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Item 1. Business

2023-09-28 compared with 2022-09-28 · 483 added, 473 removed, 463 unchanged (67% 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 on Form 10-K, 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.

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

10-K 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”

In this Annual Report on Form 10-K, references to “$” and “dollars”

are to United States dollars.

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.

are 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.

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

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

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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

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.

we plan to begin our Investigational Medicinal Product Dossier, study proposal and Investigator’s Brochure in 2023.

to then commence our study preparation process with the contract research organization (“CRO”), analytical lab and trial

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

2023 and complete the CTA compilation and submit the CTA in the second half of the 2023 calendar year.

In the fourth calendar 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 first half of the 2024 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.

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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.

Food and Drug Administration (“FDA”) in June 2017 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.

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

back” benefit from overseas research and development (“R&D”) expenses.

The finding relates to the planned Phase

Ib 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 Cancer Centre, Melbourne, Australia.

Overseas activities to be undertaken

include the development of an analytical assay for the quantification of active pharmaceutical ingredients (“API”) in PRP

and its manufacture of the finished product for the Phase Ib clinical trial.

POP1 joint research and drug discovery program (“POP1 Program”) is designed to produce a backup clinical compound to 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.

lots and without sourcing the proenzymes from animals, we are undertaking a 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,

which is 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

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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.

therapy induces the cancer cells into the pathway of terminal differentiation and eventual senescence ( i.e.

, a non-proliferative

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.

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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.

Since then, several scientists have endorsed Professor 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

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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.

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

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.

treatment affects the Transforming Growth Factor Beta (“TGFβ”) pathway, a significant tumor promoter in late-stage cancer

by inducing tumor cell migration and stimulating the EMT program.

The likely molecular targets are proteinase-activated-receptors (“PAR”)

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

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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.

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

the 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 yes-associated protein (YAP), which sequesters B-catenin in the cytoplasm,

blocking the canonical Wnt pathway and inhibiting the Notch pathway.

This 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

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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.

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.

Vivo Efficacy of PRP In Pancreatic and Ovarian Tumors

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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 .

in the context of a UK Pharmaceuticals Special Scheme at the Dove Clinic in Hampshire, UK by Dr.

Julian Kenyon, the Company’s Chief

Scientific Officer, and the results were published by the Company in a peer-reviewed journal, Scientific Reports, on behalf of Dr.

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.

Patients were treated daily with a rectal formulation containing 8.92 mg of each of the two pancreatic pro-enzymes and 1.78 mg α-Amylase

(A) per suppository.

The study was carried out under a UK “Specials” License at the Dove Clinic, Hampshire, UK for periods

up to 14 months.

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

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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.

19 of 46 patients (41.3%) with advanced malignant diseases, most of them suffering

from metastases, had a survival time significantly longer than 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

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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.

Consequently, we believe that 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)

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unknown primary (n = 1)

of clinical studies.

overview of clinical results.

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).

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 (analysis of variance) (α

= 0.05, P < 0.05).

Joint Research And Drug Discovery Program

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

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.

purification and yield of chymotrypsinogen is currently the focus of research.

POP1 Program is designed to produce a backup clinical compound to PRP, which is targeting metastatic cancer from solid tumors.

to an Emergen Research report published in January 2022, the global metastatic cancer market is projected to reach $111 billion by 2027.

date, recombinant trypsinogen and chymotrypsinogen have been 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.

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.

capitalize on the new therapeutic approach to treating cancer that PRP offers to 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 in Vienna, Austria, and are working towards full scale manufacture

of a synthetic recombinant formulation to PRP.

Target Indications

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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.

While the hope is that 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

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

to respond to treatment adequately, or the treatment has unacceptable toxicity that 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

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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,

the near-term and 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 have 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.

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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 is one of the most lethal malignancies with a median survival of less than six months and a five-year survival rate of less than

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

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

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.

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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).

of patients with pancreatic cancer depends on the extend of disease at the time of diagnosis and ranges from 11 to 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 two

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

Taking these low survival times into consideration,

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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.

In 2020, it was estimated that a total of more than 1,806,590 new cancer cases and more than 606,520 cancer deaths occurred

in the United States according to the National Cancer Institute.

Amongst these, a total of almost 50,000 new cases of pancreatic cancer

(3.2% of new cancer cases) were estimated, which resulted in more than 40,000 deaths (8.2% 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

Epithelial ovarian cancer accounts for approximately

90% 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;

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 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;

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

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 $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.

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.

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

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.

Trial Application (CTA)

‘22 - Apr ‘23

Investigational

Medicinal Product Dossier

Ib Clinical Study Protocol

Investigator’s

‘23 – Jul ‘23

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.

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.

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).

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.

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.

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.

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.

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.

2020, ovarian cancer is the eighth most diagnosed cancer among women in the world and accounts for an estimated 313,959 new cases and

207,252 deaths worldwide (World Cancer Research Fund International)., In the USA, 19,880 new cases (2015 – 2019) and 12,810 related

deaths (2016 – 2020) are estimated to occur (National Cancer Institute).

The disease typically presents at late stage when the

five-year relative survival rate is only 29%.

Few cases (15%) are diagnosed with localized tumor (stage 1), when the five-year survival

Strikingly, the overall five-year relative survival rate generally ranges between 30% to 40% across the globe and has seen

only very modest increases since 1995.

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

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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.

progress has been made within the oncology sector in developing new treatments, the overall cancer death rate has only improved by fifteen

percent over the last 30 years.

This is attributed to a reduction in smoking and an increase in 5-year survival rates for cancers.

of these new treatments have some limitations, such as:

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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).

Common side effects include fatigue, rash, hand-foot reaction, diarrhea, hypertension and dyspnea (shortness of breath).

tyrosine kinases inhibited by these drugs appear to develop resistance to inhibitors.

17 unchanged sentences

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.

Development Strategy

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

of the 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.

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 intend to:

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;

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 intellectual property or products that complement our future goals.

Development Plan and Milestones

plan to progress PRP using a conventional early-stage clinical development pathway, which entails:

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

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

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

method development.

The full-scale good manufacturing practice (“GMP”) 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 CTA,

which we plan to undertake at the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia’s largest cancer hospital.

are collaborating with CROs, manufacturing partners and consultants to complete activities prior to preparing the CTA for the Phase Ib

have 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.

We believe that the evaluation will most likely be conducted

as separate Phase IIa proof of concept, multi-trial center studies for each target indication.

The expressions of interest were confirmed

after their evaluation of our scientific literature supporting the use of proenzymes in pancreatic and ovarian cancers.

The Phase Iia

proof of concept 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 MacCallum Cancer Centre.

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

costs and expenses.

We received a refund of $192,872 AUD ($129,841) and $75,800 AUD ($ 54,977

USD) for the years ended June 30, 2023 and 2022, 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

US, Europe and Australia, and the results from our R&D 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.

fourth calendar quarter of 2023, we anticipate the submission of the CTA for PRP.

We anticipate receiving approval of the CTA in the

second half of the 2023 calendar year.

Following the CTA, we plan to commence our study preparation process, including CRO Selection

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

In connection with the CTA, this product will

be part of our Investigation Medicinal Product Dossier, study protocol and Investigator’s Brochure.

In the second half of the 2023

calendar year, we hope to complete the study preparation process together with the Preparation of Logistics and Trial Sites Initiation

Visits and complete our CTA review.

Commencing in the first half of the 2024 calendar year, we intend to initiate a Phase Ib study in

advanced cancer patients with solid tumors and we anticipate costs to 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.

2023 – February 2024

Investigational

Medicinal Product Dossier

Ib Clinical Study Protocol

Investigator’s

2023 – February 2024

2023 – April 2024

Research Organization and Contracts

2023 – February 2024

Laboratory Selection and Contracts

Site Selection and Contracts

2024 – June 2024

Site Initiation Visits

Patient/First Visit

Joint Research And Drug Discovery Program

POP1 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.

POP1 Program has produced synthetic recombinant versions of the two proenzymes, trypsinogen and chymotrypsinogen.

Our 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.

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 R&D 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

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

We intend to carefully introduce

new personnel into our Company over time as our R&D activities expand.

We plan for such personnel to 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).

Additional clinical management and development expertise will likely

be required at the outset to assist with the development of PRP.

Therefore, we anticipate hiring additional employees in order to effectively

manage our contractors as our development activities progress.