On November 11, 2016 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with cancer and rare diseases, is reporting translational data supporting the mechanism of action of intratumoral IMO-2125, a Toll-like receptor (TLR) 9 agonist from the ongoing Phase 1 dose escalating clinical trial (Press release, Idera Pharmaceuticals, NOV 11, 2016, View Source;p=RssLanding&cat=news&id=2221857 [SID1234516527]). In this trial, IMO-2125 is being evaluated in combination with ipilimumab for treatment of patients with metastatic melanoma with disease that is refractory to anti-PD-1 inhibitors, and have minimal options and low expectation of clinical response with ipilimumab treatment alone. Taken together, the previously reported early clinical responses and the supporting mechanism of action translational data being presented today, indicate that intratumoral IMO-2125 is a potent agent for the stimulation of the tumor microenvironment.

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In the oral presentation at the 2016 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (SITC) (Free SITC Whitepaper), entitled "Reactivating the anti-tumor immune response by targeting innate and adaptive immunity in a phase I/II study of intratumoral IMO-2125 in combination with systemic ipilimumab in patients with anti-PD-1 refractory metastatic melanoma," Cara Haymaker, Ph.D., from the University of Texas, MD Anderson Cancer Center, presented an overview of the modulation of the tumor microenvironment through the unique mechanism of action of intratumoral IMO-2125 and provided an update on the initial findings of the translational data through the first cohorts of the trial. Immunological analysis of the biopsy taken from the lesion injected with IMO-2125 showed rapid dendritic cell maturation which is a critical first step in the induction of the immune cascade within the tumor microenvironment. During the treatment period, T-cell expansion and activation and importantly, immune infiltration was observed in the biopsied distant lesions of the responding patients, demonstrating the abscopal effect.

From a clinical perspective, through all dosing cohorts tested to date, no dose-limiting toxicity has been seen. Preliminary clinical activity is also encouraging in this population with disease that is refractory to PD-1 inhibitors as 3 responses (including one CR) have already been recorded. The trial continues to dose escalate and enrollment into the planned anti-PD-1 inhibitor combination arm has also commenced.

"We hypothesized that the intratumoral injection of IMO-2125 into a single tumor lesion would stimulate dendritic cells to produce interferon and the downstream immune cascade in the tumor microenvironment, resulting in the recruitment and activation of tumor-killing T-cells in both the injected and non-injected tumors," said Joanna Horobin, M.B., Ch.B., Idera’s Chief Medical Officer. "When combined with a systemic checkpoint inhibitor, this change in the tumor microenvironment was expected to affect tumor responses in both injected and distant tumors. Today Dr. Haymaker presented analyses of serial biopsies from the tumors of patients with anti-PD-1 refractory melanoma in our ongoing phase 1 dose escalation trial of intratumoral IMO-2125 which clearly demonstrated these beneficial changes in the tumor microenvironment, essentially turning "cold" tumors "hot" in responding patients. We are thrilled to see what we believe to be, the clear translation of our hypothesis in patients. Moreover, in three patients the investigator has reported substantial tumor shrinkage with 2 partial and one complete response."

A copy of the slides from today’s presentation as well as a copy of a related poster presentation are currently available on Idera’s corporate website at View Source

These early results are from the phase 1 portion of study IMO-2125-204 (NCT02644967) in which cohorts of patients with metastatic melanoma unresponsive to PD-1 inhibitor therapy are being administered escalating doses of IMO-2125 ranging from 4 mg/kg through 32 mg/kg. IMO-2125 is injected intra-tumorally into a designated tumor lesion together with a standard dosing regimen of ipilimumab. The trial has recently been amended to also study the combination of IMO-2125 and pembrolizumab given intravenously. Following determination of the recommended phase 2 doses (RP2D) additional patients will be treated in an expansion phase 2 portion of the study. The primary objective of the phase 1 portion of the trial is to characterize the safety and determine a RP2D of IMO-2125 when administered intra-tumorally in combination with ipilimumab or pembrolizumab. The primary objective of the phase 2 portion is to assess the clinical activity of IMO-2125 in each combination at the respective RP2Ds. Assessment will be based on the immune-related response criteria (irRC) and additionally the traditional RECIST criteria. Serial biopsies are being taken of selected injected and non-injected tumor lesions to assess immune changes and correlate with clinical response assessments. The trial will enroll approximately 60 patients. The study is being conducted at MD Anderson and is being led by Adi Diab, MD, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, MD Anderson as part of a strategic research alliance announced by Idera and MD Anderson in 2015.

Additionally at SITC (Free SITC Whitepaper), on November 9th, Idera’s Oncology Lead, Mark Cornfeld, M.D., M.P.H., presented an overview of IMO-2125’s unique mechanism of action in an oral presentation, entitled "IMO-2125, An Investigational Intratumoral Toll-Like Receptor 9 Agonist, Modulates the Tumor Microenvironment to Enhance Anti-Tumor Immunity" during a session focused on New Clinical Agents in Development. A copy of the slides from this presentation is currently available on Idera’s corporate website at View Source

About Toll-like Receptors and Idera’s Immuno-Oncology Research Program

Toll-like receptors (TLRs) play a central role in the innate immune system, the body’s first line of defense against invading pathogens, as well as damaged or dysfunctional cells including cancer cells. The innate immune system is also involved in activating the adaptive immune system, which marshals highly specific immune responses to target pathogens or tissue. Cancer cells may exploit regulatory checkpoint pathways to avoid being recognized by the immune system, thereby shielding the tumor from immune attack. Checkpoint inhibitors such as agents targeting CTLA4 or programmed cell death protein 1 (PD1) are designed to enable the immune system to recognize tumor cells. In this setting, intra-tumoral TLR9 agonist administration may increase the tumor-infiltrating lymphocytes (TILs), and thereby potentiate anti-cancer activity of checkpoint inhibitors in the injected tumor as well as systemically.

Idera’s TLR9 agonists, IMO-2125 and IMO-2055, have been created using the company’s proprietary chemistry-based discovery platform. IMO-2125 has been shown in various scientific presentations and publications to activate dendritic cells and induce interferon. Idera selected IMO-2125 to advance into clinical development in combination with checkpoint inhibitors based on this immunological profile. In previously completed clinical trials, subcutaneous administration of IMO-2125 was generally well tolerated in about 80 patients with hepatitis C. Idera has conducted further preclinical research evaluating the potential of IMO-2125 to enhance the anti-tumor activity of other checkpoint inhibitors in cancer immunotherapy with data being presented at several medical conferences during the past twelve months. The posters from these presentations can be found at View Source

About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as by through the lymphatic system (metastatic disease). Melanoma accounts for only one percent of skin cancer cases, but causes a large majority of skin cancer deaths. The American Cancer Society estimates that in 2016, there will be 76,380 new cases of melanoma in the U.S., and about 10,130 will die of this disease.

On November 11, 2016 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported positive preclinical findings generated using the Company’s Immune Repertoire Capture (IRC) technology, presented at the SITC (Free SITC Whitepaper) 2016 Annual Meeting, which is taking place in National Harbor, Maryland, November 9-13, 2016 (Press release, Atreca, NOV 11, 2016, View Source [SID1234522962]). In a poster titled, "Immune Profiling of an Elite Responder Following Checkpoint Inhibitor Therapy Reveals Functional Anti Tumor Antibodies Within Expanded IgG Lineages," a research team including scientists at Atreca and collaborators at a leading institution reported key research findings, including:

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Atreca’s IRC technology generated diverse antibodies from the active immune response of an individual with Stage 4 melanoma who had experienced long-term non-progression of disease following cancer regimens including anti-CTLA4 immunotherapy. These antibodies were sequenced from the patient’s blood plasmablasts, activated B cells that play a critical role in immune responses.
In in vitro assays, antibodies were shown to selectively bind tumor tissue but not normal tissue and to bind tumor types beyond the cancer type of the original patient.
Select antibodies demonstrated in vitro tumor killing through antibody-dependent cellular cytotoxicity (ADCC).
"Atreca is pioneering next-generation approaches to cancer immunotherapy based on our ability to elucidate the repertoire of cancer patient antibodies and T cell receptors (TCRs) contributing to positive outcomes," stated Daniel Emerling, Ph.D., Atreca’s Senior Vice President, Research. "In our presentation at SITC (Free SITC Whitepaper), we reported sequencing of over 2500 plasmablasts and identification of clonal antibody families from one exceptional cancer responder. By generating natively paired antibody heavy and light chain sequences, we were able to confirm the ability of a patient’s antibodies to target tumor cells and destroy them, including tumor types unrelated to that of the patient."

"Atreca is advancing a pipeline of therapeutic candidates that can drive and focus the activity of immune responses in cancer immunotherapy, particularly those unleashed by checkpoint inhibitors and immune activators," said Tito A. Serafini, Ph.D., Atreca’s President, Chief Executive Officer, and Co-Founder. "We are thrilled to present data highlighting the power and productivity of our platform at one of the leading cancer immunotherapy conferences. Our lead program is rapidly advancing in preclinical in vivo studies, and we look forward to further progress of our additional programs across multiple indications."

For more information on Atreca’s product portfolio, please visit View Source

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.