Dual Diarrhea Vaccine for Bottom Billion Children

Urgent Need for a Cold Chain-Free Dual-Use Vaccine to protect the bottom billion children from Cholera and ETEC, the diarrheal diseases:

Diarrheal diseases, including cholera and ETEC diarrhea, are major causes of death among children under the age of five in 79 LMICs. Nearly, 50% of acute diarrheal infections are attributed to two major waterborne pathogens: Vibrio cholerae and Enterotoxigenic Escherichia coli (ETEC), the causative agents of cholera and travellers’ diarrhea respectively. Cholera’s impact is greatest in many low- and middle-income countries (LMICs). Incidence of cholera cases (2.9 million) & 95,000 deaths reported (WHO, 2022). Spread in 79 Countries, 83% of deaths in Sub-Saharan Countries. Around 220 million cases of ETEC diarrhoea globally, with about 75 million episodes in children less than 5 years, resulting in 18 700 to 42 000 deaths (WHO, 2022) with 4 billion economic loss. ETEC is often the first bacterial illness that children experience in endemic areas during their first three years of life which adversely affects a child's physical and cognitive development.

Diaherral diseases also affect international travellers who visit LMICs. 900 million tourists travelled internationally in 2022. Around 78% of international travellers get infected within 3 days leading to US 700 Million in medical costs. Distinctly, most diarrheal patients are concurrently infected with V. cholerae and ETEC resulting in severe diarrhea. The pathogenesis of both pathogens is quite similar. To combat these diseases, a cold chain-free, single-dose, live dual-use vaccine is crucial.

Cold chain-free, Single-dose, Dual-use Vaccine for Cholera and ETEC relieves mass vaccination challenges:

Vaccination, water, and sanitation are key to controlling diarrheal infections. The existing WHO-licensed oral cholera vaccines (Dukoral®, Shanchol™, and Euvichol®), require a cold chain supply and multiple doses. Only Dukoral with its rCTB component affords short-term cross-protection against ETEC infection. FDA approved a live cholera vaccine Vaxchora for the travellers' diarrhea market. However, the high cost of these vaccines and maintaining a cold chain supply pose significant challenges in resource-poor settings. Therefore, a cold chain-free, live, attenuated cholera and ETEC vaccine that can be stored at room temperature must be developed to increase its outreach to global immunization programs in LMICs. Eventually, cold chain-free formulation reduces vaccine wastage from heat and freeze-shocks (estimated at ~ US$15-40M/year), lowers capital costs for cold chain equipment (~ US$110M/year), and decreases stockpiling expenses, cutting total operating costs (~ US$125-150M/year) across GAVI countries.

Game-changer: Single-dose, Live, Dual-Protection Vaccine for Diarrheal Diseases:

Combined vaccines offer improved administration, broader coverage, and increased compliance with complex schedules. Our Prototype, a Cold Chain-Free Dual-Use Vaccine is a groundbreaking innovation in preventing diarrheal diseases, being the "first of its kind" for the bottom billion children.

The vaccine is patented; GLP studies are in progress and secured fund for phase 0 clinical trials from the Ministry of Science, Technology and Innovation, Malaysia.

Seeking vaccine manufacturer collaboration for the following objectives:

• To validate the production process in a GMP facility.
• To conduct Phase O Clinical trial
• To License technology for the dual-use oral vaccine to a vaccine manufacturer

MyCholTM: Prototype, Dual-Use, Live, Cold-chain Free, Oral Vaccine for Cholera and ETEC -Travellers' Diarrhoea at Technology Readiness Level 6 for licensing:

The major advantages of our Prototype, Oral, Live, Dual-use vaccine (MyCholTM) for Cholera and ETEC -Travellers' Diarrhoea in comparison to existing killed and live vaccines available in the market are: a) it mimics natural infection by colonization, therefore eliciting immune responses that are highly specific, effective, and long-lasting (b) it would prevent infection by both the Vibrio. cholerae O139 and ETEC pathogens, not just disease symptoms (c) in comparison to highly purified subunit vaccines, it is relatively cheap to produce and administer orally and does not require sophisticated downstream processing or formulation with adjuvants and (d) it is a cold-chain free, live, oral vaccine for human. In brief:

• MyCholTM costs less by 40% and remains stable at room temperature (25°C ±2°C and RH 60% ± 5%) for 180 days.
• It showed higher colonization potential in the infant mouse colonization assay, and nonreactogenic in the ligated rabbit ileal loop assay. It elicited a 275-fold increase in anti-CT IgG antibodies and a 31-fold increase in vibriocidal antibodies and provided 100% protective efficacy against WT O139 challenge in rabbits.
• Mice immunized with MyCholTM recorded higher antibody titers, including anti-CT, anti-LT, anti-CT-B, and anti-LTB IgG. Anti-CT antibodies neutralized LT toxin, preventing weight loss and diarrhoea, and provided 100% protection in ETEC H10407 challenge studies.
• Patent Granted MY-190074-A in Malaysia and PCT in 6 countries.
• The low-cost dual-use MyCholTM innovation represents a game-changer in the field of diarrheal disease prevention.

 We attained the following 3 SDG goals:

1. SDG3: Good Health & Well-being

• Live, Single dose & Thermostable
• No wastage of vaccine from heat & freeze-shocks (~US$ 15-40 million/year across GAVI)
• Storage at Room Temperature: 25°C ± 2°C, 60% RH ± 5% RH ) for 180 days

2. SDG9: Industry, Innovation & Infrastructure

• Reduction in the capital cost for cold chain equipment (estimated at ~ US$ 110 million/year)
• Reduction in the cost of stockpiling & operating costs (US$ 125-150 million/year across GAVI).
• Competitive cost (USD 2/person)

3. SDG11: Sustainable Cities and Communities

• Long term protection
• Vaccination more people/day & coverage

The major players in the vaccine industry are Sanofi-aventis Groupe, Emergent BioSolutions Inc., Valneva SE, GlaxoSmithKline plc., Intervet Inc., EuBiologics Co., Ltd., and others. Based on the product, Dukoral is predicted to hold a significant share of the market. In this context, we would explore the avenues with these vaccine manufacturers for funding / JV for the technology development and validation and its transfer for commercialization.

Reference:

Hui Xian, T.; Parasuraman, S.; Ravichandran, M.; Prabhakaran, G. Dual-Use Vaccine for Diarrhoeal Diseases: Cross-Protective Immunogenicity of a Cold-Chain-Free, Live-Attenuated, Oral Cholera Vaccine against Enterotoxigenic Escherichia coli (ETEC) Challenge in BALB/c Mice. Vaccines 2022, 10, 2161. https://doi-org.ezproxyberklee.flo.org/10.3390/vaccin...

Vaccinating the Last Child, Last Mile, at Low Cost for Diarrhoeal Diseases:

The protection of children's health and well-being plays a vital role in achieving public health and global health objectives. This importance was emphasized in the Millennium Development Goals (MDGs) which have now been succeeded by the Sustainable Development Goals (SDGs). SDG 3.2 specifically aims to reduce under-five mortality to a rate as low as 25 per 1000 live births by 2030. However, children under the age of five continue to face significant morbidity and mortality from diarrhoeal and acute respiratory infections (ARIs) worldwide. Diarrhoeal diseases alone account for approximately 9% of under-five mortality (UNICEF, 2016). The current cost of vaccination is approximately $6 per person, which poses a significant barrier in vaccination campaigns. Out of this cost, 23% is allocated for maintaining the cold chain supply, while the remaining 77% is attributed to the production of multiple doses. This cost structure highlights the need for a thermostable/ cold-chain free, live vaccine that can overcome these challenges. Developing such a vaccine is crucial to ensure cost-effective immunization strategies and to achieve the goal of vaccinating the last child, even in the most remote areas, against diarrheal diseases. We developed a Prototype, Live, Oral, Cold chain free, Dual-use Vaccine (MyCholTM)   for Diarrhoeal Diseases (Cholera and ETEC diarrhoea), the 2nd leading cause of death among children under the age of five in 79 low-middle income countries.

Our target is the bottom 2 billion children, adults in 57 LMICs and international travellers to Sub-Saharan Africa, Haiti, Cameroon, Malawi, Lebanon, Somalia, Pakistan Bangladesh, India and Central America. 

Vaccination campaigns face a significant hurdle due to the cost of vaccines, which amounts to approximately $6 per person. This expense poses a major barrier to achieving widespread immunization. Interestingly, a notable portion of the vaccination cost, specifically 23%, is allocated solely to maintaining the cold chain supply. The remaining 77% is attributed to producing multiple doses of the vaccine. In this context the developed MycholTM vaccine would eliminate the dependency on the cold chain, making it easier to reach the last child in the most remote areas. By reducing costs and ensuring stability, this approach holds the potential to achieve low-cost vaccination for diarrheal diseases, even in the most challenging regions. Our vision is:

“Vaccinating the Last Child, Last Mile, at Low Cost for Diarrhoeal Diseases”

Live, Genetically Attenuated, Cold-Chain-Free Cholera & ETEC Vaccine — A Scientific Journey of 20 Years:

It is a collaborative project between AIMST University and USM (University Sains Malaysia). It is a 20 years journey in developing the Dual-use Vaccine (MyCholTM) for Diarrhoeal Diseases (Cholera and ETEC diarrhea).

Our cholera vaccine development journey started in 2000 at Universiti Sains Malaysia with the isolation of the hemA gene from Vibrio. cholerae, followed by the development of a gene mutant vaccine candidate VCUSM2 against V. cholerae O139 in 2006. In 2010, VCUSM2 reactogenicity was reduced by replacing its two wild-type ctxA gene copies with mutated ctxA to produce strain VCUSM14. Introducing the hemA gene into VCUSM14 created VCUSM14P, a strain with the ALA prototrophic trait and excellent colonization and immunological properties (100% protection to wild-type challenged rabbits). It was further refined at AIMST (Asian Institute of Medicine, Science and Technology) University, with the completion of single- and repeated-dose toxicity evaluations in 2019 in Sprague Dawley (SD) rats, followed by the development of a novel cold-chain-free VCUSM14P formulation in 2020.

This 20-year-old study was funded by several federal funding agencies, including various grants from the Ministry of Science, Technology and Innovation and from the Ministry of Higher Education. Over the years, several students and staff members contributed to this project, and we acknowledge them gratefully for their contributions. Details of this journey are described below and summarized below pictures. 

Our vision is to achieve the goal of "Vaccinating the Last Child, Last Mile, at Low Cost for Diarrheal Diseases." Vaccination campaigns face a major hurdle due to the high cost of vaccines, which amounts to approximately $6 per person. Interestingly, a significant portion of this cost, specifically 23%, is allocated solely to maintaining the cold chain supply. 

The elimination of the cold chain supply requirement can significantly reduce the cost of vaccine distribution. Instead of allocating nearly a quarter of the cost for cold chain maintenance, resources can be directed towards producing more vaccine doses. Currently, 77% of the vaccination cost is attributed to producing multiple doses of the vaccine.

By focusing on low-cost production and efficient distribution, we can reach the last child in the most remote areas, overcoming geographical barriers and logistical challenges. This approach is crucial in achieving widespread immunization and ensuring that no child is left behind.

With our vision, we aim to improve global vaccination rates and combat diarrheal diseases effectively. We can significantly impact public health by reducing costs, ensuring stability, and reaching the last mile, particularly in underserved regions.

Prototype, Dual-Use, Live, Cold-chain Free, Oral Vaccine for Cholera and ETEC -Travellers' Diarrhoea:

We developed a prototype, live, oral, dual-protection, cold-chain-free vaccine MyCholTM. It costs less, remains stable at room temperature for 180 days and is non-reactogenic and immunogenic in vivo through challenge studies with SD rats, BALB/c mice, and New Zealand rabbits. The vaccine was evaluated extensively in three distinct animal models. It showed higher colonization potential in the infant mouse colonization assay, and non-reactogenic in the ligated rabbit ileal loop assay. It elicited a 275-fold increase in anti-CT IgG antibodies and a 31-fold increase in vibriocidal antibodies. Mice immunized with MyCholTM recorded higher antibody titers, including anti-CT, anti-LT, anti-CT-B, and anti-LTB IgG. Anti-CT antibodies neutralized LT toxin, preventing weight loss and diarrhea, and provided 100% protection in challenge studies. The dual-use  MyCholTM costs less due to its room temperature storage and distribution and protects the bottom billion poor children and global travellers from diarrheal diseases.

The projected achieved TRL 6, GLP studies are underway at IPharm, Malaysia. Patent Granted. A Strategic Research Fund from MOSTI was secured for phase 0 clinical trials. The low-cost dual-use MyCholTM innovation represents a game-changer in the field of diarrheal disease prevention.

The major Objective:

Scale-up Validation, and Transfer of Technology required for Commercializing the Dual-use, Cold-chain free live vaccine for diarrheal diseases:

MyCholTM is a prototype first-of-its-kind, live, cold-chain free, oral vaccine that provides dual protection against cholera and travellers' diarrhoea caused by Vibrio cholerae and ETEC, respectively. It costs less due to its room temperature storage and distribution and protects the bottom billion poor children and global travellers from diarrheal diseases.

The major players in the vaccine industry are Sanofi-aventis Groupe, Emergent BioSolutions Inc., Valneva SE, GlaxoSmithKline plc., Intervet Inc., EuBiologics Co., Ltd., and others. In this context, we would explore the avenues with these vaccine manufacturers for funding / JV for the technology development and validation and its transfer for commercialization.

Shanchol™ and Euvichol-Plus® are currently available through the Global OCV Stockpile. In 2022, Shantha Biotechnics, a wholly owned Indian subsidiary of the French drug maker Sanofi which produces about 15% of the world's supply of OCV, announced that it would end production and distribution of Shanchol™ by 2023. UNICEF expects an emergency stock of 30 Million doses whereas the current availability is 16 Million doses. The global stockpile of Oral Cholera vaccines (OCV) is currently insufficient to meet all requests for two doses of preventive vaccination. As a result, on 20 October 2022, the International Coordinating Group (ICG) members (IFRC, MSF, UNICEF, and WHO) took the unprecedented decision to temporarily limit all reactive OCV campaigns to one single dose. The production of OCV is a continuous process with around 2.5 million doses produced monthly. As vaccine manufacturers are producing at their maximum current capacity, there is no short-term solution to increase production. While using a single dose instead of two doses will allow more people to be protected in the short term, this strategy has its limitations, and it is unclear how long immunity will last. To solve the problem in the long term there needs to be an increase in global vaccine production. Hence, we would like to collaborate with a vaccine manufacturer on the following:

• 1)To validate the production process in an accredited GMP facility.
• 2)To compile the pre-clinical dossier to support the Licensure of Prototype cholera vaccine for Clinical Development
• 3)License the technology to produce a cold chain-free live attenuated cholera vaccine.

In our pursuit to address the challenges of vaccination for diarrheal diseases, particularly cholera and travellers' diarrhoea, we have developed MyCholTM, a first-of-its-kind live, cold-chain-free oral vaccine. MyCholTM offers dual protection against Vibrio cholerae and ETEC, providing an innovative solution that can benefit the bottom billion underprivileged children and global travellers.

Recognizing the significance of collaboration with established vaccine manufacturers, we are keen to explore avenues with major players in the industry such as Sanofi-aventis Groupe, Emergent BioSolutions Inc., Valneva SE, GlaxoSmithKline plc., Intervet Inc., EuBiologics Co., Ltd., and others. We believe that partnering with these manufacturers for funding, joint ventures, and technology development and validation would pave the way for successful commercialization.

The current availability of existing oral cholera vaccines (OCV) through the Global OCV Stockpile, such as Shanchol™ and Euvichol-Plus®, is inadequate to meet the increasing demand. The decision to temporarily limit reactive OCV campaigns to a single dose due to insufficient supply underscores the urgent need for a long-term solution.

To address this, we propose collaborating with a vaccine manufacturer on the following key areas:

1. Validation of the production process in an accredited Good Manufacturing Practice (GMP) facility: This step ensures that the manufacturing process for MyCholTM meets rigorous quality standards, ensuring consistent and reliable vaccine production.

2. Compilation of the pre-clinical dossier to support the Licensure of the Prototype cholera vaccine for Clinical Development: By compiling comprehensive pre-clinical data and documentation, we aim to obtain the necessary regulatory approvals and licensure for further clinical development.

3. Licensing the technology to produce a cold chain-free live attenuated cholera vaccine: Through this collaboration, we can transfer our technology to vaccine manufacturers, enabling them to produce the MyCholTM vaccine at scale. The elimination of the cold chain requirement reduces costs and facilitates easier distribution, ensuring broader accessibility and impact.

By joining forces with a vaccine manufacturer, we can leverage their expertise, resources, and manufacturing capabilities to accelerate the development, validation, and commercialization of MyCholTM. Together, we can overcome the challenges of vaccine supply and contribute to global efforts in combatting diarrheal diseases, ultimately improving public health outcomes worldwide.

Our solution, MyCholTM, approaches the problem of immunization for Cholera and ETEC - Travellers' Diarrhoea in a new and significantly improved way, introducing several key advancements:

1) Dual-use Vaccine: MyCholTM is the first dual-use vaccine that provides protection against both Cholera and ETEC - Travellers' Diarrhoea. By addressing two major causes of diarrheal diseases with a single vaccine, it offers a comprehensive approach to immunization, enhancing the effectiveness and efficiency of preventive measures. 

2) Oral Administration: Unlike many existing vaccines that require injections, MyCholTM is administered orally. This method is more convenient, user-friendly, and suitable for widespread vaccination campaigns, particularly in resource-limited settings. It simplifies the vaccination process, potentially increasing vaccine acceptance and coverage. 

3) Mimicking Natural Infection: MyCholTM uniquely mimics natural infection by colonization, eliciting immune responses that are highly specific, effective, and long-lasting. This approach closely replicates the natural immune response, potentially resulting in enhanced protection and durability of immunity. 

4) Cost-effectiveness and Thermostability: MyCholTM offers a cost-effective solution compared to highly purified subunit vaccines. Its production process is relatively inexpensive, and its stability at room temperature for 180 days eliminates the need for a cold chain supply. These factors reduce costs associated with cold storage and transportation, making MyCholTM more affordable and accessible.

The catalytic effect of MyCholTM on broader positive impacts within the immunization space and the market is substantial:

- Spurring Innovation: MyCholTM's innovative approach can inspire and motivate other researchers and vaccine developers to explore novel strategies for improving immunization against diarrheal diseases. It can ignite a wave of innovation, leading to the development of more effective, convenient, and affordable vaccines for other infectious diseases as well.

- Access and Equity: MyCholTM's cost-effectiveness and simplified administration have the potential to catalyze broader positive impacts by increasing access to immunization for underserved populations. It can reach remote and resource-limited areas where traditional vaccines face distribution challenges. This equity in access can contribute to reducing health disparities and achieving global immunization goals.

- Market Transformation: MyCholTM has the potential to revolutionize the market for diarrheal disease vaccines. Its dual-use nature, oral administration, and elimination of the cold chain requirement disrupt traditional paradigms and offer new possibilities. As a cost-effective and convenient option, it could drive market shifts, influencing other manufacturers to develop similar innovative vaccines and catalyzing competition, leading to broader availability and affordability of vaccines.

In brief, MyCholTM's novel approach, combined with its cost-effectiveness, oral administration, cold-chain-free, and potential for broader positive impacts, can revolutionize the field of immunization for diarrheal diseases.

Our impact goals for the next year and the next five years align with our vision of achieving widespread low-cost vaccination for diarrheal diseases, specifically targeting cholera and travelers' diarrhoea. Building upon the innovative MyCholTM vaccine and the collaborations we seek with established vaccine manufacturers, our goals are as follows:

Next Year:

Validation and production process: Within the next year, we aim to validate the production process of MyCholTM in an accredited Good Manufacturing Practice (GMP) facility. This step ensures that our vaccine meets the highest quality standards and can be produced reliably at scale.

Pre-clinical dossier compilation: Concurrently, we will compile the necessary pre-clinical data and documentation to support the licensure of the Prototype cholera vaccine for Clinical Development. This step is vital in obtaining regulatory approvals for advancing our vaccine towards clinical trials.

Partnerships and collaborations: We will actively engage with major vaccine manufacturers, such as Sanofi-aventis Groupe, Emergent BioSolutions Inc., Valneva SE, GlaxoSmithKline plc., Intervet Inc., EuBiologics Co., Ltd., and others, to establish partnerships and collaborations. These collaborations will provide the necessary funding, technology validation, and expertise to accelerate the development and commercialization of MyCholTM.

Next Five Years:

Clinical development and licensure: Over the next five years, we aim to advance MyCholTM through clinical development, conducting rigorous trials to demonstrate its safety, efficacy, and immunogenicity. By working closely with regulatory bodies, we will seek licensure and approvals for the widespread use of our vaccine.

Global production and distribution: Concurrently, we will focus on technology transfer to vaccine manufacturers to enable the production of MyCholTM at a global scale. This transfer will ensure that the vaccine is widely available and accessible, particularly in remote and underserved areas where the burden of diarrheal diseases is significant.

Impact and reach: Our ultimate goal is to have a significant impact on global vaccination rates for diarrheal diseases. Within the next five years, we aim to vaccinate a substantial number of individuals, specifically targeting the bottom billion poor children and global travellers. By eliminating the cold chain requirement and reducing costs, we can overcome barriers to immunization and ensure that vulnerable populations receive the protection they need.

To achieve these impact goals, we will continue to foster collaborations with vaccine manufacturers, engage with regulatory bodies, conduct robust clinical trials, and advocate for the importance of low-cost vaccination for diarrheal diseases. Our commitment to innovation, quality, and accessibility will drive us towards our vision of widespread immunization, ultimately saving lives and improving public health outcomes worldwide.

Our Prototype Oral Live Dual-use vaccine, MyCholTM, offers significant advantages over existing killed and live vaccines in the market for Cholera and ETEC - Travellers' Diarrhoea. The key differentiators include:

a) Mimicking natural infection: MyCholTM mimics natural infection by colonization, which leads to highly specific, effective, and long-lasting immune responses.

b) Prevention of infection: MyCholTM provides protection against both the Vibrio cholerae O139 and ETEC pathogens, preventing not just disease symptoms but also infection itself.

c) Cost-effectiveness: Compared to highly purified subunit vaccines, MyCholTM is relatively inexpensive to produce and administer orally. It does not require sophisticated downstream processing or formulation with adjuvants.

d) Cold-chain free and oral administration: MyCholTM is a cold-chain free, live, oral vaccine, making it convenient for distribution and administration.

In view of the above, we are attaining the following three SDGs.

Impact on Sustainable Development Goals (SDGs):

1) SDG3: Good Health & Well-being:

Live, single-dose, thermostable vaccine reducing wastage from heat and freeze-shocks, saving costs.
Storage at room temperature eliminates the need for cold chain equipment, reducing capital costs.

2) SDG9: Industry, Innovation & Infrastructure:

Reduction in the cost of stockpiling and operating costs, leading to significant savings.
Competitive cost per person, enabling wider access to vaccination.

3) SDG11: Sustainable Cities and Communities:

Long-term protection provided by MyCholTM ensures sustainable health outcomes.
Increased vaccination capacity allows for higher coverage, contributing to healthier communities.

The professional development and deployment of MyCholTM will revolutionize the prevention of diarrheal diseases, aligning with the Sustainable Development Goals and bringing us closer to a healthier, more resilient world.

The Theory of Change for MyCholTM is presented in the below table:

The above-tabulated representation provides a clear overview of the activities, outputs, and outcomes associated with MyCholTM's Theory of Change. It illustrates the logical progression from activities to specific outputs and ultimately to the desired outcomes, showcasing how each step contributes to the broader positive impacts on the target population and the market.

The core technology that powers MyCholTM is based on the application of scientific knowledge and evidence-based research to develop a live, oral vaccine for Cholera and ETEC - Travellers' Diarrhoea. The technology behind MyCholTM can be broadly categorized as follows: 

Vaccine Development: MyCholTM utilizes advanced techniques in genetic engineering and scientific knowledge in the field of vaccine development to create a dual-use vaccine that provides protection against both Cholera and ETEC - Travellers' Diarrhoea. Extensive research and understanding of the immune response to these pathogens are employed to design a vaccine that mimics natural infection by colonization, leading to specific and long-lasting immune responses. 

Microbial Genetics and Engineering: The technology behind MyCholTM involves the use of microbial genetics and engineering to create a live attenuated vaccine. Through genetic modifications and by rational attenuation, specific virulence factors or genes associated with pathogenicity are altered or removed, rendering the vaccine strain safe for administration while still inducing an immune response. 

Manufacturing and Formulation: The production process of MyCholTM involves state-of-the-art manufacturing techniques to ensure scalability, quality, and cost-effectiveness. The vaccine is formulated to maintain stability at room temperature, eliminating the need for a cold chain supply. This formulation technology enables easier storage, transportation, and distribution of the vaccine, particularly in resource-limited and remote areas. 

Regulatory Compliance and Licensure: MyCholTM's core technology also includes adherence to regulatory guidelines and requirements for vaccine development and licensure. The technology incorporates the necessary steps to compile pre-clinical data, conduct clinical trials, and obtain regulatory approvals, ensuring that the vaccine meets the highest safety and efficacy standards. 

The project achieved TRL 6, and GLP-Compliant Safety Studies of the vaccine are in progress at IPharm. Patent Granted MY-190074-A in Malaysia. And, a Strategic Research Fund from MOSTI was secured for phase 0 clinical trials.

Overall, the core technology behind MyCholTM encompasses a multidisciplinary approach that combines scientific knowledge, genetic engineering, formulation techniques, and adherence to regulatory standards. This technology-driven solution harnesses the power of science and evidence-based knowledge to provide an innovative and effective vaccination strategy for Cholera and ETEC - Travellers' Diarrhoea, aiming to make a significant impact on global public health.

A total of 6 Researchers are currently in the vaccine development team. Three are full-time and three are part-time. Two Professors are the lead scientists. The team has a burning desire to serve the bottom billion children across the globe.

It is a collaborative project between AIMST University and USM. The team at USM developed the vaccine strain VCUSM14P and it took 14 years (years 2000 to 2014)for the development and testing. At AIMST, it took 8 years for the cold-chain-free, dual-protection vaccine formulation development. Total = 22 years so far.

Incorporating diversity, equity, and inclusivity (DEI) is of utmost importance to us in all aspects of our work. We strive to ensure that our approach is inclusive, fair, and accessible to all individuals, regardless of their background, identity, or socio-economic status. Here are some key aspects of our approach:

• Actively cultivating a diverse workforce and engaging stakeholders from various backgrounds, ensuring that different perspectives and experiences are valued and incorporated into our work.
• Ensuring that MyCholTM is accessible and affordable for individuals in all settings, particularly those in low-resource areas, to promote equitable access to vaccination and reduce disparities.
• Prioritizing the equitable distribution of MyCholTM, targeting underserved and remote areas to ensure that vulnerable populations have equal opportunities for protection against diarrheal diseases.
• Demonstrating cultural sensitivity by deeply understanding and respecting local beliefs, practices, and norms surrounding healthcare and vaccination, fostering trust and acceptance within communities.
• Collaborating closely with local community-based organizations, advocacy groups, and governmental agencies, forging partnerships to drive inclusivity and equity in our initiatives.
• Committing to continuous learning, rigorous evaluation, and improvement of our DEI practices, adapting strategies based on feedback and conducting impact assessments to ensure effectiveness.
• Actively seeking feedback from diverse perspectives, engaging stakeholders from different communities, and integrating their insights into our decision-making processes to ensure inclusivity.
• Cultivating an inclusive and equitable work culture that values diversity, creates an environment where individuals feel respected, empowered, and have equal opportunities to contribute and thrive.

By embodying these principles in our approach, we aim to foster a powerful and professional commitment to diversity, equity, and inclusivity, enhancing the impact of our work and contributing to a more equitable and inclusive society.

Key Partners:

Vaccine Manufacturers: Collaborate with vaccine manufacturers for technology transfer, production scale-up, and global distribution of MyCholTM.

Regulatory Agencies: Work closely with regulatory agencies to obtain approvals and licensure for commercial use of MyCholTM.

Local Healthcare Providers and NGOs: Partner with local healthcare providers and NGOs for targeted distribution and administration of MyCholTM in underserved areas.

Key Activities:

Research and Development: Continuously conduct research to improve MyCholTM, validate production processes, and gather clinical trial data.

Manufacturing: Oversee and ensure quality production of MyCholTM in accredited GMP facilities, adhering to regulatory guidelines.

Collaboration and Partnerships: Engage in collaborations and partnerships with stakeholders to advance the development, distribution, and impact of MyCholTM.

Regulatory Compliance: Navigate the regulatory landscape, compile necessary documentation, and obtain approvals for the commercial use of MyCholTM.

Value Proposition:

Dual-use Vaccine: Provide a single vaccine that offers protection against both Cholera and ETEC - Travellers' Diarrhoea, addressing two significant causes of diarrheal diseases.

Cost-effectiveness and Accessibility: Offer a cost-effective solution that is accessible to individuals in low-resource settings, eliminating the need for a cold chain and reducing production and distribution costs.

Long-lasting Immunity: Deliver long-lasting immune responses through MyCholTM's mimicry of natural infection, ensuring sustained protection against Cholera and ETEC infections.

Customer Segments:

Global Travellers: Target individuals who require protection against both Cholera and ETEC - Travellers' Diarrhoea during their travels.

Low-resource Areas: Focus on reaching populations in low-resource settings, where the burden of diarrheal diseases is higher and access to vaccines may be limited.

Healthcare Providers and NGOs: Collaborate with healthcare providers and NGOs that serve vulnerable populations and have a mandate for disease prevention and public health.

Channels:

Partnerships: Leverage partnerships with vaccine manufacturers and distributors to expand the reach of MyCholTM globally.

Online Platforms: Utilize online platforms and digital marketing to raise awareness, provide information, and facilitate direct sales.

Revenue Streams:

Vaccine Sales: Generate revenue through the sale of MyCholTM vaccines to healthcare providers, NGOs, and government agencies.

Licensing: Explore opportunities for licensing the technology and know-how behind MyCholTM to vaccine manufacturers.

Cost Structure:

Research and Development: Allocate resources to ongoing research, clinical trials, and improvement of MyCholTM.

Manufacturing: Invest in production facilities, equipment, and quality assurance measures to ensure efficient and high-quality manufacturing.

Distribution: Cover costs associated with the distribution and logistics of MyCholTM, including storage, transportation, and cold chain-free infrastructure.

Key Resources:

Intellectual Property: Protect the intellectual property rights of MyCholTM through patents and licensing agreements.

Skilled Workforce: Employ a skilled team with expertise in vaccine development, manufacturing, regulatory affairs, and business operations.

Research Facilities and Laboratories: Maintain access to state-of-the-art research facilities and laboratories for the ongoing development and testing of MyCholTM.

Our plan for achieving financial sustainability revolves around diversifying our revenue streams and building a robust funding model. While we may initially rely on grants and donations from philanthropic organizations during the development and early stages, we aim to establish self-sustaining revenue sources in the long term. Our approaches are:

1) Licensing: We will explore opportunities for licensing the technology and know-how behind MyCholTM to vaccine manufacturers. This can create a passive income stream through licensing fees and royalties, allowing us to leverage the expertise and production capabilities of established manufacturers while expanding the reach of MyCholTM.

2) Partnerships and Collaborations: We will seek strategic partnerships with organizations aligned with our mission. These collaborations can involve joint research and development efforts, co-marketing initiatives, or shared distribution networks, which can bring in additional revenue and expand our reach.

3) Philanthropic Support: We will continue to engage with philanthropic organizations and individuals who share our vision and can provide sustained donations or grants to support specific research and development projects, capacity-building initiatives, or targeted vaccination campaigns.

The Dual-Use vaccine secured so far 4 grants. The total value of all the below 4 grants is RM 11.4 Million (2.5 Million US Dollars).

1) PRGS Grant for the value of RM 479,000 from the Minister of Higher Education (MoHE), Malaysia to research on “ICH GLP-Compliant Pre-Clinical Safety Studies to Support the Licensure of Prototype Cholera Vaccine for Clinical Development” in the year 2019.

2) FRGS Grant for the value of RM 185200 from (MoHE), Malaysia to research on “Evaluation of Prototype Cold Chain Free Live Attenuated Oral Cholera Vaccine for its Cross-Protective Immunity against Enterotoxigenic Escherichia Coli (ETEC) as a Dual-Use Vaccine for Diarrheal disease” in the year 2018.

3) PRGS Grant for the value of RM 250,000 from (MoHE), Malaysia to research on “Development of Cold Chain free live attenuated Cholera Vaccine formulation” in the year 2015.

4) A Strategic Research Fund of RM 10.5 Million from MOSTI was secured for phase 0 clinical trials.

In brief, the project achieved TRL 6, and GLP-Compliant Safety Studies of the vaccine are in progress at IPharm. Patent Granted MY-190074-A in Malaysia. And, a Strategic Research Fund from MOSTI was secured for phase 0 clinical trials. And way forward to collaborate with a vaccine manufacturer for technology transfer & licensing.