Clinical Catch-Up: October 4-8

Another busy week for clinical trial news. Here’s a look.

COVID-19-Related

SAB Biotherapeutics dosed the first patient in its Phase III ACTIV-2 COVID-19 trial of SAB-185. SAB-185 is a fully human, specifically targeted, broadly neutralizing polyclonal antibody for non-hospitalized patients with mild to moderate COVID-19. The ACTIV-2 trial is being led by the National Institute of Allergy and Infectious Disease (NIAID), part of the U.S. National Institutes of Health (NIH) in collaboration with the AIDS Clinical Trials Group.

RedHill Biopharma reported new data from the Phase II/III trial of opaganib in hospitalized patients with severe COVID-19 pneumonia. The treatment resulted in a 62% statistically significant decrease in mortality as well as statistically significant improved outcomes in time to room air and median time to hospital discharge. Opaganib has a unique dual antiviral and anti-inflammatory mechanism of action.

Todos Medical is re-evaluating its outpatient trial designs for its oral antiviral 3CL protease inhibitor (Tollovir) in COVID-19. This is in light of Merck and the FDA stopping enrollment after interim analysis of 775 patients demonstrated a 50% decrease in the risk of hospitalization and death in unvaccinated outpatient COVID-19 patients in Merck’s Phase III trial of its antiviral, molnupiravir.

Non-COVID-19-Related

Kyowa Kirin and Amgen announced positive data from a Phase II trial of KHK4083/AMG 451 for moderate-to-severe atopic dermatitis. The drug is a potential first-in-class anti-OX40 fully human monoclonal antibody. The study hit the primary objective, demonstrating statistically greater improvements from baseline in Eczema Area and Severity Index (EASI) score at 16 weeks.

Ultragenyx and Mereo BioPharma Group presented secondary endpoint data on UX143 (setrusumab) from the Phase IIb ASTEROID study for osteogenesis imperfecta (OI).  The drug demonstrated a clear, dose-dependent, statistically significant bone-building effects at multiple anatomical sites. UX143 is a fully human monoclonal antibody that inhibits sclerostin.

Adverum Biotechnologies announced new long-term data from the OPTIC trial of ADVM-022 single, in-office intravitreal injection gene therapy in patients requiring frequent anti-VEGF injection for neovascular or wet age-related macular degeneration. The data followed through two years post-injection.

Janssen’s respiratory syncytical virus (RSV) vaccine demonstrated an 80% efficacy level in adults over the age of 65 in its Phase III CYPRESS trial. It also provided 70% efficacy against any symptomatic RSV-associated acute respiratory infection.

Enanta Pharmaceuticals provided an update on two clinical-stage farnesoid X receptor (FXR) agonists, EDP-305 and EDP-297, for non-alcoholic steatohepatitis (NASH). The Phase IIB ARGON-2 study of EDP-305 as a monotherapy had an interim analysis of a subset of patients through week 12 and Phase I data of EDP0297 provided meaningful data on dose selection and characterization of the drugs. The company has decided to scrap the program and look for out-licensing opportunities.

AlzeCure Pharma dosed the first patient in its Phase I multiple ascending dose study of ACD856 for Alzheimer’s disease. The drug is the lead product in the company’s NeuroRestore platform. Drugs within the platform stimulate several important signaling pathways in the brain.

Revelation Biosciences received approval from the ethics committee in Australia to run a Phase Ib allergen challenge study of REVTx-99 for patients with allergic rhinitis and chronic nasal congestion. The drug stimulates the innate immune system via an alternative pathway (TLR4) to produce protectives cytokines including Type I and Type II interferons.

ContraFect Corporation announced new data from the Phase II trial of exebacase demonstrating rapid symptom resolution in patients with Staphylococcus aureus bacteremia. Exebacase is a recombinantly-produced lysin with potential bactericidal activity against S. aureus.

Incyte announced the full 24-week data from its pivotal Phase III TRuE-V trial of ruxolitinib cream (Opzelura) in adolescent and adult patients older than the age of 12 with nonsegmental vitiligo. Opzelura is a topical JAK inhibitor. The findings showed treatment resulted in greater improvement to vehicle.

Bausch & Lomb and Novaliq GmbH announced statistically significant topline data from the second Phase III MOJAVE trial of NOV03 (perfluorohexyloctane) as a first-in-class eye drop for dry eye disease associated with Meibomian gland dysfunction.

Bayer updated thyroid sub-analysis of 29 adult and pediatric cancer patients with TRK fusions. Of them, 28 were evaluable, and the ones treated with Vitrakvi (larotrectinib) demonstrated overall response rates (ORR) and duration of response (DoR). 

PDS Biotechnology completed enrollment of the first stage of the checkpoint inhibitor naïve arm of its VERSATILE-002 Phase II trial for recurrent and/or metastatic human papillomavirus (HPV16)-associated head and neck cancer. PDS0101 uses PDS’s Versamune platform with targeted antigens in HPV-expressing cancers.

Enlivex Therapeutics published clinical data from its Phase Ib sepsis trial. The data compared 10 patients admitted to the ICU with sepsis who were treated with Allocetra plus standard-of-care with 37 matched controls with sepsis who received only standard-of-care treatment at the same hospital from 2014-2019. Patients receiving Allocetra had a mortality rate of 0% at the end of the 28-day follow-up period compared to a mortality rate of 27% in matched historical controls.

Recce Pharmaceuticals announced the trial registration for RECCE 327 in the Australian New Zealand Clinical Trial Registry for a Phase I intravenous study. R327 is a new class of broad-spectrum anti-infectives. It will be administered as a single dose via a one-hour IV infusion across eight dose cohorts of 10 people each, beginning at 50 mg, or placebo.

X4 Pharmaceuticals completed enrollment in its ongoing pivotal Phase II study of mavorixafor in genetically confirmed WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. This syndrome is a primary immunodeficiency caused by gain-of-function mutations in the CXCR4 gene. Mavorixafor is a first-in-class, small-molecule antagonist of CXCR4.

MannKind Corporation enrolled the first pediatric patient in the INHALE-1 trial of Afrezza (Technosphere Insulin) in combination with basal insulin versus multiple daily injections of insulin in children and adolescents aged 4-17 with type 1 or type 2 diabetes. The trial is a 26-week open-label, randomized trial with a 26-week extension.

Sarepta Therapeutics, in partnership with Roche, initiated the EMBARK pivotal trial of SRP-9001 for Duchenne muscular dystrophy. SRP-9001 is a gene transfer therapy designed to deliver a micro-dystrophin-encoding gene to muscle tissue.

Opthea Limited initiated enrollment in Europe for its Phase III trial of OPT-302 for wet neovascular age-related macular degeneration. The ShORe and COAST registrational trial are expected to each enroll about 990 treatment-naïve patients. The primary endpoint of both trials is mean change in best corrected visual acuity from baseline to week 52 for OPT-302 combination therapy compared to anti-VEGF-A monotherapy.

Covis Pharma published data demonstrating the investigational anticoagulant reversal agent, ciraparantag, reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly patients. The Phase IIa study showed the drug rapidly and effectively reversed the anticoagulant activity of the most commonly used direct oral anticoagulants, apixaban and rivaroxaban.

Altimmune enrolled the first patient in a Phase Ib trial of pemvidutide in non-alcoholic fatty liver disease (NAFLD). Pemvidutide is an GLP-1/glucagon dual receptor agonist.

Cara Therapeutics presented data from the KARE Phase II study of oral difelikefalin for moderate-to-severe pruritus in mild-to-severe atopic dermatitis. The data was from 401 patients with AD and moderate-to-severe pruritis. Although the primary endpoint, change from baseline in Itch Numerical Rating Scale score, was not met with any of the difelikefalin dose groups in the overall population, a significant improvement in itch was observed at week 12 in the combination difelikefalin dose group.

Surface Oncology and Roche announced plans to initiate a Phase II study of SRF388 in combination with atezolizumab and bevacizumab in treatment-naïve hepatocellular carcinoma (HCC). SRF388 is Surface’s first-in-class antibody against IL-27.

Celltrion Healthcare announced two data sets linked to the use of the subcutaneous formulation of Remsima (infliximab) in inflammatory bowel disease (IBD). The first study looked at the impact of switching from IV to SC treatment in Crohn’s disease or ulcerative disease from the pivotal CT-P13 SC study. The switch conferred more favorable outcomes. The second study looked at SC infliximab monotherapy versus combination therapy with immunomodulators from the Phase III CT-P13 SC in active CD or UC. There was no significant difference between groups in the number of patients with C_trough level exceeding target exposure.

Biophytis announced full results from the SARA-INT Phase II trial of Sarconeos in Sarcopenia. There was a significant effect on the primary endpoint of the study in.

RhoVac announced the topline data from its 3-years follow-up of patients who took part in its Phase I/II trial of its RhoC peptide-based vaccination against prostate cancer. From the 1-year follow-up phase, 19 out of 21 patients agreed to participate in the 3-year study and none had progressed significantly in terms of PSA values. All but three had undetectable PSA values.

VYNE Therapeutics announced that the first patient had been enrolled in a Phase III trial in China by its partner Cutia Therapeutics. It is testing Amzeeq (minocycline) topical foam, 4% in moderate to severe acne.

UNITY Biotechnology announced 12-week data from its ongoing Phase I study of UBX1325 in patients with advanced disease from diabetic macular edema (DME) and wet age-related macular degeneration (AMD) in people where anti-VEGF therapy was no longer considered beneficial. UBX1325 is a small molecule inhibitor of Bcl-xL. The drug was showing strong and sustained responses after 12 weeks.

Pep Therapy and Institut Curie dosed the first patients in a Phase Ia/b trial of PEP-Therapy’s PEP-010 for advanced solid tumors. PEP-010 is the first of a new class of therapeutic peptides based on the company’s innovative Cell Penetrating and Interfering Peptides (CP&IP) technology.

Telix Pharmaceuticals dosed the first patient in its Phase II OPALESCENCE trial of TLX250-CDx in triple-negative breast cancer. TLX250-CDx is being developed to determine whether “indeterminate renal masses,” typically identified based on CT or MRI imaging, are either clear cell renal cell cancer (ccRCC) or non-ccRCC, using PET imaging. Girentuximab is a monoclonal antibody that targets CA9. TLX250-CDx is ⁸⁹Zr-girentuximab.

Retrotope cited data from its Phase II/III trial of RT001 in patients with infantile neuroaxonal dystrophy (INAD). They also reported on a concurrent natural history study of INAD patients’ disease onset and progression. INAD is an ultra-rare, progressive, fatal, infant genetic neurological disorder. It is on a spectrum of diseases called PLA2G6-associated neurodegeneration. RT001 is an isotopically stabilized, synthetic linoleic acid (LA) that Retrotope discovered and developed using its technology platform, which combats the oxidative stress and cellular degeneration that comes from lipid peroxidation (LPO). Polyunsaturated fatty acids (PUFAs) make up cell and mitochondrial membranes. The LPO process targets PUFAs. Retrotope’s technology generates stabilized PUFAs, such as RT001, that incorporate into all membranes and can down-regulate LOP to protect membranes from degeneration.

Takeda Pharmaceutical  suspended dosing of patients in two Phase II trials of TAK-994 in narcolepsy. TAK-994 is an oral orexin agonist. The company did not identify the safety concerns inspiring the suspension.

Apexigen announced that Simcere Pharmaceutical dosed the first patient in a Phase III study of BD0801 in combination with chemotherapy for patients with recurrent, platinum-resistant ovarian cancer. BD0801 is a humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF) and is derived from Apexigen’s APXiMAB antibody discovery technology platform.

CoCrystal Pharma received clearance in Australia to launch a Phase I trial for its CC-42344 for pandemic and seasonal influenza A. The drug is an oral PB2 inhibitor.

Elicio Therapeutics dosed the first patient in its Phase I/II study of ELI-002, an investigational lymph node-targeted therapeutic vaccine. It is being tested for treatment for patients with KRAS-driven tumors that have minimal residual tumor cells after surgery to remove the tumor. It is expected to enroll patients with mKRAS+ solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer, non-small cell lung cancer and others.

4D Molecular Therapeutics got the greenlight from the FDA for a Phase I/II trial of 4D-150 for wet age-related macular degeneration. 43-150 is a dual-transgene intravitreal gene therapy.

Intellia Therapeutics received authorization in New Zealand to initiate a Phase I/II trial of NTLA-2002 for adults with hereditary angioedema. NTLA-2002 is a systemically administered single-dose CRISPR/Cas9-based therapeutic engineered to inactivate the Kallikrein B1 gene.

Denali Therapeutics reported positive Phase I data and regulatory progress for two therapeutics it is developing for amyotrophic lateral sclerosis (ALS). The first was for its DNL343, which is from a Phase I trial in healthy volunteers. The drug is an elF2B activator. The data showed the drug was generally well tolerated for up to 14 days, with “robust distribution in the central nervous system.” They also evaluated safety, pharmacokinetics, pharmacodynamics and biomarkers related to the cellular integrated stress response (ISR). ISR is a biological pathway associated with ILS and other disorders. The second program is for SAR443820, which Denali has partnered on with Sanofi. Sanofi presented plans for a Phase II trial of the drug, which is a RIPK1 inhibitor. In the Phase I trial, the drug demonstrated robust target engagement and the drug doses were generally well tolerated. The Phase II HIMALAYA trial is a multi-center, randomized, double-blind, placebo-controlled study, which will be followed by an open-label long-term extension study. It’s expected to launch in the first quarter of 2022.

Timber Pharmaceuticals announced positive topline data from its Phase IIb CONTROL trial of TMB-001 for moderate to severe congenital ichthyosis (CI). The drug is a topical isotretinoin formulated using the company’s patented IPEG delivery system. The primary endpoint was the reduction of targeted ichthyosis severity.

Kinnate Biopharma presented design and rationale details for a Phase I trial of KIN-2787. KIN-2787 is an oral small molecule pan-RAF inhibitor being developed for patients with lung cancer, melanoma, and other solid tumors.

Prelude Therapeutics presented data on its ongoing Phase I trials of oral protein arginine methyltransferase 5 (PRMT5) inhibitors PRT543 and PRT811. They say the Phase I dose escalation trial data is encouraging, with favorable safety profiles and target engagement.

ORIC Pharmaceuticals presented initial data from its ongoing Phase Ib trial of ORIC-101 in metastatic prostate cancer progressing on enzalutamide. The drug is a glucocorticoid receptor antagonist. The combination was well tolerated without evidence of drug-drug interaction affecting enzalutamide dosing and has shown preliminary antitumor activity.

GeneTx Biotherapeutics and Ultragenyx Pharmaceutical dosed the first patient in the Phase I/II trial in Canada of GTX-102 for Angelman syndrome. GTX-102 is an antisense oligonucleotide delivered via intrathecal administration and targets and inhibits expression of UBE3A-AS.

Acumen Pharmaceuticals dosed the first patient in INTERCEPT-AD, a Phase I trial of ACU193 for Alzheimer’s disease. ACU193 is a monoclonal antibody that targets toxic amyloid-beta oligomers.

G1 Therapeutics announced results from a retrospective analysis of the pooled results of three trials of Trilaciclib. The data showed that patients with extensive-stage small-cell lung cancer who received the drug before each chemotherapy regimen had significantly lower use of supportive care therapies for chemotherapy-induced myelosuppression compared to the placebo group. Cosela (Trilaciclib) is indicated for exactly that in adult patients who are receiving a platinum-etoposide-containing therapy or topotecan-containing regimen for extensive-stage small cell lung cancer.

Jounce Therapeutics initiated patient enrollment in INNATE tumor-specific expansion cohorts for both JTX-8064 monotherapy and combination therapy with the company’s own internal PD-1 inhibitor, pimivalimab. JTX-8064 is a tumor-associated macrophage candidate, a humanized IgG4 monoclonal antibody that specifically binds to the macrophage receptor Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4).

Turning Point Therapeutics presented additional preliminary clinical data from the ongoing trials of repotrectinib and elzovantinib, a novel MET/SRC/CSF1R inhibitor. Repotrectinib data was from Phase II TRIDENT-1 trial in ROS1-positive TKI-pretreated advanced NSCLC cohorts. The elzovantinib was from a Phase I SHIELD-1 trial in gastric or gastroesophageal junction cancer, colorectal cancer, and other solid tumors harboring MET gene alterations.

Brickell Biotech announced positive topline data from the Phase III pivotal Cardigan I and II trials of sofpironium bromide gel, 15% as a once daily topical formulation for excessive underarm sweating (primary axillary hyperhidrosis). The data demonstrated early, sustained and significant improvements in signs and symptoms across all efficacy measures and was generally well-tolerated over six weeks.

Nkarta announced that they had dosed the first patient in the Phase I trial of NKJX019 in advanced B-cell malignancies. NKX019 is an NK cell immunotherapy targeting CD19. They also reported that they expect initial data from the Phase I trial of NKX101 in the first half of 2022. ThNKX101 is an engineered CAR NK cell therapy targeting the NKG2D ligand in patients with relapsed or refractory acute myeloid leukemia or higher-risk myelodysplastic syndromes.

Mirati Therapeutics and Sanofi are partnering to evaluate Mirari’s adagrasib with Sanofi’s SAR442720 in previously-treated non-small cell lung cancer (NSCLC) and KRAS^G12C mutations. Adagrasib is a KRAS^G12C inhibitor. SAR442720 is a SHP2 inhibitor.

Allogene Therapeutics announced it was halting a trial of its AlloCAR T cancer therapy after identifying a chromosomal abnormality in a patient. The issue was found after a bone marrow biopsy to evaluate the patient for pancytopenia. The patient has Stage IV transformed follicular lymphoma and c-myc rearrangement.

Cyprium Therapeutics, a Fortress Biotech partner company, with support from Sentynl Therapeutics, a wholly owned subsidiary of Cadila Healthcare, announced positive data from two completed trials in patients with CUTX-101 for Menkes disease. CUTZX-101 is a copper histidinate (CuHis). Both studies demonstrated significantly greater median OS compared to untreated historical control patients.