Science

Science

SCIENCE

CB-101

CB-101 is an FDA-approved indirect food additive which is regarded as GRAS. It is cleaved by lipases to produce NaB, slowly. While NaB is rapidly excreted through urine and high doses are required to be efficacious, a steady level of NaB in the blood with a lower dose avoids side effects associated with high doses of NaB. This treatment is under development for Huntington’s Disease (HD), Parkinson’s Disease (PD), and Glycine Encephalopathy (GE), also known as Nonketotic Hyperglycinemia (NKH).

HD is a fatal and inherited neurodegenerative disorder. No effective drugs are available to halt the disease progression. Typical symptoms include chorea, rigidity, and writhing motions or abnormal posturing. Psychomotor functions are also severely impaired together with both abnormal facial expression and difficulties in chewing, swallowing, and speaking.

The efficacy of CB-101 in HD and PD has been fully confirmed with relevant animal models. CB-101-fed animals showed improved motor and cognitive functions, suggesting a potential effective treatment for HD. CB-101 also protects dopaminergic neurons and restores striatal dopamine levels in a PD animal model. NaB, a CB-101 metabolite, has also demonstrated efficacy in improving locomotor functions in MPTP-insulted hemiparkinsonian mice.

GE is caused by an inborn error of the glycine cleavage enzyme system (GCS) leading to the accumulation of glycine in the plasma and cerebral spinal fluid (CSF). GCS is composed of 4 proteins (P-, H-, T-, and L-protein). P protein is a pyridoxal phosphate-dependent glycine decarboxylase encoded by the GLDC gene. H-protein is a lipoic acid with hydrogen-carrier protein encoded by the GCSH gene. T-protein is a tetrahydrofolate (THF)-dependent protein encoded by the AMT gene. L-protein is a lipoamide dehydrogenase. Biallelic variants in either GLDC or AMT lead to both the dysfunction of GCS and a significant impairment in glycine metabolism. Eighty-five percent of patients are very severely affected with intellectual disability, serious seizures, and spasticity.

CB-101 produces NaB molecules through lipases, thereby converting glycine to hippurate which is secreted into the urine. Thus, CB-101 attenuates hyperglycinemia with less side effects compared to NaB which requires a large amount to be effective.

Helping people reclaim the simplest things of life is a reward more than worth the
investment of our time.

Curyxbio Team
SCIENCE

CB-201

CB-201 is an intranasal peptide inhibitor of the MYD88-TLR2 interaction with a potent anti-inflammatory function. CB-201 targets Alzheimer’s Disease (AD), Dementia with Lewy Bodies (DLB), and Rheumatoid Arthritis (RA) with a unique mechanism of action not present in other treatments.

CB-201 specifically blocks the TLR2 signaling pathway which is implicated in the pathogenesis of Alzheimer’s disease (AD), Multiple Sclerosis (MS), Dementia with Lewy Bodies (DLB), and Rheumatoid Arthritis (RA). CB-201 improved short-term, long-term, and spatial memory in preclinical animal models for AD and DLB. Furthermore, in animal models of MS and RA, it significantly reduced an inflammation. CB-201 is a good candidate for treating AD, DLB, MS, and RA patients.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly. No treatment is available to cure or halt the progression of this disease. The amyloid cascade hypothesis is widely accepted as one of the underlying pathogenic causes. There is a huge unmet need to find treatments for AD due to the increasing aging population. Dementia with Lewy Bodies (DLB) is the second most common progressive dementia. Like AD, no cure is available. It is pathologically characterized by Lewy Bodies and Lewy Neurites composed of α-synucleins, a pathological hallmark for Parkinson’s Disease (PD) and Parkinson’s Disease Dementia (PDD).

Helping people reclaim the simplest things of life is a reward more than worth the
investment of our time.

Curyxbio Team
SCIENCE

CB-301/CB-401

The interleukin-12 (IL-12) family consists of four members including (1) IL-12 (p40:p35), (2) p40 monomer (p40), (3) p40 homodimer (p402), and (4) IL-23 (p40:p19). CB-301 is a monoclonal antibody which specifically blocks p402. In contrast, CB-401 is a recombinant p40 protein which is a common subunit of IL-12 family.

The safety and efficacy of IL-12 family members as an immunosuppressant have been confirmed by the blocking of the p40 common subunit. Human monoclonal antibody against the p40 monomer (STELARA (Ustekinumab)) showed a significant efficacy for Psoriasis and Inflammatory Bowel Disease. In addition, human monoclonal antibody (TREMFYA (Guselkumab)) against IL-23 showed a significant efficacy for Plaque Psoriasis.

CB-301, a monoclonal antibody highly specific to the p40 homodimer (p402) showed a significant efficacy in preclinical animal models of Multiple Sclerosis and Rheumatoid Arthritis. Because CB-301 specifically blocks the p40 homodimer (p402) without blocking other IL-12 family members, it has the potential to be both be safer and more effective. Especially, because type 1 diabetes patients showed fluctuating levels of both p40 and p402, adjusting the levels of these molecules may be efficacious for curing the disease.

Autoimmune disease is a state where the immune system abnormally attacks the body. While the immune system recognizes foreign cells, however, in autoimmune diseases, it recognizes own body as a foreign, then it releases autoantibodies to attack own body. The most common autoimmune diseases are Type 1 Diabetes caused by the self-destruction of insulin-producing beta-cells in the pancreas, Rheumatoid Arthritis (RA) caused by the self-destruction of the joints, Psoriasis caused by the multiplication of skin cells, thereby leading to buildup of silver-white scales of plaque on the skin, Multiple Sclerosis caused by the self-destruction of the myelin sheath in central nervous system, Systemic Lupus Erythematosus (SLE) caused by the self-destruction of skin, joints, kidneys, brain, and heart, Inflammatory bowel disease caused by the inflammation in the lining of the intestinal wall, Addison’s disease caused by the self-destruction of adrenal glands, and Graves’ disease caused by the self-destruction of thyroid gland.

Despite extensive efforts for more effective drugs, only a few treatments are available to treat these diseases.