10 Most Innovative CROs To Watch In 2023

1. Most Industry Sagacity The Impact of Emerging Technologies on The Pre-Clinical CRO Market Dr Ibrahim Farr Chairman and CEO Redefining Advancements Role of CROs in Shaping the Future of Clinical Research Pivotal A Name Synonymous to Innova?ons

2. RESEARCHING and Educating to SAVE lives.

4. Editor’s Note The Augmenta?ons for Perpetual Be?erments D uring the COVID-19 pandemic, if clinicians, healthcare service-providing staff, nurses, and doctors were battling at the forefront, then the Clinical Research Organizations (CROs) have been working hard in the background to develop effective vaccines to fight this novel coronavirus. With millions of cases emerging every day globally, the demand for quick vaccination raised the expectations from the CROs to rise to the occasion and intensify their vaccine research, clinical trials, testing and developmental efforts, which they did in a record time. Because of their tremendous efforts, we as a global unit came up with nearly a dozen vaccines already being deployed worldwide, with over sixty-eight per cent global population vaccinated at least once. These are tremendous achievements while these CROs are further advancing their forces to find more possible ways through novel technologies to mitigate the virus spreading and boost the global population’s immunity further.

5. The momentum will be carried forward as predicted by the Reportlinker’s report. According to the report, the global CRO market is projected to grow at a CAGR of 10.06% during 2022-26 and reach $40 billion by the end of 2026. The report further states that the market will be further driven by the growing biopharmaceutical industry, increased global R&D expenditure and investment, regulations of clinical trials, and technological innovations in the healthcare industry, particularly in the CRO end-user market segment and geographical landscape. To grasp these very positive scenarios for the present and future of the CRO industry, Insights Care’s team unveiled this exclusive edition of the ‘10 Most Innovative CROs To Watch In 2023.’ These ten CROs are among the disruptive innovators when it comes to clinical trials, R&D, and assisting the vaccine development drive. Also included in this edition are two trendy articles our in-house editorial team curated to give you a holistic view of the entire scenario. Flip through the following pages and witness CROs’ futuristic leap into a healthier tomorrow; enjoy! - Anish Miller

6. C O 08 Cover Sto PIVOTAL A Name Synonymous to Innovations

7. N T E N T S 20 24 32 CLINERGY HEALTH RESEARCH Providing Synergic Solutions for win-win Outcomes CXO GENE THERAPY AND CANCER TREATMENT OnQ Research Articles Blend of Innovations Assuring Adaptability Industry Sagacity 16 e Impact of Emerging Technologies on e Pre-Clinical CRO Market Redefining Advancements 28 Role of CROs in Shaping the Future of Clinical Research

8. Pooja Bansal Editor-in-Chief Anish Miller Senior Editor Abhishek Joshi Saloni, Drishti Managing Editor Assisting Editors Visualiser David King Mrunalinee Deshmukh Art & Design Head Co-designer Paul Belin Sonia Raizada Art & Picture Editor Amy Jones John Smith Business Development Manager Marketing Manager Sarah Wilson, John Smith, Alex Vincent Kelli, Bill, Anna Business Development Executives Sales Executives Jacob Smile Amar Sawant Technical Head Assistant Technical Head David, Robert Technical Consultants Alina Sege Renuka Kulkarni Digital Marketing Manager Assistant Digital Marketing Manager SME-SMO Executives Gemson Eric Smith Research Analyst Tanaji Fartade Circulation Manager sales@insightscare.com January, 2023 Contact Us: Insights Success Media Tech LLC 555 Metro Place North, Suite 100, Dublin, OH 43017, United States Phone - 302-319-9947 Email: info@insightscare.com For Subscription: www.insightscare.com Insights Success Media and Technology Pvt. Ltd. Office No. 22, Rainbow Plaza, Shivar Chowk, Pimple Saudagar, Pune, Maharashtra 411017 Phone - India: 7410033802, 74100058552 Email: info@insightscare.com For Subscription: www.insightscare.com https://twitter.com/Insightscare Follow us on : www.facebook.com/InsightsCare/ Copyright © 2023 Insights Success Media and Technology Pvt. Ltd., All rights reserved. The content and images used in this magazine should not be reproduced or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission from Insights success. Reprint rights remain solely with Insights Success Media and Technology Pvt. Ltd. Insights Care is powered by Insights Success Media and Technology Pvt. Ltd.

9. 10 MOST INNOVATIVE CROs TO WATCH IN 2023 COMPANY FEATURING BRIEF Enrico Perfler CEO 1MED is a Swiss-based regulatory and quality consultancy company and full service CRO. 1MED SA 1med.ch Biomapas biomapas.com Audrius Sveikata CEO Biomapas is a func?onal and full outsourcing solu?on provider to the global life science industry. CLINERGY was created to fill gaps le? by the tradi?onal outsourcing model and to leverage opportuni?es for the healthcare industry and clinical sites on a cost-effec?ve way, so that health innova?on reaches pa?ents faster. Tiago M D da Silva Managing Director CLINERGY Health Research clinergyhealth.com Ino?v ino?vco.com Through scien?fic leadership and ongoing investments, Ino?v delivers a comprehensive range of nonclinical and analy?cal services that will exceed your expecta?ons. Bob Leasure CEO LINK Medical is a full-service Nordic CRO providing product development services for the pharmaceu?cal and medical device industries across Northern Europe. Ola Gudmundsen CEO Link Medical Research linkmedical.eu NDA Regulatory Science (NDA Group) ndareg.com Chris?ne Lind Vice President Commercial NDA is a leading regulatory drug & device development consultancy, suppor?ng companies with their regulatory, pharmacovigilance, quality and strategic planning. Catherine Lund Founder and Managing Director OnQ Research is a South African contract research organisa?on that offers services to assist with the en?re con?nuum of clinical research. OnQ Research onqsa.co.za Orphan Reach is a full-service CRO with clinical opera?ons in place since 2002. Thomas Ogorka CEO Orphan Reach orphan-reach.com P.R.I.S.M.A. is a German Clinical Research Organiza?on (CRO) and dedicated to support the European por?on of the pharmaceu?cal and biotech industries’ clinical development programs. P.R.I.S.M.A.- CRO GmbH prisma-cro.com Gernot Cremer MD Pivotal is a Contract Research Organiza?on that weaves together the scien?fic insight, the technology and the resources to help customers address both current and future needs. Dr Ibrahim Farr Chairman and CEO PIVOTAL pivotalcr.com

10. 10 Most Innova?ve CROs To Watch In 2023 A Name Synonymous to Innova?ons , Pivotal’s team is proud of being involved in the ac?va?on, conduc?on and the execu?on of discrete full ac?vi?es of nearly 500 different clinical research projects in quite dis?nct therapeu?c areas and phases and with many diverse inves?ga?onal compounds, devices and products.

11. Dr Ibrahim Farr Chairman and CEO Pivotal

12. harmaceutical companies have been increasingly P and boost the ongoing commercial success of their products. This shift is accelerating M&A across many segments of outsourced pharmaceutical services. Across the pharmaceutical value chain, outsourced services are gaining traction, from drug discovery, contract research and contract manufacturing to commercialization services, safety and risk management and pharmaceutical IT. With the objective of becoming a reliable full-service CRO, Pivotalwas born back in 2001 on the principle that strategic scientific and medical advice and support should be the backbone of all clinical trials with proper and sufficient resources to cover not only the execution of all essential aspects and stages of clinical trials from setup to execution to termination, including clinical monitoring and project management. using outsourcing to be more efficient and effective in drug development, help reduce time-to-market Under the leadership of DrIbrahim Farr, Chairman and CEO,Pivotal also oversees other complementary activities such as medical monitoring and writing support, or pharmacovigilance and data-management and biostatistical services, i.e., almost all that it takes to complete a clinical trial, while just leaving some very specialized tasks (e.g., drug depot services or lab. analytics) in the hands of very specialized vendors independent from the company. CROs generally employ an expertise-driven, project-based consulting model that requires strategy and capability around managing complex trials. Most importantly, while some large service providers exist in this segment, significant consolidation opportunities exist. In comparison, the preclinical CRO market is more mature and consolidated. Over the years, many large pharmaceutical manufacturers have moved from working with a set of preferred providers to forming strategic partnerships with only one or two large CROs. , The Profound Legacy Now, almost 21 years from its foundation, Pivotal’s team is proud of being involved in the activation, conduction, and the execution of discrete full activities of nearly 500 different clinical research projects in quite distinct therapeutic areas and phases and with many diverse investigational compounds, devices and products. Nevertheless, other pharma and, preferably biotechnological, companies do still prefer to work with a set of qualified mid-size CROs in order to provide them with more personalized focused specialized services. With some more detail, Pivotal has been engaged, up to date, in a total of 361 clinical trials – from phase 1 to phase 4- that involved the management of almost 6,000 investigational sites and >40,000 patients and in close to 115 non-interventional studies (NIS) which involved, in turn, the handling of >9,000 sites and >62,000 patients. Or in “big numbers”: an accumulated experience resulting from working with >15,000 sites and >100,000 patients–a heavy backpack to support its expertise and knowledge. Pivotal’s team genuinely believe this all has only been possible because of their proven experience in and deep knowledge of the clinical research landscape. Pivotal’s team genuinely believe this all has only been possible because of their proven experience in and deep knowledge of the clinical research landscape and because of the high quality with which Pivotal´s associates face and manage all clinical projects that have been entrusted with – all of these aspects a trademark of Pivotal and which have warranted an essential number of clients repeating business with us (almost 75% of repeat business), and others turning to Pivotal to assume the rescue of their on-going trials when “not flowing” as planned (some 32 clinical trials to date). Yet, and aside from all those more general and technical features defining Pivotal, the team believes that its most essential strengths come not only from themselves but also

13. from its internal culture and a unique way of approaching their clients and their concerns, always from a personal perspective and commitment to deliver high-quality results. inputs, and put itself in their shoes to better comprehend their needs to become an extension of their teams. Last, it is important to mention that apart with its clients, Pivotal aims to stay connected with the “ecosystem” – namely, the whole clinical and innovation communities- to warrant in-time access to breakthrough science, best sites, talent, and technology—delivering daily to its clients, and making sure every deliverable, document, slide, or message is clear, adds value and, eventually, reduces time to market. This all is what, the team believes, has made Pivotal a favorite partner for a high number of Biotech and Pharma companies. The Continuum of Success Over the years, Pivotal has succeeded in attracting–and retaining- exceptional associates, all committed to and passionate about clinical research and delivering medical solutions much closer to patients. Such “exceptionality” can be found at all operational levels, and its staff–particularly its senior management teams- is absolutely approachable and directly–and personally-involved in all projects that the company collaborates with. Adapting to the post-COVID-19 Clinical Trials Scenario Pivotal and its associates are pretty aware of how costly and crucial every single project might be for the clients. They feel unable to get into any clinical study–ample or “tiny”- without putting the company’s experience and knowledge into them. It was undoubtedly unthinkable back in 2019 that a “catastrophe” like what the COVID-19 pandemic has represented could simply happen and, much less predict all the effects it brought alongside–at a global level and, obviously, at any smaller single compartment of human lives, including the clinical research ecosystem. When working with Pivotal, clients do not simply work with “individuals” but with a robust team driven by a “one- team” attitude, commitment, and integrity. Pivotal tries to keep its customers in the center of its work, listen to their Analyzing how the COVID-19 has impacted the clinical trials–and may impact in the future- is not a

14. straightforward question but rather a polyhedric complex problem requiring simultaneous looks from quite different but complementary angles. Indeed, the COVID-19 pandemic and all lessons learned will condition the clinical trials arena in the future and how all actors involved play their respective roles. And potential new clinical research scenarios and rules will need to be considered, yet still maintaining patients at the very core, warranting their rights, hopes and illusions and having them reassured at every moment–may other pandemic burst out (or any other similar event) that they, patients, will be treated as needed and deserved. Firstly, it has affected all companies developing new medical solutions for patients, including Biotech and Pharma and other supporting-services companies like clinical CROs. Then, undoubtedly, it has impacted the organization of investigators at investigational sites who had had to adapt, from one day to the next one, to a different way to handle and manage their clinical research activities and their patients–with patients not able to attend their visits at the sites. Among the lessons taken from the “COVID-19 experience, Pivotal has learned that there are alternatives to the classical face-to-face visits to sites and that data can still be collected and verified remotely as much as possible. But also, others by simply using online technologies that allow patients to transmit outcomes, as per the corresponding protocol. Or in other words, the COVID-19 pandemic has probably opened up the door to that new type of decentralized clinical trials (DCTs). Advantages, disadvantages and challenges of DCTs vs. centralized trials will require, on the other hand, deep discussion in another article and this is beyond the topics that pretend to be now covered. And last, likely the most critical link of the chain, it has had an impact on thousands of patients being treated in the context of clinical trials, frightened that the hopes they put in every new treatment they were helping to develop for themselves and for others may simply fly away. However, despite the potentially terrible scenario that COVID-19 may have resulted in, all actors involved in clinical research have found a way to move forward and overcome all hurdles encountered. , Pivotal also experienced that during this COVID-19 period, the study treatment–commonly administered at each investigational site- can be efficiently delivered to patients by post or courier to the safety of their homes for self- administration. And that even for more complex administration routes requiring, for instance, injections, specialized staff may visit patients at their places for dosing –and, why not, to collect samples as needed. Nevertheless, and despite the alternatives just pointed out and applied by Pivotal, there will surely be many procedures, trial activities and measures or trial compounds – e.g., particularly unstable- that will not allow an easy shift to this potential new model of making clinical research home-friendly. Pivotal definitely wants to play the new game of DCTs but always remains true to its client- oriented and pa?ent-centric a?tude, its commitment, and strong belief in science and quality as the basis to build on medical discoveries and advances. Be as it may, the “take-home” message from the COVID-19 outbreak is that alternative ways of doing clinical research are possible and that “rethinking” clinical trial designs and operational approaches are much more than recommended. All parties–from sponsors to investigators and sites to patients and regulators- must change their mindsets and look at these alternatives with interest since they may also help to reduce the overall costs of clinical investigations. And Pivotal and other clinical CROs, on their side, will have to adapt their operational procedures to this new clinical research (remote) environment–surely, a long way to go ahead, but much motivating.

15. Innovation and new technologies will be the basis of this potential transformation, which is already in Pivotal’s DNA. Thus, the company meets the first “inclusion criterion” for this new environment and paradigm shift. work towards giving an impulse to the science behind clinical research. With this objective in mind, the company has onboarded new talent forged in a research-making environment with a proven capacity for planning and conducting experiments and, importantly, for analyzing, interpreting, and publishing results. And for the future, the company considers, if not entirely shifting to DCT-like approaches, at least to start walking that new pathway parallel to the classical one. Pivotal definitely wants to play the new game but always remains true to its client-oriented and patient-centric attitude, its commitment, and strong belief in science and quality as the basis to build on medical discoveries and advances. Pivotal’s ultimate idea is to provide such strategic scientific analysis and advice to its clients in every new project it is awarded, in real-time, so that rapid but robust decisions on how to progress forward can be made, avoiding the compromising of a total budget in a project that may have lost sense or which may benefit from re-focusing. Embracing the Future Roadmap The CRO market is constantly moving, and on the basis thereof, “M&A” processes rely on. And as a consequence of this, new giant actors emerge every year while smaller CROs suffer, if not literally close the business. Niche specialization or shifting to new target sponsors – e.g., biotech- may help them to survive and thrive, though. An independent Look at Pivotal Pivotal is proud of being the foundation it is today, and its team believes in “we-are-Pivotal;” hence it runs the risk of acting subjectively when giving marks to the company. External independent opinions may help, though. These words of wisdom showcase the status quo of Pivotal—being one of the innovative CROs in the healthcare industry. Detailed quotes are depicted in our website at www.pivotalcr.comand at our patient journey arm division at www.pivotalpatientjourney.com and below is an example of these quotes: These are certainly the market rules but are a trend that may deprive the smaller innovators Biotech of partnering with the right-size yet experienced CROs if no other actors can be found out there. Not much to do to stop the market’s hunger, but just sending a message to smaller innovators and sharing the thought that rightsizing is still a valid principle for sponsors to consider when selecting their partner CRO–hence, mid-size CROs such as Pivotal will surely be much more agile and will put their clients´ projects among those much more important for the client. “Pivotal continues to be my CRO of choice. They complement our existing team by providing functional area expertise that we do not currently possess. Their personnel are highly engaged, experienced, and proficient in what they do. Pivotal’ s leadership team is experienced and more importantly, incredibly engaged throughout the entire study. These are some of the reasons Pivotal continues to be a trusted partner for us.” -Chief Operating Officer, at a US- based Medical Device Co Mid-size and smaller focused CROs are likely different from merged giants in that they may be just one more team member of their clients and work incredibly close to the proper clients´ internal teams. And at least, this is what the company has been doing and pretending at Pivotal and what has been the basis for its success story to date. “I have worked with Pivotal on two studies and have been particularly impressed with the care they give studies, their personal attention to the needs of sponsors, and their dedication to getting things right. Pivotal is a closely-knit group. There is no bureaucracy, simply the dedication to serving the needs of their biotech clients. They are the closest thing I can find to having my company personnel on the ground in Spain and Europe.” -Chief Medical Officer, at a US-based Biotech Co The future starts today, actually, and for 2023 Pivotal intends to keep growing while remaining faithful to the “organic growth” policy it has been following since inception – rather than basing its expansion solely on “M&A” operations-. Therefore, the company plans to offer something else to entice old and new clients. COVID-19 outbreak has pointed out the new pathway to follow-DCTs, digitalization, technology- and, as already mentioned, this is a maneuver in which the company has already been investing to get there. But in the short term, Pivotal plans to

16. , “The team at Pivotal operates as a seamless extension of our internal team, building trust with our European clinical trial sites and our confidence in our ability to execute high- quality clinical trials. The Pivotal management team acts as a true partner, equally focused on our objectives to develop innovative therapeutic treatments for patients with serious unmet medical needs.” -Group Vice President, Development Sciences Operations at a Mid-Size US Pharma Co Pivotal has succeeded in a?rac?ng – and retaining- excep?onal associates, all commi?ed to and passionate about clinical research and delivering medical solu?ons much closer to pa?ents. “As an independent investigator and head of a Cooperative Group, I have been working with Pivotal since 2014 on six projects in GU tumors and what I have encountered is a dedicated team to clinical research, very much attentive to the complex needs of independent investigators, responsiveness and quality-minded throughout. The team gets it right the first time in all the services, including regulatory and clinical operations, medical and safety monitoring, data management, and biostats. Pivotal is my favorite CROs to work with, and I have no hesitation in recommending it for any new trials in Oncology and beyond in Europe.”-Senior Researcher PSMAR/IMIM Hospital del Mar, Barcelona, Spain, and Associate Professor of Medicine Harvard Medical School “The patient recruitment process has been awe-inspiring, and I have learned a lot through your company and your C- Lys patient platform. You are making the world of research a better place with your company and your ways.” -Ophthalmologist and PI and Med. Monitor lead in FDA- monitored clinical trials. “I have worked with Pivotal on international clinical trials both of an ICU therapeutic and a cancer screening device/diagnostic. I cannot think of a better partner. A cost- effective collaborator with deep functional expertise, particularly in data management, biostatistics, medical monitoring, pharmacovigilance, and project management, but even more importantly, a company with a culture of problem-solving and shared responsibility. “And all of the above seems to be supported by the fact that Pivotal was selected as one of the few firms that attracted recognition from the Pharma IQ network as a RISING STAR.” Working with Pivotal is never “us” and “them”; it is one shared mission with a group of professionals who simply do whatever it takes to accomplish the goal. This starts at the top, with the credible, expert, and ever-present leadership of the CEO, himself a former senior Pharma drug developer, and filters through every layer of the organization.” -CEO, at a US-based Biotech Co. The research base comprised international participants from mainly big Pharma or Biotechs, SMEs pharma and consultants, government bodies, medical device manufacturers and public hospitals. We have kept doing as good as then, so we are confident we will surely be perceived now as we then were. Clients have the last word, but business coming in aligns with this feeling.

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18. Industry Sagacity 16 JANUARY | 2023 www.insightscare.com

19. The Impact of Emerging Technologies on the Pre-Clinical CRO Market T turbulent oceans of changing times are novel ways of carrying out or performing preclinical research and conducting trials. echnology is changing the health world’s future, while future technology is reshaping the present world of health. Already emerging from the Many giant Clinical or Contract Research Organizations (CROs) have already started integrating their preclinical research, testing, and trials with not only digital, virtual, and remote technologies but are also implementing Artificial Intelligence (AI), Cloud Computing, and Machine Learning (ML) technologies to efficiently conduct, perform, or carry out such experiments in increasingly enhanced environments. The process of developing a medicinal product is a long one, where there are many subprocesses like idea or concept generation, framing, discovering and developing that idea further, then the pre-clinical research stage then comes to the clinical trial stage, and finally, the FDA assessment and review stage which approves or disapproves the product based on its criteria. The Power of Modern Tech Although all these subprocesses are equally important, the stage where pre-clinical research is conducted is the most crucial one as the prospective product ideas or concepts 17 JANUARY | 2023 www.insightscare.com

20. have a strong chance of failing. This is where preclinical CROs play a very major role in opting for advanced technologies so they could research till the last element of each idea and concept from every possible angle, and find out the possibilities, and probabilities of the success and the failure of the drug or medicine in development. Due to this rapid vaccine development, according to The New York Times’ COVID vaccine tracker, as of July 2022 over 5.23 billion people or 68.2% of the world population have received a dose of a COVID-19 vaccine. Futuristic Technologies is the Future Clinical trial researchers also get benefitted by gaining actionable insights into the detailed reports created by using digital technologies. For example, AI and ML are now widely used in the most appropriate sample group selection that responds more to the pre-clinical tests and trials. Modern technologies are not only giving more power to the preclinical CROs to look at the preclinical trial process with a holistic view increasing the probability of the drug or medicine moving to the further stage but are also helping them in saving huge costs. Let us look in detail at these reasons and dig ourselves deeper to gain a broader perspective. The first major advantage of using these techs is the automated cellular level selection, data generation and analysis. These futuristic technologies modern cell-based selection offers an early-stage issue identification and problem detection with potential drug developments and testing. It aids in reducing sample wastage, time, and effort, and streamlines the entire process of research and development. For example, data samples collected during the research using AI can also be utilized for the most suitable patient matching during the clinical trials testing process. A Holistic Tech Perspective: Advance Technological Implementation lowers the Uncertainty of the preclinical experiments by streamlining and optimizing detailed data collection, easing down the pre-clinical trials’ subject selection, decreasing the time duration of research, and reducing financial costs. Research, data collection, test subject selection and continuous analysis are an integral part of drug research and medicine development. However, with increasing intricacy in the entire process, navigating through the continuous stream of incoming data gets impossible for the human researcher. Preclinical image, graphics, and sample matching and analysis process automation are also feasible using techs such as AI and ML. CROs are now increasingly using these technologies for automated testing sample analysis, identification of molecular compounds, and analyse patterns for drug discovery. This is where advanced technologies like automation, AI, cloud computing, Big Data Analysis, ML, etc. provide not only monitoring, tracing, tracking, and collecting data but also deep and machine learning of the recorded data to offer precise analysis, interpretation, flow, pattern while matching the samples with earlier available ones. For Example, AI is now being used by the Institute of Cancer Research for making predictions regarding cancer drugs’ novel prospects and performing repetitive tasks like research record up-gradation and data extraction. Likewise, scientists have successfully developed Eve, an AI Robot to help researchers in speeding up the drug discovery process. Live COVID-19 Example: It is because of using such novel technologies that in just a year and a half, CROs across the world could come up with more than a dozen coronavirus vaccines including Serum Institute of India’s COVOVAX which has been developed through three trials in one country and approved in five countries, COVISHIELD (Oxford AstraZeneca Formulation) developed through four trials in one country and approved in 49 countries; Novavax’s NUVAXOVID which has been developed through 17 trials in 13 countries and approved in 38 countries; Oxford/AstraZeneca’s VAXZEVRIA developed through 66 clinical trials in 31 countries and approved in 140 countries; and so on and so forth. -Anish Miller 18 JANUARY | 2023 www.insightscare.com

22. 10 Most Innova?ve CROs To Watch In 2023 T Acknowledging these concerns of filling up the operational gaps and solving the problems in a timely manner, Clinergy Health Research has solutions to a variety of managerial issues while also providing a full revamp of all the health care processes. he Healthcare industry usually faces problems to bridge the gap to solve the problems promptly, and isn't it something that should be taken care of? This is now more important than ever as we see what has been happing to the CRO environment over the past two decades, with so many mergers and acquisitions resulting in huge CROs with inflated structures (and costs) that surely can still serve a set of substantial clients but no longer fits to serve small biotechs, pharma companies and healthcare start-ups given their very particular needs in terms of costs, flexibility, sense of urgency and attention. Unlike most CROs, our key driver is not related to short- term financial goals. However, long-term customer satisfaction and we bring that to daily life through the way we shape our KPIs, quality control strategies, and risk- based thinking in everything we do. Another element that brings our unique mindset to life is the fact that we have made a conscious decision not to have a business development/sales team. Having this problem-solving approach and abundant experience, Tiago M D da Silva, Managing Director, has scientific and management knowledge to enhance the operational experience and deliver superior results. In an interview with Insights Care, Mr. da Silva talks about Clinergy roles and how it is making a significant difference through its solutions into the healthcare niche. Whenever clients reach out to us looking for our services, they get to talk directly with our team of medical doctors, pharmacists, nurses, biologists who will be directly involved in the client´s clinical trial/project, most of whom have been on clinical development for 15, 20+ years. Please brief our audience about Clinergy Health Research, its USPs, and how it is positioned as a reliable name in the CRO sector? Clinergy is a CRO, but we always like to highlight that our "C" stands for "Collaborative" rather than "Contract," and, while for some people, that might look like a small detail, it makes all the difference. Being a Collaborative Research Organization means that our structure, processes, values, and people are fully focused on long-term value-adding partnerships rather than on short-term transactional relationships with clients. Such a mindset allows us to truly embrace our clients´ vision and ways of working. We act as an extension of their team, focusing on what matters to them while feeling empowered to "run the extra mile" to deliver operational excellence. At the end of the day, science comes first in everything we do so that we can achieve our mission of "helping health innovation reaching patients faster." Shed some light on your offerings and how they impact the CRO industry as well as your clients. How your company provides research services to various organizations? The value we add as strategic partners to our clients is much more a result of our focus on the "how" rather than on the "what." We are equipped to provide end-to-end planning solutions, conducting and reporting clinical trials from site 20 JANUARY | 2023 www.insightscare.com

23. Tiago M D da Silva Managing Director Our values are built upon elements that are key to delivering operational excellence with a high focus on the human aspects that make a difference in how we deliver it daily. feasibility and selection to project management, regulatory submissions, risk-based monitoring, data management, statistics, medical writing, among others. However, the means we utilize to deliver are essential. We are very meticulous when it comes down to understanding what delivery methods can fit each client better so that we can offer cost-effective solutions tailored to each of them without having to choose between cost and efficiency and without trying to push "over the top" solutions only to justify we have them. 21 JANUARY | 2023 www.insightscare.com

24. While we rely on state-of-the-art tech solutions to plan and manage trials efficiently, our secret sauce is our people, no question about it. As we like to say, Clinergy is all about "humanology and technology for high-performance clinical development." informed decisions around study design, monitor workforce assignment, and conduct remote trials. At Clinergy, we can embed various levels of technology according to each trial´ needs, from eTMFs that count on machine learning to automate document filling to high-tech risk-based study execution solutions that cave save up to 40% of monitoring costs. What are the core values upon which Clinergy Health Researchis built? What is the vision and mission of your organization? Our values are built upon elements that are key to delivering operational excellence with a high focus on the human aspects that are effective in how we deliver it daily. What would be your advice to budding entrepreneurs who aspire to venture into the CRO space? Setting yourself to be able to act as a partner to companies that operate in one of the most regulated environments out there is no easy task; people should know. The most important point I would highlight to those considering entering this space is: to make sure the core values which you believe will set our company apart from other players are genuinely embedded in daily operations. All the rest is easily available to anyone else. In an expensive and complex market such as clinical development, the cost is certainly not part of the top three decision factors for most companies as they know how much more expensive it could be to have an entire clinical trial failing due to operational flaws compared to paying a bit more to have a partner who can deliver high standards by their side. They are a sense of urgency, entrepreneurship, efficiency, caring for others, integrity, and passion. We all know how hard and costly it is to put health innovation into the hands of those who needed it, and, as scientists, there is nothing more disappointing than inefficiencies playing a role in that. Our mission of "helping health innovation reaching patients faster" reminds us that we should always be acting as catalysts so that we add real value to the innovation chain. Mr Tiago, please tell us about your professional tenure in the CRO Industry. Before founding CLINERGY, I have fulfilled different clinical operations roles, including leading the Global Clinical Research Operations for medicinal products within a UK-based FTSE 100 consumer health company. I had the pleasure to spend the last 17 years driving and delivering strategic projects for companies such as Novartis, Abbott, Eli Lilly, and Reckitt Benckiser, helping patients have access to value-adding medicines and health innovation across multiple geographic locations. How do you envision scaling your organization's operations and offerings in 2022 and beyond? We have a clear view when it comes down to our growth expectations. Although the demand is very high, we have no interest in growing at any cost as we know the dangers that come with that. We suffer no external pressure to deliver better financial results every quarter as a privately held company. That allows us to entirely focus on customer satisfaction based on high-quality and high-performance output as key drivers. We have been growing steadily, and we plan to keep a close eye on the balance between growth and excellence. Having lived and worked in both hemispheres on either side of the Atlantic, I have acquired an intimate appreciation of the cultural and regulatory differences that truly impact global clinical research. Being an experienced leader, share your opinion on how modern technologies have impacted the CRO sector. How has Clinergy Health Researchincorporated such technologies into its daily operations? Clinical development has benefited a great deal from new tech solutions over the past 15 years, most notably over the past decade. CROs have a key role in making innovative solutions available to their clients by utilizing data-driven solutions to reduce operational complexity, make better- 22 JANUARY | 2023 www.insightscare.com

26. Oscar Juan MD, PhD, Medical Oncologist, Senior Medical Manager Pivotal S.L 24 JANUARY | 2023 www.insightscare.com

27. Gene THERAPY andCancer Treatment G ene therapy has evolved from being science fiction to becoming a reality with the possibility not only for treating hereditary diseases but also for treating genetically complex diseases, such as cancer. In vivo gene therapy: the therapeutic nucleic acids are introduced directly into the patient’s body. The vector- gene construct is introduced by cell-specific direct injection into tissue in need. Once inside the body and in contact with the targeted cells, the gene is incorporated into the tissue’s cells, encoding the production of the needed protein. In vivo gene therapy is less complex than in vitro gene therapy. However, in general, there is less control over the transfection of the gene and its efficacy. Ÿ Gene therapy can be defined as the set of techniques that use nucleic acids (DNA, RNA, or their variants) to replace, correct, or inhibit an endogenous gene in the cells of the organism or, acting independently of the gene, use a nucleic acid to synthesize proteins or enzymes that provide new biological properties to cells or tissues. The objective of gene therapy is to treat or alleviate a disease. Ex vivo gene therapy involves extracting the cells from the system, isolating them, growing them in a culture, and inserting the genes. Afterwards, cells are returned to the body in a similar procedure such as those used in hematopoietic stem-cell transplantation. Ex vivo gene therapy has the advantages of allowing to choose the cell type, having more control over the procedure, and having greater efficacy in gene transfection. However, its complexity is higher than in vivo gene therapy, has an increased cost, and can only use cells that can grow in culture. Ÿ Depending on the target cells on which we´d want to act, we can differentiate two kinds of gene therapy: • Germ gene therapy, which is the insertion of the therapeutic gene in germ cells, such as egg cells in females and sperm cells in males. Since this therapy alters the germ cells, finally, the changes move on to the next generation. This type of therapy could be used to definitively correct congenital diseases. However, this has not been done in humans due to its greater complexity and, especially, due to ethical considerations. Delivery strategies for therapeutic applications The goal of gene therapy is to achieve a durable expression of the gene transfected to correct the gene alteration that causes the disease. A safe, effective, and controllable delivery system is key in gene therapy. There are two types of vectors: viral vectors and non-viral vectors. • Somatic gene therapy, the objective of this therapy is to introduce or alter genes in somatic cells, i.e., the cells that make the body tissues of multicellular organisms. These changes are not transferred to a person´s offspring. In Vivo and Ex Vivo Gene Therapy Viral vectors Depending on how we manage genes, we can differentiate two types of somatic gene therapy: Viruses are, so far, the most used delivery strategy. The advantages of viral vectors are the availability of well- established protocols, high transduction efficiencies, and 25 JANUARY | 2023 www.insightscare.com

28. About the Author Oscar Juan, MD, PhD, Medical Oncologist, Senior Medical Manager at Pivotal S.L.U. Oscar is MD from Universitat de València, Spain (1991) and trained in Medical Oncology and Haematology at Hospital Clínico Universitario de Valencia, Spain (1995). He also holds a PhD Cum laude from Universitat de València (2002). He has been working as Medical Oncologist since 1996 in various hospitals in Spain and most recently at Hospital Universitari i Politècnic La Fe in Valencia, Spain. He has participated as Principal Investigator in more than 100 international trials including pivotal trials than have changed the clinical practice and paradigms in lung cancer treatment. As a member of the Biomarker and Precision Medicine Unit, he was focused on metabolomics, epigenetic and genomic biomarkers in EGFR-mutated lung cancer patients and patients receiving immunotherapy. He joined Pivotal in January 2020 as Senior Medical Manager in Oncology. He focuses on supporting the strategic clinical development of new molecules and acts as the medical reference and medical monitor for several innovative early phases trials and provide guidance to the Clinical Project team members at Pivotal to ensure adherence to study objectives and timelines. 26 JANUARY | 2023 www.insightscare.com

29. having mechanisms for introducing genetic material into cells systematically. Viral vectors include retrovirus, lentivirus, adenovirus, and adeno-associated virus (AAV). Retroviral vector was the earliest used and has a minimal risk of causing insertion mutations. of medicine, such as neurodegenerative and cardiovascular diseases, viral infections, and cancer. Since cancer is the accumulation of various mutation types that regulate gene networks promoting cell proliferation, RNAi is an attractive approach to treating tumors. Non-viral vectors Suicide gene therapy consists in introducing suicide genes to express enzymes or proteins that directly trigger the death of tumor cells (the gene encodes a protein that is cytotoxic) or indirectly (the gene expresses enzymes that are sensitive to a drug that is administered concomitantly). Ÿ Non-viral vectors can carry a higher genetic load, are safe, and generally induce a lower immune response. The liposome is one of the most attractive non-viral vectors for gene therapeutics. Liposome has no inhibition and no significant damage to normal tissues and cells around the target cells, enabling the target gene to be fully transfected into the target cells. After the success of SARS-CoV-2 vaccines, lipid nanoparticles have become a widely used vector for gene therapy. Chimeric antigen receptor (CAR)-T cell therapy is a slightly different process with respect to the more direct forms of gene therapy. CAR-T cells are a lab-generated fighter cells customized for each individual patient. They are made by collecting T cells from the patient and re-engineering them in the laboratory adding anti-cancer genetic code to produce proteins on their surface called chimeric antigen receptors, or CARs. These CARs recognize and bind to specific proteins, or antigens, on the surface of cancer cells. Ÿ Gene therapy in monogenic diseases Gene therapy was initially conceived as a treatment of genetic diseases caused by mutation of a single gene (monogenic). Hereditary diseases include various disorders in which a defective gene determines that a protein is not synthesized or is elaborated abnormally, causing many different clinical manifestations depending on the structural or enzymatic function of that particular protein (e.g., hemophilia A). These problems could be solved with gene therapy by supplying a normal copy of the defective gene to the affected tissues. CAR-T cell therapies are the most common technology used in potential cancer therapy and represent 49% of the genetically modified cell therapies pipeline. However, CAR-T cell therapies can cause severe side effects being the most frequent and serious one the cytokine release syndrome (CRS). Approaches in Cancer gene therapy To date, the FDA has approved several CAR-T cell therapies for hematological diseases. However, challenges remain for the use of CAR-T cell therapy to treat solid tumors due to their heterogeneity and localizations in the human body. Cancer occurs due to the disruption of normal cell proliferation and apoptosis processes. The aim of gene therapy in cancer is different from the treatment of monogenic diseases in which the goal is to correct a specific genetic defect. Conclusions Drawn Several gene therapy approaches have been developed for cancer management, such us: Gene therapy represents a novel therapeutic approach for managing diseases with difficult treatment. Monogenic diseases have been treated successfully with gene therapy, but cancer is a complex process in which cells have altered their normal proliferation and apoptosis. Recent progress in developing safe and effective vectors for gene delivery, understanding gene editing, and the advances in adoptive immunotherapy with CAR-T cells has opened up new avenues and strategies for treating intractable diseases. Oncolytic Virotherapy (OV) is one of the most promising approaches for tumor immunotherapy. OV introduce wild-type tumor suppressor genes into cells that lack the tumor suppressor gene leading to tumor cells’ lysis inducing an anticancer immune response (e.g., p53 gene). Ÿ Gene silencing therapy uses an RNA interference (RNAi) that induce sequence-specific degradation of complementary mRNA. RNAi is used in different areas Ÿ 27 JANUARY | 2023 www.insightscare.com

30. Role of CROs in Shaping the of Clinical Research Future P ost COVID-19 pandemic world has completely changed. The impact is most severe on the healthcare industry, especially on the clinical research and trials activities across the globe. The life science industry met unprecedented challenges which forced it to accelerate innovation, revamp its traditional mindset and embrace digital, virtual and online capabilities to ensure service continuance. Traditionally, the Industry was very cautious, slow and reticent in adopting digital and virtual clinical trial practices. It was comprehensible, evident and expected since many of the device-dependent diagnosis and treatment driven therapeutic areas added much more complexity to the digital, virtual, and remote offering evolution. Further, already established, proven, and existing decade old practices could not be abandoned or replaced or shifted to the digital, virtual or remote mode. This emerged as the major concern in the continuance of clinical research and trial niche, leading to almost 87% reduction in clinical research in England during the peak time of first wave, as later found out by University College London study. Answering the question of avoidance, the industry opened up its mindset to accept the changing realities of clinical trials and shifting nature of clinical research in the post-pandemic world. 28 JANUARY | 2023 www.insightscare.com

31. Redefining Advancements 29 JANUARY | 2023 www.insightscare.com

32. The Changing Dynamics of Clinical Research Industry modalities which will constantly keep improving the future performance of clinical trials. A rapidly growing industry, clinical research and trials is advancing due to new studies conducted in record numbers, ever-increasing patient participation expanding the clinical trial subject pool, numerous research sites of excellent quality, and a huge volume of successful trials over the years contributing to the expertise and values. Further development of technical modules and various modalities could improve clinical trial continuance and drive innovation and change to the higher level. It will provide a primary foundation for the both hybrid modelled and fully virtual research and trial environments which will be completely equipped with precise tools, adequate techniques, robust and seamless infrastructure, a well-integrated ecosystem, and big-data analytical methodologies. Creating Streamlined Ecosystem: However, all these modalities and modules must meet the standard criteria’s and benchmarks of excellence so that the safety and security of the trials could be maintained or enhanced. This is where digital, virtual, and remote technologies could aid in optimizing various processes like site feasibility, pre-screening of patients, selection and clinical trial providence. By reviewing its own trends, changes, pressures, upheavals, successes and failures during the last two and a half years, the clinical trial industry managed to come up with more than a dozen coronavirus vaccines, thus pushing forward the innovation driven momentum and accelerating the renewed focus by considering key factors of success. When cross-functional entities work jointly, all the related stakeholders could participate in offering inputs, gaining information, and mutually assessing the developmental approaches to increase the result acceptance amidst the changing market dynamics. This is crucial when deriving digital, virtual and remote clinical trial effectiveness assessment. As they have easy access to patients, clinical investigators, sites, and sponsors, partners of Clinical Research Organizations(CROs) can promptly facilitate further enhancements in digital, virtual and remote clinical trials conductions success. Futuristic CROs Transforming the Clinical Research Tech-Focus: Before the pandemic happened not any expert would have been able to predict the future of healthcare industry forget of clinical research and trial industry. Although the pandemic is unprecedented in its devastation, one thing it did good is the way it diverted the entire progress path of sector world over. With many of the restrictions still being in effect, industry’s digital mindedness is continuing. Simply, the industry has now fully adopted an entire decentralized virtual model attitude or a hybrid approach. In this new approach, organizations are compelled by the virus to continue with the clinical trial modalities which can offer at-home or remote testing facilities along with online practices and digital techniques. It will ensure clinical trial continuance for patients in a more comfortable, convenient, safe and secure manner. This will be done without any negative impact on the clinical investigators participation. The possibilities, opportunities, and probabilities it has opened up is an unimaginably positive future in itself. The journey has merely started. We could push the boundaries of now established innovation further. This way we could explore some unexplored areas in the clinical trials with many CROs coming together and creating an upbeat ecosystem which will operate like an industry organ which will facilitate a future where globally innovative modalities could be established, enhanced and advanced so that whenever any unprecedented crisis situation will arrive in the future, the industry as a whole and the world as united will be able to combat. During the last two and a half years remote pre-screening tests, e-consent practices and monitoring approval by patients and clinicians is on the rise. Since they are now established as preliminary benchmarks for future modalities, the industry could further leverage advancements in practices best suitable and feasible across the entire spectrum of life science industry to further drive safe, secure, flexible, patient-centric, comfortable, convenient, and efficient clinical research and trial -Anish Miller 30 JANUARY | 2023 www.insightscare.com

34. OnQ Research C well as for academic institutions, governmental agencies, and foundations. Using a CRO for outsourcing reduces the amount of time needed for clinical trials and product development. 10 Most Innovative CROs to Watch in 2023 Blend of Innova?ons Assuring Adaptability linical trials are carried out by contract research organizations (CROs) for the pharmaceutical, medical device, and biotechnology businesses as The Adept Leader Catherine started her clinical research journey as a study coordinator for an RSV trial. She then joined IQVIA (then Quintiles) as a clinical trial assistant in 1996 and trained to become a CRA. She started consulting in 1999 and gradually evolved the business into a CRO. She describes herself as an accidental entrepreneur and grew the team and processes as the demand grew. When compared to conducting the trial internally, working with a CRO frequently results in significant time savings. The tools and resources needed are already available to CROs, and they also have a staff of internal experts with experience in all facets of clinical testing, development, and compliance. Catherine Lund is the Founder and Managing Director of OnQ Research. She is, by training, a registered neonatal nurse who entered the clinical research arena as a research nurse, followed by her formal clinical research training at Quintiles. She left Quintiles to pursue a career in contracting. With more than 20 years of experience, OnQ Research is a full-service contract research organization (CRO). It is dedicated to offering pharmaceutical, biotech, other CROs, and allied businesses innovative, affordable, and useful clinical research services. OnQ Research was established in 1999 and has since carried out more than 500 clinical trials in southern Europe and more than 10 African nations. Without the chance to incorporate other African nations, South Africa cannot be viewed in isolation. Mozambique, Botswana, Rwanda, Ghana, Uganda, Kenya, and Tanzania are just a few of the African nations where OnQ Research has conducted extensive research. This entails assessing a new region and assisting in the creation of full-fledged, qualified clinical research sites through site evaluation and resource and capacity building. Success in all clinical trials on the African continent is guaranteed by its distinctive Clinical Monitoring Team concept and clinical study approach. The company is known for producing high-quality research quickly and effectively. Through collaborations, she then established OnQ Research, initially as a consultancy, which evolved into a full-service, South African-based CRO in 1999. Catherine Lund has served on the SACRA (South African Clinical Research Association) Exco for a period of three years. She was the Vice Chair for the South African Chapter of ACRP (Annual Review of Competency Progression) in 2003. Clients can centralize research across Africa with the help of OnQ. Due to its extensive expertise and experience, it can provide excellent patient care, lower risk, and superior data management. OnQ's clinical research team is spread across all of the major cities in each nation, allowing it to be flexible and deploy resources as needed. Catherine Lund is a registered nurse with a diploma in general, midwifery, community health, and psychiatry, a certificate in neonatal intensive care, and a BA in diplomacy and political studies from B.G. Alexander Nursing College and UNISA, respectively. Under the adept leadership of Catherine Lund, the Founder and Managing Director, OnQ Research offers 32 JANUARY | 2023 www.insightscare.com

35. Catherine Lund Founder and Managing Director OnQ Research

36. expertise for clinical trial execution. Internally, we also apply the same value. We are passionate about career growth and offering potential candidates opportunities to add value to our organization. Collaboration: OnQ collaborates with sponsors and clients to drive cost- effective delivery of clinical trials. Quality-focused. We are committed to the ethical conduct of clinical trials and delivering quality data for drug registration. OnQ Research prides itself on offering its clients a blend of innova?on, adaptability while adding real value with its highly trained staff. Being an experienced leader, share your opinion on how modern technologies have impacted the CRO sector. How has your company incorporated such technologies into its daily operations? top-notch clinical trial management and coordination through CRAs with regional bases in all major cities in the nations it operates in. This ensures close site management and reduces costly travel expenses. It is perfect for all of its clinical trial management needs due to its significant experience in carrying out successful trials. We make use of carefully selected, fit-for-purpose systems for day-to-day clinical trial management. We use a CTMS for project management tracking and are in the process of implementing a locally developed learning management system and quality management platform. As our company grows, the implementation of new technologies is crucial to improving efficiencies. Still, it requires careful risk-benefit considerations to ensure that we remain capable of delivering a high-quality product at a competitive price. Below are highlights of the interview that emphasize OnQ’s services to assist with the entire continuum of clinical research. Catherine, please brief our audience about your company, its USPs, and how it is positioned as a reliable name in the CRO sector? What would be your advice to budding entrepreneurs who aspire to venture into the CRO space? OnQ Research is a South African-based, organically grown CRO servicing primarily the African continent. OnQ Research prides itself on offering its clients a blend of innovation, adaptability while adding real value with our highly trained staff. We use science as the basic premise for our services without compromising on quality. Although I am, of course, biased, this is one of the most exciting industries in which to venture. Networking is key. Attending as many conferences as you can and accessing as much information as you can. Understand what part of the CRO space excites you and where you can see your future path. OnQ Research does not have a “one size fits all” approach.’ This applies to all aspects of the client relationship and interface, from budgets to sizes of teams, systems and processes offered, and levels of engagement. How do you envision scaling your organization’s operations and offerings in 2023 and beyond? Our company is very deliberate in its focus on being the premier CRO in Africa. Our plan to achieve this is to be intentional about investing in our staff and understanding that all our clients require a bespoke and unique service. Shed some light on your offerings and how they impact the CRO industry as well as your clients. How your company provides research services to various organizations? Please give us a few testimonials of your clients/customers and a list of awards/recognitions that accurately highlight your organization’s position in the market. (If available/permissible) We offer assistance with protocol inception and design, liaising and obtaining appropriate Health Authority and IRB approvals, selecting high quality sites through our extensive networks, project management, monitoring, data management, and medical writing. Our clients consistently offer similar feedback in that they enjoy working with our organization, which is flexible, adaptable, and up for any challenge. It has been broadly indicated that we have a “can-do” problem-solving approach to conducting clinical research without compromising on quality outcomes. What are the core values upon which your organization is built? What is the vision and mission of your organization? Our core values are Empowerment: We empower emerging biotech and pharma companies with tools, resources, and 34 JANUARY | 2023 www.insightscare.com