On November 30, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs, reported that two posters will be presented at the upcoming San Antonio Breast Cancer Symposium taking place December 6-10, 2016 in San Antonio, TX (Press release, Galena Biopharma, NOV 30, 2016, View Source [SID1234516851]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A poster will be presented on the trial design for the planned, Phase 2 investigator-sponsored clinical trial with NeuVax (nelipepimut-S) in patients with Ductal Carcinoma in Situ (DCIS). The trial is being run in collaboration with the National Cancer Institute (NCI) and The University of Texas MD Anderson Cancer Center Phase I and II Chemoprevention Consortium. The trial was suspended in July 2016, but is now open for enrollment and is expected to initiate by the end of the year. Details of the poster presentation are as follows:

Title: VADIS trial: Phase 2 trial of the nelipepimut-S peptide vaccine in women with DCIS of the breast
Session Title: Ongoing Clinical Trials: Ongoing Trials — Immunotherapy
Date: Friday, December 9, 2016
Time: 5:00 p.m. to 7:00 p.m. local time
Location: Hall 1
Poster #: 1646
Abstract #: OT3-01-04 – the abstract can be found on the conference website here
A poster will be presented on the breast cancer patients in the Company’s GALE-301 (E39) and GALE-302 (E39’) Phase 1b clinical trial targeting Folate Binding Protein. Details of the poster presentation are as follows:

Title: Determining the optimal vaccination strategy using a combination of the folate binding protein (FBP) peptide vaccine (E39+GM-CSF) and an attenuated version (E39′) to maximize the immunologic response in breast cancer patients
Session Title: Poster Session 6: Treatment: Immunotherapy (Clinical)
Date: Saturday, December 10, 2016
Time: 7:30 a.m. to 9:00 a.m. local time
Location: Hall 1
Abstract #: P6-10-04 – the abstract can be found on the conference 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). Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer.

About Ductal Carcinoma in Situ

Ductal Carcinoma in Situ (DUK-tul KAR-sih-NOH-muh in SY-too), or DCIS, is defined by the NCI as a noninvasive condition in which abnormal cells are found in the lining of a breast duct, and is the most common type of breast cancer. The abnormal cells have not spread outside the duct to other tissues in the breast. In some cases, DCIS may become invasive cancer and spread to other tissues; currently there is no way to know which lesions could become invasive. Current treatment options for DCIS include breast-conserving surgery and radiation therapy with or without tamoxifen, breast-conserving surgery without radiation therapy, or total mastectomy with or without tamoxifen. According to the American Cancer Society, in 2015 there were over 60,000 diagnoses of ductal carcinoma in situ.

About GALE-301 and GALE-302

GALE-301 and GALE-302 are cancer immunotherapies that consist of a peptide derived from Folate Binding Protein (FBP) combined with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF) for the prevention of cancer recurrence in the adjuvant setting. GALE-301 is the E39 peptide, while GALE-302 is an attenuated version of this peptide, known as E39’. FBP is a well-validated therapeutic target that is highly over-expressed in ovarian, endometrial and breast cancers, and is the source of immunogenic peptides that can stimulate cytotoxic T lymphocytes (CTLs) to recognize and destroy FBP-expressing cancer cells. Two trials are ongoing with FBP peptides: the GALE-301 Phase 2a portion of the Phase 1/2a clinical trial is ongoing in ovarian and endometrial adenocarcinomas (ClinicalTrials.gov Identifier: NCT01580696); the GALE-301 plus GALE-302 Phase 1b clinical trial is ongoing in breast and ovarian cancers (ClinicalTrials.gov Identifier: NCT02019524).

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.

1National Cancer Institute Surveillance, Epidemiology, and End Results Program

On November 30, 2016 Heat Biologics, Inc. (Nasdaq:HTBX), a leader in the development of gp96-based immunotherapies that are designed to activate a patient’s immune system to fight cancer, reported that it presented topline data from its 94-patient Phase II trial evaluating HS-410 (vesigenurtacel-L) in combination with standard of care, Bacillus Calmette-Guérin (BCG), or as a monotherapy, for the treatment of non-muscle invasive bladder cancer, at the Society of Urologic Oncology Annual Meeting in San Antonio, TX (Press release, Heat Biologics, NOV 30, 2016, View Source [SID1234516865]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the poster, "Top-Line Results from Vesigenurtacel-L (HS-410) in Combination with BCG from a Randomized, Blinded Phase 2 Trial in Patients with Non-Muscle Invasive Bladder Cancer (NMIBC)," researchers reported that there were encouraging signs of anti-tumor activity as HS-410 generated a robust antigen-specific immune response to multiple tumor-associated peptides in treated patients, while there were no immune responses of this type in the placebo. However, these responses did not translate into clinical outcomes, and there was no statistically significant difference in the primary endpoint (proportion of recurrence-free survival at one year) between the vaccine and placebo arms of the trial. To better assess the durability of the positive immunological responses, and in keeping with clinical trial guidance recently issued by International Bladder Cancer Group ("IBCG")1 recommending a 2-year study duration for NMIBC trials, Heat will continue to monitor all patients enrolled in the study for an additional 12 months. At that time, Heat will make a final determination whether to progress its bladder cancer program into a Phase 3 trial.

"The ability of HS-410 to prime T-cells suggests a strong signal that the vaccine is having an impact, as well as an opportunity to improve responses, in this challenging disease," said study principal investigator, Gary Steinberg, M.D., The Bruce and Beth White Family Professor of Surgery and Director of Urologic Oncology at the University of Chicago. "Historically, NMIBC has been very difficult to treat, with BCG being the only approved therapy in the past 40 years. We were surprised to see that all arms of this trial performed much better than historical control, which is a testament to improvements in standard of care, and validates our choice to run a controlled clinical trial. We look forward to continuing to monitor patients in this trial, per IBCG recommendations. and would like to thank the many patients and their families for the commitment to this trial and advancement of the treatment of bladder cancer."

"We were pleased to see a robust antigen-specific immune response, reinforcing our earlier clinical data," Jeff Wolf, CEO of Heat Biologics, commented. "Even though we did not achieve our desired clinical outcomes, we are encouraged by the results and believe this, and other combination therapies, have the potential to improve long-term outcomes. In particular, Heat’s ComPACT technology, combining a therapeutic vaccine with an immune co-stimulator in a single product, was designed to substantially improve immune response durability. We are actively pursuing new programs to complement our existing platforms, which we expect to announce in early 2017. Moreover, we look forward to examining the additional top-line data that will be reported next week for our combination trial of HS-110 in with Bristol-Myers Squibb’s Opdivo (nivolumab) in lung cancer."

"HS-410 stimulated antigen-specific immune responses to multiple tumor-associated peptides," commented Taylor Schreiber, M.D., Ph.D., Chief Scientific Officer. "The kinetics of these responses indicate efficient priming of CD8+ T cells, consistent with results seen in other Heat Biologics clinical trials. Remaining analyses are in progress to inform future development of other agents and/or combinations aimed at improving immune response durability. Further understanding of the secondary and exploratory endpoints will advise future development steps."

"We conducted a cost-efficient trial and will continue to gather important data with minimal ongoing costs," Mr. Wolf added. "We have maintained a solid balance sheet and intend to continue to be very prudent in managing our expenses as we generate additional clinical data and progress our programs and platforms."

Additionally, Heat will be presenting topline data on its non-small cell lung cancer study of HS-110 in combination with Bristol-Myers Squibb’s Opdivo (nivolumab) at the International Association for the Study of Lung Cancer Annual Meeting in Vienna, Austria, on December 6th. The presentation, "Viagenpumatucel-L Bolsters Response to Nivolumab Therapy in Advanced Lung Adenocarcinoma: Preliminary Data from the DURGA Trial" will occur on December 6, 2016, 8:56 AM EST (14:56 CET). Following this data release, Heat plans to hold an investor call on December 8th to discuss its overall clinical strategy moving forward.

1 Definitions, End Points, and Clinical Trial Designs for Non–Muscle-Invasive Bladder Cancer: Recommendations from the International Bladder Cancer Group, Journal of Clinical Oncology, 34(16):1935-44, June, 2016.

On November 30, 2016 Viracta Therapeutics, Inc. reported completion of its acquisition of drug development candidate, VRx-3996, from Chroma Therapeutics, Ltd (Press release, Viracta Therapeutics, NOV 30, 2016, View Source [SID1234519770]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Viracta plans to advance VRx-3996 (previously CHR-3996) into Phase 2 clinical testing for application in Viracta’s proprietary anticancer combination therapy approach. The Company will initially focus on Epstein Barr Virus-associated lymphoid malignancies. Additional applications include a range of EBV-associated cancers and other serious diseases. The Company believes that its viral activation therapy platform and VRx-3996 hold potential to treat cancers and other disease associated with a range of viral pathogens.

"We are excited to complete our acquisition of VRx-3996 from Chroma, and thank the Chroma team for the excellent work that they contributed to discover and advance the drug candidate through early clinical development," said Viracta Chief Executive Officer, Ivor Royston, M.D.

"As a leader in the viral activation therapy field, we are pleased to have Viracta advance 3996 to potentially benefit patients with viral-associated cancers," said Chroma CEO, Richard Bungay.

"VRx-3996 has demonstrated ideal characteristics for use in Viracta’s viral activation therapy approach, and we look forward to advancing into clinical testing to treat EBV-associated cancers," commented Viracta Chief Medical Officer, Marshelle Smith Warren, M.D.
About VRx-3996

VRx-3996 belongs to a clinically validated drug class called histone deacetylase (HDAC) inhibitors, which affect association of DNA with histones to alter gene expression patterns. VRx-3996 is selective for Class 1 HDACs, including isoforms targeted in Viracta’s viral activation approach. It exhibited favorable pharmacokinetic and pharmacodynamics properties as well as favorable tolerability profile after oral administration in a Phase 1b trial in cancer patients as a single agent. In non-clinical testing, VRx-3996 was among the most potent activators of targeted viral genes. When applied in combination with an antiviral pro-drug in Viracta’s viral activation therapy approach, VRx-3996 drives selective killing of EBV-positive cancer cells.
About Chroma-Viracta Transaction

Under the VRx-3996 asset purchase agreement, Viracta acquired rights to VRx-3996 for all geographies and applications in exchange for issuance of Viracta equity to Chroma.

On November 30, 2016 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, reported that interim data from its ongoing Phase 1 clinical study of bb2121, the company’s investigational anti-BCMA CAR T cell product candidate in patients with relapsed/refractory multiple myeloma, will be presented on Thursday, December 1, 2016 at the 28th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany (Press release, bluebird bio, NOV 30, 2016, View Source;p=RssLanding&cat=news&id=2226688 [SID1234516854]). bluebird bio is developing bb2121 in collaboration with Celgene Corporation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased that these early data from our ongoing Phase 1 study of bb2121 demonstrate objective anti-tumor responses in heavily pre-treated patients with multiple myeloma, with all patients in the 15.0 x 107 and 45.0 x 107 CAR+ T cell dose cohorts achieving responses, including among them, patients with stringent complete responses and elimination of minimal residual disease," said David Davidson, M.D., chief medical officer, bluebird bio. "We are also encouraged by the safety profile to date, particularly the lack of severe cytokine release syndrome or neurotoxicity. In light of these positive data, and thanks to the multiple participating clinical sites and centralized manufacturing infrastructure we and our partner Celgene have built for this program, we anticipate efficiently completing the dose escalation stage of the trial and initiating the expansion cohort."

Clinical remissions and limited toxicity in a first-in-human multicenter study of bb2121, a novel anti-BCMA CAR T cell therapy for relapsed/refractory multiple myeloma (Abstract #14, LBA)

Presenter: Yi Lin, M.D., Ph.D., Assistant Professor of Medicine and Oncology, Mayo Clinic Division of Hematology, Rochester, MN
Date: Thursday, December 1, 2016, 18:00 CET (12:00 pm ET)
Session: Plenary Session 7

The open-label Phase 1 CRB-401 study (NCT02658929) is investigating the administration of bb2121 anti-BCMA CAR T cells in patients with relapsed and/or refractory multiple myeloma. The primary endpoint of the study is incidence of adverse events (AEs) and abnormal laboratory test results, including dose-limiting toxicities (DLTs). The study also seeks to assess disease-specific response criteria including: complete response (CR), very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. The study also seeks to determine the recommended dose for further clinical trials. Patients on study were heavily pre-treated, with a median of six prior therapies (range: 5 – 13). As of the November 18th, 2016 data cut-off, 11 patients had been enrolled and dosed in four dose cohorts: 5.0 x 107, 15.0 x 107, 45.0 x 107 and 80 x 107 CAR+ T cells. All 11 dosed patients were evaluable for safety, and the first nine patients (5.0 x 107, 15.0 x 107, 45.0 x 107 dose cohorts) have undergone their first multiple myeloma tumor restaging and were evaluable for efficacy. This study is currently enrolling patients at seven sites in the U.S., with an anticipated total enrollment of 50 patients.

Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 anti-BCMA CAR T cells. The CAR T cells were produced from each patient’s own blood cells, which were modified using a lentiviral vector encoding the anti-BCMA CAR.

Results, as of November 18th, 2016 Data Cut-off:

Cohort 1 2 3
CAR+ T Cell dose 5.0 x 107 15.0 x 107 45.0 x 107
Overall Response
Rate in cohort

33% 100% 100%
Best Response PD
SD

PR

sCR (time to response: 2 months)
sCR* (time to response: 4 months)
VGPR*

*Both patients with
a minimal residual
disease (MRD)
assessment at
Month 1 were MRD
negative

PR
PR

PR

All patients in cohorts 2 and 3 with bone
marrow involvement at baseline had no
detectable multiple myeloma cells in their
bone marrow on Day 14 or beyond

Median Prior
Lines of Therapy

6 (range: 5-13); all patients had a prior autologous stem cell
transplant, as well as prior exposure to a proteasome inhibitor and
an immunomodulatory agent; 64 percent of patients had
previously received daratumumab or CD38 antibody

Safety
No dose-limiting toxicities and no Grade 3 or higher
neurotoxicities or Grade 3 or higher cytokine release syndrome
(CRS) have been observed. No patients received tocilizumab or
steroids.

On November 30, 2016 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 inhibitor drugs to improve immune cell trafficking and increase the ability for T-cells to track and destroy cancer, reported the presentation of preclinical data for X4P-001, the Company’s lead drug candidate, at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium, held November 29 – December 2 in Munich, Germany (Press release, X4 Pharmaceuticals, NOV 30, 2016, View Source [SID1234516899]). The findings in preclinical models of renal cell carcinoma (RCC) elucidate the molecular mechanism that directs the trafficking of key immune cells in the tumor microenvironment that result in synergistic anti-tumor effect of X4P-001 and axitinib, a tyrosine kinase inhibitor approved for use as a targeted therapy for RCC. The data also showed that X4P-001 blocks the critical escape mechanism that leads to resistance to treatment with axitinib, a vascular endothelial growth factor receptor (VEGF-R) antagonist cancer therapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"While treatment with VEGF-R antagonists is first line therapy, it can be hindered by acquired resistance," said James W. Mier, M.D., Associate Professor of Medicine at the Beth Israel Deaconess Medical Center and senior author of the poster presentation. "These data show clear evidence that by inhibiting CXCR4, X4P-001 blocks a critical mechanism of this resistance, resulting in a synergistic anti-tumor effect which may ultimately lead to improved patient outcomes."

The poster, entitled "MDSC trafficking and function in RCC by CXCR4 in the presence of a VEGF-R antagonist is dependent on HIF-2a expression," shows that CXCR4 inhibition with X4P-001 blocks the primary pathway that leads to resistance to VEGF-R cancer therapies in renal cell carcinoma. Acquired resistance of tumors to VEGF-R antagonists is dependent on HIF-2a, CXCR4/CXCL12, and the infiltration of myeloid derived suppressor cells (MDSCs), into the tumor. CXCR4 inhibition with X4P-001 blocks communication between the tumor and MDSCs, suppresses HIF-2a expression, reduces MDSC tumor infiltration, and improves anti-tumor effect.

"These data demonstrate the potential of X4P-001 in combination with approved therapies as a potential new treatment approach to achieve impactful clinical responses for patients with advanced ccRCC, a cancer with serious unmet needs," said Paula Ragan, PhD, Founder, President and CEO of X4. "The data provide additional compelling rationale for our ongoing Phase 1/2 clinical study evaluating the combination of X4P-001 and axitinib in patients with advanced ccRCC."

About X4P-001 in Cancer
X4P-001 is an oral, small molecule inhibitor of CXCR4, or C-X-C receptor type 4, the receptor for the chemokine CXCL12 (also known as stromal derived factor-1, or SDF-1). Recent studies demonstrate that CXCR4/CXCL12 is a primary receptor-ligand pair that cancer cells and surrounding stromal cells express and use to block normal immune function and promote angiogenesis through the trafficking of T-effector and T-regulatory cells, as well as myeloid derived suppressor cells (MDSCs), in the tumor microenvironment.1, 2 Pre-clinical studies have demonstrated X4P-001 activity alone and in combination with approved cancer therapies resulted in an increased tumor-specific immune response and significant inhibition of tumor growth. X4P-001 has been tested in over 70 subjects in four clinical trials in healthy volunteers and HIV-infected patients to date and was shown to be well tolerated.

About Renal Cell Carcinoma
Kidney cancer is among the ten most common cancers in both men and women with more than 60,000 new diagnoses each year in the United States.3 Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, and advanced ccRCC accounts for approximately 20% of the patient population. Therapies for advanced ccRCC include immunotherapies, mammalian target of rapamycin (mTOR) kinase inhibitors, and angiogenesis inhibitors, such as vascular endothelial growth factor (VEGF) inhibitors.4 There continue to be unmet medical needs with advanced ccRCC because durable responses remain a serious clinical challenge for patients with advanced disease.