Since the beginning of the COVID-19 pandemic, pharmaceutical organizations have experienced major changes, a prime example of which has been the rising requirement for collaborations on multiple different fronts across the industry. In some cases, companies have turned to doubling down on building more digital capabilities to enable virtual connectivity with healthcare professionals and patients rather than focusing on restructuring business units (1).

Many of the bio/pharma innovations that have been driven by the pandemic look like they are here for the long term, with a particular emphasis on vaccines that are being developed at the highest quality and astonishing production speeds. The future of vaccine development and the acceleration of novel delivery methods for these innovative therapies will be the most effective only if the industry manages to stay abreast of the rapid changes in technology. Some efficient tactics that will be brought into focus include improving manufacturing processes for quick vaccine delivery, reducing the need for multiple doses of a vaccine through boosting body immune response, and bettering transportation and storage of vaccines to reduce waste and improve access (2).

Preparation and cohesion in vaccine development is a must

The COVID-19 pandemic has led to many changes and shifts in the pharmaceutical industry, specifically with how pharmaceutical companies develop vaccines. Some of these organizations have turned to a new vaccination modality via the use of messenger ribonucleic acid (mRNA), according to Patrick Erbacher, chief scientific officer at Polyplus.

“The speed of development and the capacity for large-scale production make mRNA a vaccine strategy of choice. Combined with a lipid delivery system (lipid nanoparticles), this vaccine strategy has been shown to be effective with an easy and safe application through intramuscular injection,” says Erbacher. “To support this new area of development, [Polyplus has] have been working on a platform of tailored plasmids for production of mRNA or viral vectors, as well as transfection reagents that improve titer and quality and lower cost.”

In addition, the pharmaceutical industry has seen the new drug development timeline of vaccines reduced from several years to several months, remarks Park Eonyoung, lead scientist in the mRNA-based research team at Samsung Biologics.

“Pharmaceutical companies found that potential that vaccine development timelines can be reduced by several years and accelerated the development of new modalities like mRNA with advanced technologies including AI [artificial intelligence]-based approaches,” says Eonyoung. “These fast phases of the development of drugs and the need for preparation against future pandemic situations provide a positive impact on the investment of pharmaceutical companies.”

Even with the positives seen through the recent changes, there are some, like Marc Sauer, chief scientific officer at BIOVECTRA, who feel that applying parallel efforts from the COVID-19 vaccine creation to other vaccines would be a major benefit and lead to a sequential, development approach.

“Conducting manufacturing, clinical activities, and a rolling regulatory review in parallel comes with increased risk and requires a lot more funding than ‘the traditional’ way of doing development,” says Sauer. “We have certainly seen what is possible when economic pressures drive drug development.”

Another area that has changed since the COVID-19 pandemic is the use of technology transfer and how it has impacted contract development and manufacturing organizations (CDMOs). As an example, Kerstin Pohl, senior manager of Gene Therapy and Nucleic Acid at SCIEX, shared how the expectations of CDMOs have increased due to the pandemic, which has led to biopharma and pharma customers needing more accelerated timelines for new products.

“CDMO partners must therefore deploy advanced technologies for manufacturing and analytics, including digital and automated solutions, as well as apply a quality-by-design approach that ensures the development of optimal processes that can be industrialized to be robust, efficient, cost-effective and deliver high-quality, high-purity products,” says Pohl.

Sauer shared that established processes are being outsourced to CDMOs by pharma companies to create capacity for new modalities internally. “New modalities like mRNA, for example, also drive increased tech transfer activities as only a few companies have the scale and existing quality system in place to manufacture under GMP [good manufacturing practice] right now,” says Sauer. “CDMOs are certainly not immune to the financial pressures the global community has seen, and development programs require a lot more flexibility to pivot today than pre-COVID, due to increased pressure on portfolios and the ability to raise money in the market.”

On top of mRNA being used as a new vaccination modality, there has been a greater interest in non-viral delivery methods for mRNA in comparison to DNA to develop new vaccines, according to Erbacher. He explained how the delivery of mRNA occurs in the cytoplasm where the DNA needs to be transported into the nucleus of cells, which remains the bottleneck in DNA delivery.

“[MessengerRNA] vaccines seem to be appropriate to develop prophylactic vaccine especially against viral infections. However, mRNA suffers from its fragility and the encoding expression is very short,” says Erbacher. “In some cases, and particularly for anti-tumoral vaccines, it is expected to extend the expression duration to elicit more cellular immune response. Still, DNA vaccines may represent a solution for extended gene expression.”

Recently, technologies like inhaled vaccines and pill-versions of immunizations have been discussed as possible solutions for issues like storage and routes of administration for improving immune response.

Erbacher says that improving the formulation stability of both mRNA and LNPs through these options can help avoid freezing storage and increase the targeting and antigen presentation to the dendritic cells in the human body. However, Eonyoung stated that these types of vaccines continue to bring many challenges and less stability to the industry, but are still being pursued by scientists.

“Although it is difficult to develop, scientists are pursuing a nasal vaccine because respiratory viruses are found and infect cells in the respiratory tract including the nose, throat, and lungs,” Eonyoung says. “If a vaccine can create a localized immune response like the nasal cavity, it will have the advantage of capturing the virus before it gets into our body preventing transmission and spread of disease.”

Some of the major focuses for the future of vaccine development include lowering cost solutions, applying the same resources to every other disease program, developing universal vaccines, and ensuring access on a global standpoint.

Sauer is hopeful for what is to come due to the amount of effort is being made to design and build specialized manufacturing programs for vaccines that could be applied to future and existing health issues.

For Pohl, increased stability and simplified application should be given full attention to eliminate the need for a cold chain and enable self-administration without the need for injection and staying affordable. Further, she mentions how manufacturing processes should be improved to enable more rapid production of high-quality, high-purity vaccines.

“Given the complexity of modern vaccines and their potential application to millions of people, a wide range of complementary established and novel analytical technologies that can be leverage across the full development cycle should be pursued to reduce risk, optimize efficacy, and decrease development timelines,” emphasizes Pohl.

1. McKinsey & Company. A New Operating Model for Pharma: How the Pandemic Has Influenced Priorities. Dec. 21, 2021.

2. ABPI. The Future of Vaccines. ABPI.com. Jan. 10, 2023.

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Pharmaceutical companies have shifted their approach to development of vaccines as a result of the COVID-19 pandemic.

Evolutions in Vaccine Development

There is no doubt that chimeric antigen receptor (CAR) T-cell therapies have had a tremendous positive impact on patients that have received them; however, autologous cell therapies produced in centralized manufacturing facilities have inherent limitations that inhibit widespread availability and access. Allogeneic, or off-the-shelf versions, are one potential solution, but developers of these therapies must overcome different challenges, such as graft-versus-host disease, the potential for introduction of chromosomal abnormalities, ensuring successful gene editing of all donor cells, and problems with T-cell exhaustion (1).

Another option is to produce autologous therapies at the point of care (POC) (2). Companies such as Miltenyi Biotech, Lonza, SQZ Biotech, Orgenesis, and Ori Biotech have developed or are commercializing closed, automated cell- and gene-therapy production platforms with small footprints that can be installed at hospitals and institutions for good manufacturing practice (GMP) production of CAR T-cell therapies onsite. There are various university hospitals around the world exploring the potential of these systems. Orgenesis and aCGT Vector are establishing networks of POC sites leveraging their own production technologies.

A third approach being explored by several companies eliminates the need for gene editing of immune cells outside the body altogether. These solutions involve in vivo generation of CAR cells. This approach also has its challenges, but offers the potential to combine some of the benefits of both autologous and allogeneic cell therapies.

Autologous cell therapies today require collection of immune cells from the patient that are then shipped to a central manufacturing facility. Most patients are extremely ill and have endured multiple previous therapies, leading to variability in the starting material and the potential for manufacturing failures. Production slots are also limited, often creating delays that such ill patients cannot generally afford. Facilities that offer cell therapy are limited as well, and as a result, patients must travel to them, adding to the burden placed on them and their families. Furthermore, the cost of gene-modified cell therapies is high.

An IQVIA survey (3), notes Gregory Frost, chairman and CEO of EXUMA Biotech, revealed that the patient’s health status, cost to patient, and geographic distance for the patient to travel were the top three reasons why community oncologists do not refer patients for CAR-T therapy.

Allogenic cell therapies offer compelling benefits relative to autologous CAR T-cell treatments for certain indications. As off-the-shelf products, they are available immediately, eliminating the logistics complexities that add time and cost to autologous therapies. They also do not suffer from the variability associated with patient-derived cells.

Avoiding the natural immune response to foreign CAR-T cells has, however, proven much more challenging than past industry hurdles such as the advancement from mouse antibodies to human antibodies, according to Frost. “Although many different strategies are being explored, the only clinically validated solutions to this challenge to date has been sustained immunosuppressive treatment regimens to eliminate the body’s T and NK cell function, thereby increasing the risk of opportunistic infections without transplant-ward-level care,” he says. Generally as a result, the time that must be spent in the specialized care setting is often extended and introduces additional burdens for patients and their families that do not live near one of these specialized facilities.

 CAR therapies have the potential to offer the benefits of both autologous and allogeneic therapies. “The most apparent advantage that 

 CAR therapy could provide over autologous or allogeneic cellular therapy is to capture the durability benefits of autologous cell therapy with the reduced cost and complexity of an off-the-shelf product,” contends Frost.

If other safety parameters can be maintained clinically, Frost explains a CAR therapy that delivers a cost-of-goods-per-patient-treated on par with biologics may change the efficacy bar from 30–50% durable complete responses to a 30+% improvement in progression-free survival or overall survival, a particularly relevant goal for indications in solid tumors. “Moreover,” he adds, “lymphodepletion may not be necessary for 

 therapies, thereby potentially expanding the setting of care beyond tertiary care centers with intensive-care units and extending CAR therapy into indications not previously addressed (e.g., autoimmune disease) due to an unfavorable benefit-to-risk ratio.” Furthermore, as a true off-the-shelf option

 CAR therapy products are unburdened by the complex logistics for cryopreservation of a cellular drug product.

 CAR therapy “may address the significant concerns associated with autologous and allogenic gene-modified cell therapies and thus function to expand patient access to CAR therapy by making it safer, potentially more efficacious, less financially toxic, and available in settings more convenient to patients and their families,” Frost comments.

It is also worth noting that in addition to the reduced cost and complexity of therapy and the potential to expand to a wider array of care settings

 CAR/T-cell receptor (TCR) therapies reduce the complexity of cell processing validation, according to Frost. “While the product is the process,” he observes, “the 

 approach does not require the associated costs and time to develop an optimized and validated manufacturing cell process, which can introduce new challenges in comparability assessment with subsequent process changes.”

Frost also points out that enhancements and minor modifications to the transduction program encoded in the vector can easily be made, allowing for iterative evaluation preclinically and potentially clinically. “The versatility of the technology is anticipated to extend the technology broadly into academia and small and large biotechnology companies, which could result in the accelerated discovery and development of transformative therapies at substantially reduced costs,” he concludes.

 gene-modified cell therapies face their own set of technical challenges. A key issue, according to Frost, is the inability to perform preparative lymphodepletion of the patient prior to the infusion of the engineered cells. This procedure removes other immune cells that would otherwise compete with the CAR cells for growth factors and other nutrients, reducing their chances to survive, expand, and exhibit antitumor function. “Lymphodepletion is not a viable option for 

 CAR therapy since it would kill off the very cells targeted for in vivo engineering. As such, any 

 approach will need a means for ensuring robust proliferation and survival in an environment that is rife with competition for the same nutrients,” Frost says.

It is also essential that the vehicle delivering the genetic material for reengineering of the target immune cells is highly selective for the right cells. “Whether the vehicle is a viral vector or lipid nanoparticle (LNP), it must target delivery to the specific cell type to be re-engineered (e.g., T cell, natural killer cell) in order to prevent any unintended gene modification,” comments Frost.

Viral vectors and lipid nanoparticles represent two different approaches being explored for in vivo engineering. Nonviral approaches typically involve LNPs encapsulating nucleic acids, while viral approaches are generally based on the same retroviral vectors used in current 

Non-viral approaches, notes Frost, have the possible advantage of a more defined regulatory pathway based on the recent approvals of the COVID-19 vaccines. Non-integrating approaches may, however, not provide a sustained clinical response given that CAR transcripts become diluted (and eventually lost) as the cells divide, he observes.

Such therapies would likely require persistent retreatment in the absence of a clinical response, especially for the treatment of solid tumors, which require a prolonged T-cell response. “Integrating vectors, such as lentiviral (LV) vectors, may offer the benefit of stably
integrating into the host-cell genome to allow for a sustained response with a single dose,” says Frost. As such, he anticipates further investigations into the tropism of viral approaches to reduce the risks of adverse events associated with non-target cell integration.

The level of investment in in vivo gene-modified cell therapies suggests that this new approach truly does have real potential. Several startups have been established in the past few years with strong financial backing.

 CAR/TCR therapy platform, GCAR, comprises a lentivector with a CD3- targeting/activation element on its surface to target T cells and provide them with their initial proliferation stimulus. The genetic payload within the LV encodes for either a CAR or TCR, as well as EXUMA’s intracellular “DRIVER” signaling domain. Once integrated and expressed by T cells, DRIVER signaling and initial CD3 activation causes robust in vivo proliferation with persistence and antitumor activity in a lymphoreplete environment occurring from continued antigen engagement, according to Frost.

“Our proprietary LV design elements address the challenges faced by 

 CAR therapy, as the DRIVER allows for proliferation and persistence in the midst of competing cells, and the CD3-targeting moiety directs the lentivector to T cells,” Frost states. In preclinical animal models, EXUMA has confirmed enhanced tropism to T cells, circulating CAR-positive cells, and a potent, dose-dependent elimination of target cells upon 

Umoja Biopharma has developed its VivoVec surface-engineered LV vector-based off-the-shelf viral-vector particles for the generation of CAR-T cells 

 (4). The particles include rapamycin-activated cytokine receptors (RACRs) designed to selectively provide costimulatory molecules to CAR-T cells in the presence of rapamycin. Preclinical study results indicate the particle design demonstrates enhanced T-cell binding and activation both in vitro and 

, as well as generation of large numbers of CAR-T cells, thus enabling enhanced antitumor activity at lower doses.

Vector BioPharma’s Shielded, Retargeted Adenovirus (SHREAD) platform uses engineered adenoviral vectors combined with exogenous, high-avidity adapter proteins (in the form of virus-like particles) to achieve delivery to defined biomarkers on specific cells or tissues of DNA encoding various genes and regulators, allowing local production of potent drugs with reduced risk of systemic toxicities (5,6). The company was established in August 2022 to commercialize technology developed in the laboratory of Andreas Plückthun, PhD at the University of Zürich (7).

Ensoma, launched in February 2021, is also leveraging adenoviral vectors (8). Ensoma’s Engenious vectors are devoid of any viral genome, thus minimizing the chance of an immune response and freeing up to 35 kilobases of DNA packaging capacity to deliver a diverse range of genome modification technologies. The vectors can be used in vivo to engineer hematopoietic stem cells as well as erythroid, lymphoid (e.g., T cells, B cells), and myeloid (e.g., macrophages, microglia) cell types with precision. The company has entered into a strategic collaboration with Takeda Pharmaceutical Company (9).

Capstan Therapeutics, which was co-founded by Carl June, one of the original innovators in the autologous CAR T-cell-therapy space, and launched in September 2022 (10), is using mRNA technology to generate CAR-T cells 

. In one example, they injected CD-5 targeted mRNA-LNPs to reduce fibrosis and restore cardiac function in a mouse model of heart disease (11).

Interius BioTherapeutics is commercializing technology developed by Saar Gill at the University of Pennsylvania (12). The company is initially focused on treating hematologic malignancies using an in vivo CAR treatment, but hopes to expand to applications beyond immuno-oncology that address diseases not amenable to current gene-therapy modalities. It has provided minimal information about the specific technology involved.

gene-modified cell therapies at the preclinical development stage. SG295 is an 

 CAR T with CD8-targeted fusogen delivery of a CD19-targeted CAR for treatment of patients with B cell malignancies and for which the company expects to file an investigational new drug application (IND) in 2023 (13). SG418 is a hematopoietic stem cell-targeted fusosome with the ability to deliver gene-editing material 

 to repair genetic abnormalities such as those that cause sickle cell disease and beta-thalassemia. Sana hopes to demonstrate preclinical proof of concept in 2023.

Gene therapy provides a potential regulatory roadmap

gene-modified cell therapies constitute a novel drug class, they are related to direct gene therapies, several of which have received regulatory approval in the United States, European Union, and other countries around the world. These gene-therapy approvals, according to Frost, provide a helpful roadmap for regulatory evaluation of 

 CAR therapies. “While each product and platform has its own unique considerations that must be addressed for a specific indication, the FDA has also published numerous guidance documents regarding gene therapy that are helpful to sponsors developing 

As is the case with recent regulatory reviews of retroviral gene vectors in cells other than T lymphocytes, Frost expects that regulators will expect developers of 

 therapies based on retroviral vectors to demonstrate that those vectors are indeed transducing the target cell type (e.g., T cells) and not other cell types, such as hematopoietic stem cells or gametes. In this context, he notes that significant consideration must be given to the tropism of the delivery vehicle, whether viral or non-viral.

Clinical candidates anticipated in the next few years

Given the growing number of companies developing 

 CAR therapies using many different approaches, Frost anticipates candidates entering clinical trials within the next several years. The data gathered during those trials will serve to better refine the science. “With the advances that will be achieved and the growing body of evidence that will be generated as a result of these studies, it can be expected that the overall industry will become more comfortable with 

 gene therapy, ultimately facilitating the progression of other products to the clinic and eventually the market. The widespread use and breadth of enhancements to monoclonal antibodies, which were first discovered in 1975 and first approved in 1986, is suggestive of the potential for in vivo CAR therapy. With today’s technology and know-how, the innovation cycle for this technology is expected to be dramatically accelerated,” he concludes.

Preparing for the Allogeneic Cell Therapy Tipping Point

Alvaro, D. and Challener, C.A. Bedside Cell Therapies: Point-of-Care Manufacturing Is Slowly Becoming a Reality. Pharma’s Almanac, Nov. 15, 2022.

Saez-Ibañez, A. R.; Upadhaya, S.; Partridge, T.; Shah, M.; Correa, D.; and Campbell, J.Landscape of Cancer Cell Therapies: Trends and Real-world Data. Nature Reviews Drug Discovery, 2022. 21, 631-632, Supplementary Fig. 9,. doi: https://doi.org/10.1038/d41573-022-00095-1.

Umoja Biopharma. Umoja Biopharma Presents New Preclinical Data on its Integrated In Vivo CAR T and Engineered Induced Pluripotent Stem Cell Platform Technologies at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting. Press Release, Nov. 10, 2022.

Freitag, P. C. et al. Modular Adapters Utilizing Binders of Different Molecular Types Expand Cell-Targeting Options for Adenovirus Gene Delivery. Bioconjug Chem. 2022 Sep 21;33(9):1595-1601. doi: 10.1021/acs.bioconjchem.2c00346.

Smith, P. C.et al. The SHREAD Gene Therapy Platform for Paracrine Delivery Improves Tumor Localization and Intratumoral Effects of a Clinical Antibody. Proc Natl Acad Sci U S A. 2021 May 25;118(21):e2017925118. doi: 10.1073/pnas.2017925118.

Vector BioPharma AG. Versant Ventures Launches Vector BioPharma AG. Press Release. August 10, 2022.

Ensoma. Ensoma Launches to Pioneer Next-Generation 

 Approach to Deliver First “Off-the-shelf” Genomic Medicines. Press Release, Feb. 11, 2021.

Ensoma. Ensoma Announces Strategic Collaboration with Takeda to Accelerate Next-Generation 

 Gene Therapies. Press Release, February 2021.

Capstan Therapeutics. Capstan Therapeutics Launches with $165 Million to Deliver on the Clinical Promise of Precise 

 Cell Engineering. Press Release, Sept. 14, 2022.

Rurik, J.G. et al., CAR T Cells Produced 

 to Treat Cardiac Injury. Science. 2022. 375 (6576), pp. 91-96, Jan. 6, 2022. DOI: 10.1126/science.abm0594

Interius BioTherapeutics. Interius BioTherapeutics Raises $76M Series A Financing to Advance Breakthrough Cell and Gene Therapy Platform. Press Release, May 18, 2021.

Sana Biotechnology. Sana Biotechnology Confirms Key Program Timelines and Announces Portfolio Prioritization. Press Release, Nov. 29, 2022.

Cynthia A. Challener, PhD has been a freelance technical writer for over 20 years, leveraging her education from Stanford University (BS) and University of Chicago (PhD) and 10+ years of industry experience. She currently focuses on pharma/biopharma topics, writing technical articles, white papers, blogs, and other content for a variety of clients in addition to contributing regularly to 

Key challenges posed to autologous and allogeneic treatments could be resolved by in-vivo CAR-T gene therapies.

Advances in In Vivo CAR T-cell Therapies

FDA issued guidance on March 2, 2023 to provide recommendations to sponsors that help in the creation of monoclonal antibodies (mAbs) and other therapeutic proteins that target viral proteins or host cell proteins that interfere with pathogenic mechanisms of infection. A critical quality control measure for these products is the implementation of a potency assay(s) adequate to make sure that each lot is produced consistently with the potency necessary to reach clinical efficacy and that the potency is maintained over the shelf life of the product.

The new guidance provides detailed recommendations to drug developers with a target of helping to ensure that drug developers provide adequate information to assess potency at each stage of a product’s life cycle. Further, it describes approaches that sponsors should use to develop potency assay methods for release and stability that assess comprehensively known or potential mechanism(s) of action of the product. It also describes methods that sponsors should use to ensure the potency of mAbs and other therapeutic proteins intended to prevent or treat a viral infection.

News

The new guidance provides detailed recommendations to drug developers with a target of helping to ensure that drug developers provide adequate information to assess potency at each stage of a product’s life cycle.

FDA Issues Guidance on Potency for mAbs and Therapeutic Proteins

Bio-Rad Laboratories introduced its new StarBright Blue and StarBright Yellow dyes in February 2023. The dyes are designed to promote flexibility in conventional and full spectrum flow cytometry applications. Dyes in the Starbright series are conjugated to flow validated antibodies, supporting flow cytometry panel design in immunology design.

The two new variations in the Starbright series are intended to expand research capabilities across blue (488 nanometers) and yellow (561 nanometers) lasers. According to a Feb. 13, 2023 press release, the new dyes offer exceptional brightness in conjunction with narrow excitation and emission profiles, allowing for precise resolution.

StarBright dyes are compatible with most experimental protocols and flow cytometers without the need for special buffers. Additionally, minimal lot-to-lot variation helps to ensure reproducible and consistent staining, and the dyes are resistant to photobleaching with no loss of signal in fixation, according to the release.

"The continued development of the Bio-Rad StarBright Dye portfolio, now totaling 28 dyes and spanning multiple lasers, gives researchers greater choice and flexibility across multiplex flow cytometry applications, offering superior alternatives to existing dyes," said Mike Blundell, product manager, Flow Cytometry, Life Science Group, Bio-Rad, in the release. "With the launch of the StarBright Blue and StarBright Yellow Dyes, Bio-Rad now has the most comprehensive series of new dyes specifically designed for flow cytometry."

New Technology

Bio-Rad’s newly launched StarBright Blue and StarBright Yellow dyes are intended for use in various flow cytometry applications.

Bio-Rad’s New StarBright Blue and Yellow Dyes Enhance Multiplex Flow Cytometry

Eurofins Viracor, a Eurofins company specializing in testing for infectious diseases, immunology, and allergy, launched in February 2023 its Viracor ExPeCT chimeric antigen receptor T-cell (CAR-T) multiplexed quantitative real-time polymerase chain reaction (qPCR) assay. The tool is designed to monitor and optimize CAR-T therapy involving patients with pre-B cell acute lymphoblastic leukemia and B cell lymphomas.

According to a press release from Feb. 16, 2023, the test is designed to provide clinicians with an accurate and comprehensive assessment of the CAR-T cell population in the patient’s body, in turn offering potential insights into therapy effectiveness and what future treatment options may be advisable.

Eurofins Viracor ExPeCT CAR-T qPCR assay is a tool designed for monitoring and optimizating CAR-T therapies.

Eurofins Viracor Launches Test for Assessing Expansion and Persistence of CAR-T Therapy in Cancer Patients

Moderna and Life Edit Therapeutics, an ElevateBio company specializing in next-generation gene editing technologies and therapeutics, announced a strategic research and development collaboration on Feb. 22, 2023. The partnership, which will combine Life Edit’s suite of gene editing technologies with Moderna’s messenger RNA (mRNA) platform, will seek to advance 

gene editing therapies against a set of various therapeutic targets.

Under the agreement, Life Edit and Moderna will collaborate on research and preclinical studies funded by Moderna. Upon exercising an option for a target, Moderna will assume responsibility for further development, manufacturing, and commercialization. According to a company press release, Life Edit will receive an upfront payment and is eligible to receive potential development, regulatory, and commercial milestone payments for each target for which Moderna exercises an option, as well as tiered royalties on global net sales of products from the collaboration. The amount of financial compensation was not disclosed in the release.

Life Edit’s gene editing platform offers a library of base editors and RNA-guided nucleases (RGNs). According to the release, the RGNs are smaller in size when compared to conventional nucleases, which the company hopes can enable greater versatility for delivery. Additionally, the company’s nuclease collection features a range of protospacer adjacent motifs, short sequences that determine the DNA segments in the genome to which a nuclease can bind. The diversity of this range is intended to enable base editing at more sites than a single nuclease could achieve. This collaboration will apply Life Edit's RGNs and base editors together with Moderna's mRNA platform with the goal to develop curative therapies for challenging genetic diseases.

"This collaboration between Life Edit and Moderna demonstrates the strength of our respective technologies to advance programmable medicines to more specifically target disease," said Mitchell Finer, CEO, Life Edit Therapeutics, and president, R&D, ElevateBio, in the release. "Our novel editing systems have the potential to precisely modify gene targets for both 

 therapeutic development. We are excited that partners, such as Moderna, are recognizing the potential of our technology."

"At Moderna Genomics, we are constantly working to accelerate new therapeutic targets that may one day lead to the next generation of transformative mRNA medicines for patients," said Eric Huang, general manager and chief scientific officer, Moderna Genomics, in the release. "Through our collaboration with Life Edit, we hope to harness the power of gene editing technologies as part of our broader research and development engine, helping to advance our mission and deliver on the promise of mRNA."

Moderna will leverage Life Edit’s suite of gene editing technologies to advance development of in vivo gene editing therapies.

Moderna and Life Edit Therapeutics Enter Gene Editing Collaboration

AbbVie and Capsida Biotherapeutics, a biopharma company specializing in next-generation gene therapy platforms, announced an expanded strategic collaboration on Feb. 23, 2023. Building on a neurodegenerative disease partnership announced in 2021, the expanded partnership will see AbbVie work with Capsida’s novel adeno-associated virus (AAV) platform to identify and advance three programs.

According to a company press release, Capsida will lead capsid discovery efforts for all programs using its AAV engineering platform and will be responsible for process development and early clinical manufacturing. AbbVie will lead innovative therapeutic cargo approaches and be responsible for development and commercialization.

Per the terms of the agreement, Capsida will receive $79 million upfront. In addition to the upfront payment, Capsida is eligible for an additional $595 contingent on option fees and achievement of various research and development milestones. Should any therapies reach commercialization, Capsida is also eligible for further payments and low double-digit royalties.

“This expanded collaboration with Capsida has the potential to develop transformative therapies for patients with serious eye diseases,” said Jonathon Sedgwick, vice-president and global head of discovery research, AbbVie. “In pursuing the promise of genetic medicine-based therapeutics, AbbVie continues to expand our capabilities, and we are pleased to have Capsida as a partner.”

“AbbVie has been an excellent partner, and we are excited to expand our collaboration into ophthalmology with the world leader in this therapeutic area,” said Peter Anastasiou, CEO, Capsida, in the release. “Combining AbbVie’s expertise in eye disease drug development and commercialization with Capsida’s fully integrated next-generation AAV engineering platform and manufacturing capabilities offers the potential to provide novel therapies enabling unprecedented benefit to patients with serious eye diseases.”

AbbVie and Capsida have expanded their existing collaboration to advance three new gene therapy programs.

AbbVie and Capsida Strike $674 Million Gene Therapy Development Deal

Predictive Oncology, a biopharma company specializing in drug discovery, and Cvergenx, a genomics information company, announced the launch of a strategic partnership on Feb. 23, 2023. The goal of this partnership is to develop a genomics-based artificial intelligence (AI) approach to personalized radiotherapy and drug discovery.

The collaboration will utilize Predictive Oncology’s drug discovery, AI, and machine learning capabilities with Cvergenx’s precision genomics radiation therapy (pGRT) platform to pursue novel ways of optimizing radiotherapy (RT). According to a company press release, the companies believe this could potentially lead to the repurposing of existing compounds or the development of an entirely new class of drugs.

“The central principle in precision medicine is that cancer therapy should be tailored to the individual tumor biology. Even so, radiation therapy, the most commonly utilized therapeutic agent in clinical oncology, has yet to enter the era of precision therapy,” said Raymond F. Vennare, CEO, Predictive Oncology, in the release. “We believe that the next and most significant paradigm shift in the field of radiation oncology will come from exploiting tumor genomics to optimize RT prescription dose and to identify drug targets for the development of radiosensitizers and radioprotectors for biopharma and industry.”

“Today, RT is prescribed based on a one-size-fits-all approach where all tumors are treated with uniform doses of RT. pGRT provides the first clinically validated approach to optimize RT prescription dose for each individual patient,” explained Javier F. Torres-Roca, co-founder and acting CEO, Cvergenx, in the release. “The pGRT platform has been shown to correctly identify radiosensitizers and radioprotectors from large pharmacogenomic screens. We believe this knowledge can improve the clinical outcome of patients treated with radiotherapy.”

The goal of this collaboration is to develop an approach to personalized radiotherapy and drug discovery that is based in genomics and artificial intelligence.

Predictive Oncology and Cvergenx Enter Genomics-Based Personalized Therapy Collaboration

Charles River Laboratories announced on Feb. 13, 2023 the launch of its first Enzyme-Linked Immunosorbent Assay (ELISA) kit for the detection and quantitation of residual host cell proteins (HCP) in Chinese hamster ovary (CHO)-based biotherapeutics.

The new HCP-ELISA kit leverages avian immunoglobulin Y (IgY) antibodies as the primary detection technology. These antibodies are derived from specific-pathogen-free chicken (SPF) eggs developed exclusively by AVS Bio. The HCP-ELISA kit builds upon Charles River’s HCP-GAPex service, increasing the efficiency and efficacy of HCP assay development.

“With more than 30 years of impurity testing experience, host cell protein assays are one of our core competencies,” said Kerstin Dolph, corporate senior vice president, biologics solutions, Charles River, in a company press release. “Building on that expertise to bring our inaugural kit to market was the next logical step to strengthen our Biologics Testing offering.”

The kit is meant for use for the detection and quantitation of residual host cell protein.

Charles River Launches Novel IgY-based ELISA Kit

iotaSciences, a spin-out from Oxford University specializing in single-cell handling solutions, announced completion of its new single-cell picker instrument on Feb. 6, 2023. The isoPick is designed to provide temperature-controlled handling of single cells during isolation, as well as picking through a workflow guided by touchscreen interfaces.

According to a company press release, the isoPick is intended for cell and gene therapy researchers, as well as the wider single-cell research community, as a means of providing verifiable isolation of single cells with high cell viability and stable single-cell outgrowth. Like the company's other instruments, it is designed to have a small footprint instrument that requires minimal maintenance.

iotaSciences isoPick is designed to expand handling solutions for cell biology and gene therapy applications.

BioPharm International's BP Elements, March 2023