RHOC

With the American Society of Clinical Oncology (ASCO) Annual Meeting being held over the weekend, it was a hectic week for clinical trial news and updates. Here’s a look at just some of them. COVID-19-Related The National Institutes of Health (NIH) reported results from part of its Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) trial, specifically its ACTIVE-1 Immune Modulators clinical trial. The study found that both Bristol Myers Squibb’s Orencia (abatacept) and Johnson & Johnson's Remicade (infliximab) demonstrated a strong but not statistically significant improvement in time to recovery by the day of discharge from the hospital. This was the primary endpoint of the study. There were also substantial improvements in the trial’s key secondary endpoints of mortality and clinical status at 28 days. Non-COVID-19-Related Immutep presented new interim data from Part A of its Phase II TACTI-002 in first-line non-small cell lung cancer (NSCLC). The study is evaluating eftilagimod alpha in combination with Merck’s anti-PD-L1 checkpoint inhibitor Keytruda (pembrolizumab). Eftilagimod is a soluble LAG-3 protein. The drug combination demonstrated an improved overall response rate (ORR) of 37.3% in its intent to treat population and compared to 36.1% presented at last year’s ASCO meeting. Responses were seen in all PD-L1 subgroups with 32% ORR in patients with no or low PD-L1 levels, and the combination demonstrated an improved disease control rate of 73.3% compared to 66.7% at last year’s meeting. The company is also presenting an abstract for the design of its ongoing Phase IIb TACTI-003 trial at the meeting. That trial is evaluating the same drug combination as first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma. InxMed presented data from its Phase Ib trial of IN10018 in platinum-resistant recurrent ovarian cancer. The drug is an oral inhibitor of focal adhesion kinase. It was dosed with pegylated liposomal doxorubicin. Denali Therapeutics and Biogen initiated dosing on the Phase IIb LUMA trial of BIIB122 in early-stage Parkinson’s disease. BIIB122 is an investigational small molecule inhibitor of LRRK2 discovered and developed by Denali. Secarna Pharmaceuticals announced its partner Lipigon Pharmaceutical dosed the first patient in its Phase I trial of Lipisense. Lipisense is an antisense oligonucleotide for rare lipid-related diseases. PDS Biotechnology announced the expansion of its VERSATILE-002 trial of PDS0101 in combination with Merck’s Keytruda. PDS0101 is based on the company’s Versamune system and Infectimune T-cell activating technology platforms. Celltrion Healthcare presented post-hoc analysis of pivotal Phase III studies showing that the subcutaneous formulation of Remsima (infliximab) was associated with significantly greater clinical outcomes than IV formulation of the drug at week 30 in patients with rheumatoid arthritis. The drug is biosimilar to infliximab. Attgeno completed its Phase I trial of Supernitro for acute pulmonary hypertension. Supernitro is a potent substance that works by releasing NO in the pulmonary blood vessels. Attgeno also received the go-ahead in Sweden to initiate a Phase II trial of Supernitro for acute pulmonary hypertension after cardiac surgery. RhoVac AB reported that its RV001 (onilcamotide) failed to demonstrate its superiority over placebo in the Phase IIb BRaVac trial in prostate cancer and biochemical recurrence after curative therapy. RV001 stimulates the T-cells to spot and destroy cells that carry the RhoC protein. BioMarin Pharmaceutical announced updated results from its ongoing Phase I/II trial of valoctocogene roxaparvovec in severe hemophilia A. The drug is investigational gene therapy. Eureka Therapeutics and City of Hope treated the first patient with GPC3-positive advanced hepatocellular carcinoma (HCC) with ECT204, an experimental T cell therapy. The therapy targets ARTEMIS T cells. Horizon Therapeutics announced data from the Phase III trial of Uplizna in neuromyelitis optica spectrum disorder (NMOSD) patients with genetic variations. Uplizna is a highly specific CD19 B-cell depleting agent that targets an extended range of B cells. TScan Therapeutics received the go-ahead from the FDA to evaluate TSC-101 for hematologic malignancy patients undergoing allogeneic hematopoietic cell transplantation. TSC-101 targets the minor histocompatibility antigen HA-2. PolyPid completed enrollment in the Phase III SHIELD I study of D-PLEX100 for the prevention of surgical site infections in abdominal surgery. D-PLEX100 leverages Polymer-Lipid Encapsulation matrix (PLEX) technology with Active Pharmaceutical Ingredients for a prolonged and continuous release of the broad-spectrum antibiotic doxycycline. AffaMed Therapeutics dosed the first patient in its Phase I trial of AM712 for retinal diseases. The drug is a bispecific biologic molecule blocking both VEGF and Ang-2. BlueRock Therapeutics completed enrollment of its Phase I trial of pluripotent stem cell-derived dopaminergic neurons in Parkinson’s disease. The goal is to evaluate the safety, tolerability and preliminary efficacy of BRT-DA01. Antengene Corporation dosed the first patient in the Phase I STAMINA-001 trial of ATG-037 for patients with locally advanced or metastatic solid tumors. It is being tested alone and in combination with Merck’s Keytruda. ATG-037 is an oral small molecule CD73 inhibitor. Eledon Pharmaceuticals announced positive topline data from its Phase IIa trial of Tegoprubart for amyotrophic lateral sclerosis (ALS). The drug is a humanized monoclonal antibody that inhibits CD40 Ligand (CD40L). PAI Life Sciences dosed the first patient in a trial of SchistoShield, the company’s preventive vaccine against schistosomiasis. Schistosomiasis is caused by parasitic flatworms. Memo Therapeutics initiated a Phase I trial of MTX-005 against BK polyomavirus infection in renal transplant patients. The drug is a therapeutic antibody that neutralizes all strains of BKV at extremely low concentrations. Axsome Therapeutics published results from the pivotal Phase III GEMINI trial of AXS-05 (dextromethorphan-bupropion) in major depressive disorder (MDD). It was published in The Journal of Clinical Psychiatry. The study demonstrated rapid, substantial and statistically significant improvement in depressive symptoms and induction of remission. The drug is an NMDA receptor antagonist, using a proprietary formulation and dose of dextromethorphan and bupropion. Sage Therapeutics and Biogen reported their Phase III SKYLARD study demonstrated promising results for women with severe postpartum depression. The trial evaluated zuranolone, an oral GAMA signaling pathway modulator. NeuroSense Therapeutics enrolled the first patient in its Phase IIB PARADIGM trial of PrimeC for amyotrophic lateral sclerosis (ALS). The drug is a novel, patented formulation of specific doses of two FDA-approved drugs, ciprofloxacin and celecoxib. ReAlta Life Sciences dosed the first patient in its Phase Ib inhaled lipopolysaccharide (LPS) challenge trial in support of RLS-0071 for severe asthma. RLS-0071 is a dual-action complement inhibitor and innate anti-inflammatory peptide in development for hypoxic ischemic encephalopathy, severe asthma, and other rare diseases. NeoTX completed the first stage of a Simon 2 stage Phase IIa trial of naptumomab estafenatox (NAP) in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) patients previously treated with chemotherapy and checkpoint inhibitors. NAP is a Tumor Targeted Superantigen (TTS) molecule; TTS binds a genetically engineered bacterial determinant to the tumor surface while simultaneously activating an expanding tumor specific immune cells that are redirected from the periphery to the tumor. Indivior enrolled the first patient in the Phase IIb trial of AEF0117 for moderate to severe cannabis use disorder. The drug is a first-in-class synthetic Signaling Specific Inhibitor. TauRx Pharmaceuticals announced unblinding of initial data from the completion of the randomized part of their Phase III LUCIDITY trial of HMTM for Alzheimer’s disease. Participants receiving the drug showed a substantially slower rate of decline. AbbVie presented full results from two studies from the Phase III SELECT-AXIS 2 program of Rinvoq (upadacitinib) in active non-radiographic axial spondylarthritis and patients with treatment-refractory active ankylosing spondylitis with an inadequate response to biologic disease-modifying antirheumatic drugs. Both studies hit the primary endpoints. AlgoTx received clearance from the FDA for a Phase II trial of ATX01 for chemotherapy-induced peripheral neuropathy. The trial will be in the pain of CIPN in adult cancer survivors. SynDevRx opened a Phase Ib/II trial of evexomostat in triple-negative breast cancer and baseline insulin resistance. The drug will be tested in combination with standard-of-care treatment Halaven (eribulin). Evexomostat binds irreversibly to MetAP2, triggering downstream improvements in the metabolic hormones insulin, leptin and adiponectin, regulation of key lipids, and inhibiting of the bFGF and VEGF-C. Dyve Biosciences presented data from the Phase II TARGETS study of DYV702 for pain associated with acute gout flares. DYV702 is a patented transdermal cream formulation of sodium bicarbonate. Trethera announced that the independent safety review committee unanimously recommends further trial advancement after reviewing favorable data from the Phase Ia dose escalation trial of TRE-515. The drug is a first-in-class deoxycytidine kinase inhibitor to treat solid tumors. Abivax published results from its Phase IIa trial of obefazimod for moderate to severe active rheumatoid arthritis. The drug has a novel mechanism of action based on the upregulation of a single, specific micro-RNA with anti-inflammatory properties called miR-124. Bristol Myers Squibb announced results from the primary analysis of the Phase II PILOT trial of Breyanzi (lisocabtagene maraleucel) in r/r large B-cell lymphoma after first-line therapy in patients who were not deemed candidates for high-dose chemotherapy and hematopoietic stem cell transplant. Breyanzi is a CAR-T therapy. Alterity Therapeutics initiated enrollment in its Phase II trial of ATH434 for Multiple System Atrophy. MSA is a rare neurodegenerative disease similar to Parkinson’s. ATH434 is engineered to decrease the toxic accumulation of alpha-synuclein and preserve nerve cells by restoring normal iron balance in the brain. Viracta Therapeutics announced that the Safety Monitoring Committee for its ongoing Phase Ib/II trial of Nana-val in patients with EBV+ solid tumors has approved advancing to the next dose level. Nana-val (nanatinostat and valganciclovir): nanatinostat is an oral histone deacetylase (HDAC) inhibitor being developed by Viracta. Valganciclovir is an antiviral agent. InVivo Therapeutics completed enrollment in the INSPIRE 2.0 Study for acute spinal cord injury patients. The trial is to evaluate the Neuro-Spinal Scaffold. MaaT Pharma announced the completion of its Phase Ib CIMON trial of MaaT033 in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HRMS) having received intensive chemotherapy. The drug is a high-richness, high-diversity Microbiome Ecosystem Therapy (MET). VecctivBio dosed the first two patients in the Phase II STARGAZE trial of apraglutide in steroid-refractory gastrointestinal acute Graft-versus-Host Disease. The drug is a next-generation, long-acting GLP-2 analog. Vaxart reported positive preliminary data from its recently completed Phase Ib trial of its oral norovirus vaccine candidate in elderly adults. The data demonstrated a robust immune response across all doses. Braxia Scientific Corp. presented positive preliminary data from a Phase II trial of psilocybin-assisted therapy for treatment resistant depression. The data supported the feasibility of the company’s proprietary psilocybin-assisted therapy protocol with clinically meaningful improvements in depression severity. Cullinan Oncology presented updated data from its Phase I/IIa trial of CLN-081 in EGFR Exon 20 insertion mutation positive NSCLC. The drug is an orally available small molecule, next-generation, irreversible EGFR inhibitor. Biogen and Ionis Pharmaceuticals announced the Phase III VALOR trial results and an open-label extension (OLE) trial of tofersen for amyotrophic lateral sclerosis (ALS). Toferson is an antisense drug that binds to SOD1 messenger RNA (mRNA), helping it degrade by RNase-H, which decreases the synthesis of SOD1 protein production. Novo Nordisk announced results from two Phase IIIa trials of icodec, the company’s once-weekly insulin. It was non-inferior to Sanofi’s insulin glargine, Lantus. Acelyrin, Affibody and Inmagene Biopharmaceuticals reported positive Phase II data of izokibep in psoriatic arthritis. The drug appears to have better efficacy than current standard of care. Izokibep is an antibody mimetic, IL-17A inhibitor. Legend Biotech received clearance from the FDA for a Phase I trial of LB1908. The drug is an autologous CAR T-cell therapy targeting Claudin 18.2 through a high-affinity VHH antibody for the treatment of adults with r/r gastric, esophageal or pancreatic cancers. Daiichi Sankyo presented data from a Phase I/II trial demonstrating patritumab deruxtecan demonstrated clinically meaningful and durable responses in two early-stage trials in previously treated patients with HER3 expressing metastatic breast cancer or advanced NSCLC without EGFR-activating mutations. The drug is a potential first-in-class HER3 directed antibody drug conjugate. Novocure and Zai Lab announced that their Phase II pilot study of Tumor Treating Fields (TTF) with standard-of-care as first-line treatment in gastric adenocarcinoma hit its primary endpoint of objective response rate with supportive signals across secondary endpoints. TTF is an investigational device for the treatment of gastric cancer, using electric fields that disrupt cancer cell division. OliX Pharmaceuticals completed patient enrollment in the Phase IIa trial of OLX101A. OLX101A is an investigational therapy for the treatment of hypertrophic scars. Incannex Healthcare announced positive data from the Phase II trial of IHL-42X for obstructive sleep apnea. The drug is a form of unique medical cannabis. Biogen and Bio-Thera Solutions presented positive Phase III data for BIIB800. The drug is a biosimilar candidate referencing Genentech’s Actemra/Roactemra (tocilizumab), an anti-interleukin-6 receptor monoclonal antibody. OncXerna Therapeutics presented new clinical data from an investigator-sponsored Phase II trial of bavituximab combined with chemoradiation and adjuvant temozolomide in newly diagnosed glioblastoma (GBM) patients. Bavituximab is a potentially first-in-class phosphatidylserine (PS) inhibitor. Kazia presented positive final data from a Phase II trial of paxalisib in newly diagnosed GBM. The drug is a brain-penetrant inhibitor of the PI3K/Akt/mTOR pathway. PTC Therapeutics announced encouraging preliminary safety and efficacy data from its Phase Ib trial of unesbulin in advanced leiomyosarcoma (LMS) patients. The drug is an oral tubulin binding agent that arrests tumor cells in the G2/M phase, including cancer stem cells. The Janssen Pharmaceutical Companies of Johnson & Johnson announced primary data from the Phase III SHINE trial. It demonstrated that the combination of once-daily oral Umbruvica (ibrutinib) plus bendamustine-rituximab (BR) and rituximab maintenance significantly decreased the risk of disease progression or death by 25% in patients 65 years or older with newly diagnosed mantle cell lymphoma (MCL).

RhoVac AB announced Tuesday that its prostate cancer drug candidate failed to meet targets in a Phase IIB study. Results for RV001 (onilcamotide) failed to demonstrate the drug's superiority over the placebo in the Phase IIb BRaVac trial. The study began in late 2019 and evaluated patients with prostate cancer and biochemical recurrence after undergoing curative therapy. Data from RhoVac's Phase I/II trial was positive, offering hope for a potentially successful study. The U.S. Food and Drug Administration even gave RV001 a Fast Track Designation in November 2020 because of these initial observations. However, while the drug demonstrated safety, the same could not be said in terms of efficacy. The BRaVac trial showed that RV001 was unable to meet its primary endpoint of demonstrating superiority over the placebo in reducing the risk for progression. The initial data also did not show any significant data on improved outcomes. "Even though we know that benchmarks state that the probability of success for a phase II project in oncology is less than 50% and that clinical development is always a calculated risk, we are surprised and deeply saddened to find that BRaVac failed to meet its primary endpoint," Anders Månsson, chief executive officer of RhoVac said in a statement. "We will immediately minimize expenditure, while further assessing the study data, with the aim of coming up with firm recommendations on how to proceed, and to communicate this end June." RV001 is an immuno-oncologic drug that presents to the immune system as an antigen. It works by stimulating the T-cells to spot and destroy cells that carry the RhoC protein, which is over-expressed when cancer cells are metastatic. It is not designed to address solid tumors and only targets metastatic cancer cells in early formation. As of this writing, the treatments used to deal with primary tumors typically involve surgery or radiation therapy which, although effective, still leave a large unmet need for treatments that would prevent recurrence after primary tumor therapy. Based on results from the BRaVac trial alone, the company acknowledges that no license or acquisition deal will be happening anytime soon. For now, RhoVac will focus on analyzing its expenditures and devising a contingency plan. The BRaVac study enrolled its first patient in the U.K. in January 2021, to recruit more than 175 participants in six European countries and the U.S. In early 2022, the Canadian Intellectual Property Office issued a Notice of Allowance, granting the patent application for RV001, similar to the patents granted previously in Japan, Europe and the U.S.

Swedish biotech RhoVac saw its shares plummet by 90% Monday after its lead cancer vaccine candidate failed a Phase II study. In approximately 180 patients, the treatment did not stop progression of prostate cancer compared to placebo in patients who showed signs of cancer recurrence. The biotech did not sugarcoat the news, saying in its press release that “the primary outcome analysis obviously offers little hope of a license or acquisition deal based on the results of this study alone.” In follow-up analysis, the company hopes that it may be able to find a patient subgroup that may benefit from its lead candidate. “That could either happen within RhoVac or another biotech company, but it would not be a Phase III-ready asset, so it’s a different scale of course,” RhoVac CEO Anders Månsson told Endpoints News . By stopping the study, the company eliminated most of its costs, Månsson noted, adding that RhoVac functions as mostly a “virtual biotech.” RhoVac’s shares dropped from 35 kr to just over 2 kr (from $3.56 to $0.20) after the company announced the Phase II fail. The biotech had built their vaccine around prevention. Rather than treating late-stage tumors, by starting early, RhoVac had hoped its therapy could prevent metastatic tumors due to prostate cancer from forming, Månsson said. Thus far, therapeutic cancer vaccines have yet to succeed in the market. In 2010, Dendreon won approval for its cancer vaccine for metastatic prostate cancer, the same indication that RhoVac is trying to prevent, but Dendreon eventually went bankrupt in 2014 after its therapeutic vaccine Provenge underperformed as a result of its high production costs and limited efficacy compared to other treatments. However, on the heels of their Covid-19 vaccine successes, BioNTech and Regeneron are looking to use their mRNA technology in therapeutic vaccines for multiple cancers, including prostate cancer. Last year, BioNTech also began a Phase II trial for a vaccine to prevent recurrence of colorectal cancer. RhoVac was founded in 2007 and is named after its lead candidate, a cancer vaccine that targets cells with a protein known as RhoC, which is overexpressed in metastatic tumors.