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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.

Shares of NuCana have plunged more than 57% in premarket trading after the company announced its Phase III biliary tract cancer study. See more facts here. NuCana’s biliary tract cancer study halted. Shares of NuCana have plunged more than 57% in premarket trading after the company announced its Phase III biliary tract cancer study with Acelarin halted following an interim futility analysis . Scotland-based NuCana reported that an Independent Data Monitoring Committee recommended discontinuing the study of Acelarin (NUC-1031) plus cisplatin in colorectal cancer following the assessment conducted at an interim analysis. Acelarin is one of NuCana’s ProTide drugs that Founder and Chief Executive Officer Hugh S. Griffith called a “ clever bit of chemistry ” in a previous interview with BioSpace. Griffith explained that Acelarin is a transformation of Eli Lilly’s old drug Gemzar. Griffith had high hopes that the Acelarin treatment could prove to be a treatment option for biliary tract cancer, which is a notoriously difficult cancer to treat. What does NuCana Said About Biliary Tract Cancer Study In its announcement on March 3, NuCana said the interim analysis revealed a higher objective response rate in the biliary tract cancer patients who received Acelarin plus cisplatin. However, it did not translate into an overall survival benefit. The Independent Data Monitoring Committee determined that the Acelarin arm was unlikely to achieve the primary endpoint of demonstrating at least a 2.2-month improvement in overall survival compared to the standard of care, which is Gemzar (gemcitabine) plus cisplatin. Griffith called the news of the interim analysis “disappointing.” He noted that the failure “highlights the challenges associated with developing new medicines for patients with biliary tract cancer.” He said NuCana would review the data to determine the potential development pathways for Acelarin. In earlier clinical studies, Acelarin plus cisplatin posted positive data, including the doubling of response rate in these patients compared to gemcitabine plus cisplatin. In the previous ABC-08 study of first-line patients with biliary tract cancer, Acelarin plus cisplatin achieved an objective response rate of 44%. The company reported a favorable 26% gained from gemcitabine plus cisplatin. That data had fueled NuCana’s hopes that Acelarin could become a standard of care medication for this disease. That data led to the U.S. Food and Drug Administration ’s granting of Fast Track designation to Acelarin last year for biliary tract cancer. Emphasizing the difficulties of treating biliary tract cancer, Jennifer J. Knox, M.D., a professor of medicine at the University of Toronto and chief investigator of the NuTide:121 study assessing Acelarin, said biliary tract cancer includes a group of tumors that is difficult to treat. “Developing effective therapies in this setting is extremely challenging. I, along with the other NuTide:121 investigators, am dedicated to developing better treatment options for patients with biliary tract cancer. While the outcome of NuTide:121 is disappointing, it will not diminish our determination to address the unmet needs of these patients,” Knox said in a statement. While NuCana stumbled with Acelarin, Griffith noted the company has other ProTides aimed at different types of cancer. One of those, NUC-3373, will begin a Phase III study in colorectal cancer later this year. Dosing is expected to start in that study in the second half of 2022. Griffith said NUC-3373 generates promising data in the Phase Ib/II colorectal cancer study. The company is conducting other studies to determine additional solid tumors the ProTide can target. NUC-7738 is entering Phase II development in solid tumors and lymphoma patients with data readouts later this year. Griffith concluded that the company is in a “robust financial position” that will continue focusing on its strategy and anticipate the generation of essential data readouts from ongoing studies.