AbbVie Acquires Celsius Therapeutics for $250 Million to Advance First-in-Class TREM1-Targeting Therapy for Autoimmune Diseases

On June 27 local time, AbbVie announced the acquisition of Celsius Therapeutics, a private biotechnology company dedicated to translating single-cell genomics research into precision therapies for autoimmune diseases.

According to the terms of the agreement, AbbVie acquired all outstanding shares of Celsius for $250 million in cash (approximately RMB 1.817 billion), subject to certain customary adjustments. Celsius’s lead research asset is CEL383, a potential first-in-class TREM1-targeting antibody for the treatment of inflammatory bowel disease (IBD). The company has completed Phase I clinical trials for the treatment of IBD.

TREM1 (Triggering receptor expressed on myeloid cells-1) is a myeloid cell surface receptor expressed on the surface of neutrophils, monocytes, and macrophages. It is expressed in various tumor microenvironments and works synergistically with classical pattern recognition receptors (PRRs), such as the Toll-like receptor (TLR) family and the Nod-like receptor (NLR) family, to amplify inflammation responses mediated by microbial components in host defense.

In non-infectious inflammatory conditions, TREM1 is associated with autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, psoriasis, nephritis, and systemic lupus erythematosus.Studies have shown that IBD patients have a higher number of TREM1+ macrophages in the lamina propria of the intestine, and serum sTREM1 concentrations are higher than those in healthy controls regardless of whether the disease is in an active or inactive phase. In mouse models of colitis induced by T-cell transfer or dextran sulfate sodium, disease severity, inflammatory infiltration, and the expression of pro-inflammatory cytokines were significantly reduced in Trem1-/- mice.

Currently, TREM1 has been identified as a key pathogenic gene in IBD, expressed on inflammatory monocytes and neutrophils.In these cell types and other types of cells, TREM1 is upstream of multiple known inflammatory pathways and acts as an amplifier of inflammation.

As Celsius' only asset currently in the clinical stage, CEL383 is an investigational antibody targeting TREM1.In preclinical trials, CEL383 has been shown to inhibit TREM1 signaling and reduce the levels of multiple inflammatory mediators that are highly clinically relevant in inflammatory conditions. In addition, Celsius has identified TREM1 pathway-dependent biomarkers, which may enable patients with ulcerative colitis and Crohn's disease to select CEL383 with a more precise approach.

Celsius, founded in 2017, completed a $65 million Series A financing in 2018 and an $83 million Series B financing in 2022.

The company's R&D model involves conducting single-cell RNA sequencing on patient tissues, then using machine learning and artificial intelligence to analyze the massive amounts of data generated, identifying factors that drive diseases. The company’s main R&D projects currently include sequencing and screening of tissues from patients with inflammatory bowel disease, non-small cell lung cancer, and melanoma. The aim is to discover new therapeutic targets for inflammatory diseases and cancer, and to translate the research achievements in single-cell genomics into precision therapies for autoimmune diseases and cancer through technological breakthroughs.

Its main technology is licensed from the Broad Institute, including a non-exclusive license for single-cell sequencing technology and an exclusive license for early drug development projects. These technologies benefit from the research work of Professor Aviv Regev of MIT and Professor Vijay Kuchroo of Harvard Medical School, both of whom are founding scientists of the company. Using this groundbreaking approach, the Broad Institute has previously identified a small number of targets for autoimmune diseases and cancer.

For this transaction, Dr. Kori Wallace, Vice President of AbbVie and Global Head of Immunology Clinical Development, stated, "Given the potential relevance of TREM1 as a key driver of inflammation and pathology in IBD and other diseases, we are eager to advance the development of CEL383 to help more IBD patients achieve remission." Dr. Tariq Kassum, CEO of Celsius, stated, "AbbVie, like us, is excited about the potential of TREM1 inhibition for patients with inflammatory diseases. We look forward to the further development of this promising program, and we hope it will provide a new approach to treating IBD."

In fact, this is already AbbVie's third deal in the IBD field this year and the second one this month.

On March 25, 2024, AbbVie acquired Landos Biopharma, a drug immunology startup, at a premium of approximately 155%., including the payment of $137.5 million in cash and $75 million in contingent value rights (CVR), with a total transaction value of approximately $212.5 million. Landos' core project is an IBD pipeline NX-13, an oral NL-RX1 antibody currently in the enrollment phase of a Phase 2 clinical trial, being developed for the treatment of ulcerative colitis and Crohn's disease.

On June 13, 2024, AbbVie and Mingji Biotech jointly announced the signing of a licensing agreement for the development of FG-M701.FG-M701 is a next-generation TL1A antibody for the treatment of inflammatory bowel disease (IBD), currently in the preclinical development stage.Under the terms of the agreement, AbbVie will obtain the exclusive global license for the development, manufacturing, and commercialization of FG-M701. MabGenesis will receive $150 million as an upfront payment and near-term milestone payments, and is eligible to receive up to an additional $1.56 billion in clinical development, regulatory registration, and commercialization milestone payments, as well as tiered royalties of up to a low double-digit percentage of net sales.

Why is AbbVie so obsessed with the IBD field? IBD (Inflammatory Bowel Diseases), represented by Crohn's Disease (CD) and Ulcerative Colitis (UC), is a chronic lifelong disease characterized by gastrointestinal inflammation. Currently, targeted biologics for the treatment of IBD, such as anti-TNFα monoclonal antibodies, have been widely used in clinical practice. In addition, small molecule drugs represented by JAK inhibitors are already in use.

Although there are many treatment options clinically, there is currently no cure for IBD.

As a chronic disease that is difficult to cure, more than 1.5 million people in North America and over 2 million people in Europe are affected. The broad market brings the possibility of strong revenue. According to Huachuang Securities data, just in the United States, advanced therapies for IBD represent an annual commercial market of nearly $15 billion, and the scale continues to grow.

In China, according to data from荃信生物's prospectus, the number of IBD patients in China is less than that in the United States, with 449,300 patients in 2017, increasing to 626,300 in 2021, and it is expected that by 2030, the number of patients will reach 1.2 million; the drug market size has grown slightly, from US$480 million in 2017 to US$885 million in 2021. As a typical industrialized disease, the prevalence in developing countries is approaching that of developed countries.

It is not difficult to see that there is a huge unmet clinical need in the IBD field. Therefore, not only AbbVie, but also many multinational corporations (MNCs) have been rushing to enter this track in recent years.Merck, Roche, Teva Pharmaceutical, Sanofi, Eli Lilly, Takeda Pharmaceutical, Johnson & Johnson, Pfizer, and other companies have all made arrangements in this field. In addition to the hot track and large demand, the core reason for all the major companies to focus on the same area lies in their performance being constrained. The expiration of patents and the continuous emergence of new products have caused the growth of once-core products to lose speed. Each company hopes to make a breakthrough outside their traditional areas of strength.

Take AbbVie as an example. Over the past decade, AbbVie has ascended to the throne of the pharmaceutical king thanks to Humira. However, with the expiration of Humira's patent, who will succeed Humira as the new generation pharmaceutical king has become a frequently discussed topic. In response to these questions, AbbVie has been actively exploring new fields in recent years to provide answers. We look forward to the next decade when AbbVie can achieve great success again.

References:

1. PharmaCube Pro "Rising Target TREM1: Dual Hope for Cancer and Autoimmune Diseases"

2.BioMice Biocytogen "Unlocking New Targets in Inflammation and Tumor Immunotherapy: TREM1 & TREM2"