On March 3, 2020 MiNA Therapeutics, the pioneer in RNA activation therapeutics, reported the initiation and first patient treated in TIMEPOINT, a global Phase 1/1b clinical study of MTL-CEBPA in combination with anti-PD1 checkpoint inhibitor pembrolizumab in patients with advanced solid tumours (Press release, MiNA Therapeutics, MAR 3, 2020, View Source [SID1234555141]). The study is designed to assess the safety, tolerability, pharmacology and clinical activity of MTL-CEBPA in combination with pembrolizumab in these patients. MTL-CEBPA is the first therapy to specifically up-regulate CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. The drug candidate is also being investigated in an ongoing multi-centre Phase 1b clinical trial in patients with advanced liver cancer in combination with sorafenib.

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"Initiation of the Phase I TIMEPOINT clinical trial emphasizes the continued exploration of MTL-CEBPA, the first drug candidate that targets C/EBP-α, a master regulator of immune cells that play a critical role in tumour resistance," commented Robert Habib, CEO of MiNA Therapeutics. "We are excited to take the next step and test MTL‑CEBPA in additional cancer populations in a potentially synergistic combination with an anti-PD1 checkpoint inhibitor. We look forward to collaborating with our clinical investigators in evaluating this new combination."

The TIMEPOINT study consists of a dose-escalation followed by a dose expansion. MTL‑CEBPA will be administered as an intravenous infusion once weekly in cycles of three weeks of treatment followed by one week of rest. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of anti-PD1 checkpoint inhibition by reducing immune suppression from dysregulated myeloid cells in the tumour microenvironment.

The single agent activity of MTL-CEBPA in 39 patients with advanced liver cancer was previously presented by investigators at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress. MTL-CEBPA was found to be well tolerated, demonstrating pharmacodynamic target engagement and a reduction of suppressive immune cells in the tumour microenvironment. In addition, MTL-CEBPA demonstrated clear, synergistic activity in patients with liver cancer when also treated with sorafenib standard of care.

"MTL-CEBPA has shown real promise as a combination agent in patients with liver cancer and pre-clinical studies suggest that MTL-CEBPA may also be an attractive agent to enhance the benefits of checkpoint inhibitors," commented Professor Ruth Plummer, Clinical Professor of Experimental Medicine at the Clinical and Translational Research Institute, Newcastle University Centre for Cancer, and Chief Investigator of the study. "We are looking forward to evaluating this highly innovative combination treatment in the upcoming Phase I trial. We hope this combination could become an effective new treatment option for patients with solid tumour cancers."

About the TIMEPOINT Study

TIMEPOINT is a global Phase I/Ib clinical study in patients with solid tumour malignancies that will assess the safety and tolerability of MTL-CEBPA in combination with pembrolizumab in patients who are ineligible or resistant to standard therapies. The study has received clearance from the U.S. Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). To learn more about the TIMEPOINT clinical study, please visit our listing at clinicaltrials.gov.

About MTL-CEBPA

MTL-CEBPA is the first therapy to specifically up-regulate CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases and identified as a critical barrier for many therapies to induce clinical responses in solid tumour cancers. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of cancer therapies by targeting dysregulated myeloid cells and reducing their suppression in the tumour microenvironment.

On March 3, 2020 PDC*line Pharma, a clinical stage biotech company developing a new class of potent and scalable active immunotherapies for cancers, reported that the first patient was dosed with its innovative medicinal product candidate PDC*lung01 in a phase I/II trial in non-small cell lung cancer (NSCLC) (Press release, PDC Line Pharma, MAR 3, 2020, View Source [SID1234555139]). This patient is under the supervision of Dr. Anne Sibille, principal investigator for the Liege University Hospital (Belgium).

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The objectives of the phase I/II trial (PDC-LUNG-101) are to assess the safety, tolerability, immunogenicity and preliminary clinical activity of the drug candidate, PDC*lung01, associated or not with anti-PD-1 treatment in NSCLC. A total of 62 evaluable HLA-A*02:01 positive NSCLC patients are expected in three clinical centers in Belgium and six in France.

PDC*lung01 is a cell suspension of a mix, in the same proportion, of seven active agents made of irradiated human plasmacytoïd dendritic cells (PDC*line) loaded separately with a distinct synthetic human leukocyte antigen serotype-restricted peptide (HLA-A*02:01) encoded by a tumour antigen. PDC*line is a potent professional antigen-presenting cell that is able to prime and boost the antitumor cytotoxic CD8+ T-cells in the patient’s immune system.

"We are delighted to have achieved this first important milestone in the clinical development of PDC*line Pharma with our lead cancer vaccine candidate," said Eric Halioua, president and CEO of PDC*line Pharma. "Based on preclinical studies there is a strong rationale for developing PDC*lung01 in this indication and we are currently exploring a number of additional indications, where our technology may provide potential benefit for patients."

"PDC*lung01 is an innovation in the field of cancer vaccines that appears particularly suitable for the treatment of NSCLC patients, an area where there is still a high unmet medical need," said Dr. Channa Debruyne, medical director of PDC*line Pharma.

About lung cancer
Worldwide, lung cancer is the most common malignancy for male patients and for both sexes combined (2.1 million new cases per year), and the third most common for female patients (after breast and colorectal cancers). Globally, deaths from lung cancer exceed those from any other cancer, with the number of lung-cancer-related deaths for 2018 estimated at 18.1 million; 18.4% of total cancer deaths. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing 80% of cases.

About PDC*line Pharma’s technology

PDC*line’s biological features provide unique advantages:

A professional antigen-presenting cell line, much more potent than conventional dendritic cells in priming and expanding antitumor-specific cytotoxic CD8+ T cells (conventional tumor antigens and neoantigens)
While allogeneic, PDC*line is not rejected by the host immune system and can be injected several times to boost the immune response
Easily produced on a large scale, with a fully mastered and simple manufacturing process (use of bioreactors with a synthetic medium without growth, differentiation or activation factors)
Easy to use: after thawing, the same off-the-shelf product is used to treat the whole target population with a cancer type expressing the target antigens
Very versatile: tumor antigens can be provided by peptide loading, mRNA transfection or retrovirus transduction of PDC*line and the target population can be extended beyond HLA-A2 (currently used as it is expressed by 50% of the Caucasian population) by using other HLAs, either already expressed by PDC*line or added by genetic modification. Moreover, new candidates can be validated for new cancer indications in a few weeks, with ex vivo testing using human peripheral blood mononuclear cells (PBMC)
Synergizes with anti-PD-1 to activate antitumor CD8 T cells

On March 3, 2020 VBI Vaccines Inc. (NASDAQ: VBIV) ("VBI"), a commercial-stage biopharmaceutical company developing next-generation infectious disease and immuno-oncology vaccines, reported an update on Part A of the ongoing Phase 1/2a study of VBI-1901, the company’s cancer vaccine immunotherapeutic candidate, for the treatment of patients with recurrent glioblastoma (GBM) (Press release, VBI Vaccines, MAR 3, 2020, View Source [SID1234555138]). For patients who had an immunologic response to the vaccine, considered to be vaccine responders, the 12-month overall survival (OS) rate was 83% (n=5/6), compared to 33% for vaccine non-responders (n=3/9). Similarly, among patients evaluable for response and survival in Part A, vaccine responders saw a 6.25-month improvement in median OS (14.0 months) compared to vaccine non-responders (7.75 months). VBI-1901 continues to be safe and well-tolerated at all doses tested, with no safety signals observed.

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"We remain encouraged by the data from this ongoing Phase 1/2a study of VBI-1901 in the recurrent GBM setting, a setting in which it has historically been incredibly difficult to show any benefit, especially with a monotherapy," said David E. Anderson, Ph.D., VBI’s Chief Scientific Officer. "The standard of care treatment in the recurrent GBM setting is not well defined, however, commonly-used regimens, including chemotherapy and VEGF-A inhibitors as monotherapy and in combination, have demonstrated 12-month OS rates below 50% with median OS around 8 to 12 months1. Moreover, these regimens often cause significant toxicity, poorly affecting quality of life for the individual. While the data generated for VBI-1901 is early, we continue to be optimistic as we work hard to provide any meaningful benefit to patients who currently have few treatment options."

Expanded immunologic, tumor imaging, and clinical data from the Phase 2a part of the study are expected in Q2 2020 – data from the VBI-1901 + GM-CSF arm – and Q4 2020 – data from the VBI-1901 + AS01B arm. Additionally, efforts are underway to define biomarkers that may help identify patients more likely to respond to VBI-1901.

About the Phase 1/2a Study Design
VBI’s two-part Phase 1/2a study is a multi-center, open-label, dose-escalation study of VBI-1901 in up to 38 patients with recurrent GBM:

Phase 1 (Part A)
Dose-escalation phase that defined the safety, tolerability, and optimal dose level of VBI-1901 adjuvanted with granulocyte-macrophage colony-stimulating factor (GM-CSF) in recurrent GBM patients, with any number of prior recurrences.
This phase enrolled 18 recurrent GBM patients across three dose cohorts of VBI-1901: 0.4 µg, 2.0 µg, and 10.0 µg.
Enrollment completed in December 2018.
Phase 2a (Part B)
Subsequent extension of the optimal dose level, 10.0 µg, as defined in the Part A dose escalation phase.
This phase is a two-arm study, enrolling 10 first-recurrent GBM patients in each arm, assessing 10.0 µg of VBI-1901 in combination with either GM-CSF or GSK’s proprietary AS01B adjuvant system as immunomodulatory adjuvants.
Enrollment in both study arms is ongoing.
VBI-1901 is administered intradermally when adjuvanted with GM-CSF and will be administered intramuscularly when adjuvanted with AS01B adjuvant system. Patients will receive the vaccine immunotherapeutic every four weeks until tumor progression.

Additional information, including a detailed description of the study design, eligibility criteria, and investigator sites, is available at ClinicalTrials.gov using identifier NCT03382977.

On March 3, 2020 BioInvent International AB ("BioInvent") (OMXS: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, and Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported that they will be presenting preclinical data on BT-001 at several upcoming scientific congresses in March and April 2020 (Press release, BioInvent, MAR 3, 2020, View Source [SID1234555137]).

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Transgene and BioInvent have submitted the first clinical trial application for BT-001, and the first-in-human trial is expected to start before the end of 2020 in Europe and the USA.

BT-001 is a multifunctional oncolytic virus being co-developed by Transgene and BioInvent. It is based on Transgene’s Invir.IO platform and patented, large-capacity VVcopTK-RR- oncolytic virus. BT-001 has been engineered to encode a Treg-depleting, anti-CTLA4 antibody derived from BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, as well as the cytokine GM-CSF.

Both the oncolytic and the anti-CTLA4 therapeutic strategies that underpin BT-001 have demonstrated activity in humans based on their ability to induce a fundamental change in the tumor microenvironment and anti-tumoral activity. Looking at the clinical landscape, BT-001 could either be used as a monotherapy or be associated with standard of care immunotherapy options such as anti-PD1/anti-PD-L1 therapies.

"In preclinical models, BT-001 has demonstrated the benefits of its multiple mechanisms of action as well as the potential to deliver significantly improved tolerability when compared to the anti-PD-1/anti-CTLA4 combination therapies currently available," said Björn Frendéus, Ph.D., Chief Scientific Officer of BioInvent. "We believe that the potential to combine anti-CTLA4, anti-PD-1/PD-L1 and oncolytic immunotherapy could change the treatment paradigm for multiple solid tumors, and we are very much looking forward to investigate BT-001 in its first-in-human study, which is planned to start before the end of 2020."

"With BT-001, we are looking to combine Transgene’s potent oncolytic virus with the local production of a high concentration of an anti-CTLA4 antibody. We believe that BT-001 will have an improved tolerability due to its ability to generate high concentrations of the antibody in the tumor and very low systemic concentrations. With this next-generation oncolytic virus, we hope to demonstrate that we can increase the antitumor activity without exposing patients to unnecessary adverse events," added Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.

Upcoming presentations on BT-001 include:

1. Poster presentation at the Immuno-Oncology (IO) Summit Europe, March 9-12, 2020, London (UK)

– "BT-001, an oncolytic Vaccinia virus armed with a Treg-depletion-optimized recombinant human anti- CTLA4 antibody and GM-CSF to target the tumor microenvironment" presented by Jean-Baptiste Marchand (Transgene).

– Date: March 11 and 12, 2020

– Location: Poster Session C

2. Poster presentation at the Keystone Advances in Cancer Immunotherapy Symposium, March 22 – 26, 2020, Whistler (Canada)

– "BT-001, an oncolytic vaccinia virus armed with a Treg-depleting anti-CTLA4 antibody and GM-CSF to target the tumor microenvironment" presented by Monika Semmrich (BioInvent). Poster No. 3028.

– Date: March 25, 2020

– Location: Poster Session 3

3. Poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 24-29, 2020, San Diego (USA)

– A poster has been accepted. The name and abstract of the poster will be available on the AACR (Free AACR Whitepaper) website on March 24, 2020.

4. Oral presentation at the ESMO (Free ESMO Whitepaper) Targeted Anticancer Therapies (TAT) Congress, March 2-4, 2020, Paris (France)

– "Antibody armed oncolytic viruses" (ID 42) presented by Eric Quéméneur (Transgene) during the session entitled "Where next with Oncolytics".

– Date: March 3, 2020

– The congress has been cancelled due to the coronavirus outbreak.

On March 3, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX) reported its financial results for the fourth quarter and year ended December 31, 2019 and recent company developments, along with a business outlook for 2020 (Press release, TG Therapeutics, MAR 3, 2020, View Source [SID1234555131]).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "2019 was a transformational year for TG as we were able to report positive outcomes for umbralisib in both previously treated marginal zone lymphoma and follicular lymphoma from the UNITY-NHL trial. We also confirmed a submission pathway with the FDA and early this year commenced a single rolling submission based on these data, which we hope to complete in the first half of this year." Mr. Weiss continued, "Looking forward, we expect 2020 to be yet another impactful year as we await the topline results from our Phase 3 programs in CLL and MS and potentially our first FDA approval around year-end."

2019 Highlights & Recent Developments

Marginal Zone Lymphoma & Follicular Lymphoma:
° Received breakthrough therapy designation (BTD) for patients with marginal zone lymphoma (MZL) who have received at least one prior therapy including an anti-CD20 regimen, and orphan drug designation for umbralisib for the treatment of patients with MZL.
° Announced positive outcome from the MZL cohort of the UNITY-NHL Phase 2b trial, which met the primary endpoint of Overall Response Rate (ORR), as determined by Independent Review Committee (IRC).
° Presented interim safety and efficacy data from the MZL cohort of UNITY-NHL during oral presentations at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, the 55thAmerican Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and the 2019 International Conference on Malignant Lymphoma (ICML).
° Announced positive outcome from the follicular lymphoma (FL) cohort of the UNITY-NHL Phase 2b trial, with ORR results meeting the Company’s prespecified 40 – 50% target, as determined by IRC. The Company plans to present the data at a future medical conference.
° Received guidance from the FDA allowing submission of a single New Drug Application (NDA) for MZL and FL indications. In January 2020, a rolling NDA submission for umbralisib to treat adult patients with previously treated MZL and FL was initiated, with completion of submission targeted for first half of 2020.

Chronic Lymphocytic Leukemia:
° Awaiting topline progression free survival (PFS) results from the Company’s Phase 3 UNITY-CLL trial evaluating "U2" (the combination of umbralisib and ublituximab) in patients with frontline and previously treated chronic lymphocytic leukemia (CLL).
° Final long-term results from the Phase 3 GENUINE study demonstrated that ublituximab in combination with ibrutinib improved PFS, as determined by IRC.
° Presented triple therapy data at the 61stAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition from the Phase 1/2 study of ublituximab in combination with umbralisib and venetoclax, in patients with relapsed/refractory CLL, during an oral session.

Multiple Sclerosis:
° Updated Phase 2 extension trial data for ublituximab in relapsing forms of multiple sclerosis (RMS), as well as the ULTIMATE I & II Phase 3 RMS program study design and demographic data, were presented at the 35th Annual Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
° Awaiting topline data from the Company’s Phase 3 ULTIMATE I & II trials evaluating ublituximab in patients with RMS.

Early Pipeline:
° TG-1801: Commenced a Phase 1 first-in-human, dose-escalation study of TG-1801, the Company’s anti-CD47/CD19 bispecific antibody, in patients with relapsed or refractory B-cell lymphoma and presented the first preclinical data of TG-1801 at the 24th European Hematology Association (EHA) (Free EHA Whitepaper) annual congress.
° TG-1701: Presented the first clinical data from TG-1701, the Company’s once daily, oral, BTK inhibitor, as a single agent and as a triple therapy in combination with U2 at ASH (Free ASH Whitepaper) 2019.
Key Objectives for 2020

Report topline PFS results from the Phase 3 UNITY-CLL trial evaluating U2 in patients with frontline and previously treated CLL, and if successful, target a potential New Drug Application (NDA)/Biologics Licensing Application (BLA) submission by year-end.
Complete rolling NDA submission for umbralisib in patients with previously treated MZL and FL, in the first half of 2020.
Report topline results from the Phase 3 ULTIMATE I & II trials in RMS, in the second half of 2020.
Continue to advance our early pipeline candidates including TG-1501 (cosibelimab), TG-1701 and TG-1801.
Financial Results for the Fourth Quarter and Full Year 2019

R&D Expenses: Other research and development (R&D) expense (not including non-cash compensation and non-cash in-licensing expense) was $29.5 million and $148.3 million for the three and twelve months ended December 31, 2019, respectively, compared to $51.1 million and $149.8 million for the three and twelve months ended December 31, 2018, respectively. The decrease in R&D expense is primarily attributable to the winding down of our late-stage clinical development programs during the year ended December 31, 2019.

G&A Expenses: Other general and administrative (G&A) expense (not including non-cash compensation) was $2.9 million and $9.5 million for the three and twelve months ended December 31, 2019, respectively, as compared to $1.7 million and $7.9 million for the three and twelve months ended December 31, 2018, respectively.

Net Loss: Net loss was $39.6 million and $172.9 million for the three and twelve months ended December 31, 2019, respectively, compared to a net loss of $53.9 million and $173.5 million for the three and twelve months ended December 31, 2018, respectively. Excluding non-cash items, the net loss for the three and twelve months ended December 31, 2019 was approximately $34.0 million and $161.4 million, respectively, compared to a net loss of $52.4 million and $156.6 million for the three and twelve months ended December 31, 2018, respectively.

Cash Position and Financial Guidance: Cash, cash equivalents and investment securities were $140.4 million as of December 31, 2019. The Company believes its cash, cash equivalents and investment securities on hand as of December 31, 2019, will be sufficient to fund the Company’s planned operations well into 2021.
Conference Call Information

The Company will host a conference call today, March 3, 2020, at 8:00 AM ET, to discuss the Company’s fourth quarter and year-end 2019 financial results and provide a business outlook for 2020.

In order to participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics Year-End 2019 Earnings Call. A live audio webcast will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source An audio recording of the conference call will also be available for replay at www.tgtherapeutics.com, for a period of 30 days after the call.