As a recent news story in Nature Biotechnology noted, the ban could extend to institutions that receive funding from the NIH or other U.S. government agencies, which would include almost all universities, research centers, hospitals, and life sciences companies.² The potential ramifications of such a measure are profound, with the potential to disrupt supply chains and derail drug discovery and development efforts on a national scale within the current outsourcing landscape.

Supply chain implications

The reality is stark: many pharma and biotech companies have turned to contract research organizations and contract development and manufacturing organizations located in China for efficiency and affordability, often outsourcing critical aspects of their operations. However, recent allegations of intellectual property leaks have sounded a clarion call, underscoring the vulnerabilities inherent in this dependence on such entities in certain jurisdictions for crucial research and development functions.

The specter of supply chain disruption, as exemplified by the logistical challenges brought about by the COVID-19 pandemic, also looms large in the minds of industry stakeholders. The concentration of manufacturing and research activities in distant locales poses inherent risks, leaving companies vulnerable to unforeseen disruptions.

The Biosecure Act serves as a poignant reminder that safeguarding intellectual property and data security must be paramount considerations in any outsourcing strategy.

Development implications

One potential solution is to go the way of many other industries: digital and encrypted. How would this work for drug development and manufacturing?

Forward-thinking digital chemists have been crafting the printing press for molecules and chemicals, a word processor, and autocorrect in order to bring the archaic, manual field of chemistry up to date. By introducing a chemical coding language and secure online data repository, the molecule design and manufacturing process could move away from traditional laboratory environments toward a fully digital, highly reproducible model.

In such a system, a chemical description language could tell a computer compatible with any batch chemistry robot how to synthesize a drug—similar to how HTML gives instructions to the browser in your laptop. Rather than relying on scant supplies of high-demand, hard-to-access drugs, those in developing countries would be able to access a “recipe” to produce the molecules needed at the push of a button.

This dream is already a reality in a specific and limited capacity. As governments around the world were scrambling to secure supplies of the COVID-19 treatment remdesivir, for example, digital instructions for whipping up a batch of the nearly 400-atom molecule were available on the open source repository Github, freely available to anyone with the hardware needed to execute the chemical program.

The wider adaptation of this approach—in individual labs and/or larger-scale manufacturing facilities in key biotech centers—could foster collaboration, accelerate the pace of discovery, and enhance precision and efficiency across the entire chemical development process. Importantly, it would also enable greater agility in response to evolving market dynamics and address the vulnerabilities associated with far-flung outsourcing.

By embracing digitalization, prioritizing data security, and reimagining traditional paradigms, the drug development and manufacturing industry could face a future defined by resilience, agility, and unparalleled scientific discovery.

Lee Cronin is Founder and CEO of Chemify, a U.K.-based deep tech chemical science company combining chemistry, robotics and AI at scale to digitally design, discover and make new molecules, and Regius Professor of Chemistry at the University of Glasgow. He has published over 450 papers, given over 600 lectures and has written extensively on all aspects of science from the origin of life to artificial intelligence.

References

1. US bill targets Chinese biotechs. Nature Biotechnol. 2024; 42(3): 353. DOI: 10.1038/s41587-024-02191-6.
2. Debevoise National Security and Life Sciences Update: The BIOSECURE Act. Published: May 22, 2024. Accessed: July 10, 2024. 

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Alongside the PR hype, however, there are real conversations taking place among industry leaders questioning whether the money flowing into AI will meaningfully improve productivity and output in the industry. While biotechnology companies have been touting a decade-old narrative about AI drug discovery being exponentially faster and cheaper than conventional drug discovery, so far these companies have put only a few drugs into clinical trials, and none have made it through Phase III and FDA approval yet.

Early high-profile clinical failures last year, including Exscientia’s Phase I/II study of its cancer drug EXS-21546 and BenevolentAI’s Phase II study of its dermatitis drug BEN-2293, suggest the return on investment for AI in drug development may be further delayed.

The conversation around AI in the pharmaceutical industry seemingly portrays AI tools as a shortcut to clinic-ready compounds. This exaggerates the power of AI to master something as diverse and complex as human biology.

AI tools alone aren’t a shortcut to a drug in the way that ChatGPT might be a shortcut to developing a term paper comparing the existentialist philosophies of Sartre and Camus. For us, the existential question is not, “Will AI revolutionize drug discovery?” AI undoubtedly will once it is applied properly. Instead, we need to ask, “How do we eliminate the translation problems that have plagued some of the early AI-derived compound trials?” If we could answer that question, we would be in a better position to validate AI-derived findings.

Why AI hasn’t lived up to the hype

Much of the excitement around AI in the pharmaceutical industry centers around the use of AI tools to identify new drugs by using sophisticated computer algorithms to crunch through publicly available datasets. Conventional wisdom suggests that the computer can’t be wrong. But if that were the case, why are we seeing challenges in moving from the dry lab to the clinic?

The answer likely lies in the data itself and in what companies do with their AI-derived findings. AI models are excellent at identifying correlations, but as we all know, correlations do not explain causation. The success of generative AI methods using data from public datasets is dependent upon the accuracy and completeness of the datasets used to train the AI models.

There is no evidence suggesting that we have yet fully digitized human biology. Even the most accurate and complete datasets can at best get researchers to identify proper correlations. Simply put, more data is needed. Companies developing drugs need to understand causation, which requires going back to the wet lab to validate AI-derived findings.

Real biological samples and longitudinal studies

In the present land grab for access to AI, there are few AI platforms focused on the use of real biological samples to feed their AI models, and even fewer using real biological samples in longitudinal studies to produce data. Few companies and groups are pioneering Bayesian AI versus more traditional machine learning models to derive insights from their samples.

The value of initiating research with samples from pre- and post-longitudinal disease samples and using a Bayesian approach is that it offers hypothesis-free discovery and holds the potential to redefine the conceptualization, discovery, and development of drugs. Neural AI can be used in concert as a next step to decode the intricate relationships between genetic factors and common diseases, aiding crucial decision-making about drug
development pathways.

With the use of real biological samples taken from the same patients at different times, AI can help researchers go beyond preset hypotheses and the traditional try-and-fail approach, and truly understand the causation of diseases and guide us to new discoveries. By validating pharmacological approaches in real biological samples either prior to preclinical testing or as part of their efforts to understand the results of clinical trials, AI helps us not only make novel discoveries faster, but provide imperative insights to ensure clinical trial success.

Leveraging these approaches, we’ve identified trial populations for therapeutic assets that have shown early promise in clinical-stage studies for difficult-to-treat cancers including glioblastoma multiforme and pancreatic cancer.

What success with AI tools really looks like

Despite the early failures that have raised skepticism about the value of AI to pharmaceutical development, I remain bullish on the opportunity ahead. Rich, comprehensive, and free of human bias, AI tools can, with the support of wet lab validation and preclinical translational models, bring us closer to precision medicine and provide value across the value chain of pharmaceutical development.

As widely predicted, AI tools can help us identify compounds for clinical development, but we must leverage real biological inputs—that is, inputs other than those from public datasets—and rigorously validate findings derived from AI models to ensure that we understand the underlying mechanisms of action in our therapeutic candidates, and what types of patients will be most likely to benefit. From there, we can design clinical trials to include only those patients likely to benefit.

Once we run a clinical trial, we can collect and analyze clinical samples using AI modeling of the patient’s biology before and after treatment. Insights derived from this modeling can help us better understand the biological effects of our therapeutic candidate and further refine our understanding of which types of patients respond to treatment, and which do not.

Finally, AI-derived insights can help direct a path toward label expansion or drug repurposing once a therapeutic is approved, by leveraging understandings of the mechanism of action and responding population characteristics and identifying other patient populations with similar biological characteristics.

Niven R. Narain, PhD, serves as the CEO of BPGbio. 

Biology-First Artificial Intelligence

BPGbio uses its NAi Interrogative Biology AI platform to operate a clinically annotated, longitudinal, 100,000-plus patient/sample biobank, and the company’s researchers have taken tissue, blood, and urine samples and subjected them to metabolomic, lipidomic, proteomic analyses. BPGbio officials say that analyzing integrated multiomics data with domain-specific AI models enables the company to better understand the underlying biology of the diseases for which it is designing therapies, and the biological changes that occur when its therapeutic candidates are administered.

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In a case that has, appropriately, drawn enormous national attention, the Supreme Court of Alabama ruled on February 16th in LePage v. Center for Reproductive Medicine that frozen embryos can be considered children under state law. The decision was issued in a pair of wrongful death cases¹ brought by three couples who lost their frozen embryos in an accident at a fertility clinic.

The court cited anti-abortion language² in the Alabama Constitution to rule that an 1872 state law allowed parents to sue over the death of their lost “children,” because embryos are made in the image of God. The court added that its decision “applies to all unborn children, regardless of their location.”

“Unborn children are ‘children’ … without exception based on developmental stage, physical location, or any other ancillary characteristics.”

This decision can be read as granting all embryos, even those with devastating abnormalities, the same rights as other children in Alabama. Certainly, no embryo can be destroyed, since that would constitute homicide. In fact, once created, it could be argued that the court sees some duty to make sure embryos are placed in an environment (a uterus) where they can become full-fledged adults, since intentionally creating “children” only to leave them frozen in suspended animation likely infringes their right to life.

The Alabama court opinion is hugely important. It reflects national efforts to end all abortions through legislation by arguing for fetal and embryonic personhood and, thus, for fetuses and embryos to have the rights of children. Also, it may well inspire other state courts to issue similar rulings.³

A threat to the rights of women

The decision is quite simply wrong, and if allowed to stand or, worse, to expand to other locations, it would destroy the rights of women to adequate reproductive healthcare.
The decision is wrong for other reasons. It invokes a particular view of embryos based on a contentious reading of the crucial text of a single religion. This is an obvious imposition on the rights of those who do not subscribe to this particular religious interpretation.

Nor does the court follow known facts about embryos. Conception does not always create life, much less a baby. Almost half of conceptions do not implant. Of those that do, 15% miscarry⁴ due to genetic anomalies incompatible with life. Not all conceptions have the capacity to become actual children.

Indeed, embryos are not, contrary to the opinion of the Alabama court, tiny “children.” That view, preformationism,⁵ popular in late medieval times, has been completely replaced by the knowledge that an embryo contains a set of genes that is sometimes able to produce instructions for a potential child but only if it is not misprogrammed and if it is implanted in a uterus where it can receive the requisite signals from the mother to begin development.

An embryo is a potential person. An implanted embryo is a possible person. Making up factual claims to reach ideological or religiously inspired conclusions is to use bad legal reasoning to reach deeply flawed conclusions about reproduction and human development.

Indefensible and dangerous

The consequences of the absurd Alabama ruling for women and their partners are indefensible and even dangerous.

As many women’s advocacy groups and medical groups have complained, women or couples seeking in vitro fertilization⁶ (IVF) will face many obstacles following this declaration that all embryos are children. Even the Alabama legislature, under huge pressure from IVF clients and programs, stepped in and tried to write legislation that would carve out IVF and the associated common destruction of overproduced, malformed, or abandoned frozen embryos, but the Supreme Court’s decision is clear and cannot be overridden in that way. The Alabama legislature cannot declare that murdering children in some circumstances is acceptable.

It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have actual children should find it difficult to use the technique. The Alabama decision is going to mean the end of IVF.

That has a political consequence that I don’t think can be sustained by proponents of fetal or embryo personhood. There is just too much momentum to support the use of IVF to try to create lives to make that a politically viable situation.

In addition, treating embryos as children means the end of preimplantation genetic testing (PGT), which helps ensure that the embryo selected for transfer in IVF has the correct number of chromosomes, thereby reducing the chances for a failed IVF cycle and the chance of miscarriage. This testing is now increasingly used to find monogenic/single-gene diseases such as cystic fibrosis, Tay-Sachs disease, sickle cell disease, and Huntington’s disease. No PGT will be permitted in Alabama, since no embryo destruction or failure to implant “children” would be allowed.

Should a woman undergo a pregnancy that might put her life at risk, her doctors, if in Alabama, would have to try to save both her and an embryo even if her life hung in the balance. And a woman who became terminally ill at any stage of pregnancy would not have her wishes or living will honored due to the presence of another “person inside her.” Women could be forced, even when brain dead, to serve as incubators in ICUs while doctors try to save embryos, no matter the women’s wishes, those of next of kin, or the long odds, or the length of time required to try.

Even contraception could be restricted under the holding that all embryos from fertilization are children. Some pro-lifers insist that hormonal birth control and IUDs act by making it impossible for an “embryo” to implant. Medical experts do not consider preventing implantation an abortion, nor do they even agree that this is how these forms of birth control work. Still, adding bad science to more bad science may produce severe restrictions on contraceptive choices.

The decision to declare embryos children is not based on science but on religion and a long outdated state law. It is not remotely consistent with how modern biomedicine understands what embryos are and how they work. Potentiality and possibility are not the same scientifically or morally as actuality.

The consequences of this muddled and indefensible ruling are dire. Women and those who seek to treat them in Alabama will find themselves denied access to technologies that could help them make actual children, with restricted access to testing and contraceptives that reduce the use of abortions, while also putting their patients’ lives at risk in other situations.

Lawyers have an old saying: “Bad facts make bad law.” The Alabama Supreme Court has shown just how true that wisdom is.

Arthur Caplan, PhD (arthur.caplan@nyulangone.org), is the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics and founding head of the Division of Medical Ethics at NYU Grossman School of Medicine.

Links
1. bit.ly/49svPIt
2. bit.ly/3PVgA3L
3. rb.gy/147pmb
4. cle.clinic/3Jhsyks
5. bit.ly/3JdZk66
6. bit.ly/3xF2InW

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To address these issues, GEN interviewed Thomas Rohrer, Senior Director of Bioconjugate Technology Support, Samsung Biologics America, a fully integrated CDMO.

GEN: What factors may be slowing down the research into ADC functionality?

The first generation of ADCs had a significant issue of off-target toxicity, particularly due to the novelty of linker technology. However, linker technology significantly progressed with the second generation of ADCs, reducing the rates of off-target toxicity and leading to better patient outcomes. The third generation of ADC therapies introduced site-specific conjugation, improving safety and target specificity. Developers have also become more experienced at predicting potential toxicity before the therapeutic enters clinical trials through improved understanding of tumor biology and better design of animal model systems.

GEN: What are some of the primary challenges to traditional methods of analysis in developing ADCs?

ADCs require significantly more analytical work than other biopharmaceuticals such as mAbs. Because ADCs consist of a large molecule, a small molecule, and a linker component, different analytical methods are necessary to evaluate each component separately and as a unit. This leads to approximately 17–18 different analytical methods needed to release an ADC drug substance. Fortunately, analytical methods of characterization have improved, just as ADC candidates have improved. Techniques such as liquid chromatography-mass spectrometry (LC-MS) are incredibly useful tools for characterization.

GEN: What new or emerging technologies are needed to achieve success in continued ADC research and development?

A considerable amount of research is being conducted on combination therapies involving ADCs. This can manifest in multiple ways, including ADCs in combination with another small molecule, ADCs combined with other ADCs, and ADCs attached to immune system modulators.

Historically, some of the most successful small-molecule cancer treatments have been combination therapies. It makes sense that ADCs are headed in the same direction as the technology becomes more sophisticated. In addition, as work on proteins in ADCs advances, the proteins may become smaller. In the future, some treatments may not even require the full antibody and use fragment antigen-binding regions (FAbs) instead. As bispecific antibodies become more popular, the specificity of payloads can also increase.

GEN: What trends are you seeing in the ADC research landscape? Do you think these activities will help push ADC research and utility in the right direction for improved therapeutic utility, or is there another research path you would consider?

There’s a deeper potential for bioconjugation than just ADCs. The combined functionality of two moieties will be a part of the research landscape for a long time. Take Prevnar, for example, a vaccine that has an immune system-stimulating drug conjugated to different polysaccharides. Radioimmunoconjugates are another example, where antibodies are conjugated with chelating agents. Targeted nanoparticles have the potential to facilitate the delivery of small molecules that might be considered effective in cancer treatment but lack potency when administered through systemic administration. Ultimately, these kinds of technologies have the potential to push the industry into the next generation of precision and personalized medicine.

GEN: What are some hurdles or opportunities you see in the near future?

The patent landscape in biotechnology is incredibly complicated. A biotech company may have a molecule with significant potential for use in an ADC but may opt against disclosing the intellectual property to other researchers and academics. However, there’s an opportunity for inter-industry collaboration to accelerate the development of more complex therapies.

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One critical factor of this scalability is the ability to use cryopreservation to preserve cell quality, viability, and functionality. This article delves into the hidden world of cryopreservation, shedding light on its crucial but often-underestimated role in the CGT landscape. Through real-life examples and insights from industry experts, we explore the downstream repercussions of neglecting cryopreservation and advocate for industry-wide standardization to foster sustained success.

Understanding scalability

The journey from clinical trials to commercialization is a pivotal phase in CGT development. This process involves transitioning a manual, bench-level, and relatively small-scale production process so that it can meet the demands of larger patient populations. The scalability challenges faced by companies in this sector are multifaceted and require careful planning. Decisions around scale-up versus scaleout, as well as the choice between in-house production and outsourcing, play a crucial role in shaping the trajectory of CGT products. If a drug therapy holds promise, the scaling process extends beyond clinical trials into the commercialization phase. By this point, companies have already made significant strides in scaling their output, driven by the increasing number of patients. Data gathering for FDA approval is a critical aspect of this journey, and strategic choices must be made regarding the production process. These decisions lay the groundwork for the future success and efficiency of CGT products. Along the journey, researchers need to think about scaling cryopreservation as part of the process, realizing that initial decisions can have long-term implications.

Identifying top-level issues

The scalability cascade involves a series of choices that, once made, can lock out alternative options. Seemingly inconsequential decisions made at the research and development phase can have far-reaching consequences. For instance, the choice of labware, storage bags, and cassettes (the aluminum frames that encase bags during freezing and storage) during the early stages of research can determine the ease of the cryopreservation processes downstream.

When the researchers are initially working on a therapy, they often pick a tube based on whatever is currently in the lab. But such a small decision that seemed inconsequential at the time can grow into a much larger decision down the line. For instance, if the researchers choose a tube that doesn’t have a labeling system, they’re going to be generating piles of samples that are unlabeled or labeled haphazardly. The size and shape of the containers can also prove to be an issue when later automating cryopreservation at scale.

A collaborative and team-based approach is essential to address top-level scalability challenges. Operations experts, logistics planners, and researchers must work in harmony to ensure a seamless transition from small-scale research to large-scale production.

Cryopreservation: A critical aspect

Cryopreservation is a linchpin in the successful CGT journey. The delicate nature of CGT products demands meticulous planning for cryopreservation scalability. Automation in cryopreservation is still a relatively new concept, and there is limited awareness of the process among industry players. When cryopreservation is automated, it eliminates the human error factor—streamlining the process to bolster efficiency and ensure sample integrity. An automated system handles sample management and supports regulatory compliance with precision tracking.

In the early stages of CGT development, the focus is often on proving the viability of therapies through small-scale, manual processes. However, as the number of participants in clinical trials increases, so does the demand for larger-scale production. The fragility of these therapies, coupled with the substantial investments made in their development, underscores the importance of planning for cryopreservation from the outset, as well as automating the process.

An article in Frontiers in Medicine titled “Cryopreservation as a Key Element in the Successful Delivery of Cell-Based Therapies” explains that “the need for innovative designs for freezing vessels will expand as therapies in regenerative medicine develop and will certainly be required for the cryopreservation of larger materials such as cell sheets and biomimetic tissues.”

Planning ahead: Real-world examples

Real-world examples serve as cautionary tales and success stories in the realm of cryopreservation planning. Late-stage considerations for cryopreservation and automation can pose unique challenges, particularly when choices made in earlier phases limit available options. On the other hand, up-front sharing of information can help identify potential pitfalls, and cryopreservation solutions can be planned appropriately. In one example, a customer came forward early in the process, seeking to automate their therapy production. However, a crucial oversight in the choice of a container meant it was not well-suited for automation.

Fortunately, this issue was identified early enough to rectify, highlighting the importance of considering automation needs from the early stages of development. Conversely, in another case, a lack of standardization led to the inability to automate cryopreservation. A customer had planned their entire strategy around a specific consumable, only to find that it did not fit into the automated cryopreservation system. Because they were too far along in the process with many samples already generated, their bags did not fit into the cassettes we had standardized on for our system, so we were both disappointed in that outcome.

This showcases the real-world consequences of neglecting cryopreservation planning and standardization, even when a therapy is well into its development phases.

Standardization in cryopreservation

The Standards Coordinating Body for Regenerative Medicine outlines the major benefits of using standards as:

1. Facilitate innovation and product development
2. Accelerate regulatory review of new therapies
3. Reduce cost to manufacturers and patients
4. Build support for new therapies
5. Encourage collaboration and knowledge sharing.

Improving the development and use of standards and best practices in regenerative medicine has the potential to help overcome some of the complex challenges related to scientific protocols, product testing, and product quality and performance specifications.

Standardizing processes, equipment, labware, delivery, and manufacturing within the cell therapy field is crucial for reducing inefficiencies and errors by driving quality and consistency. There is currently an industry-wide effort to create cell therapy cryopreservation standards and best practices, but this is still evolving.

Challenges arise from the absence of standardized container sizes, such as agreement on standard dimensions for a 50 mL blood bag. Without common standards, the process of automation becomes complex, and issues with scalability and
shipping logistics emerge.

The industry’s collaborative efforts, including recent ISO meetings, aim to address these challenges. Discussions about potentially adding standards related to scalability, shipping, and container specifications are helping to move industry efforts forward. A pan-industry group effort is underway to establish common goals and standards that can propel the
entire CGT sector into a future marked by efficiency and reliability.

Dawn Henke, PhD, senior scientific program manager of the Standards Coordinating Body for Regenerative Medicine, comments, “Secondary containment, such as the dimensions of cassettes, has emerged as the highest priority for standardization in cryopreservation. Fortunately, this is a concrete problem that is explicit and solvable, and relevant stakeholders in the industry are coming together to formulate and recommend solutions.”

The power of best practices and standardization

Implementing best practices and standards in cryopreservation offers multifaceted benefits. Planning for data tracking, sample management, and potential automation sets the foundation for a smoother transition for the manufacturing of CGT therapies.

As the CGT industry progresses, the adoption of best practices in cryopreservation will be a cornerstone for success. Whether planning for automation or merely considering future scalability, the careful selection of containers, labeling systems, and data management practices can prevent costly setbacks down the line. A proactive approach to cryopreservation planning ensures that legacy samples are part of a well-managed and traceable system.

The transformative power of adopting best practices and standards in cryopreservation cannot be overstated. The CGT industry stands at the cusp of a revolution, where strategic planning for scalability and cryopreservation will determine long-term success. The call to action is clear: prioritize these aspects for sustained growth and innovation. By collectively embracing industrywide standardization and adopting best practices, the CGT sector can navigate the challenges ahead and help usher in an era of unprecedented advancements in cell and gene therapies.

Erica Waller is a senior product manager for cryo automation and stores at Azenta Life Sciences.

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Recent breakthroughs in spatial biology technology have transformed biomedical research. This cutting-edge technology equips scientists to dive into the molecular details of human tissues and organs like never before. Seemingly overnight, researchers gained the power to visualize nearly every single gene (we have about 20,000) in every single cell with spatial resolution, a monumental leap from previous methods, which were limited to a few genes in a few cell types.

This revolution is akin to the transformative shift from the Hubble to the James Webb telescope in space science. Recognized as the 2020 “Method of the Year” by Nature Methods, spatial biology technology ushers in a groundbreaking era. It promises to deliver unprecedented insights into complex diseases, from cancer and diabetes to Alzheimer’s and other forms of dementia.

A shift to commercialization

Embarking on this exciting journey of discovery requires significant financial backing. Notable funding from the National Institutes of Health (NIH) has fueled pioneering scientists, turning groundbreaking ideas into commercially available platforms. This funding is crucial for ensuring equitable access to resources by dismantling technological barriers.

The NIH advocates for the transition from discovery to commercialization where innovations reach companies and eventually impact human health. This shift allows for scalability and rigorous standardization, ensuring laboratories worldwide generate comparable high-quality data. As these experiments can influence medical decisions, it is critical that scientists in London or Sydney obtain the same result from a tissue biopsy as scientists in New York City. Biotechnology companies play a key role in making innovative discoveries, commercializing them, and placing them in laboratories globally, thereby advancing scientific frontiers.

A rise in litigiousness

Unfortunately, the promise of spatial biology technologies has become clouded by a troubling reality: the clash of profit, power, and attempted monopolization. What should be headlines of groundbreaking advancements in fatal diseases through the use of spatial biology are now headlines dominated by legal disputes waged by powerful companies. Instead of international collaborations driving biomedical progress, conversations have shifted to technology restrictions and legal battles.

The focus is no longer on impactful discoveries, but on which companies are at risk of succumbing to legal pressures from deep-pocketed powerhouses. It is a concerning twist in a narrative that should be about advancing science for the greater good.

In the scientific arena, litigation has turned a once exciting field into an environment filled with complex and challenging situations. These conflicts are stifling small, innovative companies from advancing new technologies and ideas due to financial constraints, irrespective of eventual legal outcomes. This poses a threat to the progress of even the most promising scientific technologies and the potential discoveries they could enable.

Unfortunately, legal battles have driven the closure of promising companies that were unable to navigate the negative repercussions of these disputes. Additionally, the litigious atmosphere is discouraging emerging companies with groundbreaking solutions in spatial biology from patenting and publicizing their innovations, fearing potential lawsuits. The short-term gains for a few companies come at the cost of losing valuable contributions to long-term advances in biology. The consequence is clear: the legal battles are casting a shadow over scientific innovation and biomedical progress.

This legal behavior undermines fundamental principles of innovation, transparency, access, and diversity. Fear of litigation stifles innovation, leading to a lack of transparent methods. The restricted access to instrumentation, with an increasing number of countries facing bans on use of some spatial biology technologies.

At present, scientists have invested in good faith in spatial biology technology that can no longer be utilized, leaving research projects supported by charitable and governmental funding in limbo. A similar situation is now even threatening the United States. Perhaps most alarming, diversity in technology is waning. Healthy market rivalries are vital for driving innovation and ensuring quality as well as competitive costs for consumers—yet, in this climate, these principles are under threat.

For example, the lack of competition and the ongoing litigation pose a threat to patient care, particularly in laboratory settings where spatial biology analysis is used to select therapies. The Clinical Laboratory Improvement Amendments (CLIA) of 1988 set federal standards for facilities testing human specimens. Only one technology from a smaller company meets the necessary criteria to be implemented in CLIA laboratories, offering patients access to promising precision oncology therapies. However, this technology is facing legal challenges that could potentially block its use.

A call for antitrust action

We are urging spatial biology companies to engage in fair competition, and we are advocating for antitrust measures. The ongoing litigious environment has negatively impacted competitive progress, and we are concerned about the potential emergence of monopolistic behavior that could hinder innovative patient care. It is a troubling state of affairs that demands attention and reform for the sake of biomedical progress.

We stand at a critical crossroads, and scientists are sounding the alarm. The legal battles are casting a dark shadow over the once-thriving collaborative and innovative spirit propelling spatial biology’s rapid progress. These legal challenges are not just courtroom dramas; they are stifling the very momentum of scientific discovery, dimming the beacon of scientific advancement, and delaying clinical impact. It is a moment of concern that demands our attention and a collective effort to safeguard the spirit of exploration and innovation in spatial biology.

Authors and affiliations: Miranda E. Orr, PhD, associate professor, gerontology and geriatric medicine, Wake Forest University School of Medicine. Arutha Kulasinghe, PhD, group leader, Clinical-o-Mx Lab, Faculty of Medicine, University of Queensland. Grant R. Kolar, MD, PhD, professor of pharmacology and physiology, Saint Louis University. Holger Heyn, PhD, team leader, Single Cell Genomics Group, Spanish National Center for Genomic Analysis. Jasmine Plummer, PhD, associate member, St. Jude Faculty, and director, Center for Spatial OMICs. Lasse Sommer Kristensen, PhD, associate professor, Department of Biomedicine, Aarhus University. Jorgen Kjems, PhD, professor, Department of Molecular Biology and Genetics, Aarhus University. Gordon Mills, MD, PhD,  professor of cell, developmental and cancer biology and director of precision oncology, Knight Cancer Institute, Oregon Health and Science University. Juan J. Garcia-Vallejo, PhD, associate professor, Molecular Cell Biology and Immunology, Amsterdam University Medical Centers, I.J. Nijman, PhD, manager, Utrecht Sequencing Facility, Bioinformatic Facility, and High Performance Compute Facility. University Medical Center Utrecht (Center for Molecular Medicine) and the Netherlands X-omics Institute. Nicholas P. West, PhD,  associate professor, Central Facility for Genomics and School of Pharmacy and Medical Science, Griffith University. Amanda Cox, PhD, senior lecturer, Central Facility for Genomics and School of Pharmacy and Medical Science, Griffith University.

Note: This point-of-view article is based on the opinions of the authors and not their employers.

Editor’s note: See the following links for GEN’s recent coverage of the patent dispute impacting the spatial biology field: story on NanoString filing for Chapter 11 bankruptcy, interview with Serge Saxonov, PhD, CEO of 10x Genomics, interview with Joe Beechem, PhD, CSO of NanoString. 

The post Sounding an Alarm over Spatial Biology appeared first on GEN - Genetic Engineering and Biotechnology News.

“We have an outreach program now to small biotechs,” explains John Kokai-Kun, PhD, director, collaborations, and partnerships, biologics at U.S. Pharmacopeia. “A lot of great innovations come from them, but [financing] is currently tight and they can’t afford to make mistakes so we’re [making them aware] we have [potentially helpful] solutions.”

Kokai-Kun spoke about U.S. Pharmacopeia’s documentary and reference standards, and analytical reference materials at the September 2023 BioProcess International Conference. According to Kokai-Kun, the organization offers an online guide to mAb analytics, which includes documentary standards, educational resources, and ten physical reference standards.

These include USP’s first analytical reference material, a recombinant Phospholipase B-like 2 protein (PLBL2). This, he says, can be used to check that host cell protein (HCP) assays used in mAb manufacturing can detect PLBL2, which often co-purifies with mAb drug products where it acts as a contaminant.

USP is also in the process of collaborating with National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) to develop best practices for adeno-associated virus (AAV) and other common materials used in gene and cell therapy.

“Cell and gene therapy is a growing area in biologics,” says Kokai-Kun. “But it’s also a wild west with people doing something as simple as [assessing] full-versus-empty capsids in multiple different ways.”

A third recent area of activity is in vaccine quality assessment toolkits, with toolkits available for mRNA, viral vectors, and inactivated vaccines, with a toolkit relating to virus-like particles added last year.

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That piecemeal approach was especially frustrating for researchers Paul Reginato, PhD, and Daniel Goodwin, PhD, co-founders of Homeworld Collective, when they entered the field of climate biotech research.

“We started this because of ourselves,” Goodwin admits.

He and Reginato met in Ed Boyden’s lab at the Massachusetts Institute of Technology (MIT). One was doing in situ DNA sequencing and the other in situ RNA sequencing, but both found they were drawn to climate biotech as their lives’ work.

“We were confident the biotech industry had the resources for this field and were confident we could find a project [easily]…but we couldn’t find one at first,” Goodwin says, despite being what he modestly characterizes as “decently competent.”

Idea generation wasn’t the problem. Reginato and Goodwin shared ideas, killed them, and developed others in a continuous cycle, talking with hundreds of people one-on-one and at workshops.

As they soon realized that “there’s not the same funding [ecosystem] in climate biotech research as there is in medical biotech, and there aren’t the same playbooks for success or connectivity,” Goodwin says. When the two, plus Sarah Sclarsic (who later became a founding partner of venture capital firm Voyager), contemplated carbon removal, the right problems weren’t immediately obvious, Reginato recalls.

“Carbon dioxide removal will become one of the world’s largest industries in the coming decades,” Reginato predicts, “but there’s not a strong community around it in biotech.” They began identifying the constraints, areas in which biotech could contribute, the type of work needed and who could do it.

Creating an opportunity roadmap

That work led to the Homeworld Collective, which aims to help climate biotech scientists answer these fundamental questions:

1. What problems should I work on?
2. How do I get funding?
3. Where can I get input from potential investors?
4. Where can I find the best colleagues to work with?

One of Reginato and Goodwin’s most significant projects is the roadmap of opportunities in biotech for carbon dioxide removal, which is part of the global decarbonization effort. Reginato recently completed the first chapter, which identifies actionable projects. “It’s at a level of granularity that someone can get started,” he says.

The team believes that simply having such a playbook will change how individuals understand the field and interact within it, thus increasing the rate of innovation.

Geobiotechnology is another area of budding interest for Homeworld Collective. Reginato and Goodwin say it is essential to developing a cleaner, more ecologically-sound mining industry.

“It hasn’t been an area of focus for funding, but there are new possibilities to use biology for more efficient mining,” Reginato says.

Already, some 20% of copper mining involves biological mechanisms. Applications include using microbes to dissolve minerals and extract metals, or to bind to specific metals to enable more efficient mining. Emerging innovations have the potential to further expand the use of clean, bio-based technologies.

Building community

By providing that foundational information, Goodwin and Reginato hope to catalyze the type of exponential growth in the climate biotech industry that CRISPR created in the biopharma industry.

“That’s really hard,” Goodwin admits. Nonetheless, they have a plan.

“The first step is building community,” Reginato says. With strong networks, it is easier for researchers to connect, identify emerging problem areas, and find corresponding research opportunities.

“Right now, we’re adding a lot of energy, which is what we’ve been funded to do,” continues Reginato. “We love the opportunity to get people who never would have geeked out, to geek out,” Goodwin adds. They estimate they’ve interacted with some 500 people in the climate biotech space.

In a sense, Homeworld Collective is trying to replicate the type of casual, cross-disciplinary conversations the pair had in the hallways at MIT.

They’ve found that online chat groups don’t scale well, and are beginning to expand to public events. They’ve hosted one workshop already, on the interface of AI and wet labs for AI-powered experimentation, and are beginning to host pop-up groups around the United States to help those in the community grow their networks.

Currently, there’s no flagship conference for climate biotech, Reginato and Goodwin point out. They say they’re considering options to fill that void. “We’re trying to identify opportunities and to help them be realized external to our organization,” Reginato explains.

Homeworld Collective also is starting a newsletter to connect more people.

The objective of all this outreach is to build a multidisciplinary ecosystem with a rich set of working knowledge in the climate biotech space, according to Reginato. Ideally, it eventually will match what he calls “medical biotech’s gold standard for hyperproductivity.”

Increasing funding options

Historically, climate research in the United States has been funded mainly by the National Science Foundation and the Department of Energy.

There is a misconception that a lot of money goes into climate research. The actual figure is about 1.5%, based on Homeworld’s preliminary analysis of approximately 180,000 National Science Foundation (NSF) grants funded between 2009 and now. Only about 11,000 of those grants included both biology and climate keywords. They comprised 6.4% of the NSF budget. At the Department of Energy, of the 180,000 papers listing funders, only 9,000 mention proteins, and about 1,000 of those involved engineering efforts.

“Philanthropy could be much more involved than it is,” notes Goodwin. Attracting philanthropic attention—which the decarbonization roadmap is doing—could increase climate biotech research opportunities significantly and assure scientists that this is a sustainable career path.

Homeworld Collective also aims to formalize the financial path for a variety of verticals within the field of climate biotech, similar to established paths in biopharma. “In biopharma, each step of the journey is priced out, from basic research to new drug approval,” Goodwin says. Developing similar metrics for climate biotech, he suggests, will help the field grow faster and attract more talent.

Success means replicating the phase change that occurred in the biopharma industry in the climate biotech industry, Goodwin and Reginato say. Specifically, they want this community to:

• Have access to additional funding
• Be able to take “big, if true” shots on goal
• Enjoy vibrant connectivity across fields
• Transfer knowledge among disciplines
• Engage in casual yet technological conversations.

Half a century since the first Earth Day and 33 years since it went global, there’s still no cohesive network of climate researchers. The field needs a roadmap for success.

The post Catalyzing the Bioclimate Industry appeared first on GEN - Genetic Engineering and Biotechnology News.

The strategic agreement combines the capacity and capabilities of OBiO process development scientists with enabling platforms and support from Univercells Technologies, according to officials at both companies, who add that the combined know-how and capabilities will put OBiO in the position to offer GMP manufacturing services from R&D to commercial stages to gene therapy developers.

“Bringing gene therapies to market safely requires reliable, scalable manufacturing technologies. We were intrigued by the potential and became early adopters of the scale-X technology in 2020. Our recently published poster details the successful scale-up of an oncolytic Herpes Simplex Virus Type-1 (HSV-1) vector from scale-X hydro (2.4 m²) to scale-X carbo bioreactor (30 m²), with  significant reductions in manpower, materials and space requirements,” said Jia Guodong, CEO, OBiO.

“We will pursue this comprehensive collaboration with Univercells Technologies in multi products, conducting process development in the advanced fixed-bed bioreactor not only for HSV, but also for Lentiviral vector, Adeno-associated virus, and other cell and gene therapy modalities.”

“As we enter this agreement, the teams are already planning to scale up the oncolytic HSV-1 process in the 600m² scale-X nitro integrated in the continuous NevoLine Upstream platform,” added Florence Vicaire, CCO, Univercells Technologies. We look forward to further increasing their OBiO’s capabilities to meet the growing demand for gene therapies at a reduced cost, in China and globally.”

cGMP manufacturing partnership

Separately, The New Hope Research Foundation, a nonprofit organization dedicated to finding a genetic cure for GM2 gangliosidosis (including Tay-Sachs) and other lysosomal storage diseases, and Forge Biologics signed a development and cGMP manufacturing partnership agreement to advance the Foundation’s novel gene therapy, NHR01, into Phase I/II clinical trials for patients with GM2 gangliosidosis.

According to Timothy J. Miller, PhD, CEO, president, and co-founder of Forge Biologics, “Forge will provide adeno-associated virus (AAV) process development, analytical services, and cGMP manufacturing. The Foundation will leverage Forge’s platform processes, including its proprietary HEK293 suspension Ignition Cells, to accelerate the initial production. All development and AAV manufacturing activities will occur at the Hearth, Forge’s 200,000 ft2 gene therapy facility in Columbus, OH.”

“We look forward to embarking on our manufacturing collaboration with their experienced team and tried and true platform process to help accelerate our therapy into clinical trials and deliver new hope for patients with GM2 gangliosidosis,” said Jack Keimel, co-founder, and president of New Hope Research Foundation.

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Under the terms of the new agreement, Samsung Biologics will provide Pfizer with additional capacity for large-scale manufacturing for a multi-product biosimilars portfolio covering oncology, inflammation, and immunology. Samsung will use its newest facility, Plant 4, for the manufacturing of products.

“We are pleased to extend the strategic collaboration with Pfizer as we share and support their strong vision to bring innovative solutions for patients around the globe,” said John Rim, president and CEO of Samsung Biologics. “This new meaningful partnership comes just as our Plant 4 is fully completed early this month as we had previously committed and are on the move for future expansion into our second campus in order to provide our clients with even more flexible and advanced manufacturing technology.”

“Pfizer is excited to continue our strategic partnership with Samsung Biologics that aims to enable greater access to medicines for more patients across the world,” said Mike McDermott, chief global supply officer, executive vp, Pfizer. “This commitment is a reflection of Pfizer’s trust in the Korean pharmaceutical industry to address emerging health challenges.”

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