On December 12, 2017 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing oral therapies that target various phases of cell cycle control for the treatment of cancer and other serious disorders, reported results from the Company’s Phase 3 SEAMLESS study (Press release, Cyclacel, DEC 12, 2017, View Source [SID1234522595]). Cyclacel had previously announced top-line results from its Phase 3 SEAMLESS study in February 2017. The study enrolled elderly patients with newly diagnosed acute myeloid leukemia (AML) and compared alternating cycles of decitabine and sapacitabine versus decitabine. Data were reported at an oral presentation on Monday, December 11, at 6:45 PM EST at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia.

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"Although the study did not reach its primary endpoint of superiority in survival, we are encouraged by the higher complete remission rate on the sapacitabine-decitabine arm, especially in the subgroup with low white blood cell count; additional analysis of the data should be pursued," said Hagop Kantarjian, M.D., Professor and Chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center, and chair of the study.

"We are pleased to report detailed results of the SEAMLESS study, which as previously announced, did not reach its primary endpoint," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "We believe that the subgroup results have defined a patient population for whom the decitabine-sapacitabine regimen may represent an improvement over low intensity treatment by decitabine alone. We plan to discuss the data, the statistical robustness of the subgroup results and the optimal baseline peripheral white blood cell (WBC) cutpoint with European and US regulatory authorities and will provide updates as appropriate. We are grateful to the patients, their families and the investigators for their contributions to this large study. In parallel, we are progressing our other clinical programs in transcriptional regulation with CYC065 and DNA damage response with sapacitabine-seliciclib in biomarker-selected patients with solid tumors, such as those with BRCA mutations or resistance to existing cancer therapies."

Study Design & Intent-to-Treat Results

The randomized, open label, Phase 3 SEAMLESS study enrolled 482 patients, aged 70 years or older, with newly diagnosed AML who were not candidates for or refused intensive therapy at 110 US and EU sites. Patients were stratified by WBC, antecedent hematologic disorder (AHD), and marrow blasts, and randomized 1:1 to receive either intravenous decitabine administered in alternating cycles with oral sapacitabine versus intravenous decitabine alone.

The trial did not meet its primary endpoint of demonstrating statistically significant improvement in overall survival. A higher complete remission (CR) rate, a secondary endpoint, was observed on the decitabine-sapacitabine arm (17% versus 11%). Other endpoints and safety were similar between the arms.

Prespecified Subgroup Analysis

Baseline WBC

In the less than 10,000 WBC subgroup (n=319) a trend towards improved overall survival (median 8.0 versus 5.8 months, HR=0.84 [0.66, 1.06], p=0.14) favoring decitabine-sapacitabine and a significantly higher CR rate (21.0% versus 8.6%, p=0.0017) was achieved on decitabine-sapacitabine.

In the 10,000 or more WBC subgroup (n=163) significantly better overall survival (median 3.8 versus 5.5 months, HR=1.57 [1.12, 2.19], p=0.007) was observed on decitabine. A trend in CR rate (8.3% versus 15.2%, p=0.18) favoring decitabine was observed but it did not reach statistical significance.

Prior AHD

In the subgroup with prior AHD (n=136) a significantly higher CR rate (16.7% versus 5.7%, p=0.0398) was achieved on decitabine-sapacitabine. There was a numerical difference in median survival (6.4 versus 5.0 months, HR=0.85 [0.59, 1.24], p=0.41) favoring decitabine-sapacitabine but overall survival did not reach statistical significance.

In the subgroup without prior AHD (n=346) there was a numerical difference in median survival (5.9 versus 6.7 months, HR=1.08 [0.86, 1.35], p=0.52) favoring decitabine and CR rate (16.6% versus 12.9%) favoring decitabine-sapacitabine but neither reached statistical significance.

Cytogenetics

In the subgroup with other than unfavorable cytogenetics (n=288) there was a numerical difference in median survival (8.2 versus 5.7 months, HR=0.89 [0.69, 1.15], p=0.38) and CR rate (19.9% versus 11.6%, p=0.16) favoring decitabine-sapacitabine but neither reached statistical significance.

In the subgroup with unfavorable cytogenetics (n=194) there was a numerical difference in median survival (3.8 months versus 5.7 months, HR=1.27 [0.94, 1.73], p=0.12) favoring decitabine but overall survival did not reach statistical significance. There was a numerical difference in CR rate favoring decitabine-sapacitabine (12.0% versus 9.6%) but it did not reach statistical significance.

In the subgroup of patients with below 50% and with 50% or higher bone marrow blasts there were no statistically significant differences in overall survival between the arms.

Presentation

The presentation (abstract 891), titled "Results of a Phase 3 Study of Elderly Patients with Newly Diagnosed AML Treated with Sapacitabine and Decitabine Administered in Alternating Cycles," is available on the Cyclacel website at www.cyclacel.com.

About Sapacitabine

Sapacitabine (CYC682), an orally-available nucleoside analogue, is currently being studied in an ongoing, extension of a Phase 1 study evaluating a combination regimen of sapacitabine and seliciclib, a first generation CDK inhibitor. Parts 1 and 2 of the study evaluated approximately 90 patients with advanced cancers. Part 3 is ongoing in patients with BRCA positive, breast, ovarian and pancreatic cancer. Over 1,000 patients with hematological malignancies and solid tumors have received sapacitabine.

About AML

AML is a rapidly progressing cancer of the blood characterized by the uncontrolled proliferation of immature blast cells in the bone marrow. The American Cancer Society estimates there will be approximately 21,380 new cases of AML and approximately 10,590 deaths from AML in the U.S. in 2017. AML is generally a disease of older adults and the median age is about 67 years. Newly diagnosed elderly patients with poor prognostic risk factors typically die within one year.

On December 12, 2017 VBI Vaccines Inc. (Nasdaq: VBIV) (TSX:VBV) (VBI) reported that Jeff Baxter, President and CEO, will present at the BMO Capital Markets Prescriptions for Success Healthcare Conference on Thursday, December 14, 2017, at 11:00 AM ET in New York (Press release, VBI Vaccines, DEC 12, 2017, View Source [SID1234522586]).

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The presentation will be webcast live and can be accessed through the below link or through the Investors page of VBI’s website at: www.vbivaccines.com/investors/events-presentations/. A replay of the presentation will be available at the same location for 90 days following the conference.

Event Details

● Event: BMO Capital Markets Prescriptions for Success Healthcare Conference

● Date: Thursday, December 14, 2017

● Time: 11:00 – 11:30 AM ET

● Event Website: View Source

● Webcast: https://cc.talkpoint.com/bmoc001/121417a_as/?entity=38_GTRNEFD

On December 12, 2017 Servier, Pfizer Inc. (NYSE: PFE) and Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS) presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta preliminary results from two phase 1 studies of UCART19, an investigational allogeneic anti-CD19 CAR T-cell product, in adult and pediatric patients with relapsed or refractory (R/R) CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) (Press release, Cellectis, DEC 12, 2017, View Source;utm_medium=feed&utm_campaign=Feed%3A+cellectis+%28Cellectis+RSS+Feed%29#When:23:42:00Z [SID1234522594]). These first-in-human data demonstrated the safety and tolerability of UCART19, resulting in an 83% complete remission rate across the adult and pediatric patient population.

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Results from the CALM (UCART19 in Advanced Lymphoid Malignancies) Trial

The CALM study (UCART19 in Advanced Lymphoid Malignancies) is an open label, dose-escalation study designed to evaluate the safety, tolerability and anti-leukemic activity of UCART19 in adult patients with R/R B-ALL. Five out seven patients treated achieved molecular remission at Day 28 post UCAR19. Molecular remission is defined by negative minimal residual disease (MRD). MRD is a measurement of the number of residual leukemic cells that remain after treatment.

"These early results for UCART19 are very encouraging both in terms of manageable safety and the impressive complete molecular remission rate in these hard-to-treat adult patients with R/R B-ALL," said Reuben Benjamin, Principal Investigator of the CALM Study and Consultant Hematologist at King’s College Hospital, United Kingdom. "This first cohort explored a lower dose of UCART19 that is approximately one tenth of that used in most autologous CAR-T trials. These results support additional evaluation of UCART19 at varying doses."

Only one Grade 1 cutaneous acute graft versus host disease (GvHD) occurred. No severe neurotoxicity was observed. Cytokine release syndromes (CRS) were mild and manageable except in one patient treated with UCART19 at the first dose level, who developed CRS Grade 4 and neutropenic sepsis leading to death at Day 15.

Results from the PALL (Pediatric Acute Lymphoblastic Leukemia) Trial

The PALL (Pediatric Acute Lymphoblastic Leukemia) study is a phase 1, open label study designed to evaluate the safety and ability of UCART19 to induce molecular remission defined by MRD negativity at Day 28 to enable allogeneic stem cell transplantation in pediatric patients with high-risk R/R B-ALL. Results showed all five children achieved MRD negativity, enabling them to proceed to allogeneic stem cell transplant. Only one Grade 1 cutaneous acute GvHD occurred. No severe neurotoxicity was observed. Cytokine release syndromes were mild in the majority of cases and were all manageable.

Servier is the sponsor of both studies that are active in Europe and the United States.

"We are proud to present the first clinical trial data with UCART19 in patients with heavily pretreated R/R ALL," said Patrick Therasse, MD, PhD, Head of Research and Development-Oncology for Servier. "We believe this innovative, allogeneic CAR T-cell approach could be disruptive to the patient community."

About UCART19

UCART19 is an allogeneic CAR T-cell product candidate being developed for treatment of CD19-expressing hematological malignancies, gene edited with TALEN. UCART19 is initially being developed in adult and pediatric ALL and is currently in Phase I. UCART19 has the potential to overcome the limitation of the current autologous approach by providing an allogeneic, frozen, "off-the-shelf" T cell based medicinal product.

In November 2015, Servier acquired the exclusive rights to UCART19 from Cellectis. Following further agreements, Servier and Pfizer began collaborating on a joint clinical development program for this cancer immunotherapy. Pfizer has been granted exclusive rights by Servier to develop and commercialize UCART19 in the United States, while Servier retains exclusive rights for all other countries.

On December 12, 2017 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company"), reported data at the 59th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition on the labeling of daratumumab, a CD38 targeting antibody which is marketed commercially by Johnson and Johnson (JNJ) under the trade name Darzalex, with the radioisotope Actinium-225 (Press release, Actinium Pharmaceuticals, DEC 12, 2017, View Source [SID1234522567]). The ARC or Antibody Radio-Conjugate of daratumumab labeled with the radioisotope Actinium-225 demonstrated enhanced targeted cancer cell killing in vitro compared with naked daratumumab. Actinium is a clinical-stage biopharmaceutical company focused on developing and commercializing targeted therapies for safer myeloablation and conditioning of the bone marrow prior to a bone marrow transplant, and for the targeting and killing of cancer cells, This initiative comes from Actinium’s AWE or Actinium Warhead Enabling Technology Platform that combines the isotope Actinium-225 with monoclonal antibodies to create ARC’s.

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The poster highlighted the capabilities of the Company’s recently announced AWE or Actinium Warhead Enabling Program that studied the effect of Actinium-225 labeled daratumumab on DAUDI, 28BM and 28PE cell lines at the 48, 72 and 96 hour time points as well as U226, a cell line that does not express CD38. The results showed that when daratumuamb is labeled with Actinium-225, cell death was increased as much as ten-fold, approaching one-hundred percent cell death in certain cell lines and at certain time points, and in all three cell lines tested the Actinium-225 labeled daratumumab had higher cell death compared to naked daratumumab. In addition, immunogenicity was preserved with most or all of daratumumab’s CD38 targeting ability maintained, high rates of radioisotope labeling of the antibody from 82-85% was demonstrated, as was high rates of stability from 73-87% at various temperatures forty-eight hours post labeling. As a result of this promising data, Actinium is continuing to investigate Actinium-225 labeled daratumumab further, with in vivo experiments ongoing.

The abstract for the poster can be accessed through the following link: View Source

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "These promising results showcase the power of our AWE Technology Platform. The ability to increase the cell killing power of an antibody while preserving its targeting ability is a powerful premise that can have profound impacts on the treatment of patients and outcomes. Given these initial positive results we look forward to continuing to expand our AWE Program by labeling additional antibodies, and even other targeting moeities, with Actinium-225 to fully leverage the targeted potency of Actinium-225, our proprietary technology, and our team’s expertise and know how."

Daratumumab (Darzalexâ, Janssen) is an immunoglobulin G1 kappa (IgG1к) cytolytic human monoclonal antibody directed against the CD38 antigen that is approved to treat patients with multiple myeloma. First approved in 2015 as a monotherapy for patients who have received three prior therapies, daratumumab is now approved for use in combination and has also received approvals in earlier lines of treatment and has achieved blockbuster sales in excess of one billion dollars in the last twelve months. Daramtumumab’s effective targeting of the CD38 antigen and its success in the clinical setting indicates a high efficacy baseline, making it an ideal candidate antibody for which to demonstrate additional benefits in efficacy as a result of Actinium-225 enablement. While daratumumab is increasingly being used to treat patients, infusion reactions are common, likely due in part to administration of a large dose at 16 mg/kg, which requires long infusion times. Additionally, the infusions must take place frequently – weekly for the first 8 weeks, followed by bi-weekly infusions up to week 25, after which monthly infusions are required.

Sandesh Seth, Actinium’s Chairman and CEO added, "There has been a renaissance in radioisotope based therapies of late while antibodies continue to prove to be beneficial therapies for patients in numerous oncology indications. Our AWE Technology Platform is able to combine the strengths of these modalities to create ARC’s or Antibody Radio-Conjugates that leverage the targeted potency of the actinium-225 isotope and our proprietary technology. With this detailed data now available, we look forward to showcasing this capability to potential partners and collaborators as an example of the value generating potential of our AWE Program. We are confident that enhanced cell killing power via Actinium-225 will be attractive to developers of both novel and approved antibodies as a means to generate pipeline opportunities via de novo efforts and life cycle management. We look forward to actively promoting our AWE program in 2018 based on the 2017 enhancements in technology, scientific capabilities and team at Actinium."

About Our Actinium Warhead Enabling Technology Platform

The Actinium Warhead Enabling (AWE) Technology Platform enables a highly potent and selective form of targeted therapy that combines the powerful alpha-emitting radioisotope actinium-225 with targeting agents, which are designed to seek out cancer cells in the body that express particular markers. Actinium-225 emits significant alpha radiation making it a potent treatment modality against targeted cancer cells while limiting damage to healthy tissues as its radiation travels extremely short distances in the body. When labeled to targeting agents, actinium-225 can be delivered directly to cancer cells where the high linear energy transfer resulting from the emission of alpha particles results in irreparable DNA double stranded breaks and ultimately cancer cell death. Despite this superior cell killing power, actinium-225 when delivered in a targeted manner is sparing of the surrounding environment in the body due to the short path length of its alpha-particle radiation and can result in a superior safety profile. Actinium Pharmaceuticals owns or has licensed the rights to several issued and pending patents that pertain to its AWE Technology Platform including technology to manufacture Actinium-225 in a cyclotron. In addition, the Company obtains actinium-225 from various sources such as the U.S. Department of Energy at Oak Ridge National Laboratories and has developed considerable know-how, expertise and validated processes related to production of antibody radio-conjugates (ARC), management of the supply chain and dealing with various regulatory bodies. The AWE Technology Platform can be utilized to potentially improve the cell-killing power of targeting agents such as antibodies, peptides, Fab fragments, nanobodies etc. via labeling with Actinium-225. In addition to increased efficacy, these Actinium-225 enhanced targeting agents can offer optimized dosing or administration and in the case of approved targeting agents provide an opportunity to extend intellectual property protection by the creation of biobetters or improved versions of the approved agent. The Company’s Actinium Warhead Enabling (AWE) Program can be accessed by biopharmaceutical companies that are interested in creating biobetters through the utilization of the AWE Platform Technology. To learn more about the AWE Technology Platform or the AWE Program please contact Keisha Thomas, Ph.D., Corporate Development at [email protected].

On December 12, 2017 TapImmune Inc. (NASDAQ: TPIV), a leading clinical-stage immuno-oncology company with ongoing clinical trials in ovarian and breast cancer, reported that the first patient has been enrolled in a Phase 2 randomized, multi-center, double-blinded, placebo-controlled clinical trial of TapImmune’s novel therapeutic vaccine candidate TPIV200 (Press release, TapImmune, DEC 12, 2017, View Source [SID1234523779]). The 280-patient trial, sponsored by Mayo Clinic, received $13.3 million in grant funding from the U.S. Department of Defense (DoD) to evaluate the prevention of cancer recurrence in women with triple-negative breast cancer (TNBC) who have completed first-line surgery and radiotherapy/chemotherapy.

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TPIV200 is a novel, multi-epitope, peptide-based cancer vaccine that has been shown to induce a robust and long-lasting "memory" T-cell immune response directed against folate receptor alpha (FRa), a molecule that is overexpressed on the surface of the vast majority of TNBC cancer cells and is associated with cancer recurrence. As an off-the-shelf vaccine consisting of several carefully chosen FRa peptides, TPIV200 is uniquely able to stimulate both T "helper" cells and T "killer" cells to target tumor cells and is expected to cover greater than 85% of human genotypes worldwide.

"We remain grateful to the U.S. Department of Defense and Mayo Clinic for enabling TapImmune to gain invaluable clinical safety and efficacy insight for TPIV200 under this grant," said TapImmune President and CEO Peter Hoang. "We believe TPIV200 and our other vaccine candidates have an important role to play within the current immuno-oncology ecosystem by potentially bridging a critical gap not currently addressed by other immunotherapies, which have shown promise in only a small number of patients. Unlike current approaches, TapImmune’s vaccines are designed to produce broad-based, durable T-cell responses in the vast majority of patients, which we believe are essential for improving clinical outcomes and ensuring potential regulatory and commercial success. We look forward to providing updates appropriately as this exciting Phase 2 study continues to enroll patients."

TapImmune and its clinical partners are evaluating TPIV200 in multiple ongoing Phase 2 trials for treating ovarian and breast cancer, including a randomized dosing trial in TNBC that recently completed patient enrollment. The four-arm trial is designed to help determine the optimal TPIV200 vaccine dose and regimen to maximize patients’ anti-tumor immune responses. Interim immunogenicity results from this ongoing study are anticipated in the first half of 2018.

Keith L. Knutson. Ph.D., Professor of Immunology in the Department of Immunology, and Edith A. Perez, M.D., Professor of Medicine in the Division of Hematology and Oncology, both at Mayo Clinic’s Florida campus in Jacksonville, Florida, are the recipients of the U.S. Department of Defense grant and are leading the Phase 2 trial.

Mayo Clinic and Dr. Knutson have a financial interest in TapImmune for the triple negative breast cancer treatment.