HBM9161 is a novel, fully human monoclonal antibody that selectively binds to and inhibits the neonatal fragment crystallizable receptor (FcRn). Since inhibition of FcRn has shown to improve multiple autoimmune diseases conditions, we are developing HBM9161 for the treatment of a large numbers of relevant disorders. In several preclinical studies and Phase 1 clinical trials in healthy volunteers in Greater China and in Canada and Australia, HBM9161 has demonstrated dose-dependent reductions in serum levels of immunoglobulin G (IgG) antibodies and was well-tolerated following subcutaneous and intravenous administration to healthy volunteers.
Mechanism of Action
The neonatal fragment crystallizable receptor (FcRn) is a cellular receptor that binds IgG antibodies and guide their transport through cells. FcRn plays a pivotal role in preventing the degradation of IgG antibodies. Therefore, inhibition of FcRn, such as through use of an FcRn targeting antibody, has been shown to reduce levels of pathogenic IgG antibodies. Completed clinical trials of other anti-FcRn antibodies in IgG-mediated autoimmune diseases have generated promising results, suggesting that FcRn is a therapeutically important pharmaceutical target to treat these relevant pathogenic conditions.
Advantages of HBM9161
Current treatments for patients with serious autoimmune diseases primarily include plasmapheresis and intravenous immunoglobulin (“IVIg”). Compared with plasmapheresis and IVIg, HBM9161 has potential benefits as a more effective, first-in-class or best-in-class treatment for rare autoimmune diseases, including subcutaneous delivery; simple dosing schedule; low immunogenicity risk; and low effector function.
Autoimmune diseases are characterized by the attacking of normal constituents of the body by immune system, which is attributed to the failure of discrimination of self and non-self antigens. Autoreactive IgG antibodies play a central role in the pathology of some autoimmune disorders, including myasthenia gravis, primary immune thrombocytopenia, systemic lupus erythematosus and Graves’ ophthalmopathy, etc. Therefore, reducing autoantibody level from peripheral or B cell depletion becomes a promising therapeutic approach. Although currently available treatments have provided effective therapeutic method for IgG-driven autoimmune disorders, their clinical application is still restricted by high economical and time burden and severe side effects, leading to the unmet medical needs of improved pathogenic IgG-reducing strategies.
Immune Thrombocytopenia (ITP)
ITP is a bleeding disease caused by an autoimmune reaction in which a patient develops auto-antibodies (IgG) that attack and destroy their own platelets, which are blood cells that help blood to clot, or their own platelet-forming cells. Platelet deficiency, or thrombocytopenia, can cause bleeding in tissues, bruising and slow blood clotting after injury.
It is estimated that the market size of the ITP drug market in China will reach US$1,167.4 million in 2024 at a CAGR of 18.5% from 2019 to 2024, and further reach US$2,124.2 million in 2030 at a CAGR of 10.5% from 2024 to 2030.
Patients diagnosed with severe ITP are primarily offered corticosteroids and intravenous immunoglobulin (“IVIg”) or, to a lesser extent, plasmapheresis. While these therapies lead to increases in blood platelet counts, they do not address the underlying cause of the disease, which is the destruction of platelets by the immune system.
Graves Ophthalmopathy (GO)
GO is an inflammatory disorder of the orbit that occurs in association with autoimmune thyroid disease and that affects the muscles and other tissues around the eyes. Initial symptoms may include a dry and gritty ocular sensation, sensitivity to light, excessive tearing, double vision and a sensation of pressure behind the eyes. By the time that GO is clinically diagnosed, many patients have retraction of their upper eyelids, swelling and redness surrounding the eyes and protrusion of the eyes.
It is estimated that the market size of the GO drug market in China will reach US$14.8 million in 2024 with a CAGR of 52.2% from 2019 to 2024, and further reach US$450.5 million in 2030 with a CAGR of 76.8% from 2024 to 2030.
Immunosuppressive therapy such as high-doses of intravenous corticosteroids, is usually recommended for moderate-to-severe active GO patients, but they may not effectively reverse the severity and about one-third of the treated patients will relapse.
Myasthenia Gravis (MG)
MG is an autoimmune disorder associated with muscle weakness. MG patients develop auto-antibodies (IgG) that lead to an immunological attack on critical signaling proteins at the junction between nerve and muscle cells, thereby inhibiting the ability of nerves to communicate properly with muscles. This leads to muscle weakness, which can be localized to the ocular muscles or which can be more generalized throughout the body. Patients with localized disease suffer from the mildest symptoms, including droopy eyelids and blurred or double vision due to partial paralysis of eye movements. Many patients find it difficult to perform daily activities due to both insufficient improvement in symptoms even after treatment and the long-term side effects of oral corticosteroids, a common treatment for MG. Approximately 15% to 20% of MG patients will experience at least one myasthenic crisis over their lifetimes. During myasthenic crisis, the impairment of muscles required to breathe can become life-threatening, leading to death in approximately 2% to 5% of cases.
It is estimated that the market size of the MG drug market in China will reach US$148.5 million in 2024 at a CAGR of 28.1% from 2019 to 2024, and further reach US$1,077.5 million in 2030 at a CAGR of 39.1% from 2024 to 2030.
Patients with very early stage MG are treated with acetylcholinesterase inhibitors. As MG becomes more advanced, patients can be treated with immune suppressive agencies. For sever diseases, IVIg or plasmapheresis could be options. However, none of currently available treatments could help patients to achieve stable remissions，and with significant side effects. So, there is huge unmet medical needs.
Neuromyelitis Optica Spectrum Disorder (NMOSD)
NMOSD is a unifying term for neuromyelitis optica, previously known as Devic’s disease, and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord and brain stem, and often leads to irreversible blindness and paralysis. AQP4-IgG autoantibodies, produced by plasmablasts and plasma cells, bind primarily to astrocytes in the central nervous system, triggering attacks, which can damage the optic nerve, spinal cord and brain stem. Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease. There is currently no cure for NMOSD.
It is estimated that the market size of the NMOSD drug market in China will reach US$118.5 million in 2024 at a CAGR of 20.5% from 2019 to 2024, and further reach US$303.7 million in 2030 at a CAGR of 17.0% from 2024 to 2030.
There currently is no cure for NMOSD. Patients are treated with immunosuppressants, steroids and, in some cases, off-label use of rituximab, in an effort to prevent NMOSD attacks. Patients experiencing an attack are treated with steroids, intravenous immunoglobulin, or IVIG, and plasmapheresis. However, there has been no treatment approved for acute attack of NMOSD. And all available treatments are known to cause adverse events that may lead to treatment discontinuation prematurely.
We are conducting clinical trials on multiple indications of autoimmune diseases, including MG, ITP, NMOSD and GO.
We have the right to develop and commercialize HBM9161 in Greater China.