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Progenics Doses First Patient in Pivotal Phase 3 Study of PyL, PSMA PET Imaging Agent, for the Detection of Prostate Cancer

On December 3, 2018 Progenics Pharmaceuticals, Inc. (NASDAQ:PGNX), an oncology company developing innovative medicines and imaging analysis technology for targeting and treating cancer, reported that the first patient has been dosed in the Company’s Phase 3 CONDOR study evaluating the diagnostic performance and clinical impact of PyL (18F-DCFPyL) in men with biochemical recurrence of prostate cancer (Press release, Progenics Pharmaceuticals, DEC 3, 2018, View Source [SID1234531895]). PyL is the Company’s PSMA-targeted small molecule PET/CT imaging agent designed to visualize prostate cancer.

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Dr. Lawrence Saperstein, Assistant Professor of Radiology and Biomedical Imaging and Chief of Nuclear Medicine at Yale Smilow Cancer Hospital, and a principle investigator of the trial said, "PyL has demonstrated excellent positive and negative predictive values in detecting the presence or absence of prostate cancer. This valuable information has the potential to provide earlier diagnoses, more informed treatment decisions, the ability to monitor responses, and ultimately improve patient outcomes."

The Phase 3 CONDOR trial is a multi-center, open label study and will enroll approximately 200 patients with biochemical recurrence of prostate cancer in 14 sites in the United States and Canada. The primary endpoint is based on positive predictive value and will assess the correct localization rate (CLR), defined as a percentage of subjects with a one-to-one correspondence between localization of at least one lesion identified by PyL and the composite truth standard. Secondary measures include the percentage of subjects with a change in intended prostate cancer treatment plans due to PyL PET/CT imaging.

"The initiation of this landmark trial marks an important milestone in the development of PSMA-targeted imaging agents which have the potential to transform the treatment landscape for recurrent prostate cancer," stated Mark Baker, CEO of Progenics. "With PyL, physicians may be able to detect very small lesions that are currently missed with conventional imaging methods, which in turn could change the treatment path. We look forward to reporting data from this trial in early 2020."

Progenics Initiates Phase 3 Trial of PyL PSMA PET Imaging Agent Page 2

In prior studies, PyL has shown strong positive predictive value to detect prostate cancer, with high sensitivity (93-99%) in reliably detecting metastatic prostate cancer lesions and high specificity (96-99%) in confirming the absence of pelvic lymph node disease.

About PyL for PET Imaging of Prostate Cancer

PyL (also known as [18F]DCFPyL) is a fluorinated PSMA-targeted Positron Emission Topography ("PET") imaging agent that enables visualization of both bone and soft tissue metastases to determine the presence or absence of recurrent and/or metastatic prostate cancer.

About Prostate Cancer

Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven men will be diagnosed with prostate cancer in his lifetime. The American Cancer Society estimates that each year approximately 164,690 new cases of prostate cancer will be diagnosed and about 29,430 men will die of the disease. Approximately 2.9 million men in the U.S. currently count themselves among prostate cancer survivors

Xencor Presents Initial Data from Phase 1 Study of XmAb®14045 in Acute Myeloid Leukemia at the 2018 ASH Annual Meeting

On December 3, 2018 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic diseases, and cancer, reported initial data from its ongoing Phase 1 dose-escalation study of XmAb14045, a CD123 x CD3 bispecific antibody, in patients with relapsed/refractory acute myeloid leukemia (AML) (Press release, Xencor, DEC 3, 2018, View Source [SID1234531893]). The data were presented in an oral session at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Farhad Ravandi, M.D., Professor of Medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at the University of Texas – MD Anderson Cancer Center.

Key Highlights

66 patients with relapsed/refractory AML received XmAb14045. Patients were a median of 61 years old and were heavily pretreated, having had a median of three prior therapies and 30% (n=20) with a history of allogeneic stem cell transplantation. 86% of patients (n=57) were refractory to their last therapy, and 53% (n=35) were categorized as adverse risk at diagnosis by the European LeukemiaNet (ELN 2017) system.
A maximum tolerated dose (MTD) has not been reached. Cytokine release syndrome (CRS) was the most common toxicity occurring in 55% of patients (n=36). 6% of patients (n=4) experienced Grade 3 or 4 CRS. CRS was more severe on the initial dose and was generally manageable with premedication. Additional adverse events consistent with CRS but not reported as such, including chills, fever, tachycardia, hypotension and hypertension within 24 hours of infusion, were reported in an additional 29% of patients (n=19).
28% of evaluable patients with AML achieved either complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the two highest initial dose levels studied (1.3 and 2.3 mcg/kg weekly; n=5/18).
Two patients with responses were bridged to stem cell transplantation, and a third transplant-ineligible patient has remained in remission for 16+ weeks after discontinuation of therapy.
"We have observed multiple complete remissions in heavily pretreated, relapsed/refractory AML patients from XmAb14045 dosed weekly, and we continue to optimize dosing regimen," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Xencor’s XmAb technology enables bispecific antibodies to retain natural antibody properties, simplifying their use and production. Our platform enables the rapid development of new bispecific antibody drug candidates addressing a breadth of targets, and throughout 2019 we anticipate several new clinical trial initiations and additional data readouts."

The data presentation is available under Archived Scientific Presentations on the Events & Presentations page in the Investors section of www.xencor.com.

Analyst & Investor Event and Webcast Information
Xencor will host an analyst and investor event tonight from 8:00 to 10:00 p.m. PST with formal remarks at 8:30 p.m. PST. The formal remarks will feature a discussion of the data presented at ASH (Free ASH Whitepaper) and Xencor’s bispecific oncology pipeline. It will be webcast live and can be accessed under Events & Presentations in the Investors section of www.xencor.com, where it will be archived for 30 days.

About XmAb14045
XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

Generon Presented Pre-Clinical Immunotherapy Results With CD3-Activating Bi-Specific Antibody Targeting CD19 on B Cells in Mono- and Bi-Valent Format

On December 3, 2018 Shanghai, Generon BioMed Holding Ltd (Generon), reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting the pre-clinical study results of two novel immunotherapies, A-319 (mono-valent) and A-329 (bi-valent), two CD19×CD3 bi-specific antibodies designed using Generon’s ITab platform (Press release, Generon (Shanghai), DEC 3, 2018, View Source [SID1234531890]). A series of studies were conducted to evaluate the bioactivities of A-319 and A-329 in vitro and in vivo. The in vitro data showed that the mono-valent and bi-valent CD19 binding had little effect on the CD3-associated activities including CD3 antigen binding affinity, T cell binding, and T cell activation. In contrast, the bi-valent binding format of A-329 showed better potency compared to the mono-valent format of A-319 in CD19 binding (KD 0.89 nM and 19.4 nM respectively) and in vitro human B cell killing (EC50 0.2 pM and 3.4 pM, respectively). Both A-319 and A-329 were capable of mediating tumor cell lysis with EC50 at 0.03~4.0 pM. A-329 demonstrated a greater killing activity on B cell lines with a low expression of CD19 antigen. In addition, The CD19 bi-valent format of A-329 revealed more B cell killing in monkeys. No significant differences of cytokine induction or liver injuries between A-319 and A-329 were observed. In human PBMC engrafted mouse models, in vivo efficacies of both formats on inhibiting tumor growth or improving animal survival rate were also confirmed. These results demonstrated that both A-319 and A-329 may benefit patients with B cell malignancies with less frequent dosing and lower levels of cytokine inductions than comparator therapies. A-329 especially has the potential to eliminate low CD19 expressing tumor stem cells.

Dr. David Lacey, chairman of Generon’s scientific advisory board, commented, "The prosecution of A-319 and A-329 ITabs targeting underscores the broadening of Generon’s portfolio into the immune-oncology space. The inherent flexibility of the ITab design and the competitive attributes of its manufacture make this bi-specific platform particularly attractive for CD19 as well as future targets."

Dr. Xiao Qiang Yan, CEO and CSO of Generon, commented, "Targeting CD19 to treat patients with B cell malignancies remains a substantial unmet medical need. Generon has been focusing on developing CD3-activating bi-specific ITabs with the goal to serve patients better through more convenient dosing, improved efficacy and reduced side-effects. The preclinical data suggest that A-319 and A-329 may have unique advantages over other technologies or therapies targeting CD19".

About A-319 and A-329

A-319 and A-329 are T cell activating bi-specific antibodies (BsAb) designed to target CD19 and CD3 (anti-CD19, anti-CD3) and are under development for the treatment of patients with B cell malignancies including B cell leukemia and B cell lymphoma. Both A-319 and A-329 activate T lymphocytes in a patient to kill CD19 expressing malignant B-cells, and A-329 may also activate T lymphocytes in a patient to kill low CD19 expressing malignant B cells. A-319 was recently approved by SFDA to initiate a phase I study in patients with B cell malignancies in China.

ATARA BIOTHERAPEUTICS ANNOUNCES NEXT-GENERATION CAR T DISCOVERIES AND POSITIVE T-CELL IMMUNOTHERAPY RESULTS IN PATIENTS WITH EBV+ PTLD INVOLVING THE CNS AT 60TH AMERICAN SOCIETY OF HEMATOLOGY (ASH) ANNUAL MEETING

On December 3, 2018 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported results presented by collaborators at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. One study presents details of a next-generation CAR T technology that increases T cell persistence and decreases T cell exhaustion (Press release, Atara Biotherapeutics, DEC 3, 2018, View Source [SID1234531881]). Another important study presents positive Phase 2 clinical results in patients with EBV+ PTLD involving the CNS. PTLD patient treatment patterns and health outcomes are described in additional ASH (Free ASH Whitepaper) presentations.

"Our highlighted ASH (Free ASH Whitepaper) presentations this year demonstrate the promise of Atara’s next-generation CAR T and off-the-shelf, allogeneic T-cell immunotherapy pipeline," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "Cutting-edge CAR T discoveries by our Moffitt Cancer Center collaborators may have wide applications including as a component of our CAR T programs in acute myeloid leukemia (AML) and B-cell malignancies. Our collaborating investigators at Memorial Sloan Kettering also showed promising Phase 2 clinical results for patients with EBV+ PTLD involving the CNS, a difficult-to-treat and often lethal complication of bone marrow and organ transplantation. We are encouraged by these robust results and the broad potential of our CAR T technologies and T cell immunotherapy platform."

60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting Summary:

Abstract 966: Mutation of the CD28 Costimulatory Domain Confers Increased CAR T Cell Persistence and Decreased Exhaustion
Session: 703. Adoptive Immunotherapy: Preclinical Studies to Improve Safety and Efficacy of CAR-T Cells
Oral Presentation Date and Time: Monday, December 3, 2018 at 5:45 pm PST
Location: Marriott Marquis San Diego Marina, San Diego Ballroom B
Authors: Justin C Boucher, Gongbo Li, Bishwas Shrestha, Maria L Cabral, Dylan Morrissey, Lawrence Guan, Marco L Davila
Affiliations:Moffitt Cancer Center

Abstract 4590: Adoptive Therapy with EBV-Specific T Cells for Treatment of CNS EBV Post-Transplant Lymphoproliferative Disease Arising after Hematopoietic Stem Cell Transplant or Solid Organ Transplant
Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster III
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location:San Diego Convention Center, Hall GH
Authors: Susan Prockop, MD, Stephanie Suser, Ekaterina Doubrovina, MD, PhD, Hugo R. Castro-Malaspina, MD, Esperanza B. Papadopoulos, MD, James W. Young, MD, Victoria Szenes, PNP, Alison Slocum, MA, Karim Baroudy, MS and Richard J. O’Reilly, MD
Affiliations: Memorial Sloan Kettering Cancer Center
Overview:

This poster presentation evaluated EBV-specific T-cells generated from primary and third party (tab-cel) donors.
Patients with EBV+ PTLD involving the CNS following allogeneic hematopoietic stem cell transplant (HCT) or solid organ transplant (SOT) who failed prior rituximab from the Phase 2 studies 95-024 (NCT00002663) and 11-130 (NCT01498484) were included in the analysis.
Abstract 4777: Treatment Patterns for Patients with Post-Transplant Lymphoproliferative Disorder Who Fail Rituximab after Allogeneic Hematopoietic Stem Cell Transplantation: Findings from a Systematic Literature Review
Session: 902. Health Services Research—Malignant Diseases: Poster III
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location:San Diego Convention Center, Hall GH
Authors: Hairong Xu, MD, PhD, Crystal Watson, MS, Shan Ashton Garib, MA, Anna Forsythe, PharmD, MSc, MBA and Arie Barlev, PharmD
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 3556: Estimating Long-Term Survival in a Cohort of Allogeneic Hematopoietic Stem Cell Transplant Patients
Session: 902. Health Services Research—Malignant Diseases: Poster II
Poster Presentation Date & Time: Sunday, December 2, 2018 from 6:00 pm – 8:00 pm PST
Location:San Diego Convention Center, Hall GH
Authors: Stephen Palmer, MSc, Casey Quinn, PhD, MPhil, Crystal Watson, MS and Arie Barlev, PharmD
Affiliations:Centre for Health Economics, University of York, PRMA Consulting Ltd., Atara Biotherapeutics

Abstract 4596: Dual-Sensitized T-Cells Responding to EBV Blcl and Either CMVpp65 or WT-1 Peptide Pools Have Distinct or Shared HLA Restrictions That May Depend on the Presenting HLA Alleles
Session: 723. Clinical Allogeneic and Autologous Transplantation
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location: San Diego Convention Center, Hall GH
Authors: Ekaterina Doubrovina, MD, PhD, Aisha N. Hasan, MD, Susan Prockop, MD, Karim Baroudy, MS, and Richard O’Reilly, MD
Affiliations: Memorial Sloan Kettering Cancer Center

Abstract 5839: A Systematic Literature Review of Real-World Evidence in Post-Transplant Lymphoproliferative Disorder
Authors: Hairong Xu, MD, PhD, Anna Forsythe, PharmD, MSc, MBA, Arie Barlev, PharmD, Nazia Rashid, PharmD and Crystal Watson, MS
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 5841: Younger Patients Are Impacted By Post-Transplant Lymphoproliferative Disorder: Findings from a Systematic Literature Review of Real-World Evidence
Authors: Crystal Watson, MS, Hairong Xu, MD, PhD, Anna Forsythe, PharmD, MSc, MBA, Shan Ashton Garib, MA and Arie Barlev, PharmD
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 5840: Risk of Patients Developing Post-Transplant Lymphoproliferative Disorder within the First Year after an Allogeneic Hemopoietic Stem Cell Transplant, 2011 to 2016: A US Claims Database Analysis
Authors: Arie Barlev, PharmD, Hairong Xu, MD, PhD, Nicole Fulcher, MA, Crystal Watson, MS, Ila Sruti, MPH and Akshay Sudhindra, MD
Affiliations:Atara Biotherapeutics, IBM Watson Health

About EBV+ PTLD
Since its discovery as the first human oncovirus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders, including lymphomas, and other cancers. EBV is widespread in all human populations and persists as a lifelong, asymptomatic infection. In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), EBV-associated post-transplant lymphoproliferative disorder (EBV+ PTLD) represents a life-threatening condition. The expected median survival for patients with EBV+ PTLD following HCT who have failed rituximab first line therapy is 16-56 days. In EBV+ PTLD following SOT, patients failing rituximab are considered to have increased risk for chemotherapy-induced treatment-related mortality compared to other lymphoma patients. One- and two-year survival in patients with high-risk EBV+ PTLD following SOT is estimated to be 36% and 0%, respectively.

About tab-cel (tabelecleucel)
Atara’s most advanced T-cell immunotherapy in development, tab-cel, is a potential treatment for patients with Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+ PTLD) who have failed rituximab, as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, the FDA granted tab-cel Breakthrough Therapy Designation for EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tab-cel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. In addition, tab-cel has orphan status in the U.S. and EU. Tab-cel is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study), and Atara recently initiated a Phase 1/2 study in NPC.

Geron Announces New Overall Survival Data from IMbark in Imetelstat-Treated Patients with Intermediate-2 or High-Risk Myelofibrosis and Relapsed/Refractory to Janus Kinase Inhibitor Therapy

On December 3, 2018 Geron Corporation (Nasdaq: GERN) reported that results from IMbark, a Phase 2 clinical trial of imetelstat treatment in Intermediate-2 or High-risk myelofibrosis (MF) patients who are relapsed or refractory to a Janus Kinase (JAK) inhibitor, were presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California (Press release, Geron, DEC 3, 2018, View Source [SID1234531880]). The oral presentation was made on December 3, 2018 by John Mascarenhas, M.D., Associate Professor of Medicine in the Myeloproliferative Disorders Program of the Tisch Cancer Institute, Division of Hematology/Oncology at the Icahn School of Medicine at Mount Sinai, and an IMbark clinical investigator.

"The IMbark results suggest a meaningful survival outcome in this poor-prognosis, relapsed/refractory MF patient population where there are currently no approved treatments," said John A. Scarlett, M.D., Geron’s President and Chief Executive Officer. "We plan to explore potential late-stage development opportunities for imetelstat in MF through discussions with experts in MF and regulatory authorities and expect to provide a decision regarding future development of imetelstat in this patient population by the end of the third quarter of 2019."

Clinical Data Presentation

Title: Imetelstat is Effective Treatment for Patients with Intermediate-2 or High-Risk Myelofibrosis Who Have Relapsed on or Are Refractory to Janus Kinase Inhibitor Therapy: Results of a Phase 2 Randomized Study of Two Dose Levels (Abstract #685)

IMbark is a Phase 2 clinical trial that evaluated two starting dose levels of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered by intravenous infusion every three weeks) in more than 100 patients with Intermediate-2 or High-risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor. The oral presentation highlighted efficacy and safety data from the primary analysis, as well as overall survival data with a clinical cutoff of October 22, 2018 and a median follow up of approximately 27 months.

The co-primary efficacy endpoints for the trial are spleen response rate, defined as the proportion of patients who achieve a ≥35% reduction in spleen volume assessed by imaging; and symptom response rate, defined as the proportion of patients who achieve a ≥50% reduction in Total Symptom Score, at 24 weeks. Key secondary endpoints are safety and overall survival.

For the 9.4 mg/kg dosing arm (n=59), the spleen response rate was 10% (6/59) and the symptom response rate was 32% (19/59). In addition, improvement in bone marrow fibrosis was observed in 25% (15/59) of patients.

The new data presented at ASH (Free ASH Whitepaper) indicate that median overall survival (OS) for the 9.4 mg/kg dosing arm was 29.9 months, which suggests a meaningful survival outcome with imetelstat treatment in this poor-prognosis patient population, all of whom met rigorous criteria for having failed or not responded to JAK inhibitor treatment prior to enrollment in the trial. Other observational studies of similar patient populations published in medical literature have reported median OS ranged from approximately 12-14 months.

The safety profile reported for imetelstat-treated patients in IMbark was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified. Cytopenias, particularly neutropenia and thrombocytopenia, were the most frequently reported adverse events which were predictable, manageable and reversible.

The slides from the oral presentation at ASH (Free ASH Whitepaper) are available on Geron’s website at www.geron.com/r-d/publications.

Future Plan for Imetelstat in Relapsed/Refractory MF

Based on the data from IMbark, Geron plans to discuss the potential future development of imetelstat in MF with MF experts and regulatory authorities. Such discussions will consider how the IMbark results compare with other therapies currently available to MF patients and enable a better understanding of the potential significance of the IMbark results to patients and physicians. The Company expects to outline a decision regarding potential future MF development by the end of the third quarter of 2019.

Analyst and Investor Event

On December 10, 2018, Geron will host a webcasted event for analysts and investors. At the event, Dr. John Mascarenhas will reprise the oral presentation made at the ASH (Free ASH Whitepaper) Annual Meeting, as well as describe the unmet medical need in relapsed/refractory MF. A live audio webcast of the event will be available on Geron’s website, www.geron.com/investors/events. If you are unable to listen to the live presentation, an archived webcast of the event will be available on the Company’s website for 30 days.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat include a Phase 2/3 trial called IMerge in lower risk myelodysplastic syndromes (MDS) and a Phase 2 trial called IMbark in Intermediate-2 to High-risk myelofibrosis. Imetelstat received Fast Track designation from the United States Food and Drug Administration for the treatment of patients with transfusion-dependent anemia due to lower risk MDS who are non-del(5q) and refractory or resistant to an erythroid stimulating agent.