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KDDF-201609-04 Development of HDAC6 inhibitor (CKD-506) for the treatment of Rheumatoid arthritis(Immunology, Chemical) [01.31.2017]

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Development and Market Objectives

The goal of this project includes Phase I clinical study (SAD, MAD and Food effect for healthy subjects and PK/PD analysis for Inflammatory Bowel Disease patients, IBD), nonclinical study for Phase II clinical study and approval of IND for Phase 2 clinical study.

Unmet Medical Need & Target Patients

Target patient population Rheumatoid arthritis (RA) is a chronic autoimmune disorder which affects 1% of adults in the developed world. The market size of RA is bigger than any other autoimmune diseases. The treatment guideline of RA recommends to use methotrexate (MTX) as 1st option. MTX single treatment for 3 months did not control the symptom of 30~40% RA patients appropriately. The guideline recommends to consider other therapeutic options such as DMARDs (biologics or Xeljanz) in combination with MTX for MTX-resistant RA patients.

 

In nonclinical animal study, CKD-506 showed synergistic therapeutic efficacy when combined with MTX, suggesting that CKD-506 may provide better therapeutic efficacy in combination with MTX for MTX or DMARDs resistant RA patients.

 

Currently, MTX-resistant patient is considered as 1st target population. DMARDs resistant patient is also considered as additional target population because DMARDs resistant patient does not have adequate next therapeutic option. Thus, it is important to confirm the therapeutic efficacy of CKD-506 monotherapy and CKD-506/MTX combination for DMARDs resistant patient, too.

 

Unmet medical needs Current RA therapeutics have diverse adverse effects which limit their clinical use significantly. MTX has liver toxicity and low therapeutic efficacy for 30~40% RA patients. Biologics develop neutralizing antibodies which restrict their therapeutic efficacy and should be administered IV or SC. Thus, it is required to develop oral drug with less adverse effects.

 

Recently, an oral anti-rheumatic drug Xeljanz was launched but it was reported that Xeljanz significantly induces LDL-c within 1 months (15% with 5mg and 30% with 10mg) and increases risk of carcinogenesis.

In addition, the development of oral inhibitors for other targets such as p38 MAPK was halted due to lack of efficacy or severe adverse effects. Thus, oral small molecule therapeutics for new targets is still required.

 

In addition, the high cost of biologics for RA is a significant financial burden for national health insurance as well as patients. Taken together, the development of new oral small molecule therapeutics is urgent task to meet the medical needs.

Status

In nonclinical animal study, CKD-506 showed excellent efficacy such as protection of bone loss, alleviation of joint edema and decrease in inflammation indices in rat AIA and mouse CIA models. In addition, CKD-506 improved RA patient’s Treg activity to inhibit Teff cell proliferation and repressed TNFa secretion from IL1beta-stimulated RA patients’ fibroblast-like synoviocytes.   

 

Based on these results, Phase I clinical study of CKD-506 is on-going in Europe. The Phase I clinical study includes SAD/MAD/FE for healthy subjects and MAD for IBD patients. 13-week GLP tox study for phase 2 clinical study is on-going at CRO specialized in nonclinical GLP tox study.

 

The action mechanism of CKD-506 may be applied to various autoimmune diseases and the efficacy was proven in nonclinical animal studies for IBD, Multiple sclerosis and systemic lupus erythematosus models, implying that its indication will include more autoimmune diseases in addition to RA.

Intellectual Property

Title : Novel compounds for selective histone deacetylase inhibitor, and the pharmaceutical composition comprising thereof
The patent of CKD-506 was granted in Korea, and filed in 53(fifty-three) countries. 
 

Competitive Advantages

The action mechanism of CKD-506 includes repression of TNFa secretion, induction of CLTA4 expression and suppression of cell adhesion. These mechanisms has been exploited for clinical purpose by TNFa neutralizing biologics, Orencia (CTLA4-Fc) and Tysabri (anti-Integrin a4 neutralizing antibody). However, oral small molecule drug with those mechanisms is absent. Because CKD-506, oral small molecule drug candidate, shares the mechanism with those biologics, CKD-506 may have efficacy in the indications where those biologics were approved for their clinical use.

 

MTX combination efficacy is important because MTX is 1st line therapeutics in RA. Xeljanz showed more adverse effects than improvement of efficacy in combination with MTX whereas CKD-506 showed significant synergistic improvement in therapeutic efficacy in combination with MTX.

 

TNFa neutralizing biologics approved for IBD treatment but not any oral small molecules although IBD prevalence is increasing in Asian countries as well as western countries. CKD-506 has the same action mechanism with the biologics approved for IBD, suggesting that it can be a new oral IBD therapeutics.

 

Taken together, the differentiation point of CKD-506 is that CKD-506 is oral drug which can be combined with MTX in RA to replace the current biologics drugs with a strong potential of indication expansion including IBD.

 

Based on these differentiation points, the chance of global partnering will be pursued after phase I or II clinical study.

Indication

Rheumatoid arthritis

Research Period

Jan. 1, 2017 ~ Jun. 30, 2018

Company

Chong Kun Dang

Developmental Stage

Phase I

Additional Information

Contact Information

Contact
Address Company Name: Chong Kun Dang
WebSite Homepage: http://www.ckdpharm.com/ Contact Person: Sei-Hwan Kim
E-mail: seihwan@ckdpharm.com Contact: +82-31-340-1250

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