Amcure GmbH, of Eggenstein-Leopoldshafen, Germany, presented in vivo and in vitro data on its lead development candidate, AMC303, highlighting its mechanism of action in inhibiting CD44v6 and signaling three cancer relevant receptor tyrosine kinases: c-MET, RON and VEGFR-2. AMC303 is currently being evaluated in a phase I/Ib study as a monotherapy in patients with advanced metastatic malignant solid tumors of epithelial origin, for example pancreatic, head and neck, colorectal, gastric and lung cancers.
Bellicum Pharmaceuticals Inc., of Houston, presented preclinical results from its dual-switch technology for use in CAR T and T-cell receptor candidates. Testing the dual-switch platform in solid tumors by combining both the inducible MyD88/CD40 (iMC) co-stimulatory and Rapacide apoptotic signaling switches inside a first-generation CAR targeting HER2 showed that Rapacide was as effective as the company's Caspacide switch at activating apoptosis, while the iMC co-stimulatory switch enhanced tumor killing and T-cell proliferation. The study demonstrated that the company's dual-switch GoCAR-T technology effectively controlled tumor growth, T-cell proliferation/persistence and elimination in a solid tumor model.
Bioxcel Corp., of Branford, Conn., presented preclinical data confirming the ability of BXCL701 to synergistically enhance the antitumor activity of immune checkpoint inhibitors. An in vivo study of BXCL701 in combination with an anti-PD-1 agent in the syngeneic MC38 colon adenocarcinoma mouse model demonstrated an increase in antitumor cytokines, including IL-2 and IL-12, as well as increased tumor growth inhibition. BXCL701, an immune-modulator, is in development for castration-resistant prostate cancer.
Boston Biomedical Inc., of Cambridge, Mass., reported preclinical data from a study evaluating napabucasin in combination with an anti-PD-1 antibody, an immune checkpoint inhibitor, showing that the combination was able to sensitize mice with colorectal cancer to checkpoint inhibitors. An additional preclinical study revealed napabucasin may overcome resistance to paclitaxel in stemness-high cells, further supporting that the compound can be effectively combined with that standard-of-care therapy. Napabucasin is an orally administered agent designed to inhibit cancer stemness pathways by targeting STAT3. Preclinical data for amcasertib also was presented, showing that it was able to target Nanog via the STK33 pathway and beta-catenin via the STK17A pathway in models.
Cantex Pharmaceuticals Inc., of Weston, Fla., reported preclinical results demonstrating antitumor efficacy of CX-02, its combination of disulfiram (DSF) and copper, in a series of brain tumor cell lines. The results demonstrated significant sensitivity of glioblastoma (GBM) and, for the first time, medulloblastoma, cells to CX-02. In addition, CX-02 increased the sensitivity of temozolomide-resistant, methylator+ve GBM cells to temozolomide. Cantex said findings support the investigation of DSF plus copper as a treatment strategy for GBM and medulloblastoma.
CBT Pharmaceuticals Inc., of Santa Clara, Calif., presented preclinical data showing that CBT-101 (bozitinib, PLB-1001, CBI-3103), a highly specific small-molecule inhibitor of c-MET receptor tyrosine kinase, demonstrated selectivity, safety and efficacy in suppressing tumor growth in lung, gastric, hepatic and pancreatic human primary tumor models. CBT-101 inhibited c-MET activation in a range of human primary cancer cell lines and inhibited in vivo dephosphorylation of c-MET in a dose-dependent manner in a human gastric cancer model.
Checkpoint Therapeutics Inc., of New York, reported preclinical data for its third-generation EGFR inhibitor, CK-101, also known as RX518, showing that the irreversible, orally administered drug, which targets mutant forms of EGFR, including T790M, demonstrated mutant-selective inhibitor activity of both the activating (exon 19 deletion) and resistance mutations (L858R/T790M double mutation). It also inhibited tumor growth as a single agent in a non-small-cell lung cancer model with a single activating mutation (exon 19 deletion) and showed dose-dependent inhibition of tumor growth as a single agent in a L858R/T790M double mutant NSCLC model. CK-101 is in a phase I/II trial. Preclinical data for the firm's anti-PD-L1 monoclonal antibody, CK-301, showed similar activity to anti-PD-L1 drugs used as active controls and demonstrated similar activity to approved anti-PD-L1 Bavencio (avelumab, EMD Serono). A phase I trial is set for this year.
Corvus Pharmaceuticals Inc., of Burlingame, Calif., reported interim results from its phase I/Ib study, showing that treatment with CPI-444 as a single agent and in combination with Tecentriq (atezolizumab, Roche Holding AG) was well-tolerated and resulted in antitumor activity in patients with multiple types of advanced solid tumors, including those resistant or refractory to prior treatment with anti-PD-1 or anti-PD-L1 antibodies. Disease control, with a median follow-up of 16 weeks, was observed in 38 percent of patients in the CPI-444-only arm and in 39 percent of the combination arm, for an overall disease control rate of 38 percent. CPI-444 is a selective inhibitor of the adenosine A2A receptor. Shares of Corvus (NASDAQ:CRVS) fell $10.35, or 50 percent, to close Tuesday at $10.36.
Exscientia Ltd., of Dundee, U.K., reported results from its collaboration with Evotec AG, of Hamburg, Germany, to develop adenosinergic small molecules focused on immuno-oncology, including a selective adenosine 2A receptor (A2AR) antagonist, currently being explored for candidate selection, as well as first demonstration of a bispecific small molecule capable of simultaneously antagonizing A2AR and inhibiting CD73. The companies inked their collaboration in April 2016.
Galena Biopharma Inc., of San Ramon, Calif., presented data from an investigator-sponsored phase II trial in high-risk HER2 3-positive patients testing immunotherapy candidate Neuvax (nelipepimut-S) in combination with Herceptin (trastuzumab, Roche Holding AG) when given to prevent breast cancer recurrence. An interim analysis demonstrated that the agent is well-tolerated with no increased cardiotoxicity associated when given with Herceptin. The data monitoring committee recommended in February for the study to continue as planned.
H3 Biomedicine Inc., of Cambridge, Mass., presented data including preclinical activity seen with H3B-8800, an oral, SF3b modulator, demonstrating activity across spliceosome mutant cancers. Oral dosing of H3B-8800 led to selective antileukemic activity in spliceosome mutant xenograft models grown in mice, while the drug showed activity in patient-derived xenograft models of chronic myelomonocytic leukemia bearing SRSF2 mutations. The company also reported results from a survey of spliceosome gene mutations and identified in-frame deletions in SF3B1 around K700 that result in aberrant RNA splicing in patients with chronic lymphocytic leukemia.
Ignyta Inc., of San Diego, reported preclinical data showing that immunomodulatory agent RXDX-106, in a commonly studied syngeneic mouse colon carcinoma model in matched immunocompetent and immunocompromised mice, had greater tumor growth inhibition in the immunocompetent animals, which suggested that RXDX-106 effects in that system were modulated by the immune system. Immuno-phenotypic modulation by RXDX-106 was also observed in the mouse model, including an increase in tumor-infiltrating lymphocytes, an increase in the ratio of M1/M2 macrophages and an increase in expression of CD69 and PD-1 on CD8 T cells. In another syngeneic mouse model, RXDX-106 inhibited tumor growth as a single agent and demonstrated further tumor growth inhibition in combination with anti-PD-1 or anti-CTLA-4 antibodies, which was accompanied by increased levels of IFN-gamma in the blood.
Immunomedics Inc., of Morris Plains, N.J., reported that labetuzumab govitecan (IMMU-130), its second investigational agent from its antibody-drug conjugate platform, delivers greater than 300-fold more SN-38 to CEA-producing tumors compared to irinotecan, while also reducing levels of potentially harmful SN-38 and glucuronidated SN-38 (SN-38G) in normal tissues. Labetuzumab govitecan, which is composed of a humanized anti-CEACAM5 antibody conjugated via the firm's linker to topoisomerase I inhibitor SN-38, is in clinical development as a monotherapy for patients with metastatic colorectal cancer.
Intensity Therapeutics Inc., of Westport, Conn., reported preclinical data showing that INT230-6 resulted in complete responses of tumors in rodent models, induced protective T-cell immunity and is synergistic with checkpoint inhibitors. Subsequent protective effect against re-inoculation decreased when CD4-positive and CD8-positive T cells were depleted prior to treatment or re-challenge, indicating that the observed complete response and durable, vaccine-like anticancer effect of INT230-6 is immune-mediated.
Karyopharm Therapeutics Inc., of Newton, Mass., updated interim data from its phase IIb SADAL study testing lead candidate selinexor (KPT-330), an oral SINE compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Results showed selinexor achieved a 28.6 percent overall response rate in patients with relapsed or refractory DLBCL and the responses were shown to be durable with a median duration of response of greater than seven months, including prolonged complete responses. Top-line data from SADAL are expected in mid-2018 and, if positive, could allow the firm to file for accelerated approval in relapsed/refractory DLBCL.
Medigene AG, of Planegg, Germany, presented an update on clinical compassionate-use data of a dendritic cell (DC) vaccine using the firm's DC vaccine technology. Results show that in four out of five acute myeloid leukemia patients, Toll-like receptor-polarized DC vaccination induced or supported specific T-cell responses. Three patients continue to be in complete remission after 21, 25 and 33 months, respectively, following suboptimal primary chemotherapy. A fourth, younger patient also showed specific immune responses against WT-1 during 10 months of vaccination.
Nektar Therapeutics Inc., of San Francisco, reported preclinical data showing that NKTR-214, an immunostimulatory CD122-biased agonist, as a single agent, provided durable responses in an aggressive orthotopic rat brain tumor model and that treatment of even very large tumors was effective with NKTR-214, prolonging survival in a significant proportion of animals. Preclinical data for NKTR-255, its IL-15 therapeutic candidate, showed that the drug induced multiple memory CD8-positive T-cell subtypes, including effector, central and stem memory populations. A single dose of NKTR-255 resulted in sustained IL-15-mediated activity not achievable with conventional IL-15 agents, and NKTR-255 showed single-agent efficacy in the CT-26 lung metastatic model, demonstrating significant lung nodule inhibition.
Onconova Therapeutics Inc., of Newtown, Pa., reported preclinical data for its dual inhibitor of CDK4/6 plus ARK5, ON 123300, showing that the myelodysplastic syndromes candidate exhibited antitumor activity in vivo and was as effective as Ibrance (palbociclib, Pfizer Inc.) in an Rb + ve xenograft model. Preclinical data from ON 150030, a dual inhibitor of FLT3 and Src pathways in development for relapsed and refractory acute myeloid leukemia, showed that the drug specifically inhibited the growth of MV4-11 cells harboring the FLT3-ITD mutation. Western blot analysis demonstrated that MAPK and PI3K/AKT pathways in those cells are inhibited with increasing dose of ON 150030. The JAK-independent phosphorylation of STAT5 seen in the context of FLT3-ITD is also reduced in response to ON 150030. Peregrine Pharmaceuticals Inc., of Tustin, Calif., presented results of a new analysis of the phase III SUNRISE trial of bavituximab, a chimeric monoclonal antibody that targets phosphatidylserine, in patients with previously treated locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC), showing that for patients in the study's bavituximab plus docetaxel treatment arm who received subsequent immunotherapy, the median overall survival (mOS) was not reached, while mOS was 13 months for patients in the study's placebo plus docetaxel arm who received subsequent immunotherapy (p=0.005). Analysis also highlighted that, overall, low peripheral interferon-gamma correlated with more favorable OS in the patients receiving bavituximab plus docetaxel and is a biomarker of interest. Peregrine halted the SUNRISE trial early last year after an independent data monitoring committee concluded the bavi group showed insufficient improvement in OS to warrant continuation. (See BioWorld Today, Feb. 29, 2016.)
Pharmamar SA, of Madrid, Spain, presented data on the mechanisms of action of plitidepsin and lurbinectedin, showing that plitidepsin acts by inhibiting some of the functions of the eEF1A2 protein and promoting cancer cell death, while lurbinectedin has shown an ability to reverse cisplatin resistance in ovarian cancer cells caused by the overexpression of the IRF-1 transcription factor.
Pieris Pharmaceuticals Inc., of Boston, presented data informing the design of its first clinical trial of PRS-343, a 4-1BB/HER2 bispecific, which demonstrated in preclinical studies an ability to elicit robust T-cell expansion in the tumor microenvironment while avoiding unwanted peripheral T-cell activation in HER2-positive cancer models. Data showed PRS-343 elicited T-cell activation when engaging HER2 on cell lines derived from tumors resistant to Herceptin (trastuzumab, Roche Holding AG) therapy, as well as tumor cell lines with elevated HER2 expression in the IHC 2+ range. The compound was well-tolerated and led to no significant findings in IND-enabling preclinical safety and nonhuman primate toxicology studies. Clinical development is set to start in the first half of this year.
Poseida Therapeutics Inc., of San Diego, presented preclinical data from its B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell drug candidate, P-BCMA-101. Data demonstrated potent and persistent antitumor activity, with P-BCMA-101 treatment reducing tumor burden to the limit of detection within seven days. Conversely, all untreated controls succumbed to disease within four weeks. Data also showed elimination of tumors following relapse without re-administration of the drug and prolonged survival compared to other BCMA CAR T agents in the same preclinical model. Poseida plans to initiate a phase I trial of P-BCMA-101 for the treatment of patients with relapsed or refractory multiple myeloma in 2017.
Puma Biotechnology Inc., of Los Angeles, reported interim results from a phase II trial of PB272 (neratinib) showing the effects of adding budesonide or colestipol to loperamide prophylaxis on neratinib-associated diarrhea in patients with HER2-positive early stage breast cancer. The results showed that the incidence of grade 3 diarrhea for the 137 patients who received the loperamide prophylaxis was 30.7 percent. For the 64 patients who received the combination of loperamide plus budesonide, the incidence of grade 3 diarrhea was 23.4 percent. (See BioWorld Today, Dec. 28, 2015.)
Siamab Therapeutics Inc., of Newton, Mass., presented preclinical data showing that its anti-STn antibody-drug conjugates (ADCs) demonstrated in vivo efficacy and depleted STn-expressing cells vs. isotype ADC in an ovarian xenograft mouse model. The study also showed that STn is highly expressed both in colorectal cancer patient tumors and granulocytic myeloid-derived suppressor cells (MDSCs). Based on those findings, Siamab will explore targeting STn on MDSCs to reduce or eliminate that population and determine whether that approach can augment antitumor responses induced by checkpoint blockade antibodies. Additional preclinical data described proof-of-concept results for the firm's bispecific antibody approach to target STn and CD3 on T cells.
Spectrum Pharmaceuticals Inc., of Henderson, Nev., presented preclinical data showing that the duration of severe neutropenia (DSN) in rats treated with eflapegrastim as a single dose 24 hours after administering cyclophosphamide (CPA) was 0.2 days. In contrast, the DSN was 3.04 days with filgrastim administered for five days after CPA. At the lowest eflapegrastim dose of 8.8 mcg/kg – about 1/10 of G-CSF equivalent dose for pegfilgrastim – the DSN in eflapegrastim-treated rats was 2.94 days. A pivotal trial of eflapegrastim is ongoing, with a BLA filing anticipated next year.
Syros Pharmaceuticals Inc., of Cambridge, Mass., reported preclinical data on SY-1425, its selective RAR-alpha agonist, showing that it increased the antitumor activity of hypomethylating agents, including azacitidine, in in vitro and in vivo models of acute myeloid leukemia (AML) with high RAR-alpha expression. In patient-derived xenograft models of AML with high RAR-alpha expression, SY-1425 in combination with azacitidine showed greater clearance of tumor cells and duration of response, compared to either azacitidine or SY-1425 alone, and showed a reduction of tumor burden to less than 5 percent in bone marrow and other tissues. SY-1425 is in phase II testing in genomically defined subsets of patients with AML and myelodysplastic syndromes.
TG Therapeutics Inc., of New York, presented preclinical data from its anti-PD-L1 monoclonal antibody, CK-301, showing that it is a high-affinity PD-L1-specific fully humanized IgG1 antibody that blocks binding of PD-L1 to PD-1. Activity of CK-301 in all assays tested was similar to anti-PD-L1s used as active controls and, similar to the approved anti-PD-L1 Bavencio (avelumab, EMD Serono), CK-301 has the potential to induce antibody-dependent cell-mediated cytotoxicity. A phase I study is set to start this year.
VBL Therapeutics Ltd., of Tel Aviv, Israel, presented data from clinical biopsies showing that MOSPD2 is prevalent in invasive human breast cancer tissue and that levels of MOSPD2 correlate to breast cancer invasiveness. It was further observed that a knockdown of MOSPD2 in a human breast cancer cell line using CRISPR technology led to blockade of EGF signaling and significant reduction of breast cancer cell migration in vitro and metastasis in a mouse model.