Overview


Chemotherapeutic agents are known to have side effects due to significant off-site targeting. We intend to develop Duonco, a drug delivery system that minimises the off-site targeting effect of the chemotherapeutic agent. Currently, we are developing the system for use in HER2-positive breast cancer cases; however, we hope to extend this to other types of cancer by changing the targeting epitopes on the surface of the OMVs. We also see great potential for Duonco in personalised medicine, wherein novel epitopes specific to the patient can be expressed on the OMVs and used for drug delivery. To achieve these broader goals for the project, we have outlined a detailed plan of further experiments before moving forward to animal and clinical trials. We also drew the roadmap for the industrial production and market analysis of Duonco.


Prodrug-Enzyme System


An essential component of our project is using the prodrug enzyme system integrated within the dual OMV system. The prodrug-enzyme system allows for an additional check point of specificity, wherein only when the two types of OMVs are internalised by a single cell expressing both types of cell surface receptors will the conversion of the prodrug to its active cytotoxic form occur. In the absence of simultaneous double internalisation, significant cytotoxic activity will not be observed. There are numerous prodrug and enzyme combinations available in the market at present. However, selecting the best combination is a laborious process. Several safety aspects and other challenges need to be taken into consideration while selecting the optimal combination, such as [1]:

  • The half-life of the prodrug (before and after it is activated): We would want our active drug to have a short half-life so that it would not escape from the site of the tumour and invade the normal tissues killing the normal cells. This depends on the enzyme kinetics and how long it takes for both the OMVs to reach the tumour site. As many prodrugs are alkylating agents and they are well known for their mutagenic and carcinogenic properties, so it is best to restrict their action by localising it to the tumour tissue.

  • The half-life of the enzyme: Our enzyme should stay active long enough to allow for the entry of the prodrug into the cell. If the enzyme were to degrade way before the prodrug enters the cells, the purpose of the prodrug-enzyme system would be defeated.

  • Time for OMVs to reach our target tissue: The time taken for the OMVs to reach the tumour site should be longer than 10 minutes. This is primarily because the half-life of the enzyme that we would be selecting would be between 10-20 minutes. Also, the longer the OMVs stay in the bloodstream the higher the chances of them being attacked by the immune system and giving rise to inflammatory responses in non-target tissues.

  • Off-site targets of the enzyme and prodrug: The enzyme we plan on using should have very high specificity for our prodrug and minimal interactions with other proteins present in the cells. If a specific enzyme has an inherent negative interaction with components of the mammalian cell, this will lead to adverse effects even in the absence of the prodrug.

  • Bystander effect of the activated drug: Many drugs tend to diffuse outside of the cells into the extracellular matrix of the tissue and tend to affect other cells. While selecting a prodrug, we should keep in mind that the bystander effect and the diffusion of this activated drug into the extracellular matrix is minimum.

  • Enzyme kinetics and its origin: The origin of enzymes is very important because a human enzyme is likely nonimmunogenic. However, if it is a non-mammalian enzyme with no human analogue, then it would have the benefit of being more specific but would be immunogenic, which would limit the repeated use due to host response. Bacterial enzymes also have superior kinetics, converting the prodrug more efficiently than mammalian enzymes. However, a mutated human enzyme that would have a prodrug as its only substrate can be a long-term possibility, but the production and development of such an enzyme is a difficult task.


Our System


After doing an extensive survey on the widely used prodrug-enzyme combinations taking into consideration all of the above factors, we have come to a conclusion that the perfect fit as of now to our project would be the combination of 5-Fluorocytosine (5FC) and Cytosine deaminase (CD) [2][3]. Cytosine deaminase converts 5FC to 5-Fluorouracil (5FU). 5FU traverses into the neighbouring cells, hence if injected at the core of the tumour then even a small amount of the activated drug should be enough to cause a significant decrease in the size of the tumour. Also, phase 1 and phase 2 trials have been performed for this particular drug. It exerts its anticancer action through inhibition of thymidylate synthase and incorporation of its metabolites RNA and DNA.

A few side effects and safety aspects are associated with this drug, such as mucositis, myelosuppression, dermatitis and cardiac toxicity. However, due to the modular design of Duonco, we can minimise the impact of the side effects because of the increased specificity and also by optimising the drug and enzyme concentration that will be injected. These side effects occur only when the drug is active, if and only if the prodrug comes in contact with the enzyme. The half-life of the active form of the drug, i.e., 5FU, is around 10-20 minutes. This will ensure that the drug is degraded before it starts spreading into the neighbouring tissues and killing non-tumorous cells. We could also try to develop a completely new combination of prodrug and enzyme, but that would be a considerable challenge to overcome.

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Figure 1. Mechanism of 5-FU action


Loading of Prodrug and Enzyme


Before loading our OMVs with the drug and enzyme, a calibration curve would be plotted to determine the drug's concentration in a given volume. Once a standard Absorbance vs Concentration curve with a linear fit and the R^2 value are obtained. The OMVs will then be incubated/ electroporated with the drug and the enzyme. After 24 hrs of incubation, at the optimum temperature, pH and ionic concentration, centrifuge the samples at 100,000g. Remove the supernatant and check the concentration using a spectrophotometer. From this, we can get the concentration of the drug/enzyme in the pellet (OMVs) by comparison with the calibration curve. To find the IC50 value of the OMVs containing drug and enzyme, the MTT assay would be performed. Finding out the perfect vehicle for injection is another challenge; this could be overcome only by clinical trial tests[4].


Characterization of OMVs


After the production of vesicles, we would need to purify, quantify and characterise them using lipid and protein profiling in order to move forward with the rest of the phases.


Purification


One more challenge we will be facing when producing OMVs on a large scale would be their purification while maintaining safety standards. However, there are a few methods we have looked into. Purification of native OMVs is carried out by tangential flow filtration (TFF), density gradient centrifugation or gel filtration. Tangential flow filtration involves using membranes with pore sizes between 0.1 um to 10 um. The sample is fed parallelly to the membrane; this leads to particle accumulation over the membrane, and a portion of the sample to pass through the membrane. The first round separates the supernatant with OMVs from the bacteria, and the second round separates other impurities from the OMVs [5]. The second method of OMV purification is using density gradient centrifugation, wherein a gradient is created using substances such as dextran and sucrose, and the sample will be distributed in a certain specific position in the gradient during ultracentrifugation. This would allow us to obtain homogeneously sized OMVs while separating out the impurities. Gel filtration involves using molecular sieves to separate OMVs with the same protein molecular weight[6]. Employing strategies such as size exclusion chromatography and gel sieving. All these methods are in use already; however, these methods would require optimisation to meet our needs.


Protein and lipid profiling


The protein distribution in the outer membrane vs the OMVs are significantly different. Some proteins are exclusively present in OMVs, and some in the outer membrane. This is very important when considering the safety aspect of our system. This is because unwanted proteins can enter the membrane of the OMVs and might cause unnecessary problems. This preferential translocation of proteins to OMVs is thought to be due to the interaction of proteins and lipids. Techniques such as lipid chromatography, mass spectroscopy and advanced protein profiling can be employed to analyze the lipid and protein profile of OMVs. Once the profiles have been established, they can be used to check for contaminants and standardise each production run [7].


LPS content


OMVs isolated from gram-negative bacteria such as E.coli have an inherent level of LPS associated with them. LPS toxicity is a major concern because the presence of LPS in the blood or interstitial fluid can lead to several infections and side effects like inflammation, fever, leukopenia, damage to blood vessels etc., all of this majorly because of the endotoxin lipid A. The safe limit for LPS in circulation is up to 5 picogram LPS/mL of blood [8]. LPS reactogenicity can be attenuated by creating msBb and lpxl1 gene knockouts in E.coli. Upon creating the knockout strain, the Chromogenic Endotoxin Quant Kit (LAL test kit) can be used for detecting LPS toxicity and HPLC/MS for LPS quantification.


Quantification


Using NTA, the OMV samples can be observed by light scattering using a light microscope, while sequential videos are recorded, after which the NTA software tracks the Brownian motion of individual vesicles and calculates the size and concentration of our particles. Upon processing and purifying our OMV samples, we would perform a Bradford assay of the samples to determine the protein concentration. The samples are then loaded into the chamber after dilution of 1:500 or 1:1000 in 0.9% PBS. 3-5 individual videos of the 60s each are recorded for each sample. Then, the analysis is done using the NTA software. All the experiments are done at room temperature. [9]


Preclinical and Clinical Studies


Preclinical studies include drug administration as well as efficacy and safety testing. The various routes of administration must be investigated, the maximum drug dose must be determined, and the off-target effects of the drug delivery system must be monitored. Following the successful completion of the preclinical studies, we will proceed to the next phase, clinical trials, in which we will confirm the system's optimal functioning in human subjects.


Mode of Administration


The environment in which the tumour thrives creates inherent barriers to therapeutics, reducing drug efficacy. Uncontrolled drug exposure to non-tumor compartments in the patient's body can impair drug efficacy and potentially elicit toxic or immune responses. Furthermore, because intravenous administration of OMVs into the bloodstream is a potent immune response stimulator, OMVs may be phagocytosed before reaching the target tissue. As a result, localised delivery methods are preferred. As preferred options, subcutaneous, transdermal, intratumoral, and transpapillary injections should be evaluated.

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Figure 2. Challenges associated with administration of certain anti-cancer drugs


Ex-Vivo Testing


We intend to use 3D cell culture models in order to simulate physiological and pathophysiological conditions as closely as possible. Upon culturing the patient-derived xenografts to generate the spheroids, the following treatment plan would be followed [10][11].

Drug Treatment Plans:

  1. The PDX tumour spheroids would be divided into 5 different sub-groups which would be as follows:
    • PBS (vehicle) only treatment
    • Non-modified OMVs
    • Type 1 OMVs only
    • Type 2 OMVs only
    • Type 1 + Type 2 OMVs
    • Doxil treatment

  2. The spheroids from a 6-day culture would be seeded with 1000 cells/well and given the above treatments.

  3. All the experimental groups would be cultured with RPMI culture media only or with supplemented with 20% of dimethyl sulfoxide (DMSO).

  4. After 24, 48 and 72 h of treatment, the cell viability of three spheroids would be assessed using the CellTiter-Glo 3D assay.

  5. Viability was calculated according to the equation:
    ((S - PC)/(NC - PC))*100, where
    • S = Sample
    • PC = Positive control
    • NC = Negative control

  6. The prodrug-enzyme and the OMV concentrations would be based on the 2D culture experiments of MTT assay.


In-vivo Testing


Animal Trials


Animal testing will be conducted in accordance with New Drugs and Clinical Trials Rules, India 2019. Four groups of mice would be all injected with 0.2 ml/mouse of 5 * 10^6 cell/ml EMT6 breast cancer cells in the skin under the right forelimb subcutaneously. This would be used to demonstrate the safety and efficacy of the bioengineered OMVs as well as OMVs in conjugation with the prodrug-enzyme system. Potential off-target effects associated with the system will also be analysed via animal studies. [12][13][14]


Testing the efficacy of the system:
When the average size of the tumour would reach 50 mm^3, mice would be randomly divided into 5 groups to receive daily intratumoral injection of the following treatments:

  1. Vehicle control (PBS)
  2. Free drug (concentration determined from above)
  3. Type 1 and Type 2 OMVs without the drug/enzyme loaded
  4. OMV type 1 with drug loaded
  5. OMV type 2 with enzyme loaded
  6. Doxil treatment (as a positive control)

Tumours would be measured every day, and tumour volumes would be calculated from the following equation:

Tumour Volume=(L×W2)/2

Eleven days later, the mice would be subjected to dissection, and the tumours as well as the main organs would be removed for various analyses. Blood samples would also be collected for biochemical detection.


Testing the safety of the system
The animal testing would take place in two phases:

  • Phase 1: Using unloaded bioengineered OMVs
  • Phase 2: Using bioengineered OMVs loaded with the prodrug and the enzyme
Single-dose toxicity testing using mice and rodent species will be carried out. Intravenous and transdermal, to test for effects of local toxicity and to analyse the correlation between the efficacy of the delivery system and the mode of administration. Ten times the intended dosage for humans will be administered, and the models will be observed for a period of 14 days; the Minimum Lethal Dose (MLD) and Maximum Tolerated Dose (MTD) will be established. Symptoms, mode of death, effects on body weight, and gross pathological changes have to be reported.

Repeated dose toxicity testing uses two mammalian species (one rodent and one non-rodent), both being HCC1954 xenograft models, wherein the unloaded and loaded OMVs will be administered for seven continuous days. Four groups will be created to allow for different levels of doses. A control, low level (produces no observable toxicity), intermediate level (causes symptoms, but not gross toxicity or death), and the highest dose (causing observable toxicity). All four groups will be analysed for behavioural, physiological, biochemical, and microscopic effects. Upon completion of the 7-day repeated dose test, 14-, 28-, 90- and 180- day repeated dose toxicity studies will be conducted.

In addition to analysing the toxicity, off-target effects will be monitored in both single and repeated dose testing by measuring the drug concentration in the tumour vis-à-vis the plasma and other organs such as the liver, spleen, kidney etc.


Clinical Trials


In India, clinical trials are divided into 4 phases; yet again, we would perform the clinical trials in two phases[15].

  • Phase 1: Using unloaded bioengineered OMVs
  • Phase 2: Using bioengineered OMVs loaded with the prodrug and the enzyme

Human Pharmacology:
This will be a non-therapeutic trial, and we’ll aim to determine the safety of our drug, its maximum tolerated dose and the nature of adverse reactions that can be expected from it. These studies include single and multiple-dose administration and will ideally be carried out at an adequately equipped site.
In this phase, we also study pharmacokinetics and pharmacodynamics, i.e., the characterisation of a drug's absorption, distribution, metabolism and excretion by the body. Preliminary studies about the potential therapeutic benefits may also be conducted in Phase I as a secondary objective.

Therapeutic Exploratory Trials
These controlled studies will be conducted on a limited number of patients of both sexes in order to determine the therapeutic effects, effective dose range, and further evaluation of patient safety and pharmacokinetics. In general, a strict inclusion criterion is maintained for patients in order to determine effective doses; consequently, the study population will be fairly homogeneous.
Additional objectives of Phase II studies would be to include evaluation of potential study endpoints, therapeutic regimens and target populations (e.g. mild versus severe disease) for further studies in Phase II or III.

Therapeutic Confirmatory Trials:
This phase will be carried out in order to collect sufficient data on the efficacy and safety of our drug in a larger number of patients of either sex, usually in comparison to a standard drug. This is done to validate the efficacy and safety discovered in Phase II, with the goal of providing an adequate foundation for marketing approval. Phase III studies would allow us to investigate the dose-response relationship to drug concentration in blood, the clinical response of the drug in larger populations at various stages of the disease, or the safety and efficacy of the drug in combination with other drugs. These Phase III studies will provide the necessary prescribing information to support adequate drug use instructions.

Post-marketing Surveillance:
Following marketing approval, phase IV studies or post-marketing surveillance are conducted to obtain additional information about the risks and benefits of long-term drug use. To draw markers for future warnings of potential adverse events likely to occur with other drugs, the adverse events reported during Phase IV trials must be correlated with the toxicity data generated in animals. This step may not be required for marketing approval of the new drug, but the Licensing Authority may require it for optimising its use. Additional drug-drug interaction, dose-response, safety studies, and trials designed to support use under the approved indication will be included in Phase IV trials.


Limitations


We will face numerous other challenges when putting the project into action in the real world. Despite their wide range of applications and potential for targeted drug delivery, OMV isolation and purification rely on time-consuming ultracentrifugation and filtering techniques, reducing manufacturing efficiency as a biotechnological device [16]. Given the possibility of heterogeneity in the OMVs produced, strategies to optimise the production of homogeneous OMVs have yet to be developed [17]. To efficiently use OMVs for mass production, the yield of OMV production must be increased, even from hyper-vesiculating strains. OMV processing and storage conditions have yet to be optimised for therapeutic use, despite the fact that some researchers have discovered OMV stability under certain storage conditions. Drug encapsulation within OMVs may reduce the transport issues that limit the efficacy of many antibiotics against gram-negative bacteria. The standardisation of techniques for working with OMVs and their global implementation would hasten the use of OMVs for broader therapeutic advancements.


Future Directions


Though Duonco is being developed as a breast cancer drug delivery system, it is a versatile system that can be adapted for a variety of applications.

Bioreactor
We want to investigate various methods for economically mass-producing these engineered OMVs. For this purpose, we propose the creation of a bioreactor that could enhance their production. Starting with 400 mL of bacterial culture, an OMV isolation yields only 400 uL of OMV suspension with a protein concentration of 25 ug/mL. Even though the protocol ensures minimal contamination and high-quality OMVs, the net yield remains a concern. This can be circumvented by constructing a bioreactor, a more secure alternative to single-batch cultures. Minimising the number of times human intervention is required makes it possible to maintain a continuous culture with a reduced risk of contamination. Gerritzen et al. investigate this technique for increasing volumetric productivity by means of a continuous Neisseria meningitidis culture [18]. They claim that the steady state of high OMV production can be replicated and maintained for at least 600 hours. Our proposed bioreactor would be capable of handling large volumes of bacterial cultures and would incorporate a centrifuge (to gain higher speeds to isolate OMVs). Following the processing, the culture would be filtered to eliminate cell debris, proteins, and other bacterial components. The final isolated OMVs will be concentrated in the chamber to a smaller volume. This type of mechanism reduces human contact and protects against accidental exposure. 

Increasing specificity:
Duonco is currently being developed as a dual targeting system; however, it can be expanded in the future to have multiple antigens expressed on the surface and segment the drug into various types of vesicles to provide greater control over drug delivery.

Co-Encapsulation:
Drug cocktails can be loaded inside vesicles to increase intracellular drug concentration and ensure drug synergy for maximum therapeutic effects; the formulation can be developed on a patient-by-patient basis.

Expanding to other cancers:
Duonco's modular design enables it to be expanded to treat any type of cancer by changing the relevant targeting epitopes on the surface of the OMVs as well as the prodrug/enzyme packaged inside.

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Figure 3. List of receptor ligand pairs for different types of cancer



Personalised medicine:
With the increased use of genetic sequencing, patients' unique gene expression profiles can be used to tailor drug delivery systems in a highly personalised manner. Upon tissue profiling, novel patient-specific epitopes can be expressed on OMVs and used for drug delivery.

Imaging and diagnostics:
OMV encapsulated with melanin can be used in photoacoustic imaging, allowing for non-invasive monitoring of cancer tissues [19]. OMVs can be loaded with fluorescent molecules and express a targeting epitope, to facilitate highly specific detection of the target tissue [20].


Market Analysis and Entrepreneurship


The project's real-world implementation is contingent on getting the drug delivery system from the lab bench to the end users. To accomplish this, we examined aspects of our product such as scalability, existing interest in nanovesicle and nanoparticle drug delivery systems, and SWOT analysis. We also considered end-user factors such as global and local market sizes for cancer therapeutics and personalised precision medicine, potential customers, business models, competitors, and so on. With this information in hand, we decided to learn the first steps of launching a real startup by interacting with people in the startup community.

Scalability:
The flexibility and modularity of our drug delivery systems allow us to change the epitopes expressed on the surface of the vesicles, allowing us to target any other cancer. This adaptability can be used to broaden the delivery system to include both common cancer markers and to tailor the targeting epitopes to markers that are overexpressed in a person.This expands the number of people who can benefit from this product and increases the potential market size, extending into personalised cancer therapy.

Dual targeting is a largely untapped concept of targeted therapies. The nanovesicle drug delivery system overcomes existing problems with cancer therapeutics such as non-specific distribution to healthy cells and monotherapies' limited therapeutic efficacy. This enables the product to usher in a new paradigm of therapy throughout the field of cancer therapeutics.

The innovative dual targeting system broadens the possibilities for personalised therapies, increasing therapy efficacy. To make this scalability a reality, vesicle production, safety, and immunogenicity would need to be standardised. This would entail a more thorough examination of the quality control procedures, as well as clinical trials to ensure safe use for the intended therapeutic effect.



Scientific and Business Interest:
There is growing interest in using outer membrane vesicles to treat cancer. Outer membrane vesicles have been used in vaccines as adjuvants, and their immunogenic properties have been used to improve vaccine formulation and development[20]. Anticancer molecules have also been delivered to breast cancer tumors using these vesicles[21].

Silde 1. Research interest in OMV therapies Silde 2. Research interest in nanoparticle drug delivery systems [23]


This review paper and its connected works, look at the newfound interest in extending outer membrane vesicles beyond their use as adjuvants and into the field of functional delivery platforms for various therapeutic, diagnostic and even theranostic purposes. The interest also has been towards several cancers, virulence regulation and other diseases as well. [25]

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Figure 4. Interest in applications of OMV’s


Academics are not the only ones who are interested in developing efficient drug delivery systems. In India, BIRAC (Biotechnology Industry Research Assistance Council) offers potential startups seed funding to develop commercial ideas in the drug delivery sector, including drug delivery systems, through its BIG (Biotechnology Ignition Grant). C-CAMP (Centre for Cellular and Molecular Platforms) has Discovery to Innovation Accelerators with Nanoparticle Drug Delivery System technologies ready for licensing.

Silde 1. C-Camp DIA program licensing dual nanoparticle drug delivery systems Silde 2. BIRAC Biotechnology Ignition Grant sectors include drug delivery


In the US Clinical trials registry, there were approximately 19 clinical trials associated with the keyword "outer membrane vesicles." The majority of them are for meningitis vaccines based on OMV. They are based on OMVs isolated from meningococcal bacteria and are designed to provide disease immunity. The potential of OMVs in cancer therapeutics has not been fully exploited, but there is a clear path forward and an opportunity for investment if we are to translate the existing body of academic work into clinical trials.

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Figure 5. List of US Clinical Trials regarding Outer Membrane Vesicles

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There do not appear to be any registered clinical trials in India related with the phrase "outer membrane vesicles." This is conceivable since OMV-based therapies and solutions are still a largely untapped market in India. However, as evidenced by a search for "drug delivery systems" in India, there is a growing interest in drug delivery systems for various diseases.

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Figure 6. List of Indian Clinical Trials for Drug Delivery Systems


We conducted a SWOT analysis to assess the project's strengths, weaknesses, and opportunities for development. To that aim, we've identified our vulnerabilities and threats and are working on solutions to establish a place in the international market.

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Figure 7. SWOT Analysis for Duonco


Global and Local Market Sizes
In order to propose the formation of a startup to eventually put our proposal into reality, the international market for drug delivery systems and cancer therapies must be assessed in terms of economic parameters such as size, projected growth, key players, and segmentation. In this section, we will look at the prospective growth and rivals in the drug delivery market, as well as the global cancer therapeutics market, with a brief glance at the APAC area for cancer therapeutics and breast cancer. Then there's a quick glance at the tailored cancer therapies market.

  • The drug delivery market:
    The global drug delivery systems market is expected to be worth USD 71.75 billion by 2029, growing at a 9.0% CAGR during the forecast period. The increased frequency of chronic diseases and patients' increasing preference for sophisticated medication delivery systems are expected to drive market expansion. In 2021, the market was worth USD 34.70 billion, and in 2022, it was worth USD 39.33 billion. The market segments were based on Type, Device Type, Distribution Channel and Geography.

    The coronavirus pandemic may have accelerated the expansion of the worldwide medication delivery systems market. The increased production of injectable medication delivery devices has significantly fueled the market expansion. The increasing quantity of vaccinations delivered globally is boosting the market growth. Furthermore, the increasing use of self-injection devices and simple homecare solutions is increasing demand for improved drug delivery systems, supporting market growth.

  • The cancer therapeutics market:
    According to Precedence Research, the global cancer therapies and biotherapeutics market is estimated to be $339.44 billion by 2030, rising at an 8.6% CAGR between 2022 and 2030. The Asia-Pacific area is the fastest expanding market for cancer treatments and biotherapeutics.[26]

    The cancer therapeutics market can be segmented as Application-Based (breast cancer, lung cancer), Top Selling Medicines (Revlimid, Herceptin), Product Type (chemotherapy, hormone therapy), By the End User (household, hospitals), Geographical(NA, Europe, APAC, MEA).

    The rising prevalence of cancer is propelling the cancer therapies and biotherapeutics industry forward. During the projection period, the targeted therapy segment is expected to achieve the greatest CAGR and maintain its large market share.
    picture

    Figure 8. Cancer Therapeutics Market [26]


    China and India are the market leaders in cancer therapies and biotherapeutics in the Asia-Pacific region. Because of increased cancer awareness in countries like India, China, South Korea, and Japan, the Asia-Pacific cancer therapies and biotherapeutics market is expanding. The governments of these countries invest considerably in research and development.

    The Asia Pacific oncology market was worth USD 52.2 billion in 2021. It is predicted to develop at an 11.7% annual pace between 2022 and 2028, owing to increased cancer treatment programmes by various government and non-government organisations.
    picture

    Figure 9. APAC (Asia Pacific) Oncology Market [29]


    The increased focus of vendors on growing markets such as Asia-Pacific and Latin America is likely to drive market expansion. Because of increased R&D expenditure and cancer awareness, Asia-Pacific is expected to rise significantly. Furthermore, because existing markets are rather saturated, this region presents an exceptional potential for venture capitalists and investors.

  • Breast Cancer:
    Breast cancer has been a significant health concern in the Asia Pacific for several decades. Despite remarkable gains in many high-income nations in reducing breast cancer mortality, low- and middle-income countries have achieved little progress.
    China, India, Australia, South Korea, Japan, Thailand, Philippines, Indonesia, New Zealand, Malaysia, and Singapore comprise the Asia Pacific breast cancer therapies industry's regional geography. Given the increased need for sophisticated cancer care, the Chinese breast cancer therapeutics market is estimated to be worth USD 1.9 billion by 2028.

    Eisai Co. Ltd, Sanofi S.A., Merck & Co. Inc., F. Hoffmann-La Roche AG, Amgen Inc., Novartis International AG, Bristol-Myers Squibb Co., Pfizer Inc., Eli Lilly and Company, and AstraZeneca plc are the leading companies defining the competitive landscape of the Asia Pacific breast cancer business space.

    Breast cancer captured a substantial market share in 2019 and is expected to expand at the fastest CAGR, creating enormous prospects for players in the India Cancer Treatment Market. In April 2020, Roche launched atezolizumab in India. The medication atezolizumab is used to treat advanced triple-negative breast cancer. This strategy expanded the company's product line and brought new cancer biology therapy clients.

    The main competitors in the India Cancer Treatment Market are Amgen, AstraZeneca Plc, Merck and Co., Novartis AG, Pfizer Inc., Bayer AG, Astellas Pharma Inc., Celgene Corporation, Bristol-Myers Squibb, F. Hoffmann-La-Roche Ltd., Johnson & Johnson, and others.

  • Personalized Cancer Therapies
    The market is expected to reach $272.1 billion by 2027, increasing at a CAGR of 10.6% between 2022 and 2027. Personalized medicines are also known as precision medicines since they are created using molecular profiling and medical imaging of specific patients to improve the efficacy of cancer treatments. The primary goal of using precision medicine or predictive biomarkers is to tailor the proper treatment to the right patient.

    Several modern sequencing techniques, such as cancer genome sequencing and next-generation sequencing, aid gene discovery and give genomic data. Furthermore, biomarkers, capable of determining the patient's response to specific medical medications, play an important part in the development of tailored medicines. However, some patients' bodies do not adjust to therapies, such as chemotherapy, which worsens their predicament. As a result, precision medications make it simple for doctors to determine which therapy a patient should have in order to avoid further health complications.

    The North America Personalized Medicines in Oncology Market is expected to account for the largest revenue share in 2021. It is due to the high presence of strong Med-tech businesses, which both government and private venture investors frequently back. However, Asia-Pacific is expected to lead the market between 2022 and 2027. It is due to an increase in research and development activities, particularly in cancer research.
    picture

    Figure 10. Personalised Medicine Market [31]


    Product demand is expected to rise as research and development activities expand and technologies evolve. Increased cancer cases are expected to boost product demand. Not without obstacles, since a lack of understanding about precision medicines and pricey cancer therapies are expected to stymie market growth. Abbott, Exact Science Corporation, GE Healthcare, Illumina, Celera Diagnostics, Biogen, Decode Genetics, Danaher Corporation, Novartis, and Genelex Corporation are key players in this market.

  • Potential Customers and Business Models
    Pharmaceutical firms, healthcare providers, and individuals seeking medical care would all be possible clients. We intend to establish a B2B relationship with pharmaceutical companies by licensing our drug delivery technology for testing with their drugs. Health care professionals and patients are our primary target market, and we provide them two distinct services: first, a generic drug delivery system set with typically expressed epitopes against cancer; second, our personalized vertical, in which we get the biomarker levels of individuals and synthesize a personalized set of our dual delivery system adjusted according to the biomarker levels, with a suitable prodrug-enzyme combination.


Startup
Given the scientific and financial potential of our project and the need for real-world implementation of our drug delivery system, we propose the formation of a start-up to license, distribute, and manage the technology, which consists of the dual targeting system with checkpoint and the system design. It is vital to consider the prior study while financing this enterprise because, despite its lucrative potential, there is no defined competition, and the design of the drug delivery system is not standardised for all variables.

This restricts financing within the context of sector corporations (or an early start-up acquisition). As a result, the most viable option would be to obtain funds from so-called "seed capital" to cover the business's first costs and investments in exchange for a variable part of the company. Completing the regulatory process takes time, but it is vital to having a market-ready product for real-world use. Despite the challenges inherent in starting a business, we are keen to see our product used in the real world to aid patients and lessen the cancer burden.


References


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  5. Gerritzen, M. J. H., Salverda, M. L. M., Martens, D. E., Wijffels, R. H., & Stork, M. (2019). Spontaneously released Neisseria meningitidis outer membrane vesicles as vaccine platform: production and purification. Vaccine, 37(47), 6978–6986. Link here.

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