Trailblazing The Immuno-Oncology Frontier Best Companies Of 2024

February Issue 01 2024 Healing with Precision The Latest Advances in Immuno-Oncology Empowering the Immune System Best Prac?ces in Oncology Care Jacques Bouchy EVP Investor Rela?ons & Business Development Thierry Guillaudeux Chief Scien?fic Officer Shawn Iadonato Chief Execu?ve Officer Empowering Immunity, Defeating Cancer Kineta

Pioneering Pioneering Progress Progress I Everything" proudly presents the standout companies reshaping the cancer treatment landscape. n the dynamic world of healthcare, 2024 places us at the cutting edge of revolutionary advancements in Immuno-Oncology. Our latest edition of "Healthcare over adversity. It's an acknowledgment of the collaborative efforts propelling us toward a future where cancer is not an inescapable fate but a surmountable challenge. Join us in recognizing and applauding these exceptional companies that are shaping the narrative of Immuno- Oncology in 2024. As we navigate this groundbreaking frontier together, we are reminded that every discovery is a victory in healthcare, and every step forward is a triumph for humanity. This edition is dedicated to spotlighting the Best Companies of 2024 in Immuno-Oncology, whose tireless dedication and innovative methodologies are rewriting the narrative of cancer care. Like pioneers in uncharted territories, these companies are pushing the boundaries of what was once considered conceivable. From leveraging the immune system's potential to crafting avant-garde therapies, they stand at the forefront of a medical revolution. Wishing you an insightful reading and a renewed sense of hope! Editor’s Note Within the pages of this edition, anticipate captivating stories of perseverance, resilience, and the indomitable spirit of those who have devoted their lives to redefining the benchmarks of cancer care. The Immuno-Oncology Frontier isn't solely a scientific battleground; it vividly illustrates human determination and the collective will to overcome one of the most formidable adversaries we face. -Pea Shaw "Trailblazing The Immuno-Oncology Frontier Best Companies Of 2024" isn't just a compilation of success stories; it's a celebration of the triumph of the human spirit Managing Editor

Contents 08 Profile Empowering Immunity, Defeating Cancer Kineta Kineta Sensius Radiant Hope, Revolu?onary Healing 22 CXO Lisa-Jean Clifford Ar?ficial Intelligence, Image Analysis and Machine Learning in Pathology – Is it Really Valuable? 30 Articles Empowering the Immune System Best Prac?ces in Oncology Care 18 Cover Story Healing with Precision The Latest Advances in Immuno-Oncology 26

Editor-in-Chief Managing Editor Executive Editor Visualiser Art & Design Head Co-designer Art & Picture Editor Business Development Manager Marketing Manager Business Development Executives Sales Executives Technical Consultants Assistant Technical Head Technical Head Digital Marketing Manager Assistant Digital Marketing Manager SME-SMO Executives Alan Wahl CEO Abacus Bioscience abacusbioscience.com Shawn Iadonato, CEO Thierry Guillaudeux, CSO Jacques Bouchy, EVP Investor Relations & Business Development Kineta kineta.us Research Analyst Circulation Manager Alan Watt CEO NodThera nodthera.com February, 2024 Contact Us: Sensius sensiusthermo therapy.com Paul Van Den Biggelaar CEO and Co-founder Triumvira Immunologics triumvira.com Paul Lammers CEO

Empowering Immunity, Defeating Cancer Empowering Immunity, Defeating Cancer Kineta Kineta Cover My focus has always been on new drug development involving the immune system in cancer, infec?ous disease, and inflamma?on. ‘‘ - Shawn Iadonato ‘‘ Jacques Bouchy EVP Investor Rela?ons & Business Development Thierry Guillaudeux Chief Scien?fic Officer Shawn Iadonato Chief Execu?ve Officer

Trailblazing the Immuno-Oncology Fron?er: Best Companies of 2024 C biological processes. In the ongoing struggle between cancer and the immune system, a relentless battle unfolds where tumors strive to escape detection, and the immune system seeks to recognize and eradicate them. ancer presents a formidable challenge with its complex strategies of immune evasion, and Kineta is at the forefront of deciphering these complex areas such as cancer, infectious disease, and inflammation. He states, "My focus has always been on new drug development involving the immune system in cancer, infectious disease, and inflammation." Shawn sheds light on the transformative nature of his role, stating, "The CEO role has really allowed me to narrow the focus of the company to the immunotherapies that I thought were most exciting. Most exciting scientifically, and most exciting from a commercial perspective." Going beyond conventional therapies, Kineta delves into the profound world of innate immunity, seeking to retrain the body's ability to detect and kill cancer. Guided by the seasoned expertise of Shawn Iadonato, Thierry Guillaudeux, and Jacques Bouchy, the company is on a mission to unravel the strategies of immune evasion employed by tumors and develop innovative drugs to offer patients new treatment options for managing cancer. Under his leadership, Kineta underwent a strategic refocusing, redirecting assets to align with the company's emphasis on oncology. Shawn expresses his enthusiasm, affirming, "My fundamental motivation is that I'm really interested in groundbreaking science and new drug development. I really like biotech and the process of developing new drugs." As a clinical-stage biotechnology firm, Kineta is dedicated to transforming the lives of cancer patients through groundbreaking immunotherapies. Focused on addressing mechanisms of cancer immune resistance, the company actively engages in the development of immunotherapies poised to revolutionize and uplift the lives of patients facing serious health challenges. In describing the excitement fundamental in their work, Shawn highlights the uniqueness of the areas they research, emphasizing, "A lot of the areas that we work in are very novel. So, it's not like people have done the same thing before, and that novelty and innovation is very motivating." Shawn Iadonato, as Chief Executive Officer, brings over twenty years of expertise in guiding startup biotech companies and is also one of the co-founders of Kineta. Thierry Guillaudeux, the Chief Scientific Officer, brings over thirty years of experience in Immuno-Oncology, steering Kineta's scientific initiatives from discovery to clinical trials. Jacques Bouchy, the Executive Vice President of Investor Relations and Business Development, adds a wealth of commercial pharmaceutical industry experience, ensuring Kineta's growth and impact. Explore the strategies, leadership, and transformative initiatives that position Kineta as a trailblazer in the Immuno-oncology frontier, charting a course toward a future where cancer can be met with resilience, innovation, and hope. Innovating for Patient Well-being in Immuno-Oncology In explaining Kineta's mission, Thierry passionately articulates, "The mission of Kineta is to develop new drugs that are therapeutically very different than anything that's been done before." ‘‘ Kineta directs its focus towards patients fighting with advanced stages of cancer, those who have traversed multiple lines of therapy and seek new treatments. Thierry underscores the vision, stating, "Our mission is to develop next-generation immunotherapies that transform patients' lives." complexity of science and the need for concentrated efforts in a specialized area. Kineta's is developing KVA12123, a new immunotherapy that blocks an innate immune target called VISTA. VISTA is a negative immune checkpoint that suppresses T cell function, a key cancer fighting function, in a variety of different types of tumors. Blocking VISTA can induce an effective immune response to re-engage a suppressed immune system to enable an anti-tumor response. This monoclonal antibody is in clinical development as a twice weekly infusion drug. KVA12123 is being evaluated in a Phase 1/2 clinical trial as a monotherapy as well as in combination with pembrolizumab in patients with advanced solid tumors. The company is also developing another monoclonal immunotherapy targeting CD27 that can address exhausted T cells, another way to fight cancer. The mission of Kineta is to develop new drugs that are therapeu?cally very different than anything that's been done before. ‘‘ Emphasizing the importance of strategic focus in fostering innovation, Thierry echoes Shawn's sentiments, noting, "Actually, I really think that if you want to be innovative, you need to focus on a specific area." The strategic pivot to immuno-oncology aligns with Thierry's lifelong dedication to this field, driven by a recognition of cancer as a pervasive challenge affecting both the young and the old worldwide. Shawn's Odyssey in Drug Development Shawn has played an important role in steering the course of innovation as the Founder and former Chief Scientific Officer of multiple companies in Seattle. He transitioned to the role of CEO at Kineta in 2016, bringing his passion for advancing healthcare solutions to a new level. Thierry notes, "To be on the top of innovation, you need to focus the whole company in this specific field." Our focus on immuno-oncology is a deliberate choice, recognizing the - Thierry Guillaudeux Reflecting on his journey, Shawn emphasizes his commitment to advancing drug development in critical

As an antibody-focused company, Kineta distinguishes itself through the development of fully human antibodies. Thierry emphasizes the significance of this approach, stating, "Our antibodies are innovative because they are fully human, and that's also important for us because it prevents some possible adverse events in patients." Safety remains paramount in Kineta's attempts, with a deep-seated concern for patients' well-being during drug administration. Sharing Shawn's vision, Thierry adds, "I think that was also one of the visions that Shawn had in the company—to develop drugs that are safe and improve efficacy for patients that need better drug treatment options." Navigating the Frontier In the evolving landscape of cancer treatment, Thierry articulates a pivotal shift from traditional approaches, stating, "The field of cancer is evolving to new immunotherapies that hold the promise of shrinking tumors and turning cancer into a chronic disease that can be managed" With a historical reliance on chemotherapy, radiation and the subsequent emergence of targeted therapy in the early 2000s, the current industry focus lies in the space of immuno- oncology." Highlighting the progression of therapeutic generations, Thierry explains, "And the current generation is focused on immuno-oncology, and that's where Kineta is leading." This latest wave encompasses drugs that target PD1, PD-L1 and CTLA-4, marking a significant breakthrough in 2010 and 2011. Their primary objective is to reinvigorate the immune system, enabling it to naturally combat cancer. However, Thierry acknowledges the variability in efficacy across different types of cancer. Kineta's focus is on the ongoing development of immuno-oncology drugs. Thierry states, "Our focus is to try to stimulate more immune cells and different immune cells to really help the immune system to fight back against cancer." While still in the clinical development phase, this approach holds promise and remains a key area of concentration for the company. Delving into the complicated dynamics between cancer cells and the immune system, Thierry explains, "Our immune system has a really important role in

exceptional experience of the management team, with Thierry's extensive background in immuno-oncology and immunology, complemented by seasoned professionals with vast experience in major pharmaceutical companies. a substantial barrier in drug development, where initial success often gives way to the tumor's ability to grow, evade and evolve. This is a frightening challenge for patients and clinicians, given tumors' remarkable mutation rates compared to normal healthy tissue. overnight." He underscores the reality that success in developing a new drug requires overcoming numerous obstacles, and true greatness is a product of sustained effort over time. Jacques further notes the strategic prowess of the team, citing, "The management team has demonstrated continued success, and they are the right team in place to advance KVA12123 through clinical development and to keep moving the company forward." With a background from Schering-Plough and Glaxo Smith Kline, Jacques brings his own wealth of commercial pharmaceutical experience to the table. Reflecting the spirit of endurance, Thierry emphasizes the importance of optimism in the face of complexities. He acknowledges the challenges posed by intricate scientific endeavors, the need for patience in navigating difficulties, and the unpredictable nature of the market. Thierry asserts, "You have to be deeply positive and persistent to keep this program moving forward and reach success." Intrinsic positivity becomes a driving force in moving projects forward despite the inevitable hurdles and challenges that Kineta faces in the drug discovery and development process. While the scientific community has achieved a breakthrough with immune checkpoint inhibitors, Thierry notes that only 20-30% of individuals treated benefit from first-generation immunotherapies. Thus, the team at Kineta remains committed in their belief that pursuing new innate immune drug targets and developing novel immunotherapies is imperative. The multi-pronged strategy involves developing new drugs, combining them with others, and persistently advancing to enhance cancer- fighting efficacy. Jacques further highlights, "Kineta is an entrepreneurial, nimble company that's been able to advance our drug programs very effectively in a capital efficient manner." This, coupled with a strong leadership team and a commitment to innovation, positions Kineta as a trailblazer in the field. Redefining Cancer Treatment through Unique Drug Innovation Shawn emphasizes the importance of perseverance in this pioneering endeavor, stating, "I really think that because what we're doing is new, there's an element of determination that's really important. We have to stick with it and explore new solutions to address the medical needs of cancer patients." Refusing to accept 'no' as an answer from scientists, clinicians, investors, or regulators is a key driver, allowing the team to forge ahead and seek innovative new treatment alternatives for patients and healthcare providers. preventing cancer, and once a tumor becomes established, it's usually because that tumor was able to defeat the immune system in some way." Kineta's research is deeply rooted in innate immunity and understanding how tumors evade the immune response and devising strategies to reverse this process, allowing the immune system to resume its natural role in eliminating cancer cells. Kineta's unique identity is forged in its pursuit of pioneering innate immunity-focused drugs that possess the transformative capability to shrink tumors—a distinctive objective that sets the company apart as a trendsetter in the field of oncology. The core mission is to develop next- generation immunotherapies that transform patients' lives. Immunotherapies demonstrate efficacy to achieve tangible, unprecedented health outcomes for patients and marking a departure from conventional approaches. Charting the Oncological Arms Race In the battle against cancer, Thierry underscores the perpetual challenge of tumors adapting and genetically modifying themselves. The dynamic nature of tumors poses ‘‘ A Spotlight on Innovation and Expertise Adding a business perspective, Jacques aligns with Shawn's emphasis on perseverance, highlighting the uniqueness of Kineta's endeavors. He points out that differentiation is crucial in the marketplace for attracting investors today and ultimately clinicians seeking distinctive immunotherapies for their patients. Jacques states, "Everything we do is unique. Shawn shares the company's bold approach, stating, "Our company only works on things that are innovative and novel. Novel drug targets and immunotherapies that haven't been proven in the clinic yet. That's a high-risk, high- reward proposition, and we've really positioned the company in that space." Emphasizing the importance of focus and resilience, the team at Kineta is persistent in their commitment to proving the efficacy of KVA12123, their lead drug program as well Everything we do is unique. Developing immunotherapies that are differen?ated is crucial for a?rac?ng investors today and ul?mately clinicians seeking novel immunotherapies for their pa?ents. Expanding on this distinctive strategy, Thierry dives into the technical complexities, stating, "We decided to focus on a specific part of the immune response called innate immunity. It may be a little bit technical, but most of the companies right now are working on a specific type of cell that we call the T cells." Thierry emphasizes the company's differentiation by directing their focus toward a different facet of the immune response—innate immunity, a critical component in the early stages of the immune response. Jacques further emphasizes the importance of differentiation in instilling confidence in patients regarding the effectiveness of new medicines. He notes, "Ultimately, patients want to have confidence that a new medicine they're going to take is going to help them achieve an improved survival outcome for their cancer." ‘‘ Insights from Pioneers Shawn, a seasoned entrepreneur, imparts invaluable advice for those embarking on the entrepreneurial journey, emphasizing the need for perseverance and commitment. He states, "I think that people have to understand that in order to do something really great and amazing, it takes real determination and commitment, and it doesn't happen Highlighting the uniqueness that sets Kineta apart, Jacques underscores several key points. Firstly, he credits the innovative science and the essential work of Thierry and Shawn, particularly in the domain of innate immunity, as the core area of research. Secondly, he points to the - Jacques Bouchy

as the second drug program targeting CD27 that is also focused on improving cancer treatment outcomes. The aim is not only to showcase the success of each of these drug programs independently but also to demonstrate the potential of these drugs when used in combination with other cancer therapies, radiation, and surgery. Kineta's Vision for Transformative Healthcare In a society heavily reliant on continuous medical advancements, the impact of new drugs and vaccines on human lives is profound, reshaping our ability to combat diseases effectively. Cancer, a significant health challenge, remains a focal point for innovation. The evolving landscape holds promise for unique and transformative approaches, offering substantial improvements in patient treatment and tangible effects on their lives. Taking a tactical approach to these aspirations, the company sets specific milestones to mark its progress in drug development. One such milestone involves the release of clinical data for KVA12123, the lead asset targeting VISTA, slated for the second quarter of 2024. These key scientific updates, shared at major cancer conferences, serve as crucial checkpoints for investors, clinicians and patients, offering insights into the program's advancement. Addressing the pressing needs of individuals in the advanced stages of their cancer journey, Shawn expresses Kineta's commitment to developing new treatment options. These innovations aim to make an enormous difference for those who are running out of treatment alternatives. The mission to develop next-generation immunotherapies that transform patients' lives. As a society, the dependence on revolutionary solutions is pivotal, and Kineta envisions playing a pivotal role in this transformative journey. The success of the company is tied to the positive impact it can make on patients' lives. By consistently pushing the boundaries of what is possible in medical innovation, Kineta aspires to be a pillar of progress, providing hope and new possibilities for individuals navigating the complexities of cancer treatment. Looking ahead, Kineta outlines its phased approach, with plans to commence a phase two study in the third quarter of 2024. As the journey unfolds into 2025, the company anticipates releasing additional clinical data as both single agent therapy and in combination with other drugs that will further highlight the uniqueness and differentiation of the assets under development.

Empowering the Immune System Practices in Oncology Oncology Care Best Best T years, researchers and healthcare professionals have delved into innovative approaches that go beyond conventional treatments. This shift towards harnessing the power of the immune system marks a significant advancement in oncology care, providing new hope for patients struggling with the complexities of cancer. he landscape of oncology care has been evolving, with a growing emphasis on empowering the body's immune system to combat cancer. In recent Discover the transformative power of immunotherapy in cancer care – a journey towards personalized treatment and enhanced well-being awaits you! Understanding the Immune System's Role The human immune system, a formidable defense mechanism, is designed to identify and eliminate foreign invaders, including cancer cells. In oncology care, the focus is on bolstering this inherent ability to recognize and attack malignant cells. Unlike traditional therapies such as chemotherapy and radiation, which aim both healthy and cancerous cells, immunotherapy seeks to enhance the body's natural defenses, providing a more targeted and personalized approach. Immunotherapy Modalities Several modalities fall under the umbrella of immunotherapy, each designed to engage different facets of the immune system. Checkpoint inhibitors, for instance, 19 | February 2024 www.healthcareeverything.com www.healthcareeverything.com 18 | February 2024

Subscribe Today block proteins that hinder immune cells from accepting and attacking cancer cells. Adoptive cell therapy involves extracting, modifying, and reintroducing a patient's immune cells to enhance their cancer-fighting capabilities. Monoclonal antibodies, another type of immunotherapy, are designed to bind to specific proteins on cancer cells, marking them for the destruction of the immune system. their treatment options, potential side effects, and the rationale behind therapeutic decisions fosters a collaborative relationship between patients and healthcare providers. This shared decision-making process not only enhances treatment adherence but also contributes to a more positive and informed patient experience. Research Frontiers and Future Prospects Combining Traditional and Immunotherapy Ongoing research in immunotherapy is uncovering new frontiers and expanding the arsenal of available treatments. Combination therapies, utilizing multiple immunotherapeutic agents or combining immunotherapy with other modalities, are currently under investigation. Moreover, the exploration of novel targets and the development of next-generation immunotherapies hold promise for further refining and expanding the scope of immune-based interventions. The integration of immunotherapy with traditional treatments is becoming a hallmark of comprehensive oncology care. This approach acknowledges the strengths of both modalities, leveraging the immediate impact of conventional treatments like surgery or chemotherapy while empowering the immune system for long-term defense. The synergy between these approaches represents a dynamic shift towards a more holistic and patient-centered model of cancer care. Conclusion Personalized Medicine and Biomarkers The paradigm shift towards immunotherapy in oncology care marks a profound advancement in the fight against cancer. By harnessing the body's natural defenses, healthcare professionals are navigating uncharted territory, offering patients a more targeted and personalized approach to treatment. The integration of immunotherapy with traditional modalities, coupled with personalized medicine and ongoing research endeavors, paints a promising picture for the future of oncology care. As we continue to unravel the complexities of the immune system and its interactions with cancer, the journey towards empowering the body's defenses is a testament to the resilience of both science and the human spirit in the face of this formidable adversary. Never Advancements in genomic research have paved the way for personalized medicine in oncology. By analyzing the exclusive genetic makeup of a patient's tumor, healthcare professionals can tailor treatment strategies to target specific mutations driving cancer growth. Biomarkers play a crucial role in identifying individuals who are most likely to benefit from immunotherapy, enabling a more precise and effective intervention. This personalized approach not only enhances treatment efficacy but also minimizes unnecessary side effects, promoting a higher quality of life for patients. Miss an Issue Addressing Challenges and Side Effects While immunotherapy offers promising outcomes, it is not without challenges. Adverse reactions, known as immune- related adverse events (irAEs), can occur as the immune system becomes hyperactive. Managing these side effects requires a nuanced understanding of the patient's overall health and a proactive approach to mitigate potential complications. Striking a balance between activating the immune system and preventing collateral damage remains a key consideration in optimizing immunotherapy interventions. -Pearl Shaw Patient Education and Empowerment In the realm of oncology care, patient education plays a pivotal role. Empowering individuals with knowledge of www.healthcareeverything.com 20 | February 2024

Trailblazing the Immuno-Oncology Fron?er: Best Companies of 2024 Sensius Radiant Hope, Revolutionary Healing Our thermotherapy is used in combination with radio- chemo- and immunotherapy. Thermotherapy is the next quality level in hyperthermia and provides focus and controlled mild heating of the tumor to max 45 C. Sensius' unique and patented technology enables us to focus the heat to the tumor and protect nearby tissues from the heat. At least five different biological methods of action are triggered by this effect. The mild heating is an immunomodulator and sensitizer for radio- and chemotherapy. Research of prof. Weigelin (University of Tübingen, Germany) demonstrates that mild heating of the tumor increases T-cell killing efficiency with as much as 500%. additional treatment option to the benefit of the patient (survivorship, quality of life). Healthcare payers (insurance companies, governments) will need to recognize how our economic benefits (reduced recurrence, lower cost of treatment of toxic effects, faster reintegration in society) will reduce the economic burden of cancer. o What are some of the key products or therapies in your current portfolio that demonstrate your commitment to immuno-oncology? Our launching product is the FocusCollar for treatment of solid tumors in the head and neck area. This product is based on the extensive experience of Eramus University Medical Center and incorporates the experience of at least 5 more clinical research centers from all over the world. We are also part of a consortium of 4 Dutch universities to develop the FocusCup, a solution to treat breast cancer. More tumor types are on our roadmap for the future. Sensius will collaborate with clinical research centers, universities and other companies on research and clinical studies to improve quality of life and survivorship for cancer patient. healthcare, politics, and technology, Paul brings a well- rounded skill set and profound industry insight to the table. His leadership is instrumental in guiding Sensius towards its mission of enhancing the perspective for cancer patients through the innovative application of thermotherapy. How does your company's approach to immuno- oncology differ from other players in the field? Paul Van Den Biggelaar CEO and Co-Founder Sensius We use 20 microwave antennas, guided by AI software and sensory data, to focus the heat to the tumor. Thermotherapy by Sensius is non-invasive and is significantly more cost effective than existing therapies. Adoption in clinics is facilitated through alignment with established radiotherapy workflow. The approach can be applied on a range of different solid tumors. Thermotherapy can be applied safely and cost-effectively without additional toxicity for patients. In an exclusive interview with Paul, we delved into the intricate details of Sensius' approach and discovered how they are leading a transformative change in the immuno- oncology frontier. Please share about your professional background and career highlights that led you to your current position. As a former member of the Executive Team of Nucletron (now an Elekta company), world leader in brachytherapy, I was intrigued by hyperthermia, as it improves the effect of existing therapies without additional toxicity. I have studied its commercial feasibility since 2007. The work of Prof. Van Rhoon and Prof. Paulides at Erasmus University Medical Center (Rotterdam, the Netherlands) demonstrated a paradigm shift in technology and workflow. They had support letters from other universities. It was obvious to my partner and serial entrepreneur Peter van Paassen and myself that we needed to team up with Van Rhoon and Paulides to build Sensius into a company that will change the way we treat cancer. What are some of the challenges your company faces in the immuno-oncology field, and how are you addressing them? Many phase III studies have demonstrated the positive effects of mild heating on tumor response without additional toxicity, but current commercial solutions are not widely adopted because of substantial technical limitations which prevent robust and reproducible routine clinical use. C about eliminating tumor cells; it's about preserving life's quality throughout the process. In this relentless pursuit of comprehensive cancer care, Sensius emerges as a source of hope and innovation. ancer, a malignant disease that affects millions of lives, necessitates a thoughtful approach beyond conventional methods of treatment. It's not just Sensius offers improved clinical efficacy and ease-of-use and economic benefits of its thermotherapy: it is our challenge to make oncologists comfortable with this Can you provide an overview of your company and its focus on immuno-oncology? Going beyond the conventional trio of radiotherapy, chemotherapy, and immunotherapy, Sensius integrates controlled heating of deep-seated tumors into their treatment methodology. The result is not only the effective eradication of malignant cells but also a meticulous preservation of surrounding tissues and organs. The driving force behind this transformative endeavor is Paul van den Biggelaar, Co-Founder and CEO of Sensius. With rich experience spanning entrepreneurship, Thermotherapy by Sensius is non-invasive and is significantly more cost effec?ve than exis?ng therapies. Sensius is a medical device company that provides microwave-based clinical thermotherapy solutions intended as adjuvant treatment of specific solid cancers. The Sensius system is a combination of proprietary and patented hardware, software and expert services. Sensius aspires to become the leading brand in the segment of Thermotherapy by providing the adjuvant clinical tools for the treatment of certain types of cancer. 23 | February 2024 www.healthcareeverything.com www.healthcareeverything.com 22 | February 2024

Can you share any innovative technologies or techniques that your company is currently exploring or implementing in its research and development efforts? Sensius uses a combination of technologies to achieve performance, ease-of-use and economic benefits. Performance to focus and control energy deposition on only the tumor is implemented through 20 microwave antennas emitting energy at a carefully selected frequency and positioned strategically around the tumor area. AI-based software calculates the exact setting for each antenna individually to protect tissues around the tumor. This secures a personalized treatment plan, which can be adapted during treatment to accommodate for the specific situation of the patient. A patented waterbolus (a flexible water container between the device and the patient) secures the transfer of the energy from the antennas into the body and makes the patient comfortable. Workflow and patient positioning are similar to radiotherapy, while a modular system architecture support the treatment of different tumor sites in the body. What are the key milestones and achievements in your company's history, particularly in the field of immuno- oncology? On our clinical prototypes, Erasmus University Medical Center has already treated over 70 patients for head and neck cancer. The results are published (Paulides et al 2016, Verduijn et al 2018, Kroesen et al 2021) and show significant benefits. Erasmus MC will start a new clinical trial in the first half of 2024 with support of Sensius. The commercial solution for head and neck cancer, the FocusCollar will be ready for commercial deployment at the end of 2025. Already over 15 clinics in Western-Europe, the UK and in the USA want to participate in multi-center international confirmation studies using the FocusCollar. How do you see the immuno-oncology market evolving in the next few years, and how is your company positioned to capitalize on these changes? Thermotherapy will improve the life of people with cancer as it offers the possibility to improve survivorship and quality of life. It can be used on multiple tumor sites in combination with radiotherapy, chemotherapy and immunotherapy. It is easy to adopt in oncology clinics and will reduce the economic burden of cancer for society. Therefore, we believe thermotherapy will become the 4 pillar in cancer treatment. th www.healthcareeverything.com 24 | February 2024

Healing with Precision The Latest Advances in Immuno-Oncology Immuno-Oncology I formidable adversary. Recent breakthroughs in this field have ushered in an era of precision medicine, offering targeted treatments tailored to each patient's unique biological makeup. patient's immune cells to target cancer cells specifically. Beginning with the extraction of T cells from the patient's blood, genetic engineering introduces chimeric antigen receptors (CARs) that recognize cancer cells. These modified cells are then transferred into the patient. CAR-T therapy has shown promise in treating certain blood cancers, showcasing the potential of personalized immunotherapies. n the dynamic world of cancer care, immuno-oncology has emerged as a transformative force, leveraging the body's own defenses to combat the complexities of this Discover the future of cancer care – from personalized treatments to overcoming challenges. Embrace immuno- oncology's transformative journey for hope and healing! Monoclonal Antibodies: Precision Strikes Against Cancer Monoclonal antibodies, designed to target specific proteins on cancer cell surfaces, represent another pivotal development. By attaching to these proteins, these antibodies flag cancer cells for immune system destruction. Trastuzumab and rituximab have demonstrated success in treating breast cancer and lymphomas, highlighting the precision and efficacy of this targeted approach. The Foundation of Immuno-Oncology At its core, immuno-oncology utilizes the innate ability of the immune system to identify and eliminate cancer cells. Unlike traditional approaches, such as chemotherapy and radiation, which directly attack tumors, immuno-oncology focuses on enhancing the body's natural ability to recognize and eradicate malignant cells. This not only promises increased efficacy but also suggests a potential reduction in side effects compared to conventional therapies. Combination Therapies: Maximizing Impact Researchers are discovering the potential of combining different immuno-oncology agents to maximize impact. Combinations of checkpoint inhibitors with other immunotherapies or conventional treatments such as chemotherapy create a synergistic effect, enhancing the body's ability to recognize and eliminate cancer cells. These approaches not only improve response rates but also contribute to a more comprehensive treatment strategy. Checkpoint Inhibitors: Releasing the Immune Response A pivotal advancement in immuno-oncology is the development of checkpoint inhibitors. These drugs block specific proteins that contribute to the immune system, enabling it to recognize and attack cancer cells more effectively. Pembrolizumab and nivolumab, prominent members of this drug class, have demonstrated remarkable success in various cancers, including melanoma and lung cancer. Biomarkers: Guiding Treatment Decisions In the time of precision medicine, biomarkers are essential in guiding treatment decisions. Biomarker testing allows healthcare professionals to identify specific characteristics or genetic mutations in a patient's tumor, helping determine the most effective immuno-oncology approach. This CAR-T Cell Therapy: A Personalized Approach Another groundbreaking avenue is CAR-T cell therapy, a personalized treatment involving the modification of a 27 | February 2024 www.healthcareeverything.com www.healthcareeverything.com 26 | February 2024

Cost and Accessibility personalized approach minimizes trial-and-error, ensuring patients receive interventions most likely to be beneficial for their unique cancer profile. Despite the promise of immuno-oncology, concerns about cost and accessibility persist. These advanced therapies can be expensive, posing challenges for widespread adoption and equitable access. Researchers and policymakers are keenly addressing these issues, working towards developing more cost-effective approaches and ensuring that these cutting-edge treatments are accessible to a broader population. Tumor Microenvironment: A Critical Player Understanding the tumor microenvironment is becoming increasingly crucial in immuno-oncology. The interactions between cancer cells and their surroundings can influence the effectiveness of immunotherapies. Ongoing research explores ways to modulate the tumor microenvironment, making it more receptive to immune system attacks and enhancing the overall success of immuno-oncology interventions. Challenges and Future Directions While immuno-oncology holds immense promise, challenges exist. Managing side effects, known as immune- related adverse events, requires a nuanced approach to ensure patient safety. Researchers are actively exploring ways to expand the applicability of immuno-oncology to a broader spectrum of cancers and investigating novel targets for intervention. Patient Advocacy and Support Amidst the scientific strides, the importance of patient advocacy and support cannot be overstated. Empowering patients with information, providing emotional support, and fostering a collaborative healthcare environment contribute significantly to the overall success of immuno-oncology treatments. Active participation in patient advocacy groups and support networks helps amplify patients' voices, ensuring that their unique needs and challenges are addressed in the evolving landscape of cancer care. Conclusion As we navigate this dynamic frontier of immuno-oncology, the expanding horizons bring both promise and challenges. Understanding the intricacies of the tumor microenvironment, prioritizing patient advocacy, integrating artificial intelligence for precision, exploring immunotherapy in early-stage cancers, addressing concerns about cost and accessibility, and continuing research endeavors are pivotal steps in advancing the field. The strides made in immuno-oncology are not only scientific breakthroughs but also a testament to the collaborative efforts of researchers, healthcare professionals, and advocates. Embracing these innovations and addressing challenges collectively will pave the way for a future where immuno-oncology becomes an integral part of standard cancer care, offering hope and healing with unprecedented precision. Precision Oncology and Artificial Intelligence Advancements in artificial intelligence (AI) are increasingly playing a role in immuno-oncology. AI algorithms analyze vast datasets, including genomic information, patient records, and treatment outcomes, to identify patterns and predict the most effective treatment strategies. This intersection of technology and medicine is paving the way for more precise and personalized cancer care, offering tailored interventions based on comprehensive data analysis. Immunotherapy in Early-Stage Cancers While immuno-oncology has shown significant success in treating advanced-stage cancers, there is a growing interest in its application in early-stage cancers. Research is underway to explore the efficacy of immunotherapy as an adjuvant or neoadjuvant treatment, aiming to eliminate residual cancer cells after surgery or to shrink tumors before surgical removal. This expansion of immuno-oncology into earlier stages of cancer holds the potential to further improve outcomes and reduce the risk of recurrence. -Pearl Shaw www.healthcareeverything.com 28 | February 2024

Algorithms also contribute to significant efficiency and accuracy gains in use by pathologists. They can perform calculations and computational work that software can do exponentially faster than a human. This also removes the need for tedious, manual tasks to be performed by high- quality resources, such as pathologists, and affords them the ability to focus on their expertise, the interpretation and diagnosis of the patient. Quality Assurance or Control Algorithms can also be configured, or deployed, to provide either an automatic review of all cases or be set to do a review of a predetermined number or percentage of cases to support regulatory requirements for review or for internal training and safety. In this use case, the algorithms would be run either before a case is signed out, but after it is diagnosed, or after it is signed out to flag any questionable diagnosis. It can highlight areas that may have been missed, flag a tumor that may have been identified as a grade 2 when it was determined to be a 4 by the algorithm, etc. T here has been a vast uptick in technological advancements in the laboratory industry for digital pathology and Artificial Intelligence solutions. In fact, AI is the buzzword of the day. What is the difference between algorithms, uses and accuracy? some are for a subset and some are for a limited set of uses. The second is anti-adoption. Overall, these use cases fall into the following general categories: Diagnosis It's very easy to conflate the terminology and in some cases, the differences are very clear while in others the lines are a bit less distinguishable. In short, Artificial Intelligence (AI) and Machine Learning (ML) are closely related, but you can think of it more as a hierarchical relationship. They both relate to computers and programming; however, AI algorithms rely on human input and ML algorithms are taught. In other words, AI requires humans to provide inputs such as visual perception, interpretation, decision making, and results in algorithms that can make decisions based on data that they have been trained on. The second set of professionals in this community are not bought into the safety or use of algorithms in diagnostic practice. There is the argument that many of these are not fully tested, they are not able to be used "out of the box" for a variety of reasons leading to a wide variation in how images are viewed (color saturation, stain types, scanner file formats, etc.). Many of the algorithms are rated on their accuracy by a correlation factor and pathologists are not always in concordance with themselves 100% of the time, never mind with each other. AI and ML algorithms are typically deployed for use in diagnosis. They can be used for preprocessing images to provide a pathologist with an interpretation of the specimen. This can include the image which typically overlays on the original and shows a 'hot spot' view of the cancer within that slide and can also provide textual and contextual data i.e.: percentage of proliferation, grade of cancer, number of positive and negative cells, etc. This type of algorithm can often be used as a region of interest (ROI) that is manually invoked by the pathologist on a slide or area of a slide that they are looking for more insight on. When integrated within a digital pathology solution, this can also provide a streamlined workflow to include capturing the image and output to include in a final report in support of the pathologist's diagnosis. These algorithms can be used (if FDA cleared for diagnosis or validated as an LDT by the laboratory/pathologist) as diagnostic or as an aid to the pathologist in rendering their diagnosis. For more than 2 decades, Lisa-Jean Clifford has been a noteworthy leader in the high-tech healthcare solu?ons space. Lisa-Jean's passion for making a posi?ve impact on the lives of pa?ents through technology can be traced back to her tenure at McKesson and IDX, now GE Healthcare, where she served in vital business development and marke?ng roles and to Psyche Systems, an LIS solu?on provider, where she was the CEO for eleven years. Now, recognized as an industry expert, she ac?vely par?cipates in numerous boards including the Associa?on of Pathology Informa?cs and MLO's Editorial Advisory Board. She is widely published in many top laboratory publica?ons and noteworthy news sources, such as Forbes, CAP Today, Medical Laboratory Observer, and Health Data Management. Also, she is a highly sought-a?er speaker and focuses on delivering valuable content in cri?cal areas such as lab automa?on including so?ware and interoperability, digital pathology, AI in pathology, lab informa?cs, oncology, and women's health. Whereas ML algorithms are based on building models, or neural networks, that are trained to identify patterns and trends in information to make decisions. ML is used to classify data and recognize patterns; this is actually essential to many AI algorithms. Then, there is the concern that drift results can occur. Recently, Fortune reported that a study conducted by Stanford University found that "Over just a few months, ChatGPT went from correctly answering a simple math problem 98% of the time to just 2%". While this is not indicative of what a commercially available, tested pathology algorithm would encounter, it does add to the doubt of those who are in this community of adaptors. Image Analysis (IA) is more about extracting data for a purpose, or multiple purposes from an image. This is very useful in workflow application optimization and can provide significant added value to AI and ML, but more to digital pathology solutions and their adoption. Workflow Optimization In summary, algorithms, when tested and validated by each laboratory for deployment within a digital workflow solution can provide improved efficiency, streamlined workflow, reduce errors and increase the experience for the pathologist. Lisa-Jean's success can be a?ributed to her perseverance, integrity, her high-regard for ethics, and her desire to con?nue to learn, grow, and move technology solu?ons in a forward direc?on for healthcare. Her collabora?on with industry partners, customers, colleagues, and compe?tors combined with her commitment to excep?onal customer rela?onships is what dis?nguishes her drive to foster a win- win for the healthcare industry as a whole. IA algorithms provide a streamlined workflow through the preprocessing analysis of images. These algorithms can perform such tasks as auto registration of images, ensuring that the images in a virtual slide tray are in the correct order, analyzing images to make a priority assessment and move cases with a higher probability of being positive, or more complex, higher in the pathologist's worklist. There are two factions of thought on the overall use of these technologies in patient diagnosis and care. The first is pro- innovative technology and this group sees the benefits of being able to use well-developed, trained and tested algorithms in a variety of workflows. Some of the professionals who fall in this community are for all uses, 31 | February 2024 www.healthcareeverything.com www.healthcareeverything.com 30 | February 2024

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Trailblazing The Immuno-Oncology Frontier Best Companies Of 2024

Trailblazing The Immuno-Oncology Frontier Best Companies Of 2024

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