Breakthrough Clinical Results
C4 Therapeutics announced that its partner, Biogen, received FDA IND acceptance for BIIB142, an IRAK4 degrader. BIIB142 is intended for the treatment of autoimmune diseases. This advancement stems from a 2018 collaboration where C4T provided expertise in targeted protein degradation, and Biogen contributed scientific and drug development capabilities. C4T delivered two development candidates to Biogen under this agreement; Biogen is responsible for clinical development and commercialization. C4T will receive a $2 million milestone payment upon patient dosing in the BIIB142 clinical trial. The collaboration highlights the success of targeted protein degradation in addressing unmet needs in autoimmune diseases.
Key Highlights
- FDA accepts Biogen's IND application for BIIB142, an IRAK4 degrader.
- BIIB142 is intended to treat autoimmune diseases.
- The drug is a result of a collaboration between C4 Therapeutics and Biogen.
- C4T will receive a $2 million milestone payment upon patient dosing.
Incidence and Prevalence
Global Prevalence and Incidence of Autoimmune Diseases
According to the most recent data, autoimmune diseases cumulatively affect 5-10% of the industrial world population and represent a significant cause of morbidity and mortality. A 2012 global study identified 81 autoimmune diseases with an overall estimated global prevalence of 4.5%, with 2.7% for males and 6.4% for females.
The most detailed country-specific data comes from Germany (2022), where 8.61% of the population had at least one autoimmune disease, corresponding to approximately 1 out of 12 individuals. Of those with autoimmune diseases in Germany, 67% were females.
In the United States, a 2024 study reported that over 15 million people (4.6% of the US population) have been diagnosed with at least one autoimmune disease from January 2011 to June 2022. Females represent 63% of those with autoimmune disease and are almost twice as likely as males to be diagnosed with an autoimmune condition. Notably, 34% of those diagnosed have more than one autoimmune condition.
The prevalence of specific autoimmune diseases varies widely. In Germany, prevalence ranges from 0.008% (pemphigus) to 2.3% (autoimmune thyroiditis). Other common conditions include psoriasis (1.9%), rheumatoid arthritis (1.4%), and type 1 diabetes (0.75%).
A study from Sardinia, Italy (2012) reported prevalence per 100,000 for various conditions: autoimmune thyroiditis (2,619), psoriasis/psoriatic arthritis (939), rheumatoid arthritis (552), type 1 diabetes (464), ulcerative colitis (124), celiac disease (124), systemic lupus erythematosus (81), myasthenia gravis (35), systemic sclerosis (35), Crohn's disease (15), and Sjogren's syndrome (31).
Gender disparities are significant in autoimmune diseases. In Germany, prevalence was higher in females for 25 of 31 autoimmune diseases studied, with the highest female-to-male ratios for autoimmune thyroiditis (5.92), primary biliary cirrhosis (5.60), and systemic lupus erythematosus (5.15). Conversely, males were more likely to be diagnosed with type 1 diabetes (1.37), ankylosing spondylitis (1.40), and Guillain-Barré syndrome (1.31).
The typical age-of-onset for most autoimmune diseases is 40-50 years.
Geographically, industrial regions, particularly Northern Europe and North America, exhibit the highest rates for most autoimmune diseases. However, in recent decades, rates are rising worldwide, and autoimmunity can no longer be associated solely with more developed "Western" countries.
The global prevalence and incidence of autoimmune diseases are increasing dramatically, particularly over the last 50 years in western countries. This trend has made autoimmune diseases a major threat to public health globally.
Individuals with one autoimmune disease have a higher probability of developing a second autoimmune disorder, highlighting the interconnected nature of these conditions.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Autoimmune Diseases
Recent research has identified several promising mechanisms of action for treating autoimmune diseases:
JAK-STAT Pathway Inhibition has emerged as a central therapeutic approach. JAK inhibitors suppress intracellular signaling mediated by multiple cytokines involved in autoimmune pathology. Due to safety concerns with pan-JAK inhibition, research now focuses on developing isoform-selective JAK inhibitors. Selective inhibition of tyrosine kinase 2 (TYK2) balances efficacy and safety, with deucravacitinib (FDA-approved allosteric inhibitor) and ropsacitinib (active site-directed inhibitor) in clinical trials.
Bruton's tyrosine kinase (BTK) inhibition represents another significant advancement. BTK links B-cell receptor signals to B-cell activation and is expressed in both B cells and myeloid cells. While first-generation BTK inhibitors showed efficacy in B-cell malignancies, they had unfavorable safety profiles for autoimmune treatment. Second-generation BTK inhibitors with superior specificity are being investigated for rheumatoid arthritis and systemic lupus erythematosus, with at least 22 BTK inhibitors in clinical development.
Antigen-specific immunotherapies (ASITs) are moving beyond traditional disease-modifying drugs. Research focuses on using biomaterials to harness features unique to specific delivery routes for diseases like multiple sclerosis and type 1 diabetes. Processing-independent CD4+ T-cell epitopes (PIPs) show promising results in several autoimmune diseases.
Toll-like receptor (TLR) modulation targets innate immune system activation. Aberrant activation of TLR7 and TLR8 pathways occurs in autoimmune disorders due to recognition of self-RNA. 2-pyridinylindole compounds have been identified as potent dual inhibitors of TLR7 and TLR8 with good selectivity.
Adenosine A receptor (AR) targeting shows potential for controlling experimental autoimmune encephalomyelitis. AR antagonists confer protection by targeting the choroid plexus (CP) niche, reducing T cell trafficking through inhibiting the CCR6-CCL20 axis.
TNFα converting enzyme (TACE) regulation addresses upregulated TACE activity in Crohn's disease. Silencing inhibitory rhomboid proteins 1 and 2 (iRHOMs 1/2) reduces TACE trafficking, decreases TNFα release, and restores immunosuppressive capabilities of TGFβ signaling.
Cellular immunotherapies offer targeted approaches including chimeric antigen receptor (CAR) T cells, chimeric auto-antibody receptor (CAAR) T cells, regulatory T cells (Tregs), and tolerogenic dendritic cells (TolDCs). These therapies aim to either deplete autoreactive cells or promote immune tolerance.
Variable domain glycosylation of IgG autoantibodies has been observed in several autoimmune diseases. These N-linked, complex-type, and α2-6 sialylated variable domain glycans interact with inhibitory receptor CD22, providing insights into potential mechanisms of autoimmunity.
Combination therapies show increasing promise, as research has opened prospects for successful antibody combination therapy for autoimmune diabetes with curative potential, since monotherapies cannot achieve this goal.
These emerging mechanisms represent significant advances in our understanding and treatment of autoimmune diseases, moving toward more targeted, effective, and potentially curative approaches.
Drug used in other indications
BIIB142 Clinical Trials Information
There is currently no available information about BIIB142 clinical trials for indications other than autoimmune diseases. The data does not reveal what other conditions this investigational compound might be targeting or what intervention models are being used in any potential trials.
Without specific clinical trial data, it's not possible to describe the intervention methodologies, study designs, or treatment protocols that might be employed in BIIB142 studies for non-autoimmune indications.
Any developments regarding BIIB142's potential applications beyond autoimmune diseases would require updated clinical trial registry information or official announcements from the developing company.