Feliza Mirasol is the science editor for 

Feliza Mirasol

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.

Articles

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.

CordenPharma Launches New LNP Starter Kits for mRNA Formulation

The management and analysis of vast data generated by advanced analytical technologies are revolutionizing the drug discovery and development process.

Drug Digest: The Rush for Quality Data and the Means to Protect It

In this episode of Drug Digest, industry experts discuss why data is the biopharma industry’s most valuable asset today. The discussion also delves into the means by which the industry as a whole is learning to upgrade data integrity practices to better protect their data and the use of innovative technologies, such as advanced graph technologies, to better shape the drug discovery and development process.

Nathalie Batoux, Product Manager, Research Innovation, IDBS

Nathalie Batoux left the lab and joined IDBS in 2005, driven by her passion to help scientists with workflows and informatics tools to expedite their research. At IDBS, Batoux is a product manager for Research and Innovation. In her role, she regularly interacts with customers and researchers to gain an understanding of their data management needs and drives the development of platform capabilities to provide a solution. Batoux is an organic chemist by training and started her career as a post-doctoral researcher in chemistry working in the domain of nucleoside and dinucleotide analogues.

Thierry Dorval, Head of Data Science & Data Management, Servier

Thierry Dorval received a PhD in image analysis and artificial intelligence (AI) from University Pierre & Marie Curie and then joined the institut Pasteur Korea in 2005 as a group leader specializing in high content screening applied to cellular differentiation and toxicity prediction. In 2012, he joined AstraZeneca, where he focused on developing and advising on quantitative image and data analysis solutions in support of high content phenotypic screening. In 2015 he joined Servier, France, to lead the Data Sciences & Data Management pole of activities where he is in charge of optimizing the early stages of the drug discovery process by taking advantage of cutting-edge computational approaches. This includes usage of AI, knowledge graph database, system modeling and sequences design applied to multiple modalities including small molecules, antibodies, and oligonucleotides.

Jeremy Grignard, Data & Research Scientist, Servier

Jeremy Grignard holds a PhD in computer science, data, and artificial intelligence (AI) from École Polytechnique. He also earned a master’s degree in applied mathematics in Data Science and an engineering degree in computer science and big data. In 2019, he joined the Servier Research & Development Institute to complete his thesis with Inria Saclay, during which he developed computational methods using knowledge graphs, data science, and mathematical modeling to improve early drug discovery. Since 2022, he has been designing and implementing AI projects related to gene inference, explainable machine learning, heteromodality algorithms, biologically constrained deep learning models, knowledge graphs, and large language models.

This episode of Drug Digest is sponsored by:

Drug Digest is a tech talk video series with the 

® editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products.

Videos

This discussion explores how the management and analysis of vast data generated by advanced analytical technologies are revolutionizing the drug discovery and development process within the biopharma industry.

On Feb. 26, 2024, Nona Biosciences, a wholly owned subsidiary of HBM Holdings Limited, announced that it has entered into a collaboration agreement with Boostimmune, a biotech company specializing in next-generation anti-cancer therapies via modulating immune systems, to develop antibody-drug conjugates (ADCs) against novel targets using Nona’s proprietary Harbour Mice H2L2 (two light and two heavy chain) platform.

The platform technology generates fully human monoclonal antibodies in the classical two light and two heavy chain (H2L2) format, and heavy chain only (HCAb) format. Nona focuses on integrating its Harbour Mice platform with a single B cell cloning platform to innovate the development of next-generation drugs.

“By leveraging our accumulated knowledge of ADC discovery and utilizing our advanced therapeutic antibody platforms validated by partners worldwide, this collaboration will expedite the development of first-in-class ADCs targeting cancer. Working alongside Boostimmune, we anticipate delivering transformative treatments, ultimately improving outcomes for all patients affected by cancer,” said Jingsong Wang, chairman of Nona Biosciences, in a company press release.

“We are excited to collaborate with Nona Biosciences. Our strategic alignment of resources and knowledge will accelerate the development of ADC therapies against novel targets. Through this collaboration, we are confident in making significant strides in addressing the unmet needs of cancer patients,” said Gwanghee Lee, founder and CEO of Boostimmune, in the release.

Nona Biosciences and Boostimmune will collaborate to develop ADCs against novel targets using Nona’s proprietary platform technology.

Nona Biosciences Partners with Boostimmune on ADC Development

Genezen, a cell and gene therapy contract development and manufacturing organization (CDMO), announced on Feb. 21, 2024 that it has entered into a licensing agreement with biotechnology company CSL for CSL’s proprietary stable lentiviral vector (LVV) production system, Cytegrity, which Genezen will implement in its Fishers, Ind., facility.

The system allows for scalable and cost-effective generation of LVVs at clinically effective titers for both gene and cell therapies, according to a company press release. Cytegrity is validated through early clinical testing and has demonstrated safety and efficacy. Traditionally, LVVs are produced at limited scale using plasmid-based transient transfection technology. Cytegrity offers continuous production from a stably transfected adherent or suspension cell line, which eliminates the need for costly plasmid, reduces process complexity, and allows for large-scale batch production. The system also allows for multiple harvests and less batch-to-batch variability, according to the press release.

"I am excited that Genezen is the first CDMO to license the Cytegrity cell line. We have significant, hands-on experience scaling up and producing LVV using this stable production system at our GMP [good manufacturing practice] vector facility in Fishers, Indiana,” said Steve Favaloro, president and CEO of Genezen, in the release. “Stable producer cell lines can be developed for clients in under four months, and this system will help alleviate the current global viral vector shortage by providing customers with a scalable, high-quality vector platform. This licensing capability is a significant value-add for our current and future LVV customers and furthers our collective mission to bring gene and cell therapies more efficiently to patients."

"We are excited to share access to the Cytegrity cell line with Genezen and the broader cell and gene therapy community, including innovators and manufacturers. Following many years of investment in the development of the cell line at CSL in collaboration with our partners, the Cytegrity cell line will potentially lower cost of goods and enable quicker scaleup to clinical and commercial manufacture which, in turn, will benefit patients in gaining access to therapies faster," said Vicky Pirzas, senior vice-president, Biopharmaceutical Product Development, CSL, in the release.

CSL will share access to Cytegrity, its proprietary stable production system for lentiviral vector production, with Genezen. 