PPCB filing — read by section

Item 1. Business

Item
1. Business 

 GENERAL 

 As
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. 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. 

 We
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 “$” and “dollars”
are to United States dollars. 

 OVERVIEW 

 Propanc
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. 

 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, 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 2023 calendar
year. 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 2023 and
complete the CTA compilation and submit the CTA in the first half of 2023. In the second quarter of 2023, 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 2023 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. 

 PRP
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. 

 4 

 We
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. 

 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 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. 

 Our
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. 

 OUR
FOCUS 

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

 Common
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. 

 Our
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
irradiation. 

 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. 

 There
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
and fats. 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. 

 We
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. 

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

 ● 
 Reduces
 cancer cell growth via promotion of cell differentiation 

 ● 
 Enhances
 cell adhesion and may suppress metastasis progression 

 ● 
 Exhibits
 no observable serious side effects and improves patient survival 

 ● 
 Alters
 the external microenvironment of malignant tumors, preventing tumors from returning and spreading. 

 5 

 PRP 

 PRP
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. 

 Mechanism
Of Action 

 Metastasis
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. PRP also
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. 

 Selectivity 

 PRP
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. 

 Effects
Against Cancer Stem Cells 

 Cancer
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. 

 PRP
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. 

 PRP
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. 

 PRP
Impairs Niche Formation and Tumor Initiation 

 The
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. Several assays, in vitro and in vivo studies confirm that PRP exerts an anti-tumor
effect and acts selectively against all malignant, or tumor elements without affecting the non-tumor microenvironment and preventing
its malignification. 

 In
Vivo Efficacy of PRP In Pancreatic and Ovarian Tumors 

 The
effect of the pro-enzyme formulation PRP at different doses on tumor weight in orthotopically implanted pancreatic and ovary tumors was
evaluated. 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). Furthermore,
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%). 

 6 

 Overview
Of Clinical Studies 

 The
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. 

 No
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
observed. 

 In
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. 

 PRP
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. 

 Cancer
 Type 
 
 Life
 Expectation 

 (months) 
 
 Survival
 ** 

 (months) 
 
 Pancreatic
 carcinoma (n = 4) 
 
 2 
 
 8 

 4 
 
 * 

 <3 
 
 7 

 <3 
 
 4 

 Ovarian
 Cancer (n = 7) 
 
 4 
 
 11 

 6 
 
 12 

 6 
 
 11 

 <12 
 
 38 

 <1 
 
 1 

 4 
 
 * 

 3 
 
 * 

 Breast
 Cancer (n = 6) 
 
 6 
 
 9 

 6 
 
 * 

 2 
 
 * 

 12 
 
 * 

 <12 
 
 * 

 12 
 
 * 

 Colon
 Rectal Cancer (n = 5) 
 
 6 
 
 * 

 6 
 
 * 

 12 
 
 * 

 6 
 
 40 

 12 
 
 * 

 Gastric
 Cancer (n = 2) 
 
 2 
 
 8 

 <3 
 
 7 

 Prostate
 Cancer (n = 8) 
 
 4 
 
 * 

 1 
 
 5 

 4 
 
 * 

 <12 
 
 * 

 12 
 
 14 

 12 
 
 * 

 12 
 
 * 

 12 
 
 * 

 Non-Hodgkin
 Lymphoma (n = 1) 
 
 2 
 
 9 

 Mesothelioma
 (n = 1) 
 
 3 
 
 9 

 Melanoma
 (n = 2) 
 
 6 
 
 * 

 <3 
 
 4 

 Neuro-endocrine
 Tumor (n = 1) 
 
 10 
 
 24 

 Bladder
 (n = 2) 
 
 <3 
 
 * 

 12 
 
 * 

 NSCLS
 (n = 2) 
 
 3 
 
 5 

 6 
 
 * 

 Bowel
 (n = 2) 
 
 <12 
 
 * 

 <3 
 
 3 

 Small
 Cell Carcinoma (n = 1) 
 
 <12 
 
 * 

 Renal
 Cancer (n = 1) 
 
 <3 
 
 * 

 Abdomen
 unknown primary (n = 1) 
 
 <12 
 
 * 

 Overview
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). 

 7 

 POP1
JOINT RESEARCH AND DRUG DISCOVERY PROGRAM 

 The
POP1 Joint Research and Drug Discovery Program is designed to produce a backup clinical compound to PRP, which is targeting metastatic
cancer from solid tumors. According to Emergen Research, the global metastatic cancer market is projected to be worth $111 Billion by
2027. 

 To
date, recombinant trypsinogen and chymotrypsinogen were synthesized and purified in the laboratory. In the case of trypsinogen, the initial
success of producing trypsinogen synthetically has advanced to the stage where optimization of protein production is underway. Whereas
purification and yield of chymotrypsinogen is currently the focus of research. 

 A
synthetic version of trypsinogen and chymotrypsinogen could have additional benefits to the global healthcare system that could further
capitalize on the new therapeutic approach to treating cancer that the Company’s lead product candidate PRP offers cancer sufferers.
For example, both proenzymes synthesized by an in vivo (living organism) system to produce crystalized proteins that could be
maintained for long periods without suffering degradation, even in the 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. The program’s joint researchers at the Universities of Jaén and Granada are currently
collaborating with the Institute of Microbiology and Microbial Biotechnology, at the University of Natural Resources and Life Sciences,
Vienna, Austria, Europe, and are working towards full scale manufacture of a synthetic recombinant formulation to PRP. 

 8 

 PRP
TARGET INDICATIONS 

 The
management of cancer differs widely, with a multitude of factors impacting the choice of treatment strategy. Some of those factors include: 

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

 ● 
 the
 extent to which it has spread beyond its original location; 

 ● 
 the
 availability of treatments, driven by multiple factors including cost, drugs approved, local availability of suitable facilities,
 etc.; 

 ● 
 regional
 and geographic differences; 

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

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

 For
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. 

 Should
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: 

 1. 
 In
 the early-stage management of solid tumors, most likely as part of a multi-pronged treatment strategy in combination with existing
 therapeutic interventions; 

 2. 
 As
 a product that can be administered long term for patients following standard treatment approaches, such as surgery, or chemotherapy,
 in order to prevent or delay recurrence; and 

 3. 
 As
 a preventative measure for patients at risk of developing cancer based on genetic screening. 

 In
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. 

 Pancreatic
Cancer 

 Pancreatic
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. 

 Pancreatic
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. 

 Since
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. 

 9 

 Each
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
(NAACCR). 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. 

 Ovarian
Cancer 

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

 Ovarian
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. 

 PRP
DEVELOPMENT STRATEGY 

 Our
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. 

 As
part of that commercial strategy, we will: 

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

 ● 
 seek
 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; 

 ● 
 aggressively
 pursue the protection of our technology through all means possible, including patents in all major jurisdictions, and potentially
 trade secrets; and 

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

 PRP
DEVELOPMENT PLAN AND MILESTONES 

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

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

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

 10 

 Preclinical
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. Propanc
Biopharma is collaborating with contract research organizations, manufacturing partners and consultants to complete activities prior
to preparing the CTA for the Phase Ib study. 

 The
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. The Phase
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. 

 In
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 $75,800 AUD ($54,977 USD) and $151,767 AUD ($113,415 USD) for the
year ended June 30, 2022 and 2021, 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. 

 We
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. 

 Our
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. 

 Anticipated
timelines 

 In
second quarter of 2023 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 2023. 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
Brochure. In the second half of 2023 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. Commencing in the second half of 2023 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. 

 11 

 Research
 Activity 
 
 Timeline 

 Clinical
 Trial Application (CTA) 
 
 Nov
 ‘22 - Apr ‘23 

 Investigational
 Medicinal Product Dossier 
 
 Phase
 Ib Clinical Study Protocol 
 
 Investigator’s
 Brochure 
 
 CTA
 Compilation 
 
 Mar
 - May ‘23 

 CTA
 submission 
 
 May
 ‘23 

 CTA
 Approval 
 
 Jun
 ‘23 

 CTA
 Review 
 
 June
 ‘23 – Jul ‘23 

 Contract
 Research Organization & Contracts 
 
 Jan
 – May ‘23 

 Analytical
 Laboratory Selection & Contracts 
 
 Trial
 Site Selection & Contracts 
 
 Preparation
 of Logistics 
 
 May
 – Sep ‘23 

 Trial
 Site Initiation Visits 
 
 First
 Patient/First Visit 
 
 Sep
 ‘23 

 POP1
JOINT RESEARCH AND DRUG DISCOVERY PROGRAM 

 As
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. 

 The
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. 

 FINANCIAL
OBJECTIVES 

 Multiple
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. 

 We
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. 

 CORPORATE
STRATEGY 

 Our
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). 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. 

 This
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. 

 12 

 We
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. 

 As
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, 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. 

 CURRENT
OPERATIONS 

 We
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. 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. 

 CURRENT
THERAPIES 

 We
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. 

 Current
therapeutic options for the treatment of cancer offer, at most, a few months of extra life or tumor stabilization. Some experts 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. Tumor cells, however, can develop resistance to drugs. 

 Limitations
of Current Therapies 

 PRP
was developed because of the limitation of current cancer therapies. While surgery is often safe and effective for early-stage cancer,
many standard therapies for late-stage cancer urgently need improvement; current treatments generally provide modest benefits, and frequently
cause significant adverse effects. Our focus is to provide oncologists and their patients with therapies for metastatic cancer which
are more effective than current therapies, and which have a substantially reduced side effect profile. 

 13 

 While
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: 

 1. 
 significant
 toxic effects; 

 2. 
 expense;
 and 

 3. 
 limited
 survival benefits. 

 We
believe that our treatment will provide a competitive advantage over the following treatments: 

 ● 
 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. 

 ● 
 Targeted
 therapies: 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). Further,
 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. 

 ● 
 Monoclonal
 antibodies: 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. 

 ● 
 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 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
 growth. 

 MARKET
OPPORTUNITY 

 The
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. 

 We
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. 

 14 

 Anticipated
Market Potential 

 It
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
as follows: 

 ● 
 The
 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 cancer. The developments
 performed by the companies are helping the market to grow in the coming years. 

 ● 
 The
 global market for ovarian cancer drugs expected to reach $10.1 billion by 2027, according to iHealthcareAnalyst. This will 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. 

 New
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. 

 Based
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. 

 LICENSE
AGREEMENTS 

 University
of Bath 

 We
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. 

 15 

 On
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: 

 ● 
 University
 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; 

 ● 
 The
 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; 

 ● 
 Propanc
 shall pay to University of Bath a royalty of two percent of any and all net revenues; 

 ● 
 Propanc
 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; and 

 ● 
 Propanc
 shall take out with a reputable insurance company and maintain liability insurance coverage prior to the first human trials. 

 In
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. To date, no amounts
are owed under the agreement. 

 University
of Jaén 

 We
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. 

 The
ownership of potential intellectual property rights that may arise as a result of the knowledge obtained through the project will belong
to Propanc. 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. 

 In
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. 

 A
second collaborative research project is underway with the Universities of Jaén and Granada investigating the effect of pancreatic
proenzymes against the tumor microenvironment and premetastatic niche. The specific tasks developed under this collaboration focuses
on the effects of PRP on cancer associated fibroblasts within the tumor microenvironment. Consistent with existing rights, Propanc will
own any intellectual property developed. The personnel of the investigation team of the University of Jaén and Granada whose work
has contributed to the creation of knowledge that give rise to industrial property rights should be listed as inventors. Further, Professors
Macarena Perán from the University of Jaén and Marchal from the University of Granada should receive one percent (1%) of
the net revenue to Propanc Biopharma from sales of any products sold by the contracting entity, or on behalf of the contracting entity,
which fall within the scope of protection of such industrial property rights. The commencement date for the experiments is September
1, 2022, and the estimated length of time for completion is 24 months. 

 Future
Agreements 

 We
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. 

 16 

 INTELLECTUAL
PROPERTY 

 The
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. 

 In
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 43 granted, allowed, or accepted patents and 22 patents filed, or under examination in key global jurisdictions relating to the use of proenzymes against solid
tumors, covering the lead product candidate PRP. 

 Further
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. 

 REGULATORY
MATTERS 

 United
States 

 Government
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. 

 Before
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. 

 Federal
Food, Drug and Cosmetic Act and Public Health Service Act 

 Prescription
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. 

 17 

 New
Drug Applications (“NDAs”) 

 The
FDA’s NDA approval process generally involves: 

 ● 
 Completion
 of preclinical laboratory and animal testing in compliance with the FDA’s good laboratory practice, or GLP, regulations; 

 ● 
 Submission
 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; 

 ● 
 Performance
 of adequate and well-controlled human clinical trials to establish the safety, purity and potency of the proposed product for each
 intended use; 

 ● 
 Satisfactory
 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; and 

 ● 
 Submission
 to and approval by the FDA of an NDA. 

 The
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. 

 For
purposes of an NDA submission and approval, human clinical trials are typically conducted in the following sequential phases, which may
overlap: 

 ● 
 Phase
 I: Initially conducted in a limited population to test the product candidate for safety and dose tolerance; 

 ● 
 Phase
 II: 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; 

 ● 
 Phase
 III: 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 indication. These
 studies are intended to establish the overall risk/benefit ratio of the product and provide adequate basis for product labelling;
 and 

 ● 
 Phase
 IV: 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. 

 18 

 Progress
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. 

 The
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. A Priority Review takes the FDA six months to review a NDA. 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. 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. 

 The
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. 

 Other
U.S. Regulatory Requirements 

 After
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. 

 Propanc,
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. 

 19 

 With
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
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. 

 Changes
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. 

 Adverse
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. 

 In
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. 

 In
October 2017, we submitted a request for a second orphan drug designation for PRP, this time for ovarian cancer. 

 On
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. 

 European
Union 

 In
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. 

 Under
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. 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. 

 20 

 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 effectuated on January
31, 2020. 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. 

 Australia 

 In
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. 

 Third-Party
Payor Coverage and Reimbursement 

 Although
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. 

 Eligibility
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,
development, manufacture, sale and distribution. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient
to cover costs and may not be made permanent. 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. 

 In
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. 

 The
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.
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. 

 21 

 Government
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. 

 Other
Regulations 

 We
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. 

 COMPETITION 

 The
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. 

 Many
of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical
testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Smaller or early-stage
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
programs. 

 EMPLOYEES 

 As
of September 26, 2022, we have one full-time 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. 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. 

 CORPORATE
INFORMATION 

 Our
principal executive office is located at 302, 6 Butler Street, Camberwell, VIC, 3124 Australia. 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. 

 AVAILABLE
INFORMATION 

 Copies
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. 20549. 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. 

 We
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. 

 22 

 ITEM
1A. RISK FACTORS 

 We
are not required to provide this information as we are a smaller reporting company. 

 Item
1B. Unresolved Staff Comments. 

 None.
Text extracted from the filing as submitted to EDGAR. Formatting, tables and exhibits are simplified for reading; the original document is authoritative for anything you rely on.
Propanc Biopharma, Inc. 10-K

Item 1. Business
