On December 1, 2016 Unum Therapeutics, a clinical stage biopharmaceutical company developing a universal cellular immunotherapy to treat multiple cancers, reported that the Company has been selected for two poster presentations on its Antibody-Coupled T-cell Receptor (ACTR) platform at the 58th ASH (Free ASH Whitepaper) Annual Meeting, which is being held in San Diego, California, December 3-6, 2016 (Press release, Unum Therapeutics, DEC 1, 2016, View Source [SID1234516896]).
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In addition, Dr. Michelle Poon of the NUH in Singapore, will be presenting initial results of an ongoing Investigator Sponsored Trial using autologous T-cells with ACTR transiently expressed through mRNA electroporation in combination with rituximab in patients with relapsed/refractory CD20+ B-cell Non Hodgkin lymphoma (B-NHL) (ATTCK20; ClinicalTrials.gov No. NCT02315118). Following the initial results of this ongoing trial, Unum recently announced the initiation of a clinical trial for patients with relapsed/refractory CD20+ B-NHL in which ACTR is durably expressed through viral delivery in autologous T-cells (ACTR087; ClinicalTrials.gov No. NCT02776813).
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Presentation Details:
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Presentation Title: Targeting CD20+ Relapsed Refractory B-Cell Lymphoma with ACTR087, Antibody-Coupled T-Cell Receptor (ACTR) Engineered Autologous T-Cells, in Combination with Rituximab
Presenter: Heather A. Huet, Senior Director of Drug Discovery, Unum Therapeutics
Presentation Date: Sunday, December 4, 2016
Presentation Time: 6:00 p.m.‐8:00 p.m.
Room: Hall GH (San Diego Convention Center)
Session: 801. Gene Therapy and Transfer: Poster II
Abstract Number: 3512
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Presentation Title: ACTR Platform as an Adaptable, Universal T-Cell Therapy That Can Target Multiple Tumor Antigens to Overcome Antigen Escape
Presenter: Greg Motz, Senior Scientist, Unum Therapeutics
Presentation Date: Sunday, December 4, 2016
Presentation Time: 6:00 p.m.‐8:00 p.m.
Room: Hall GH (San Diego Convention Center)
Session: 703. Adoptive Immunotherapy: Poster II
Abstract Number: 3362
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Presentation Title: A First-in-Human Study of Autologous T Lymphocytes with Antibody-Dependent Cell Cytotoxicity (ADCC) in Patients with B-Cell Non-Hodgkin Lymphoma (NHL)
Presenter: Michelle Poon, MD Senior Consultant, Department of Hematology-Oncology,
National University Cancer Institute, Singapore (NCIS)
Presentation Date: Sunday, December 4, 2016
Presentation Time: 6:00 p.m.‐8:00 p.m.
Room: Hall GH (San Diego Convention Center)
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster II
Abstract Number: 3031
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The posters will be posted on Unum’s website following the presentations.
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About Antibody-Coupled T-Cell Receptor (ACTR) Technology and ACTR087
Unum’s proprietary ACTR is a chimeric protein that combines components from receptors normally found on two different human immune cell types – natural killer (NK) cells and T-cells – to create a novel cancer cell killing activity. T-cells bearing the ACTR receptor protein can be directed to attack a tumor by combining with a monoclonal antibody that binds antigens on the cancer cell surface.
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In contrast to other T-cell therapy approaches for cancer that are limited to a single cancer cell surface target and, therefore, treat a narrow set of tumors, Unum’s approach is not restricted by a specific tumor cell antigen and, thus, may have applications for treating many different types of cancers when combined with the right antibody.
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Unum is developing ACTR in combination with a range of tumor-targeting antibodies for use in both hematologic and solid tumor indications. ACTR087, Unum’s most advanced product candidate, combines Unum’s proprietary ACTR, with rituximab, an anti-CD20 antibody. The ACTR087 study will be the first clinical trial using a viral vector to permanently insert the ACTR gene into the genome of patient T-cells.

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On December 1, 2016 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the "company"), an oncology-focused, clinical stage biotechnology company, reported a data update on the first two cohorts of the company’s Phase I clinical study of CLR 131 in patients with relapsed or refractory multiple myeloma (Filing, 8-K, Cellectar Biosciences, DEC 1, 2016, View Source [SID1234516868]).

The clinical benefit rate for this study is 80 percent despite patients receiving an average of four prior treatments, including stem cell transplant and triple drug combinations. The patients in Cohort 1 received a single 12.5 mCi/m2 dose and patients in Cohort 2 received a single 18.75 mCi/m2 dose. At this time, Cohort 1 and Cohort 2 patients have demonstrated post treatment median survival of 11.9 months and 4.9 months, respectively. The median survival for all evaluable patients in both cohorts continues to increase and will be followed to determine overall survival benefit. Currently, the median overall survival (mOS) for each cohort is not yet evaluable. All evaluable patients in the clinical study experienced progression free survival (PFS). In Cohort 1, patients averaged 88.5 days of PFS. While patients in Cohort 2 have already achieved an average PFS of 127 days, the average PFS in Cohort 2 continues to increase as one of the four patients is still experiencing PFS. It is important to note that overall survival of 11.9 months and PFS of 127 days in this heavily pretreated patient population is better than or equivalent to that reported by several recently approved multiple myeloma drugs.

"The efficacy observed with CLR 131 at the 12.5 and 18.75 mCi/m2 single dose compares favorably to drugs recently approved for relapsed or refractory multiple myeloma. We believe that the 18.75 mCi/m2 dose could represent an acceptable single dose or multi-dose regimen for future studies," said Jim Caruso, president and CEO of Cellectar Biosciences. "Combined with its clean safety profile, we are optimistic regarding the potential of CLR 131 and look forward to seeing results from our recently initiated Cohort 3 at a single 25mCi/m2 dose."

An evaluation of adverse events between Cohort 1 and Cohort 2 reveal a similar profile. Patients in Cohort 1 experienced an average of 4.75 adverse events per patient while patients in Cohort 2 experienced an average of 4.25 events per patient. The median severity grade of the adverse events in both cohorts was 2.0 (mild to moderate), as graded by the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE).

In the multi-center, open label Phase I dose escalation study, CLR 131 was administered as a single dose, 30-minute intravenous infusion on Day 1 with 40 mg dexamethasone orally weekly for 12 weeks. The primary study objective is to characterize the safety and tolerability of CLR 131 with and without dexamethasone in patients with relapsed and/or refractory multiple myeloma. Secondary study objectives include establishment of a recommended Phase II dose, both with and without dexamethasone, as well as an assessment of therapeutic activity, including progression-free survival (PFS) and additional efficacy endpoints.

Dose-escalation in this study uses a minimally modified, standard 3+3 schema with dose-limiting toxicities (DLTs) assessed through day 85 post-infusion. Each cohort consisted of four evaluable patients (three men, one woman in Cohort 1 and two men, two women in Cohort 2). Patients in both cohorts received an average of 4 prior treatments. All patients received and were relapsed or refractory to proteasome inhibitors and immunomodulatory drugs prior to enrollment, and all patients had received triple combination therapy as a single line of therapy at least once. One patient in Cohort 1 and three in Cohort 2 received autologous stem cell transplantation and three Cohort 1 patients and one Cohort 2 patient each received the latest approved drugs for multiple myeloma prior to enrollment. Patient’s ages range between 55-76 (Cohort 1) and 55-85 (Cohort 2) and averages were essentially identical at 68 and 69 years of age, respectively.

The company is currently enrolling patients into the study’s third cohort at a single 25 mCi/m2 dose and plans to provide an additional data update in the first half of 2017.

About CLR 131

CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated in a Phase I clinical trial in patients with relapsed or refractory multiple myeloma. The company plans to initiate a Phase II clinical study to assess efficacy in a range of B-cell malignancies in the first quarter of 2017. Based upon pre-clinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating hematological diseases and may provide patients with therapeutic benefits, including overall response rate (ORR), an improvement in progression-free survival (PFS) and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131 directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About Phospholipid Drug Conjugates (PDCs)

Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in over 70 different xenograft models of cancer.

About Relapsed or Refractory Multiple Myeloma

Multiple myeloma is the second most common blood or hematologic cancer with approximately 30,000 new cases in the United States every year. It affects a specific type of blood cells known as plasma cells. Plasma cells are white blood cells that produce antibodies to help fight infections. While treatable for a time, multiple myeloma is incurable and almost all patients will relapse or the cancer will become resistant/refractory to current therapies.

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On December 1, 2016 ERYTECH Pharma (Paris:ERYP) (ADR:EYRYY) (Euronext Paris: ERYP), the French biopharmaceutical company developing ‘tumor starvation’ treatments for acute leukemia and other oncology indications with unmet medical needs, reported the presentation of promising preliminary data for the Company’s lead product candidate, eryaspase, also known as ERY-ASP or under the trade name GRASPA, at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held December 3-6, 2016 in San Diego, California (Press release, ERYtech Pharma, DEC 1, 2016, View Source;p=irol-newsArticle&ID=2226733 [SID1234516898]).

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The research was conducted at The University of Texas MD Anderson Cancer Center. Dr. Philip Lorenzi,

Co-Director of the Proteomics and Metabolomics Core Facility and lead author of the poster, will present a summary of the findings from a preclinical study which demonstrates that eryaspase, L-asparaginase encapsulated in red blood cells (RBC), has differential dual activity on its main targets, asparagine and glutamine, when compared to non-encapsulated native asparaginase (L-ASP), during a poster session.

Abstract #1266: Red Blood Cell-Encapsulation of L-Asparaginase Favorably Modulates Target Selectivity and Pharmacodynamics

Date:

Saturday, December 3, 2016
Time:
5:30 – 7:30 p.m. PST
Location:
Hall GH of the San Diego Convention Center
Poster Session:
101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and
Survival, Excluding Iron: Poster I

The anticancer effect of asparaginase products is attributed to the systemic degradation of asparagine, a critical amino acid for the growth and survival of cancer cells. Asparaginase is also known to have a glutaminase effect. The degradation of glutamine has been demonstrated to be associated with clinical toxicity. The study aimed to characterize the transport and degradation of the different amino acids between the plasma and the RBC cytoplasm in the presence of L-ASP or eryaspase. Using a new bioanalytical method, MD Anderson researchers analyzed several metabolites to study differential conversion of asparagine and glutamine. In the presence of eryaspase, asparagine was rapidly and extensively converted to aspartic acid inside the RBC, whereas eryaspase displayed significantly decreased glutaminase activity as compared to L-ASP. The approximately 3.5-fold increase in selectivity for asparagine over glutamine may explain the observed decrease in frequency of adverse events in clinical trials with eryaspase compared to L-ASP. Altered target selectivity is believed to be an additional beneficial property of the encapsulation in the RBC, on top of improved half-life and decreased immunogenicity. The results also provided further evidence of the ‘bioreactor’ mode of action of eryaspase, demonstrating that the enzymatic activity is essentially happening inside the RBC.

Dr. Lorenzi at The University of Texas MD Anderson Cancer Center, stated, "This work presents what we believe to be the first known solution to a long-standing challenge associated with measuring the pharmacodynamics of L-asparaginase products. Using a stable isotope-based correction method, we are now able to accurately determine the concentration of amino acids present at the time of sample collection. In this study, we used this method to identify reduced selectivity for glutamine as a plausible explanation for the improved toxicity profile of GRASPA over L-asparaginase that has been observed in prior clinical studies."

Dr. Iman El-Hariry, MD, PhD, Chief Medical Officer of ERYTECH, added, "We are pleased with these findings and believe that GRASPA has the potential to offer a new treatment option for cancer patients. This preclinical work demonstrates the unique mechanism of action of GRASPA and the important role of the RBC membrane in modulating the enzymatic activity of the encapsulated L-ASP on both asparagine and glutamine. The toxic side effects of L-ASP are believed to stem from its activity in degrading glutamine. These preclinical observations from MD Anderson researchers provide further support for our previously reported findings and demonstrate an improved therapeutic index of GRASPA in a clinical setting. We look forward to sharing our research to date with the global hematology community at the ASH (Free ASH Whitepaper) Annual Meeting."

On December 1, 2016 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported data from an ongoing Phase 1/1b study of RXDX-105—Ignyta’s VEGFR-sparing, potent RET inhibitor—at the 2016 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany, highlighting RXDX-105’s clinical activity in patients harboring RET molecular alterations, with five out of nine patients with RET fusion-positive cancers who were RET inhibitor-naïve achieving a RECIST response (1 complete response, 3 partial responses, and 1 unconfirmed partial response), for a preliminary objective response rate (ORR) of 56% (Abstract number 437, Poster number P116) (Press release, Ignyta, DEC 1, 2016, View Source [SID1234516870]).

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"This substantial update of our Phase 1/1b clinical data on RXDX-105 provides compelling evidence of its potent anti-tumor activity with promising durability and acceptable safety in patients with RET-fusion positive tumors," said Pratik Multani, M.D., Chief Medical Officer of Ignyta. "With approximately 500-fold higher potency against RET than VEGFR2 in vitro, RXDX-105 has the potential to address a critical unmet medical need in RET-positive patients for whom the clinical utility of multikinase inhibitors with both RET and VEGFR activity is constrained by safety liabilities and limited efficacy. We look forward to the continuation of the study to further explore the safety and efficacy of RXDX-105."

As of the November 2016, data cut-off, the findings showed:

Safety

A total of 91 patients with a range of solid tumors have been treated in the Phase 1/1b clinical trial, with 55 patients treated in the Phase 1 study and 36 patients treated in the Phase 1b study.

RXDX-105 continues to demonstrate a safety profile similar to what has been previously reported: across both studies, the most common treatment-related adverse events ( > 10% incidence) were rash (31%), fatigue (22%), diarrhea (20%), nausea (18%), hypophosphatemia (14%), vomiting (14%), muscle spasms (13%), and decreased appetite (10%);
The majority of treatment-related adverse events were Grade 1 or 2, and were reversible with dose modification;
The most common Grade 3 treatment-related adverse events ( > 5% incidence) were rash (9%), hypophosphatemia (7%), and ALT increase (6%);
One patient experienced a Grade 3 drug reaction with eosinophilia and systemic symptoms, in which the patient recovered with drug discontinuation. One patient experienced Grade 3 rash complicated by fatal alveolar hemorrhage. No other treatment-related Grade 4 or higher events were observed.
Toxicities commonly associated with VEGFR inhibition, such as hypertension, hypothyroidism, proteinuria, and neurotoxicity, were rarely observed ( < 5%).
Efficacy

Of the 36 patients treated in the Phase 1b study, 35 had RET or BRAF molecular alterations.

Nine RET inhibitor-naïve patients (n = 8 in the Phase 1b cohort; n = 1 in the Phase 1 cohort) with RET fusion-positive tumors were treated at a daily dose of 275 mg or 350 mg in the fed state, and were evaluable for response.

A preliminary ORR of 56% was observed in patients with RET fusion-positive solid tumors who were RET inhibitor-naïve (five out of nine treated patients had a RECIST response);
Of the five patients demonstrating a RECIST response, one patient with metastatic colorectal cancer (mCRC) achieved a complete response; three patients, all with non-small cell lung cancer (NSCLC), achieved a partial response; and one patient with NSCLC had an unconfirmed partial response;
Among the seven patients with RET fusion-positive NSCLC who were RET inhibitor-naïve, three achieved a partial response and one achieved an unconfirmed response (a second scan had not been obtained at the date of data cutoff), for a preliminary ORR of 57%;
Duration of response to RXDX-105 ranged from 2+ to 7+ months, with all responder patients currently continuing on treatment in active response; median duration of response, therefore, has not yet been determined;
Additionally, a previously disclosed Phase 1 patient with RET-mutated M918T medullary thyroid cancer had a confirmed partial response and continues on treatment after ten cycles.
These data confirm that RXDX-105 is active across a range of different histologies, with confirmed RECIST responses now observed in medullary thyroid cancer, NSCLC, and mCRC, and across a range of RET molecular alterations, including the M918T point mutation, and CCDC6-, EML4-, and PARD3-RET fusions.
Among the remaining patients treated in Phase 1b who were either RET fusion-positive and received prior RET inhibitor treatments (n = 4) or had BRAF molecular alterations (n = 23), durable disease control but no objective responses have been observed to date.

Based on the promising efficacy data observed thus far in patients with RET fusion-positive solid tumors who are RET inhibitor-naïve, this population will remain the primary focus of future development of RXDX-105. Enrollment in the Phase 1b study is ongoing to further explore the safety and efficacy of RXDX-105 in various molecular baskets at several doses.

On December 1, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that a poster featuring data related to FPA144 in urothelial cancer (UC), also known as bladder cancer, was presented today at 28th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany (Press release, Five Prime Therapeutics, DEC 1, 2016, View Source [SID1234516876]). The Poster titled "FGFR2b Represents a Novel Target for Treatment of Urothelial Cancer," is available at View Source

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"This translational data suggest that FGFR2b protein is expressed in a subset of bladder cancers," said Robert Sikorski, M.D., Ph.D., senior vice president and chief medical officer of Five Prime. "In our Phase 1 clinical trial, a patient with bladder cancer that expressed FGFR2b achieved a complete response after treatment with FPA144. We are actively investigating FPA144 as a treatment for gastric cancer and are now exploring its clinical potential in bladder cancer."

FPA144 is an isoform-selective antibody in development as a targeted immuno-therapy for tumors that overexpress FGFR2b, a splice variant of a receptor for some members of the fibroblast growth factor (FGF) family. FPA144 has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) to increase direct tumor cell killing by recruiting natural killer (NK) cells.

As reported at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, in the dose escalation phase of the Phase 1 clinical trial, a 76-year-old patient diagnosed with stage 4 bladder cancer received FPA144 at the 3 mg/kg dose level. That patient achieved a durable complete response, suggesting potential efficacy for FPA144 in bladder cancer. As of the November 4, 2016 cutoff, the patient has remained on treatment with FPA144 for 571 days.

The poster presented today includes data showing positive FGFR2b immunohistochemistry (IHC) staining in 11.6% of 387 archival primary bladder cancer tumor samples tested. Five Prime believes bladder cancer patients could be selected for treatment with FPA144 using an IHC molecular diagnostic test, similar to what is being used to identify gastric cancer patients for treatment with FPA144.

FivePrime has completed dose escalation testing in the ongoing Phase 1 study of single-agent FPA144 in patients with solid tumors including gastric cancer, and the drug was well tolerated with no dose limiting toxicities, and no maximum tolerated dose was reached. Enrollment continues in the expansion portion of the trial evaluating the safety, pharmacokinetics (PK) and efficacy of biweekly 15 mg/kg infusions of FPA144 in patients with gastric cancer whose tumors overexpress FGFR2b as well as in a new cohort to evaluate FPA144 in patients with bladder cancer whose tumors overexpress FGFR2b.

About FPA144
FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FGFR2 gene over-expression is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.

FPA144 is designed to block tumor growth through two distinct mechanisms. First, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells and T cells. Second, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. When combined with PD-1 blockade, FPA144 has shown an additive effect in tumor growth inhibition in preclinical models. Five Prime retains global development and commercialization rights to FPA144.