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.

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 an investigational therapeutic aryl hydrocarbon receptor modulating agent (TAMA) for the treatment of psoriasis and atopic dermatitis. It has been evaluated as a topical therapy in multiple Phase 1 and Phase 2 studies involving over 800 human subjects.

In a double-blind, placebo-controlled global phase 2b dose-ranging study that enrolled 247 patients with atopic dermatitis, tapinarof demonstrated clinically meaningful, dose-dependent improvements over vehicle on the primary endpoint of the study. Tapinarof was generally well tolerated. The most frequently reported adverse events were folliculitis, contact dermatitis and the common cold. Efficacy assessments were made on a modified intent-to-treat population.

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.

RVT-1501 is the first clinical candidate in a new chemical class of oral agents called the glimins by the World Health Organization. In several studies conducted to date, RVT-1501 has demonstrated potential glucose-lowering effects through increased insulin secretion in response to glucose, increased insulin sensitivity, and suppression of gluconeogenesis. RVT-1501's mechanism of action also has the potential to prevent diastolic dysfunction and to provide protective effects on beta cell survival and function.

A dozen clinical trials studying imeglimin in patients with T2D have met their primary and secondary endpoints, including a statistically significant decrease of HbA1c and fasting plasma glucose versus placebo with a favorable side effect profile. Metavant aims to initiate a Phase 3 program in patients with type 2 diabetes and chronic kidney disease (CKD) stages 3b/4 in the US and Europe. In December 2019, Poxel and Sumitomo Dainippon Pharma (DSP) announced positive Phase 3 results of imeglimin for the treatment of T2D in Japan.

RVT-1601 (formerly PA101) is a novel formulation of inhaled cromolyn sodium delivered through a proprietary nebulizer device designed to yield high lung deposition and distribution. In a completed Phase 2a trial, RVT-1601 demonstrated a statistically significant reduction in daytime and 24-hour cough frequency among idiopathic pulmonary fibrosis (IPF) patients versus placebo after 14 days of treatment. This reduction was supported by positive trends in cough-specific quality of life and cough severity, as assessed by patients in the study. 

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.

DMVT-504 is a combination of the muscarinic antagonist oxybutynin with the muscarinic agonist pilocarpine. DMVT-504 uses proprietary technology to control the release and dosing of pilocarpine with the goal of reducing the frequency and severity of dry mouth and potentially other side effects associated with oxybutynin.

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.

CVT-TCR-01 is a T cell receptor therapy being developed for the treatment of solid tumors. T cell receptor therapies utilize a patient’s own immune system to target tumor cells. In preparation for the therapy, a patient’s T cells are modified to express tumor-specific receptors that are then able to activate and mount an antitumor response. Through ex-vivo modification of a patient’s T cells, T cell receptor therapies can overcome natural T cell tolerance toward cancer cells and tumor-induced immunosuppression. Unlike CAR-T therapy, TCR-T therapy is designed to recognize intracellular antigens in addition to extracellular antigens, which may increase the number of tumors that can be successfully targeted.

Atopic dermatitis is a chronic, pruritic inflammatory skin disease that occurs primarily in children. Both environmental and genetic factors drive disease pathology, which is characterized by breakdown of the skin barrier and concurrent inflammation. Atopic dermatitis progresses in a chronic intermittent fashion, and is characterized by periods of acute symptom worsening, known as flares, followed by periods of quiescence. Flares can be triggered by a variety of factors including infections, heat, sweating, food allergies, and anxiety. DMVT-501 is a highly potent and selective topical phosphodiesterase-4 inhibitor being evaluated for the treatment of atopic dermatitis.

DMVT-503 is an investigational drug candidate with a novel mechanism of action being developed for the topical treatment of acne.

By developing products in-house and forming partnerships, Genevant is building a diverse pipeline of RNA therapeutics across multiple modalities. Through its proprietary LNP and ligand conjugate delivery platforms, Genevant is able to pursue mRNA, RNAi, and gene editing modalities and select the optimal approach for any given disease.

Genevant is pursuing the co-development and co-commercialization of five mRNA therapeutic programs for rare diseases with high unmet medical need in collaboration with BioNTech AG. The collaboration combines Genevant’s industry-leading lipid nanoparticle (LNP) delivery technology with BioNTech’s cutting-edge mRNA drug discovery platform. Both companies have established GMP-grade manufacturing capabilities and infrastructure.

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.

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. Gimsilumab has demonstrated a favorable safety and tolerability profile based on data collected to date, with no adverse events reported.

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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