Calithera Biosciences Announces Four Abstracts Selected for Presentation at the Society for Immunotherapy of Cancer (SITC) 2016 Annual Meeting

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]).

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

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

                  Schedule Your 30 min Free Demo!

"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

Advaxis to Present Phase 1 Combination Data and New Preclinical Data Using AXAL at Upcoming Society for Immunotherapy of Cancer (SITC) 2016 Annual Meeting

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.

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

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

                  Schedule Your 30 min Free Demo!

A 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.

Atreca Presents Promising Findings from Lead Antibody Program at Society for Immunotherapy of Cancer (SITC) Annual Meeting

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:

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

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

                  Schedule Your 30 min Free Demo!

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

Genocea’s Proprietary ATLAS™ Technology Identifies Unique Candidate Antigens for Potential Personalized Cancer Vaccines

On November 11, 2016 Genocea Biosciences, Inc. (NASDAQ:GNCA), a company developing T cell-directed vaccines and immunotherapies, reported new findings supporting the potential of ATLASTM, the Company’s proprietary rapid antigen identification screening system, to identify clinically meaningful personalized neoantigens that could guide development of neoantigen vaccines (Press release, Genocea Biosciences, NOV 11, 2016, View Source [SID1234516539]). This study, conducted in collaboration with Memorial Sloan Kettering Cancer Center (MSK), analyzed neoantigens in one non-small cell lung cancer (NSCLC) patient successfully treated with pembrolizumab (KEYTRUDA) and will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 31st Annual Meeting & Associated Programs in National Harbor, Maryland on Saturday, November 12, 2016.

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

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

                  Schedule Your 30 min Free Demo!

Genocea’s ATLAS technology screened 103 patient-specific tumor mutations with the patient’s own T cells to determine which were true neoantigens and potentially contributing to their anti-tumor immune response. Specifically, ATLAS discovered several neoantigens as biologically relevant T cell targets associated with significant cytotoxic T cell responses. Many of the neoantigens were not identified by commonly used predictive computer algorithms. Furthermore, the majority of neoantigens that were identified by those algorithms were not associated with meaningful T cell responses in ATLAS. Additionally, multiple neoantigens were identified by ATLAS that were associated with a downregulation of immune response. (Poster #374: Genome-scale neoantigen using ATLASTM prioritizes candidates for immunotherapy in a non-small cell lung cancer patient). As part of this ongoing collaboration, further analysis of multiple additional patient tumor samples will be conducted.

"These data are the first evidence that personalized neoantigens can be comprehensively identified using functional evidence of T cell responses through ATLAS," said Jessica Baker Flechtner, Ph.D., chief scientific officer at Genocea. "The differences between neoantigens identified by ATLAS and those noted by standard predictive algorithms reinforces the weaknesses of these algorithms and the potential for ATLAS to find better neoantigens. We believe that by improving antigen selection we can develop more effective cancer vaccines."

Genocea’s proprietary ATLAS technology comprehensively re-creates a patient’s actual T cell immune response to cancer ex vivo. This means ATLAS can potentially identify – not just predict – targets to which patient T cells are responding to kill a tumor. It may also allow ATLAS to distinguish between neoantigen candidates that stimulate productive T cell responses and those that are irrelevant or are associated with inhibitory responses.

"For the immune system’s T cells to effectively activate tumor destruction, they must first recognize antigens that direct them to specific, impactful targets at the site of the tumor. If this system fails, disease can progress," said Timothy A. Chan, M.D., Ph.D., Vice Chair, Department of Radiation Oncology at MSK. "These findings support the hypothesis that next-generation personalized T cell immunotherapies with biologically evidenced neoantigens may improve outcomes for patients for whom current therapies are ineffective."

The collaboration between Genocea and Timothy A. Chan, M.D., Ph.D., Vice Chair, Department of Radiation Oncology, and Jedd D. Wolchok, M.D., Ph.D., Chief of Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center, will seek to further validate these findings in ongoing studies and continue to provide a meaningfully different picture of relevant – and potentially inhibitory – antigens than traditional methods currently produce.

About ATLAS
ATLAS is a first of its kind proprietary rapid antigen identification screening system that is designed to find targets of protective T cell responses. The technology solves challenges to date associated with finding targets of T cell responses. ATLAS can examine T cell responses from large, diverse human populations, and comprehensively screen every potential antigen from a pathogen or target indication in a rapid, high-throughput manner, taking weeks versus years to find relevant antigens. Because targets identified by ATLAS are based on actual human immune responses to all potential antigens, with no guesswork or predictions, by the time these candidates reach clinical trials there may be a greater likelihood of success in clinical development. This approach provides the ability to identify smarter targets for use in developing vaccines and immunotherapies to treat infectious disease, cancer and autoimmunity.

TRACON Pharmaceuticals Announces Presentation of Updated Data from Phase 1b/2 Study of TRC105 and Votrient® in Patients with Angiosarcoma

On November 11, 2016 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, reported updated data from the Company’s Phase 1b/2 study of TRC105 and Votrient (pazopanib) at the Connective Tissue Oncology Society (CTOS) annual meeting taking place in Lisbon, Portugal (Press release, Tracon Pharmaceuticals, NOV 11, 2016, View Source [SID1234516501]).

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

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

                  Schedule Your 30 min Free Demo!

In poster presentation 2569989 entitled, "TRC105 in Combination with Pazopanib in Patients with Advanced Angiosarcoma," data from 18 angiosarcoma patients treated with either the combination of TRC105 (carotuximab) and Votrient, or with single agent TRC105 followed by the combination of TRC105 and Votrient, were presented:

For the initial five angiosarcoma patients enrolled in the original Phase 1b/2 clinical trial, the median progression-free survival (mPFS) is greater than 16.6 months. For the nine chemotherapy-refractory angiosarcoma patients treated with the combination of TRC105 and Votrient, three of whom had also previously progressed on Votrient treatment (and includes the initial five patients), mPFS is 5.6 months. Three of the nine patients remain on treatment, including two patients with durable complete responses (CRs), now on treatment for 19 and 26 months, respectively. For comparison, mPFS with single agent Votrient was 3.0 months with no CRs in a previously completed retrospective analysis of 30 chemotherapy-refractory and Votrient-naive angiosarcoma patients.
An additional group of nine angiosarcoma patients was enrolled and treated initially with single agent TRC105 followed by the combination of TRC105 and Votrient at progression. The mPFS in these nine patients treated initially with single agent TRC105 was similar to the mPFS reported in late-stage trials of single agent VEGF inhibitors, including Votrient and Nexavar (sorafenib). Four of the nine patients remain on study with either single agent TRC105 or the combination of TRC105 and Votrient, including one patient with a partial response.
TRC105 administered at its recommended Phase 2 dose of 10 mg/kg weekly was well-tolerated in combination with Votrient at its approved dose, which allowed for prolonged dosing without an increase in the frequency or severity of adverse events typical of each individual drug.
"The combination of TRC105 and Votrient has now been used to treat a total of 18 angiosarcoma patients and we continue to see encouraging signs of activity in this group of patients with limited therapeutic options," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "Looking forward, we remain on track to initiate a randomized Phase 3 study of TRC105 with Votrient in patients with angiosarcoma at sites in the U.S. and Europe later this year or early 2017. Using the valuable input previously received from both U.S. and EU regulators, the trial will utilize an adaptive design that allows sample size re-estimation and patient enrichment. Importantly, we have submitted the trial design to the FDA for a Special Protocol Assessment (SPA)."

The poster is available on TRACON’s website at www.traconpharma.com.

About TRC105 (carotuximab)

TRC105 (carotuximab) is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in multiple Phase 2 clinical trials sponsored by TRACON or the National Cancer Institute for the treatment of solid tumor types in combination with VEGF inhibitors. The ophthalmic formulation of TRC105, DE-122, is currently in a Phase 1/2 trial for patients with wet AMD. TRC205, a second generation antibody to endoglin, is undergoing preclinical testing in models of fibrosis.