On November 5, 2015 BioLineRx Ltd. (NASDAQ, TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported positive results from the dose escalation part of BL-8040’s Phase 2 clinical trial in relapsed or refractory acute myeloid leukemia (r/r AML) (Press release, BioLineRx, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107352 [SID:1234507989]). The results will be presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, to be held December 5-8, 2015 in Orlando, Florida.

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Results showed that BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well tolerated at all doses tested up to and including the highest dose level of 1.5 mg/kg, with no major adverse events. The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving only one cycle of BL-8040 treatment at doses of 1 mg/kg and higher (n=16). Patients included in this part of the study were patients that had undergone a significant number of prior treatment cycles or that were refractory to induction treatment.

Treatment with BL-8040 had a triple effect on the leukemic cells. First, following only two days of monotherapy, BL-8040 triggered an average 40-fold mobilization of immature AML progenitor cells from the bone marrow to the peripheral blood, thereby sensitizing these cells to the Ara-C chemotherapy and improving its efficacy. Second, BL-8040 showed a direct and significant apoptotic effect on the immature leukemia progenitor cells in the bone marrow following the two days of monotherapy. Last, BL-8040 induced leukemia progenitor cells towards differentiation, as evidenced by a 58% median decrease in the number of bone marrow leukemia progenitor cells, along with a three-fold increase in differentiated granulocytes, in the bone marrow biopsy conducted on Day 3 of the treatment cycle prior to the Ara-C treatment, as compared to the biopsy performed at baseline.

Dr. Jorge Cortes, Chief of the AML and CML Sections at the MD Anderson Cancer Center in Houston, stated, "The clinical results from the dose escalation stage of the Phase 2 study for BL-8040 in r/r AML are very encouraging and fully support continued development of the compound in the AML space."

Dr. Kinneret Savitsky, CEO of BioLineRx, commented, "We are very pleased and encouraged by the positive results from the first part of this Phase 2 trial with BL-8040 for the treatment of r/r AML, especially in light of the severity of the patient population recruited and the short treatment regimen of one cycle. The results continue to demonstrate that BL-8040 not only significantly induces mobilization of leukemic cells from the protective microenvironment of the bone marrow into the peripheral blood, but also directly leads to apoptosis of leukemic progenitor cells and triggers terminal differentiation of the cells into granulocytes. Combined with the reported 38% remission rate from subjects receiving BL-8040 doses of at least 1 mg/kg, the results strongly suggest that BL-8040 has potent anti-leukemic activity and, in combination with Ara-C, may improve the response typically achieved in this advanced AML population." Dr. Savitsky continued, "In light of the encouraging results, we look forward to discussions with the regulatory authorities regarding the future development plan for AML. We currently anticipate reporting topline results from the full study by early next year."

"In order to further expand and enhance the potential of this unique oncology platform, we are continuing to perform and plan multiple additional clinical studies for BL-8040. These include a Phase 2b study which we recently initiated for BL-8040 as an AML consolidation treatment; a Phase 2 study in the planning stages as a novel stem cell mobilization treatment, based on input that we received from the FDA last month; and two additional studies in certain bone marrow failure indications and for the treatment of AML patients with the FLT3-ITD mutation," concluded Dr. Savitsky.

About the r/r AML Phase 2 study

The Phase 2 trial is a multicenter, open-label study under an IND, conducted at ten clinical sites in the U.S. and Israel, and is designed to assess the safety, efficacy pharmacodynamics and pharmacokinetic parameters of BL-8040 in combination with Cytarabine (Ara-C) for the treatment of adult relapsed or refractory AML patients. Twenty-two patients with r/r AML were enrolled in the dose escalation stage of the study (16 of which received a dose of 1 mg/kg and higher), which includes a dose escalation stage followed by an expansion stage. In the dose escalation stage, each patient received a once daily dose of BL-8040 monotherapy (from 0.5 to 1.5 mg/kg) on days 1-2 followed by the same dose of BL-8040 plus Ara-C on days 3-7. Extensive pharmacodynamic parameters, such as mobilization of leukemic cells and induction of apoptosis, were assessed after monotherapy with BL-8040 using peripheral blood sampling and bone marrow aspirates at baseline and on Day 3 prior to Ara-C administration. Clinical response to treatment was evaluated by bone marrow biopsy on Day 30.

About BL-8040

BL-8040 is a clinical-stage drug candidate for the treatment of acute myeloid leukemia, as well as other hematological indications. It is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis (growth of new blood vessels in the tumor), metastasis (spread of the disease to other organs or organ parts) and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a Phase 1/2, open-label, dose escalation, safety and efficacy clinical trial in 18 multiple myeloma patients, BL-8040, when combined with G-CSF, demonstrated an excellent safety profile at all doses tested and was highly effective in the mobilization of hematopoietic stem cells and white blood cells from the bone marrow to the peripheral blood. Additionally, in a Phase 1 stem-cell mobilization study in healthy volunteers, BL-8040 as a single agent was safe and well tolerated at all doses tested and resulted in efficient stem-cell mobilization and collection in all study participants. Importantly, the results of this study support the use of BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care.

BL-8040 also mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer effect by inducing apoptosis. Pre-clinical studies show that BL-8040 inhibits the growth of various tumor types including multiple myeloma, non-Hodgkin’s lymphoma, leukemia, non-small cell lung carcinoma, neuroblastoma and melanoma. BL-8040 also significantly and preferentially stimulated apoptotic cell death of malignant cells (multiple myeloma, non-Hodgkin’s lymphoma and leukemia). Significant synergistic and/or additive tumor cell killing activity has been observed in-vitro and in-vivo when tumor cells were treated with BL-8040 together with Rituximab, Bortezomib, Imatinib, Cytarabine and the FLT-3 inhibitor AC-220 (in NHL, MM, CML, AML, and AML-FLT3-ITD models, respectively). In addition, the current Phase 2 clinical trial in AML patients has demonstrated robust mobilization and apoptosis of cancer cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. According to the American Cancer Society, approximately 19,000 new cases of AML were diagnosed in the United States in 2014, and the median age of AML patients was 67 years old. The first treatment line for patients with AML includes a combination of chemotherapy drugs and is called induction treatment. The median survival for AML patients receiving induction chemotherapy is less than two years, with shorter survival for patients over the age of 60 or for those with certain gene or chromosome aberrations. Due to relapsed or refractory disease (where the disease is not responsive to standard treatments), the overall five-year survival rate for AML is between 10 and 40 percent.

On November 5, 2015 Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutic candidates that regulate cellular growth and repair, reported that data in six abstracts on the investigational protein therapeutics sotatercept, luspatercept and ACE-1332 will be presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held in Orlando, Florida on December 5-8, 2015 (Press release, Acceleron Pharma, NOV 5, 2015, View Source [SID:1234507988]).

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Oral presentations

Title: Luspatercept Treatment Leads to Long Term Increases in Hemoglobin and Reductions in Transfusion Burden in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Preliminary Results from the Phase 2 PACE-MDS Extension Study (Abstract #92)
Session: 637. Myelodysplastic Syndromes – Clinical Studies: New Therapeutic Approaches
Date: Saturday, December 5th
Time: 12:15 pm EST (Orange County Convention Center, W331)

Title: TGFβ1 Antagonist Inhibits Fibrosis in a Murine Model of Myelofibrosis (Abstract #605)
Session: 635. Myeloproliferative Syndromes: Basic Science II
Date: Monday, December 7th
Time: 11:30 am EST (Orange County Convention Center, W331)

Title: RAP-536 (Murine ACE-536/Luspatercept) Inhibits Smad2/3 Signaling and Promotes Erythroid Differentiation by Restoring GATA-1 Function in Murine β-Thalassemia (Abstract #751)
Session: 112. Thalassemia and Globin Gene Regulation: Therapeutic Approaches to Thalassemia and Their Mechanisms
Date: Monday, December 7th
Time: 4:35 pm EST (Orange County Convention Center, Valencia A (W415A))

Title: Luspatercept (ACE-536) Reduces Disease Burden, Including Anemia, Iron Overload, and Leg Ulcers, in Adults with Beta-Thalassemia: Results from a Phase 2 Study (Abstract #752)
Session: 112. Thalassemia and Globin Gene Regulation: Therapeutic Approaches to Thalassemia and Their Mechanisms
Date: Monday, December 7th
Time: 4:45 pm EST (Orange County Convention Center, Valencia A (W415A))

Poster presentations

Title: Biomarkers of Ineffective Erythropoiesis Predict Response to Luspatercept in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Final Results from the Phase 2 PACE-MDS Study (Abstract #2862)
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Poster II
Date: Sunday, December 6th
Time: 6:00 – 8:00 pm EST (Orange County Convention Center, Hall A)

Title: Phase 1 Dose-Escalation Study of Sotatercept (ACE-011) in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma (Abstract #4241)
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster III
Date: Monday, December 7th
Time: 6:00 – 8:00 pm (EST) (Orange County Convention Center, Hall A)

The posters and presentation slides will be available in the "Publications" section on Acceleron’s website (www.acceleronpharma.com).

About Luspatercept

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-beta) superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Acceleron and Celgene are initiating phase 3 clinical trials that are designed to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the "MEDALIST" study) and in patients with beta-thalassemia (the "BELIEVE" study). For more information, please visit www.clinicaltrials.gov.

About Sotatercept

Sotatercept is an activin receptor type IIA fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-β) superfamily involved in the late stages of erythropoiesis (red blood cell production). Sotatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing sotatercept as part of a global collaboration. Sotatercept is currently in multiple phase 2 clinical trials. For more information, please visit www.clinicaltrials.gov.

On November 5, 2015 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported business highlights and financial results for the third quarter ended September 30, 2015 (Press release, Agios Pharmaceuticals, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107178 [SID:1234507987]).

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"We have made significant progress this year toward realizing our goal of what’s possible for patients with our IDH inhibitors, by deploying a comprehensive development strategy of speed and breadth with AG-221 and AG-120 in AML and other cancers," said David Schenkein, M.D., chief executive officer at Agios. "In addition, we are pleased to have selected our fifth molecule, AG-519, for clinical development in PK deficiency. This coupled with DRIVE PK, our ongoing Phase 2 study of AG-348, may optimize our potential to help people with this rare genetic disorder."

KEY UPCOMING MILESTONES IN CANCER METABOLISM

Agios anticipates the following milestones from its IDH clinical development programs in collaboration with Celgene:

AG-221: a first-in-class, oral, selective, potent inhibitor of the mutated IDH2 protein

Present new data from the ongoing Phase 1 dose-escalation and expansion studies of AG-221 in advanced IDH2-mutant positive hematologic malignancies at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place December 5-8, 2015 in Orlando.

AG-120: a first-in-class, oral, selective, potent inhibitor of the mutated IDH1 protein

Present first data from the ongoing Phase 1 dose-escalation trial of AG-120 in advanced IDH1-mutant positive solid tumors in an oral presentation at AACR (Free AACR Whitepaper)-EORTC-NCI AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) on November 8, 2015 in Boston.

Present new data from the ongoing Phase 1 dose-escalation and expansion studies of AG-120 in advanced IDH1-mutant positive hematologic malignancies at the ASH (Free ASH Whitepaper) Annual Meeting.

Initiate a global registration-enabling Phase 3 study in patients with acute myeloid leukemia (AML) harboring an IDH1 mutation in the first half of 2016.

AG-221 and AG-120 front-line AML combination trials

Initiate a Phase 1b combination study of either AG-221 or AG-120 with standard induction (7+3, Ara-C and idarubicin/daunorubicin) and consolidation (Ara-C, or mitoxantrone with etoposide) chemotherapy in newly diagnosed AML patients eligible for intensive chemotherapy by the end of 2015.

Initiate a Phase 1/2 combination study of either AG-221 or AG-120 with VIDAZA (azacitidine) in newly diagnosed AML patients not eligible for intensive chemotherapy in the first quarter of 2016.

KEY UPCOMING MILESTONES IN RARE GENETIC METABOLIC DISORDERS

AG-348: a novel, first-in-class, oral activator of pyruvate kinase-R (PKR) for the treatment of pyruvate kinase (PK) deficiency

Present data from the Phase 1 healthy volunteers study of AG-348 and new findings from the Natural History Study of PK deficiency (being conducted with Boston Children’s Hospital) at the ASH (Free ASH Whitepaper) Annual Meeting.
AG-519: a novel, oral activator of PKR for the treatment of PK deficiency

Initiate an integrated single ascending dose (SAD) and multiple ascending dose (MAD) placebo-controlled Phase 1 study in healthy volunteers in the first quarter of 2016.
RECENT DEVELOPMENT UPDATES IN CANCER METABOLISM

Agios has provided the following updates on its clinical development programs in collaboration with Celgene:

AG-221

IDHENTIFY, the Phase 3 study of AG-221, was initiated in October. This is an international, multi-center, open-label, randomized clinical trial designed to compare the efficacy and safety of AG-221 versus conventional care regimens in patients 60 years or older with IDH2 mutant-positive AML that is refractory to or relapsed after second- or third-line therapy. This study is being conducted by Celgene.

The expansion phase of the Phase 1 trial of AG-221 is on track and continues to enroll. It includes four cohorts with 25 patients each and a fifth expansion cohort of 125 patients with IDH2 mutant-positive AML who are in second or later relapse, refractory to second-line induction or reinduction treatment, or have relapsed after allogeneic transplantation.
The ongoing Phase 1 trial of AG-221 in IDH2-mutated advanced solid tumors and angioimmunoblastic T-cell lymphoma continues to enroll patients.

AG-120

The expansion phase of the Phase 1 trial of AG-120 is on track and continues to enroll. It includes three expansion cohorts of a total of 175 patients with IDH1-mutated advanced hematologic malignancies, including one cohort with 125 patients with relapsed and/or refractory AML.

The ongoing Phase 1 trial of AG-120 in IDH1-mutated advanced solid tumors continues to enroll.
AG-881: a brain-penetrant, first-in-class, oral, potent pan-inhibitor of the mutated IDH1 and IDH2 proteins

Two Phase 1, open-label, dose-escalation and expansion studies are on track and continue to enroll – the first in advanced IDH mutant-positive solid tumors and the second in patients with advanced IDH mutant-positive hematologic malignancies whose cancer has progressed on a prior IDHm inhibitor therapy.

RECENT DEVELOPMENT UPDATES IN RARE GENETIC DISORDERS OF METABOLISM

AG-348

DRIVE PK, a global Phase 2, open-label safety and efficacy trial in adult, transfusion-independent patients with PK deficiency, is on track and enrolling.
A natural history study of PK deficiency is also ongoing and patient enrollment is on track.

AG-519

Agios selected a fifth molecule for clinical development, AG-519, a novel, oral activator of PKR for the treatment of PK deficiency.

THIRD QUARTER 2015 FINANCIAL RESULTS

Cash, cash equivalents and marketable securities as of September 30, 2015 were $408.0 million, compared to $467.4 million as of December 31, 2014. The decrease was driven by cash used to fund operating activities of approximately $101.2 million, which was offset by funding of approximately $54.8 million made by Celgene during the nine months ended September 30, 2015 related to our collaboration agreements.

Collaboration revenue was $5.5 million for the third quarter of 2015, compared to $33.9 million for the comparable period in 2014. In July 2014, the company amended its collaboration agreement with Celgene. As a result, for the third quarter of 2014 the company recognized a total of $25.9 million under the previous accounting guidance and upon the modification in addition to $8.0 million in revenue subsequent to the modification through September 30, 2014.

Research and development (R&D) expense was $36.0 million, including $4.9 million of stock- based compensation expense in the third quarter of 2015, compared to $25.5 million, including $1.4 million in stock-based compensation expense for the comparable period in 2014. The increase in R&D expense was primarily due to increased costs to support advancement of the company’s lead investigational medicines toward later-stage development.

General and administrative (G&A) expense was $9.9 million, including $4.5 million of stock-based compensation expense, in the third quarter of 2015, compared to $5.2 million, including $1.4 million of stock-based compensation expense, for the comparable period in 2014. The increase in G&A expense was largely due to increased headcount and other professional expenses to support growing operations.

Net loss for the third quarter of 2015 was $40.3 million, compared to net income of $3.7 million for the comparable period in 2014. The third quarter of 2014 includes additional revenue recognition related to the amendment of the company’s collaboration agreement with Celgene.

FINANCIAL GUIDANCE FOR THE FULL YEAR 2015

Agios is reiterating that it expects to end 2015 with more than $350.0 million of cash, cash equivalents and marketable securities. The anticipated year end 2015 cash position does not include any additional program-specific milestone payments. Agios expects that its cash, cash equivalents and marketable securities would be sufficient to fund its operating expenses and capital expenditure requirements until late 2017.

On November 5, 2015 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO) reported that new data from the ongoing dose-escalation and expansion studies of AG-221 and AG-120 in advanced hematologic malignancies will be presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, December 5-8, 2015 (Press release, Agios Pharmaceuticals, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107405 [SID:1234507986]).

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In total, five abstracts led by Agios describing new clinical data from the company’s cancer metabolism and rare genetic metabolic disorders programs have been accepted for presentation at ASH (Free ASH Whitepaper), as well as two abstracts detailing new findings from the Natural History Study of pyruvate kinase (PK) deficiency being conducted with Boston Children’s Hospital. Agios’ IDH inhibitors AG-221 and AG-120 are being developed in collaboration with Celgene.

The accepted abstracts are listed below and are now available online on the ASH (Free ASH Whitepaper) conference website: View Source

Oral Presentation

Date & Time: Sunday, December 6, 2015 at 5:30 p.m. ET
Session Title: 613. Acute Myeloid Leukemia: Clinical Studies: Advances in Targeted Therapy
Abstract Number: 323
Presentation Title: Safety and Efficacy of AG-221, a Potent Inhibitor of Mutant IDH2 That Promotes Differentiation of Myeloid Cells in Patients with Advanced Hematologic Malignancies: Results of a Phase 1/2 Trial
Location: Orange County Convention Center, W110

Poster Presentations

Date & Time: Saturday, December 5, 2015 from 5:30 p.m. to 7:30 p.m. ET
Session Title: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Abstract Number: 1306
Presentation Title: Molecular Profiling and Relationship with Clinical Response in Patients with IDH1 Mutation-Positive Hematologic Malignancies Receiving AG-120, a First-in-Class Potent Inhibitor of Mutant IDH1, in Addition to Data from the Completed Dose Escalation Portion of the Phase 1 Study
Location: Orange County Convention Center, Hall A

Date & Time: Saturday, December 5, 2015 from 5:30 p.m. to 7:30 p.m. ET
Session Title: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Abstract Number: 1310
Presentation Title: Longitudinal Pharmacokinetic/Pharmacodynamic Profile of AG-120, a Potent Inhibitor of the IDH1 Mutant Protein, in a Phase 1 Study of IDH1-Mutant Advanced Hematologic Malignancies
Location: Orange County Convention Center, Hall A

Date & Time: Sunday, December 6, 2015 from 6:00 p.m. to 8:00 p.m. ET
Session Title: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II
Abstract Number: 2509
Presentation Title: Evaluation of the Pharmacokinetics of AG-221, a Potent Mutant IDH2 Inhibitor, in Patients with IDH2-Mutation Positive Advanced Hematologic Malignancies in a Phase 1/2 Trial
Location: Orange County Convention Center, Hall A

Date & Time: Sunday, December 6, 2015 from 6:00 p.m. to 8:00 p.m. ET
Session Title: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster II
Abstract number: 2136
Presentation Title: The Phenotypic Spectrum of Pyruvate Kinase Deficiency (PKD) from the PKD Natural History Study (NHS): Description of Four Severity Groups By Anemia Status
Location: Orange County Convention Center, Hall A

Date & Time: Monday, December 7, 2015 from 6:00 p.m. to 8:00 p.m. ET
Session Title: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III
Abstract Number: 3337
Presentation Title: Molecular Characterization of 140 Patients in the Pyruvate Kinase Deficiency (PKD) Natural History Study (NHS): Report of 20 New Variants
Location: Orange County Convention Center, Hall A

Date & Time: Monday, December 7, 2015 from 6:00 p.m. to 8:00 p.m. ET
Session Title: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III
Abstract Number: 3336
Presentation Title: Population Pharmacokinetics and Pharmacodynamics of AG-348 in Healthy Human Volunteers Guide Dose Selection for the Treatment of Pyruvate Kinase Deficiency
Location: Orange County Convention Center, Hall A

On November 5, 2015 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in the use of TCR engineered T-cell therapy to treat cancer, reported updated data on its lead clinical program, an affinity enhanced T-cell receptor therapy targeting the NY-ESO-1 cancer antigen in synovial sarcoma, at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) (Press release, Adaptimmune, NOV 5, 2015, View Source [SID:1234507985]).

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Also being presented are an extended follow-up and correlative data from Adaptimmune’s study of its Tcell therapy targeting NY-ESO in patients with multiple myeloma, and preclinical safety assessments of its next affinity enhanced T-cell therapy product directed at MAGE A-10, for which a clinical trial is expected to initiate later this year.

The data presented demonstrate the following:

 In the primary efficacy analysis, 50 percent of synovial sarcoma patients receiving Adaptimmune’s affinity enhanced T-cell therapy targeting NY-ESO responded, and 75 percent remain alive and on long term-follow up. Sixty (60) percent of patients receiving the target dose responded, and 90 percent remain alive and on long term-follow up;

 Adaptimmune’s affinity enhanced T-cell therapy targeting NY-ESO in multiple myeloma generated responses that were better than expected for autologous stem cell transplant (ASCT) alone, despite the patients having advanced stage disease with 60 percent of patients having tumor chromosomal abnormalities; and

 Adaptimmune’s platform technology enables the generation of multiple TCRs to a large number of cancer targets. Once affinity engineered, these TCRs are subjected to an extensive preclinical safety and efficacy package.

In the synovial sarcoma poster presentation, entitled: "Optimizing engineered TCR T-cell therapy for synovial sarcoma," Sandra P. D’Angelo, M.D., Assistant Attending, Sarcoma Medical Oncology / Immunotherapeutics Core at Memorial Sloan-Kettering Cancer Center is providing an update on Adaptimmune’s NY-ESO-1 synovial sarcoma study, including all patients in the original cohort (n=12), and longer follow-up and time-to-event, as well as updated correlative and safety data, and characterization of the product pre- and post-infusion. All patients enrolled in the study had metastatic or relapse inoperable synovial sarcoma, and failed prior ifosfamide and/or doxorubicin therapy. The authors of the poster conclude:

 Adaptimmune’s affinity enhanced T-cell therapy targeting NY-ESO demonstrated robust clinical responses in synovial sarcoma, including a 50 percent (6/12) overall response rate (ORR) in patients receiving T-cells, and a 60 percent (6/10) response rate in a subset of patients who received the target dose of one to six billion total engineered T-cells. Two patients received below the target dose, and neither responded. This compares favorably to a historical partial response rate of approximately four percent observed with pazopanib, which is the only approved drug in this patient population.

 Seventy-five (75) percent (9/12) of all subjects who received any dose of NY-ESO-1 T cells – and 90 percent (9/10) of subjects who received the minimum intended cell dose – are alive and on long term follow-up. Forty-two (42) percent (5/12) of patients who received any dose have survival data beyond one year.

 NY-ESO-1 T-cells durably persist and maintain function without accumulation of exhaustion markers; persistence detected at up to 21 months in those receiving the minimum intended cell dose. Poor persistence was observed in subjects receiving less than 1 billion NY-ESO-1 T-cells, with no detectable cells beyond day 25.

 The encouraging anti-tumor activity considered in the context of a generally manageable safety profile is supportive of a favorable benefit:risk for NY-ESO-1 T-cells in this patient population. Most treatment related adverse events resolve within 30 days of treatment. The most common adverse events include: nausea, anemia, pyrexia, lymphopenia, and neutropenia. There were no
treatment related deaths. Cytokine release syndrome was seen in 4 subjects; Grade 3 cytokine release syndrome was observed in 2/4 subjects, no grade 4 events were observed.

 The evidence of relapse seen in some patients provides rationale for testing of combination approaches or second generation T-cells designed to overcome the immune suppressive environment of selected tumors.

Dr. Rafael Amado, Adaptimmune’s Chief Medical Officer, said, "Adaptimmune’s core focus is the development of affinity enhanced T-cell therapies that may offer promising treatment options to patients with a broad range of solid and hematologic malignancies. We are encouraged by the response and survival data we are observing in patients with chemotherapy refractory synovial sarcoma, and we have expanded this trial as we progress the development of our NY-ESO T-cell therapy in this disease. We also continue to see promising clinical outcomes with our NY-ESO T-cell therapy in patients with relapsed or refractory multiple myeloma. And importantly, we continue to refine our proprietary in vitro predictive safety package, which we now utilize to assess each of our candidate T-cell therapies."

In the myeloma update entitled, "Deep phenotypic characterization of NY-ESO TCR engineered T cells and tumor in patients with advanced myeloma", Eduardo Davila, Ph.D., Associate Professor of Microbiology and Immunology at the University of Maryland School of Medicine, Program Leader for Tumor Immunology and Immunotherapy Research Program at the Greenebaum Cancer Center at the University of Maryland, is presenting follow-up data from the Nature Medicine paper (published July 20, 2015)reporting results of the first 20 patients. This update includes data from the full 25 patient cohort, long term follow-up data, and details on NY-ESO-1 T-cell phenotyping and functional data, as well as clinical and basic correlative data in myeloma patients. Patients in this study had an average of 3 prior therapies; 24 percent had received prior transplant and 60 percent have tumors with chromosomal abnormalities. Early studies indicate upregulation of PDL-1 in relapsing tumor. Relapse occurs upon loss
of NY-ESO-1 c259T in the peripheral blood, suggesting that therapies designed to improve persistence or enhance multi-targeting of tumor would be beneficial. The authors conclude that the depth of responses on study, including a complete response rate of 59 percent, are better than expected for ASCT alone, despite the patient population being advanced with risk factors of tumor chromosomal abnormalities, and prior ASCT. Median overall survival amongst treated patients is 32 months, and
median progression free survival is 19 months.

Adaptimmune also presents preclinical data supporting its next first in human study in a poster entitled, "Preclinical safety testing of an Optimized Enhanced-Affinity MAGE-A10 -specific T cell receptor for adoptive T cell therapy". Andrew Gerry, Ph.D., Director of Preclinical Research at Adaptimmune is providing a summary of the preclinical safety testing of an affinity-enhanced T-cell therapy specific for MAGE-A10, for which a dose escalation study in patients with non-small cell lung cancer is expected to initiate shortly. The Investigational New Drug (IND) application is open, and the study is expected to initiate in 2015. Adaptimmune has the ability to generate multiple TCRs against cancer target antigens and select the optimal TCR based on specificity; the company can then optimize the affinity of the TCR. Once affinity optimized, the company has established an extensive, first-in-class in vitro-based
preclinical safety and efficacy package including molecular peptide mapping, 2D and 3D primary cell line screening, and alloreactivity screening, which capitalizes on the ability to map the linear peptide target of the TCR. The authors of the poster conclude that Adaptimmune’s preclinical strategy has been shown to be able to predict off target toxicity observed in a prior study with a MAGE-A3 TCR. This strategy, under continuing refinement, will be used for all new candidate enhanced affinity TCRs for adoptive T
cell therapy for cancer and other diseases.

Adaptimmune’s affinity enhanced T-cell candidates are novel cancer immunotherapies that have been engineered to target and destroy cancer cells by strengthening a patient’s natural T-cell response. T-cells are a type of white blood cell that play a central role in a person’s immune response. Adaptimmune’s goal is to harness the power of the T-cell and, through its multiple therapeutic candidate, significantly impact cancer treatment and clinical outcomes of patients with solid and hematologic cancers.