HMPL-011
HMPL-011 is a novel cytokine modulator that controls the production of pro-inflammatory cytokines and is advanced into development for rheumatoid arthritis (RA) and other autoimmune diseases. Hutchison MediPharma has global rights to HMPL-011.
Key Features
- First-in-class potential for a variety of autoimmune indications
- Novel chemical entity
- Novel MOA offers potential for combo therapy
- Strong IP position
- Back up identified
- Currently in Phase I clinical study
Mechanism of Action (MOA)
- Increase the level of IL-10
- Decrease the levels of IL-6, TNF-a, INF-g and MCP-1
Preclinical Studies
a) Efficacy
- Significantly reduced the collagen induced joint inflammation in mice arthritis model
- Significantly inhibited the onset and relapses in Experimental Autoimmune Encephalomyelitis (EAE) model of multiple sclerosis (MS)
- Good efficacy in acute liver injury
- Good efficacy in delayed-type hypersensitivity reaction (DTH) via topical treatment
b) Toxicity
- Negative in in vitro genetox screens (Ames and MN)
- hERG inhibition IC50>30 uM
- Rat 4-week GLP toxicity study and monkey 4-week GLP toxicity study showed an acceptable safety margin
c) Drug metabolism and pharmacokinetics
- Good bioavailability in all species (mouse, rat, dog and monkey) and low to moderate clearance
- AUC values generally proportional to the doses
Phase I study
- Phase I: single ascending dose (SAD) and multiple ascending dose (MAD) trials in healthy male volunteers
- SAD completed: well tolerated, good PK properties with AUC above expected efficacious exposure achieved
- MAD results expected by May 2010
Manufacturing
Kilogram quantities of API and drug product have been manufactured under cGMP for the human clinical studies.
Intellectual Property
Hutchison MediPharma filed patent applications both in US and China in 2007 and PCT application in 2008. The applications claimed the chemical series and their potential uses.
Potential Market
The total autoimmune disease market was worth $13.6 billion in 2006 in the seven major markets. Datamonitor expects this to almost double to around $25.6 billion in 2016.
In 2006, RA sales were by far the highest in the autoimmune market across all geographical regions. In the US, RA and MS were estimated to constitute the largest shares of autoimmune sales, at 44% ($4.4 billion) and 32% (almost $3.2 billion), respectively. Psoriasis/psoriatic arthritis was a lot lower compared to the top two indications, with sales of $1.2 billion (12%). Launches of novel products will serve to grow the RA market from $6 billion in 2006 to $10 billion in 2016, the MS market from $4.6 billion in 2006 to $10.1 billion in 2016 and the psoriasis/psoriatic arthritis market from $1.5 billion in 2006 to $2.3 billion in 2016.
In 2006, RA sales were by far the highest in the autoimmune market across all geographical regions. In the US, RA and MS were estimated to constitute the largest shares of autoimmune sales, at 44% ($4.4 billion) and 32% (almost $3.2 billion), respectively. Psoriasis/psoriatic arthritis was a lot lower compared to the top two indications, with sales of $1.2 billion (12%). Launches of novel products will serve to grow the RA market from $6 billion in 2006 to $10 billion in 2016, the MS market from $4.6 billion in 2006 to $10.1 billion in 2016 and the psoriasis/psoriatic arthritis market from $1.5 billion in 2006 to $2.3 billion in 2016.
The RA market and the psoriasis/psoriatic arthritis market are both dominated by the TNF-inhibitors, and the MS market is currently dominated by the beta-interferons. There are strong unmet medical needs in developing effective, less in side effects and less expensive small molecule drug for RA and in developing an effective oral treatment for MS. The novel mechanism of action of HMPL-011 potentially makes HMPL-011 a “first-in-class” agent for autoimmune disease.
