Scrip Jan 27, 2023
Expectations high for precision medicine, artificial intelligence and RNA technologies
The confluence of data science and molecular biology fuels expectations among biopharma industry leaders for another year of breakthrough innovation in human therapeutics. More than 70 executives and experts reveal what they are most excited about on the technology front.
Convergence was a recurring theme in the commentary from the 70 or so biopharma leaders who shared with Scrip their predictions around technology. Asked what technological advance would have the biggest impact on biopharma in 2023, they frequently referred to the way multiple scientific advances – in cell and gene therapy, in RNA technologies, in different -omics and so on – would be amplified by advances in artificial intelligence to bring transformative progress across the therapeutic landscape. With additional technologies from different fields also being brought to bear, the impact should be felt across drug discovery, clinical trials, manufacturing, and the patient journey.
“AI – whether it’s termed artificial or amplified intelligence – has been demonstrated to accelerate decision-making and define clinical targets. The mRNA successes of 2020 herald a new era in drug development. But so has our willingness to cluster technologies such as wearables, digital tools and telehealth that invite a diverse community of participants into the clinical trial process,” commented Gil Bashe, managing partner, chair global health at Finn Partners and a member of the incubators, accelerators and equity committee of the Prix Galien Award. “Our biggest innovation challenges are the availability of technology and the application of these tools through collaboration and streamlined regulatory parameters.”
G1 Therapeutics Inc.’s CEO Jack Bailey made the point that “innovation is a mindset.”
He went on: “Technology facilitates the execution of innovative ideas, but it isn’t the spark that ignites creativity. Take virtual clinical trials, for example. The technology for telehealth visits existed well before COVID, but it wasn’t embraced until COVID forced us to bring trials to patients’ homes rather than patients to trial sites. Likewise, technology can facilitate disruptive change – genome editing and cancer vaccines, for example – but companies must be willing to adopt a mindset that the reward of pursuing a novel compound or platform is worth the risk. You have to continually cultivate that mindset by encouraging people to speak up.”
And this is where leadership plays its part. “As a leader, I see myself as a player-coach at the ground level listening to what every employee has to say, so I can close the gap between what we think is occurring and what’s really occurring,” Bailey said, warning also that “innovation can easily be stunted by layers of bureaucracy.”
Others focused on how technology is helping to deepen our understanding of disease so that we can treat it in a more fundamental way. “The most important advances in biopharma will be those that enable us to shift from treating the symptoms of a disease to targeting its root cause,” said Ira Spector, CEO of SFA Therapeutics, Inc. “2023 promises to be an important year for disease-modifying therapies as innovations are emerging in different fronts, from genome editing and mRNA therapeutics to microbiome-derived drugs and molecularly targeted approaches.”
And Marcus Schindler, executive vice president for research and early development and chief scientific officer at Novo Nordisk A/S, had his eye on the holy grail of therapy: cure. “Whilst I see a diversification of molecular formats for novel therapeutics, I am particularly excited about advances towards therapies that have the potential to be curative. Whilst early days, areas such as cell therapy and gene therapy/gene-editing hold tremendous promise and I think we will hear more about these in 2023,” he said.
“Advancements in AI and ML will propel personalized medicine forward by maximizing drug efficacy and safety for patients.”Sirj Goswami, InsightRX
“Artificial intelligence and machine learning will catalyze the next breakthroughs in precision medicine by enabling real-time analysis and outcome predictions during a clinical trial,” said Sirj Goswami, CEO of health care technology firm InsightRX. “This will empower sponsors with reliable pharmacological and clinical insights about the drug and accelerate the identification of optimal doses across different patient populations. Ultimately, advancements in AI and ML will propel personalized medicine forward by maximizing drug efficacy and safety for patients.”
David Harel, CEO of CytoReason, also pinpointed the value of data science in drug development. “We’re seeing incredible advancements in data science these days. Specifically, the integration of molecular and clinical data sets in drug development. I expect that combining multi-omics with real-world data, while integrating a growing number of longitudinal data sets, will deliver major breakthroughs in precision medicine in 2023,” he said.
“The biggest impact on biopharma will be realized when we unlock the potential of precision medicine to pave the way to finding cures of devastating diseases, including label expansion for existing drugs using AI,” declared David Morgan, CEO of Zephyr AI Inc. “By finding new indications for existing drugs, the development costs will come down and create new opportunities for combination therapies. Advances in data automation and harmonization tools combined with powerful AI allows for use of real-world data in innovative and groundbreaking ways. Major breakthroughs will occur when we leverage the power of artificial intelligence and machine learning to identify trends and uncover insights that extend and improve the quality of patients’ lives, save payers and providers money and enable clinicians to confidently predict and prevent adverse events.”
“In 2023 we expect precision medicine […] to make tangible progress towards radically altering the course of the global human and socioeconomic crisis currently posed by neurodegenerative disease.”Andrea Pfeifer, AC Immune
Andrea Pfeifer, CEO of AC Immune SA, pinpointed advances in precision medicine as a gamechanger for Alzheimer’s and similar conditions. “In 2023 we expect precision medicine […] to make tangible progress towards radically altering the course of the global human and socioeconomic crisis currently posed by neurodegenerative disease,” she said. “This will be enabled by new diagnostic technologies, PET-tracers and exquisitely sensitive blood tests, as well as novel vaccines targeting toxic proteins in neurodegenerative diseases, which are entering mid-stage clinical development. As we begin to evaluate the potential benefits of offering more and more pre-symptomatic, at-risk individuals with therapeutic candidates that could significantly delay or even prevent disease emergence, we think the industry’s focus for future treatments of Alzheimer’s, Parkinson’s and other neurodegenerative diseases will shift towards this new paradigm.”
“For the last several years the biopharma industry has been talking about the power of precision medicine and there have been several significant advancements that are making this more of a reality. As biopharma shifts its R&D strategies, we believe high-throughput proteomics – the use of automated equipment to rapidly test thousands of protein samples for biological activity – will have the greatest impact in identifying biomarkers for disease and in also predicting a patient’s response to certain therapies,” said Todd Johnson, executive vice president of the diagnostics business unit at SomaLogic, Inc. “Up until this point, leveraging the power of the proteome has been staggeringly complex. But we’re finally at the point where groundbreaking proteomic technologies can impact biopharma’s efforts across disease research areas such as cardiovascular disease, oncology, and much more, at a scale that was not previously possible.”
Konrad Paszkiewicz, chief technology officer at Hummingbird Bioscience, had a similar perspective: “In 2023, I expect that we will see further developments in high-throughput expression, screening and characterization of proteins/antibodies that will contribute to the dynamism of the biopharma industry,” he said.
Homing in on genomics technologies were Aaron Bensimon, CEO of Genomic Vision, and Terry Lo, CEO of Vizgen Corp.
“We are in the midst of a biopharmaceutical revolution, developing increasingly sophisticated and targeted advanced therapies – and doing so in ways that are faster, better and cheaper. Highly accurate, fast and accessible genomic analysis is the foundation for this trend, enabling the development of ever-better cell and gene therapies and supporting the industrialization of bioproduction with the required levels of quality control throughout the process,” said Bensimon. “As such, the technological advance that will have the biggest impact on biopharma in 2023 and beyond is the development of advanced genomic analysis technologies, such as DNA combing combined with automated AI-based data analysis to provide single DNA molecule resolution.”
Lo said: “Now that there is a robust commercially available platform for spatial genomics, we anticipate we’ll start to see these tools used more and more in biomarker and drug discovery, and adding an extra level of detailed analysis to biological discovery and clinical trial data.”
Taking the broad view was Andrew Hopkins, CEO of AI drug discovery firm Exscientia Ltd.
“We will see an evolution – from individual omics technologies advancing to multi-modal omics coming together at single-cell level, along with the ability to leverage and interpret this complex data for patient-driven research – allowing the field to envision precision medicine as a reality,” said Hopkins. At Exscientia, we saw early signs of this last year with our EXALT-1 study, in which a drug selected by algorithms and precision oncology machine-learning impacted clinical outcomes in people living with cancer for the first time. This is the true embodiment of personalized medicine, and in 2023, we’ll realize it’s only the beginning.”
Asit Parikh, CEO of MOMA Therapeutics, Inc., had the distinction of offering the briefest response to the question of which technological advance would have the biggest impact in biopharma this year. His answer was simply: “AI.”
Several other leaders identified artificial intelligence and data science too.
“2023 will be a year where algorithms and data engines will be utilized more than ever before in history to help biopharma re-imagine how to discover, develop, and bring medicines to patients,” predicted Hisham Hamadeh, Genmab A/S’s vice president and global head of data science.
“AI will revolutionize everything. It will be a transformative step in disease diagnosis, drug discovery and pharma development.”Apollon Papadimitriou, iOmx Therapeutics
“For me the key topic will be digitalization, specifically, the use of artificial intelligence (AI) in the biopharmaceutical industry, be it in diagnostics or therapeutics. AI will revolutionize everything. It will be a transformative step in disease diagnosis, drug discovery and pharma development. I think we are at the very beginning of this transformation, but over the next years we will see a lot of artificial intelligence, digitalization and machine learning in drug design, drug development and diagnosis of disease,” said Apollon Papadimitriou, CEO of iOmx Therapeutics AG.
He elaborated: “Take for example, digital pathology in the context of cancer diagnosis and tumor analysis. With a new level of data granularity from 3D analysis of individual cell types and biomarkers – plus greater spatial and temporal resolution – we will be able to dissect a tumor on the cellular and molecular level and understand much more about it. How it begins to grow, how it seeds up, and how it evolves over time. This will be seen within the tumor microenvironment where there are not only tumor cells, but also vascular cells, connective tissue cells, and a diverse set of immune cells, the interplay of them influencing tumor growth and treatment options. If you see the tumor with this level of granularity and can analyze the situation at any point in time – looking at multiple parameters in parallel – this will revolutionize our understanding of tumor biology, open new opportunities for therapeutic intervention, and change the way we develop drugs towards personalized medicines.
“This multi-parametric analysis generates a huge amount of data. The task now is, how can we correlate these data? Can we create patterns of disease progression or predict response to a given drug based on a pattern that artificial intelligence creates through analysis of these highly complex and large data sets?” Noting that “currently, in immuno-oncology, 60% to 70% patients do not respond right to available treatments,” Papdimitriou concluded: “Bioinformatic data integration will allow drug developers to provide more therapeutic options for patients and save costs to the health care system by providing the right treatment for the right patient with greater certainty.”
“The rapid advancement of artificial intelligence now being reduced to practice means that unique and highly connected data sources have become essential and highly valuable. I believe the greatest overall impact will come from including what is called ‘longitudinal deep phenotyping’ in conjunction with multi-omic clinical trials, EHR [electronic health record] data integration and the blossoming of wearables,” said Nathan Price,chief science officer of health tests and supplements firm Thorne HealthTech.
“Tying together data that spans not only case/control disease designs but also incorporates deep multi-omic profiling starting from better quantifying health itself opens up new pathways to understanding the earliest transition states to disease,” he continued. “Bringing together streams of data starting with wellness and extending through early-stage disease provides critical and novel paths to discovery for therapeutics, diagnostics, and, most importantly, precision prevention for improved population health. The convergence of these types of densely interconnected data and AI advancements will also enable precision medicine via digital twins that more deeply represent each patient’s biology uniquely. 2023 will be just the tip of the iceberg of this approach, but believe we will see the first examples start to emerge.”
“Protein structure prediction using deep learning has the opportunity to greatly impact biopharma, not just due to having the 3D structure of any protein, but also the related algorithms people will develop inspired by it (eg, folding a PROTAC, E3 ligase and POI all at the same time),” said Laksh Aithani, CEO of CHARM Therapeutics.
BridGene Biosciences, Inc. CEO Ping Cao also highlighted the potential of AI in protein modeling and addressing previously inaccessible targets. “With the latest progress in AlphaFold’s machine learning methodology, AI is positioned to greatly accelerate the discovery of new drugs, especially small-molecule drugs,” he said, referring to the artificial intelligence program developed by Alphabet subsidiary DeepMind. “AlphaFold’s AI-powered high-speed protein prediction technology will predict a 3D protein structure so medicinal chemists can apply structure-based drug design to achieve precise binding of a small molecule to a defined region of the target protein in order to modulate its function. Structure predictions are particularly important to understand binding of small molecules to many so-called ‘undruggable targets’ (where we are focusing our chemoproteomics effort) because often no X-ray crystallography structure exists and the binding pockets for covalent hits may be shallow or transiently formed from protein: protein interactions in live cells.
“The continuously improving accuracy of protein structure prediction by AlphaFold’s machine learning and more small-molecule protein interaction data obtained from the chemoproteomics field will boost drug discovery and development and open a new era for targeting ‘undruggable’ targets,” predicted Cao.
Arecor Therapeutics plc CEO Sarah Howell agreed that we would “continue to see the advancement of the use of AI and digital health in clinical research with the primary goal of ensuring that life-changing treatments can be developed quickly and at a lower cost, and hence, enabling broader access to all,” thereby driving “a continued shift to broad access and value-based care.”
“Innovative organizations have fully embraced this change, regulators are following, and lagging organizations will be forced to adapt or be left behind.” Shawn Tedman, ixlayer
“As someone who was in technology for many years and moved into biotech over a decade ago, I was always excited about the potential of technology to revolutionize drug discovery. Looking ahead, I think that ‘AI in drug discovery’ is a great example of a big idea whose time has come and we will see big momentum in 2023,” said Yochi Slonim, CEO of Anima Biotech Inc. “There is tremendous innovation going on in this space. The first AI-discovered drugs are now in the clinic. Many small biotechs and even big pharma are working on hundreds of projects. I am excited about finally seeing how technology can meet biology and the intersection point of AI in drug discovery is one of the most promising directions.”
“In so many ways, biopharma lags other industries when it comes to technological advances,” commented Shawn Tedman, vice president of biopharma innovation at health testing platform company ixlayer. But he saw change happening. “Rather than a single technology, advances in data science are dramatically reshaping the biopharma landscape. These advances hold the promise of reducing protocol complexity, decreasing timelines, and getting new medicines to patients more efficiently.”
Tedman finished with a warning to biopharma companies: “Innovative organizations have fully embraced this change, regulators are following, and lagging organizations will be forced to adapt or be left behind.”
Gene And Cell Therapies
“Given the number of late-stage traditional AAV-based gene therapy programs across the industry heading towards potential FDA approvals next year, 2023 could be the year we start seeing more approved gene therapies across a range of diseases,” said Brent Warner, president, gene therapy at Poseida Therapeutics, Inc. Unsurprisingly, he was not the only executive who picked gene and/or cell therapy as an area to highlight for 2023.
“Over the last few years, we have begun to see a tangible shift in gene therapy from 1.0 technologies to 2.0 technologies. In 2023, I think we can expect to see demonstrable evidence of this progress through preclinical proof-of-concepts with INDs using these technologies on the near-term horizon,” said Apertura Gene Therapy CEO Joseph La Barge, adding: “Hard-to-access tissues such as the CNS [central nervous system] will become tractable, and innovative approaches to treating devastating neurological diseases will begin to offer hope to patients suffering from these diseases.”
Chris Tapper, senior associate, Cambridge Innovation Capital, had his eye on “novel and next-generation methods of delivering therapeutic cargos within the body,” predicting “the pandemic has turbo-charged the development of non-viral vectors for therapeutic delivery and we expect to see more and more modalities taking advantage of this technology to create more effective and better tolerated therapies for patients.”
“Off-the-shelf allogeneic cell-based treatments that can be produced at a larger-scale and thus hold the distinctive promise of rapid delivery to patients in need are likely to drive increased access.” Hamid Khoja, FibroBiologics
“It is not difficult to foresee a continuing trend of more cell- and gene-therapy based treatments and cures being implemented across a range of diseases, including cancers, infectious and autoimmune diseases, as well as in orthopedic applications,” commented Hamid Khoja, chief scientific officer of FibroBiologics. “In addition, off-the-shelf allogeneic cell-based treatments that can be produced at a larger-scale and thus hold the distinctive promise of rapid delivery to patients in need are likely to drive increased access to these approaches.”
Tom Burt, a partner at venture capital firm Sofinnova Partners, also tipped allogeneic cell therapy as the area to watch. “Recent data from Allogene is very compelling and suggestive of equivalency to autologous in response and durability, but with the huge benefits of being off-the-shelf and utilising young, healthy cell populations rather than tired, old autologous cell populations,” he noted.
Allogene Therapeutics Inc.’s CEO David Chang highlighted the journey from the earlier breakthroughs of autologous cell therapies – which use a patient’s own cells – to off-the-shelf alternatives. “The first-generation autologous CAR-Ts changed how many difficult-to-treat blood cancers were managed. As the growing patient demand far outweighs the ability for autologous therapies to meet the growing need, we now face a crisis with CAR-T access,” he said. “The field needs a CAR-T cell therapy that is on-demand, more reliable and available at a greater scale. Allogeneic CAR-T is a product that can serve the many, not just the few, and we now know that it can achieve durable responses comparable to those seen with autologous CAR-T therapies. In 2023, we anticipate that allogeneic CAR-T will stand out as one of the most promising and powerful cancer technologies developed, and that this new modality will have the potential to address the supply bottleneck crisis associated with autologous CAR-Ts.”
“The combination of promising cell therapies like CAR-T with new modalities (including immunotherapeutics like oncolytic viruses), especially in treatment of solid tumors, will be promising.” Helena Chaye, KaliVir Immunotherapeutics
Helena Chaye, CEO of KaliVir Immunotherapeutics, LLC, said: “The future of gene and cell therapies remains very promising, and the innovation and growth driven by the ongoing scientific research in the field will continue to make progress. Notably, the combination of promising cell therapies like CAR-T with new modalities (including immunotherapeutics like oncolytic viruses), especially in treatment of solid tumors, will be promising, and with the right selection of indication and clinical trial design, can make a tremendous impact in cancer treatment.”
Atara Biotherapeutics, Inc.’ chief scientific officer Cokey Nguyen was also thinking about ways of improving cell therapies. “Within the past couple of decades, significant progress has been made in the landscape of immunotherapy, evolving how certain cancers are targeted and treated. As allogeneic CAR-T cell therapies start to enter the clinic for hematological and solid tumor indications, researchers are investigating ways to build on nature’s T-cells by applying new technologies aimed at enhancing certain CAR-T capabilities to prevent cell death and improve cell persistence, especially in tumor microenvironments,” he said. “Next-generation armoring techniques, like novel 1XX costimulatory domain technology to help avoid cell exhaustion, reduce cytokine release syndrome, and improve persistence, and PD-1 dominant negative receptors that can be added to CAR-T cells aimed to circumvent the hostile tumor microenvironment, may help improve antitumor activity which could be the key to target solid tumor malignancies.
“By leveraging next-generation CAR-T cell designs or armored CAR-Ts, or a combination of both, we and other researchers seek to harness the immune system to make deeper inroads into our fight against cancers, autoimmune disorders, and other diseases,” he said.
“In 2023, we must work together to unlock the full curative potential of hematopoietic stem cell (HSC) transplants and gene therapy, with the goal of providing more patients with access to these life-saving therapies,” declared Ron Martell, CEO of Jasper Therapeutics, Inc. “HSC transplants and gene therapy are among the most innovative advancements in modern medicine, but key challenges continue to limit their broader use. Both require toxic processes to eliminate diseased cells, make space for transplanted cells via bone marrow conditioning, and support the survival and expansion of therapeutic cells. Specifically, current conditioning regimens that use chemotherapy can have significant toxicities for patients. New conditioning approaches that are effective but have minimal to no toxicity are urgently needed so more patients who could benefit from an HSC transplant or gene therapy could receive these procedures.”
Philip Toleikis, CEO of regenerative medicine company Sernova Corp, said: “We anticipate that the advancement of cell therapeutics that provide a complete therapeutic solution with the potential to provide functional cures for chronic, debilitating diseases will have the biggest impact on biopharma in 2023. Of note, I believe that induced pluripotent stem cell (iPSCs)-derived technologies, that can provide a replacement for missing cells such as the replacement of islets for people with diabetes, will be a driving factor in this advancement. Currently, many patients rely on costly, burdensome monitoring protocols and treatments for chronic diseases like diabetes. Using iPSC-derived technologies, new treatments are being developed and tested in clinical trials that can be produced at scale, allowing for greater accessibility, lower long-term costs, and better quality of life for patients.”
Genome And Epigenetics
“We continue to see significant advances in biopharma as a result of genome engineering, and I expect that to accelerate rather than slow down in 2023,” said Vor Biopharma Inc. CEO Robert Ang. “Whether giving us completely new ways to treat diseases or helping us find ways to improve upon longstanding therapeutic approaches, we have only started to see the full promise of genome engineering and I expect to see new breakthroughs in the year ahead.”
“By developing technologies able to modulate epigenetic pathways, researchers may be able to improve upon the current standard of care for certain diseases.” James Brown, DURECT
“Gene editing will have a major impact on biopharma, through 2023 and beyond, making direct interventions in the genetic basis of underlying disease much more widespread,” predicted Carlo Russo, chief medical officer and head of development at Genenta Science srl. “However, taking full advantage of this technology will require an objective assessment of the various gene editing options plus a dialogue with regulators not only to ensure the necessary significant changes in requirements for marketing approvals but equally important, early access to patients with urgent needs.”
James Brown, CEO of DURECT Corporation, flagged up epigenetics as an area to watch. “In 2023, technologies that continue to grow our understanding of gene regulation and its association with health and disease will have a significant impact on the industry. Unlike gene therapies that tackle specific pathways or genes associated with disease, epigenetic therapies work to modify the expression of multiple genes involved in relevant cellular functions, and which may be dysregulated in many diseases,” he explained. “By developing technologies able to modulate epigenetic pathways, researchers may be able to improve upon the current standard of care for certain diseases.”
“Following the revolutionary use of mRNA vaccines to help quell the COVID-19 pandemic, I look forward to seeing the continued evolution of RNA platform technologies in 2023,” said Moriah Nachbaur, interim chief business officer at Elixirgen Therapeutics Inc. “Many companies are actively working to expand our understanding of RNA and its potential application to various diseases for which effective or accessible treatments are currently unavailable. The possibility for RNA technologies to benefit patients affected by these diseases, and their families, is extremely exciting.”
“As we saw in 2022 and 2021, through the game-changing mRNA COVID vaccines, innovation in biopharma is revolving around RNA technologies,” agreed Daniel de Boer, CEO of ProQR Therapeutics N.V. “I anticipate that we will see continued progress in RNA and, in particular, RNA-editing in 2023, especially as it pertains to developing treatments for previously unmet patient needs.”
“RNA will have the biggest impact on pharma and biotech in the coming year(s). While there are many innovative approaches and modalities today, such as for example protein degradation and CRISPR, etc, the pandemic has significantly advanced mRNA-based vaccines, and essentially provided clinical proof of concept for the whole field,” said Klaas Zuideveld, CEO of Swiss RNA-based therapeutics developer Versameb. “Today RNA still has number of challenges, but its success in vaccines has given confidence in its broad applicability and spurred a significant amount of research increasing its bioavailability, potency and effectiveness, which we will start to see in clinical trials in years to come.”
“We believe RNA therapeutics will see several key advances in 2023. RNA therapeutics already represent a highly flexible modality which have been used from treating SMA (Spinraza) to the COVID vaccines,” stated Josh Cohen and Justin Klee, co-CEOs of Amylyx Pharmaceuticals, Inc. “There is high interest in further exploring these modalities and we expect to see advances in areas such as: use of oligonucleotides in neurodegenerative diseases; new delivery mechanisms broadening the use of mRNA therapeutics; and next-generation modalities such as modified oligos to target specific organs or oligo-antibody conjugates. We expect concurrent with this greater manufacturing capacity will come online and new companies will grow to utilize these new technologies.”
“2023 will be the year of further advancing transcriptomic technology in rare genetic diseases – transferring the lessons of widespread mRNA medicine to that of targeted drug discovery and development.” Peter Bauer, CENTOGENE
Peter Bauer, chief medical and genomic officer at Centogene NV, said: “Over the past decades, we have witnessed remarkable progress in the field of molecular genetic analysis and mapping. But we are really just at the tip of the iceberg when it comes to looking at the other omics. Based on the incredible progress of messenger ribonucleic acid (mRNA) COVID vaccines, 2023 will be the year of further advancing transcriptomic technology in rare genetic diseases – transferring the lessons of widespread mRNA medicine to that of targeted drug discovery and development.
“Unfortunately, many drug candidates are not making it across the line in the final stretch due to false positives, safety issues, and previously undetected side effects. By truly understanding patient-derived transcriptomics, we will be able to better predict and track how compounds interact within the cell from the very beginning. Ultimately, this will accelerate the entire process, but with an entirely new level of certainty that has never been seen before in precision medicine.”
“In our opinion, the oligonucleotide space will advance meaningfully in 2023,” said Michael King, head of healthcare research at investment bank EF Hutton. “We measure this in several ways. First, commercial sales from the products that Alnylam Pharmaceuticals Inc.’s product portfolio has created are expected to exceed $2.2bn. In addition, the company has nine stated development candidates, a number of which have blockbuster potential for conditions such as Alzheimer’s disease, NASH, and hypertension. Ionis Pharmaceuticals, Inc., which we acknowledge has been around a while, is also hitting its stride and has multiple late-stage assets, including nine Phase III/registration-ready and 18 Phase II molecules, advancing in the hands of partners. Arrowhead Pharmaceuticals, Inc. is an emerging leader in the space with one program in Phase III, two in Phase II and a total pipeline of 15 programs. The company recently announced that it sold its royalty stake in AMG 890 (olpasiran) to Royalty Pharma plc for $250m and announced a program it refers to as “20 by 25”, meaning 20 clinical-stage programs by 2025. While gene editing is very exciting and beginning to deliver benefits to patients, oligos are real and [bringing] robust benefits to patients right now.”
COVID-19 did wonders for the field of vaccines as several executives acknowledged in their 2023 predictions.
“Monoclonal antibodies and vaccines will have large, renewed interest following their COVID-19 successes,” foresaw Daniel Sindelar, CEO of Keystone Biologics, Inc.
Manoj Gandhi, senior medical director of Thermo Fisher Scientific, thought that “mRNA vaccine technology will continue to have the biggest impact. This is due to the ongoing evolution of SARS-CoV-2 and the adaptability of this technology to the issue of antigenic drift. The question is whether this technology will be able to be used in other indications. One could envision mRNA vaccines being used in influenza and possibly even a COVID-flu combination mRNA vaccine to cover these respiratory pathogens.”
“mRNA technology will shape therapeutic areas beyond COVID-19, including, but certainly not limited to, influenza vaccines, due to the flexibility and speed at which the mRNA platform can be applied.” Ethan Settembre, CSL
“As we look to 2023 and beyond, I anticipate that mRNA technology will shape therapeutic areas beyond COVID-19, including, but certainly not limited to, influenza vaccines, due to the flexibility and speed at which the mRNA platform can be applied,” said Ethan Settembre, vice president, research at CSL Seqirus vaccines innovation unit. “In addition, the next generation of mRNA technology, self-amplifying mRNA (sa-mRNA), which offers the potential for improved immune responses, lower dosing and favorable safety and tolerability compared to currently marketed mRNA vaccines, will likely drive technological advances in multi-pathogen pandemic preparedness, influenza vaccines and therapeutic areas beyond vaccines.”
Shankar Musunuri, CEO of Ocugen Inc., thought that new approaches to COVID-19 would be important: “In the ever-evolving COVID-19 landscape, it’s critical that biopharma companies continue to explore next-generation solutions to address virus transmission,” he said. “Leaders in the field believe that producing a mucosal vaccine that provides immunity at the point of transmission rather than immunity in the bloodstream may be an effective way to directly slow down the circulation of the virus and to limit the speed at which further variants emerge. The technologies behind these vaccines, whether intranasal or inhaled, are not new themselves but are being used in a revolutionary way to make a significant impact on the battle against COVID-19.”
“The COVID-19 pandemic spurred a wave of innovation, as new technologies emerged that allowed us to prevent the spread of the virus and save tens of millions of lives. In 2023, we can expect to see developments that will diversify the COVID-19 vaccine options currently available,” agreed Stan Erck, who retired as CEO of Novavax, Inc. on 23 January (but will remain at the company in advisory capacity for 15 months). “We think choice will empower vaccination, and that the lessons learned from COVID will allow us to continue to innovate and develop immunizations to fight an even broader range of infectious diseases, from influenza and RSV to malaria, and provide us with the tools to rapidly respond to the ‘next virus’.”
A number of leaders identified oncology, and more specifically immuno-oncology, as an area of likely technological impact this year.
“We are optimistic about advances in immuno-oncology, in particular approaches that leverage the innate immune system in the fight against a number of hard-to-treat cancers,” said Randall Schatzman, CEO of Bolt Biotherapeutics, Inc. “One approach that is gaining fresh momentum is immune-stimulating antibody conjugates, or ISACs, which are engineered to convert immunologically cold tumors into hot tumors by combining a tumor antigen-targeting antibody, a linker and an immune stimulant that engages the tumor microenvironment. By retraining the immune system, the goal for ISAC technology is to provide a safe, targeted tumor-killing approach with a durable response. This is one example of a promising biopharma technology that can overcome the limitations of existing therapies to promote long-term anti-tumor activity, giving hope to patients and families.”
For Vishal Doshi, CEO of AUM Biosciences, “the call to conquer resistance to cancer therapies is urgent. We need to unite to advance new therapies that reverse mechanisms of resistance. We must get smarter about drug development. AUM has a mandate of ‘No Biomarker, No Drug.’ This strategy improves the probability of future success and reducing the risk of failure of the drugs at late stages of drug development.”
“The advance that will have the biggest impact on the industry in 2023 is proof-of-concept for cancer neoantigen vaccines.” Andrew Allen, Gritstone bio
“The advance that will have the biggest impact on the industry in 2023 is proof-of-concept for cancer neoantigen vaccines,” predicted Andrew Allen, CEO of Gritstone bio, Inc. “For decades, many efforts to prove out this modality have failed. This is largely due to the fact that the foundational technologies to make these vaccines successful – AI/ML to identify neoantigens based on tumor DNA/RNA sequence, and the need for powerful vectors to deliver them – did not exist or were still in development. Today, these technologies have matured and could change the paradigm for cancer treatment and potentially drive cures in the deadliest and hardest-to-treat solid cancers.
“There were 100,000 new cases of colon cancer in the US in 2022 and per American Cancer Society, 50,000 people will succumb to the disease; devastating figures that show we need a new approach,” he noted. “Success of an individualized neoantigen vaccine approach in this disease would be a fundamental advance for colorectal cancer patients and would likely then extend to many other ‘cold’ solid tumors (breast, ovarian, prostate) where immunotherapy today offers little if any benefit to most patients.”
Allen added: “Multiple cards will be turned over in this space in the coming year; first datasets from randomized trials will be presented by Merck & Co., Inc./Moderna, Inc. as early as December 2022 [editor’s note: positive results from this trial were subsequently reported. (Also see “Moderna Chalks Up Industry Milestone With mRNA Cancer Vaccine Efficacy Success” – Scrip, 14 Dec, 2022.)], then BioNTech SE/Genentech, Inc. and Gritstone. If we ‘crack the code’ with individualized neoantigen vaccines, we will be encouraged in our efforts to develop ‘off-the-shelf’ products – a second wave of cancer vaccine therapeutics. As immune checkpoint inhibitors have become obligatory in many cancers, given strong efficacy, augmenting their activity and scope further by driving endogenous tumor antigen-specific T-cells is an attractive and scientifically coherent strategy that may become part of a new, improved standard-of-care.”
Saurabh Saha, CEO of Centessa Pharmaceuticals plc, meanwhile highlighted that “there’s been a silent reinvigoration of creatively engineered cancer bispecifics which are being designed to selectively engage tumor antigens while stimulating the immune system through activation of potent immune effectors – with a favorable safety profile. Anticipate more data across the industry in 2023 and beyond showcasing potential anticancer effects of this class of molecules, analogous to a similar type of resurgence in ADCs [antibody-drug conjugates] which the industry has seen over the past few years.”
Manufacturing And Delivery
Innovation in manufacturing and delivery was where Owen Smith, Partner at venture capital firm 4BIO Capital, expected a big impact in 2023. “Strong investment into a plethora of varied and transformative approaches to produce and deliver complex biologics and advanced therapeutic medicinal products is paying off with a stepwise commoditization of production methods and better in vivo specificity from more elegant delivery solutions,” he said.
“The biggest impact on delivering biopharma’s promise will be through new manufacturing technologies, combined with new regulatory approaches and policies to enable more widespread patient access.” Jason Foster, Ori Biotech
Jason Foster, CEO of UK cell and gene manufacturing company Ori Biotech, similarly highlighted innovation in the production of advanced therapeutics. “Within biopharma and more specifically cell and gene therapies, 2022 was an amazing year, with the first pediatric patient in the world – Emily Whitehead – reaching 10 years cancer-free, and our industry starting to use the term ‘cures for cancer’,” he commented. “In addition, we have seen the approval of five additional cell (x2) and gene (x3) therapies to treat certain cancers and rare diseases including the first gene therapy for hemophilia B (Hemgenix).
“The continued challenge is that today’s approved therapies remain out of reach for the vast majority of eligible patients, current estimates showing less than 2% of the addressable patient population are able to access these therapies. With the potential regulatory approvals of a dozen or more new CGTs in 2023, the biggest impact on delivering biopharma’s promise will be through new manufacturing technologies, combined with new regulatory approaches and policies to enable more widespread patient access.”
Denis Dufrane, CEO of Novadip Biosciences SA, thought that a breakthrough in production of advanced therapeutics in 2023 could unblock a bottleneck in clinical trials, particularly in areas outside hematology and oncology.
“The evolution of medicines from small molecules to proteins drove increased therapeutic benefits, and the next generation of cell and gene therapies holds tremendous promise for patients. Although the approval of mRNA-based Covid-19 vaccines opened the window, COVID isn’t the end for mRNA. In fact, it’s just the beginning for novel therapeutic platforms with other nucleic acid therapeutics and cell and gene therapies,” he noted. “However, hematology and oncology currently remain the major field of interest of this technology. Rare diseases, immunology, rheumatology and neurology remain under investigation with cell and gene therapeutic approaches, due to the current limited capacity of producing therapeutics that meet regulatory requirements. Unresolved scale-up and regulatory issues are certainly evident in the laboratory-scale platforms for cell and gene therapies. Significant challenges come from the complexity, cost, and availability of the many investigational materials, which include plasmids and viral vectors. Phase II/III clinical trials are currently limited by these factors.”
Dufrane concluded: “In 2023, the rise of cell and gene manufacturing platforms (including mRNA and exosomes) will have a heavy hand in the clinical development of new therapeutic field for these innovative technologies.”
Harlan Weisman, interim CEO of TFF Pharmaceuticals, Inc., was hopeful about progress in making the formulation of biologics more robust in a way that will strengthen supply chain resilience as well as improving drug delivery options for patients. “With increasing demand for biologics like gene therapies and RNA-based treatments comes an increasing need for innovative formulation solutions that allow these therapies to be conveniently administered and reduce off-target toxicities,” he said. “Biologics are extremely fragile and are currently very limited in their formulation. They often also require storage at ultra-cold temperatures. Delays in mRNA-based COVID-19 vaccine accessibility early in the pandemic were in part due to reliance on cold-chain processes, thus, to stay ahead of the next pandemic, we as an industry need to investigate ways to make biologics more shelf stable and improve global accessibility. I expect that these technologies will have a major impact in biopharma in 2023 and that the industry will begin to home in on patient-friendly, targeted ways to deliver biologic-based medicines especially as we continue to see an uptick in respiratory viruses like flu and RSV where biologic-based treatments could play an increasingly important role.”
Along similar lines, specialty pharma company TheraKind’s CEO Susan Conroy thought that a major impact would be felt by the “advancement of more non-invasive methods, such as intranasal drug delivery and buccal delivery, for prevention and treatment of diseases with a high societal burden, which can be rapidly deployed in emergency situations.”
Frazer Morgan, co-founder and chief development officer of Kinaset Therapeutics, Inc., flagged up improved delivery options too. “Despite the recent and welcomed introduction of parenterally delivered antibody treatments, patients diagnosed with moderate-to-severe uncontrolled asthma continue to suffer from significant unmet needs. Although highly effective in this population, pricing strategies limit access to such therapies whose administration via injection is also considered suboptimal by patients and prescribers. Consequently, an opportunity exists for the development of effective and orally inhaled small molecule therapeutics that, by virtue of lower cost of goods, can present a cost-effective alternative to biological alternatives,” he said.
Meanwhile, Jeffrey Graves, CEO of 3D Systems, thought that 3D printing (also known as additive manufacturing) would be a key area of progress. “Organizations have continued to integrate additive manufacturing (AM) into their production operations to mitigate supply chain risks, enhance product design flexibility and reduce manufacturing costs. Looking ahead to the coming year, I believe we’ll see significant momentum in the use of AM to increase the velocity of innovation in the healthcare, industrial, and pharmaceutical industries,” he said.
“For chronic diseases, patient engagement throughout the treatment journey has been shown to be vital to success – yet very challenging to achieve if a patient sees their physician for about six minutes every three months,” pointed out Olivier Bogillot, Head of US general medicines at Sanofi. “Consumers are looking for increasingly connected healthcare. A recent survey found that nearly 60% of consumers are open to remote health monitoring through at-home devices and another survey found that 80% of consumers said they prefer digital communications with their providers at least some of the time. When patients increase their use of personalized digital tools (smartphones, wearables, etc), it allows for continuous engagement, versus episodic patient visits. Using human-centered design and behavior modification techniques, digital tools can increase patient adherence with therapy (medication and lifestyle changes) and improve shared decision-making.”
“The adoption and implementation of sensors and wearable technology in clinical trials will continue to significantly affect biopharma in 2023.” Stephen Pyke, Parexel
Stephen Pyke, chief digital and data officer at Parexel International Corp., noted that such tools would also be important in drug development. “The adoption and implementation of sensors and wearable technology in clinical trials will continue to significantly affect biopharma in 2023,” he said. “These technologies enable patients to have a voice in the clinical trial process in a passive and reliable way while providing an opportunity to provide subjective feedback directly to their clinical trial lead. They also allow us to objectively measure data points. Insights provided by wearables and sensors are transforming our understanding of how patients experience disease and treatments, ultimately enabling us to bring more effective therapies to market that incorporate the patient perspective.”
For Kyowa Kirin North America’s chief information officer Nancy Maher, the benefits of remote monitoring will be even broader. “The Internet of Things (IoT) is having a big impact on biopharma activities, and can be connected to other digital trends to have an even greater impact,” she told Scrip, noting that “IoT-enabled devices can:
- Be used to increase data collection in clinical trials – collecting data from participants outside the clinic through the use of wearables. Reduced frequency of in-person visits may drive participant recruitment and retention in trials.
- Aid supply chain in tracking and chain of custody, ensuring records are correct and unaltered from a quality and regulatory perspective.
- With AI, wearables or sensor-enabled delivery systems can change the patient experience by coupling data collection with patient education that encourages persistence.
“More ambitious applications of IoT – that properly consider patient privacy and data security – can help biopharma achieve its commercial goals, shorten development cycles, and enhance regulatory compliance,” she said.
Bristol Myers Squibb Company’s chief digital and technology officer Greg Meyers identified the use of technology in clinical development as a likely area of growth in 2023. “As we continue to move toward a post-COVID world, major healthcare networks around the globe are still coping with a significant backlog of patient caseload, which is making it more challenging to get investigational drugs through the clinical trial process,” he commented. “In a shift good for medicine and for society, I expect we will continue seeing an acceleration of technology adoption. This will make it possible for smaller clinical trial investigators who serve patients in more remote areas to access valuable medicines through a clinical trial process not only helping increase enrollments, but also increasing access to a more diverse population of communities.”
Christina Masturzo, Citeline’s head of product – patient engagement and recruitment, emphasized the need for clinical trial technology to be joined up across the continuum. “There’s been a massive technological boom within the industry over the past few years, yet barriers to entry remain a burdensome reality for clinical trials. End-to-end, data-driven platforms that support the interconnectivity of all technology will increase efficiency through centralized operations, will create a seamless experience for all stakeholders, and will ultimately smooth the path to life-changing treatments with greater speed and ease,” she said.
For Joseph Kim, chief strategy officer at ProofPilot, “Protocol automation will have the biggest impact as it greatly simplifies already complex work, while removing a great deal of waste and cost in the system inherent to manual (un-automated) tasks – whether it be implicit tasks related to preparing a patient for a clinical procedure, randomization of investigational drug, or co-ordinating disparate DCT [decentralized clinical trial] methods.”
“The emergence of highly advanced AI software platforms can help biopharma optimize their clinical trials, particularly with patient selection.” Jeff Wyrtzen, Brainomix
“The emergence of highly advanced AI software platforms can help biopharma optimize their clinical trials, particularly with patient selection, where imaging-based biomarkers can more accurately identify patients suitable to certain trials, which ensures a more successful, faster, and cheaper clinical trial,” said Jeff Wyrtzen, chief marketing and business development officer of medical software firm Brainomix.
For Parexel’s Pyke, “Any advancements that can be made to progress real-time data extraction from electronic medical records will have a huge impact. While there are currently several aggregators who have helped providers optimize their data and make it accessible to clinical research organizations and pharmaceutical companies, the technology to enable the real-time extraction and abstraction is lacking. If we can improve this, it will benefit clinical research greatly.”
Executives at 3D Systems predicted that bioprinting would play an important role in 2023. “In 2023, I believe there will be significant progress made using bioprinted human tissue models to accelerate drug discovery and development. The ability to accurately simulate the human response to an experimental drug in the laboratory, early in the development process, can significantly shorten the process to bring a new drug to market, and could eventually eliminate the need for animal testing,” commented CEO Graves, while Menno Ellis, executive vice president, healthcare solutions, expected to see collaborations “leveraging advancements in bioprinting to create human-based organ and disease models that are more translatable. These innovations can help pharmaceutical researchers obtain rapid feedback from experiments, and the data generated can even be leveraged in silico, using machine learning to accelerate the rate at which new drugs are discovered.”
“Despite market headwinds biopharma is still in a golden age of innovation. My favourite innovative modalities are in vivo gene and cell therapy (eg, in vivo reprogramming), next-generation mRNA technologies that increase efficacy and duration of response and novel platforms that expand the druggable target universe (eg, macrocycles, degraders etc),” said Søren Møller, managing partner at Novo Seeds.
“Our growing understanding of the oral microbiome has a significant impact on our ability to develop treatments for a large number of diseases driven by inflammation,” said Sindelar, whose company Keystone Bio is focused on addressing diseases ranging from Alzheimer’s and cancer to diabetes and cardiovascular disease by targeting the oral bacterium Porphyromonas gingivalis.
Thermo Fisher Scientific’s Gandhi flagged up diagnostics. “The biggest impact would be point-of-care (POC) molecular testing; whether that be in-clinic testing for conditions like influenza-like-illnesses (ILI) or sexually transmitted infections (STI) or near-bedside indications like sepsis, such technology has the ability to provide stat results and significantly impact patient management.”
For James Foster, CEO of Virax Biolabs Group Ltd., immune system testing is the hot new area. “After the COVID-19 pandemic the public has become more aware about the threats viruses impose on our lives and livelihoods. However, while vaccines as well as social distancing and PPE strategies saved millions of lives during the pandemic, now that we are entering the endemic phase of the disease many people want more information on their risk and greater autonomy with regards to healthcare decisions,” he said. “In order to achieve this autonomy, individuals must be able to have a snapshot of the state of their immune system – do I have the relevant and sufficient amounts of T-cells to mount an effective response against a given viral threat? With this knowledge and the consultation of a physician, patients will be equipped with information to make personalized proactive and protective decisions rather than a one-size-fits-all and reactionary approach that was evident in the global management of COVID-19.”
And for Russell Potterfield, CEO of Endevica Bio, “the continued rollout of 3D interaction visualization platforms like Nanome will make it easier for novice medchems to understand molecular interactions in ways that have been historically opaque. This will have the effect of helping new entrants understand molecular interactions much more quickly, which should speed drug development. 3D interaction visualization technology certainly helped COVID-19 comprehension and control.”
There is no lack of innovation in biopharma, but for it to be of value it must deliver tangible benefits: getting over the line, integrating into real lives and making a difference to patients.
“Pharma will face an uphill battle if they invest in the R&D of new therapeutics but fail to deliver on a robust commercialization strategy.” Deepak Thomas, Phil Inc
“Life science companies must invest in technology that removes barriers to medication access, so that patients can seamlessly start and adhere to therapy. Pharma will face an uphill battle if they invest in the R&D of new therapeutics but fail to deliver on a robust commercialization strategy – one that uses technology to unlock coverage and maximize reimbursement for brands,” warned Deepak Thomas, CEO of medication access software company Phil Inc.
“The technology advances that will have the biggest impact on pharma, physicians and patients are the solutions that integrate with systems that are already in place and integrate seamlessly into the lives of users,” offered Phil Inc.’s chief product officer Jonas Boli.
“Overall, 2023 will be a validation year for several innovations that are now shifting from the science stage to the commercial product stage. For example, gene therapies are already going through that shift in several key indications, the microbiome field just got its first regulatory validation in the drug world, and cell therapies expect incremental data and regulatory decisions in the solid tumors and allogeneic fields. However, this shift requires maturity at both the product and company levels and a transversal approach is critical to connecting the different development components together,” said Joris Pezzini, partner at consultancy Alira Health.
“We saw too many examples of innovative companies stalling in the past months as they had good science but failed to anticipate regulatory or access needs, underestimating the difficulty to integrate them all in their early evidence-generation plan,” he went on. “And it’s not to mention the manufacturing challenges that are still today limiting a true scale-up of most cell therapies. Therefore, beyond technological platforms, we believe that 2023 winners will be the cool-headed companies able to transversally cover all product development fundamentals, from science to market, resisting to take shortcuts in a cash-limited environment (exacerbated by the current crisis).”