AXER-204

Spinal cord injuries are serious issues impacting hundreds of thousands of people in the United States. It’s estimated there are more than 17,000 new cases of spinal cord injuries each year, which can cause permanent damage in patients. With the prevalence of such injuries in the U.S., as well as the rest of the world, multiple companies are focusing their efforts on developing regenerative medicines to treat these injuries, which can result in permanent changes in strength, sensation and other body functions below the site of the injury, according to the Mayo Clinic. In addition to profound persistent neurological impairment, patients with chronic SCI suffer a variety of other health consequences including respiratory complications, cardiovascular complications, urinary and bowel complications, spasticity, pain syndromes, pressure ulcers, osteoporosis and bone fractures. According to the National Spinal Cord Injury Statistical Center, the leading cause of spinal cord injury is vehicle crashed, followed closely by falls. Other common causes of spinal cord injuries include sports injuries and acts of violence, such as gunshot wounds. Developing therapeutics to help patients regain full function are underway. BioSpace takes a look at recent work undertaken by researchers in the field: Keio University – Japanese researchers at Tokyo’s Keio University are aiming to use induced pluripotent stem (iPS) cells to treat spinal cord injuries. Until this particular study, the use of induced pluripotent stem cells had only been allowed in treating, eyes, hearts, cranial nerves and blood platelets of patients as part of regenerative medicine research. The trial will attempt to take the induced pluripotent stem cells and grow them into nerve cells. The Japanese research team will transplant two million of these new nerve cells into the injured areas of each patient via injection in hopes of inducing a response. The patients will also be given immunosuppressant drugs to prevent a rejection of the transplanted cells. InVivo Therapeutics – In February, Massachusetts-based InVivo published research data in the Journal of Neurosurgery: Spine describing the previously presented complete six-month primary endpoint results from the company's single-arm INSPIRE 1.0 study. Invivo’s biodegradable device is surgically implanted in patients who are dealing with a complete thoracic AIS A spinal cord injury. The article pointed to data that showed a probable benefit of a bioresorbable polymer scaffold for safety and neurological recovery in patients with complete thoracic spinal cord injury. InVivo has officially closed the INSPIRE 1.0 study and is actively enrolling patients into a second pivotal clinical study of the Neuro-Spinal Scaffold in patients with acute SCI, dubbed INSPIRE 2.0. Lineage Cell Therapeutics – California-based Lineage Cell Therapeutics, Inc. provided an update on its oligodendrocyte progenitor cell (OPC) therapy for the treatment of acute spinal cord injury in December. The company said it developed enhanced differentiation process, leading to major improvements in production and quality of its OPC1 cell therapy drug product. Improvements included ready-to-inject formulation of OPC1, which enables clinical use at a much larger number of spinal cord treatment centers, accelerating enrollment for a larger and potentially registrational clinical trial, the company said. The company also saw improvements in OPC1 functional activity, as assessed by cellular migration and secretion of key growth factors. OPC1 is an oligodendrocyte progenitor cell (OPC) transplant therapy designed to provide clinically meaningful improvements in motor recovery in individuals with acute spinal cord injuries. ReNetx Bio – In January 2020, Connecticut-based ReNetX Bio received Fast Track designation from the FDA for its clinical asset AXER-204 for the potential treatment of Chronic Spinal Cord Injury. ReNetX Bio is currently conducting a Phase I/II clinical trial dubbed RESET in patients with SCI. Topline results are expected to be announced this year. AXER-204 is designed to block axonal growth inhibitors in the central nervous system to promote neural repair. While Damage to axons in the CNS is permanent, ReNetx believes damaged and remaining undamaged axons provide an opportunity for restoration of function if new connections can be grown. In preclinical studies, AXER-204 has been shown to promote axonal growth and recovery of neurologic function in the central nervous system by acting as a decoy and binding the 3 key inhibitors Nogo-A, MAG, and OMgp. This interrupts their activation of NgR1 thereby promoting axonal growth. MicroCures – New York-based MicroCures’ lead product is siFi2. Preclinical research suggests that siFi2 may help overcome these natural inhibitors and trigger successful axon regeneration and reattachment at the site of injury. In preclinical studies of spinal cord injury in rats, MicroCures has demonstrated that treatment with siFi2 allowed axon growth to occur through the injury’s inhibitory barriers. Researchers did not witness similar axon growth among control animals, according to the company’s website.

As summer winds its way to an end, biopharmaceutical companies continue to conduct clinical trials and release news related to them. Here’s a look at last week’s clinical trial headlines. As summer winds its way to an end, biopharmaceutical companies continue to conduct clinical trials and release news related to them. Here’s a look at last week’s clinical trial headlines. Oncologie and Merck will l aunch a Phase II trial to investigate Merck’s Keytruda (pembrolizumab) and Oncologie’s bavituximab, an antibody that blocks the activity of phosphatidylserine (PS) in advanced gastric or gastroesophageal cancer. The trial is expected to enroll about 80 patients in the U.S., UK, Korea and Taiwan and begin enrollment in the second half of 2019. Eli Lilly ’s psoriasis drug Taltz showed superiority to Johnson & Johnson ’s Tremfya in a Phase IV post-marketing study. At 12 weeks, Taltz showed superiority over Tremfya in patients with moderate to severe plaque psoriasis. They had higher rates of complete skin clearance. Taltz also met all major secondary endpoints. Deciphera Pharmaceuticals ’ Phase III trial of ripretinib hit its primary endpoints in advanced gastrointestinal stromal tumors (GIST). It showed a median progression-free survival (PFS) rate of 6.3 months compared with one month in the placebo cohort. The drug significantly decreased the risk of disease progression or death by 85%. The company plans to submit its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2020. Innovate Biopharmaceuticals dosed the first patient in its Phase III clinical trial of INN-202 for celiac disease. INN-202, larazotide acetate, is a tight junction regulator designed to restore “leaky” or open junctions to a normal state. The trial is a national, multicenter, double-blind, placebo-controlled, randomized, parallel-group trial that plans to enroll about 600 patients. The primary objective is to evaluate the drug as adjunct therapy in celiac disease patients who still experience symptoms after being on a gluten-free diet. Vaccinex announced it had fully enrolled its ongoing CLASSICAL-Lung Phase Ib/II clinical trial. The trial is evaluating its VX15/2503, pepinemab, in combination with Pfizer’ s checkpoint inhibitor Bavencio (avelumab) in non-small cell lung cancer (NSCLC). The trial is being conducted in collaboration with Merck KGaA , Darmstadt, Germany and Pfizer. The trial is looking at NSCLC patients who are either immunotherapy naïve or who failed in previous therapies using checkpoint inhibitors. Mustang Bio announced that City of Hope had received a $9.28 million grant from the California Institute for Regenerative Medicine (CIRM) to fund an ongoing Phase I trial of MB-103 in HER2-positive breast cancer with brain metastases. City of Hope holds patents covering the HER2 CAR that were licensed to Mustang Bio in 2017. The trial is expected to enroll 21 City of Hope patients with the primary objective to determine safety and dosing for intraventricular delivery of HER2-specific CAR-T cells. Passage Bio is launching a Natural History Study to evaluate patients with Type 1 and Type 2 GM1 gangliosidosis. The disease is a rare autosomal recessive genetic disorder that progressively destroys nerve cells in the brain and spinal cord. The study is being run by the Orphan Disease Center (ODC) in the Perelman School of Medicine at the University of Pennsylvania. The study will be launched at several sites in the U.S., Europe and Brazil to gather information on the natural course and outcomes of the disease, without treatment or intervention, and to collect demographic, genetic, environmental and other data that may be related to the disease. Regeneron Pharmaceuticals announced positive results from its pivotal Phase III clinical trial of evinacumab in homozygous familial hypercholesterolemia (HoFH). HoFH is a genetically inherited form of severely increased “bad” cholesterol, low-density lipoprotein cholesterol or LDL. Patients with this disease often show early atherosclerotic disease and sometimes have cardiac events as teenagers. In the trial, evinacumab showed a 49% decrease in LDL cholesterol from baseline compared to placebo, which showed a 2% increase. This was the primary endpoint of the trial. The trial also demonstrated a 132 mg/dL absolute change in LDL cholesterol from baseline compared to 3 mg/dL decrease in the placebo group. Of the evinacumab group, 47% achieved LDL cholesterol levels less than 100 mg/dL compared to 23% of the placebo group. The drug was also effective in the most difficult-to-treat patients who don’t typically respond to other therapies. The drug also decreased apolipoprotein B, non-HDL cholesterol and total cholesterol compared to the placebo. AstraZeneca and Merck ’s Lynparza hit the mark in the Phase III PAOLA-1 clinical trial. The trial compared Lynparza and standard-of-care treatment bevacizumab ( Genentech ’s Avastin) in women with advanced ovarian cancer against Avastin alone. The women were with or without BRCA-gene mutations. In the trial, the combination showed a statistically-significant and clinically-meaning improvement in progression-free survival. Henry Ford Cancer Institute enrolled the first patient in the GBM AGILE Phase II/III trial to identify the most effective therapies for glioblastoma. The trial sponsor is Global Coalition for Adaptive Research (GCAR) and it is designed to test multiple therapies concurrently against a standard-of-care control. The trial concept was first brought up in 2015 by an international group of more than 130 clinicians, researchers, biostatisticians, imagers, pathologists, patient advocates, and industry and government leaders. ReNetX Bio dosed the first patient in a Phase I clinical trial of AXER-204. The RESET trial will evaluate the safety, tolerability and pharmacokinetics of AXER-204 in chronic spinal cord injury. The drug is a fusion protein designed to remove inhibitor proteins from the CNS environment, allowing for axonal regrowth and increased plasticity. Hepion Pharmaceuticals dosed the first patient in its 28-day ascending dose clinical trial of CRV431 for hepatitis B. Four cohorts of patients will be given the therapeutic in doses ranging from 75 mg to 375 mg in combination with 300 mg tenofovir disoproxil fumarate (TDF) antiviral therapy over a 28-day period. There are four patients in each cohort divided between hepatitis B e-antigen (HBeAg) positive and negative. Cellectar Biosciences completed the first cohort of its Phase I trial of CLR 131 in children and adolescents with select solid tumors, lymphoma, and malignant brain tumors. They will now advance to a second cohort utilizing an identified bolus dose of the drug. CLR 131 has received a Rare Pediatric Drug Designation (RPDD) for four separate pediatric diseases: neuroblastoma, rhabdomyosarcoma, osteosarcoma and Ewing’s sarcoma. Gritstone Oncology dosed the first patient with SLATE in metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation. SLATE immunotherapy is made up of a priming adenoviral vector used to deliver the cassette of 20 shared tumor-specific neoantigens (TSNA), and the TSNA cassette is delivered using a self-amplifying RNA vector in a repeated boost sequence that drives and sustains high numbers of tumor-targeted T-cells. The company used its proprietary EDGE artificial intelligence platform to identify the top 20 immunogenic shared TSNAs to engineer the cassette. The ongoing Phase I trial is evaluating SLATE in combination with Bristol-Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab), both checkpoint inhibitors. The trial is evaluating patients with metastatic lung adenocarcinoma, pancreatic ductal carcinoma and microsatellite-sable colorectal cancer, as well as other solid tumors with relevant mutation/human leukocyte antigen (HLA) combination. Mallinckrodt announced positive topline results from its pivotal Phase III CONFIRM trial of terlipressin for hepatorenal syndrome type 1 (HRS-1). The primary endpoint of verified HRS-1 was reversal, which included three components: renal function improvement, avoidance of dialysis, and short-term survival. HRS-1 is a life-threatening, rare and acute disease marked by liver complications that lead to kidney failure. Telipressin is a vasopressin analogue selective for V1 receptors.