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.

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"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.

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]).

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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.

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]).

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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.

On November 15, 2018 INmune Bio, Inc., an immunotherapy company developing treatments to reprogram the patient’s innate immune system, reported that Lazar Vujanovic, Ph.D., a research instructor at the University of Pittsburgh, presented results from a preliminary study at the 33rd annual Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting on November 9 (Press release, INmune Bio, NOV 15, 2018, View Source [SID1234531521]). The results of the research conducted at the University of Pittsburgh, demonstrated the potential effectiveness of INB03TM, the company’s lead drug candidate in treatment of drug-resistant melanoma, which was developed from patented intellectual property licensed from the University of Pittsburgh.

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"The study’s findings indicate a potential shift in approach to how clinicians may treat patients who harbor treatment-resistant cutaneous melanomas by using TNF receptors as biomarkers," said Dr. Vujanovic. "These results, showing the effectiveness of biomarker-guided soluble TNF-targeting strategy, are an encouraging development in potentially raising the standard of care for patients with treatment-resistant melanoma, which kills thousands each year."

Soluble TNF (sTNF) is an immunologic protein that has multiple functions in the development of cutaneous melanoma, the deadliest form of skin cancer. In a cohort of patients, sTNF facilitates tumor growth and drug resistance. Dr. Vujanovic’s data shows that sTNF may induce drug resistance and suggests that some melanoma patients may benefit from neutralization of sTNF with a drug like INB03. As an innate immunotherapy drug currently in Phase I trials, INB03 is being used in patients to neutralizes sTNF using a novel Dominant-Negative TNF technology.

"At INmune Bio we believe that, when possible, a patient’s cancer therapy should be guided by biomarkers that can better predict a favorable response to therapy," said INmune Bio co-founder and CEO, Raymond J. Tesi, M.D. "Dr. Vujanovic’s work is an example of how laboratory studies are the foundation of important concepts that can alter the treatment of cancer patients."

SITC is one of the leading organizations for the exchanging of ideas and discovery in the cancer immunotherapy field.

On November 15, 2018 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported that Lori Kunkel, M.D. has been named acting chief medical officer, effective November 26, 2018 (Press release, Tocagen, NOV 15, 2018, View Source;p=RssLanding&cat=news&id=2377408 [SID1234531471]). Asha Das, M.D., senior vice president and chief medical officer will be leaving the company effective November 23, 2018 to allow her to focus on unforeseen and immediate personal matters. The company has initiated a search process to fill the position.

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"On behalf of the management team and Board of Directors, we are thankful for the significant contributions Asha has made over the past three years," said Marty J. Duvall, chief executive officer of Tocagen. "With Lori’s remarkable track record in the biotechnology industry coupled with her deep familiarity of our program and clinical data we look forward to working closely with her to advance our cancer-selective gene therapy platform, and our lead product candidate. This transition is not expected to impact our current business plans or development timelines."

Among other responsibilities, Dr. Kunkel previously served as acting chief medical officer of Loxo Oncology, Inc, chief medical officer of Pharmacyclics LLC, acquired by AbbVie Inc., and chief medical officer of Proteolix, Inc., acquired by Onyx Pharmaceuticals. Dr. Kunkel currently serves on the board of directors of Loxo Oncology, Inc., a publicly held biotechnology company, Curis, Inc., a publicly held biotechnology company, and Maverick Therapeutics, Inc., a privately held biotechnology company. A full biography is available here. In connection with Dr. Kunkel’s appointment as acting chief medical officer of Tocagen, Dr. Kunkel will be temporarily leaving the board of directors of Tocagen in order for the company to maintain compliance with the Nasdaq listing rules regarding independent directors.

"Being dedicated to the development of new treatment options for patients with brain cancer, I am extremely grateful to have worked closely with the Tocagen team on advancing Toca 511 & Toca FC and regret having to leave the company at this time," said Dr. Das. "I am excited about the potential of the Toca 5 trial and future development in newly diagnosed brain cancer to positively impact patients around the world."