On November 9, 2016 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported financial results for the third quarter ended September 30, 2016 (Press release, Bellicum Pharmaceuticals, NOV 9, 2016, View Source;p=RssLanding&cat=news&id=2221084 [SID1234516507]).

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"We are pleased with recent progress, as the pediatric trial of our lead product candidate BPX-501 continues to enroll at a strong pace. We are preparing for a comprehensive data update of this program at ASH (Free ASH Whitepaper) 2016, and are working with regulators in the European Union and the U.S. to finalize registration pathways for BPX-501 and rimiducid," said Tom Farrell, President and Chief Executive Officer of Bellicum. "In the coming weeks, we expect to initiate the Phase 1 clinical trials of our BPX-601 GoCAR-T and BPX-701 TCR product candidates. We continue to build upon our differentiated technology platform and believe its potential to address the safety and efficacy issues of adoptive cell therapies will provide competitive advantage."

Third Quarter and Recent Highlights

Bellicum continued to advance its BPX-501 lead program and will provide a clinical update at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December. The BP-004 pediatric clinical trials in the U.S. and Europe have enrolled over 100 patients with orphan inherited blood disorders and blood cancers. Three abstracts, including an oral presentation focused on pediatric patients with immune deficiencies, were accepted for presentation at ASH (Free ASH Whitepaper) 2016. Bellicum will also host an investor and analyst luncheon on Monday, December 5, 2016. A full schedule can be found in the News & Events section of the Company’s website.
The Company is completing preparations for the start of Phase 1 clinical trials for BPX-601 and BPX-701. BPX-601 GoCAR-T contains Bellicum’s proprietary iMC activation switch and is designed to treat solid tumors expressing prostate stem cell antigen, with the initial clinical trial in non-resectable pancreatic cancer to be conducted at Baylor Sammons Cancer Center. BPX-701 incorporates the CaspaCIDe safety switch and is designed to target malignant cells expressing the preferentially-expressed antigen in melanoma (PRAME), with the initial clinical trial in Refractory or Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes, to be conducted at Oregon Health and Science University and Leiden University Medical Center.
Bellicum expanded its collaboration with Ospedale Pediatrico Bambino Gesù (OPBG) to develop novel CAR T and TCR cell therapies engineered with the CaspaCIDe safety switch. Under the agreement, the organizations agreed to jointly develop CARs and other cell therapies discovered by OPBG, with a clinical trial for a CaspaCIDe-enabled CD19 CAR T cell therapeutic anticipated to begin in 2017.
Bellicum continued to innovate and build upon its differentiated cellular control technologies; will present data highlighting preclinical results from the application of its GoCAR-T and GoTCR technologies in two poster presentations at ASH (Free ASH Whitepaper) 2016.
Third Quarter and Nine Months Ended September 30, 2016 Financial Results

Bellicum reported a net loss of $17.7 million for the third quarter of 2016 and $49.3 million for the nine months ended September 30, 2016, compared to a net loss of $13.4 million and $31.7 million for the comparable periods in 2015. The results included non-cash, stock-based compensation charges of $3.1 million and $9.2 million for the third quarter and nine months ended September 30, 2016 and $2.3 million and $5.9 million for the comparable periods in 2015.

As of September 30, 2016, cash and investments totaled $129.1 million, which included $5.0 million borrowed in September under the agreement with Hercules Capital. Bellicum now expects that it will end 2016 with at least $100 million in cash, cash equivalents and investments, and continues to expect that current cash resources will be sufficient to meet operating requirements through 2017.

Research and development expenses were $13.3 million and $36.5 million for the three and nine months ended September 30, 2016, respectively, compared to $9.8 million and $23.5 million during the comparable periods in 2015. The higher expenses in the 2016 periods were primarily due to an increase in manufacturing and clinical expenses as a result of increased patient enrollment in the BPX-501 clinical trials, increased expenses for the IND-enabling activities for product candidates BPX-601 and BPX-701, and increased personnel and infrastructure costs.

General and administrative expenses were $4.3 million and $12.7 million for the three and nine months ended September 30, 2016, respectively, compared to $3.9 million and $8.9 million during the comparable periods in 2015. The higher expenses in the 2016 periods were primarily due to the growth of the organization, including an increase in costs related to personnel, higher facility costs and increased legal, accounting and travel related expenses.

On November 9, 2016 Nektar Therapeutics (Nasdaq: NKTR) reported that new Phase 1 clinical data for Nektar’s lead immuno-oncology agent, NKTR-214, were presented at the SITC (Free SITC Whitepaper) 2016 Annual Meeting (Press release, Nektar Therapeutics, NOV 9, 2016, View Source [SID1234516469]). NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting T cells and Natural Killer (NK) cell abundance directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. The results were presented by Adi Diab, MD, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in an oral presentation during today’s session entitled "New Cancer Immunotherapy Agents in Development."

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Interim results presented were from the ongoing Phase 1 dose-escalation, first-in-human, trial of single-agent NKTR-214 in patients with locally advanced or metastatic solid tumors, including melanoma, renal cell carcinoma (RCC), bladder, colorectal and other solid tumor cancers. A total of 20 patients were treated in four separate every three-week (q3w) dose cohorts (ranging from 0.003 mg/kg q3w to 0.012 mg/kg q3w) with 18 of these patients evaluable for anti-tumor activity. Based upon encouraging anti-tumor activity and tolerability of NKTR-214 observed at the 0.006 mg/kg q3w dose, an every two week (q2w) cohort of the 0.006 mg/kg dose began enrolling in September 2016 with an additional 5 patients enrolled to this cohort, all of which are continuing on therapy.

"NKTR-214 resulted in robust activation of the immune system and encouraging anti-tumor activity, including a partial response observed in a patient who continues to be treated with NKTR-214," said Dr. Ivan Gergel, Senior Vice President, Drug Development & Chief Medical Officer of Nektar. "NKTR-214 was also well tolerated in patients when administered as an every two-week or every three-week outpatient therapy. We are very encouraged by the clinical profile emerging for NKTR-214 and the totality of the data from this ongoing single-agent trial of NKTR-214."

Preliminary encouraging evidence of anti-tumor activity has been observed to date in the ongoing study:

12/18 (67%) evaluable patients had stable disease at the initial 8 week scan
7/18 (39%) evaluable patients had radiographic reductions in tumor size per RECIST 1.1 on NKTR-214
One patient with metastatic melanoma (prior treatment with ipilimumab and a BRAF inhibitor) has received 13 cycles of treatment (0.003 mg/kg q3w) with stable disease and continues on therapy with NKTR-214
In the 18 evaluable patients, a total of 5 patients with metastatic RCC who had progressed on 1 prior tyrosine kinase inhibitor (TKI) were treated with NKTR-214 at the 0.006 mg/kg q3w dose level:
1/5 (20%) of these RCC patients had a uPR per RECIST 1.1 (at 16 week scan) and treatment with NKTR-214 is ongoing
2/5 of these RCC patients had additional tumor reductions of 6% and 10% per RECIST 1.1 while on NKTR-214
NKTR-214 also demonstrated a favorable safety and tolerability profile with convenient, outpatient q2w or q3w administration in 25 patients evaluable for safety to-date:

No immune-related AEs were observed (e.g. colitis, dermatitis, hepatitis pneumonitis, adrenal insufficiency)
No deaths or grade 4 AEs related to NKTR-214
No capillary leak syndrome was observed at any dose
One patient experienced a dose-limiting toxicity (DLT) of hypotension/syncope at 0.012 mg/kg q3w and continued on treatment at 0.006 mg/kg q3w
3/25 patients experienced grade 3 hypotension, which was rapidly reversed with fluid administration and all patients continued on treatment with NKTR-214
Most common grade 1-2 adverse events were fatigue, pruritis, cough, decreased appetite, pyrexia, and hypotension
Immune pheno-typing was conducted and biomarkers of immune activation were measured in patients with evaluable tumor biopsies and blood samples. Treatment with NKTR-214 produced a robust elevation in immune cell frequency and activation, including:

Increase in total and newly proliferating (Ki67+) CD4+ T cells, CD8+ T cells, and Natural Killer (NK) cells in 9/9 patients with blood samples evaluated in the trial to-date, with increases of up to 30-fold observed
Increase in frequency of PD-1+ T cell subsets of up to 9-fold in the blood
Increase in CD8+ T cells and Natural Killer (NK) cells of up to 10-fold in the tumor micro-environment in patients with evaluable tumor biopsies (pre-dose and post-dose at week 3), with minimal intratumoral changes to T regulatory cells
Increase in expression of cell-surface PD-1 on T cell subsets of up to 2-fold in the tumor micro-environment
Induction of an activation gene signature in the tumor micro-environment, including increases of 5-fold or greater in expression of interferon γ, perforin and granzyme B genes
Changes in T cell repertoire (TCR), which is a measure of T cell clonality, in the tumor micro-environment
"We are extremely pleased with the single-agent activity of NKTR-214 and the potential of NKTR-214 to transform the immuno-oncology landscape," said Howard W. Robin, President & CEO of Nektar Therapeutics. "As the first I-O agent to demonstrate that it can increase tumor-infiltrating lymphocytes (TILs) and increase PD-1 expression on immune cells in humans, NKTR-214 complements not only existing checkpoint inhibitors, such as nivolumab, but also other I-O mechanisms in development."

In September 2016, Nektar entered into a clinical collaboration with Bristol-Myers Squibb to evaluate NKTR-214 as a potential combination treatment regimen with Bristol-Myers Squibb’s Opdivo (nivolumab) in five tumor types and seven potential indications. The Phase 1/2 clinical trials will enroll up to 260 patients and will evaluate the potential for the combination of Opdivo (nivolumab) and NKTR-214 to show improved and sustained efficacy and tolerability above the current standard of care in melanoma, kidney, triple-negative breast cancer, bladder and non-small cell lung cancer patients. The initial dose-escalation trial is underway with Opdivo (nivolumab) and NKTR-214.

NKTR-214 is an experimental therapy designed to stimulate cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells, known as CD8+ effector T cells and Natural Killer (NK) cells. In preclinical studies, treatment with NKTR-214 resulted in a rapid expansion of these cells and mobilization into the tumor micro-environment.1 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines. A Phase 1/2 clinical study is ongoing to evaluate single-agent NKTR-214 in cancer patients.

On November 9, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that Tom Dubensky Jr., Ph.D., chief scientific officer of Aduro, presented today about the company’s personalized LADD technology at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) distinct session titled New Cancer Immunotherapy Agents in Development being held in conjunction with the SITC (Free SITC Whitepaper) annual meeting (Press release, Aduro BioTech, NOV 9, 2016, View Source;p=RssLanding&cat=news&id=2221061 [SID1234516456]).

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LADD is Aduro’s proprietary platform of live, attenuated double-deleted Listeria monocytogenes strains that have been engineered to express tumor-associated antigens to induce an innate immune response and tumor-specific T cell-mediated immunity. Personalized LADD, or pLADD, is a second generation LADD technology that is being designed for individualized, patient-specific immunotherapy. The pLADD approach leverages the immune activating activity of the Listeria bacterial vector in combination with neoantigens, or the tumor markers specific to an individual’s cancer, which are derived from the patient’s own unique tumor cells. Once administered, pLADD therapies are expected to mobilize the immune system through first an immediate recognition of the presence of Listeria as being foreign and then second a specific and customized immune attack on cells containing the tumor neoantigens presented by pLADD. An Investigational New Drug (IND) application has been accepted, and a Phase 1 trial evaluating the safety and immunogenicity of pLADD in patients with advanced gastro-intestinal cancers is planned.

"There is tremendous excitement in the oncology field to develop personalized therapies as the next new wave in immunotherapy to specifically customize treatment for each patient based on neoantigens that are unique to a patient’s tumor," said Tom Dubensky Jr., Ph.D., chief scientific officer of Aduro. "We are excited about the potential of our pLADD program, which has been shown to induce anti-tumor immune responses specific to tumor neoantigens and correlate with longer survival in preclinical models. Additionally, in these models, we observed a synergistic anti-tumor effect when pLADD was combined with an anti-PD-1 antibody, resulting in a significant reduction in tumor volume and increased survival."

The pLADD technology platform is well-suited to maximize the potential benefit of personalized therapy through the ability to engineer the therapy with multiple tumor-specific neoantigens, as well as to leverage an efficient small-scale manufacturing process in its production.

To create a patient-specific pLADD therapy, a physician begins by removing tumor cells from the patient. These cells are analyzed in order to molecularly characterize (sequence) the tumor, including any mutations that are unique to the patient’s own tumor cells. Predictive algorithms for antigen processing are run to identify pertinent tumor antigens. Aduro then creates a LADD strain that includes the patient-specific neoantigens for administration.

Preclinical Data with pLADD
Preclinical data showed that pLADD induced a robust immune response, including broad innate immune responses involving cytokines, chemokines, natural killer, and gamma delta T cells, as well as antigen-specific adaptive T cell responses (CD8+ and CD4+). In preclinical models, pLADD remodeled the tumor microenvironment, whereby an increase in infiltration of neutrophils, T cells and dendritic cells was observed. The combination of pLADD with an anti-PD-1 led to a sustained immune response and significant prolongation of survival in these models.

Detailed preclinical data will be presented by Aduro scientist Meredith Leong, Ph.D., on Saturday, November 12, 2016 at the SITC (Free SITC Whitepaper) Annual Meeting (Poster #366).

(Presentation, Idera Pharmaceuticals, NOV 9, 2016, View Source [SID1234516451])

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On November 9, 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, reported that new data from the Phase 1/2 clinical trial for intratumoral IMO-2125, a TLR9 agonist, being evaluated for the treatment of late-stage metastatic melanoma, will be presented at the 2016 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in National Harbor, MD, November 9-13, 2016 (Press release, Idera Pharmaceuticals, NOV 9, 2016, View Source;p=RssLanding&cat=news&id=2220898 [SID1234516450]).

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Oral Presentations

Date: Wednesday, November 9, 2016, Presentation Time: 11:15 AM E.T.
Session Title: Clinical New Agents in Development
Presentation Title: IMO-2125, An Investigational Intratumoral Toll-Like Receptor 9 Agonist, Modulates the Tumor Microenvironment to Enhance Anti-Tumor Activity
Presenter: Mark J. Cornfeld, M.D. M.P.H., Vice President, Oncology Medical Lead, Idera Pharmaceuticals
Location: Gaylord National Hotel & Convention Center, Cherry Blossom Ballroom

Date: Friday, November 11, 2016, Presentation Time: 3:15 PM E.T.
Session Title: State of the Art Immunotherapies: Challenges and Opportunities
Presentation Title: 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
Presenter: Presenter: Cara Haymaker, Ph.D., Instructor, The University of Texas MD Anderson Cancer Center
Location: Gaylord National Hotel & Convention Center, Maryland Ballroom

Poster Presentation
Date: Saturday, November 12, 2016: Presentation Time: 11:45 AM E.T. – 1:00 PM E.T.
Session Title: Immunotherapy
Poster Number: 216
Presentation Title: 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
Presenter: Cara Haymaker, Ph.D., Instructor, The University of Texas MD Anderson Cancer Center
Location: Gaylord National Hotel & Convention Center, Prince George’s Exhibition Hall AB

A copy of the slides from Dr. Cornfeld’s presentation will be made available on Idera’s corporate website at View Source on Wednesday, November 9 at 11:15 AM E.T. Copies of Dr. Haymaker’s presentation and related poster will be also be made available on Idera’s corporate website on Friday, November 11 at 3:15 PM E.T., in accordance with the embargo policies set forth by SITC (Free SITC Whitepaper).

"As we noted in late September, we are extremely excited by the initial clinical outcomes we have generated with intratumoral IMO-2125, in combination with ipilimumab," stated Joanna Horobin, M.B., Ch.B., Idera’s Chief Medical Officer. "The translational data from this trial is adding to our understanding of how IMO-2125 positively modulates the tumor microenvironment and enabling previously cold tumors an opportunity for regression and ultimately successful outcomes for patients. The translational research from this trial is critical to further this understanding as well as to help guide the direction of IMO-2125’s development."

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 The University of Texas MD Anderson Cancer Center 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.

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.