On November 11, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported the presentation of data at the 2016 Society for Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) annual meeting (Press release, Adaptimmune, NOV 11, 2016, View Source;p=RssLanding&cat=news&id=2221778 [SID1234516497]). The posters summarize: (1) preclinical data from Adaptimmune’s wholly-owned MAGE-A4 SPEAR (Specific Peptide Enhanced Affinity Receptor) T‑cells; (2) preclinical data from the Company’s second generation SPEAR T-cell, which is engineered to overcome immunosuppression in the tumor microenvironment by blocking the effects of transforming growth factor Beta (TGF-Beta); and (3) a single-patient case study from the Company’s ongoing synovial sarcoma study. The 2016 SITC (Free SITC Whitepaper) annual meeting is being held at the Gaylord National Hotel & Convention Center in National Harbor, Maryland on November 9 through 13, 2016.

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"We are pleased to present the preclinical data that underpins the decision to progress our next SPEAR T‑cell candidate, MAGE-A4, into clinical trials and we plan to file an IND in early 2017," said Gwendolyn Binder-Scholl, PhD Adaptimmune’s Chief Technology Officer. "MAGE–A4 is an attractive target which is broadly expressed in multiple solid tumors. Our MAGE-A4 SPEAR T-cell candidate has shown promising activity without any major safety concerns identified by our extensive preclinical testing. In addition, we are presenting initial data from a second generation NY-ESO SPEAR T-cell to overcome TGF‑Beta immunosuppression in the tumor microenvironment, as well as translational results from a case study of a patient with synovial sarcoma treated with NY-ESO SPEAR T‑cells. We believe that this type of data underscores our leadership in the field, and helps us to improve the function of SPEAR T-cells and inform future clinical study design."

Preclinical Testing of Wholly-owned MAGE-A4 SPEAR T-cells
In a poster presentation entitled, "Preclinical evaluation of an optimal-affinity MAGE-A4 T-cell receptor for adoptive T-cell therapy," Daniel Williams, Ph.D. of Adaptimmune, presented data examining MAGE-A4 expression in tumor and non-tumor tissues, and generation of an optimal affinity-enhanced MAGE-A4 SPEAR T‑cell.

MAGE-A4 is a cancer‑testis antigen, one of a number of genes with expression in adult tissues restricted to the testes, but also known to be expressed in several tumor types;
Target validation data indicates that MAGE-A4 is a very attractive target due to widespread and frequent expression in multiple tumor types including non‑small cell lung cancer, bladder, melanoma, head and neck, ovarian, esophageal, and gastric cancers with no detectable expression in non-tumor, non-germline tissues;
No major safety concerns were identified for MAGE-A4 SPEAR T-cells using Adaptimmune’s extensive in vitro preclinical testing platform;
MAGE-A4 SPEAR T-cells displayed strong cytotoxicity towards MAGE-A4+ melanoma and NSCLC cell lines, and;
These data will support filing of an IND, with submission planned for early 2017.
Second Generation SPEAR T-cell Engineered to Overcome TGF-Beta Tumor-mediated Immunosuppression
In a poster presentation entitled, "Engineering 2nd generation SPEAR T-cells to overcome TGF-Beta-mediated immunosuppression for adoptive cell therapy," Andrew Gerry, Ph.D. of Adaptimmune presented preclinical data regarding the development of this second generation SPEAR T-cell.

NY-ESO SPEAR T-cells have shown promising activity in clinical trials for both solid and liquid tumors. However, the depth and durability of response may potentially be affected by inhibitory factors in the tumor microenvironment;
One such factor is an inhibitory cytokine known as TGF-Beta that inhibits many T‑cell functions including proliferation, cytotoxicity, and cytokine production. Truncation of the intracellular signaling domain of the TGF-Beta receptor produces a dominant negative form of this receptor (dnTGFBetaRII), and data from the literature indicate that expression of this dominant negative receptor negates the inhibitory effects of TGF-Beta;
Adaptimmune engineered a second generation NY-ESO SPEAR T-cell co-expressing dnTGFBetaRII to produce resistance to TGF-Beta immunosuppression, and;
Data indicate that these second generation NY-ESO SPEAR T-cells co-expressing dnTGFBetaRII are resistant to inhibition by TGF-Beta in vitro.
Case Study Demonstrating Long-term SPEAR T-cell Persistence and Maintenance of Tumoricidal Activity
In a poster presentation entitled, "Case Report: Specific Peptide Enhanced Affinity Receptor T-Cells (SPEAR T-cells) demonstrate long-term persistence and both in vivo and ex vivo tumoricidal activity," Samik Basu M.D. and Gareth Betts Ph.D., both of Adaptimmune, presented translational data from a single patient who was treated in October 2013 in Cohort 1 of the ongoing study of NY-ESO SPEAR T-cell in synovial sarcoma. This patient was included in analyses that have been previously presented.

Data indicate that NY-ESO SPEAR T-cells have long-term persistence as they were readily detectable in the patient’s peripheral blood at 28 months post-infusion;
These cells exhibited markers of long‑term, self-renewing memory T-cells with minimal expression of phenotypic markers of exhaustion;
NY-ESO SPEAR T-cells retained tumoricidal activity when they were evaluated ex vivo against tumor targets exhibiting substantial killing of NY-ESO-1+ cells without additional re-stimulation, and;
Mechanisms underlying tumor progression remain under investigation and broadly appear to be related to T-cell exclusion by tumor, supporting consideration of rational combination study designs.

On November 11, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported an oral presentation with updated data on its study of NY‑ESO SPEAR (Specific Peptide Enhanced Affinity Receptor) T‑cells in the ongoing synovial sarcoma trial at the 2016 Connective Tissue Oncology Society (CTOS) annual meeting presented by Dr. Sandra P. D’Angelo of the Memorial Sloan Kettering Cancer Center (Press release, Adaptimmune, NOV 11, 2016, View Source;p=RssLanding&cat=news&id=2221814 [SID1234516498]). This presentation included an update to Cohort 1 median survival data. The meeting is being held at the Corinthia Hotel in Lisbon, Portugal from November 9 through 12, 2016.

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In an oral presentation entitled, "Open Label Non-Randomized Multi-Cohort Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO SPEAR T-cells in HLA-A*02+ Patients with Synovial Sarcoma," Dr. Sandra P. D’Angelo of the Memorial Sloan Kettering Cancer Center described that median survival for Cohort 1 is now calculated to be ~18 months (80 weeks), compared to ~13 months (56 weeks) as previously reported. The updated median survival calculation is based on analyses of additional patient follow-up data (cutoff of September 30, 2016). Other updates indicate that there continue to be additional partial responses among low NY-ESO expressors in Cohort 2, which is ongoing.

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 10, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported financial results for the third quarter ended September 30, 2016 (Press release, Adaptimmune, NOV 10, 2016, View Source;p=RssLanding&cat=news&id=2221279 [SID1234516506]).

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"Adaptimmune has delivered strong momentum since our last update," said James Noble, Adaptimmune’s Chief Executive Officer. "We have initiated the first site for a triple tumor study with our wholly-owned MAGE-A10 SPEAR T-cells under our new partnership with MD Anderson, and initiated Cohort 4 in our NY‑ESO synovial sarcoma study, as well as commenced recruitment of new patients in our NY-ESO ovarian cancer study under an amended protocol. In addition, we have executed a number of strategic agreements to accelerate our ability to develop, evaluate, and manufacture our affinity enhanced T-cell therapies for patients suffering from a wide array of solid tumor cancers. We are well placed for continued execution and to generate data from studies in multiple cancers with our SPEAR T-cell therapies in 2017."

Mr. Noble continued, "As we recently announced, the FDA has lifted the partial clinical hold on the planned NY-ESO MRCLS study, and we expect to start screening patients shortly. Our goal remains to be the first company to file for approval with a TCR therapy."

Recent Corporate and R&D Highlights:

Partial clinical hold lifted by FDA of NY-ESO SPEAR T-cell therapy study in MRCLS;
Initiation of screening in up to 15 MRCLS patients expected in 4Q 2016 with results from this revised study informing a potential future registration trial;
Established collaboration and supply agreement for combination study of Merck’s PD-1 inhibitor and the Company’s NY-ESO SPEAR T-cell therapy in multiple myeloma; initiation expected in 1H 2017;
Secured strategic agreement with PCT for dedicated manufacturing capacity;
Entered strategic alliance with MD Anderson to expedite T-cell therapy development;
Initiated MD Anderson as the first site for MAGE-A10 SPEAR T-cell therapy triple tumor study in urothelial cancer, melanoma, or squamous cell carcinoma of the head and neck;
Presented data demonstrating response to NY-ESO SPEAR T-cell therapy in synovial sarcoma patients with low NY-ESO expression (Cohort 2) (ESMO 2016);
Presented data indicating that fludarabine is required in preconditioning (Cohort 3) (ESMO 2016);
Commenced enrollment in NY-ESO synovial sarcoma Cohort 4 with a modified preconditioning regimen including fludarabine;
Started recruitment of additional ovarian cancer patients under an amended protocol using NY‑ESO SPEAR T-cell therapy with a modified preconditioning regimen including fludarabine;
Completed preclinical evaluation of MAGE-A4 SPEAR T-cells, with data demonstrating that MAGE-A4 is an attractive target with widespread expression in multiple tumor types; IND planned to be filed in 2017 (data to be presented at SITC (Free SITC Whitepaper) 2016); and
Completed initial evaluation of a second generation NY-ESO SPEAR-T cell expressing a dominant negative TGF-Beta receptor, with data indicating that these SPEAR T-cells may overcome TGF-Beta tumor-mediated immunosuppression (to be presented at SITC (Free SITC Whitepaper) 2016).
Financial Results for the Three-Month Period ended September 30, 2016

Cash / liquidity position: As of September 30, 2016, Adaptimmune had $140.4 million of cash and cash equivalents and $47.1 million of short-term deposits representing a total liquidity position1 of $187.5 million. For the three months ended September 30, 2016, the decrease in cash and cash equivalents was $10.5 million and the decrease in short-term deposits was $7.9 million, representing a decrease in total liquidity position of $18.4 million.
Revenue: For the three months ended September 30, 2016, revenue was $2.4 million compared to $4.9 million for the three months ended September 30, 2015. This decrease was primarily due to the impact of development milestones achieved in the three months ended in September 30, 2015 under the GSK Collaboration and License Agreement.
Research and development ("R&D") expenses: R&D expenses increased to $15.6 million for the three months ended September 30, 2016 from $8.9 million for the three months ended September 30, 2015, primarily due to increased period-over-period costs associated with ongoing clinical trials of the Company’s NY-ESO and MAGE-A10 SPEAR T-cell therapies; preparation for a study with the Company’s SPEAR T-cell therapy targeting AFP; and increased personnel expenses.
General and administrative ("G&A") expenses: G&A expenses were $5.4 million for the three months ended September 30, 2016 compared to $4.4 million for the three months ended September 30, 2015. The increase was primarily due to increased personnel costs.
Net loss: Net loss attributable to holders of the Company’s ordinary shares was $18.5 million for the three months ended September 30, 2016. This equates to $(0.04) per ordinary share or $(0.26) per American Depositary Share.
1 Total liquidity position is a non GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below.

Financial Guidance
Adaptimmune is reiterating its guidance. For the full year 2016, the Company expects its decrease in total liquidity position to be between $80 and $100 million and expects its total liquidity position at December 31, 2016, including cash, cash equivalents and short term deposits, to be at least $150 million. This guidance excludes the effect of any potential new business development activities.

On November 10, 2016 Argos Therapeutics Inc. (Nasdaq:ARGS) ("Argos"), an immuno-oncology company focused on the development and commercialization of individualized immunotherapies based on the Arcelis technology platform, reported that the company will be presenting at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 31st Annual Meeting to be held November 11-13 at the Gaylord National Hotel and Convention Center in National Harbor, Maryland.

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Mark DeBenedette, Ph.D., director of immunology for Argos, will present two posters on Friday, November 11th from 12:15-1:30pm ET in Prince George’s Exhibition Hall AB:

"Immunological impact of check point blockade on dendritic cell driven T cell responses; A cautionary tale" (205)
"Multi-Kinase Inhibitors for the Treatment of mRCC: Implications for Combined Therapy with AGS-003; an Autologous Dendritic Cell Immunotherapy" (259)
The SITC (Free SITC Whitepaper) 31st Annual Meeting provides a multidisciplinary educational and interactive environment focused on improving outcomes for current and future patients with cancer by incorporating strategies based on basic and applied cancer immunotherapy. For more information visit View Source

About the Arcelis Technology Platform
Arcelis is a precision immunotherapy technology that captures both mutated and variant antigens that are specific to each patient’s individual disease. It is designed to overcome immunosuppression by producing a specifically targeted, durable memory T-cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to the treatment of a wide range of different cancers and infectious diseases, and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized immunotherapies. The Arcelis process uses only a small disease sample or biopsy as the source of disease-specific antigens, and the patient’s own dendritic cells, which are optimized from cells collected by a leukapheresis procedure. The proprietary process uses RNA isolated from the patient’s disease sample to program dendritic cells to target disease-specific antigens. These activated, antigen-loaded dendritic cells are then formulated with the patient’s plasma, and administered via intradermal injection as an individualized immunotherapy.