Clinical Catch-Up: December 6-10

There were a lot of clinical trial announcements this week, driven by the European Society for Medical Oncology (ESMO) annual conference. Here’s a look.

COVID-19-Related

Johnson & Johnson announced preliminary data from a subset of participants in its COV2008 study run at Beth Israel Deaconess Medical Center. It demonstrated that a booster of the J&J COVID-19 vaccine given six months after a two-dose regimen of the Pfizer-BioNTech COVID-19 vaccine increased both antibody and T-cell responses. This supports other studies suggesting that a mix-and-match approach to the booster regimens works fine.

Molecular Partners presented results from the Phase IIa trial of ensovibep for COVID-19 patients. The drug appeared safe and well tolerated and there was a viral load decline comparable for both dose levels. Ensovibep is an antiviral drug. 

GlaxoSmithKline and Medicago announced positive results from the Phase III trial of Medicago’s plant-based COVID-19 vaccine in combination with GSK’s adjuvant. The trial was run in 24,000 participants in six countries. The vaccine also demonstrated efficacy in several variants, which are the ones predominantly circulating. The vaccine rate against all variants was 71%. In people with no previous exposure, it was 75.6%, and 75.3% against Delta, 88.6% against Gamma. No cases of Alpha, Lambda, Mu or Omicron were circulating during the study.

Non-COVID-19-Related

Aeglea Biotherapeutics reported what initially appears to be positive outcomes for its Phase III PEACE trial of pegzilarginase in Arginase 1 Deficiency (ARG1-D). ARG1-D is a rare, progressive and debilitating disease marked by high levels of the amino acid arginine. Symptoms include spasticity, developmental delay, intellectual disability and seizures. The trial hit the primary endpoint of a statistically significant drop in plasma arginine from baseline after 24 weeks of treatment. It also showed a “positive trend” in Gross Motor Function Measure Part E (GMFM-E), which is a key clinical assessment of the patients’ physical abilities, such as the ability to walk, run and jump.

Stoke Therapeutics presented data on the effectiveness of its STK-001 in Dravet syndrome. The drug showed that 70.6% of patients receiving the drug had a decrease in convulsive seizure frequency between Day 29 and Day 84. The drug upregulates NaV1.1 protein expression by harnessing the wild-type copy of the SCN1A gene.

Kazia Therapeutics announced positive Phase II study of paxalisib in glioblastoma. The median OS in the ITT population was 15.7 months compared to 12.7 months which had been seen in historical data on patients treated with temozolomide.

Mesoblast reported data from the DREWAM-HF Phase III trial of rexlemestrocel-L in patients with chronic heart failure and low ejection fraction (HFrEF) and diabetes and/or myocardial ischemia. The patients benefited the most in major adverse cardiovascular events (MACE) in terms of a non-fatal heart attack or stroke, or cardiovascular death.

Biohaven Pharmaceutical announced topline results from the second pivotal trial of intranasal zavegepant for acute migraine in adults. The study hit the regulatory endpoints of pain freedom and freedom from most bothersome symptom at two hours. The drug is a CGRP receptor antagonist.

Adicet Bio reported positive interim data from its Phase I trial of ADI-001 for B-cell Non-Hodgkin’s Lymphoma. ADI-001 is an allogeneic gamma delta CAR-T cell therapy. It generated positive early responses from three of four participants who could be evaluated, two who achieved complete responses (CR) and one a partial response (PR) that the researchers called “near complete.”

Adagene announced clinical data on its ADG116 and ADG106. ADG116 is an anti-CTLA-4 monoclonal antibody and the results were from an ongoing dose-escalation study of it as a monotherapy in advanced metastatic tumors. ADG116 is an anti-CD137 agonist being investigated in advanced solid tumors. The drug was well tolerated.

Cyclo Therapeutics received the go-ahead from the FDA for a Phase II trial of Trappsol Cyclo for early Alzheimer’s disease. Trappsol Cyclo is a proprietary formulation of hydroxypropyl beta cyclodextrin.

Surface Oncology presented new data from the ongoing Phase I study of SRF617. It is an antibody targeting CD39. It showed promising signs of activity as a monotherapy and in combination with chemotherapy and Merck’s Keytruda (pembrolizumab).

Biofrontera enrolled the first participant in a Phase I trial of photodynamic therapy (PDT) for actinic keratosis (AK) using three tubes of Ameluz together with the company’s BF-RHodoLED XL lamp. Ameluz is an FDA-approved drug indicated for the treatment of actinic keratoses, a precancerous skin condition.

PDS Biotechnology Corporation announced the reopening of recruitment in the NCI-led Phase II trial of PDS0101 (Versamune-HPV16) in combination with two investigational immune-modulating agents in advanced HPV cancers. PDS010 combines its Versamune platform with targeted antigens in HPV16-expressing cancers.

NGM Biopharmaceuticals announced a clinical trial collaboration and supply deal with Merck to evaluate NGM707 with Merck’s Keytruda in a Phase I/II trial as a monotherapy and combination in adults with advanced or metastatic solid tumors with elevated ILT2 and ILT4 expression. NGM707 is an ILT2/ILT4 dual antagonist antibody.

Ventyx Biosciences dosed the first patient in a Phase II trial of VTX002 for moderate-to-severe ulcerative colitis. The drug is a peripherally-restricted, potent and selective, oral small molecule modulator of the S1P1 receptor.

IO Biotech is launching a trial with Merck to test its IO102-IO103 in combination with Merck’s Keytruda in previously untreated patients with three different tumor types — metastatic non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), and metastatic urothelial bladder cancer. IO102-IO103 is a novel immunotherapeutic that targets mechanisms mediated by immunosuppressive proteins such as Indoleamine 2,3-dehydrogenase (IDO) and PD-L1.

Bellicum Pharmaceuticals announced positive interim data from its ongoing Phase I/II GoCAR-T trials, including a confirmed partial response in the first cohort of mCRPC patients in the trial treated with BPX-601. The drug is a dual-switch GoCAR-T product using Bellicum’s iMC activation and CaspaCIDe safety switch technologies.

Purple Biotech initiated Part 2 of its ongoing Phase I/II trial of NT219 for multiple cancers. The drug is a novel small molecule inhibiting IRS1/2 and STAT3 simultaneously.

GH Research reported the successful outcome of the Phase 2 Part of the Phase I/II trial of GH001 in treatment-resistant depression. The drug is an inhalable 5-MeO-DMT product.

Catalyst Pharmaceuticals and DyDo Pharma initiated a Phase III trial in Japan of Catalyst’s Firdapse (amifampridine) for Lambert-Eaton myasthenic syndrome. The drug is an oral, nonspecific, voltage-dependent, potassium channel blocker.

Fulcrum Therapeutics announced positive results from the 20mg and 30mg dose cohorts in healthy adults in its Phase I trial of FTX-6058. FTX-6058 is an oral HbF inducer being developed for sickle cell disease and other hemoglobinopathies like beta-thalassemia.

Kronos Bio dosed the first patient in the Phase III AGILITY trial of entospletinib in combination with standard of care anthracycline and cytarabine (7+3) chemotherapy in acute myeloid leukemia. The drug is a selective inhibitor targeting spleen tyrosine kinase (SYK).

MediWound completed patient enrollment in its Phase II trial of EscharEx in debridement of venous leg ulcers compared to gel vehicle and non-surgical standard-of-care. EscharEx is a bioactive therapy, a concentrate of proteolytic enzymes enriched in bromelain.

SpringWorks Therapeutics dosed the first patient in the Phase Ib/II trial of nirogacestat in combination with elranatamab in r/r multiple myeloma. Nirogacestat is SpringWorks gamma secretase inhibitor. Elranatamab is Pfizer’s B-cell maturation antigen (BCMA) CD3-targeting bispecific antibody.

Sequana Medical  completed patient enrollment in the Phase III POSEIDEON trial to support the alfapump system for treatment of recurrent or refractory ascites due to liver cirrhosis. The alfapump is a fully implanted wireless device that automatically pumps fluid from the abdominal cavity into the bladder.

Hutchmed completed patient enrollment of FRESCO-2, its Phase III trial of fruquintinib for metastatic colorectal cancer. Fruquintinib is a highly selective and potent oral VEGFR-1, -2 and -3 inhibitor.

HiberCell presented new data from the ongoing Phase II trial of odetiglucan (Imprime PGG) with Merck’s Keytruda in metastatic breast cancer. Odetiglucan is a Dectin-1, pattern recognition receptor agonist. The data supports the combination enhances mBCA patient sensitivity to checkpoint inhibitors in patients who have progressed through hormonal therapy with a CDK4/6 inhibitor.

Vaccitech reported promising interim data in its Phase Ib/IIa HBV002 trial in chronic Hepatitis B. It demonstrated noted changes in the surface antigen levels, especially in a group receiving low-dose nivolumab with the heterologous boost (VTP-300). 

Aligos Therapeutics presented new clinical data from its Phase Ib study of ALG-000184 in Hepatitis B. After once daily oral dosing for 28 days with 100 mg, there was a measurable reduction of HBV DNA and HBV RNA. 

Recce Pharmaceuticals updated its Phase I/II trial of RECCE 327 in patients with infected burn wounds. The antibiotic demonstrated visible infection reduction in less than 24 hours in all patients.

MeiraGTx announced positive preliminary data from the ongoing Phase I AQUAx trial of AAV-hAQP1 for grade 2/3 radiation-induced xerostomia (RIX). AAV-hAQP1 is an investigational gene therapy.

Prometheus Biosciences reported positive topline data from its Phase I trial of PRA023. The company also announced it is adding a third indication for the drug, Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD), with a Phase II trial to start in the first quarter of 2022. PRA-23 is an IgG1 humanized monoclonal antibody that blocks tumor necrosis factor-like ligand 1A. It is being developed for ulcerative colitis, Crohn’s disease, and now SSc-ILD.

Daiichi Sankyo and AstraZeneca presented new data from the TROPION-PanTumor-1 Phase I trial of datopotamab deruxtecan for metastatic triple negative breast cancer with disease progression after standard treatment. The drug is a TROP2 directed DXd antibody drug conjugate.

Checkpoint Therapeutics initiated the Phase III CONTERNO trial of cosibelimab with chemotherapy in first-line non-squamous non-small cell lung cancer (NSCLC). Cosibelimab is a potential best-in-class anti-PD-L1 antibody licensed from the Dana-Farber Cancer Institute.

Celldex dosed the first patient in a Phase I trial of CDX-0159 for prurigo nodularis. CDX-0159 is a humanized monoclonal antibody that binds to the receptor tyrosine kinase KIT.

SOTIO Biotech inked a deal with Merck to run a Phase II AURELIO-04 study of SOTIO’s SOT101, an IL-15 superagonist with Merck’s checkpoint inhibitor Keytruda in selected advanced/refractory solid tumors.

Affimed initiated patient recruitment for its Phase I/IIa trial of AFM24 in combination with Roche’s anti-PD-L1 checkpoint inhibitor Atezolizumab. AFM24 is an innate cell engager. It is being evaluated in solid tumors.

MRM Health dosed the first patient with MH002 in a Phase Ib/IIa multi-center trial in mild-to-moderate ulcerative colitis. The therapy is the first candidate from the company’s CORAL platform, which leverages disease-driving mechanisms to guide therapeutic microbial strain selection.

CSL Behring and uniQure announced that their etranacogene dezaparvovec hit the pre-specified primary endpoint in their Phase III clinical trial in severe to moderately severe hemophilia B. The therapy is an investigational adeno-associated virus five (AAV5)-based gene therapy. The primary endpoint was non-inferiority in annualized bleeding rate (ABR) 18 months after administrated compared to baseline Factor IX (FIX) prophylactic therapy. Etranacogene dezaparvovec delivers a gene cassette with the patent-protected Padua variant of Factor IX. It is transported in an AAV5 viral vector.

IO Biotech published results from its Phase I/II MM1636 Melanoma trial. It evaluated IO102-IO1-3, a multi-antigen immunotherapeutic, in combination with Bristol Myers Squibb’s Opdivo (nivolumab) in melanoma.

Dermavant Sciences published results from its PSOARING 1 and 2 Phase III trials for tapinarof topical cream in plaque psoriasis in adults. The drug is a novel, steroid-free, therapeutic aryl hydrocarbon receptor (AhR) modulating agent. It demonstrated efficacy across virtually all study endpoints.

Acer Therapeutics announced the FDA cleared its IND for a Phase I trial of ACER-801 (osanetant) for induced Vasomotor Symptoms (iVMS). Osanetant is a selective non-peptide neurokinin 3 receptor (NK3R) antagonist.

Clover Biopharmaceuticals and Ascentage Pharma will collaborate on a Phase Ib/II trial of Clover’s SCB-313 and Ascentage’s APG-1387 for advanced peritoneal carcinomatosis. SCB-313 is a recombinant human TRAIL-Trimer fusion protein. APG-1387 is a second mitochondria-derived activator of caspase (SMAC)-mimetic/inhibitor of apoptosis proteins (IAP) antagonist.

Aligos Therapeutics initiating dosing in its Phase I trial of ALG-055009 for nonalcoholic steatohepatitis (NASH). The drug is a thyroid hormone receptor beta (THR-b) agonist.

CinCor Pharma dosed the first subject in the brigHTN Phase II trial of CIN-107. CIN-107 is a once daily, highly selective aldosterone synthase inhibitor being developed for treatment resistant hypertension.

Brainsway published results from its clinical trial of Deep TMS System for adults with alcohol use disorder. The primary endpoint was reduction in percentage of heavy drinking days over a 122-week period. Deep TMS is a Deep Transcranial Magnetic Stimulation platform technology.

Aurinia Pharmaceuticals announced positive topline data from the AURORA 2 continuation study of Lupkynis (voclosporin) for adults with active lupus nephritis. Lupkynis is the first FDA-approved oral treatment for adults with active lupus nephritis. It is a structurally modified calcineurin inhibitor with a dual mechanism of action.

Novartis announced positive results from year two of the Phase III trial of Beovu (brolucizumab) in diabetic macular edema. The data confirmed the visual acuity gains, fluid reduction and safety profile from year one.

Roche announced promising results for its anti-TIGIT checkpoint inhibitor tiragolumab in PD-L1-positive metastatic non-small cell lung cancer. TIGIT is an immune receptor found on some T cells and natural killer (NK) cells. After two-and-a-half years median follow-up, the combination continued to demonstrated improvement in the intention-to-treat (ITT) population, particularly driven by the population with high PD-L1 levels. In the ITT group, the combination decreased risk of progression-free survival (PFS) by 38% and improved overall response rates (ORR) by 38.8% compared to 20.6% for Tecentriq alone.

Intensity Therapeutics presented promising data on its intratumoral therapy INT230-6 at the SABCS. The therapy is being tested both with and without Merck’s checkpoint inhibitor Keytruda (pembrolizumab) in heavily pretreated refractory breast cancer patients in a Phase I/II trial.

Infinity Pharmaceuticals presented updated data from the ongoing MARIO-3 Phase II trial of eganelisib in combination with Roche’s Tecentriq (atezolizumab) and Abraxane (nab-paclitaxel) in frontline metastatic triple negative breast cancer (TNBC). Eganelisib is a first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic. Tumor reductions in 88.6% of evaluable patients were associated with a disease control rate of 81.4% in patients with PD-L1 negative tumor.

Novartis announced new data on its Phase II BYLieve trial of Piqray (alpelisib). It is an ongoing Phase II, open-label, 3-cohort non-comparative trial of Piqray with endocrine therapy, including men and pre- and postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer who have progressed on or after previous therapies, including CDK4/6 inhibitor plus endocrine therapy.

Arvinas and Pfizer announced an update on its Phase I trial of ARV-471 in locally advanced or metastatic ER-positive/HER2-negative breast cancer. ARV-471 is a novel PROTAC estrogen receptor degrader being co-developed by the companies. The drug demonstrated antitumor activity in CDK4/6 inhibitor-pretreated patients with clinical benefit rate (CBR) of 40% in the 47 patients who could be evaluated. Three patients had confirmed partial responses (PR). The drug demonstrated a favorable tolerability profile.

Moderna announced positive interim results from its experimental seasonal influenza vaccine. In early data from a Phase I trial of the quadrivalent flu vaccine (mRNA-1010), they reported it successfully boosted titers against all four strains in older and younger adults. The company also announced it has fully enrolled a Phase II trial of the vaccine that will compare it against existing vaccines on the market.

BeyondSpring Pharmaceuticals presented additional analyses from the Phase III portion of the PROTECTIVE-2 trial of plinabulin and pegfilgrastim for prevention of chemotherapy-induced neutropenia (CIN) in breast cancer patients. The combination significantly alleviates pegfilgrastim-related bone pain, decreases toxicity and improves health related quality-of-life.

UCB announced positive topline results from the Phase III MycarinG study of rozanolixizumab for generalized myasthenia gravis. The drug is a subcutaneously infused monoclonal antibody targeting FcRn.