NTRA-2112

The biopharma industry ended February and began March with plenty of clinical trial news. BioSpace shares the highlights. The biopharma industry ended February and began March with plenty of clinical trial news. Let’s take a look. COVID-19-Related Ocugen reported that the FDA had lifted a clinical hold on its Investigational New Drug (IND) application for Covaxin, its COVID-19 vaccine. India-based Bharat Biotech developed the vaccine. The lift will allow Ocugen to run a Phase II/III trial supporting its Biologics License Application (BLA) for the vaccine. Adamis Pharmaceuticals announced that due to the acceleration of patient enrollment in the Phase II/III trial for Tempol for COVID-19, the Data Safety Monitoring Board determined the study could continue. There were no safety or clinical concerns observed. Data from the first 50 participants will be reviewed again in March. Tempol has demonstrated strong, broad in-vitro anti-cytokine activity and anti-inflammatory properties. RedHill Biopharma announced positive results from the Phase II portion of the Phase II/III trial of RHB-107 (upamostat) in nonhospitalized symptomatic COVID-19 patients. The trial is designed to evaluate the drug for symptomatic COVID-19 patients in the early stages of the disease. The trial was conducted in the U.S. and South Africa, and during that period of the study, it primarily treated patients infected with the Delta variant. The data demonstrated a 100% reduction in hospitalization from COVID-19 compared to 15% hospitalization in the placebo-controlled arm. Non-COVID-19-Related Celyad Oncology announced that it was voluntarily pausing a clinical trial it is conducting with Merck after reports of two patient deaths. The CYAD-101-002 (KEYNOTE-B79) Phase Ib trial is evaluating Celyad’s CYAD-101 administered simultaneously with FOLFOX chemotherapy followed by Merck’s anti-PD-1 checkpoint inhibitor Keytruda (pembrolizumab) in patients with refractory metastatic colorectal cancer. CYAD-101 is a TCR Inhibitor Molecule (TIM)-based allogeneic NKG2D CAR T therapy. Celyad was informed of two deaths with similar pulmonary symptoms. The FDA formalized it on March 2. GlaxoSmithKline , after pausing three clinical trials of its vaccine for respiratory syncytial virus (RSV) in pregnant women, decided to stop enrollment and vaccination. The company stated it was conducting analyses of the safety data that had been accumulated to date in the three trials, NCT04605159 (GRACE), NCT04980391 and NCT05229068. Transcenta Holdings dosed the first patient in China of its Phase IIa Study of TST001 in combination with cisplatin and gemcitabine for first-line treatment of systemic treatment-naïve locally advanced or metastatic biliary tract cancer patients. The drug is a Claudin18.2 monoclonal antibody. Evelo Biosciences announced data from the post-treatment follow-up (Part B) of its Phase II study of EDP1815 in mild and moderate psoriasis. The drug is an oral biologic in development for inflammatory diseases, including psoriasis, atopic dermatitis, and COVID-19. The data suggests durable and deeper clinical responses. NervGen Pharma completed dosing for five subjects in the first cohort of its multiple ascending dose portion of the Phase I study of NVG-291. NVT-291 is a close analog to NVG-291-R, which is an intracellular signaling peptide. NVG-291 is being developed for Alzheimer’s disease, multiple sclerosis and spinal cord injury. Humacyte published five-year data from a Phase II study of its Human Acellular Vessel (HAV) for arteriovenous (AV) access in hemodialysis. The study reported durable long-term use and ongoing clinical function of the HAV in patients with end-stage renal disease who are undergoing hemodialysis. LivaNova implanted the first patient in its OSPREY clinical trial of its LivaNova aura6000 System, an implantable hypoglossal neurostimulator to treat adults with moderate to severe obstructive sleep apnea. The device is designed to maintain muscle tone of the tongue and upper airway so that airway obstruction and resulting sleep apnea are reduced or eliminated. Intellia Therapeutics and Regeneron Pharmaceuticals announced that the Phase I study of NTLA-2001 demonstrated a mean serum TTR reduction of 93% at the highest dose level by day 28 in patients with transthyretin amyloidosis (ATTR). The therapy is a CRISPR-based genome editing therapy. Intellia also announced it had dosed the first patient with NTLA-5001, its ex vivo CRISPR-Cas9 candidate for acute myeloid leukemia. NTLA-5001 is an autologous T cell receptor (TCR)-T cell therapy that targets the Wilms’ Tumor (WT1) antigen. DURECT Corporation dosed the first patient in Europe as part of its Phase IIb AHFIRM study of larsucosterol in severe alcohol-associated hepatitis (AH) patients. Larsucosterol binds to and inhibits the activity of DNA methyltransferases (DNMTs), an epigenetic enzyme that is elevated and associated with hypermethylation found in AH patients. NewAmsterdam Pharma dosed the first patient in its Phase III PREVAIL study of obicetrapib in patients with a history of atherosclerotic cardiovascular disease who do not have adequate control of their low-density lipoprotein cholesterol (ODO-c) despite being on maximally tolerated lipid-modifying therapies. The drug is a novel cholesteryl ester transfer protein (CETP) inhibitor. Boehringer Ingelheim and Eli Lilly and Company announced results from the Phase III EMPULSE trial. They found that adults hospitalized for acute heart failure were 36% more likely to experience clinical benefit over 90 days if initiated on Jardiance (empagliflozin) after stabilization and before discharge compared to placebo. The clinical benefit reflected a composite primary endpoint including all-cause mortality, frequency of heart failure events, time to first heart failure event and symptoms as measured by the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS). Actuate Therapeutics and The University of Kansas Cancer Center enrolled the first patient in a Phase II trial of elraglusib plus retifanlimab combined with gemcitabine/nab-paclitaxel for advanced pancreatic cancer in the first-line setting. Elraglusib is the company’s small molecule glycogen synthase kinase-3 beta inhibitor. Retifanlimab is Incyte Corporation’s intravenous PD-1 checkpoint inhibitor. Suzhou Kintor Pharma dosed the first patient in its Phase II study of KX-826 (pyrilutamide) in the U.S. for male androgenetic alopecia (AGA). KX-826 is an androgen receptor antagonist. NeuroGenesis and Hadassah Medical Center reported positive NF-L biomarker data from a Phase II trial in progressive multiple sclerosis treating NG-01 cells therapy. NF-L is a protein released into the CSF by damaged neurons. The company’s technology involves collecting bone marrow form the patient, then using a proprietary process, identifying a subpopulation of bone marrow cells cultured and enhanced towards remyelinating biofactory cells (NG-01) that also possess neurotrophic and neuroprotective properties. ProjenX initiated dosing in the Phase I study of prosetin in healthy volunteers and people with ALS. Prosetin is a potent, oral, brain-penetrant, mitogen-activated protein kinase kinase kinase kinase (MAP4k) inhibitor that targets endoplasmic reticulum (ER) stress. AmMax announced additional positive data from its Phase II trial of AMB-05X via intraarticular (IA) injection for the treatment of tenosynovial giant cell tumor (TGCT). AMB-05X is a monoclonal antibody against CSF1R. Genprex dosed the first patient in the Phase I/II Acclaim-1 study of Reqorsa Immunogene Therapy in combination with Tagrisso (osimertinib) in late-stage non-small cell lung cancer (NSCLC) patients whose disease progressed after treatment with AstraZeneca’s Tagrisso. Reqorsa (quaratusugene ozeplasmid) is a systemic gene therapy delivery platform. The active ingredient is the TUSC2 gene, a tumor suppressor gene. Innocoll reported positive topline results from a Phase III STUDY INN-CB-024 of Xaracoll in patients undergoing abdominoplasty. In patients receiving the drug, a decrease in pain intensity and opioid use was observed 24 hours after surgery. Xaracoll (bupivacaine HCL) implant is a bioresorbable collagen implant that provides pain relief by delivering bupivacaine at the surgical site. Xalud Therapeutics dosed the first patient in a Phase IIa study of XT-150 for facet joint osteoarthritis (FJOA) pain. The drug is a locally injectable plasmid DNA gene therapy expressing IL-10v, a proprietary modified variant of human interleukin-10 (IL-10). LEXEO Therapeutics announced positive initial expression and biomarker data from the low-dose cohort (cohort 1) of its Phase I/II trial of lX1001. LX1001 is an AAV-based investigational gene therapy that delivers the protective APOE2 gene into the CNS of APOE4 homozygous Alzheimer’s patients to halt or slow disease progression. Cytokinetics opened enrollment for Cohort 4 of its Phase II REDWOOD-HCM trial of aficamten for hypertrophic cardiomyopathy. The cohort will enroll patients with non-obstructive hypertrophic cardiomyopathy. The drug is a next-generation cardiac myosin inhibitor. Elgan Pharma announced “outstanding results” from the Phase III trial of ELGN-GI. GLGN-GI is a proprietary enteral insulin formulation for the treatment of intestinal malabsorption that causes feeding intolerance in preterm infants. Sanofi and AstraZeneca reported positive results from the Phase III MELODY study of nirsevimab for the respiratory syncytial virus (RSV). Nirsevimab is a vaccine. NuCana halted its Phase III biliary tract cancer study with Acelarin after an interim futility analysis. The analysis found a higher objective response rate (LRR) in the biliary tract cancer patients who received the drug plus cisplatin, but it did not translate into an overall survival benefit. Aravive announced positive new data from the Phase Ib portion of the ongoing Phase Ib/II trial of batiraxcept in clear cell renal cell cancer (ccRCC) and new data from a biomarker high subgroup. Batiraxcept is an ultra-high affinity decoy protein that binds to GAS6, the sole ligand that activates AXL, which inhibits metastasis and tumor growth, and restores sensitivity to anti-cancer drugs. Evofem Biosciences completed enrollment in its Phase III EVOGUARD trial of EV100 for the prevention of chlamydia infection in women and the prevention of urogenital gonorrhea infection in women. EVO100 (Phexxi) is lactic acid, citric acid, potassium bitartrate, an on-demand method of birth control.

Elgan Pharma, a late-stage clinical biopharmaceutical company focusing on innovative treatments for critical conditions in neonates, announced today outstanding results from a Phase III study evaluating the safety and efficacy of ELGN-GI, a proprietary enteral insulin formulation for the treatment of intestinal malabsorption, that causes feeding intolerance in preterm infants. The study results indicate an unprecedented improvement in gastrointestinal (GI) function and a reduction in related complications, including reduction in time until life threatening central line can be removed, reduction in hospital stay and a reduction in the number of life-threatening necrotizing enterocolitis (NEC) events. ELGN-GI was well tolerated, and no drug-related adverse effects were observed. The findings were recently published in JAMA Pediatrics. "Feeding intolerance is a common condition among preterm infants due to immaturity of the gastrointestinal tract," commented Prof. Hans van Goudoever, former Division Chair of Pediatrics, Emma Children's Hospital Amsterdam UMC, Professor of Pediatrics and since 2022 Dean at the University of Amsterdam and Chief investigator of the ELGN-GI program. "Feeding intolerance prolongs dependence on parenteral nutrition which, in turn, is associated with increased risk of short- and long-term life-threatening complications. We are very excited to see the positive results of this trial, showing multiple clinical benefits for ELGN-GI in improving intestinal maturation and the wellbeing of preterm infants. I trust that ELGN-GI holds the potential to improve the lives of premature infants and neonates suffering from short bowel syndrome." "One out of ten babies is born premature. The challenge that faces us is developing new therapies for unique unmet medical needs of this special population," said Miki Olshansky, CEO of Elgan Pharma said. "We are confident that ELGN-GI will be an important therapy for premature infants given its remarkable consistent clinical data across several trials to date. We look forward to initiating our second Phase III trial for ELGN-GI in the second half of 2022 towards registration." "In addition, we are on track to launching a Phase IIb clinical trial for ELGN-EYE, our second product candidate, for the treatment of pre-term infants' retinopathy of prematurity. In the past decades, there has been a lack of novel drugs specifically addressing infant health, and we are excited to be pioneers and propel this important underserved population forward with two promising additions," added Ms. Olshansky.