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(KDDF-201412-07) Development of CKD-506, an HDAC6 selective inhibitor, for rheumatoid arthritis treatment
Immunology, Chemical
Preclinical GLP study and IND approval for Phase I clinical trial
CKD-506 is a current preclinical candidate to treat rheumatoid arthritis by repressing inflammation and by enhancing Treg function.
Target population
Methotrexate or biologics-resistant RA patients
- Rheumatoid arthritis (RA) is a chronic inflammatory disease which affects about 1% of world population. It usually results in severe joint pain and bone deformation.
- The goal of RA treatment is to improve symptoms and slow the progress of the disease. The first line therapy is methotrexate. However, in short term use, about 30 to 40% of RA patients develop resistance against methotrexate. In long term use, 80% of RA patients develop the resistance.
- If the methotrexate treatment for 3 months does not improve the symptom, the RA patients are prescribed with the expensive biologics drugs such as Orencia (CTLA4-Fc) or other TNFα neutralizing agents. For the last 10 years, the biologics use increased gradually.
- Some patients develop resistance against biologics drugs but the exact mechanism of resistance is unclear. One hypothesis of such resistance is anti drug antibody because the anti drug antibody in about 30% of RA patients on biologics reduce the efficacy of biologics due to the augmented clearance of the biologics.
- CKD-506 represses inflammation synergistically with methotrexate by reducing TNFα secretion and inducing CTLA4 expression even in the presence of anti drug antibody against biologics. Thus, CKD-506 may be used for methotrexate resistant or biologics resistant patients.
Medical unmet needs
- Methotrexate may induce liver toxicity and methotrexate resistance as explained above.
- The demand of new oral small molecule drug is increasing to improve patient compliance (oral drug instead of IV injection) and to reduce high cost of biologics use (20,000USD/patients-year).
- Although tofacitinib, a new oral Jak3 inhibitor, was launched for the treatment of rheumatoid arthritis, it induces LDL cholesterol in a dose dependent manner (15% induction with 5 mg bid and 30% induction with 10 mg bid) and has an increased risk of carcinogenesis.
- Other drug candidates such as p38 MAPK inhibitor or Syk inhibitor have been discontinued due to toxicity or lack of efficacy.
- The demand on new oral small molecule drug is huge to enhance patient compliance and to reduce the financial burden on national health insurance and patients.
CKD-506 is at pre-IND stage
- CKD-506 showed significant therapeutic efficacy in RA animal models.
- Oral treatment of CKD-506 improved various inflammatory indices such as bone deformation and joint edema.
- The action mechanism of CKD-506 can be applied to other inflammatory diseases such as inflammatory bowel disease (IBD).
- The GLP toxicity and ADME study is ongoing in the abroad preclinical CRO.
The patent was filed in 2014.
Patent: Novel compounds for selective histone deacetylase inhibitors, and pharmaceutical composition comprising the same
Status
| Application number | Filing date | |
| KR | 2014-0051151 | 2014-04-29 |
| PCT | PCT/KR2014/003776 | 2014-04-29 |
License-Out after preclinical study or phase I clinical study
CKD Pharma is a leading company in the field of HDAC6 selective inhibitor development. Due to the huge unmet needs of orally available small molecule drug in the market, various multinational pharmaceutical companies showed strong interest on CKD’s HDAC6 inhibitor development program.
CKD-506 may be an excellent orally available small molecule drug to replace the current biologics.
Immunology (Rheumatoid arthritis)
May 01, 2015 - Sep. 30, 2016
ChongKunDang Pharmceutical Corp.
Nonclinical