Feliza Mirasol is the science editor for 

Feliza Mirasol

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ProBioGen, a Germany-based contract development and manufacturing organization, announced on  March 13, 2024, that it has entered into services and license agreements with Mapp Biopharmaceutical to develop a cell line for an afucosylated antibody that targets Marburg virus (MARV) infection. The companies will leverage ProBioGen's GlymaxX technology to adjust the afucosylation levels of antibody and enhance its therapeutic potential.

Under the agreement, ProBioGen will use its expertise in cell-line development, including its proprietary DirectedLuck transposase system and GlymaxX technology, to enhance the candidate’s antibody-dependent cellular cytotoxicity (ADCC). According to the company in a press release, “ADCC enhancement is a key strategy for improving therapeutic antibody-drug efficacy.”

The GlymaxX technology is designed to optimize antibody activity. It does so by enhancing antibody-mediated cell killing of cancerous or infected cells. The technology is based on the stable introduction of a gene into producer cells; the gene encodes for an enzyme that blocks the cells' fucose biosynthesis pathway and, thus, the formation of fucose. As a result, no fucose is added in the antibody-producer cells to the antibody's N-linked carbohydrate part. The absence of fucose in antibodies is known to significantly enhance ADCC, ProBioGen stated in its press release.

GlymaxX can be applied to both novel or already existing antibody producer cell lines as well as to entire antibody expression and discovery platforms. ProBioGen stated that “GlymaxX does not negatively affect cellular productivity or other product characteristics. Furthermore, a GlymaxX cell line can be flexibly used to produce differently fucosylated products, depending on the upstream process: in fucose-free medium the antibody is literally afucosylated.”

"We are excited to collaborate with [Mapp Biopharmaceutical] in the development of a cell line for an afucosylated antibody targeting MARV infection, utilizing our GlymaxX technology," said Volker Sandig, chief scientific officer, ProBioGen, in the press release. "This again confirms the versatility of our technology which is broadly used for cancer therapeutics but can also make a meaningful impact in the fight against life-threatening infections."

The Marburg virus poses a significant public health threat, and there is urgent need for advanced therapies to treat it, which this collaboration aims to address. MARV infections cause severe and often fatal illness. The development of an antibody offers a promising route for treatment. In this case, by reducing fucose levels in the antibody's glycan structure, ProBioGen’s GlymaxX technology can enhance the antibody’s effector functions, which can potentially improve its overall efficacy against MARV infection.

The project is being funded in whole or in part by federal funds from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50122C00076 (1).

"We are pleased to partner with ProBioGen to develop a cell line to produce our afucosylated antibody to treat MARV infection," said Ronald Aimes, vice-president, Development—Marburg, Mapp Biopharmaceutical, in the press release. "This collaboration exemplifies our shared commitment to addressing unmet medical needs and underscores the potential of combining our capabilities to deliver innovative and impactful biopharmaceutical solutions for infectious diseases."

Mapp Biopharmaceutical specializes in the infectious disease space within the biopharma industry. The company has received funding from BARDA to advance the development of MBP091, a single monoclonal antibody (mAb) therapeutic for treating Marburg virus disease. This would be the first mAb therapy to specifically treat MARV infections, according to the company in the press release.

1. HHS Office of the Assistant Secretary for Preparedness and Response (ASPR). 

www.highergov.com/contract/75A50122C00076/

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Mapp Biopharmaceutical will use ProBioGen’s GlymaxX technology for the development of an afucosylated antibody against Marburg virus infection

Mapp Biopharmaceutical Teams Up with ProBioGen and to Develop Antibody Against Marburg Virus Disease

Domain Therapeutics (Domain), a clinical-stage biopharmaceutical company developing innovative drug candidates in immuno-oncology that target G protein-coupled receptors (GPCRs), entered into a manufacturing agreement with Chime Biologics, a contract development and manufacturing organization. Chime Biologics will produce Domain’s regulatory T cell (Treg)-depleting anti-CCR8 antibody candidate, DT-7012, Domain announced in a March 12, 2024 press release.

Under the agreement, Chime Biologics will ensure stable cell line development (CLD) and manufacturing services for the candidate to support clinical trials in strategic countries. Chime Biologics operates a global modular facility that employs single-use bioprocessing technology. According to the company, this facility meets international current good manufacturing practice standards and holds proven audit track records.

The candidate, DT-7012, is a novel anti-CCR8 comprising monoclonal antibody (mAb)-depleting tumor-infiltrating Tregs, which are major immunosuppressive cells. The company stated, in the press release, that, “Treg depletion with anti-CCR8 mAb has demonstrated a unique anti-tumor potency as a monotherapy” and noted that, “DT-7012 has a proven best-in-class potential compared to other clinical-stage CCR8 antibodies, paving the way for effective GPCR-targeting immunotherapies, aiming to activate antitumor immunity for cancer patients unresponsive to other treatments”.

The company expects to start Phase I clinical studies of the candidate in early 2025 for solid tumors. In mid-2025, it expects to start Phase I clinical studies in cutaneous T-cell lymphoma.

Domain nominated DT-7012 in June 2023 (1). The company choose this candidate because of its unique ability and potential as a monotherapy to cure cancer in preclinical studies. The company expects the candidate to achieve a position that will enable its fast-track development and accelerated market access. According to the company, DT-7012 is able to preserve CCR8-modulation capacity in the presence of high concentrations of CCR8 in the tumor microenvironment. It also has the ability to recognize different forms of CCR8 that have different post-translational modifications (1).

“We look forward to progressing this strategic partnership, which combines Domain’s leading anti-CCR8 antibody candidate with Chime Biologics’ CLD-to-commercial manufacturing expertise, contributing to the development of DT-7012 for various cancers,” said Jimmy Wei, president of Chime Biologics, in a company press release.

“We’re thrilled to collaborate with Chime Biologics, a great scientific and manufacturing expert, to advance DT-7012, our leading anti-CCR8 candidate, to the next development stage. This new GPCR-targeting immunotherapy has immense potential to unlock the immune system’s cancer fighting abilities and help patients globally. At Domain, we prioritize precision research and innovation and embrace new partnerships with organizations that share our vision and passion to advance immuno-oncology,” said Stephan Schann, chief scientific officer of Domain Therapeutics, in the release.

In addition to DT-7012, Domain’s pipeline of GPCR-targeting immunotherapies also includes:

PAR2 NAM antagonist (DT-9045): a small-molecule candidate expected to begin a Phase I study by mid-2025

EP4 receptor antagonist (DT-9081): a small-molecule candidate expected in an ongoing Phase I ascending dose study

A2a/A2b antagonist (M1069): a small-molecule candidate being developed in partnership with Merck KGaA that is in an ongoing Phase I ascending dose study.

1. Domain Therapeutics. Domain Therapeutics Announces Nomination of Best-in-class CCR8 Antibody Candidate, DT-7012, Further Strengthening Its Unique Portfolio of GPCR-targeting Immunotherapies. Press Release, June 29, 2023.

In a new manufacturing pact, Chime Biologics will produce DT-7012, Domain Therapeutics' antibody candidate for treating cancer that will soon be entering Phase I studies.

Chime Biologics to Manufacture Novel Antibody Cancer Immunotherapy for Domain Therapeutics

The European Medicines Agency (EMA) announced on March 4, 2024 that it has validated two marketing authorization applications (MAAs) submitted by AstraZeneca and Daiichi Sankyo for their antibody drug conjugate (ADC) candidate, datopotamab deruxtecan (Dato-DXd). The parallel applications are seeking indications in two types of cancer: locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and unresectable or metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer in patients who have progressed on and are not suitable for endocrine therapy and who have received at least one additional systemic therapy.

The agency’s validations confirm that the MAAs are complete, and the agency can now commence the scientific review process, which is to be carried out by EMA’s Committee for Medicinal Products for Human Use. The two applications are based on data from two pivotal Phase III clinical trials (TROPION-Lung01 and TROPION-Breast01), which were presented during two Presidential Symposia at the 2023 European Society for Medical Oncology Congress.

Datopotamab deruxtecan is an ADC specifically engineered to target TROP2, a protein broadly expressed in several solid tumors, including the majority of NSCLC and HR-positive, HER2-negative breast cancer cases. High TROP2 expression is associated with increased progression of tumors and poor survival. Currently, there is no approved TROP2-directed ADC for treating lung cancer, according to an AstraZeneca press release.

Datopotamab deruxtecan was discovered by Daiichi Sankyo and is being jointly developed by AstraZeneca and Daiichi Sankyo. The companies entered into a global collaboration for the ADC in July 2020 (1). AstraZeneca has rights to the product except in Japan, where Daiichi Sankyo maintains exclusive rights. Meanwhile, Daiichi Sankyo is responsible for the manufacturing and supply of the ADC.

“Our ambition is for datopotamab deruxtecan to improve upon and replace conventional chemotherapy in the treatment of multiple cancer types. Today’s dual validation of our applications in lung and breast cancers brings this potential medicine a meaningful step closer to redefining treatment expectations for patients with two of the most common cancers in Europe,” said Susan Galbraith, executive vice-president, Oncology R&D, AstraZeneca, in the press release.

“The EMA validation is an important first step toward bringing this TROP2-directed antibody drug conjugate to eligible patients in Europe with nonsquamous lung cancer and HR-positive, HER2-negative breast cancer. This news builds on our recent regulatory progress in the [United States], where our lung cancer application has been accepted and our breast cancer application is underway, underscoring our commitment to changing the standard of care by developing new medicines to help as many patients worldwide as possible," said Ken Takeshita, global head, R&D, Daiichi Sankyo, in the press release.

Regulatory submissions for the ADC in lung cancer and breast cancer are also underway in the US and globally.

1. AstraZeneca. AstraZeneca and Daiichi Sankyo Enter Collaboration to Develop and Commercialize New Antibody Drug Conjugate. Press Release, July 27, 2020.

EMA has validated two MAAs submitted by AstraZeneca and Daiichi Sankyo for datopotamab deruxtecan in two types of cancer.

EMA Validates Parallel Applications for Datopotamab Deruxtecan in Two Types of Cancer

On March 7, 2024, Johnson & Johnson (J&J) announced the completion of its acquisition of Ambrx Biopharma, a clinical-stage biopharmaceutical company, in a deal valued at approximately $2 billion. Ambrx specializes in a proprietary synthetic biology technology platform to design and develop next-generation antibody drug conjugates (ADCs).

The acquisition provides J&J the opportunity to design, develop, and commercialize targeted oncology therapeutics using Ambrx’s proprietary ADC technology, which incorporates highly specific-targeting monoclonal antibodies (mAbs) securely linked to a potent chemotherapeutic payload. The goal of the platform is to achieve targeted and efficient elimination of cancer cells without the prevalent side effects that are typically associated with chemotherapy, according to a company press release.

“We’re pleased to welcome Ambrx’s talented scientific team and proprietary ADC platform to Johnson & Johnson. We look forward to continuing the development of ARX517, which represents a potential first- and best-in-class PSMA [prostate-specific membrane antigen]-targeting ADC for the treatment of metastatic castration-resistant prostate cancer,” said Yusri Elsayed, global therapeutic area head, Oncology, Johnson & Johnson Innovative Medicine, in the press release. “This significant opportunity sets the stage for advancing next-generation ADCs with the aim of delivering differentiated solid tumor therapies that improve patients’ lives.”

“The Ambrx team has developed a promising pipeline and ADC platform that will be a strong complement and strategic fit to our oncology innovation strategy,” said Biljana Naumovic, worldwide vice-president, Oncology, Johnson & Johnson Innovative Medicine, in the release. “ADCs are transforming the solid tumor treatment paradigm by leveraging antibody–antigen interactions to release cytotoxic payload directly to tumor cells. This acquisition underscores our ambition to deliver enhanced, precision biologics to transform the treatment of cancers, including prostate cancer.”

In earlier news, the company announced on March 6, 2024 (1) that it has submitted a Type II variation application to the European Medicines Agency seeking approval for an indication extension of DARZALEX (daratumumab) subcutaneous (SC) formulation. Specifically, the application is seeking approval of the mAb in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) to treat adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT).

This submission is supported by data from a Phase III study (PERSEUS) evaluating D-VRd induction and consolidation therapy, ASCT, and daratumumab with lenalidomide (D-R) maintenance therapy in comparison to VRd, ASCT, and R maintenance. Results demonstrated that the study met its primary endpoint of progression-free survival.

“The impressive results from the PERSEUS study highlight the potential of this daratumumab subcutaneous-based regimen to transform patient outcomes and provide an effective therapy option in newly diagnosed, transplant-eligible multiple myeloma,” said Craig Tendler, vice-president, Clinical Development, Diagnostics, and Global Medical Affairs, Johnson & Johnson Innovative Medicine, in a company press release. “We are committed to advancing innovative regimens, such as D-VRd, as we strive towards the elimination of this complex disease. We now look forward to working with the EMA on the review of this submission.”

1. Johnson & Johnson. Johnson & Johnson Submits Application to the European Medicines Agency for DARZALEX (daratumumab)-based Quadruplet Therapy for the Treatment of Patients with Transplant-Eligible, Newly Diagnosed Multiple Myeloma. Press Release. March 6, 2024.

Johnson & Johnson’s $2 billion acquisition of Ambrx boosts its pipeline of next-generation ADCs for cancer treatment.

J&J Completes $2 Billion Ambrx Acquisition, Boosts Pipeline for Next-Gen ADCs

AbbVie and OSE Immunotherapeutics, a clinical-stage immunotherapy company, announced on Feb. 28, 2024 that they have entered into a strategic partnership to develop OSE-230, a monoclonal antibody (mAb) in development to treat chronic and severe inflammation. The mAb is currently in pre-clinical development.

Under the agreement, OSE Immunotherapeutics will receive a $48 million upfront payment and is eligible to receive up to an additional $665 million in clinical development, regulatory, and commercial milestones. OSE Immunotherapeutics will also be eligible to receive potential tiered royalties on global net sales of OSE-230. AbbVie will have an exclusive global license to develop, manufacture, and commercialize OSE-230.

OSE-230 is designed to activate ChemR23, a G-protein coupled receptor (GPCR) target, which may offer a new mechanism by which chronic inflammation can be resolved. Activating ChemR23 may modulate the functions of both macrophages and neutrophils, according to a company press release.

"This collaboration underscores our commitment to expanding our immunology portfolio with the ultimate goal of improving the standard of care for patients living with inflammatory diseases globally," said Jonathon Sedgwick, senior vice-president and global head of discovery research, AbbVie, in the press release. "By leveraging our expertise in immunology drug development, we look forward to advancing OSE-230, which offers a novel mechanism-of-action to treat chronic inflammation."

"We are very pleased to collaborate with AbbVie … to drive our OSE-230 program forward," said Nicolas Poirier, chief executive officer, OSE Immunotherapeutics, in the release. "This partnership represents a major milestone in our company's progress and recognizes the value of our innovative R&D capabilities. I would like to thank all our employees who helped us reach this milestone through dedication and hard work."

OSE Immunotherapeutics' pipeline also includes the following candidates:

Tedopi (immunotherapy-activating tumor-specific T-cells, off-the-shelf, neoepitope-based).

 This candidate is a cancer vaccine and is the company's most advanced product. It has generated positive results in a Phase III trial (Atalante 1) in patients with non-small cell lung cancer who are experiencing secondary resistance after checkpoint inhibitor failure. Tedopi is also in other ongoing Phase II trials, sponsored by clinical oncology groups, in combination treatment scenarios for solid tumors.

OSE-279 (anti-programmed cell death protein 1 [PD-1]).

 This candidate has generated its first set of positive results in an ongoing Phase I/II study in solid tumors. OSE-279 is the primary therapy derived from the company’s bispecific fusion protein platform, BiCKI.

OSE-127 - lusvertikimab (humanized mAb antagonist of interleukin 7 [IL-7] receptor).

 This candidate is in an ongoing Phase II study in ulcerative colitis and in ongoing preclinical research in leukemia.

 This mAb was developed in partnership with Veloxis Pharmaceuticals, an Asahi Kasei company, for use in transplantation treatment. It is in ongoing Phase I/II studies in renal transplant and an ongoing Phase I study in the United States.

BI 765063 and BI 770371 (anti-signal-regulating protein alpha [SIRPα] mAb on CD47/SIRPα pathway).

 These candidates were developed in partnership with Boehringer Ingelheim for treatment of advanced solid tumors. They have demonstrated positive Phase I dose-escalation results in monotherapy and in combination, particularly with the anti-PD-1 antibody, ezabenlimab. They are also in an ongoing international Phase Ib clinical trial in combination with ezabenlimab alone or with other drugs for treating patients with recurrent/metastatic head and neck squamous cell carcinoma and hepatocellular carcinoma.

In addition to these pipeline candidates, OSE Immunotherapeutics also expects to generate further potential candidates based on its three proprietary drug discovery platforms:

Pro-resolutive mAb platform, which focuses on targeting and advancing the resolution of inflammatory conditions and optimizing the therapeutic potential of targeting neutrophils and macrophages in immunology and inflammation (I&I). OSE-230 is the first candidate generated by this platform. Additional discovery programs are ongoing on new pro-resolutive G protein-coupled receptors.

Myeloid Checkpoint platform, which aims to optimize the therapeutic potential of myeloid cells in immuno-oncology (IO) by targeting immune regulatory receptors that are expressed by macrophages and dendritic cells. BI 765063 and BI 770371 are the most advanced candidates generated by this platform. There are also additional ongoing discovery programs, with positive preclinical results obtained in monotherapy studies with new anti-C-type lectin-like receptor-1 mAbs.

Cytokine platform, which focuses on leveraging the Cis-delivery of cytokine in IO and I&I. BiCKI is a bispecific fusion protein platform. It is built on the key backbone component of anti-PD-1 combined with a new immunotherapy target. This combination aims to increase anti-tumor efficacy. BiCKI-IL-7v is the most advanced candidate generate by the BiCKI platform, which targets anti-PD-1xIL-7. There are ongoing additional discovery programs on Cis-demasking technologies.

Under a global license and collaboration agreement, AbbVie and OSE Immunotherapeutics will aim to develop OSE-230, a mAb for treating chronic inflammation.

AbbVie Partners with OSE Immunotherapeutics on Novel mAb for Chronic Inflammation

On Feb. 28, 2024, CordenPharma International announced the launch of its new Lipid NanoParticle (LNP) Starter Kits for the formulation of messenger RNA (mRNA)-based therapeutics, such as mRNA vaccines or gene therapies. The starter kits are designed to provide researchers and developers with the essential components needed to create and optimize their own LNPs for mRNA delivery.

The new LNP kits include four key lipids: ionizable lipids, helper lipids, sterols, and PEGylated lipids. In addition, the kits are curated using representative materials from commercial-scale sources. These characteristics mitigate potentially negative outcomes and loss of valuable payload due to subpar lipid quality, and eliminate the risk associated with changing lipid sources from the R&D phase to clinical phases, according to a company press release.

The kits are designed to facilitate easy formulation screening and enable the generation of LNPs that can provide efficient transfection in different cell types, including immortalized and/or primary cell cultures. The kits can be used for animal 

 applications, including pharmacokinetic/pharmacodynamic studies and mRNA transfection efficacy proof-of-concept studies. They have also been tested with green fluorescent protein-mRNA as cargo and have successfully implemented testing for synthetic RNAs (such as small interfering RNA) and DNA.

The kits allow users to fine-tune the LNP formulation process and achieve production of nanoparticles with the desired physicochemical characteristics, such as polydispersity index ≤0.2 and a size range between 30–150 nm, depending on specific LNP reaction conditions, lipid composition, and cargo used.

“CordenPharma is proud to introduce this new LNP Starter Kit concept, as it represents a great synergy between our Lipid and LNP expertise that helps accelerate time to market and provide access to the most efficient compositions of the LNP-based drug development field for the delivery of RNA, DNA and gene therapy payloads across various important therapeutic indications, with an ultimately profound effect on saving the lives of patients,” said Matthieu Giraud, CordenPharma’s senior director, Global Lipids & Carbohydrates Platform, in the press release.

CordenPharma’s new starter kits are designed to enable effective formulation in the development of mRNA-based therapeutics.