On November 11, 2016 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported new clinical data from a Phase II Investigator Sponsored Trial led by the University of California, San Francisco (UCSF) (Press release, OncoSec Medical, NOV 11, 2016, View Source [SID1234516530]). The data was presented today at an oral poster presentation (#466) by Dr. Alain Algazi at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) ("SITC") Annual Meeting in National Harbor, MD.

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This single-arm, open-label trial assessed the combination of OncoSec’s investigational intratumoral therapy, ImmunoPulse IL-12, and Merck’s KEYTRUDA (pembrolizumab) in patients with unresectable metastatic melanoma. A predictive biomarker was used to enroll patients that have a low likelihood of response to an anti-PD1 agent alone, and the purpose of the trial is to assess whether the addition of ImmunoPulse IL-12 can increase response rates in these patients.

The full-text abstract is available and can be viewed on SITC (Free SITC Whitepaper)’s website at www.sitcancer.org. The poster presentation and handout showing the data of the 40% overall response rate (ORR) in patients predicted not to respond to pembrolizumab are available in the Publications section of OncoSec’s website.

For more information about this trial, please visit: View Source;rank=3

On November 11, 2016 Delcath Systems, Inc. (NASDAQ: DCTH), an interventional oncology company focused on the treatment of primary and metastatic liver cancers, reported financial results for the three and nine months ended September 30, 2016 (Press release, Delcath Systems, NOV 11, 2016, View Source;p=RssLanding&cat=news&id=2221745 [SID1234516515]).

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Highlights for the third quarter of 2016 and recent weeks include:

Raised $1,275,000 through an underwritten public offering of common stock and warrants;
Expanded the FOCUS Phase 3 Trial in hepatic dominant ocular melanoma to include 10 new research centers in the U.S. and Europe;
Presented data from two single-institution studies conducted in Germany on the use of the Delcath Hepatic CHEMOSAT Delivery System to treat patients with liver metastases in scientific posters at the Cardiovascular and Interventional Radiology Society of Europe (CIRSE) annual meeting;
Announced acceptance for publication of a retrospective review study, "Chemosaturation Percutaneous Hepatic Perfusion: A Systemic Review," by Dr. Arndt Vogel, et al, in the prestigious journal Advances in Therapy; and
Sponsored the Ocular Melanoma Foundation Eye Am Not Alone patient education retreat.
"Throughout the third quarter we continued to make steady progress in our clinical development program for Melphalan/HDS and in our efforts to advance CHEMOSAT as a commercially viable treatment option for primary and metastatic liver cancers in Europe," said Jennifer K. Simpson, Ph.D., MSN, CRNP, President and Chief Executive Officer of Delcath. "We also recently secured an additional $1.275 million in financing via a small fundraise in October, which will bridge us to receipt of the first cash release from the committed financing we announced in June 2016. Assuming all conditions are satisfied, we expect the anticipated quarterly releases throughout 2017 will fund our clinical development plan through the end of 2017, while also supporting our commercial activities in Europe.

"The presentation and publication of data supportive of CHEMOSAT continued during our third quarter. This includes a retrospective review study conducted by a team led by Dr. Arndt Vogel of the University of Hanover in Germany, which was accepted for publication by the prestigious peer-reviewed journal, Advances in Therapy. This study originated as a white paper produced by our Experts Panel in 2015, and we are pleased that the potential for CHEMOSAT to treat primary and metastatic liver cancers as identified by our experts will now reach a wider audience. Also during the quarter investigators from Asklepios Barmbek Clinic and Hanover Medical School in Germany, and Southampton University Hospital in the United Kingdom, presented compelling data from their single-institution investigations. These data provide us with considerable confidence that similar results may be formally validated by the trials that comprise our Clinical Development Plan, and we look forward to additional presentations and publications of data in support of CHEMOSAT throughout the remainder of the year and beyond.

"Negotiations by hospitals in Germany to determine reimbursement levels for CHEMOSAT under the ZE national system are expected to conclude during our fourth quarter. We believe that favorable reimbursement levels defined through this process will support growth in procedure volumes in Germany and provide important validation for reimbursement appeals in other markets in Europe.

"The advances we made in 2016 have positioned us to achieve important clinical inflection points in our FOCUS trial and our global Phase 2 program in HCC and ICC, as we work to expand global access to CHEMOSAT for the benefit of patients suffering with primary and metastatic liver cancers," concluded Dr. Simpson.

Third Quarter Financial Results

Total revenues for the third quarter of 2016 and 2015 were $0.4 million. Selling, general and administrative expenses for the third quarter of 2016 were $2.4 million, compared with $2.3 million for the same period in 2015, primarily attributable to a slight increase in facility and professional expenses. Research and development expenses increased to $2.7 million for the 2016 third quarter from $1.7 million for the same period in 2015, primarily due to increased investment in clinical development initiatives, specifically the global Phase 3 FOCUS clinical trial.

Total operating expenses for the third quarter of 2016 increased to $5.0 million from $4.0 million for the same period in 2015. This reflects an increase in clinical development initiatives.

The Company recorded a net loss for the three months ended September 30, 2016 of $1.0 million, or $0.66 per share, a decrease of $1.4 million from a net loss of $2.4 million, or $1.96 per share, for the same period in 2015. This was primarily driven by amortization of debt discounts related to the convertible note issued in June 2016 and a change in the fair value of the warrant liability, a non-cash item.

Nine Month Financial Results

Total revenues for the first nine months of 2016 and 2015 were $1.3 million. Selling, general and administrative expenses for the first nine months of 2016 were $7.0 million, an improvement of $0.8 million or 11% from $7.8 million reported for the same period in 2015, primarily attributable to a reduction in facility expenses related to the lease restructurings. Research and development expenses during the first nine months of 2016 increased to $6.0 million compared with $4.1 million for the same period in 2015, primarily due to increased investment in clinical development initiatives.

Total operating expenses for the first nine months of 2016 were $13.0 million compared with $12.0 million for the same period in 2015.

The Company recorded a net loss for the nine months ended September 30, 2016 of $9.5 million, or $6.39 per share, a decrease of $0.1 million from a net loss of $9.6 million, or $10.75 per share, for the nine months ended September 30, 2015. This was primarily driven by amortization of debt discounts related to the convertible note issued in June 2016 and a change in the fair value of the warrant liability, a non-cash item.

Balance Sheet Highlights

As of September 30, 2016, Delcath had cash and cash equivalents of $3.7 million, compared with $12.6 million as of December 31, 2015. During the first nine months of 2016, the Company used $10.6 million in cash to fund its operating activities. In June 2016, Delcath issued $35.0 million of senior convertible notes and related common stock purchase warrants and in October 2016, the Company raised $1,275,000 through an underwritten public offering of common stock and warrants. As a result, Delcath believes it has sufficient capital to fund its operating activities through the end of 2017.

On November 11, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical stage biotechnology company developing cancer immunotherapies, reported new data highlighting the potential therapeutic benefit of Advaxis’ lead immunotherapy candidate, axalimogene filolisbac (AXAL), both as a monotherapy and in combination with antibody-based immunotherapies in multiple patient populations with HPV+ cancers (Press release, Advaxis, NOV 11, 2016, View Source [SID1234516490]). These data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting & Associated Programs this week in National Harbor, MD.

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A Phase 1/2 study of durvalumab alone or in combination with AXAL in recurrent/persistent or metastatic cervical or human papillomavirus (HPV)+ squamous cell cancer of the head and neck (HNSCC): Preliminary Phase 1 results (SITC 2016 abstract no. 215354)
This Phase 1 (Part A; 3+3) dose-escalation study was designed to assess the overall safety and select the recommended phase 2 dose (RP2D) of AXAL in combination with durvalumab in patients with recurrent/metastatic cervical or HPV+ HNSCC cancer. Patients received AXAL (1×109 colony-forming units [CFU]) every four weeks and durvalumab (3 mg/kg or 10 mg/kg) every two weeks.

Preliminary results from Part A dose escalation showed that there were no dose limiting toxicities observed, and the safety profile was consistent with previous findings for both AXAL and durvalumab. The recommended phase 2 dose was established as 1×109 CFU for AXAL and 10 mg/kg for durvalumab. One patient with cervical cancer achieved a complete response, which remains ongoing after 12 months of follow-up, and one patient, also with cervical cancer, achieved a partial response with subsequent disease progression. In addition, two patients with HNSCC achieved stable disease. Treatment related adverse events (TRAE) were reported in 91 percent of patients; the majority were either grade 1 or grade 2 events such as chills, fever, nausea and hypotension. Grade 3 TRAEs occurred in three patients, and one patient experienced a grade 4 event.

"When treating or evaluating investigational therapies for these kinds of metastatic, recurrent tumors, it is rare for an immunotherapy to result in a complete response," said Brian Slomovitz, MD, principal investigator and Director of the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology at the University of Miami Miller School of Medicine. "These early data show encouraging anti-tumor activity of the combination of AXAL and durvalumab and the regimen was generally well tolerated, which supports continued study of this combination regimen."

Combination of Listeria-based human papillomavirus (HPV)-E7 cancer vaccine (AXAL) with CD137 agonistic antibody provides an effective immunotherapy for HPV+ tumors in a mouse model (SITC 2016 abstract no. 215321)
A preclinical study evaluated the ability of AXAL to control tumor growth, prolong survival and reprogram the tumor microenvironment in combination with agonistic antibodies of T cell co-stimulatory receptors or with antagonistic antibodies of immune checkpoint inhibitors in an HPV+ tumor model. Of the monoclonal antibodies (mAbs) tested, anti-CD137 mAb and anti-CTLA-4 mAb were the most effective at synergizing with AXAL to eradicate established HPV+ tumors and to provide long-term survival (>8 weeks). Complete tumor regression was observed in 28 percent of the AXAL + anti-CD137 mAb treatment group and in 33 percent of the AXAL + anti-CTLA-4 mAb treatment group.

The study demonstrated a reprogramming of the tumor microenvironment in favor of antitumor immunity in both of the combination treatment groups. Importantly, there were increased percentages of tumor antigen-specific T cells and mature dendritic cells as well as decreased percentages of regulatory T cells and immunosuppressive macrophages compared to the single-agent treatments. Together, these data show that AXAL in combination with a CD137 agonistic antibody or with a CTLA-4 antagonistic antibody synergize to enhance antitumor immunity.

AIM2CERV: a randomized phase 3 study of adjuvant AXAL immunotherapy following chemoradiation in patients who have high-risk locally advanced cervical cancer (HRLACC) (SITC 2016 abstract no. 214095)
Advaxis’ Phase 3 AIM2CERV trial is a double-blind, placebo-controlled, multinational, multicenter, randomized study (NCT02853604). AIM2CERV is designed to demonstrate the efficacy and safety of AXAL as an adjuvant treatment in patients with stage I-IVA high risk, locally-advanced cervical cancer who have received cisplatin-based concurrent chemoradiation therapy (CCRT). Following CCRT, patients will receive AXAL for up to one year. A disease-free survival analysis will be conducted following at least 184 events. The study will enroll approximately 450 patients at 150 sites. Several trial sites are currently open and actively screening patients. In July, Advaxis received a Special Protocol Assessment for the AIM2CERV trial, as well as Fast Track designation for AXAL as an adjuvant therapy for HRLACC patients. For more information on Advaxis clinical trials, visit www.clinicaltrials.gov.

The presentation slides and audio are now available at www.advaxis.com.

On November 11, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported that data for its drug candidates CB-839, the company’s novel glutaminase inhibitor, and CB-1158, the company’s novel arginase inhibitor, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2016 Annual Meeting, which is being held from November 9-13, 2016 in National Harbor, Maryland (Press release, Calithera Biosciences, NOV 11, 2016, View Source;p=RssLanding&cat=news&id=2221726 [SID1234516491]).

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"Both CB-839 and CB-1158 have the distinction of targeting metabolic and immune checkpoints which we believe, through rational combinations, have the potential to be transformational in the treatment of cancer. CB-839 and CB-1158 are each in clinical trials with cohorts planned in combination with approved immunotherapy agents," said Susan Molineaux, Ph.D., President and Chief Executive Officer of Calithera. "We are pleased that CB-1158 shows significant pharmacodynamic effects in patients at the first dose level tested."

Preclinical CB-839 data will be presented in a poster titled, "Targeting tumor glutamine metabolism with CB-839 enhances the efficacy of immune checkpoint inhibitors," by Andy MacKinnon, Ph.D., Calithera Biosciences (Poster #230). Included in the presentation are data that provide further insights into the mechanism by which inhibition of glutaminase by CB-839 enhances T-cell activation and increases the anti-tumor activity of anti-PD-L1 and anti-PD-1 antibodies. Glutamine deprivation during T-cell activation was shown to block Myc expression and Myc-driven metabolic re-programming, and to promote expression of T-cell suppressive markers such as BTLA, CTLA-4, PD-1, and CD73. In two syngeneic animal models, CT26 (colon cancer) and B16 (melanoma) the combination of CB-839 and anti-PD-L1 or anti-PD-1 showed significantly enhanced anti-tumor activity over checkpoint inhibition alone resulting in increased tumor regressions in the CT26 model. Depletion of CD8+ T-cells from these tumor-bearing animals reversed the anti-tumor effects of the combination, confirming an immune-mediated mechanism of action.

CB-1158 data will be presented in a poster titled, "Arginase inhibitor CB-1158 alleviates immunosuppression and enhances anti-tumor responses as a single agent and in combination with other immunotherapies," by Amani Makkouk, Ph.D., Calithera Biosciences (Poster #231). Arginase is expressed in myeloid derived suppressor cells (MDSCs) and exerts an immunosuppressive effect on T-cells and NK cells by depleting arginine and blocking activation. Tumor cell infiltrates in patients with solid tumor cancers contain significant numbers of arginase-expressing MDSCs; as a result, these patients have increased levels of plasma arginase and decreased levels of plasma arginine compared to healthy individuals. CB-1158, a highly selective, orally bioavailable, small molecule inhibitor of human arginase with nanomolar potency, has single agent immune-mediated efficacy in multiple syngeneic animal models. Inhibition of tumor growth was accompanied by an increase in the local concentration of arginine, and the induction of multiple pro-inflammatory changes in the tumor microenvironment. Treatment with CB-1158 also enhanced the anti-tumor activity of adoptive T-cell therapy, checkpoint blockade and chemotherapy in these animal models. CB-1158 is currently being tested in a Phase 1 clinical trial in patients with solid tumors. Three patients in the first cohort were treated with 50 mg of CB-1158 twice daily. This dose was well-tolerated and was pharmacologically active, resulting in sustained elevation of arginine in the plasma of all three patients. The trial is continuing to enroll patients to complete the dose escalation phase of the study, to be followed by combination studies with a PD-1 antibody.

In addition, two posters describing trial design will be presented during the "Clinical Trials in Progress" session:

CX-1158-101: A first-in-human phase I study of a small molecule inhibitor of arginase (CB-1158) as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor in patients with solid tumors

Presenter: Siqing Fu, M.D., Ph.D., University of Texas, MD Anderson Cancer Center, Poster #155

CX-839-004: A phase I/II study of the safety, pharmacokinetics, and pharmacodynamics of the glutaminase inhibitor CB-839 combined with nivolumab in patients with renal cell carcinoma, melanoma, and non-small cell lung cancer

Presenter: Elaine Lam, M.D., University of Colorado, Denver, Poster #166

On November 11, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported a poster with updated interim results from its on-going Phase 1b/2 trial of aldoxorubicin in combination with ifosfamide/mesna in patients with advanced sarcomas at the 2016 Annual Meeting of the Connective Tissue Oncology Society (CTOS) being held in Lisbon, Portugal (Press release, CytRx, NOV 11, 2016, View Source;p=RssLanding&cat=news&id=2221789 [SID1234516494]).

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Forty-two patients have been enrolled to date and 36 were evaluable as of the data cutoff. Of the 36 evaluable patients receiving either 170mg/m2 (n=7) or 250mg/m2 (n=29) of aldoxorubicin plus ifosfamide and mesna, 14 of 36 (39%) achieved a partial response of the target lesion by RECIST 1.1 criteria, 21 of 36 (58%) had stable disease, and one patient had progressive disease. As previously reported in October at the 2016 ESMO (Free ESMO Whitepaper) Congress, median progression-free survival has not yet been reached. Dose-limiting toxicities were not observed in either cohort, and no clinically significant cardiac toxicities were seen. The most common Grade 3 or 4 adverse events were neutropenia (71%), anemia (54%), thrombocytopenia (17%) and febrile neutropenia (14%). There were nine treatment-related serious adverse events, and no treatment-related deaths. The trial has been expanded to allow continued enrollment of additional sarcoma patients at the 250 mg/m2 dose of aldoxorubicin with ifosfamide and mesna.

"The CTOS annual meeting is the preeminent medical conference focused on sarcomas and provides an opportunity to update the international sarcoma community with the latest results for aldoxorubicin, said Sant Chawla, M.D., F.R.A.C.P., the trial’s principal investigator and Director of the Sarcoma Oncology Center in Santa Monica, California. "Our poster highlights that nearly 40% of the sarcoma patients receiving the combination of aldoxorubicin with ifosfamide and mesna achieved a partial response of the target lesion by RECIST criteria, and half of those had greater than 50% shrinkage of their tumors. This is important because it allowed some patients who initially could not have surgery to become eligible for surgery."

The Phase 1b/2 clinical study is a single-center trial that has enrolled 42 patients to date with locally advanced, unresectable, and/or metastatic soft tissue sarcoma, intermediate-grade or high-grade chondrosarcoma or osteosarcoma. In the dose escalation phase, patients received either 170mg/m2 or 250mg/m2 of aldoxorubicin in combination with up to a 14-day continuous infusion of ifosfamide (1g/m2/day) plus mesna over a 28-day cycle. Up to six cycles of ifosfamide/mesna with aldoxorubicin can be administered, and aldoxorubicin may be continued until tumor progression or unacceptable toxicity occurs. The expansion phase is enrolling patients at the 250mg/m2 dose of aldoxorubicin and will allow for patients that had received prior chemotherapy to be included. The primary endpoint of the study is safety, and secondary endpoints include overall response rates and progression-free survival.

About Aldoxorubicin

Aldoxorubicin is a rationally-engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of doxorubicin in excess of 5,000 mg/m2. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized global Phase 2b clinical trial in first-line STS.