may be obtained by calling the SEC at (800) SEC-0330.

The SEC maintains a website that contains reports, proxy and information

statements and other information regarding registrants that file electronically with the SEC.

The SEC’s website is www.sec.gov .

Our telephone number is 61 03 9882 0780.

Our website is www.propanc.com.

We can be contacted by email at www.propanc.com/contact.

Our website’s information is not, and

will not be deemed, a part of this Annual Report or incorporated into any other filings we make with the SEC.

of our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other documents that we will file

with or furnish to the SEC will be available free of charge by sending a written request to our Corporate Secretary at our corporate

headquarters.

Additionally, the documents we file with the SEC are or will be available free of charge at the SEC’s Public Reference

Room at 100 F Street, N.E., Washington, D.C.

Other information on the operation of the Public Reference Room may be obtained by

calling the SEC at (800) SEC-0330.

The SEC maintains a website that contains reports, proxy and information statements and other information

regarding registrants that file electronically with the SEC.

The SEC’s website is www.sec.gov.

maintain a corporate website at www.propanc.com.

You will be able to access our Annual Reports on Form 10-K, Quarterly

Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports, proxy statements and other information to be

filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act with the SEC free of charge at our website as soon as

reasonably practicable after such material will be electronically filed with, or furnished to, the SEC.

The information contained

in, or that can be accessed through, our website is not part of this Annual Report.

You will be able to access our Annual Reports on Form 10-K, Quarterly Reports on Form

10-Q, Current Reports on Form 8-K and amendments to those reports, proxy statements and other information to be filed or furnished pursuant

to Section 13(a) or 15(d) of the Exchange Act with the SEC free of charge at our website as soon as reasonably practicable after such

material will be electronically filed with, or furnished to, the SEC.

The information contained in, or that can be accessed through,

our website is not part of this Annual Report.

are not required to provide this information as we are a smaller reporting company.

Unresolved Staff Comments.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business