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amcure Presents Preclinical Data on Lead Cancer Compound AMC303 at AACR Annual Meeting

On April 4, 2017 amcure, a biopharmaceutical company developing first-in-class cancer therapeutics, reported vivo and in vitro data on its lead development candidate, AMC303, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 in Washington DC (Press release, amcure, APR 4, 2017, View Source [SID1234518473]). The poster presentation highlighted AMC303’s unique and novel mode of action which inhibits CD44v6 and thus, signals three cancer relevant Receptor Tyrosine Kinases (RTKs), c-MET, RON and VEGFR-2. AMC303 is currently being evaluated in a Phase I/Ib clinical 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 cancer.

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"So far the data generated with AMC303 indicate that it combines a strong anti-tumor and anti-metastatic effect," said Klaus Dembowsky, CEO of amcure. "These encouraging results solidify our belief in AMC303’s potential as a novel solid tumor treatment option and bode well for the ongoing Phase I study results."

In the study, researchers elucidated the unique mechanism of action of AMC303, a CD44v6 inhibitor, demonstrating the specific inhibition of three key RTKs (c-MET, RON and

VEGFR-2) in vitro that play a significant role in tumor growth and metastasis formation. Furthermore, in a pancreatic tumor mouse model, a three-week treatment with AMC303 resulted in a clear inhibition of tumor growth and metastasis formation as well as a marked reduction of preformed metastases. Overall, this data confirms AMC303’s potential as a novel mechanism for the treatment of patients with advanced solid tumors that have already formed metastases.

The poster, "Allosteric inhibition of the Receptor Tyrosine Kinases c-MET, RON and

VEGFR-2 via the co-receptor CD44v6 by the novel compound AMC303" presented at the AACR (Free AACR Whitepaper) Annual Meeting 2017 is available on the Company’s website under "Research and Development" or by accessing the following link: View Source

About AMC303

amcure’s lead compound, AMC303, is being developed as a potential treatment for patients with advanced and metastatic epithelial tumors, e.g. pancreatic cancer, head and neck cancer, gastric cancer, colorectal cancer, breast cancer and lung cancer. AMC303 has a high specificity for inhibiting CD44v6, a co-receptor required for signaling through multiple cellular pathways (c-Met, VEGFR-2, RON) involved in tumor growth, angiogenesis and the development and regression of metastases. AMC303 has demonstrated strong effects in various in vitro and in vivo assays.

Atossa Genetics Enrolls First Cohort of Eight Subjects in Endoxifen Study

On April 4, 2017 Atossa Genetics, Inc. (NASDAQ: ATOS) reported that it has fully enrolled the first of six cohorts (eight participants per cohort) in its Phase 1 study of endoxifen, which is an active metabolite of tamoxifen, an FDA approved drug for breast cancer and breast cancer prevention in high risk women (Press release, Atossa Genetics, APR 4, 2017, View Source [SID1234518472]). The objectives of this double-blinded, placebo-controlled, repeat dose study of 48 healthy female subjects is to assess the pharmacokinetics of proprietary formulations of both oral and topical endoxifen dosage forms over 28 days, as well as to assess safety and tolerability. The study is being conducted in two parts based on route of administration.

"Less than ten months ago we announced that we had begun a program to develop endoxifen for cancer patients who don’t benefit from taking tamoxifen and for women at high risk of developing breast cancer who are not taking tamoxifen, often due to concerns about side effects from system exposure. Through the hard work and dedication of Atossa’s employees and our collaborators we have obtained a qualified manufacturer of the active pharmaceutical ingredient, performed formulation development for both oral and topical dosage forms, established a manufacturer of the finished dosage forms, and launched the first human testing in a Phase 1 study," stated Steven Quay, CEO and President. "I am not aware of any oncology company that has completed the pre-clinical phase of drug development so quickly."

Galena Biopharma Presents Positive Interim Safety Data on the NeuVax™ (nelipepimut-S) Clinical Trial in Combination with Trastuzumab in High-Risk HER2 3+ Patients at the AACR Annual Meeting 2017

On April 4, 2017 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company developing hematology and oncology therapeutics that address unmet medical needs, reported a poster was presented on the Company’s NeuVax (nelipepimut-S) investigator-sponsored Phase 2 clinical trial (IST) in high-risk, HER2 3+ patients at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 in Washington, DC (Press release, Galena Biopharma, APR 4, 2017, View Source [SID1234518471]). The Phase 2 trial is a multi-center, prospective, randomized, single-blinded, placebo-controlled trial combining NeuVax and trastuzumab in the adjuvant setting to prevent recurrence in HER2-positive (HER2 3+) breast cancer patients.

The poster, entitled, "Pre-specified interim analysis in a prospective, randomized phase II trial of trastuzumab vs trastuzumab + NeuVax to prevent breast cancer recurrence in HER2+ breast cancer patients," presented the interim safety analysis that was initiated after enrollment of the 50th patient in the trial (vaccine group (VG) n=22, control group (CG) n=28). The analysis demonstrated that the agent is well tolerated with no increased cardiotoxicity associated with giving NeuVax in combination with trastuzumab.

In the trial, there were no significant clinicopathologic differences between groups. The vast majority of toxicities were grade 1 and there were no related grade 4 or 5 toxicities and no differences in related toxicities between the VG and CG (Grade 1: 96% vs 98.5%; Grade 2: 3.2% vs 1.5%; Grade 3: 0.8% vs 0%, p=0.14). There was no significant reduction in cardiac ejection fraction (EF) pre- to post-treatment in either group (VG: 61.1±5.4% vs 60.1±4.8%, p=0.55; CG: 62.3±5.7% vs 61.9±4.0%, p=0.74) and no notable difference in EF was observed between the baseline (pre-treatment) and the follow-up (post treatment) within the vaccine and control groups (p=0.54).

"As we reported in February, this data was the basis for the Data Safety Monitoring Board (DSMB) to perform a futility analysis and recommend the study continue as planned. Additionally, the DSMB determined that there were no safety concerns," said Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer. "The poster presented at AACR (Free AACR Whitepaper) provides a more detailed safety analysis of the ongoing IST with NeuVax in combination with trastuzumab in HER2 positive breast cancer patients. We are pleased that the combination of agents are well tolerated and that there is no additive cardio toxicity."

Dr. Nejadnik continued, "The Phase 2 trial is expected to complete enrollment by the end of this year with immunologic and clinical outcomes data to be reported via the planned primary analysis after 24-months follow-up. This trial in HER2 3+ patients complements our other ongoing IST with NeuVax in combination with trastuzumab in HER2 1+/2+ patients with an interim data analysis also expected by the end of the year."

The trial is enrolling HLA-A2 and HLA-A3 positive breast cancer patients with stage I-III HER2 positive disease at high risk for recurrence, which is defined as patients not achieving a complete response after trastuzumab-containing neoadjuvant therapy or those undergoing up-front surgery with any node-positive disease (if ER/PR- or ≥4 positive nodes if ER/PR+). Patients are enrolled after surgery, radiation and neo-adjuvant/adjuvant chemotherapy with an approved trastuzumab-containing regimen. Patients are randomized to receive trastuzumab + NeuVax in the VG or trastuzumab + GM-CSF only in the CG. Patients receive vaccinations of NeuVax or GM-CSF intradermally every 3 weeks for 6 total vaccinations (primary vaccine series, PVS) starting with the third dose of trastuzumab maintenance therapy. Starting 6 months after the completion of the PVS, patients receive 4 booster inoculations, one every 6 months. EF is assessed by either echo or MUGA at baseline and serially during treatment. For this analysis, demographic and safety data were collected and analyzed, and the interim safety analysis was initiated after enrollment of the 50th patient.

The abstract (#8734) can be found on the conference website here, and the poster presentation from the conference will be available on Galena’s website here.

About NeuVax (nelipepimut-S)

NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).

NeuVax is currently in two breast cancer studies in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). A Phase 2 clinical trial is also ongoing with NeuVax in patients with ductal carcinoma in situ (DCIS) (clinicaltrials.gov identifier: NCT02636582), and a Phase 2 trial is planned in patients with gastric cancer.

About Breast Cancer1

New cases of breast cancer occur at an annual rate of 125 per 100,000 women in the U.S., with an estimated 246,660 new cases and 40,450 deaths in 2016. Approximately 89.7% of breast cancer patients are expected to survive five years after diagnosis. Approximately 12.4% of women will be diagnosed with breast cancer at some point during their lifetime (2011 – 2013 data). The prevalence data from 2013 showed an estimated 3,053,450 women living with breast cancer in the United States.

VBL Therapeutics Presents Data on MOSPD2, a Novel Immuno-Oncology Target

On April 4, 2017 VBL Therapeutics (NASDAQ:VBLT), reported the presentation of new data on MOSPD2, a novel potential target in oncology (Press release, VBL Therapeutics, APR 4, 2017, View Source [SID1234518470]). VBL’s study, entitled "MOSPD2, a Newly Characterized Protein, Promotes Breast Cancer Metastasis" by Mendel et al., will be presented today at the American Association of Cancer research (AACR) (Free AACR Whitepaper) conference in Washington, DC. The study observed from clinical biopsies 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.

"The current publication indicates involvement of MOSPD2 in motility and metastasis of cancer cells in a breast cancer model, with correlative clinical specimens expression pattern that is associated with breast tumor invasiveness," said Eyal Breitbart, PhD, VP for Research and Operations at VBL. "We believe that MOSPD2 may be involved in the regulation of cell motility in addition to breast cancer, as it is found in other tumor tissues as well. We recently reported its role in monocyte migration and are studying its expression and potential involvement in additional tumor types," added Dr. Breitbart.

The company believes that targeting of MOSPD2 may have several therapeutic applications, including inhibition of tumor cell metastases and targeting of MOSPD2-positive tumor cells, as well as inhibition of monocyte migration in chronic inflammatory conditions. VBL’s "VB-600 series" of pipeline candidates is being developed towards these applications.

TG Therapeutics, Inc. Announces Preclinical Data Presentation on the Company’s Anti-PD-L1 Monoclonal Antibody at the American Association for Cancer Research Annual Meeting

On April 4, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX), reported the first presentation of preclinical data on the Company’s novel fully human anti-PD-L1 monoclonal antibody at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, being held this week, April 1-5, 2017, at the Walter E. Washington Convention Center in Washington, D.C (Press release, TG Therapeutics, APR 4, 2017, View Source [SID1234518469]).

The following poster was presented today, April 4, 2017, during the Immunoconjugates and Antibodies Session in Halls A-C.

Preclinical Characterization of a Novel Fully Human lgG1 Anti-PD-L1 mAb CK-301

Based on the various assays performed, the poster concluded:

CK-301 is a high affinity PD-L1 specific fully humanized lgG1 antibody which blocks binding of PD-L1 to PD-1.
Activity of CK-301 in all assays tested was similar to anti-PD-L1’s used as active controls (surrogates of avelumab, atezolizumab, or durvalumab).
Similar to the approved anti-PD-L1, avelumab, CK-301 has the potential to induce ADCC (antibody-dependent cell-mediated cytotoxicity).
A first-in-human Phase 1 study of CK-301 is planned to commence this year.

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "The team has worked hard to develop a high quality anti-PD-L1 antibody which we believe is the cornerstone of any proprietary immune-oncology (I/O) strategy. While anti-PD-1/PD-L1 therapy has been broadly explored in solid tumors, we are still in the very early days of understanding their utility and best applications in B-cell malignancies. As a company, we have been highly focused on developing best-in-class combination therapies for patients with B-cell malignancies and believe the next generation of combinations will include both targeted therapies, like TG-1101 and TGR-1202, plus I/O agents like our anti-PD-L1 antibody presented here today. We look forward to commencing the first-in-human study this year."