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Stemline Therapeutics Announces Oral Presentation of SL-701 Phase 2 Data in Second-Line Glioblastoma at the 23rd Annual Meeting of the Society of Neuro-Oncology (SNO)

On November 16, 2018 Stemline Therapeutics, Inc. (Nasdaq: STML), a biopharmaceutical company focused on the development and potential commercialization of novel oncology therapeutics, reported that data from the Phase 2 trial of SL-701 in patients with second-line glioblastoma (GBM) were selected for oral presentation at the 23rd Annual Meeting of the Society of Neuro-Oncology (SNO) being held November 15-18, 2018 in New Orleans, LA (Press release, Stemline Therapeutics, NOV 16, 2018, View Source [SID1234531394]).

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Details on the presentation are as follows:

Title: Phase 2 trial of SL-701 + bevacizumab in patients with previously treated glioblastoma (GBM) meets primary endpoint of OS-12, with preliminary correlation between long-term survival and target-specific CD8+ T cell immune response
Presenter: David Peereboom, MD; Cleveland Clinic
Abstract: ATIM-06 Date/Time: Friday, November 16, 2018 – 4:25 PM CT

A copy of the oral presentation will be available on the Stemline website (www.stemline.com), under the Scientific Presentations tab, following the SNO presentation.

VBL Therapeutics Presents Results from Phase 3 GLOBE Study in Patients with Recurrent Glioblastoma at the 2018 Society for Neuro-Oncology Annual Meeting

On November 16, 2018 VBL Therapeutics (Nasdaq: VBLT), is reported its results today from its Phase 3 GLOBE study in patients with recurrent glioblastoma (rGBM) which was designed to evaluate VB-111 in combination with bevacizumab (Avastin) (`treatment arm`), compared to bevacizumab (`control arm`) (Press release, VBL Therapeutics, NOV 16, 2018, View Source [SID1234531393]). In March 2018, VBL announced top-line data for the study, which did not demonstrate a benefit in overall survival (OS) or progression-free survival for the treatment arm relative to the bevacizumab control.

The GLOBE data are being presented today at the 2018 Society for Neuro-Oncology Annual Meeting by Dr. Timothy Cloughesy, MD, Professor of Clinical Neurology and Director of the Neuro-Oncology Program, UCLA School of Medicine and principal investigator of the GLOBE trial. The data include further analyses of the GLOBE data including baseline prognostic factors and subgroups analysis. Data show that the baseline tumor volume, which is a significant prognostic factor in rGBM, was higher in the treatment arm compared to the control arm. Overall, the subjects in the study had relatively high tumor volume, as large-volume tumors were not an exclusion criterion. It is of interest that patients with smaller tumors (<15 cm3) appeared to respond better to the treatment arm, with numerically higher response rate and overall survival observed. Furthermore, a trend towards greater survival was observed in patients treated with VB-111 who reported fever. VB-111 was well tolerated, with a similar early termination rate in both the treatment and control arms. Most frequent adverse event was self-limited fever, starting several hours post therapy and usually resolving by 24 hours. As expected, a higher rate of SAEs and grade >=3 AEs was reported in the combination treatment arm.

Subsequent analyses have focused on the potential reasons for the major differences in outcomes between the positive VB-111 Phase 2 clinical trial in rGBM and the unsuccessful GLOBE results. The Phase 2 trial of VB-111 met the primary endpoint of OS benefit with median OS (mOS) of 13.6 months upon treatment with VB-111 as a single drug (`priming`) followed by adding bevacizumab to VB-111 upon further progression, compared to mOS of 6.8 months for the treatment arm in GLOBE (co-administration of VB-111 and bevacizumab, without any VB-111 monotherapy `priming` period).

Thorough analyses of the baseline risk factors of the Phase 2 and the Phase 3 treatment groups did not reveal any differences. Therefore, patient selection or different patient populations could not explain the difference between the results of the two studies. The only significant change between the Phase 2 and Phase 3 treatment cohorts was in the treatment regimen – the regimen for Phase 2 trial included priming with VB-111 whereas the regimen for GLOBE trial did not.

To test the hypothesis that concomitant treatment with bevacizumab may have a negative effect on VB-111 activity, the Company investigated this combination in a pre-clinical tumor model. The results indicate that treatment with VB-111 in combination with bevacizumab appears to block the anti-tumor the effect of VB-111, compared to VB-111 monotherapy. In addition, a retrospective analysis of a small cohort of 10 patients who were treated concomitantly with VB-111 and bevacizumab for safety evaluation (no priming), was inferior to what was observed with VB-111 priming in the Phase 2 study.

To better understand these results, the Company is collaborating with UCLA scientists in performing thorough analyses of MRI scans for VB-111-primed combination arm patients from the Phase 2 trial, compared to the un-primed combination arm patients in the GLOBE trial.

"Our initial exploratory analyses demonstrate clear radiologic responses over time in rGBM patients treated with VB-111 in the Phase 2 trial, both on VB-111 monotherapy and in combination with bevacizumab after priming with VB-111 alone, which were translated to overall survival. We are currently analyzing the GLOBE MRI scans to see if this signature of VB-111 activity is lost in the GLOBE combination group and will report the outcome upon completion of the analysis," said Dr. Cloughesy.

"The new analyses we have been conducting provide insight into how the VB-111 treatment regimen may influence its anti-tumor effect and help us understand why the positive Phase 2 data were not replicated in the GLOBE Phase 3 study," said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics. "We believe that priming with VB-111 without bevacizumab may be critical for the immune and vascular-disruptive/anti-angiogenic mechanism of VB-111 in rGBM. We continue to have confidence in the ongoing OVAL Phase 3 study of VB-111 in platinum-resistant ovarian cancer patients, whose protocol takes into account lessons learned from our GBM trial. The OVAL Phase 3 study is evaluating VB-111 in combination with chemotherapy rather than Avastin. The combination of VB-111 with paclitaxel worked well both in pre-clinical settings and in our Phase 2 for ovarian cancer, including in patients whose tumors progressed on prior treatment with Avastin. In OVAL, we are repeating exactly the same successful Phase 2 regimen."

For a link to the GLOBE presentation at SNO see: LINK

About the GLOBE study

The GLOBE pivotal Phase 3 trial was a randomized, controlled, double-arm, open-label study of VB-111 dosed every two months in combination with bevacizumab dosed every two weeks, compared to bevacizumab monotherapy. Key inclusion criteria included first or second progression of glioblastoma following standard of care treatment with temozolomide and radiation, a histologically confirmed diagnosis of glioblastoma and measurable disease by RANO criteria at progression.

The study was conducted under a Special Protocol Assessment (SPA) granted by the FDA, with full endorsement by the Canadian Brain Tumor Consortium (CBTC). VB-111 has received orphan drug designation in the United States and Europe and was granted Fast Track designation by the FDA for promising and meaningful long-term survival in patients with glioblastoma that has recurred following treatment with standard chemotherapy and radiation.

About Ofranergene Obadenovec (VB-111)

VB-111, a potential first-in-class anticancer therapeutic candidate, is the Company’s lead oncology product currently being studied in a Phase 3 trial for ovarian cancer. VB-111 has received orphan drug designation in both the US and Europe, and fast track designation in the US for prolongation of survival in patients with rGBM. In addition, VB-111 successfully demonstrated proof-of-concept and survival benefit in Phase 2 clinical trials in radioiodine-refractory thyroid cancer and recurrent platinum-resistant ovarian cancer. VB-111 has received an Orphan Designation for the treatment of ovarian cancer by the European Medicines Agency (EMA).

BeiGene Announces Preliminary Clinical Data on PARP Inhibitor Pamiparib Presented at Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology

On November 16, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported the presentation of preliminary clinical data from an ongoing Phase 1/2 trial of its investigational PARP inhibitor, pamiparib, in combination with radiation therapy (RT) and/or temozolomide (TMZ) in patients with newly diagnosed or recurrent/refractory (R/R) glioblastoma multiforme (GBM) (Press release, BeiGene, NOV 16, 2018, View Source;p=irol-newsArticle&ID=2377491 [SID1234531392]). These data are being presented at the 23rd Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO), being held November 15 to 18 in New Orleans, LA. Discovered by BeiGene scientists in Beijing, pamiparib is currently in Phase 3 trials globally and in China as a monotherapy and in Phase 1/2 trials in combination with chemotherapy or immunotherapy for a variety of solid tumors.

"There are limited treatment options available for patients with newly diagnosed and recurrent/refractory glioblastoma. This trial was designed to evaluate the potential synergies between DNA damaging therapies and/or agents and our investigational PARP inhibitor, pamiparib, which in pre-clinical studies has demonstrated brain penetration and PARP trapping activity. We are excited to continue to assess the potential of pamiparib combinations for a variety of difficult-to-treat cancers where there is urgent global need," commented Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology at BeiGene.

"While response data are still maturing, these preliminary results demonstrated signs of antitumor activity of pamiparib in combination with radiation therapy in patients with newly diagnosed glioblastoma, as well as in combination with low-dose TMZ in patients with recurrent/refractory glioblastoma including those who previously progressed on TMZ, and support the continued development of these combinations," said Kent Shih, M.D., Senior Investigator of the Neuro-Oncology Program at Sarah Cannon Research Institute.

Summary of Preliminary Results

This open-label, multi-center global Phase 1b/2 multiple-dose and dose-escalation trial of pamiparib plus RT and/or TMZ (NCT03150862) was designed to evaluate the safety, efficacy and clinical activity of the combination in patients with newly diagnosed or R/R GBM. Patients with newly diagnosed GBM with unmethylated MGMT promoter status (Arm A) received pamiparib (60 mg twice a day) over escalating time periods (two, four, or six weeks) in combination with RT over six to seven weeks. Patients with R/R GBM (Arm C) received pamiparib (60 mg twice a day) continuously plus TMZ administered on Days 1 to 21 of each 28-day cycle. After evaluation of safety and tolerability from Arm A and C, Arm B will enroll patients with newly diagnosed GBM and treat them with the triple combination of RT, pamiparib, and TMZ.

As of September 14, 2018, a total of 18 patients with newly diagnosed GBM were enrolled in Arm A (n=3, 6 and 9 in the two-, four-, and six-week cohorts respectively). The median study follow-up duration is 19 weeks (2-54). Five grade >3 adverse events (AE) (chills, diarrhea, fatigue, nausea, vertigo, one [5.6%] each) were considered related to pamiparib or RT. Dose-limiting toxicities of fatigue, vertigo, and chills (one each) were reported.

As of the data cutoff date, 15 of the 18 patients were evaluable for response per modified response assessment in neuro-oncology (mRANO) criteria. Two of 15 patients achieved a partial response (PR, one was confirmed) and six patients achieved stable disease (SD); the disease control rate was 53.3% (95% CI: 26.6-78.7).

In Arm C, eight patients received TMZ at a fixed dose of 40 mg for 21 of 28 days and seven patients received 20 mg TMZ. The median study follow-up duration is 12.9 weeks (0.3-31.4). Grade >3 AEs included anemia (20%), fatigue (13.3%), and decreased lymphocyte (13.3%), which were considered related to pamiparib or TMZ. Dose-limiting toxicities of nausea and neutropenia were reported. The combination of 21 days of 40 mg TMZ with pamiparib was not tolerable; a lower 20 mg TMZ dose evaluation in combination with pamiparib is ongoing.

Ten of the 15 patients were evaluable per mRANO criteria and there were two PRs (one unconfirmed and one confirmed after data cutoff) and three SD.

About Glioblastoma Multiforme
Glioblastoma multiforme, also called glioblastoma, is an aggressive type of cancer where malignant grade IV tumors occur in the brain or spinal cord.2 These are the most common type of malignant brain tumors among adults.3 Symptoms include worsening headaches, nausea, vomiting and seizures. Patients can also present with neurological symptoms which are dependent on the tumor location (for example, weakness or sensory changes of face, arm or leg, balance difficulties and neurocognitive/memory issues).4 Glioblastoma can occur at any age but tends to occur more often in older adults. The five-year relative survival rates for patients with glioblastoma are: 19 percent (age 20-44), eight percent (age 44-54), and five percent (age 55-64).5

About Pamiparib
Pamiparib (BGB-290) is an investigational inhibitor of PARP1 and PARP2 which has demonstrated pharmacological properties such as brain penetration and PARP-DNA complex trapping in preclinical models. Discovered by BeiGene scientists in Beijing, pamiparib is currently in global clinical development as a monotherapy and in combination with other agents for a variety of solid tumor malignancies.

GT BIOPHARMA REPORTS THIRD QUARTER 2018 FINANCIAL RESULTS AND PROVIDES BUSINESS UPDATE

On November 15, 2019 GT Biopharma, Inc. (OTCQB: GTBP and Euronext Paris GTBP.PA) ("GT Biopharma" or the "Company"), an immuno-oncology biotechnology company focused on innovative treatments based on the Company’s proprietary NK-engager and Bispecific Antibody Drug Conjugate platforms, reported its financial results for the third quarter ended September 30, 2018 (Press release, GT Biopharma , NOV 15, 2018, View Source [SID1234539520]).

The Company also provided an update on its corporate progress, clinical status and anticipated milestones for its pipeline of immuno-oncology products based off the Company’s proprietary Tri-specific Killer Engager (TriKE), Tetra-specific Killer Engager (TetraKE) and bi-specific Antibody Drug Conjugate (ADC) technology platforms.

Recent Corporate Highlights:

Received FDA clearance to commence first-in-human Phase 1 study of first-in-class TriKE, GTB-3550 (OXS-3550), for the treatment of acute myelogenous leukemia, myelodysplatic syndrome and mastocytosis.

Announced positive preclinical data for two next generation TriKEs in ovarian and head and neck cancers. The studies were conducted by Dr. Daniel Vallera, Director, Section of Molecular Cancer Therapeutics and Dr. Martin Felices, Co-Director of the Translational Therapy Laboratory at the Masonic Cancer Center, University of Minnesota.

Announced agreement with major pharmaceutical company and initiated preclinical combination trial of GTB-1550 (OXS-1550) and multi-billion dollar oncology drug for testing in several hematologic malignancies.

Bolstered leadership team with appointments of Dr. Raymond W. Urbanski M.D., Ph.D. as CEO and Chairman of the Board (formerly Chief Medical Officer of the Company); well-respected industry veteran, Dr. John N. Bonfiglio as a new independent Board Member and David Cardino, CPA, as VP, Finance.
"We have made significant progress in building a solid foundation for the Company in what we believe is an important transitional phase for GT Biopharma. The additions and changes to the leadership team and execution of key preclinical, clinical and regulatory milestones are a testament to this progress," commented Raymond Urbanski, M.D., Ph.D., Chief Executive Officer of GT Biopharma. "However, as we navigate through this phase, we certainly face challenges, including ensuring we are properly funded and have the right team in place to propel the Company to our next phase of growth. Successfully completing a financing and bolstering our management team and Board in the near term remains a priority. I, along with our Board, believe GT Biopharma has a first-in-class platform technology and the potential to provide revolutionary advancements in the treatment of various cancers where there remains significant unmet need. We are committed to securing the necessary capital to continue to aggressively execute on our strategy and advance our development programs to drive significant shareholder value. I believe we are taking the necessary steps to position GT Biopharma for a transformational 2019."

Clinical Program Updates

The Company’s TriKE product candidates are single-chain, tri-specific scFv recombinant fusion proteins composed of the variable regions of the heavy and light chains (or heavy chain only) of anti-CD16 antibodies, wild-type or a modified form of IL-15 and the variable regions of the heavy and light chains of an antibody designed to precisely target a specific tumor antigen. GT Biopharma utilizes the NK stimulating cytokine human IL-15 as a crosslinker between the two scFvs which is designed to provide a self-sustaining signal leading to the proliferation and activation of NK cells thus enhancing their ability to kill cancer cells mediated by antibody-dependent cell-mediated cytotoxicity (ADCC).

The Company’s TetraKE product candidates are single-chain fusion proteins composed of human single-domain anti-CD16 antibody, wild-type IL-15 and the variable regions of the heavy and light chains of two antibodies that are designed to target two specific tumor antigens expressed on specific types of cancer cells.

GT Biopharma’s TriKEs and TetraKEs are designed to act by binding to a patient’s NK cells and a specific tumor antigen enabling an immune synapse between the now IL-15-enhanced NK cell and the targeted cancer cell. The formation of an immune synapse can induce NK cell activation which can lead to the death of the cancer cell. The Company believes the self-sustaining signal caused by its IL-15 cross-linker may enable prolonged and enhanced proliferation and activation of NK cells similar to the increased proliferation of T-cells caused by 41BB-L or CD28 intracellular domains in CAR-T therapy but without the need to enhance the patient’s NK cells ex vivo.

GTB-1550 (OXS-1550): Most Advanced Bi-specific ADC Candidate

The Company’s most advanced bi-specific ADC in development, GTB-1550, targets CD19+ and/or CD22+ hematological malignancies and is currently in the Phase 2 component of a Phase 1/2 Non-Hodgkin’s Lymphoma (NHL)/Acute Lymphocytic Leukemia (ALL) trial which is an open-label, investigator-led study.

GTB-1550 targets cancer cells expressing the CD19 receptor or CD22 receptor or both receptors. When GTB-1550 binds to cancer cells, the cancer cells internalize GTB-1550, and are killed due to the action of drug’s cytotoxic diphtheria toxin payload. GTB-1550 has demonstrated success in a Phase 1 human clinical trial in patients with relapsed/refractory B-cell lymphoma or leukemia.

The Company recently assembled a Bi-Specific ADC Advisory Board to collaboratively assess and interpret the GTB-1550 pre-clinical and clinical data, including an interim review of the Phase 1/2 study. Eighteen patients have been enrolled to date, including 12 NHL and six ALL patients. At the time of the interim review, 13 patients met the evaluation criteria, including nine NHL and four ALL patients. More than 50% of patients (seven of 13) exhibited a clinical benefit, defined as stable disease, partial remission or complete remission at Day 29. Of the seven patients, one demonstrated a complete remission (CR), one demonstrated a partial remission (PR) and five demonstrated stable disease (SD).

The efficacy signal was more prominent in ALL patients with 75% (three of four) exhibiting clinical benefit including one CR, one PR and one SD. In the NHL population, four of nine patients exhibited SD. Adverse events were mostly grade 1 and 2 and reversible. One patient had a grade 4 low platelet count, two patients had a grade 3 increase in liver function tests, or LFTs, and one patient had a grade 3 capillary leak. The Company currently expects final data for this trial to be available in the first quarter of 2019.

This work is being conducted by and under the guidance of Dr. Veronika Bachanova, Associate Professor of Medicine, Division of Hematology, Oncology and Transplantation at the University of Minnesota.

GTB-3550 (OXS-3550): TriKE product candidate

GTB-3550 is the Company’s first Tri-specific Killer Engager (TriKE) product candidate being initially developed for the treatment acute myelogenous leukemia (AML). GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of IL-15. When the NK stimulating cytokine human IL-15 is used as a crosslinker between the two scFvs, it provides a self-sustaining signal that activates NK cells and enhances their ability to kill.

GT Biopharma recently announced that its Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) is now open and it is authorized to initiate a first-in-human Phase 1 study with GTB-3550, its first-in-class TriKE, for the treatment of AML, myelodysplatic syndrome (MDS) and mastocytosis. The study will be led by Principal Investigator, Sarah A. Cooley, MD, MS, Associate Professor, Division of Hematology, Oncology and Transplantation at Masonic Cancer Center, University of Minnesota.

This single center, first-in-human Phase 1 clinical trial of GTB-3550 will enroll up to 60 subjects with CD33-expressing refractory/relapsed AML, high-risk MDS, or advanced systemic mastocytosis. Subjects will receive a single course of GTB-3550 given as 3 weekly treatment blocks. Each block consists of four consecutive 24-hour continuous infusions of GTB-3550 followed by a 72-hour break after Block #1 and #2. Disease response will be assessed by bone marrow biopsy performed between Day 21 and Day 42 after the start of the 1st infusion. Follow-up for response and survival continues through 6 months from treatment start. The primary objective from the Phase 1 dose finding portion of the study will be to identify the maximum tolerated dose (MTD) of GTB-3550 defined as the dose level that most closely corresponds to a dose limiting toxicity rate (DLT) of 20%. The primary objective from the Phase 2 extended portion of the study will be the potential efficacy of GTB-3550, measured using rates of complete and partial remission. Subjects experiencing clinical benefit and no unacceptable side effects may be considered for a 2nd course of GTB-3550 on a compassionate basis.

The Company believes that GTB-3550 could serve as a relatively safe, cost-effective, and easy-to-use therapy for refractory/relapsed AML, high-risk MDS and advanced systemic mastocytosis and could also be combined with chemotherapy and/or other agents as frontline therapy thus targeting a much larger patient population.

GT Biopharma’s initial and ongoing work is being conducted in collaboration with the Masonic Cancer Center at the University of Minnesota under research agreements led by Dr. Jeffrey Miller, the Deputy Director and Dr. Daniel Vallera, Director, Section of Molecular Cancer Therapeutics.

GT Biopharma has an exclusive worldwide license agreement with the University of Minnesota to further develop and commercialize cancer therapies using proprietary TriKE technology developed by researchers at the university to target NK cells to cancer.

Upcoming Milestones Expected to Drive Value

Initiate Phase 1 first-in-human clinical trial of GTB-3550 for the treatment of Relapse/Refractory AML, High Risk MDS, and Advanced Systemic Mastocytosis in the first half of 2019;
Announce topline results from Phase 2a trial of GTB-1550 in Q1 2019;
Conduct end of Phase 2a (EOP2a) meeting for GTB-1550 with U.S. FDA in the first half of 2019;
Advance ongoing GTB-C3550 IND-enabling studies & TetraKE pre-clinical program to target the larger solid tumor population and are working towards beginning clinical trials in 2019;
Bolster executive management team and board with key expertise to continue to transform the Company;
Participate in key scientific conferences;
Make progress in advancing potential corporate and business development opportunities; and
Uplist to a National Exchange.
Summary of Financial Results for Third Quarter 2018

For the quarter ended September 30, 2018, the Company reported a net loss of approximately $235,783,000 or a net loss per diluted share of $4.70, compared to a net loss of $130,625,000 or a net loss per diluted share of $8.15 for the same quarter 2017. For the nine months ended September 30, 2018, GT Biopharma reported a net loss of approximately $254,955,000 or a net loss per diluted share of $5.09, compared to $138,146,000 or a net loss per diluted share of $24.54 for the same period 2017.

At September 30, 2018, the Company has an accumulated deficit of $524,453,000 and cash of $1,232,000.

Celyad to Participate at Upcoming Healthcare Conferences

On November 15, 2018 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell-based therapies, reported that management will participate at both the Bryan, Garnier & Co 6th European Healthcare Conference and the Piper Jaffray 30th Annual Healthcare Conference (Press release, Celyad, NOV 15, 2018, View Source [SID1234532509]).

The Bryan, Garnier & Co 6th European Healthcare Conference will take place in Paris, France, on November 22-23, 2018. The Company will participate in investor meetings at the Conference.

The Piper Jaffray 30th Annual Healthcare Conference will take place in New York, NY on November 27-29, 2018 and the Company is scheduled to participate in a fireside chat on Tuesday, November 27 at 11:30 am Eastern Time. A live webcast of the discussion can be accessed here. An archived webcast recording will also be available under Events & Webcasts in the Investors section of the Company’s website.