Future Trends and Technological Advances in Vaccine Treatment

1. Life Sciences & Healthcare Research and Analytics Services WHITEPAPER Future Trends and Technological Advances in Vaccine Treatment and Disease Prevention A 10-year Outlook

2. Future Trends and Technological Advances in Vaccine Treatment and Disease Prevention: A 10-year Outlook Traditionally, vaccines were thought to be a disease prevention tool. They exert their action by triggering an immune response to an antigen introduced into the body, enabling the body to fight the foreign infection. In recent years, the introduction of vaccines for key diseases, such as meningococcal meningitis A, hepatitis E, and malaria, has helped to save mortality and morbidity in large global population.1 At the same time, in diseases involving protozoal infections (such as hookworm, schistosomiasis, and leishmaniasis) and viral diseases (like Zika, Lassa fever, Nipah and henipaviral diseases, Rift Valley fever, Crimean–Congo hemorrhagic fever, and filoviruses) vaccines are yet to be developed.2,3 Currently the spotlight has been shifted to the development of therapeutic vaccines, which helps in the treatment of diseases like cancer and viral infections as compared to a traditional approach of prevention using vaccines. Vaccine Market Size and Commerce Pre-pandemic vaccines represented only 4% of the total value of the pharmaceutical market in 2019, which surged to about 10% of the total market when COVID-19 vaccines were introduced. Therefore, in 2021, the global vaccine market saw a significant increase, providing approximately 16 billion vaccine doses, a substantial rise from the 5.8 billion doses in 2019. The total value of this market also grew substantially, reaching US$ 141 billion, up from US$ 38 billion in 2019. The dominant vaccines in 2021 included COVID-19 and seasonal influenza vaccines, as well as the oral polio vaccine (OPV) used in supplemental immunization activities (SIAs), which comprised the largest volumes. Among these, the top 10 vaccines by volume, each surpassing 200 million doses, collectively constituted an impressive 92% of the global vaccine volume. Excluding COVID-19 vaccines, the Serum Institute of India (SII), the China National Biotechnology Group (CNBG), Sanofi, GSK, MSD, and Pfizer are the exclusive top 10 manufacturers recognized for their contributions in both value and volume. Top 10 Manufacturers by Value, 2021 Top 10 Manufacturers by Volume, 2021 Moderna 12% Sinovac 12% Sll 15% Sinovac 13% Others 20% MSD 7% GSK 6% AZ 6% Moderna 6% Others 12% AZ 3% GSK 2% Pfizer 30% CNBG 7% Sanofi 5% Sll 4% BioNTech 2% Pfizer 16% CNBG 11% BBIL 5% Sanofi 4% Haffkine 2% Source: Global vaccine market report 2022: a shared understanding for equitable access to vaccines. Geneva: World Health Organization; 2023. License: CC BY-NC-SA 3.0 IGO.4 2

3. Future Trends and Technological Advances in Vaccine Treatment and Disease Prevention: A 10-year Outlook Emerging Trends and Technologies Ever since the development of the first vaccine in 1796 for smallpox, the field of vaccine treatment and disease prevention has been constantly evolving, with new trends and technologies continually emerging. Some of the most notable emerging trends that are likely to play an important role in the coming years include: • New Vaccine Platforms: Researchers are developing new vaccine platforms that can be used to target a wider range of diseases and provide more durable protection. Some of these new platforms include mRNA vaccines, DNA vaccines, and self-amplifying RNA (saRNA) vaccines, and protein peptide-based vaccines. Each of these platforms is expected to provide its own advantages. mRNA vaccines, for instance, produce proteins that trigger immune response in the body. As mRNA vaccines do not contain live viruses, the chances of associated adverse effects with live viral vaccines are immediately eliminated.5 • Precision Medicine in Vaccine Development: Precision vaccinology is being facilitated by advancements in biotechnology and a systems biology approach leading to a better understanding of human host response and microbial interactions. This allows researchers to use precision medicine to develop vaccines that are tailored to the individual’s immune system. This could lead to more effective and personalized vaccines within a decade.6,7 • Artificial Intelligence (AI) in Vaccine Development: AI is being used to accelerate the vaccine development process in several ways. For example, AI can be used to identify new vaccine targets, design new vaccine candidates, and predict how vaccines will perform in clinical trials.8,9 • Combination Vaccines: Industry researchers are developing combination vaccines that can protect against multiple diseases at the same time. They could simplify immunization schedules and improve vaccine coverage. DT-based combination vaccines, which contain diphtheria toxoid (D) and tetanus toxoid (T) in combination with other antigens, have been in use since the 1950s; however, combination trails of COVID-19 and influenza vaccines have been carried out, more recently.10 • Nanotechnology for Vaccine Delivery: Nanotechnology is being used to develop new and improved vaccine delivery systems that have the potential to overcome many of the challenges of traditional vaccines, such as poor delivery efficiency, a lack of targeting, and the need for multiple doses. Some of the most promising nanotechnology-based vaccine delivery systems include Gardasil vaccine (liposomes) developed against HPV, Covaxin vaccine (polymer nanoparticles) developed against COVID-19, and StarVax vaccine (dendrimers) developed against HIV.11 • Vaccines against Non-communicable Diseases: Researchers are developing vaccines against a variety of non-communicable diseases, such as heart disease, Alzheimer’s disease, and HIV/AIDS. These vaccines are still in the early stages of development, but it is hoped that they will revolutionize the way we prevent and treat these diseases.12 • Universal Vaccines: Universal vaccines can protect against a wide range of pathogens. This type of vaccine would be particularly valuable for protecting against emerging infectious diseases and bioterrorism threats.13 • Edible Vaccines: Edible vaccines can be delivered orally, such as through fruits, vegetables, or milk. This type of vaccine would be more convenient and easier to administer than traditional vaccines, which are typically injected. Oral Vaccines is a US-based company that is developing edible vaccines produced in potatoes using Recombinant Protein Expression technology against cholera, typhoid, and polio.14 3

4. Future Trends and Technological Advances in Vaccine Treatment and Disease Prevention: A 10-year Outlook mRNA vaccines Intranasal vaccines DNA vaccines Emerging technologies Edible vaccines saRNA vaccines Nano-particle delivery systems Status and Prospects of mRNA and DNA-based Vaccines mRNA and DNA-based vaccines are a new generation of vaccines that are still in their early stages of development. However, they have shown great promise in clinical trials. Some of the advantages of mRNA and DNA-based vaccines include: • They can be developed and manufactured quickly as compared to traditional vaccines. • They are highly effective at inducing an immune response. • They are relatively safe and well-tolerated. • They can be used to target a wide range of pathogens and diseases, including infectious diseases, cancer, and autoimmune diseases. mRNA and DNA-based vaccines could also be used to develop vaccines against non-communicable diseases, such as cancer, Alzheimer’s disease, HIV/AIDS, and to develop personalized vaccines. These vaccines would be tailored to the individual’s genetic makeup or immune system, making them more effective and less likely to cause side effects as compared to traditional vaccines.5,15 Challenges in Developing mRNA and DNA Vaccines There are still some challenges that need to be addressed before mRNA and DNA-based vaccines can be rolled out to the market – one is the need for effective and affordable delivery systems; another is the need to develop vaccines that are stable and can be stored at room temperature. Researchers are designing new mRNA vaccines that are more stable and less expensive to produce and developing new ways to deliver them, such as through oral or nasal administration. They are also working to improve the efficacy, safety, and cost of DNA vaccines. Currently, there are two mRNA vaccines for COVID-19, which are approved for use in the United States: • BNT162b2 (Comirnaty), developed by Pfizer and BioNTech • mRNA-1273 (Spikevax), developed by Moderna 4

5. Future Trends and Technological Advances in Vaccine Treatment and Disease Prevention: A 10-year Outlook Vaccines for Diseases with High Disease Burden with Focus on Diabetes and Cancer Diabetes and cancer vaccines are still in their early stages of development but have displayed their potential to revolutionize the prevention and treatment of these diseases. There is no vaccine available to prevent either Type 1 or Type 2 diabetes. However, there are several research programs underway to develop diabetes vaccines. Companies are developing a vaccine that targets the beta cells in the pancreas, the autoantibodies that attack beta cells in people with Type 1 diabetes, and proteins that are involved in insulin resistance. The research in this area is promising and it is possible that a diabetes vaccine could be available within the next decade or two.16,17 Here are some examples of diabetes vaccines that are in clinical trials18: Drug Name Lead Company Indication Name Current Phase Target Glutamic Acid Decarboxylase (GAD), Immune System Diamyd Diamyd Medical Diabetes Mellitus, Type I II Immune System, Interferon- alpha (IFNa) IFNa Kinoid NEOVACS Diabetes Mellitus, Type I Preclinical Immunotech Laboratories ITV-1 Diabetes Mellitus, Type II Preclinical gp120, gp41, Immune System PIpepTolDC Vaccine City of Hope Diabetes Mellitus, Type I I Dendritic Cells, Immune System PRV-101 Sanofi Diabetes Mellitus, Type I I Immune System TOL-3021 Tolerion Diabetes Mellitus, Type I I/II Immune System On the other hand, the status of cancer vaccines is promising, with a number of vaccines in clinical trials and a few already approved by the FDA. • HPV vaccine can protect against human papillomavirus (HPV), which can cause cervical cancer and other types of cancer. • The hepatitis B vaccine can protect against hepatitis B virus (HBV), which can cause liver cancer. • BCG vaccine is used to prevent tuberculosis (TB), which can cause lung cancer. Sipuleucel-T (Provenge) is used to treat metastatic castration-resistant prostate laherparepvec (T-VEC) is used to treat advanced melanoma. Here are some examples of cancer vaccines that are in clinical trials18: cancer. Talimogene Current Phase Drug Name Lead Company Indication Name Target Colorectal Cancer, Pancreatic Cancer, Esophageal Cancer, Gastric Cancer GCC Vaccine (Liminatus) Guanylyl cyclase C Receptor, Immune System Liminatus Pharma II Epitopoietic Research Corporation Brain Cancer (Malignant Glioma and Glioblastoma) Gliovac II Immune System Immunomic Therapeutics Brain Cancer (Malignant Glioma and Glioblastoma) ITI-1000 II Dendritic Cells, pp65 Hepatocellular Cancer (Including Secondary Metastases) ABX196 Abivax I/II Natural killer T Cells ATP-128 Boehringer Ingelheim Colorectal Cancer I/II Immune System ELI-002 Elicio Therapeutics Solid Tumors I/II Immune System, KRas 5

6. Future Trends and Technological Advances in Vaccine Treatment and Disease Prevention: A 10-year Outlook Conclusion: The future of vaccine development is very promising, with a continuous flow of new and innovative technologies. mRNA and DNA-based precision medicine, and AI are a few approaches of vaccine improvement. In the next decade, we can expect to see new vaccines developed against a wider range of diseases, including those with high disease burdens such as diabetes and cancer. We can also expect to see the development of more personalized vaccines, tailored to the individual’s immune system. We can anticipate the use of AI and machine learning (ML) for vaccine design, improved vaccine distribution, and storage logistics, and a greater emphasis on global vaccine equity and accessibility. advancements in nanotechnology and immunotherapy may revolutionize the way we combat diseases, offering more effective and targeted prevention strategies. These advances will help to improve public health and well-being around the world and at the same time create valuable commercial opportunities for the industry. vaccines, Additionally, References: 1. Immunization Vaccines and Biologicals (2020, June 14). Global Vaccine Action Plan Monitoring, Evaluation & Accountability: Secretariat Annual Report 2020. Immunization Vaccines and Biologicals. (2023, October 11). Vaccines and Immunizations | CDC. (accessed on 2023, October 19) Agenda, Policy & Strategy. (2023, May 8). Global vaccine market report 2022: a shared understanding for equitable access to vaccines. MRNA Vaccines. Cleveland Clinic. (accessed on 2023, October 19) CIOs’ 5-year plans for precision medicine and emerging technologies. (2022, January 24). Healthcare IT News. Lee, B., Nanishi, E., Levy, O., et al. (2023). Precision vaccinology approaches for the development of adjuvanted vaccines targeted to distinct vulnerable populations. Pharmaceutics, 15(6), 1766. Texas Medical Center. (2023, July 27). Using AI to speed up vaccine development against Disease X - Texas Medical Center. Collins, C. (2023, April 18). New AI-Generated T-Cell vaccine showcases Long-Lasting immunity against COVID-19. SciTechDaily. 10. Ye, Q., Wu, M., Zhou, C., et al. (2022). Rational development of a combined mRNA vaccine against COVID-19 and influenza. Npj Vaccines, 7(1). 11. Bezbaruah, R., Chavda, V. P., Nongrang, L., et al. (2022). Nanoparticle-Based delivery systems for vaccines. Vaccines, 10(11), 1946. 12. A new wave of vaccines for Non-Communicable Diseases: What are the regulatory challenges? (2015). PubMed. 13. Bonner, K., Ssekyanzi, H., Sicsic, J., et al. (2022). What drives willingness to receive a new vaccine that prevents an emerging infectious disease? A discrete choice experiment among university students in Uganda. PLOS ONE, 17(5), e0268063. 14. Rajangam, J., Gosula, S., Satya, et al. (2018). An overview on Edible vaccines: A novel approach to oral immunization. IJRIAS, 3(8). 15. Jackson, N. a. C., Kester, K. E., Casimiro, D. R., et al. (2020). The promise of mRNA vaccines: a biotech and industrial perspective. Npj Vaccines, 5(1). 16. Chellappan, D. K., Bhandare, R. R., Shaik, A. B., et al. (2022). Vaccine for Diabetes—Where do we stand? International Journal of Molecular Sciences, 23(16), 9470. 17. Cancer Research Institute. (2023, August 2). Cancer vaccines | Cancer Research Institute. 18. ClinicalTrials.gov - NCBI. (accessed on 2023, October 19) 19. Company Websites, Annual Reports, Press Releases, and Investor Presentations 2. 3. 4. 5. 6. 7. 8. 9. 6

7. Future Trends and Technological Advances in Vaccine Treatment and Disease Prevention: A 10-year Outlook About the Author Rajiv Kalia • Vice President, Life Sciences & Healthcare 18+ years of combined experience and expertise in leading teams as well as a subject matter expert focused on life sciences & healthcare Industry. He has led teams carrying out strategic market assessments, opportunity evaluation – strategic & financial evaluation, project management qualitative and quantitative industry research. He has extensively worked with leading global clients in life sciences & healthcare research projects. He holds a master’s degree in pharmacy with a specialization in pharmacology from Manipal Academy of Higher Education and holds a management diploma in financial management. Sonali Phale • Senior Analyst, Life Sciences & Healthcare 6+ years of experience in pharma and healthcare industries research and consulting. She holds a master’s degree in microbiology and has qualified the GATE Exam in life sciences. She has extensively worked on CI trackers and intelligence databases. She has experience in producing country-based reports covering the healthcare, regulatory, and reimbursement landscape. Disclaimer This document makes descriptive reference to trademarks that may be owned by others. The use of such trademarks herein is not an assertion of ownership of such trademarks by SG Analytics (SGA) and is not intended to represent or get commercially benefited from it or imply the existence of an association between SGA and the lawful owners of such trademarks. Information regarding third-party products, services, and organizations was obtained from publicly available sources, and SGA cannot confirm the accuracy or reliability of such sources or information. Its inclusion does not imply an endorsement by or of any third party. Copyright © 2023 SG Analytics Pvt. Ltd. www.sganalytics.com Pune | Hyderabad | Bengaluru | London | Zurich | New York | San Francisco | Amsterdam | Toronto | Wroclaw 7 GET IN TOUCH