Tapinarof is a potential first-in-class, once-daily therapeutic aryl hydrocarbon receptor modulating agent (TAMA) topical cream being developed for the treatment of plaque psoriasis and atopic dermatitis. In August 2020, Dermavant announced positive results from PSOARING 1 and PSOARING 2, two identical, multi-center, randomized, vehicle-controlled, double-blind, parallel studies to evaluate the efficacy and safety of tapinarof cream, 1% in adult patients with plaque psoriasis.

In both PSOARING 1 (N=510) and PSOARING 2 (N=515), tapinarof cream demonstrated highly statistically significant improvement in Physician Global Assessment (PGA) score of clear (0) or almost clear (1) with a minimum 2-grade improvement compared to vehicle from baseline at Week 12 (both P<0.0001), thus meeting the primary endpoint of each trial. In addition, all secondary endpoints were achieved in both trials, including PASI75. To date, over 2,200 subjects have enrolled in 17 clinical trials of tapinarof.

Sinovant is initially developing lefamulin for community-acquired pneumonia, one of the leading causes of mortality in Mainland China. Due to its novel mechanism of action, low incidence of cross-resistance between other antibacterial agents commonly used to treat community-acquired pneumonia, and low propensity for bacterial resistance to develop, lefamulin has the potential to be used as a first-line empiric monotherapy for the treatment of community-acquired pneumonia.

Lefamulin has successfully completed two global Phase 3 studies in patients with moderate and severe community-acquired pneumonia. Lefamulin has been granted Qualified Infectious Disease Product (QIDP) designation from the US FDA and is currently in preparation for an MAA in Europe.

In June 2019, the China National Medical Products Administration approved Sinovant’s Clinical Trial Application for lefamulin. In August 2019, Sinovant’s partner Nabriva Therapeutics received FDA approval of lefamulin to treat community-acquired bacterial pneumonia.

Sinovant is initially developing derazantinib, a potent, orally administered inhibitor of the fibroblast growth factor receptor (FGFR) family, for the treatment of intrahepatic cholangiocarcinoma (iCCA), a devastating form of biliary tract cancer with high incidence in Greater China and parts of Asia and no approved therapies. In a Phase 1/2 study in patients with iCCA harboring FGFR2 gene fusions, treatment with derazantinib resulted in an objective response rate of 21%, nearly 3 times higher than standard-of-care chemotherapy.

Derazantinib is currently being evaluated in a registration-enabling study in patients with FGFR2 fusion-positive second-line iCCA in the United States and Europe.

Delayed graft function (DGF) is a form of acute kidney injury that manifests postoperatively in 20-30% of renal transplantation patients globally and is associated with a 40% decrease in long-term graft survival. In Greater China, persistent organ shortages have led to greater use of deceased donor kidneys, which is expected to drive increases in observed rates of DGF.

SNV-003 is an investigational small molecule mimetic of hepatocyte growth factor (HGF) being developed by Sinovant in Greater China for DGF.

ARU-1801 is an investigational gene therapy for sickle cell disease and β-thalassemia. ARU-1801 utilizes proprietary technology intended to increase functioning red blood cells by inserting a modified fetal hemoglobin gene into autologous stem cells through a lentiviral vector. Studies have indicated that sickle cell patients with elevated levels of fetal hemoglobin have fewer vaso-occlusive crises and hospitalizations. 

ARU-1801 was developed in the laboratory of Dr. Punam Malik, Director of the Cincinnati Comprehensive Sickle Cell Center at Cincinnati Children’s. Preliminary clinical data from an ongoing Phase 1/2 study of ARU-1801 in patients with sickle cell disease conducted using a reduced-intensity conditioning (RIC) regimen enabled by the unique properties of modified fetal hemoglobin was presented by Dr. Malik in an oral presentation on Monday, December 3^rd, 2018, at the Annual Meeting and Exposition of the American Society of Hematology in San Diego, CA.

AXO-Lenti-PD is an investigational gene therapy for Parkinson’s disease that delivers three genes via a single lentiviral vector to encode a set of critical enzymes required for dopamine synthesis, with the goal of reducing variability and restoring steady levels of dopamine in the brain. The gene therapy aims to provide patient benefit for years following a single administration.

Axovant announced positive 12-month data results from the first cohort of patients in its ongoing SUNRISE-PD Phase 2 trial of AXO-Lenti-PD in January 2020 and announced positive initial 6-month data from the second cohort of patients in February 2020.

AXO-AAV-GM1 delivers a functional copy of the GLB1 gene via an adeno-associated viral (AAV) vector, AAV9, which is effective in crossing the blood-brain barrier and transducing neurons, with the goal of restoring β-gal enzyme activity for the treatment of GM1 gangliosidosis. The gene therapy is delivered intravenously, which has the potential to broadly transduce the central nervous system and treat peripheral manifestations of the disease.

In preclinical studies, AXO-AAV-GM1 was shown to improve β-gal enzyme activity, reduce GM1 ganglioside accumulation, improve neuromuscular function, and extend survival. Magnetic resonance imaging (MRI) of felines with GM1 gangliosidosis treated with AXO-AAV-GM1 showed normal brain architecture through at least two years of age.

AXO-AAV-GM2 delivers functional copies of the HEXA and HEXB genes via two, co-administered AAVrh8 vectors delivered directly to the central nervous system with the goal of restoring Hex A enzyme activity to address both Tay-Sachs and Sandhoff diseases. The preclinical data for AXO-AAV-GM2 in murine models showed dose-dependent increases in Hex A enzyme activity, reductions of GM2 gangliosides in the brain and prolonged survival rates.

Initial data with AXO-AAV-GM2 suggest stabilization of disease course, attainment of normal developmental milestones, and improvement in myelination on brain MRI.

CVT-DC-01 is a dendritic cell vaccine being developed for post-remission acute myeloid leukemia. Dendritic cell vaccines are patient-derived therapies in which a patient’s own dendritic cells are loaded with tumor antigens to elicit immune responses against cancerous cells. Different tumor antigens can be loaded into dendritic cells to treat various forms of cancer. As DC vaccines are designed to activate immune responses against tumor antigens over the course of vaccine administration, these therapies may be particularly suitable for cancer patients for whom prevention of disease relapse is the main treatment goal.

Cerdulatinib is a topical dual janus kinase (JAK) and spleen tyrosine kinase (Syk) inhibitor. Dermavant is developing cerdulatinib as a topical therapy for a variety of dermatologic conditions. Dermavant believes that the profile of cerdulatinib is ideal for development in skin diseases where a growing body of evidence suggests that both JAK and Syk are important drivers of disease manifestation.

Tapinarof is a potential first-in-class, once-daily therapeutic aryl hydrocarbon receptor modulating agent (TAMA) topical cream being developed for the treatment of plaque psoriasis and atopic dermatitis. In August 2020, Dermavant announced positive results from PSOARING 1 and PSOARING 2, two identical, multi-center, randomized, vehicle-controlled, double-blind, parallel studies to evaluate the efficacy and safety of tapinarof cream, 1% in adult patients with plaque psoriasis.

In both PSOARING 1 (N=510) and PSOARING 2 (N=515), tapinarof cream demonstrated highly statistically significant improvement in Physician Global Assessment (PGA) score of clear (0) or almost clear (1) with a minimum 2-grade improvement compared to vehicle from baseline at Week 12 (both P<0.0001), thus meeting the primary endpoint of each trial. In addition, all secondary endpoints were achieved in both trials, including PASI75. To date, over 2,200 subjects have enrolled in 17 clinical trials of tapinarof.

Warm autoimmune hemolytic anemia (WAIHA) is a rare hematologic disease in which autoantibodies mediate hemolysis, or the destruction of red blood cells. WAIHA approximately affects 42,000 people in the United States and 66,000 people in Europe. The clinical presentation is variable and most commonly includes non-specific symptoms of anemia such as fatigue, weakness, skin paleness, and shortness of breath. Symptoms typically develop chronically over several weeks to months, but rapid progression over a span of days has also been observed.

Immunovant is developing IMVT-1401, a novel, fully human monoclonal antibody that selectively binds to and inhibits the neonatal fragment crystallizable receptor (FcRn), for the treatment of immunoglobulin G (IgG) mediated diseases, such as WAIHA. IMVT-1401 is being developed as a subcutaneous injection, providing a convenient and minimally invasive treatment option for patients.

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease characterized by weakness and fatigue of voluntary muscles. Symptoms typically emerge in the eyes (e.g., drooping eyes, double-vision, blurred vision) and progress into the face, throat, and limbs. MG is a rare disease that affects approximately 65,000 people in the United States and 104,000 people in Europe, with a greater prevalence among younger women and older men.

The chronic nature of MG requires patients to cope with fluctuating symptoms and multiple treatment regimens for management. Persistent muscle weakness associated with MG often negatively interferes with patients’ ability to engage in daily and physical activities, including demands of work, family, and social functions.

Immunovant is developing IMVT-1401, a novel, fully human monoclonal antibody that selectively binds to and inhibits the neonatal fragment crystallizable receptor (FcRn), for the treatment of immunoglobulin (IgG) mediated diseases, such as MG. IMVT-1401 is being developed as a subcutaneous injection, providing a convenient and minimally invasive treatment option for patients.

Thyroid eye disease (TED), also known as Graves’ ophthalmopathy, is an autoimmune disorder that affects the muscles and other tissues around the eyes. TED approximately affects 33,000 people in the United States and 52,000 people in Europe. Moderate-to-severe TED is characterized by swelling and redness of the eyelids, proptosis (protrusion of the eyeball), double vision, and, in severe cases, corneal ulceration and decreased visual acuity.

Immunovant is developing IMVT-1401, a novel, fully human monoclonal antibody that selectively binds to and inhibits the neonatal fragment crystallizable receptor (FcRn), for the treatment of immunoglobulin (IgG) mediated diseases, such as TED. IMVT-1401 is being developed as a subcutaneous injection, providing a convenient and minimally invasive treatment option for patients.

COVID-19, an infectious disease caused by SARS-CoV-2, has become a global pandemic. Patients with severe cases of COVID-19 experience severe viral pneumonia that often persists despite a decrease in viral load, and can progress to ARDS and death. When implementing standard of care, including mechanical ventilation, ARDS has an overall mortality rate of 41%.

Roivant is developing gimsilumab, a monoclonal antibody that targets GM-CSF, a pro-inflammatory cytokine found to be up-regulated in COVID-19 patients with or at risk of developing ARDS. Gimsilumab has been tested in numerous non-clinical and two clinical studies for rheumatoid arthritis, including a 4-week Phase 1 study in healthy volunteers conducted by Roivant which completed dosing in February.

In April 2020, Roivant announced the dosing of the first patient in the BREATHE Phase 2 clinical trial of gimsilumab in COVID-19 patients for the prevention and treatment of ARDS.

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