Innovating the Canadian Biotech Sector with Joseph Mancini, adMare BioInnovations

About the Interviewee (Sourced from adMare BioInnovation’s Official Website)

Dr. Joseph Mancini is the Vice President of Research at adMare BioInnovations. With a strong track record of globally competitive scientific discovery, Canadian life sciences is primed to lead the world. To make this a reality adMare BioInnovations uses its scientific and commercial expertise, specialized R&D infrastructure, and seed capital to build strong life sciences companies, robust ecosystems, and industry-ready talent.

As Vice President of Research, Dr. Joseph Mancini plays a central role in leading adMare’s R&D team and the strategic development and advancement of adMare’s pipeline of drug development projects to support the building of strong Canadian life sciences companies. Joe brings more than 30 years of experience in drug discovery to the role and is responsible for overseeing the biology and pharmacology efforts at both adMare’s Montreal and Vancouver Innovation Centres.

Prior to joining adMare in 2020, Joe spent 20 years at Merck, a leading global biopharmaceutical company, where he was responsible for developing novel therapies to treat inflammation, diabetes, and obesity – including being key in the discovery of Vioxx^TM and Arcoxia^TM, and the Biology Lead for a PDE 4-inhibitor for Asthma, and for four INDs and human proof-of-concept trials.

Following his tenure at Merck, Joe joined Vertex Pharmaceuticals where, as Head of Pharmacology and Biology Project Leader, he led the Pharmacology group and a team that developed a therapy to treat Crohn’s disease (licensed to Takeda), as well as initiated new programs in ADPKD and a rare muscular disease.

Joe has been an Adjunct Professor at one of Canada’s top research universities, Montreal’s McGill, since 2000, and is credited with 94 publications and seven patents. He holds a PhD in Biochemistry from McGill University.

The Discussion

adMare BioInnovations, Fostering Biotechnology Innovations in Canada

[Dex Marco]: It’s such a pleasure to have you here with us today, Dr. Joseph. With over 30 years of proven track record in leadership in pharmaceutical drug discovery and development (the bulk of which you spent at Merck), industrial and academic research, and scientific and technical advising, what would you say drove you towards this field, and what brought you to eventually lead the research department of adMare BioInnovations?

[Dr. Joseph]: Well, thank you for having me here today. My journey into the world of pharmaceutical drug discovery and development has been an incredible one, marked by a deep passion for science and innovation. I originally started with a foundation in medical training, which gave me a firsthand understanding of the impact healthcare decisions have on human lives. Yet, it became clear to me that my true calling was in the realm of research and discovery, where I believed I could make a profound difference in the course of human health.

Over three decades ago, I had the privilege of interacting with clinicians who often emphasized the importance of independent judgment when it came to clinical treatment. However, there was one exception to their rule – Merck. They consistently praised Merck for its unwavering commitment to rigorous and groundbreaking science. This was the catalyst that led me to Merck, and it was there that I embarked on my journey in drug discovery.

I am a PhD in Biochemistry by training, and my time at Merck was transformative. I had the opportunity to learn every facet of the drug discovery process, working alongside pioneers who were responsible for the first statins and ACE inhibitors. During my two decades at Merck, I was fortunate to be part of teams that successfully brought two important drugs to market.

Following my tenure at Merck, I moved to Vertex Pharmaceuticals, where I further honed my skills in the fascinating field of rare genetic diseases. This experience opened my eyes to the immense potential of genetics in driving drug discovery. The culture at Vertex, like at Merck, was marked by an unwavering commitment to scientific excellence.

It was during this time that Dr. Youssef Bennani, a former VP at Vertex and now a key figure at adMare, approached me with a compelling mission. He shared the vision of building novel biotech companies and fostering growth in the Canadian biotech landscape. This resonated deeply with me, as I’ve always been drawn to the idea of creating innovative biotech enterprises and contributing to the advancement of science on a national scale.

So, this is how I came to join adMare BioInnovations. Our mission to build novel biotech companies across Canada is one I wholeheartedly embrace. It represents a commitment to pushing the boundaries of science and innovation, a journey I’m honored to be a part of. It’s a privilege to lead our research department as we continue to shape the future of drug discovery and development, making a lasting impact on human health.

Science, Sustainability, and Systems Thinking

[Dex Marco]: With a wealth of globally competitive scientific discovery, Canada is primed to lead the world of life sciences. To make this a reality, adMare BioInnovations uses its scientific and commercial expertise, specialized R&D infrastructure, and seed capital to build strong life sciences companies, robust ecosystems, and industry-ready talent — and re-invest its returns back into the Canadian industry to ensure long-term sustainability. Could you tell us more of this very unique company portfolio that adMare BioInnovations offers?

[Dr. Joseph]: Sure, let me elaborate on adMare BioInnovations’ distinctive approach. At adMare, our mission is rooted in nurturing innovation that has the potential to transform lives and shape the future of life sciences. While our primary focus is Canadian innovation, we recognize that groundbreaking discoveries can emerge from any corner of the globe. As such, we collaborate extensively with researchers across Canada and, when the opportunity arises, beyond our borders.

We strategically channel our efforts into several therapeutic areas, with a heightened commitment to two major domains: neurodegenerative diseases and oncology. Our emphasis on these areas is driven by the critical need for innovative solutions. However, we are by no means confined to these domains; we also embrace rare diseases and remain open to pioneering breakthroughs in any disease area. If there’s a genuine, unmet need and a promising new therapy in development, we are prepared to engage and support its growth.

Our modus operandi involves working hand in hand with academics who bring forth ingenious ideas. Internally, we have a formidable team of over 55 scientists spanning a wide range of disciplines, including Medicinal Chemistry, Biology, Cellular Biology, Molecular Biology, and Pharmacology. These brilliant minds collaborate with our academic partners to usher in the next era of innovation, thereby incubating and nurturing new companies. One such success story is Abdera Therapeutics, a company that originated within our walls. Abdera is based in Vancouver and has made remarkable strides in developing a novel antibody-targeted radiotherapeutic for cancer. Their ability to secure over 140 million USD in venture capital funding is a testament to the promise and potential of the innovation we foster.

Beyond Abdera, we are also proud of other promising ventures in earlier stages of development. For example, Find Therapeutics is dedicated to addressing autoimmune diseases, and Neurasic has ventured into the realm of novel therapeutics for pain management. We also take pride in Specific Biologics, a Toronto-based company with pioneering research in gene editing, aiming to revolutionize the treatment of rare genetic diseases.

In essence, we span a wide spectrum of therapeutic areas, aiming to drive innovation, and it’s a substantial undertaking, to be sure. We believe that by investing in specialized research and development infrastructure, cultivating thriving ecosystems, and nurturing talent, we can contribute to Canada’s position at the forefront of the global life sciences arena. It’s a multifaceted journey, and I’m delighted to have the opportunity to discuss it with you.

Organoids Pave the Way for Personalized Medicine

[Dex Marco]: In the context of leveraging organoids for drug screening, the replication of key functional and structural aspects of an organ is an impressive feat. Considering the inherent variability in human biology and the intricacies of different disease states, how do you address the potential limitations of organoids in accurately representing the diverse patient population, and what innovative strategies do you propose to ensure that the responses observed in these 3D tissue models reliably translate to meaningful outcomes in personalized treatment approaches?

[Dr. Joseph]: Indeed, the use of organoids in drug screening is a remarkable advancement in biomedical research. While we acknowledge the inherent variability in human biology and the complexity of different disease states, addressing these limitations and ensuring that our findings translate into meaningful personalized treatments is at the forefront of our efforts.

Having been deeply immersed in drug discovery for a substantial period, my previous focus predominantly revolved around in vivo mouse models. However, as we have learned, these models often fall short in replicating human disease accurately, presenting significant challenges in the drug development process.

The emergence of 3D organoids, particularly in the context of human genetic diseases, is indeed a pivotal moment in our field. These models grant us the unique ability to mimic the architecture and genetic mutations specific to individual patients, thereby striving to recreate the closest possible representation of the patient’s condition. This is a goal we’ve long aspired to achieve in the pursuit of precision medicine.

To illustrate this, during my tenure at Vertex, I was involved in a project related to a kidney disease. While I’m unable to delve into the specifics, I can assure you that the results were truly astonishing. We successfully replicated the exact human disease using organoids, in collaboration with esteemed experts in the academic realm. This was a labor-intensive process, but it underscored the potential of organoids as the next generation of human tissue models for drug development.

Our ongoing work in this area is not only exciting but also essential. We firmly believe that this cutting-edge approach will not only contribute to the creation of more effective medications but also enable us to make more accurate predictions regarding their human efficacy. The potential here is enormous, and we are poised to make significant strides in the near future.

From a Reliable Proof of Concept to a More Accurate Pathophysiologic Mimicry

[Dex Marco]: As we embark on the complex task of developing bioengineered human disease models with high clinical mimicry, the potential to revolutionize drug development is undeniable. However, these models must not only replicate disease pathology but also encompass the intricate interplay of genetic, epigenetic, and environmental factors that contribute to disease progression. Given the dynamic nature of these interactions, how do you propose to accurately capture the complexity of genetic disease mechanisms within these bioengineered models? Furthermore, how can you ensure that the therapeutic targets identified and potential drug candidates tested within these models adequately address the multifaceted aspects of the disease, ultimately leading to successful translation from bench to bedside?

[Dr. Joseph]: Certainly, and I appreciate the depth of this question as it truly underscores the intricacies of our work. When it comes to developing bioengineered human disease models with high clinical mimicry, we are indeed venturing into a complex and revolutionary realm of drug development. To accurately capture the complexity of genetic disease mechanisms within these models, we must adopt a multifaceted approach.

Firstly, it’s vital to acknowledge that the gold standard for clinical proof of concept remains human testing. Nevertheless, human trials are not only ethically challenging but also prohibitively costly. Hence, bioengineered models serve as invaluable surrogates to study disease pathways comprehensively.

For instance, let’s consider the remarkable success story of cystic fibrosis research conducted by Vertex Pharmaceuticals. They took an innovative approach by utilizing lung explants from both normal and disease patients, allowing them to closely mimic the disease environment. Specifically, in the case of cystic fibrosis, they focused on the malfunction of the CFTR chloride channel and its impact on mucous production and cilia function within the lungs.

Vertex created an epithelial layer that mimicked the lung’s air-liquid interface, thereby replicating the critical physiological dynamics. This enabled them to test and identify compounds that could correct the channel dysfunction. The outcome was groundbreaking, as the previously immobile cilia suddenly started beating, representing a significant therapeutic breakthrough. Vertex progressed from these in vitro systems to human trials, eventually leading to the approval of four drugs for cystic fibrosis.

This success story underscores the potential of bioengineered models to provide deep insights into complex disease mechanisms. To ensure that therapeutic targets and drug candidates adequately address the multifaceted aspects of the disease, we must continue to evolve these models. This means collaborating closely with biomedical engineers and pushing the boundaries of 3D tissue and culture systems. The more closely we can mimic the pathophysiology, the more reliable these models become as predictive tools.

In the end, the integration of these advanced in vitro systems can significantly reduce the cost and time associated with drug development. By showing proof of concept earlier in the process, we can streamline the journey from bench to bedside, making novel therapeutics more accessible and affordable. This approach will not only revolutionize drug development but also improve patient outcomes, aligning with our ultimate goal of advancing healthcare for all.

Microfluidics: Addressing Seamless Integration, Screening Constraints, and Safety Issues

[Dex Marco]: In the pursuit of urgently needed drug development solutions, the demand for novel techniques and streamlined processes is indisputable. However, the dichotomy between the pressing need for new drugs and the inherent challenges of cost and time in development poses a formidable hurdle. While microfluidic-based systems offer promising advantages over conventional methods, the integration of these systems into the existing drug development pipeline requires meticulous consideration. How would you navigate the intricate landscape of balancing the imperative for accelerated drug screening with the potential resource constraints, and what innovative strategies can you propose to ensure a seamless transition to microfluidics, while maintaining the rigorous standards of safety, accuracy, and regulatory compliance that are paramount in the pharmaceutical industry?

[Dr. Joseph]: Thank you for this insightful question, which truly touches upon a topic very close to my heart. Microfluidics, in my view, represents an exciting frontier in drug development, particularly when considering its potential to revolutionize integrated organ-on-a-chip technology.

Microfluidics is not a straightforward path, and let’s be honest, it’s far from an easy road to navigate. We need to harness the talents of biochemical engineers with a unique mindset and approach. To illustrate, during my tenure at Vertex, I had the privilege of working with a brilliant biomechanical engineer. Together, we embarked on a journey to understand the intricacies of capillary flow rates, delving into the physics of blood flow through capillaries. This collaboration led to the creation of a kidney model with accurate capillary flow rates—a significant feat, but not without its fair share of time and financial investments. Setting up such a system took over a year, and some may question the wisdom of dedicating so much time and resources.

However, we must remember that while quicker in vivo models exist, they don’t always guarantee reliable results. The ratio of candidates successfully advancing from phase one to becoming actual drugs is dishearteningly low, often less than 10 percent. Many potential drugs fail because they lack efficacy, causing a massive loss of compounds. This is where robust preclinical models like the ones we’re striving to develop come into play. Even if it takes a year to establish them, the investment may be well worth it.

The critical question, of course, is whether these models can serve as better predictors. While it’s early days, and we’re still refining these systems, there are encouraging signs. As we continue using these models to guide our drug development endeavors, we’ll gain a clearer understanding of their predictive power. Take, for example, our success in developing a model for cystic fibrosis—an inspiring testament to the potential of these systems. Admittedly, this journey wasn’t a walk in the park; it demanded dedication, late nights, and even long weekends. But when you see the impact of your work, changing lives for the better, the challenge becomes more than worthwhile.

While the integration of microfluidic-based systems into the drug development pipeline is undoubtedly complex, the potential benefits make it a journey worth undertaking. It requires a mix of vision, collaboration with experts, and a willingness to invest time and resources. We’re on a path toward more reliable and efficient drug screening, and the results we’ve achieved so far are a testament to the possibilities ahead.

Standing on the Shoulders of Giants: Synergy for Scientific Excellence

[Dex Marco]: Dr. Joseph, your remarkable career journey showcases a consistent ability to bridge the gap between cutting-edge research and tangible clinical impact. As you reflect on your leadership roles and contributions to the development of clinical candidates in various fields, we’re eager to hear some final insights on the strategic decision-making process that underpins your successes. Considering the intricate intersection of multidisciplinary teams, cutting-edge technologies, and high-stakes clinical development, could you elaborate on how you’ve effectively managed the orchestration of resources, knowledge, and innovation to consistently deliver clinical candidates that align not only with scientific potential but also with real-world patient needs?

[Dr. Joseph]: Again, that’s a very good question. Reflecting on my journey, I’d like to acknowledge the tremendous impact that my mentors, colleagues at Merck, Vertex, and adMare BioInnovations, as well as my academic collaborators, have had on my career. Their invaluable contributions to the world of science and the unwavering support from dedicated staff have been instrumental in shaping my path.

Ultimately, it is the insatiable thirst for knowledge and the privilege of working alongside exceptional colleagues that keeps one steadfast on the path towards a common goal. That goal, in our realm, is the betterment of patient lives. When patients come forward and share how a therapy we’ve developed has transformed their lives, it’s a profound game-changer. I’ve witnessed it firsthand with osteoarthritis patients who regained their mobility, and those suffering from rare genetic diseases who can now lead fulfilling, hospital-free lives. Their testimonials are a testament to the power of scientific innovation.

It’s this human connection that fuels our drive. The impact we make is not an individual effort but a result of collective teamwork. I recall my early days at Merck when I was astounded by the sheer size of the interdisciplinary team for one project, with over 50 experts working together in the pre-clinical stages and growing to hundreds when clinical development commenced. In reality, this doesn’t even include the crucial support staff. Developing a single drug can involve up to a thousand individuals, each contributing a unique perspective and skill set. It’s the harmony within these diverse teams that makes the real magic happen.

The core of it all lies in staying at the forefront of scientific advancements. By collaborating with some of the brightest minds in academia, I’ve often encountered seemingly audacious ideas that, upon further exploration and discussion, have led to groundbreaking developments. At adMare BioInnovations, we have a unique opportunity to engage with academics who are not only passionate about their work but also eager to create transformative technologies. We work together to bridge the gap between novel scientific concepts and clinical reality, helping these innovations reach the people who need them most.

It is the spirit of teamwork, the synergy of collaboration, and the unwavering commitment to scientific excellence at every stage that drive our success in the field of clinical development. This journey is a testament to the collective effort of numerous individuals who share the same vision: to improve the quality of life for patients in need. It’s a journey I’m immensely proud to be a part of, and one that continues to inspire me daily.

Engr. Dex Marco Tiu Guibelondo, B.Sc. Pharm, R.Ph., B.Sc. CpE

Editor-in-Chief, PharmaFEATURES

Join Proventa International’s 10th Annual Drug Discovery Biology Strategy Meeting at Le Meridien Boston Cambridge, Massachusetts this 7th of November 2023 to learn more about In Vivo and In Vitro Pharmacology (Track 3) in the realm of drug development. Click on the photo below to download the brochure for the event.