RMIT Classification: Trusted

Commercialisation Report

Project Identification

Working Title: RRM-Az: A unique antimicrobial peptide designed to combat drug resistance

Principal Scientist Suzana Krkic S3640279

Lab Head Assoc. Prof. Taghrid Istivan
Date of report 28/04/2023

Executive Summary (please provide a summary of the project in no more than 250 words)
Antimicrobial peptides offer a promising alternative to traditional antibiotics due to their unique
mechanism of action against microbes and potential to address antimicrobial resistance. RRM-Az,
a novel antimicrobial peptide designed using the RRM of Native Azurocidin, exhibits
antimicrobial activity against a wide range of microorganisms, including gram-positive and gram-
negative bacteria, MRSA strains, yeast, and their biofilm. Incorporation of RRM-Az into
liposomes or attachment to nanoparticles could enhance its direct delivery to the site of infection.
RRM-Az presents a versatile molecule with diverse applications beyond healthcare, such as
cosmetics, food industry preservatives, agriculture pesticides, and peptide signals in diagnostics.
The global market for antimicrobial peptides is substantial, with the urgent need for RRM-Az-like
drugs to combat antimicrobial resistance driving further growth. As such, RRM-Az represents a
highly attractive investment opportunity.

Figure 1: Schematic representation of the innovation, production, testing and commercialisation of

our product: A timeline depicting past (blue), present (green), and future (pink) steps.

Proposed next steps

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1. Testing for anti-viral, and anti-cancer activity

2. Testing for proteolytic stability and cytotoxicity.
3. Provisional patent application
4. Publishing in scientific journals
5. Acquiring a partnership with big company that can assist us in manufacturing and clinical trials
6. Investor acquisition
7. Upscaling
8. Commercialisatio

1- Science and Technology

Science Status
Describe the status of the science on which the opportunity is based.
Overuse, over-prescription, and over-reliance on antibiotics contribute to high rates of
antibiotic resistance (1), which is considered a major health crisis by WHO. By 2050,
infections caused by resistant pathogens are predicted to cost 100 trillion USD and result in
10 million deaths (1). To combat this crisis, scientists have been challenged to develop or
discover new antimicrobial compounds, with antimicrobial peptides being a promising
alternative to traditional antibiotics.
Antimicrobial peptides (AMPs) are small, cationic, amphipathic, and helical molecules
encoded by genes, also known as ribosomal antimicrobial peptides (2). They are found in
almost all forms of life, including mammals, insects, amphibians, and microbes (3), and can
be constitutively expressed or induced by infection or inflammation (4). AMPs can be
classified in various ways (5), but their strong structure-function relationship leads to the most
common classification based on their tertiary structure: alpha-helical, beta-sheet, alpha-beta,
or non-alpha beta (Figure 2) (6) Their activity is closely related to their structure, as shown
in Figure 3 (6).

A B C D

Figure 2: Structural classification of AMPs into (A) alpha helices, (B) beta-sheets, (C) alpha-
beta structure, and (D) extended structure (6).

Cationic AMPs are attracted to negatively charged microbial membrane through

electrostatic force (3). This property makes AMPs selective for microbes over mammalian cells,
due to the zwitterionic nature of eukaryotic cells, and it makes them potential candidate for
anticancer therapeutics, as cancer cells tend to adopt a negative charge (3). AMPs kill microbes
by disrupting their cell membrane and/or by targeting intracellular components (1). The
membrane disruption occurs through various mechanisms, including the toroidal pore-
forming model, the barrel/stave model, and the carpet model (Figure 3). In the toroidal pore-
forming model, the AMPs interact with the lipid membrane to form a hydrophilic ring, which
then recruits lipids and expands to form a transmembrane pore (2). The barrel/stave model
involves the aggregation of AMPs to form a barrel-like structure that spans the membrane,
whereas the carpet model involves the insertion of AMPs into the lipid membrane, leading to
its disintegration (3). These mechanisms ultimately lead to the disruption of the microbial

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membrane, causing the death of the microbe. These characteristics are true for majority of
AMPs, but not all.
Azurocidin, and therefore Azurocidin analogue, RRM-Azu, belong to the group of AMPs
that target intracellular component of microbial cells. Azurocidin inhibits microbial DNA,
RNA and protein synthesis, and activates autolytic enzymes (4). Apart from directly killing
microbes, RRM-Azu can protect the body from harsh inflammatory response and aid wound
healing (5). These immunomodulatory properties of RRM-Azu make the peptide attractive to
developers because these properties further broaden the peptides mode of action and area of
application.

1a 2a

1b 2b

1c 2c

Figure 3: Mode of action of AMPs is guided by their structure: 1: Carpet-like mechanism in which
AMPs accumulate on membrane surface (1a). Peptides are bound electrostatically to the surface of microbial membrane in
carpet-like manner, so that hydrophobic groups (black) face the membrane, and polar groups (red) face the water molecules.
When AMPs reach critical mass, interaction between hydrophobic groups of the peptide with inner bilayer of the membrane
causes the membrane to fold in on itself, thus forming micelle-like structures (1b). Micelle formation resembles action of
detergents, therefore this mechanism is also known as detergent-like mechanism; 2: Pore forming models in which AMPs
are electrostatically attracted to microbial membrane. When near the membrane, AMPs adopt rigid alpha-helical and
amphipathic conformation (2a). Interaction between hydrophobic groups of the peptide and inner lipid bilayer of the
membrane causes the lipid moieties to fold inward, forming a continuous channel, or toroidal pore (2b). Barrel/stave model:
the peptide monomers are arranged parallel to the phospholipids of the membrane. Hydrophobic side of the peptide are in
contact with the lipid bilayer, while hydrophilic residues are facing inwards, thus effectively forming a hydrophilic
transmembrane channel (2c) (6).
The peptide of our invention is designed using resonant recognition modelling (RRM)(6).

ProtParam (http://au.expasy.org/tools/protparam.html) was used as a tool to compute physical and chemical

parameters of the synthetic Azu-RRM peptide analogue. This computationally designed peptide (18 mer long) is
4.4358 kDa; theoretical pI: 6.00; estimated half-life in mammalian reticulocytes: 5.5 h; and instability index: 16.84
which classifies the protein as stable [

2- Prior Art , Patentability, and Freedom to Operate

List any patents or articles found in this search and briefly describe how they would impact on (i) novelty, (ii) non-obviousness, and/or (iii)
the freedom to operate of ourselves and/or our partners.

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Our invention is a synthetic antimicrobial peptide RRM-Azu, an analogue of native human defence peptide (HDP)
Azurocidin. RRM-Az is a unique invention that has great potential for commercialisation in various applications,
such as food additive, cosmetic product, therapeutic agent for coating and preventing infections in medical devices
and treating common and antibiotic-resistant infections.
Application for patent would include amino acid sequence of the RRM-Azu peptide, application of the peptide in
food, agriculture, beauty and cosmetics, and healthcare industries, delivery of the peptide to the site if infection via
liposomes and/or nanoparticles, and any other use of the peptide such as aerosol in disinfectant cleaning products.
Patent search was performed using terms “antimicrobial peptides”, “azurocidin”, “Heparin binding protein’,
“liposomes AND antimicrobial peptides”, “nanoparticles AND antimicrobial peptides”. This search has returned
over 5000 results, of which majority are only patent applications, rather than granted patents.
There were not many granted patents for antimicrobial peptide therapeutic. Patents granted to antimicrobial
peptides are usually specific for presence of amino acids, peptide modifications, type of bond used to link peptide to
the delivery moiety etc. Although most patented invention seem to undermine our invention’s innovation, closer look
at these products reinforces uniqueness of our invention. There are no patents for Azurocidine analogues designed by
RRM. Patented inventions that are like ours are listed in Table 1.
The most similar product to our peptide is a Azurocidin analogue designed by Kasus-Jacobi et al., (7). The
synthetic peptides are short homologues of amino acid sequences thought to encode active sites of Azurocidin. Some
of these short synthetic peptides have antimicrobial properties against gram negative bacteria comparable to
antimicrobial activity of the native Azurocidin (2). These peptides resemble Azurocidin active site and therefore they
resemble our peptide. Having a patented peptide with structure, and by default, function that closely resembles ours
may have negative impact on novelty and freedom to operate of our invention. Fortunately, no patent exists for their
product, and its possible they did not pursue a patent due to concerns about our invention’s impact on their own
freedom to operate and innovation.
RRM-Az, like most antimicrobial peptides, is most likely susceptible to proteolytic degradation in serum, blood,
and saliva (8). Modification of amino acid sequence of the peptide is a common method of increasing proteolytic
stability (8).Due to its unique sequence that in its entirety folds into tertiary structure of Azurocidin active site, any
attempted modification of amino acid sequence resulted in peptide’s loss of structure (9). Instead of amino acid
modifications, our team is considering the use of nanoparticles and liposomes as delivery vehicles for the peptide (10).
A search of the patent database revealed the existence of 30 pages of filed patents related to nanoparticles, and 11
pages related to liposomes. These patents predominantly concern the methods of packaging drugs into liposomes or
nanoparticles, or specific antimicrobial peptides packaged into these delivery vehicles. Notably, no filed patents were
found for the attachment of Azurocidine analogues to nanoparticles or liposomes loaded with antimicrobial peptides.
The majority of patents regarding liposomes and nanoparticles pertain to packaging of AMPs, potentially impacting
our freedom to operate. Developing a novel approach to liposome loading and/or nanoparticle attachment can
mitigate these issues. Alternatively, collaboration with the patent holder or acquisition of the formulation rights may
be necessary.

Table 1: Patents that may impact the inventions innovation, non-obviousness and freedom to operate
Third Party Patents/ Publications Relevance/Impact
(Authors, Assignee, Title, Reference)
Kasus‐Jacobi A, Noor‐Mohammadi S, Kasus-Jacobi, et al. developed synthetic peptides based on the amino
Griffith GL, Hinsley H, Mathias L, Pereira acid sequences present in the native Azurocidin peptide(7). They have
HA. A multifunctional peptide based on the found strong antimicrobial activity against gram negative bacteria in
neutrophil immune defense molecule, peptides based on amino acid sequence of some of these regions. This
CAP37, has antibacterial and wound‐ synthetic peptide analogue could have presented significant challenge to
healing properties. Journal of leukocyte the novelty and freedom to operate of our invention, as it poses a strong
biology. 2015;97(2):341-50. potential for direct competition. However, it is fortuitous to note that no
patent has been granted for the Azurocidin analogues in question. It is
plausible that the authors may have refrained from pursuing such
protection, potentially due to concerns regarding the negative impact
our peptide could have on their patentability and freedom to operate.
Malmsten, Martin This invention is a novel peptide derived from human Azurocidine
Schmidtchen, Artur; Pergamum AB; AU; peptide. As an analogue of Azurocidin that possesses heparin binding
2005; activity, this invention could potentially affect our invention’s novelty, as
Novel antimicrobial peptide with heparin both our peptide and this peptide are based on the same parent peptide
binding activity and as such share functional traits. Due to unique design of our peptide,
we can be confident that this invention does not affect our invention’s

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freedom to operate. Novelty and non-obviousness are not affected

because peptide designs are based on different premises.
These competing peptides do not impact the novelty, uniqueness, or
O'Neil, Deborah; freedom to operate of our invention, as they are based on alpha helical,
NovaBiotics Limited, UK. cationic and amphipathic structure that differs greatly from the
structure of our peptide.
Patent granted 2006.
.
Cyclic antimicrobial peptides (11).

Zheng, Jie ; Knolhoff, Ann Marie ; Brown,

Eric Wayne ; Croley, Timothy Ray;
Department of Health and Human Services,
USA
Patent granted 2015.
Antimicrobial peptides, pharmaceutical
compositions, and methods of use thereof
(12).

Cherkasov, Artem ; Hilpert, Kai ; Hancock,

Robert E. W. ; Fjell, Christopher; The
University of British Columbia, Canada.
Patent granted 2007.
Small Cationic antimicrobial peptides (13)

O'Neil, Deborah; NovaBiotics Limited; UK.

Patent granted 2005.
Antimicrobial peptides comprising an
arginine- and/or lysine-containing motif
(14).

Walensky, Loren D. ; Mourtada, Rida; This peptide is like the peptide of our invention in that they are both
Dana-Farber Cancer Institute, Inc; USA. acting on intracellular component of microbes. This can impact
Patent granted 2017. uniqueness of our invention, however due to different mode of entry
into the cell adopted by the two peptides, freedom to operate and
Stapled intracellular-targeting antimicrobial novelty of our invention are not affected by this patent.
peptides to treat infection (15).

Bachnoff, Niv ; Cohen-Kutner, Moshe The Cecropin family of peptides exhibits cationic and alpha helical
properties, and serves as a potential competitor to our invention as an
Omnix Medical Ltd., Israel.
antimicrobial agent. However, it is important to note that this peptide
Patent granted 2016. differs structurally from our own, and originates from a distinct animal
Antimicrobial peptides (16). kingdom. As a result, there exists sufficient dissimilarity between the two
peptides such that our invention's novelty, uniqueness, and freedom to
operate remain unaffected.
The invention at hand concerns a dimer featuring a connecting bubble
region, with a focus on combating antibiotic-resistant pathogens.
Jaynes, Jesse ; Clemens, L. Edward ; Lopez,
Although the application of this invention competes with our own, the
Henry W. ; Martin, George R. ; Woodburn, unique structure of our peptide remains unaffected, as the competing
Kathryn; Riptide Bioscience, Inc; USA. invention's structure differs significantly. As a result, our innovation and
Patent granted 2016. freedom to operate remain intact.

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Antimicrobial peptides and methods of use

thereof (17).

The use of PLA-PED copolymer nanoparticles for drug delivery to

infection sites represents a promising approach for antimicrobial and
Bazile, Didier ; Couvreur, Patrick ;
anti-cancer treatment, particularly when used in combination with
Lakkireddy, Harivardhan Reddy ; antimicrobial peptides. However, without the development of an
Mackiewicz, Nicolas ; Nicolas, Julien; alternative approach, the implementation of these nanoparticles would
Sanofi, France. impact our freedom to operate. To utilize this technology, collaboration
with the inventors or acquisition of their technology rights would be
Patent gr.anted 2013 necessary. It is important to note that the novelty and uniqueness of our
product remain unaffected..
Functional PLA-PEG copolymers, the
nanoparticles thereof, their preparation and
use for targeted drug delivery and imaging

Peptides modified to methyl esters, ethyl esters or amide forms, packed

Chakrabarti, Ajoy ; Clark-Lewis, Ian ; into liposomes for targeted drug delivery. No impact in novelty,
uniqueness or freedom to operate for our invention.
Cullis, Pieter R.; Transave, Inc.; CA.
Patent expired 2011.

Accumulation of amino acids and peptides

into liposomes (18)

Richter, Yoram ; Zelig, Yehuda ; The development of uniformly sized liposomes for
Elmalak, Omar ; Eyal, Dror; Zuli delivering compounds to phagocytes requires collaboration
Holdings Ltd.; Israel. with the inventors or acquisition of formulation rights.
Patent granted 2013. Without an alternative method developed by our team, our
freedom to operate is affected by this technology,
Liposome formulation and specifically in terms of liposome production. It is important
manufacture(19) to note, however, that this invention does not impact the
uniqueness or innovation of our product.
Sichuan University; name of Liposome of the invention loads AMP of specific amino
inventor in Chinese; acid sequence via N-coupling to liposome, together with
Granted 2020; classical antibiotic, and delivers them to the site of infection.
Ideal for drug targeting MRSA.
Antibacterial peptide modified drug- The peptide in question is hydrophobically modified AMP.
loaded liposome and preparation Since our invention cannot be modified this invention has
and application thereof no effect on our invention’s innovation, non-obviousness
and freedom to operate.
Evaluation
Give an evaluation of the University/Inventor()/ Creator(s) proprietary position
How many competitors use my technology
Can I patent my product
3- Commercial Evaluation
Commercial Rationale
Describe the commercial rationale for the opportunity including potential markets, i.e. what useful
application(s) we believe it could lead to and why we think industrial partners would be interested
in this.
Identify the key assumptions in this rationale.
The rising incidence of antimicrobial resistance is expected to provide lucrative growth
opportunities for the peptide antibiotics market (20). Large companies are reluctant to invest in new

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antibiotic development (21) due to high production and development value compared to low
returns over the life of patent. Some countries have offered extended patent life of extra 5 years,
and subsidised Phase III trials in order to motivate development of new antibiotics(22).

The antimicrobial peptides market is currently valued at 4.7 billion dollars globally. It is projected
that by 2030, revenue will increase to US 8 billion dollars with an estimated compound annual
growth rate (CAGR) of 5% between 2023 and 2029. The fastest growing market during the
forecast years is in the Asia-Pacific region (23). The synthetic peptide, RRM-Azu, exhibits extensive
potential across various industries, as indicated in Table 2. However, the prime function of this
peptide remains that of an antimicrobial agent, upon which its diversified applications are based.
Ideally, the peptide utilization lies in its injectable form as an antibiotic. Unfortunately, for oral or
intravenous administration to be feasible, significant limitations posed by synthetic antimicrobial
peptides need to be addressed. These limitations include the peptide's cytotoxicity towards
eukaryotic cells, susceptibility to proteolytic degradation, serum instability, brief half-life, and the
likelihood of peptide-induced allergic reactions (24). Due to unique design, it is not possible to
modify RRM-Azu peptide by addition of deletion of amino acid residues (9). According to Istivan
(19), any such attempts at modification resulted in the loss of structural integrity. While this
characteristic gives our invention creative and innovative edge, it could mean they we might lose
out on the highest share of antimicrobial peptide market, that of injectable antibiotics.

The 2021 global market size for diabetic foot ulcer treatment was USD 4.67 billion, with an
expected CAGR of 5.9% from 2022 to 2030. Diabetes affects around 537 million adults globally in
2021 and is projected to increase to 643 million by 2030 and 783 million by 2045 (23) RRM-Az, a
small molecule that can be absorbed through the skin and packaged into a bio-dressing, is an ideal
candidate for treating diabetic foot ulcers. Partnering with a high-end medical products
manufacturer such as CSL Behring could result in mutual benefits through incorporation of RRM-
Azu to enhance product efficacy in treating diabetic foot ulcers. The partnership could also result in
development of novel delivery systems for RRM-Az and methods for peptide synthesis, purification
and clinical trial evaluation. This would enable my team to contribute the peptides to the
partnership while leveraging the expertise of CSL Limited in medical research and development.

Global burn ointment market valued at USD 813.7 million in 2019, expected to grow at a CAGR
of 6.1% from 2020-2027. Topical antibiotics segment had the largest market share of 34.7% in
2019 and is predicted to have significant growth (23). RRM-Az is an ideal candidate for treating
burns, as it can be applied topically and can be incorporated into wound dressings and burn
ointments. The clinical use of antimicrobial peptides (AMPs) for treating burns is exemplified by the
FDA-approved Polymyxin B drug, which has successfully completed Phase III clinical trials. In this
context, collaboration with companies specializing in bio-engineered dressings such as PolyNovo,
which has already developed a product for treating burn patients, could yield benefits. Combining
PolyNovo's NovoSorb BMT with RRM-Az could improve the prospects of recovery from full-
thickness wound infections caused by P. aeruginosa in burn patients.

Table 2: Potential applications of synthetic RRM-Azu peptide across industries

INDUSTRY APPLICATION DETAILS
Beauty and cosmetics Rejuvenating cream/serum Peptide included in ointment to
promote healing after cosmetic
procedure or as a daily application.
Antimicrobial additive Acne treatment.

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Food Industry Preservatives As additives to perishable food or as a

coating of containers used to pack
preserved foods, like jams or
precooked meals.
Hospital Coating on medical devices Coating of medical devices by AMPs
prevents biofilm formation and
decreases incidence of infection
implant recipients and/or cathedra
uses.
Health Intravenous antibiotics, Topical treatment of burns and
Wound/Burns treatment, infections.
HAI/SSI. Treatment of surgical site infections.
AMPs incorporated into wound
dressings and ointments.

The medical biomimetics market is projected to reach a value of USD 31.07 billion in 2022,
with a forecasted revenue of USD 52.2 billion by 2030, exhibiting a compound annual growth
rate (CAGR) of 6.7% from 2022 to 2030. The applications of medical biomimetics include
wound healing, tissue engineering, drug delivery, and diagnostics. In particular, antimicrobial
peptides (AMPs) can be utilized in conjunction with drug delivery systems for wound healing and
diagnostics. In the realm of diagnostics, AMPs can serve as a biomarker. When labeled or tagged,
AMPs are attracted to the site of infection by negatively charged microbes, thereby aiding in the
identification and localization of the infection site.

In 2019, the Surgical Site Infections (SSIs) segment dominated the market for HAIs
therapeutics and held the largest revenue share of 31.8% due to the rising number of surgical
procedures and subsequent rising cases of SSIs. SSIs affect as many as 300,000 patients in the
U.S. every year. Such types of infections tend to increase the hospitalization by 7 to 10 days and
the hospitalization cost by USD 3,000. The antibacterial drugs segment dominated the market
for HAIs therapeutics and accounted for the largest revenue share of 87.3% in 2019. antibacterial
therapy is the first line of treatment for any type of hospital-acquired infection.
Some key players operating in the HAI therapeutics market include Merck & Co., Inc.; Pfizer
Inc.; Bayer AG; GlaxoSmithKline Plc.; Daiichi Sankyo Company, Limited.
According to recent market research, the skin infection segment has been identified as the
largest revenue contributor, accounting for 30.3% in 2021 and is expected to maintain its
dominance throughout the forecast period. The growth of this segment can be attributed to the
increasing prevalence of skin infections such as cellulitis, impetigo, furuncles, and carbuncles,
among others. The availability of a wide range of products for the treatment of bacterial skin
infections has also contributed to the growth of this segment. For example, Merck & Co., Inc.
manufactures CUBICIN RF (daptomycin for injection), which is a lipopeptide product used for
treating complicated skin and skin structure infections caused by S. aureus, S.pyrogenes, and S.
agalactiae, in both paediatric patients and adults.Some key company in this market are: Johnson &
Johnson Private Limited (U.S), Merck & Co., Inc. (U.S), Alexion Pharmaceuticals, Inc. (U.S).

The RRM-Az product has multiple applications, and one of its significant advantages for our
team is having Irena Cosic, the developer of RRM technology, on board. Although RRM
technology is accessible for all, its optimal use requires specialized knowledge, and having Irena
on the team ensures the best utilization of RRM and the development of unique and innovative
peptides. This is a big advantage, and in the market in which only 3 of 3000 peptides
areapproved by the FDA, any advantage is welcome.

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Competition
Summarise products in development by companies that are technically the same or are based on a the same scientific rationale
Product and Company References Product details and specifications, Development stage

Dalvance; Allergan Pic (AbbVie Inc.) Approved by the FDA for therapeutic use, Dalvance is AMP infusion
administered via IV route. It is used for treatment of various skin infections
Polymyxin B; Xellia Polymyxin is used for the treatment of blood-stream infections
PHARMACEUTICALS due to strains such as, E.coli, Pseudomonas aeruginosa, H. influenza.
Vancomycin hydrochloride; Pfizer Inc.
This peptide is given by IV infusion for the treatment of severe
infections caused by susceptible strains of methicillin-resistant
staphylococci.
Cubicin RF; Merc & Co.
Cubicin is a type of lipo-peptide product that is used for the
treatment of paediatric patients and adults with complicated skin
and skin structure infections caused by S. aureus, S.pyrogenes, S.
agalactiae.
Daptomycin; AuroMedics Pharma manufacture Daptomycin for an injection.
LLC
Summary of Competitive Position
What technical and commercial advantage does the opportunity have over the competing technologies?
(outline any risks and proposed risk management options)
Our invention is based on a peptide design that utilizes the native Azurocidin AMP as a foundation
through the utilization of Resonant Recognition Modelling (RRM).
The unique design of our product provides both commercial and therapeutic advantages.
Typically, synthetic AMPs require modifications to enhance stability and bioavailability. Our
peptide is exceptionally short, enabling increased bioavailability via enhanced skin penetration,
higher stability, and lower production costs. Any competing product, particularly a peptide
analogue of Azurocidin, will be at a disadvantage due to its size, as our entire peptide is a functional
group of Azurocidin, making it likely the shortest possible analogue.
Due to its similarity in structure and function to the native parent peptide, our peptide is less likely
to induce allergic reactions in human patients as it is perceived and accepted by the human body as
its own.
Our peptide’s antimicrobial activity involves inhibition of DNA, RNA and protein biosynthesis,
inhibition of biosynthesis of lipid II in peptidoglycan, and activation of lytic enzymes (2). Due to this
diverse and multi-faceted mode of action, our peptide is less likely to induce resistance in microbes
than antibiotics that have one specific target.
RRM-Azu was testen by my team and is found to have antimicrobial effect against all test
organisms compared to control (23,24). Notably, our peptide has been found to be potentially
effective against MRSA 344 (25). These findings suggest the potential for our peptides to be
effective antimicrobial agents against common and drug resistant pathogens. Peptide’s effectiveness
against drug resistant bacteria provides the competitive and market edge, while its unique design
acts as protection against intellectual property theft and copying.
.

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References:

1. Spindler EC, Hale JDF, Giddings Jr TH, Hancock REW, Gill RT. Deciphering the Mode of
Action of the Synthetic Antimicrobial Peptide Bac8c. Antimicrobial Agents and Chemotherapy.
2011;55(4):1706-16.
2. Tuerkova A, Kebelka, I., Kralova, T., Sukenik, L., Sarka, P., Hof, M., Vacha, R. Effect of
Helical Kink in Antimicrobial Peptides on Membrane Pore Formation. Department of Oharmaceuticsl
Chemistry. 2020.
3. Zhou M, Zheng, M., & Cai, J. Small Molecules with Membrane-Active Antimicrobial Activity.
ACS Applied Material and Interfaces. 2020;12.
4. Le C-F, Fang C-M, Sekaran SD. Intracellular Targeting Mechanisms by Antimicrobial Peptides.
Antimicrobial Agents and Chemotherapy. 2017;61(4):e02340-16.
5. Jenssen H, Hamill P, Hancock REW. Peptide Antimicrobial Agents. Clinical Microbiology
Reviews. 2006;19(3):491-511.
6. Cosic I, Hodder AN, Aguilar M-I, Hearn MTW. Resonant recognition model and protein
topography. Model studies with myoglobin, hemoglobin and lysozyme. European Journal of
Biochemistry. 1991;198(1):113-9.
7. Kasus‐Jacobi A, Noor‐Mohammadi S, Griffith GL, Hinsley H, Mathias L, Pereira HA. A
multifunctional peptide based on the neutrophil immune defense molecule, CAP37, has antibacterial
and wound‐healing properties. Journal of leukocyte biology. 2015;97(2):341-50.
8. Boöttger R, Hoffmann R, Knappe D. Differential stability of therapeutic peptides with different
proteolytic cleavage sites in blood, plasma and serum. PloS one. 2017;12(6):e0178943-e.
9. Istivan T. Modification of RRM-Azu. In: Krkic S, editor. 2023.
10. Istivan T. Potential delivery methods for the peptide. In: krkic s, editor. email ed2023.
11. O'Neil D. CYCLIC ANTIMICROBIAL PEPTIDES. 2016.
12. Croley TR, Zheng J, Brown EW, Knolhoff AM. Antimicrobial peptides, pharmaceutical
compositions, and methods of use thereof. 2021.
13. Hancock REW, Hilpert KAI, Fjell C, Cherkasov A. SMALL CATIONIC ANTIMICROBIAL
PEPTIDES. 2016.
14. O'Neil D. ANTIMICROBIAL PEPTIDES COMPRISING AN ARGININE- AND/OR LYSINE-
CONTAINING MOTIF. 2011.
15. Walensky LD, Mourtada R. Stapled intracellular-targeting antimicrobial peptides to treat
infection. 2022.
16. Bachnoff N, Cohen-Kutner M. Antimicrobial peptides. 2021.
17. Woodburn K, Lopez HW, Clemens EL, Martin GR, Jaynes J. ANTIMICROBIAL PEPTIDES
AND METHODS OF USE THEREOF. 2022.
18. Cullis PR, Chakrabarti A, Clark-Lewis IAN. ACCUMULATION OF AMINO ACIDS AND
PEPTIDES INTO LIPOSOMES. 6 ed1996.
19. Richter Y, Eyal D, Zelig Y, Elmalak O. Liposome formulation and manufacture. 2017.
20. CDC. Centre for Disease Control and Prevention 2023 [Available from: www.cdc.gov
.
21. Wenzel RP. The Antibiotic Pipeline — Challenges, Costs, and Values. The New England
journal of medicine. 2004;351(6):523-6.
22. Cooper MA, Shlaes D. Fix the antibiotics pipeline. Nature (London). 2011;472(7341):32-.
23. Research DBM. Global Antimicrobial Peptides Market - Industry Trends and Forecast to 2029.
Web Page. 2023.
24. Bradshaw JP. Cationic Antimicrobial Peptides. BioDrugs. 2003;17(4):233-40.

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25. Krkic S. Effects of RRM-Az18 and RRM-Az35 against S.aureus 25923 and P.aeruginosa
27853. . Laboratory note book ed2023.

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