NLRX1

Taylor Tieden for BioSpace The size of the global immunology market is projected to nearly double by 2032 to a quarter of a trillion dollars. Here are this year’s standout deals in the space. After a rough patch for biotech investment in early 2023, the immunology and inflammation (I&I) space rejuvenated the industry with Merck’s blockbuster acquisition of Prometheus Biosciences for $10.8 billion . Overall, the therapeutic I&I space saw $12.3 billion in M&A action last year, according to data from biotech entrepreneur Andrew Pannu . “I&I has always been an area of high particular interest for pharmaceutical companies . . . driven primarily by the idea that . . . immune disorders and inflammatory conditions many times have a common mechanism of action,” said Graig Suvannavejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas. “Any drug that is proven to be safe and effective and gets approved in multiple diseases or multiple indications … that’s the gift that keeps on giving.” Indeed, the global immunology market is projected to grow from nearly $103.2 billion in 2024 to $257.4 billion by 2032. In addition to a large patient population (one in 10 individuals suffers from at least one immune disorder), reimbursement is a motivating factor for investment activity in I&I, according to a report from Janus Henderson Investors. “Many patients with autoimmune conditions are children or of working age and therefore stay on therapies for long periods of time. In addition, in the U.S., these patients typically fall under commercial insurance plans, which are not subject to the drug price negotiation now allowed in Medicare, the government insurance plan for the elderly,” according to the report . And it’s not just traditional I&I disease like rheumatoid arthritis, psoriasis, Type 1 diabetes, multiple sclerosis and Crohn’s disease that are in focus. Neurodegenerative diseases such as Alzheimer’s and Parkinson’s —which are hypothesized to have neuroinflammatory causes—are also inching into the space. “There’s been a renaissance of sorts, where the neurology, neurodegenerative disease [and] neuropsychiatry spaces have come back in vogue,” Suvannavejh said. A lot of large pharma companies had huge franchises in neuroscience in the late 1990s and early 2000s, he said, but many of the resulting drugs went generic and interest in the space died down. The current resurgence is due to multiple factors, he said, such as patent cliffs and great strides being made in the science and innovation across both the public and private sectors. Here are this year’s standout I&I deals: Traditional I&I Deals Vertex-Alpine April, $4.9B Alpine’s lead asset povetacicept is a dual antagonist of the BAFF and APRIL cytokines, both of which play crucial roles in the activation, differentiation and survival of B-cells. Povetacicept is being investigated for the treatment of IgAN, a progressive autoimmune disease that afflicts the kidneys and ultimately leads to end-stage renal disease. Eli Lilly-Morphic July, $3.2B Morphic is working on a class of proteins called integrins, which traffic T cells. “There’s this idea that integrins are important for the ability of your T cells to get to areas of inflammation,” Suvannavejh said. Morphic’s lead candidate MORF-057 is a small molecule inhibitor of the α4β7 integrin. It is currently being developed for ulcerative colitis and Crohn’s disease, both inflammatory bowel diseases. Biogen-HI-Bio June, $1.8B In a move to de-risk its portfolio, Biogen acquired HI-Bio for its asset felzartamab. The candidate’s mechanism of selectively depleting CD38+ cells could give Biogen “applicability across a range of immune-mediated diseases,” Bank of Montreal Capital Markets analysts said in a May note to investors. BMS-Repertoire April, $1.8B Bristol Myers Squibb recently inked a 3-year deal with Repertoire to create tolerizing vaccines for up to three autoimmune diseases, although details were not released about which diseases are being targeted. “Our collaboration with Repertoire aims to selectively reset the immune system, reflecting a key component of our immunology research strategy, which we believe may offer long term benefit while mitigating unintended consequences associated with broad immune suppression,” Francisco Ramírez-Valle, head of the Immunology & Cardiovascular Thematic Research Center at BMS, said in a statement . AbbVie-OSE February, $713M Representing the I&I “flagship” drug Humira and popular Skyrizi, AbbVie acquired OSE Therapeutics’ early-stage monoclonal antibody OSE-230 as a treatment for chronic and severe inflammation. The antibody works by targeting and activating ChemR23 , a G protein–coupled receptor that plays a central role in certain signaling pathways that help dampen inflammation. Humira lost exclusivity last year and is facing competition from biosimilars, so AbbVie is seeking to make up the losses from the patent cliff via new deals. “They have a legacy presence with Humira , so they already have a commercial infrastructure in place,” Suvannavejh said. “They know how to market these drugs in immune disorders and inflammatory diseases.” Sanofi-Belharra June, $700M This collaboration will leverage Belharra’s non-covalent chemoproteomics platform to identify and advance small molecules against undisclosed Sanofi-designated immunology targets. “By leveraging Belharra’s chemoproteomics platform, we hope to explore immunology targets that, to date, have been considered undruggable,” said John Bertin, the global head of immunology and inflammation research at Sanofi, in a statement. AbbVie-Landos March, $212M Landos’ lead asset NX-13 is an oral NLRX1 agonist for ulcerative colitis and Crohn’s disease. Its mechanism of action is anti-inflammatory and facilitates epithelial repair, a natural function compromised in ulcerative colitis and Crohn’s. Landos’s founder argued that the deal “reflects an understanding that the market is ready for new options, particularly drugs that employ novel mechanisms of action.” Also of Note Sanofi-Inhibrx January, $2.2B Inhibrx’s lead asset, INBRX-101, addresses a deficiency in alpha-1 antitrypsin (AATD), a rare disease that puts patients at risk for lung, liver or skin disease. According to Inhibrx, INBRX-101 normalizes patients’ serum AAT levels with fewer doses than currently available drugs. This deal addresses a problem with a deficiency, rather than a disease that arises from an overactive immune system, Suvannavejh said, putting it in a different category than I&I in his opinion. But Houman Ashrafian, head of research and development at Sanofi, said in a statement that this acquisition is part of the company’s efforts to grow its presence in immune-mediated respiratory conditions. The drug may help to reduce inflammation and prevent the deterioration of lung function, the statement noted.

Pictured: AbbVie's headquarters in California/iStock, Michael Vi AbbVie on Thursday announced that it has bought Cambridge, Massachusetts-based startup Celsius Therapeutics and its lead inflammatory bowel disease antibody CEL383. Details of the acquisition agreement were sparse, with the companies only revealing that AbbVie will snap up all of Celsius’ remaining equity for $250 million in cash, subject to certain adjustments. The companies have not yet announced when they plan to close the transaction. “We are eager the advance the development of CEL383 with a goal of helping more patients with [inflammatory bowel disease (IBD)] achieve remission,” Kori Wallace, global head of immunology clinical development at AbbVie, said in a statement. Developed using Celsius’ proprietary SCOPE platform, which allows the startup to “understand the cells that drive disease progression,” CEL383 is a potentially first-in-class monoclonal antibody that works by targeting the TREM1 protein. TREM1 mediates the interaction between the microbiome and the immune system while amplifying mucosal inflammation, according to the biotech’s website. Preclinical studies have validated this mechanism of action, showing that CEL383 could disrupt TREM1 signaling and lowering the concentration of several inflammatory mediators. CEL383 has recently completed a first-in-human, placebo-controlled, single-ascending-dose Phase I trial in healthy volunteers, designed to evaluate its safety, tolerability and pharmacokinetic profile. Thursday’s acquisition of Celsius is part of AbbVie’s strategy to deepen its portfolio as it weathers a particularly steep patent cliff for its blockbuster immuno therapy Humira (adalimumab). Since losing its most important patent protections, Humira has mostly retained market dominance despite the flurry of biosimilars that flooded the U.S. market. However, in April 2024, fueled by CVS Caremark delisting Humira from its major national commercial formularies, copycats have enjoyed a surge in demand and sales. To shore up its revenues and target future growth, AbbVie has been striking a series of deals giving it access to promising assets and technologies. In February 2024, the pharma put $713 million on the line for an exclusive right to develop, manufacture and commercialize OSE Immunotherapeutics’ investigational antibody OSE-230, being assessed for chronic and severe inflammation. Soon after, AbbVie dropped $212 million to acquire Landos Biopharma gaining access to the oral NLRX1 agonist NX-13, which is being studied as a treatment for ulcerative colitis and Crohn’s disease. AbbVie has joined a recent biopharma spending spree in the projected $257 billion immunology market. Outside the immuno space, AbbVie has also invested heavily in the mental health market entering a potential $2 billion deal with Gilgamesh Pharmaceuticals in May 2024 to develop neuroplastogens for psychiatric disorders. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Pictured: AbbVie’s headquarters in California iStock, Michael Vi AbbVie on Thursday announced it has acquired Celsius Therapeutics to expand its immunology portfolio with a first-in-class TREM1 inhibitor CEL383, following other big players looking to cash in on the hot immuno market. AbbVie on Thursday announced that it has bought Cambridge, Massachusetts-based startup Celsius Therapeutics and its lead inflammatory bowel disease antibody CEL383. Details of the acquisition agreement were sparse, with the companies only revealing that AbbVie will snap up all of Celsius’ remaining equity for $250 million in cash, subject to certain adjustments. The companies have not yet announced when they plan to close the transaction. “We are eager the advance the development of CEL383 with a goal of helping more patients with [inflammatory bowel disease (IBD)] achieve remission,” Kori Wallace, global head of immunology clinical development at AbbVie, said in a statement. Developed using Celsius’ proprietary SCOPE platform , which allows the startup to “understand the cells that drive disease progression,” CEL383 is a potentially first-in-class monoclonal antibody that works by targeting the TREM1 protein. TREM1 mediates the interaction between the microbiome and the immune system while amplifying mucosal inflammation, according to the biotech’s website . Preclinical studies have validated this mechanism of action, showing that CEL383 could disrupt TREM1 signaling and lowering the concentration of several inflammatory mediators. CEL383 has recently completed a first-in-human, placebo-controlled, single-ascending-dose Phase I trial in healthy volunteers, designed to evaluate its safety, tolerability and pharmacokinetic profile. Thursday’s acquisition of Celsius is part of AbbVie’s strategy to deepen its portfolio as it weathers a particularly steep patent cliff for its blockbuster immuno therapy Humira (adalimumab). Since losing its most important patent protections, Humira has mostly retained market dominance despite the flurry of biosimilars that flooded the U.S. market . However, in April 2024, fueled by CVS Caremark delisting Humira from its major national commercial formularies, copycats have enjoyed a surge in demand and sales . To shore up its revenues and target future growth, AbbVie has been striking a series of deals giving it access to promising assets and technologies. In February 2024, the pharma put $713 million on the line for an exclusive right to develop, manufacture and commercialize OSE Immunotherapeutics’ investigational antibody OSE-230, being assessed for chronic and severe inflammation. Soon after, AbbVie dropped $212 million to acquire Landos Biopharma gaining access to the oral NLRX1 agonist NX-13, which is being studied as a treatment for ulcerative colitis and Crohn’s disease. AbbVie has joined a recent biopharma spending spree in the projected $257 billion immunology market. Outside the immuno space, AbbVie has also invested heavily in the mental health market entering a potential $2 billion deal with Gilgamesh Pharmaceuticals in May 2024 to develop neuroplastogens for psychiatric disorders. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com .