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Phio Pharmaceuticals to Present at the Tumor Targeted Lymphocytes Summit in Boston on December 13

On December 4, 2018 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA) therapeutic platform, reported that Dr. Gerrit Dispersyn, President and Chief Operating Officer, will give a presentation at the Tumor Targeted Lymphocytes Summit being held at the Hilton Boston Back Bay in Boston on December 11-13 (Press release, Phio Pharmaceuticals, DEC 4, 2018, View Source [SID1234531867]).

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Dr. Dispersyn’s presentation, titled "Therapeutic Enhancement of TILs with Self-Delivering RNAi through Targeted Gene Silencing," will take place at 12:10 p.m. ET on Thursday, December 13. He will present an overview on the use of RNAi to improve the immunobiology of tumor infiltrating lymphocytes (TILs) and other immune effector cells, how its use compares to other approaches in Adoptive Cell Therapies (ACT), and considerations for clinical and commercial applicability.

Dr. Dispersyn’s presentation will be available under the "Investors – Events and Presentations" section of the Company’s website, www.phiopharma.com, approximately one hour following the presentation.

The Tumor Targeted Lymphocytes Summit is focused on the topic of optimizing the clinical translation of TILs and endogenous T cells to improve the efficacy of ACT

Amgen Announces First-In-Human Data Evaluating Investigational Novel BiTE® Immunotherapies AMG 420 And AMG 330 At ASH 2018

On December 4, 2018 Amgen (NASDAQ:AMGN) reported the first clinical results from studies evaluating investigational novel bispecific T cell engager (BiTE) immunotherapies AMG 420 and AMG 330 (Press release, Amgen, DEC 4, 2018, View Source;p=RssLanding&cat=news&id=2379192 [SID1234531859]). In two separate Phase 1 dose escalation studies, AMG 420, which targets B-cell maturation antigen (BCMA), and AMG 330, which targets CD33, provided early evidence of tolerability and anti-tumor activity in patients with relapsed and/or refractory multiple myeloma and relapsed or refractory acute myeloid leukemia (AML), respectively. These data were highlighted during oral presentations at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego.

BiTE antibody construct technology, pioneered by Amgen, is an innovative treatment approach that helps the body’s immune system attack cancer cells without the removal of immune cells from the patient. Amgen is studying a number of "off-the-shelf" investigational BiTE immunotherapies, with distinct targets, across a range of hematologic and solid tumors.

"Building on our success with the only approved BiTE immunotherapy available for patients, Amgen is emphasizing our commitment to the potential of this platform by advancing the development of approximately a dozen novel molecules across hematologic and solid tumor targets in hopes of continuing to offer meaningful advances to patients in need," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We’re encouraged by the early results of investigational BiTE immunotherapies AMG 420 and AMG 330, especially when considered in the context of these heavily pre-treated patients, many of whom have run out of available options. We look forward to sharing more results from our BiTE pipeline at future medical meetings."

ASH Abstract #1010: Treatment with AMG 420, an anti-B-Cell Maturation Antigen (BCMA) Bispecific T-cell Engager (BiTE) Antibody Construct, Induces Minimal Residual Disease (MRD) Negative Complete Responses in Relapsed and/or Refractory (R/R) Multiple Myeloma (MM) Patients: Results of a First-in-Human (FIH) Phase 1 Dose Escalation Study

The data shared at ASH (Free ASH Whitepaper) were the first presentation of all endpoints from this Phase 1 dose-escalation trial of AMG 420 in patients with relapsed and/or refractory multiple myeloma. The objectives of the study included assessment of safety, tolerability and anti-tumor activity of AMG 420 per International Myeloma Working Group 2006 Uniform Response Criteria for Multiple Myeloma.

In the study, 42 patients with relapsed and/or refractory multiple myeloma who had progression after at least two prior lines of treatment (including a proteasome inhibitor and an immunomodulatory imide drug) received AMG 420 at varying doses [0.2 to 800 µg/day (d)]. AMG 420 induced clinical responses in 13 patients, including complete responses (CR) in seven patients. Four patients treated at the 400 µg/d dose achieved minimal residual disease (MRD) negative complete responses, meaning that no cancer cells were detectable in the bone marrow. The objective response rate at 400 µg/d was 70 percent (seven of 10 patients), with six patients still responding up to 7.5 months. One dose-limiting toxicity was observed up to the 400 µg/d dose (peripheral polyneuropathy, which improved to baseline after intravenous immunoglobulin and corticosteroid treatment).

Of those patients with serious adverse events (AEs) (n=20, 48 percent), 17 required hospitalization and four had prolonged hospitalization. Serious AEs included infections (n=12), peripheral polyneuropathy (n=2), and one each of liver failure, cardiac failure, edema, biliary obstruction, spinal cord compression, renal failure and weight loss. Treatment-related serious AEs included polyneuropathy (n=2, both grade 3) and edema (n=1, grade 3). Cytokine release syndrome (CRS) was seen in 16 patients (grade 1, n=13; grade 2, n=2; grade 3, n=1). In this study, 800 µg/d was determined to not be tolerable, as two out of the three patients treated at this dose experienced dose-limiting toxicities.

Two patients died during the course of the study from AEs not considered treatment-related. One patient died after the first cycle of treatment from acute respiratory distress due to concurrent flu and aspergillosis. The second patient died from liver failure secondary to a viral infection during the course of treatment.

"These first-in-human data of a BCMA-targeting BiTE immunotherapy showed encouraging evidence of AMG 420 activity, with no major toxicities up to the 400 µg/d dose in patients with relapsed and/or refractory multiple myeloma who received a median of four prior therapies," said Max S. Topp, M.D., professor, Hospital of Wuerzburg, Germany and AMG 420 clinical study investigator. "Despite recent treatment advances, multiple myeloma continues to be a disease characterized by cycles of relapse and recurrence requiring additional therapies to help control the disease."

Additionally, AMG 420 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA). Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.

ASH Abstract #25: A Phase 1 First-in-Human Study of AMG 330, an Anti-CD33 Bispecific T-cell Engager (BiTE) Antibody Construct, in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

In a separate first-in-human Phase 1 dose escalation study, 40 patients with relapsed or refractory AML were enrolled to receive AMG 330 in 12 dose cohorts with a target dose range of 0.5 to 480 µg/d. The study objectives were to evaluate the safety, pharmacokinetics and pharmacodynamics of AMG 330 and to estimate the maximum tolerated dose. Results showed that two patients in the trial achieved a CR at the 240 µg/d dose and two patients achieved a CR with incomplete blood count recovery, one at the 240 µg/d dose and one at the 120 μg/d dose. The CRs were not sustained beyond one cycle of treatment.

Patients in the trial received a median of one (range: 1-6) cycle with AMG 330; the majority of patients discontinued treatment for disease progression. Other reasons for study discontinuation included AEs (n=6, 2 treatment-related) and patient request (n=2).

Serious AEs were seen in 73 percent of patients (treatment-related in 17 patients). The most common serious AEs seen in more than one patient included CRS (n=11), febrile neutropenia (n=7), pneumonia (n=4), leukopenia (n=4), pyrexia (n=3), thrombocytopenia (n=3) and subdural hematoma (n=2). One patient died on study due to AML progression and one due to intracranial hemorrhage (neither treatment-related). There were dose-limiting toxicities of grade 2 CRS and grade 4 ventricular fibrillation with a target dose of 480 μg/d administered as a single-step regimen.

"The majority of adult AML patients will not be cured with standard chemotherapy, underscoring the need for innovative treatment options for those who have relapsed or are refractory to currently available treatments1," said Farhad Ravandi, M.D., Janiece and Stephen A. Lasher professor of medicine and chief of section of Developmental Therapeutics in the Department of Leukemia at the University of Texas – MD Anderson Cancer Center and AMG 330 clinical study investigator. "These early data are encouraging as they indicate AMG 330 may have anti-leukemic activity in heavily pretreated patients with relapsed or refractory AML, validating the need for continued evaluation of the BiTE platform in targeting CD33."

About BiTE Technology
Bispecific T cell engager (BiTE) antibody construct is an innovative technology that can be engineered to target any tumor antigen expressed by any type of cancer. The protein molecules are designed to kill malignant cells using the patient’s own immune system by bridging T cells to tumor cells. BiTE antibody construct helps connect the T cells to the targeted cell, with the intent of causing T cells to inject toxins which trigger cancer cell death (apoptosis). Amgen is developing BiTE antibody constructs to uniquely (or specifically) target numerous hematologic malignancies and solid tumors.

TG Therapeutics, Inc. Announces Oral Presentation of Follow-Up Data from the Triple Combination of Ublituximab, Umbralisib, and Pembrolizumab in Patients with Relapsed/Refractory CLL and Richter’s Transformation at 60th American Society of Hematology Annual Meeting and Exposition

On December 4, 2018 TG Therapeutics, Inc. (NASDAQ: TGTX), reported updated clinical data from its Phase I/II trial of ublituximab (TG-1101), the Company’s novel glycoengineered anti-CD20 monoclonal antibody in combination with umbralisib (TGR-1202), the Company’s oral, next generation PI3K delta inhibitor, and pembrolizumab, in patients with relapsed/refractory Chronic Lymphocytic Leukemia (CLL) and Richter’s Transformation (RT) (Press release, TG Therapeutics, DEC 4, 2018, View Source [SID1234531857]). Data from this trial were presented yesterday during an oral session at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We were excited to share the data presented from the combination of U2 plus pembrolizumab. Due to potentially overlapping immune-mediated toxicity, this is the first trial where a PI3K delta inhibitor has been combined with a PD-1/PD-L1 inhibitor, again highlighting the unique combinability of the U2 regimen. In addition to demonstrating that these drugs could be safely combined, we were encouraged to see favorable response rates in both RT and BTK refractory CLL patients, a subset of patients that are historically challenging to treat." Mr. Weiss continued, "Our proprietary anti-PD-L1, TG-1501, has now completed Phase 1 dose escalation, and we believe the data presented today set the stage for the commencement of the combination of U2 plus TG-1501, in the coming months."

Below summarizes the oral presentation.

Phase I/II Study of Umbralisib (TGR-1202) in Combination with Ublituximab (TG-1101) and Pembrolizumab in Patients with Relapsed/Refractory CLL and Richter’s Transformation (Publication Number: 297)

This oral presentation includes data from patients with relapsed or refractory CLL or Richter’s Transformation treated with the triple combination of ublituximab, umbralisib, and pembrolizumab. Fifteen patients were evaluable for safety (10 CLL patients and 5 RT patients) and 14 were evaluable for efficacy (10 CLL and 4 RT), with one RT patient too early to evaluate. Data highlights include:

● The triple combination was well tolerated, with immune mediated toxicities not appearing above what would be expected with either umbralisib or pembrolizumab alone
● 90% (9 of 10) Overall Response Rate (ORR) in patients with relapsed/refractory CLL, including one Complete Response (CR)
● 80% (4 of 5) ORR in BTK refractory CLL patients, of which 3 of 4 BTK refractory CLL responders achieved their response to U2 alone prior to introduction of pembrolizumab
● 50% (2 of 4) ORR in RT, with both responses being a CR
● Responses have been durable, and a median progression-free survival has not yet been reached
● The first patient treated remains progression-free for 36+ months, having now been off therapy for more than 24 months

KOL webcast and conference call (on Tuesday, December 4, at 5pm CET): Innate Pharma announces updated results that support advancement of IPH4102 in refractory Sézary syndrome at the American Society of Hematology (ASH) 2018 annual meeting

On December 4, 2018 Innate Pharma reported its updated results that support advancement of IPH4102 in refractory Sézary syndrome at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 annual meeting (Press release, Innate Pharma, DEC 4, 2018, View Source [SID1234531856]).

Pierre Dodion, Chief Medical Officer, Innate Pharma, will be joined by Prof. Martine Bagot, Head of Dermatology Department at the Saint Louis Hospital, Paris and lead investigator of the study, for a live webcast and conference call with a Q&A session on Tuesday, December 4 at 5pm CET to discuss the announcement.

The presentation and access to the live webcast will be available at this link: View Source

Participants can also join the conference call using the following dial-in numbers:

Location

Purpose

Phone number

France

Participant

+33 (0)1 76 77 22 57

United Kingdom

Participant

+44 (0)330 336 9411

United States

Participant

+1 929-477-0324

Standard International Access

Participant

0800 279 7204

The participation code is: 4535688

New Venclexta/Venclyxto data demonstrate deep responses in two of the most common types of leukaemia

On December 4, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported new data from the Venclexta/Venclyxto (venetoclax) clinical development programme, including longer-term results from the phase III MURANO study in people with previously treated chronic lymphocytic leukaemia (CLL) and updated data from two phase Ib/II studies in people with previously untreated acute myeloid leukaemia (AML) ineligible for intensive chemotherapy due to coexisting medical conditions (Press release, Hoffmann-La Roche, DEC 4, 2018, View Source [SID1234531851]). Data from the Venclexta/Venclyxto clinical development programme that ranges across multiple blood cancers, including CLL, AML, non-Hodgkin lymphoma and multiple myeloma, will be featured in more than 30 abstracts, including 12 oral presentations, at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting.

"We’re excited by the versatility of Venclexta/Venclyxto in treating a range of distinct types of blood cancer, including difficult-to-treat forms with limited options," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "These data support our broad clinical development programme through which we hope to discover more ways Venclexta/Venclyxto can be used alone or in combination with other medicines to treat additional types of cancer."

Updated data in CLL
Two new analyses of the phase III MURANO study in relapsed or refractory (R/R) CLL demonstrated the continued clinical benefit of Venclexta/Venclyxto plus MabThera/Rituxan (rituximab) was sustained after patients completed the chemotherapy-free, two-year fixed-duration course of therapy.

An analysis showed the combination reduced the risk of disease progression or death (progression-free survival; PFS, as assessed by investigator) by 84% (HR=0.16; 95% CI: 0.12-0.23; p<0.0001) compared to standard of care bendamustine plus MabThera/Rituxan (BR) after a median three-year follow-up. At three years, 71% of patients in the Venclexta/Venclyxto plus MabThera/Rituxan arm had not experienced disease progression, compared to 15% of patients in the BR arm (median PFS: not reached vs. 17.0 months, respectively). A clinically meaningful benefit in overall survival was also observed in the Venclexta/Venclyxto arm compared to the BR arm (88% vs. 80%, HR=0.50; 95 percent CI: 0.30-0.85). Consistent benefit was observed in all patient subgroups for Venclexta/Venclyxto plus MabThera/Rituxan compared to BR, including high-risk and low-risk groups. Data were presented in an oral session on Saturday, 1 December at 14:45 PST (Abstract #184).
A separate analysis showed higher rates of minimal residual disease (MRD)-negativity observed with Venclexta/Venclyxto plus MabThera/Rituxan compared to BR were sustained after patients completed treatment (62% vs. 13%). MRD-negativity means no cancer can be detected using a specific, highly sensitive test, and was defined as less than 1 CLL cell in 10,000 leukocytes. Importantly, these results were observed in the majority of patients in the Venclexta/Venclyxto arm, including patients in high-risk subgroups and were consistent with the maintained PFS benefit seen with longer follow-up. These data support the utility of MRD in peripheral blood as a predictive marker of clinical outcome. No new safety signals were observed with the treatment combination of Venclexta/Venclyxto plus MabThera/Rituxan. These data will be presented in an oral session on Monday, 3 December at 11:30 PST (Abstract #695).
Updated data in AML
Updated data from the phase Ib M14-358 and phase I/II M14-387 studies evaluating Venclexta/Venclyxto in combination with a hypomethylating agent or low-dose cytarabine (LDAC) in people with previously untreated AML who are ineligible for intensive chemotherapy, will also be presented. These results showed that among patients who were dependent upon blood transfusions at baseline, about half were able to achieve transfusion independence (the absence of transfusions during any consecutive 56 days during the study treatment period). No unexpected safety signals were observed with Venclexta/Venclxyto in combination with hypomethylating agents or LDAC.

The M14-358 study showed high rates of complete remission (with at least partial blood count recovery, CR+CRh) of 67% for those who received Venclexta/Venclyxto plus azacitidine and 71% for those who received Venclexta/Venclyxto plus decitabine. For people taking Venclexta/Venclyxto and azacitadine or decitabine who were dependent on blood transfusions at baseline, 50% and 52% achieved red blood cell transfusion independence, respectively; and 58% or 60% achieved platelet transfusion independence, respectively.
The M14-387 study showed rates of complete remission (with or without full recovery of normal blood cell count, CR+CRi) of 54% in people who received Venclexta/Venclyxto in combination with LDAC and a median duration of remission of 8.1 months. For people taking Venclexta/Venclyxto with LDAC, 48% achieved red blood cell transfusion independence and 60% achieved platelet transfusion independence.
Results from the two studies were presented in an oral session on Sunday, December 2 at 7:45 PST and 8:00 PST, respectively (Abstract #284 and #285).

Based on earlier results from the M14-358 and M14-387 studies, Venclexta was granted accelerated approval by the US Food and Drug Administration (FDA) for the treatment of people with newly-diagnosed AML who are age 75 years or older, or for those ineligible for intensive induction chemotherapy due to coexisting medical conditions. A robust clinical development programme for Venclexta/Venclyxto in AML is ongoing, including two ongoing phase III studies evaluating Venclexta/Venclyxto in combination with azacitidine or with LDAC for people with previously untreated AML who are ineligible for intensive chemotherapy based on results from the M14-358 and M14-387 studies.

About the MURANO study
MURANO (NCT02005471) is a phase III open-label, international, multicentre, randomised study evaluating the efficacy and safety of Venclexta/Venclyxto in combination with MabThera/Rituxan compared to bendamustine in combination with MabThera/Rituxan (BR) in patients with relapsed or refractory chronic lymphocytic leukaemia (CLL). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta/Venclyxto, patients on the Venclexta/Venclyxto plus MabThera/Rituxan arm received six cycles of Venclexta/Venclyxto plus MabThera/Rituxan followed by Venclexta/Venclyxto monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with CLL who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta/Venclyxto plus MabThera/Rituxan or BR. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included overall survival, overall response rate and complete response rate (with or without complete blood count recovery).

About the M14-358 study
The M14-358 study (NCT02203773) is an open-label, non-randomised, phase Ib dose escalation and expansion study evaluating the safety and efficacy of Venclexta/Venclyxto in combination with hypomethylating agents, azacitidine or decitabine, in 115 newly-diagnosed people with acute myeloid leukaemia who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions. Study endpoints included complete remission rates, transfusion independence, overall survival and safety.

About the M14-387 study
The M14-387 study (NCT02287233) is an open-label, single-arm, phase I/II dose escalation and expansion study evaluating the safety and efficacy of Venclexta/Venclyxto in combination with low-dose cytarabine (LDAC) in 82 newly-diagnosed people with acute myeloid leukaemia who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions. Study endpoints included complete remission rates, transfusion independence, overall survival and safety.

About Venclexta/Venclyxto
Venclexta/Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States, and commercialised by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood and other cancers.

In the US, Venclexta has been granted four Breakthrough Therapy Designations by the FDA: in combination with Rituxan for people with relapsed or refractory chronic lymphocytic leukaemia (CLL); as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukaemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine for people with untreated AML ineligible for intensive chemotherapy.

About Chronic Lymphocytic Leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world.[1] CLL mainly affects men and the median age at diagnosis is about 70 years.[2] Worldwide, the incidence of all leukaemias is estimated to be more than 400,000[3] and CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia.[1]

About Acute Myeloid Leukaemia
Acute myeloid leukaemia (AML) is an aggressive form of leukaemia that starts in immature forms of blood-forming cells, known as myeloid cells, found in the bone marrow.[4] AML is the most common type of aggressive leukaemia in adults. It has the lowest survival rates of all types of leukaemia.[5] Even with the best available therapies, older patients aged 65 and over have survival rates comparable to patients with advanced lung cancer, with a five year overall survival rate of <5%.[6;7] Approximately 20,000 people in the US and 18,000 in Europe are diagnosed with AML each year.[8;9]