Prior to submitting an investigational new drug (IND) application to FDA, there is much for companies to plan and consider in advance. Collecting the appropriate data and determining just how much data are required to prove a drug product is reasonably safe for initial testing on humans are some of the challenges facing companies in the pre-clinical stage of development and planning for IND activities.

According to Mara Holinger, SVP, regulatory affairs, Veristat, the drug product, biologic, or other proposed assets should be tested in 

to demonstrate that the product is efficacious in a therapeutic model.

“Next, or in parallel, a contract development and manufacturing organization (CDMO) needs to be selected,” Holinger continues. “The drug product formulation needs to be carefully considered and then manufactured per good manufacturing practice (GMP) standards. The drug product will need to undergo toxicology studies, typically in two animal species, for both acute and repeat dose testing. These studies are generally required to be conducted per good laboratory practice (GLP) standards.”

Additional testing that might be required, depending on the product type and indication, includes the following:

It is also essential that all necessary information is collected for the drug substance, the drug product, and the non-clinical and clinical investigations, Paola Tocchetti, senior VP, head of global regulatory affairs, Evotec, explains. Some of the required information includes an investigator brochure, a clinical protocol, and IND sections in electronic common technical document (eCTD) format.

“It is our best practice to have all these documents included in an internal tracking system, an ‘IND tracker’ allowing us to follow the progress of the IND documents preparation according to the set timelines. The IND tracker also enables us to order priorities for any critical paths,” says Tocchetti.

As might be expected, some believe the best time to plan for IND activities is as early as can be managed.

“The regulatory strategy should be in place as early as possible in the development process—ideally at the step when the candidate is nominated for development,” says Tocchetti. “This is then followed by the IND edition, which requires the drug substance, drug product, and non-clinical reports. The health authorities’ regulations are the driving factor for the drug development process; for example, compendial tests from [the United States] and 

and regulated toxicology programs to support the first-in-human study must be performed.”

Meanwhile, Kevin Hennegan, senior regulatory strategist, Veristat, shares that there isn’t a single answer for when to start planning for an IND application, explaining that most companies should think about a regulatory plan once there are data to support a possible clinical benefit for an investigational product.

“To set the IND up for success, I think the two most important things a company can do are to engage an experienced regulatory professional (either an employee or a consultant) who can help you navigate the process; and take advantage of the free advice offered by FDA through the pre-IND meeting program,” Hennegan explains.

But the data are not the only important factor for INDs. A clear presentation of data is also critical. Hennegan adds that the success of an IND submission depends largely on how clearly the data are presented—in addition to complying with regulatory guidance.

“For a regulatory reviewer, it is important that the document that he/she receives is coherently worded, linguistically correct, [and] consistent in terms of content and connection between the different sections. The goal is to provide a document that the reviewer ‘enjoys’ reading,” says Tocchetti. “We also find that the timely and accurate input of all the R&D functions and the integrated management of their different contributions is crucial to ensure the success of an IND submission.”

From a manufacturing perspective, selecting a CDMO is a common pitfall. According to Hennegan, CDMOs can create significant delays in programs if they are low-performing.

“One other pitfall that is sometimes missed is not thinking product quality through all the way to delivery to the patient,” says Hennegan

 “If there is a dilution step or a novel (i.e., investigational) device required for delivery, you will need to provide data that those processes do not adversely affect the product.”

Hennegan further breaks down potential pitfalls into non-clinical and clinical:

: One pitfall is species selection. Costly additional studies can result from failing to perform toxicology studies in a relevant species. Meanwhile, costs can also be increased—without adding value—when selecting burdensome species. Selecting the best species to use should be discussed in a pre-IND meeting.

: Measures must be put in place to mitigate risks to the study subjects—such as frequent vital sign assessments, safety labs, follow-up visits, and rules for stopping a study—which can be done through risk analyses of the first-in-human protocol.

Tocchetti adds the most common pitfalls they have come across:

The reviewer can’t determine if the administration of a drug product in the clinical study is safe due to a lack of information in the IND.

The most recent FDA and European Medicines Agency guidelines aren’t adhered to when designing the nonclinical development.

GMP and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines aren’t followed, and a reason why the rules were not followed isn’t documented properly.

The quality level of the drug substance and/or drug product quality level isn’t sufficient to administer it to humans.

The findings of toxicology don’t support dosing in humans.

Moreover, one significant misconception about IND applications, according to Holinger, is the turnaround time.

“[I’ve] worked with several sponsors that believe the IND writing and submission process can be completed in a month or two. If a sponsor is starting from scratch (does not have a previous IND to reference), it typically takes four to six months to write an entire IND, pull together all of the documents, and publish/submit the IND,” says Holinger. “Another misconception I’ve come across is the assumption that an IND is a single document. INDs need to comply with eCTD standards including administrative information (module 1), summaries (module 2), CMC/quality (module 3), non-clinical testing (module 4), and clinical (module 5).”

“Companies who excel [in the IND application process] have an integrated and multidisciplinary approach to IND planning and execution,” says Tocchetti. “Thus, a tightly integrated approach and expertly coordinated delivery strategy enable them to carefully perform risk-management and rapid decision-making. The increase in quality allows for timely delivery of a robust and comprehensive regulatory data package for IND submission without ever needing to compromise on quality because of lack of time.”

In addition, the probability of a successful IND is increased by running a pre-IND meeting with the relevant regulatory agency, such as FDA, according to Tocchetti.

Proper planning and project management, according to Erin Flynn, regulatory strategist, Veristat, are also key to excelling in the IND application process.

“Proper planning and project management are critical aspects of IND preparation that are often underrated,” says Flynn. “The IND is a granular collection of documents that can sometimes be composed of upwards of one hundred individual documents, with multiple authors, and often with overlapping review cycles. It is imperative that all authors are aligned on product-specific details in order to maintain consistency throughout the IND and present the best face forward to the FDA. Project management is also key. It can be easy to get off track or overwhelmed by the sheer number of documents to prepare; so, effective tracking and timeline management streamline the IND preparation process.”

When looking ahead to 2022 and beyond, both Holinger, Hennegan, and Flynn predict the number of IND applications for COVID-19 vaccines will decrease. In addition, they predict a potential increase in the number of INDs for the treatment of COVID-19. Furthermore, they anticipate that trends in existence prior to the pandemic will re-emerge, such as an increase in INDs for personalized therapies, along with a general increase in INDs for mRNA-based products.

Meanwhile, Ralf Geiben Lynn, PhD, MBA, senior business development director, Evotec, foresees regulatory changes for large molecules.

“As more and more innovative treatments arise, we expect that the FDA guidance documents in non-traditional non-small molecule fields like biologics or gene-therapy products [to] evolve and mature,” says Lynn. “Thus, it is expected in the future, that the sponsors and specialized CROs will continue to keep up-to-date with these new treatments.”

Where the future of IND applications is headed, only time will tell. But one trend is clear: planning ahead whenever possible has the potential to provide a positive impact on INDs and their success rate.

Articles

Features

Avoiding roadblocks through strategic planning early on can help facilitate IND application filings. 

IND Applications Face Challenges Early On in Development Cycle

Beyond traditional monoclonal antibodies (mAbs), other antibody therapeutics are in development, such as bispecific antibodies (bsAbs). There is a significant focus on bringing bsAbs to market. Because most human diseases are complex and are often driven by multiple redundant or distinct mechanisms, a single-target approach such as a mAb may not be sufficient to achieve optimal therapeutic efficacy, says Jijie Gu, PhD, chief scientific officer and executive vice-president, WuXi Biologics.

In addition, many therapeutic concepts need physical linkage of two or more targets. In this case, bsAbs or multi-specific antibodies (msAbs) that target two or more targets may offer novel therapeutic applications that are difficult or impossible to achieve with mAbs, Gu confirms.

BsAbs show promising effectiveness because they can simultaneously bind two different antigens—a functional parameter with a wide variety of applications and benefits that enable precise targeting and higher potency and a broad range of mode-of-actions that are inaccessible for traditional mAbs, explains Nikki Nogal, global director of Technical and CMC for Upstream, Lonza. In addition, multiple binding sites can help reduce the development of subsequent clinical resistance. These advantages have led to the significant focus on both research and development of bsAbs.

BsAbs have broad clinical applications in tumor immunotherapy, and other fields where they can be applied are in neurological disorders, targeted drug delivery, or infective diseases, Nogal adds.

“The biologics pipeline has been evolving towards more complex protein formats for the past few years. A total of 273 bispecific molecules successfully entered the clinic since 2001,” Nogal says. “We expect bispecific proteins and other complex protein formats to dominate the drug development pipeline in the next five to 10 years.”

Nogal explains that this class of biotherapeutics offers not only improvements in treatment accuracy but also flexibility, including treatment approaches, which are factors that have played decisive roles in the pursuit of bispecific therapies by drug developers. “Leveraging known drug administration methods, bispecifics hold promise for patients unable to be treated in traditional environments, thereby removing obstacles and creating inroads to care,” she states.

The term “bispecific antibodies” describes molecules that recognize two different antigens or epitopes, compared to conventional mAbs, which are molecules that can only recognize one antigen. BsAbs range from small proteins—two linked antigen-binding fragments—to large immunoglobulin molecules with other attached domains, according to Nogal.

“The key difference between bsAbs and mAbs—that is, bsAbs’ ability to bind with two antigens simultaneously and mAbs just one—is their fundamental ‘improvement’. With bsAbs, we are now able to target more than mAbs,” Nogal explains.

Furthermore, bsAbs in cancer therapy can provide a higher binding specificity, which results in increased precision, allowing for the immune system to directly contact the tumor cells as well as enhancing their cytotoxicity. Nogal notes that this effect can possibly decrease the required dosage, making for an improved patient experience, which has been a paramount goal in oncology. Additionally, when paired with other treatments, bsAbs help reduce the development of clinical resistance because of their ability to bind to multiple sites and avoid the regulation of parallel pathways, Nogal adds.

Traditional mAbs, in comparison, exhibit singular antigen-target-binding specificity primarily due to the structural symmetry of the antibody. This consequently imposes limits to both the function and medical benefits of mAbs, Nogal emphasizes.

“By contrast, the two halves of the antibody are not alike for bispecific antibodies, enabling concurrent specificity for either two different epitopes on the same antigen or two different antigen targets,” she states.

Another factor with mAbs is that, given that the two symmetrical domains are alike, construction of the molecule is typically less challenging. Conversely for bispecific formats, molecular assembly is an integral component of construction. This assemblage is a challenge that has long hamstrung development efforts of bsAbs due to the propensity towards mispairing, that is, until the advent of the “knobs-into-hole” technology that offered an effective, albeit partial, solution, Nogal reveals.

Besides having an additive effect or synergistic effect, the most fascinating applications of bsAbs are their potential to enable novel and often therapeutically important concepts otherwise impossible by using mAbs alone or in combination, specifies Gu. “This so-called obligate bsAbs could open up completely new avenues for developing novel therapeutics,” Gu says.

As disease mechanisms are often complex and involve a myriad of signaling pathways, bsAbs offer the advantage of tackling a disease from multiple angles with just a single molecule instead of a combination of multiple mAbs, as previously stated. One interesting application, furthermore, is the potential to recruit the cell-mediated immune response to the tumor site by targeting the appropriate antigens and driving co-location through the bsAbs, highlights Ahmad Sediq, principal scientist, group leader, Lonza.

Nogal, meanwhile, goes on to explain that because each half of a bispecific molecule possesses a different function, this characteristic allows these molecules to recruit and activate various immune cells, interfere/inactivate receptor signaling and signaling ligands, and force association of a plethora of protein complexes. “This improvement in versatility over conventional mAbs is desirable from a therapeutic standpoint,” Nogal says.

Further, Nogal notes that implementing a combinatorial approach of bsAbs in conjunction with existing new therapies represents significant improvements to response rates and durability compared to bsAbs alone.

Gu points out that by January 2022 FDA had approved five bsAbs, among which four are obligate bsAbs whose mechanism-of-actions cannot be achieved by simply using mAbs alone or a mAb combination. For example, Gu notes that the recently approved amivantamab (brand name Rybrevant, a Janssen Pharmaceutical Companies of Johnson & Johnson product), which targets both Gu the mesenchymal-epithelial transition factor (c-MET) pathway and the epidermal growth factor receptor (EGFR), showed significant therapeutic benefits in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) carrying EGFR exon 20 insertion mutations (1).

“This type of NSCLC is resistant to common EGFR inhibitor (EGFRi) therapies. [C]ombined with EGFRi therapy, EGFR mAb therapy [has shown] some clinical benefit in patients with this type of NSCLC, [but] the associated severe toxicity [associated with this combination therapy] may limit its application,” says Gu. Data published by Janssen for its bsAb product, however, show that by carefully selecting and designing the cMET and EGFR target arms in its bsAb product, amivantamab not only demonstrated promising therapeutic efficacy but also demonstrated improved safety profile (2,3), which led to its accelerated approval in 2021, Gu observes.

Nogal points out that bsAbs currently have major applications in cancer immunotherapy and drug delivery. In addition, corporations are exploring many applications of bsAbs in other diseases, such as hematologic malignancies (e.g., hemophilia A), diabetes, and Alzheimer’s disease.

Conventional mAbs typically do not activate T-lymphocytes, as this is a property unique to bispecific formats, Nogal explains, noting that it is this distinction that translates to bsAbs’ outstanding clinical efficacy in hematological malignancies. Despite these advantages, a significant therapeutic effect on solid tumors remains elusive. This elusiveness is primarily attributed to the fact that advanced solid malignancies are notorious for their suppressive tumor microenvironment (TME), which hinders activity of T cells, thus leading to sub-optimal immune function. “Therapies with the ability to dysregulate the TME by activating T cells hold potential for significant therapeutic impacts where traditional mAbs may either be lacking or have failed,” says Nogal.

“Because bispecifics are more customizable, they can be designed to have higher cytotoxic potential and bind relatively weakly expressed antigens, making this cohort of molecular formats best suited to cancers,” Nogal states.

Among the five launched bsAbs that Gu mentioned previously, three are for cancer treatment, one for hemophilia A, and one for age-related macular degeneration. Gu notes that the bsAb clinical development pipeline is composed predominantly by programs for cancer treatment.

“Autoimmune disease is the second largest area for bsAbs’ applications. The reasons that the majority of the programs are focusing on cancer treatment is not only because of the huge unmet medical needs, but also because as a unique class [of drugs], bsAbs can redirect the immune effector cells to eliminate tumor cells, specifically, by engagement of both of the arms of the bsAb onto the effector cell and tumor cell, respectively,” Gu states.

The first FDA-approved bsAb, BLINCYTO (blinatumomab) by Amgen (4), belongs to this category of drugs that redirect T cells to kill tumor cells, Gu specifies. “Now, with the deep understanding of how immune cells kill tumor cells, a new wave of many immune-cell-engager bsAbs with improved clinical efficacy and better safety profile is in clinical development,” Gu asserts.

“BsAbs and msAbs open up tremendous opportunities to explore previously unexplored therapeutic options,” Gu continues. “We believe that the next decade will witness the clinical success of bsAbs or msAbs employing some novel mechanisms of action (MOAs) in cancer and in infectious, metabolic, ocular, and other diseases with significant unmet medical needs.”

Although they are a promising new wave of therapeutics, bsAbs have historically been challenging to move from research to clinical stages of development.

Compared to mAbs, bsAbs display significant complexity in the research and development stages. In particular, technical considerations, especially chemistry, manufacturing, and controls (CMC) and mechanistic or biological complexities are major challenges, explains Gu.

In addition to CMC challenges, special testing systems are needed to characterize the potential therapeutic efficacy, toxicity, pharmacokinetic/pharmacodynamic profiles, and immunogenicity risk of bsAb therapeutic candidates at research stage as well as at the preclinical and clinical development stage, Gu adds. “Many of these systems may be quite complicated, as compared to the systems used to evaluate mAbs,” Gu says.

Many companies are therefore developing various bsAb technologies to tackle these technical challenges. For example, WuXi Biologics has established technology platforms (WuXiBody, SDArBody) that enable the development of novel bsAbs. One of the company’s platforms (WuXiBody) exhibits enhanced compatibility for the assembly of almost any mAb sequence pairs, offers a unique structural flexibility for building multi-valent formats, and offers developability advantages that can address CMC challenges, according to Gu. Gu also states that two molecules born out of this technology platform (WuXiBody) are now in clinical development, with one molecule having reached the investigational new drug (IND)-filing stage.

WuXi Biologics’ other platform (SDArBody) is a single-domain antibody-based msAb platform that allows the flexibility to build multi-specific or multi-functional antibodies to enable unique MOAs for therapeutic applications. Molecules developed from this platform also exhibit good CMC developability. Gu notes that WuXi Biologics’ experience working on bsAb technologies, as well as a variety of generic bsAb formats, has given it experience in the stable cell-line generation, protein expression, purification, characterization, as well as manufacturing and formulation of bsAb drug substance and drug product. This experience has led to success in enabling translating bsAb molecules from the research phase to clinical development.

Nogal notes that manufacturing bsAbs possess unique challenges specifically related to their expression in upstream processing and their separation and purification in downstream processing. “As bsAbs are comprised of two distinct heavy and light chains, multiple combinations are possible during assembly in production. Mispairing between light and heavy chains during expression could lead to misassembled unwanted antibody species that are difficult to remove due to their similarity to the correct format,” she states.

Lonza also developed a platform (bYlok) that addresses the technical limitations of bsAb development. This technology relies on adjustments of the position of one of the disulfide bridges, which, when used in combination with knobs-into-holes, favors the formation of a correct heterodimer species. According to Nogal, the platform delivers more than 95% correct heavy and light chain (HC–LC) precision pairing. The platform uses a mAb-like approach and generates bsAbs that mimic parental antibodies in key characteristics, such as yield, stability, immunogenicity, and functionality.

The advantages and versatility of bispecifics, compared to conventional mAbs, not only renders them more attractive from a therapeutics perspective but distinguishes them as more complex proteins that can be challenging to construct, design, and produce, Nogal adds.

Bispecifics are often grouped into one of two categories: immunoglobulin G (IgG)-like and non-IgG-like. “The relatively large molecular weight of IgG-like molecules simplifies purification due to the presence of the heavy chain Fc [fragment crystallizable] region. This also improves attributes, including stability and solubility, and increases the serum half-life and affinity, thereby enhancing biological activity,” Nogal says.

Sediq, meanwhile, explains that, as these molecules exhibit a large variety of formats, partially exhibiting a complex structure not resembling native proteins, complex BsAbs may have a higher risk of unwanted immunogenicity. The combination of multiple antigen specificities furthermore poses challenges to safety evaluation (e.g., in selecting relevant animal models and the need to test very low doses to establish product safety).

“The plethora of different bsAbs formats and emerging novel formats also pose a major challenge in creating stable formulations. Unlike conventional mAbs where much prior experience and knowledge is available and established, this is not yet the case for bsAbs. This means that ‘platforms’ cannot be leveraged and bespoke approaches for every specific molecule is needed; this may thus result in longer development timelines,” Sediq says.

While bsAbs offer the advantage of increased binding specificity as compared to conventional mAbs, this may, however, come with a downside for in-use and compatibility studies required for early-stage clinical trials (e.g., dose-finding studies). “For highly potent molecules, the concentrations may go down to µg/mL for an intravenous administration, posing significant challenges to the analytical panel to assess quality/stability as well as quantity of the bsAb,” Sediq emphasizes.

“It is well known that vibrations, heat, or sunlight exposure (e.g., occurring during transport, handling, and distribution) may affect the stability of proteins. However, there is little research about the stability of biologic products after they leave manufacturing sites—which is unfortunate, as the medicines’ journey does not end there but continues until the final dosing solution is delivered to the patient at a hospital or a clinic,” Sediq explains.

Over the past 20 years, there have been numerous cases of severe adverse reactions or even deaths associated with improper and/or erroneous drug preparations in hospitals, Sediq also points out. Due to their sensitive nature, handling of protein-based solutions such as bsAbs may jeopardize their quality by increasing levels of physical instabilities through aggregation or chemical degradation, such as oxidation. These impurities can lead to adverse drug reactions and/or alteration in the drug effectiveness, he cautions.

To help solve this problem, Lonza participates in the Real-World Handling of Protein Drugs—Exploration, Evaluation and Education (RealHOPE) project. This is an initiative that was started by the Innovative Medicines Initiative and European Federation of Pharmaceutical Industries and Associations partners; the project aims to measure real-life events during drug handling that can destabilize protein-based therapeutics.

“By becoming part of the RealHOPE Project, our goal is to thoroughly map out the real-life handling of these drugs in clinical practice or at a patient’s home, to develop simulation models and analytical methodologies assessing the impact of the handling on product quality and introduce best practices to control or avoid these stability and efficacy challenges,” says Sediq.

1. FDA, “FDA Approves First Targeted Therapy for Subset of Non-Small Cell Lung Cancer,” Press Release, May 21, 2021.
2. S. Zheng, et al., 

 8 (3) 551–561 (2016).
3. J. Neijssen, et al., 

 296, 100641 (January 2021).
4. Amgen, “FDA Approves BLINCYTO (Blinatumomab) Immunotherapy for the Treatment of Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia,” Press Release, Dec. 3, 2014.

Feliza Mirasol is the science editor for 

The recent approvals of bispecific antibodies have opened the gate for the further development of these complex molecules. 

Development of Bispecific Antibodies Pushes Forward

Coya Therapeutics, a clinical-stage biotechnology company, secured an option agreement in June 2022 for exclusive worldwide rights to a novel technology platform from Carnegie Mellon University. The technology platform enables exosome engineering.

The agreement will grant Coya intellectual property rights to the research, development, and manufacturing of exosome-polymer hybrids (EPHs), according to a June 15, 2022 press release. The company will use a tether-based exosome strategy that enables regulatory T-cells (Tregs) exosomes to be homed to proteins of interest while delivering select payloads into the targeted cells.

According to the release, the use of EPHs differs from traditional techniques that modify exosomes via complex molecular biology tools or degradation of exosomes' innate functionality; EPHs overcome these limitations by modifying exosomes with a DNA-cholesterol tether. By leveraging single stranded synthetic DNA with attached cholesterol, this approach binds a complementary strand of DNA to a bioactive agent. Ultimately, this allows a number of different types of cargos to be attached to the exosome surface while also tethering immune modulating cargos inside the exosome.

“This collaboration with Carnegie Mellon University further solidifies Coya’s thought leadership in the global exosome therapeutics field, beyond Treg-derived exosomes alone,” said Howard Berman, CEO, Coya Therapeutics, in the press release. “Nanoengineering exosomes with such manufacturing efficiency to produce EPHs that can be customized to any surface protein, delivering growth factors or drugs, while enhancing cellular uptake and bioactivity is the future of targeted therapies.”

News

Coya Therapeutics has secured intellectual property rights to the research, development, and manufacturing of exosome-polymer hybrids.

Coya Therapeutics Secures Rights to Exosome Engineering Technology from Carnegie Mellon University

Bio-Rad Laboratories’s new CFX Opus Deepwell Real-Time Polymerase Chain Reaction (PCR) Detection System is designed to support researchers in developing nucleic acid detection assays. The product, launched in June 2022, is the latest in Bio-Rad’s portfolio of CFX Opus Real-Time PCR instruments.

The CFX Opus Deepwell has a 96-well block and a reaction volume of up to 125 µl, the largest in the CFX Opus range, according to Bio-Rad in a June 27, 2022 press release. The system can multiplex up to five targets simultaneously and supports fluorescence resonance energy transfer applications.

According to the release, the deeper sample wells are designed for workflows requiring larger reaction volumes for pooling, certain sample prep procedures, and other specialized protocols, such as food and industrial testing or veterinary pathogen detection. The CFX Opus Deepwell can be linked to Bio-Rad’s BR.io platform, which provides remote setup, instrument monitoring, and cloud data management solutions.

"We are witnessing an increasing demand for improved real-time PCR systems that offer more efficient workflows and enhanced data management and analysis," said Steven Blakely, director, Gene Expression and Software Technology, Bio-Rad, in the press release. "We're pleased to expand our portfolio of CFX Opus Detection Systems with the Deepwell format to help researchers perform experiments more efficiently and to consistently deliver robust datasets."

New Technology

Bio-Rad’s CFX Opus Deepwell Real-Time PCR Detection System is designed to support researchers in developing nucleic acid detection assays.

Bio-Rad Launches CFX Opus Deepwell Real-Time PCR Detection System

Bio-Rad Laboratories has launched its EconoFit Low-Pressure Prepacked Chromatography Column Packs. The EconoFit columns are designed for resin screening, allowing customers that are developing protein purification workflows to select the optimal chemistry for different targets.

The columns offer various resins in a prepacked format, including mixed-mode, cation, and anion exchange resin columns, as well as a pack designed for polyhistidine protein purification. According to a June 28, 2022 press release, they are fully compatible with Bio-Rad’s next-generation chromatography systems in addition to other commonly used chromatography systems. The columns are available in 1 mL and 5 mL sizes.

“Similar resins can give different results for different target molecules, and with Bio-Rad’s EconoFit Column Packs our customers can easily perform resin scouting to identify the one [that] yields the best outcome for their chromatography application,” said Ertan Ozyamak, global product manager for lab-scale chromatography products, Bio-Rad, in the press release. “Our columns deliver run-to-run uniformity to support preparative scale purifications and/or method development for new target proteins, as well as to improve existing workflows.”

Bio-Rad’s EconoFit Chromatography Column Packs support resin screening experiments in the development of protein purification workflows.

Bio-Rad Launches New Chromatography Column Packs

VeriSIM Life (VeriSIM), a US-based artificial intelligence (AI)-enabled company that provides drug discovery and drug development services, has entered into a collaboration with Mayo Clinic to improve the preclinical translation of promising drug candidates for development.

Under the agreement, VeriSIM will use its proprietary BIOiSIM platform and Translational Index technology to reduce the number of outsourced preclinical experiments. These platforms are also expected to help de-risk R&D decisions early on to ensure expedited development of novel, safe, and highly efficacious drugs, according to a June 28, 2022 company press release. Mayo Clinic physician researchers will work with VeriSIM in key disease areas, including oncology, hematology, bone/joint-disorders, and neurological diseases.

“This collaboration will explore the full potential of our combined approach to developing best-in-class drug candidates to serve patients’ unmet needs,” said Jo Varshney, founder and CEO of VeriSIM Life, in the press release.

VeriSIM Life and Mayo Clinic are collaborating to develop new promising drug candidates.

VeriSIM Life and Mayo Clinic Team Up to Co-develop New Therapies

LG Chem Life Sciences (LG Chem), the life sciences division of the South Korean LG Group, is moving forward with investigational new drug (IND)-enabling studies that prompted the company to exercise its renewal option as part of an ongoing collaboration with Avacta Group, a clinical stage biopharmaceutical company. The renewal option has triggered a license renewal fee payment of $2 million to Avacta, according to a June 30, 2022 company press release.

Under the agreement, LG Chem has the exclusive rights to develop and commercialize Avacta’s Affimer programmed death ligand 1 (PD-L1) inhibitor with Affimer XT serum half-life extension on a global basis and for a range of indications. LG Chem will progress the PD-L1/XT candidate by starting pre-clinical studies, which are intended to form the basis of an IND submission.

Avacta and LG Chem had entered into a multi-target development agreement in December 2018 to develop Affimer therapeutics in several disease areas. In 2020, the companies expanded their partnership to include Avacta’s Affimer XT technology, which can be used to control the amount of time a drug spends in the blood, according to the press release.

“The initiation of IND-enabling studies represents a significant step towards first-in-human clinical trials of the Affimer platform, which is a key value driver for the technology and for Avacta,” said Alastair Smith, CEO, Avacta Group, in the release.

LG Chem has decided to proceed with IND-enabling studies and has renewed a license with Avacta.

LG Chem Renews License with Avacta for IND Studies

On June 30, 2022, Inceptor Bio, a US-based biotechnology company specializing in cell therapies for difficult-to-treat cancers, announced a collaboration with the University of Minnesota. Under the collaboration, the two parties plan to build a novel induced pluripotent stem cells (iPSC) platform to accelerate Inceptor Bio’s next-generation cell therapies platforms.

Inceptor Bio will receive an exclusive license to the technology developed under this collaboration. The company plans to advance multiple cell therapy products into clinical studies by incorporating the iPSC platform into its proprietary K62 platform for chimeric antigen receptor macrophage (CAR-M) therapy. CAR-M therapy increases the phagocytic capabilities of macrophages and supports a macrophage 1 (M1) anti-tumor phenotype as well as its novel co-stimulatory domain, M83, for CAR-natural killer cell therapies.

"iPSC-derived cell therapies have the potential to enable the next frontier of cell therapies. We are excited to work with [Beau] Webber at University of Minnesota and his team to develop this unique platform," said Mike Nicholson, president and chief operating officer, Inceptor Bio, in a company press release.

"The team at University of Minnesota is confident that Inceptor Bio is the right partner for building a differentiated iPSC platform to advance novel cell therapies," said Beau Webber, assistant professor in the Department of Pediatrics, Division of Hematology and Oncology, University of Minnesota, in the press release. "We are deeply encouraged by Inceptor Bio’s progress in the cell therapy arena, and we look forward to being part of future developments to help cure difficult-to-treat cancers."

Inceptor Bio and the University of Minnesota aim to build a novel iPSC platform to accelerate cell therapy drug development.

Inceptor Bio Collaborates with University of Minnesota to Develop Cell Therapy Platform

Avid Bioservices, a biologics-focused contract development and manufacturing organization, announced the opening of new analytical and process development (AD/PD) suites within their recently built 53,000-ft2 viral vector development and manufacturing facility. Build-out of the suites is currently ongoing and expected to be completed by mid-2023.

According to a June 14, 2022 press release, the new suites will be equipped with complete upstream, downstream, and analytical development capabilities. The suites will be able to support up to 500-L suspension culture in single-use bioreactors and various adherent cell modes. The company's viral vector AD/PD team has worked on technologies for viral vector production and purification processes focused on adeno-associated viruses (AAVs), lentiviruses, oncolytic viruses, and other viruses for gene therapy and vaccine applications.

“We believe that we are uniquely positioned to leverage our deep expertise in the manufacturing of traditional biologics to address the growing demand for high quality manufacturing of cell and gene therapies,” said Nick Green, president and CEO, Avid Bioservices, in the press release. “Today’s launch of our AD/PD labs is a crucial first step in our expansion into the viral vector space as we remain laser focused on smart and sustainable revenue growth for our business.”

Avid Bioservices has expanded its viral vector development and manufacturing facility with the addition of analytical and process development suites.

Avid Bioservices Launches New Analytical and Process Development Suites at Viral Vector Facility

According to a June 15, 2022 press release, a new polymer surface material has been invented by researchers at Chalmers University of Technology (Gothenburg, Sweden) that uses electrical signals to both capture and release biomolecules.

The new material may have an impact in the way that biomedicines are developed and could provide opportunities in the development of remote-controlled medication and electronic pills. The results of the research were published in a scientific journal, 

“Our polymer surfaces offer a new way of separating proteins by using electrical signals to control how they are bound to and released from a surface, while not affecting the structure of the protein,” said Gustav Ferrand-Drake del Castillo, doctor in Chemistry, Chalmers, CEO of Nyctea Technologies, and lead author of the study, in the press release.

The initial research behind the material was performed by Ferrand-Drake del Castillo while studying under the stewardship of Chalmers professor Andreas Dahlin within the university’s Division of Applied Surface Chemistry. The research project involved polymer surfaces that can change their state when the pH of the surrounding solution is adjusted—so, changing between neutral and charged.

“Shortly afterwards we discovered that we could use the electrical signals to control the binding and release of proteins and biomolecules, and that the electrode material works in biological solutions such as serum and centrifuged blood. We believe and hope that our discoveries may be of great benefit in the development of new medicines,” explained Dahlin, in the press release.

Additionally, the material was found to also work within biological fluids with the ability to counteract changes in pH values. Through this specific property of the polymer surface material, it may be possible for the researchers to create a new technique for implants and electronic pills, whereby the medicine is released within the body through electronic activation.

“You can imagine a doctor, or a computer program, measuring the need for a new dose of medicine in a patient, and a remote-controlled signal activating the release of the drug from the implant located in the very tissue or organ where it’s needed,” added Ferrand-Drake del Castillo. “Being able to control the release and uptake of proteins in the body with minimal surgical interventions and without needle injections is, we believe, a unique and useful property. The development of electronic implants is only one of several conceivable applications that are many years into the future. Research that helps us to link electronics with biology at a molecular level is an important piece of the puzzle in such a direction.”

A new polymer surface material has been invented by researchers in Sweden that uses electrical signals to both capture and release biomolecules.

BioPharm International's BP Elements, July 2022