On April 1, 2019 Apollomics, Inc. (the "Company"), an innovative biopharmaceutical company committed to the discovery and development of oncology combination therapies, reported positive data for the Company’s multi-kinase inhibitor, APL-102, as both a single agent and in combination with an anti-PD-1 antibody in multiple preclinical studies (Press release, Apollomics, APR 1, 2019, View Source [SID1234534819]).

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"Our preclinical data presented today demonstrates a mechanism of action for APL-102 anti-tumor activity and a synergistic effect of the agent when combined with a check-point inhibitor (CPI)," said Sanjeev Redkar, PhD, President. "APL-102 treatment increased the total T-cells and the CD8 T-cells, and significantly decreased macrophages in the tumor, both as a single agent and in combination with an anti-PD1 antibody. We see a potential path forward for the agent as a single agent or in combination with CPIs which may improve the efficacy of APL-102 and broaden the efficacy of CPIs."

The studies, in multiple murine models, evaluated the effect of anticancer therapies that target components within the tumor microenvironment (TME) as opposed to the tumor itself. Colony stimulating factor 1 receptor (CSF-1R) was a key target as a means of controlling tumor associated macrophages in the TME. As a monotherapy, the results demonstrated that APL-102 inhibits CSF-1R in a radiometric enzyme activity assay with an IC50 of 43nM, and that APL-102 inhibited growth in cells dependent on CSF1-CSF1R signaling. APL-102 also demonstrated targeting of Vascular Endothelial Growth Factor Receptors (VEGFR) dependent angiogenesis and the Mitogen-Activated Protein Kinases (MAPK) pathway.

When APL-102 was given in combination with an anti-PD1 antibody, the results produced a more robust response than either single agent alone in syngeneic mouse models, which was associated with macrophage inhibition in the TME.

About APL-102

APL-102 is an oral, small molecule multi-kinase Inhibitor targeting several key oncogenic drivers. APL-102 inhibits both receptor tyrosine kinase (RTKs) and serine/threonine-kinases, including: angiogenesis via Vascular Endothelial Growth Factor Receptors (VEGFR) and Platelet-Derived Growth Factor Receptors (PDGFR); Mitogen-Activated Protein Kinases (MAPK) pathway via B-RAF and C-RAF; and, RET, CSF1R, DDR1 (discoidin domain receptor tyrosine kinase 1) and c-KIT. APL-102 is currently in preclinical, IND-enabling studies. The agent has demonstrated broad and potent antitumor activity in patient derived xenografts of liver cancer, breast cancer, colorectal cancer, gastric, esophageal and non-small cell lung cancer models with excellent oral bioavailability, biopharmaceutical properties, and a well-tolerated safety profile in a chronic safety study. Apollomics retains worldwide rights to APL-102.

On April 1, 2019 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported the presentation of updated findings from the melanoma and non-small cell lung cancer (NSCLC) cohorts of ENCORE 601, the Company’s Phase 1b/2 trial evaluating the efficacy and safety of entinostat, its once-weekly, oral, small molecule, class I HDAC inhibitor, in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy (Press release, Syndax, APR 1, 2019, View Source [SID1234534836]). The data were presented during oral presentations at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held March 29 – April 3, 2019 in Atlanta, Georgia. A copy of each presentation is available via the Syndax website at View Source

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"We are very pleased to report that updated findings announced today continue to support our prior observation that the addition of entinostat to pembrolizumab may overcome resistance in a subset of melanoma and NSCLC patients who are refractory to anti-PD-1 therapy," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "Both indications represent areas of high unmet need and we believe that available data warrant consideration to move the entinostat-pembrolizumab combination into one or more registration trials. As previously communicated, we look forward to determining next steps for the combination program following availability of overall survival results from E2112, our Phase 3 registration trial of entinostat plus exemestane in HR+, HER2- breast cancer, the next interim readout of which is expected in the second quarter of this year."

Melanoma Update

During an oral presentation today titled, "Efficacy and safety of entinostat (ENT) and pembrolizumab (PEMBRO) in patients with melanoma previously treated with anti-PD1 therapy", Ryan J. Sullivan M.D., Assistant Professor, Hematology/Oncology, Massachusetts General Hospital, presented results from the ENCORE 601 melanoma cohort that enrolled patients whose disease had progressed on or after anti-PD-1 therapy. Of 53 patients treated, a confirmed objective response was observed in 19% of patients per irRECIST criteria (1 complete response (CR), 9 partial responses (PR); 95% CI: 9-32%), with a clinical benefit rate of 36% (CR, PR, stable disease (SD) > 6 months; 95% CI: 23%-50%). Median duration of response is 13 months (range 3-20 months). Four responders, all of whom have been on study therapy for over a year, currently remain on treatment. Efficacy results in patients who also received prior YERVOY (ipilimumab) therapy (n=37, 70%) were consistent with the overall population. The entinostat-pembrolizumab combination was well tolerated with a manageable toxicity profile.

Correlative analyses consistent with entinostat’s hypothesized mechanism of action indicate a trend in decreased circulating myeloid derived suppressor cells (MDSCs) and increased CD8+ T cells in responding patients. Gene expression changes in post-treatment tumor biopsy samples in responders versus non-responders support up-regulated immune response signatures and down-regulation of immune resistance pathways.

NSCLC Update

During an oral presentation on Sunday titled, "Identification of gene signatures associated with response in a Phase 2 trial of entinostat (ENT) plus pembrolizumab (PEMBRO) in non-small cell lung cancer (NSCLC) patients whose disease has progressed on or after anti-PD-(L)1 therapy", Suresh S. Ramalingam, M.D., Assistant Dean for Cancer Research and Deputy Director of the Winship Cancer Institute at Emory University, presented updated clinical results and findings from gene expression analyses of pre-treatment tumor samples conducted in a subset of patients. Updated results continue to support the association of high baseline classical monocytes with improved clinical outcome to entinostat plus pembrolizumab in anti-PD-1 pre-treated NSCLC patients and with extended follow up, the median duration of response is 8 months (range 3-18 months).

Results from gene set analyses revealed a significantly enriched Myc regulated gene signature in responders versus non-responders. Multiple studies have implicated elevated Myc signaling as a resistance factor to anti-PD-(L)1 therapy1-3, and separately have shown that entinostat can downregulate Myc activity4,5. These findings provide further insight into the potential mechanistic basis for response to the entinostat-pembrolizumab combination treatment in PD-(L)1 pretreated patients.

About Entinostat

Entinostat, Syndax’s selective, oral, once-weekly inhibitor of class I histone deacetylases (HDACs), has been shown to resensitize Hormone Receptor positive (HR+) advanced breast cancer to endocrine therapy, and is currently being evaluated in a pivotal Phase 3 clinical trial in combination with exemestane for advanced HR+ breast cancer, an indication for which it has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration. Entinostat has also been shown to block the function of immune suppressive cells in the tumor microenvironment, and in a Phase 2 clinical trial in combination with KEYTRUDA (pembrolizumab) from Merck & Co., Inc, demonstrated evidence of clinical benefit in patients with melanoma and non-small cell lung cancer.

On April 1, 2019 AngioDynamics, Inc. (NASDAQ: ANGO), a leading provider of innovative, minimally invasive medical devices for vascular access, peripheral vascular disease, and oncology, reported that Michael C. Greiner, Executive Vice President and Chief Financial Officer, will present at the 18th Annual Needham Healthcare Conference at 1:30 p.m. ET on Tuesday, April 9, 2019 in New York, NY (Press release, AngioDynamics, APR 1, 2019, View Source [SID1234534852]).

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A live webcast of the presentation will be accessible through the "Investors" section of the Company’s website at www.angiodynamics.com and will be available for replay following the event.

On April 1, 2019 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that new preclinical data from the Company’s innovative portfolio of next generation immunotherapies has been presented in a conference session by Pr. Eric Vivier, Chief Scientific Officer, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held from March 29–April 3, in Atlanta (Press release, Innate Pharma, APR 1, 2019, View Source [SID1234534820]).

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Eric Vivier, Chief Scientific Officer of Innate Pharma, said:"Innate Pharma has always been driven by scientific leadership and we are very proud to present new preclinical data from our broad and innovative portfolio of next generation cancer immunotherapies. For the first time, we also shared data from our multi-specific NK-cell engager technology that highlight a new generation of molecules for fighting cancers."

While chairing the conference session"Innate Immunity and Complement in Solid Tumors", the following findings were presented by Eric Vivier in a lecture titled "Targeting innate immunity in next generation cancer immunotherapies" yesterday at AACR (Free AACR Whitepaper):

IPH5201 (anti-CD39) and IPH5301 (anti-CD73), targeting the adenosine pathway:

CD39 and CD73 are membrane-bound extracellular enzymes which play a major role in promoting immunosuppression through the pathway degrading adenosine triphosphate (ATP) into immunosuppressive adenosine (Ado). The blockade of CD39 and CD73 has the potential to promote anti-tumor immune responses across a wide range of tumors.

New data demonstrate that a combination of Innate Pharma’s anti-CD39 monoclonal antibody, IPH5201, and ATP-inducing oxaliplatin had a synergistic effect that improved the control of tumor growth in a preclinical mouse model.

Previous findings showed that IPH5201 enhances the stimulatory effect of ATP on antigen presenting cells and abrogates the suppressive effect of ATP-derived Ado on the proliferation of T cells from healthy donors and cancer patients. In October 2018, Innate Pharma and AstraZeneca entered into a development collaboration and option for further co-development and co-commercialization for IPH5201.

New data from a crystal structure of the CD73/IPH5301 complex support a model for the differentiated mode of action of IPH5301 and enhanced efficacy compared to competitors. Analysis by electron microscopy revealed that the IPH5301 monoclonal antibody interacts mainly with CD73 dimer in an intra-dimer mode, constraining the CD73 enzyme in an inactive state in which AMP could not be hydrolyzed, in contrast to other antibodies in development that interact in an inter-dimer mode. Findings presented at the 2018 American Association of Cancer Research (AACR) (Free AACR Whitepaper) conference demonstrated that IPH5301 is more potent in vitrothan benchmark anti-CD73 antibodies currently under clinical development, on both membrane-bound and soluble CD73, in enzymatic activity as well as T cell proliferation assays.

Innate expects INDs to be filed for IPH5201 in the second half of 2019 and for IPH5301 in the first half of 2020.

First-in-class trifunctional NKCEs create a new generation of molecules for fighting cancer:

Innate Pharma’s proprietary multifunctional NKCE technology targets two activating receptors, NKp46 and CD16, on NK cells and a tumor antigen on cancer cells.

New pre-clinical data outlined in the presentation demonstrate that these first-in-class trifunctional NKCEs are more potent in vitroand in vivo than clinical therapeutic monoclonal antibodies targeting the same tumor antigen, such as rituximab, obinituzumab or cetuximab, with nooff-target effects. The data also demonstrate that co-engagement of NKp46 synergizes with CD16 to potentiate both tumor cell lysis and NK cell activation.

NKCEs stimulate NK cells instead of T cells and have been designed to improve the benefit-risk profile for the treatment of solid tumors.

Innate Pharma has a research collaboration and licensing agreement with Sanofi for the generation and evaluation of up to two multifunctional NK cell engagers, using both Innate Pharma’s and Sanofi’s technology and tumor targets. Under the terms of the license agreement, Sanofi is responsible for the development, manufacturing and commercialization of products resulting from the research collaboration. Innate Pharma is eligible for up to €400m in development and commercial milestone payments as well as royalties on net sales.

On April 1, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage oncology therapeutics company, taking a precision medicine approach to develop drugs that target cell division (mitosis) for the treatment of leukemias, lymphomas and solid tumor cancers, reported its new data from its ongoing Phase 1b/2 study evaluating onvansertib in combination with standard-of-care chemotherapy in Acute Myeloid Leukemia (AML) (Press release, Trovagene, APR 1, 2019, View Source [SID1234534837]).

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The data, featured at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), demonstrates the safety, tolerability, preliminary efficacy and relative durability of response in patients treated with onvansertib, in combination with either low-dose cytarabine (LDAC) or decitabine, in patients with relapsed/refractory acute myeloid leukemia (AML). The prognosis for these patients is poor with short survival time and limited treatment options. Onvansertib is a first-in-class, 3rd generation, highly-selective oral Polo-like Kinase 1 (PLK1) Inhibitor that is being evaluated in an ongoing Phase 1b/2 clinical trial at nine sites in the U.S.

Presentation Highlights

Anti-Leukemic Activity:

Objective response rate (anti-leukemic activity) has been observed at last 3 highest dose levels of onvansertib with 5 of 19 evaluable patients achieving a complete response (CR and CRi, 2 patients); a morphologic leukemic-free state (MLFS, 2 patients); and a partial response (PR, patient). Furthermore, stable disease (SD) was observed in 12 patients
The greatest anti-leukemic activity has been observed in the onvansertib + decitabine arm, with 2 of 4 (50%) evaluable patients from the two highest dose levels tested to-date (27mg/m2 and 40mg/m2) achieving a complete response (CR and CRi)
Early indication of safety, tolerability and durability of response has been demonstrated by 16 of 24 patients who have completed ≥2 cycles of treatment, including 2 patients who have been on treatment for 11.5 months (patient with PR) and 5.4 months (patient with CRi)
Biomarker Analysis:

Positive biomarker status to-date (the phosphorylation of translational control tumor protein (pTCTP), which is a specific marker for PLK1 activity, has been observed in 8 out of 22 patients (33%) and has been associated with a statistically significant greater response to treatment (p=0.019)
Safety/Tolerability:

There have been no dose-limiting toxicities through the completed dose level of 40mg/m2
No serious adverse events (SAEs) reported to-date have been considered related to onvansertib
"While we are still in the dose escalation part of the trial, the preliminary efficacy data is encouraging, in particular that we are seeing some complete and relatively durable responses," said Dr. Amer Zeidan, lead investigator and assistant professor of Medicine at Yale School of Medicine, and Hematology expert at Yale Cancer Center. "AML patients with relapsed or refractory disease have short survival time and very limited treatment options. As we continue to dose escalate through the Phase 1b trial, we are not only encouraged by how safe and well-tolerated onvansertib appears to be thus far in this patient population, but also by the evidence of clinical activity we are seeing especially with the decitabine-based combination at the higher doses of onvansertib. For example, one of my patients, who responded to treatment, is nearly one year out from the time of enrollment in this trial and continues to do quite well. We hope, as we continue in the trial and reach the recommended Phase 2 dose, that we will see additional evidence of clinical efficacy."

Details of the poster presentation are provided below:

Title: Phase 1b Safety, Preliminary Anti-Leukemic Activity and Biomarker Analyses of the Polo-like Kinase 1 (PLK1) Inhibitor, Onvansertib, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine in Patients with Relapsed/Refractory Acute Myeloid

Session Title: Phase I-III Trials in Progress: Part 1

Date and Time: Monday, April 1, 2019; 1:00 PM – 5:00 PM EDT

Session Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 17

About the Ongoing Onvansertib Phase 1b/2 Acute Myeloid Leukemia Trial

The Phase 1b/2 trial (NCT03303339) is a multi-center, open-label trial to evaluate the safety and efficacy of Onvansertib in combination with standard-of-care chemotherapy in AML patients who are ineligible for intensive induction therapy or whose disease is relapsed or refractory. In Phase 1b dose-escalation segment of the trial, the primary objective is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), using a traditional 3+3 design. In Phase 2 the MTD or RP2D will be administered to 32 patients to evaluate preliminary antitumor activity and to continue to evaluate the safety and tolerability of Onvansertib in combination with standard-of-care chemotherapy. This trial is being led by Amer Zeidan, MBBS, MHS, assistant professor of Medicine at Yale School of Medicine, and Hematology expert at Yale Cancer Center, and Jorge Cortes, M.D., Deputy Department Chair, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. The trial is being conducted at nine sites in the U.S.

About Onvansertib

Onvansertib is a first-in-class, 3rd generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple cancers, including leukemias, lymphomas and solid tumors. Separate studies with other PLK inhibitors have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in Acute Myeloid Leukemia (AML) where response rates of up to 31% were observed when combined with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate. A Phase 1 open-label, dose escalation safety study of Onvansertib has been completed in patients with advanced metastatic solid tumor cancers and published in Investigational New Drugs. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) in this trial was 24 mg/m2. Trovagene has an ongoing Phase 1b/2 clinical trial with onvansertib in AML that was accepted by the National Library of Medicine (NLM) and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is NCT03303339. Onvansertib has been granted Orphan Drug Designation by the FDA in the U.S. and by the EC in the European Union (EU) for the treatment of patients with AML.

Onvansertib targets the PLK1 isoform, only (not PLK2 or PLK3), is orally administered, has a 24-hour drug half-life with only mild to moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK1 inhibitor, onvansertib, with other compounds has the potential to improve clinical efficacy in Acute Myeloid Leukemia (AML), metastatic Castration-Resistant Prostate Cancer (mCRPC), Non-Hodgkin Lymphoma (NHL), Colorectal Cancer, Triple Negative Breast Cancer (TNBC), as well as other types of cancer.