On September 23, 2019 TLC (Nasdaq: TLC, TWO: 4152), a clinical-stage specialty pharmaceutical company dedicated to the development and commercialization of novel nanomedicines designed to target areas of unmet medical need in pain management, ophthalmology and oncology, reported that new in vivo data on the efficacy and enhanced tumor accumulation of TLC178 will be presented at the European Society for Medical Oncology Congress (ESMO 2019). ESMO (Free ESMO Whitepaper) 2019 takes place from September 27 to October 1, 2019 in Barcelona, Spain (Press release, Taiwan Liposome Company, SEP 23, 2019, View Source [SID1234539710]). TLC178 is a proprietary NanoX formulation of vinorelbine, an anticancer drug frequently used off-label to treat soft tissue sarcoma.

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Details of the poster presentation (#1722P) are as follows:

Title: In Vivo Efficacy and Enhanced Tumor Accumulation of Liposomal Vinorelbine (TLC178) in Human Sarcoma Xenograft Mouse Models
ID#: 1844
Location: Poster Area (Hall 4), Fira Gran Via
Speaker: Wan-ni Yu, PhD
Date/Time: 12:00pm to 1:00pm CEST, September 28, 2019

The objectives of the studies were 1) to compare the anti-tumor activity of TLC178 to the reference drug in human soft tissue sarcoma xenograft mouse models, and 2) to investigate the pharmacokinetic and the drug distribution of vinorelbine (VNB) from a single intravenous injection of TLC178 or VNB in a tumor-bearing mouse model.

Key findings are as follows:

TLC178 remarkably suppressed fibrosarcoma tumor growth compared with doxorubicin, an approved drug for treatment of sarcomas. TLC178 reached 14% complete regression (CR) and 86% partial regression (PR) while no tumor regression was observed with doxorubicin.

TLC178 showed a better inhibitory effect than both VNB alone and VNB + cyclophosphamide treatments in the rhabdomyosarcoma xenograft model.

TLC178 was well tolerated in all listed studies, as shown by no body weight loss and no lethality, compared to body weight loss and one lethality in doxorubicin-treated mice.

TLC178 showed an improved in vivo systemic pharmacokinetic profile and a five-fold accumulation at the tumor site compared to non-liposomal VNB, which resulted in superior anti-tumor activity.

TLC178 could potentially be used as a single or combination treatment for sarcomas with decreased dosing frequency, reduced toxicity, and enhanced efficacy.

"We are pleased that TLC178 data was selected for presentation at this prestigious conference," said George Yeh, President of TLC. "TLC has long been active in the oncology space, with two oncology products already approved and sold in Asia, and we remain committed to developing medicines with the potential to deliver a better quality of life for patients."

The poster presentation can be accessed under "Publications" in the Pressroom section of TLC’s website at www.tlcbio.com.

About TLC178

TLC178 is TLC’s proprietary NanoX liposomal formulation of vinorelbine, an anticancer drug frequently used off-label to treat soft tissue sarcoma. TLC178 is designed to increase the therapeutic index and reduce side-effects through prolonged circulation time and increased accumulation of vinorelbine in tumor tissues, with the potential to decrease toxicity, improve tolerability, and increase durable response rates. The US Food and Drug Administration (FDA) has granted TLC178 Rare Pediatric Disease Designation in rhabdomyosarcoma, which will qualify TLC178 in this indication for priority review. The FDA and the European Medicines Agency (EMA) have both granted TLC178 Orphan Drug Designation for the treatment of soft tissue sarcoma, which can provide seven and ten years of marketing exclusivity in the US and the EU, respectively.

On September 23, 2019 CARsgen Therapeutics Inc., a clinical-stage biopharmaceutical company reported the European Medicines Agency (EMA) has granted PRIority MEdicines (PRIME) eligibility to its investigational CAR-T cell therapy fully human anti-BCMA (B Cell Maturation Antigen) autologous chimeric antigen receptor (CAR) T Cells (ct053) for the treatment of relapsed or refractory multiple myeloma (Press release, Carsgen Therapeutics, SEP 23, 2019, View Source [SID1234539727]).

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PRIME eligibility was based on clinical data from an ongoing CT053 BCMA CAR-T phase 1 study in China. The results from the trial were presented at an oral presentation on September 14, 2019 in Boston at the 17th International Myeloma Workshop. As of June 30, 2019, 21 out of 24 myeloma patients (87.5%) who received a median of 4.5 prior lines of myeloma therapy showed objective response. 19 out of 24 patients (79.2%) achieved complete response. There was no grade 3 or higher cytokine release syndrome. The duration of response data will be reported at a future date.

"PRIME eligibility is an important regulatory milestone in the continued development and commercialization of CT053 anti-BCMA CAR T cells," said Zonghai Li, M.D., Ph.D., chief executive officer of CARsgen. "CT053 has demonstrated the potential to become the best-in-class BCMA CAR-T therapy. PRIME designation is invaluable to the advancement of this cutting-edge therapeutic to potential market approval and being available to patients as quickly as possible." The CT053 anti-BCMA CAR-T program has received Investigational New Drug (IND) clearance and Orphan Drug designation from the U.S. Food and Drug Administration and authorization of its Clinical Trial Application (CTA) from Health Canada.

EMA’s voluntary PRIME scheme supports the development of promising medicines that show a high potential to benefit patients and target a significant unmet medical need. The status is granted to medicines that may offer a major therapeutic advantage over existing treatments. The program provides developers with enhanced interaction and early dialogue with the EMA to expedite drug development. Between the launch of PRIME in March 2016 through July 25, 2019, the EMA has received and assessed a total of 246 requests for eligibility. Of these, only 24 out of a total of 76 requests in oncology and hematology have been accepted into the scheme.

On September 23, 2019 Genprex recently reported that independent researchers found that company’s TUSC2 (tumor suppressor candidate 2) prevented tumor growth in triple-negative breast cancer (TNBC) (Press release, Genprex, SEP 23, 2019, View Source [SID1234551277]). These independent researchers have no affiliation with Genprex.

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Genprex takes a deeper dive into the data of the study to provide analysis and a better understanding of what the study found and what it means for TUSC2.

The study, "MicroRNA-138 is a Prognostic Biomarker for Triple-Negative Breast Cancer and Promotes Tumorigenesis via TUSC2 repression," takes a look at one particular subtype of breast cancer, triple-negative breast cancer (TNBC).

Triple Negative Breast Cancer

According to the National Breast Cancer Foundation, TNBC occurs in about 10-20 percent of diagnosed breast cancers, and is more likely to affect younger patients (under the age of 50 years old), African Americans, Hispanics and those with a BRCA1 gene mutation.1,5

A diagnosis for TNCB means that the patient does not have any of the three most common types of receptors that enable breast cancer growth, including estrogen, progesterone and the HER2 gene, thus the name for triple-negative breast cancer.1 TNBC progresses rapidly and is more likely to metastasize to the brain and viscera relative to HER2+ cancers.5

Treating TNBC with today’s emerging targeted therapies and immunotherapies are typically ineffective because these receptors are not present. This makes TNBC difficult to treat, and as an aggressive cancer, it is increasingly a feared diagnosis. With few treatment options, most TNBC patients must undergo a lumpectomy, a mastectomy, radiation, chemotherapy or a combination of these treatments.2TNBC patients are significantly less likely to survive than other breast cancer patients following the first metastatic event.5

The Role of MicroRNA-138

MicroRNA, or miRNA, help to downregulate gene expression in a variety of manners.3Thousands of miRNAs have been identified, and miRNAs possess the capacity to target between tens and hundreds of genes simultaneously. They perform a key role in tumorigenesis as important modulators in cellular pathways by regulating target gene expression through translation repression or mRNA degradation.4

Increased miR-138 expression is highly specific to TNBC, and the Nature report notes that miR-138 correlates with poor prognosis in patients, and it is functionally relevant to cancer progression.

The independent researchers explored the role of miR-138 in TNCB and found that it is a specific molecular signature of TNBC and a prognostic biomarker for breast cancer pathogenesis. Researchers also found miR-138 to be a pro-survival oncomiR for TNBC, meaning that overexpression of the gene leads to cancerous tumor growth.6Lastly, when miR-138 is depleted, it leads to apoptotic cell death in vitroand prevents tumorigenesis in vivo. In finding a way to deplete miR-138, this could lead to cancer cell death.

The Role of TUSC2

The independent researchers also found that TUSC2, which is the active agent in Genprex’s lead drug candidate, was a direct target downregulated by miR-138. TUSC2 expression is elevated and TUSC2 protein levels are enhanced following miR-138 knockdown.In TNBC mouse model studies using TUSC2, tumors were barely detectable under miR-138 knockdown conditions, and the implantation of TUSC2 overexpressing cells yielded tumors that are significantly smaller than those in the control group. TUSC2 expression was found to substantially mimic miR-138 knockdown and prevent tumor growth, revealing a potential new treatment for TNBC.

On September 23, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that data from two Phase 1/2 trials were presented at the XVIII International Workshop on Chronic Lymphocytic Leukemia (iwCLL), currently being held in Edinburgh, Scotland (Press release, TG Therapeutics, SEP 23, 2019, View Source [SID1234539695]). These data were previously presented earlier this year at the 15th International Conference on Malignant Lymphoma (ICML), held in Lugano, Switzerland. Highlights from the presentations are included below.

Presentation Title: A Phase 2 Study to Assess the Safety and Efficacy of Umbralisib in Patients with Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK or PI3K Delta Inhibitor Therapy

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This presentation includes data from patients with CLL who are intolerant to prior BTK or PI3K delta inhibitor therapy who were then treated with single agent umbralisib. To be eligible for the study patients had to have received prior treatment with a BTK inhibitor or a PI3K delta inhibitor and discontinued therapy due to intolerance and were in need of subsequent therapy. Fifty-one patients were evaluable for safety of which 50 were evaluable for Progression Free Survival (PFS).

Data highlights include:

Umbralisib demonstrated a favorable safety profile in patients intolerant to prior BTK (ibrutinib or acalabrutinib) or PI3K delta (idelalisib) therapy

Only 12% discontinued due to an umbralisib adverse event, of which only one patient discontinued due to a recurrent adverse event (AE) previously experienced with prior kinase inhibitor therapy (ibrutinib)

In this previously treated CLL population, 67% had a high-risk molecular / genetic marker and 6% had an ibrutinib resistance mutation, the estimated median progression free survival (PFS) was 23.5 months and overall survival (OS) not reached at a median follow-up of 15.7 months

As of the cut-off date, 58% of patients have been on umbralisib for a duration longer than their prior BTK or PI3k inhibitor

Presentation Title: Phase I/II Triple Therapy Study of Umbralisib and Ublituximab (U2) Combined with Checkpoint Inhibition in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Richter’s Transformation (RT)

This presentation includes data from patients with relapsed or refractory CLL or RT treated with the triple combination of ublituximab, umbralisib, and pembrolizumab. Patients with CLL received 2 cycles of the U2 regimen before pembrolizumab was added for an additional 4 cycles, followed by umbralisib maintenance. Patients with RT received U2 + pembrolizumab for the first 4 cycles, followed by U2 maintenance. Twenty patients were evaluable for safety (11 CLL patients and 9 RT patients) and 19 were evaluable for efficacy (11 CLL and 8 RT).

Data highlights include:

The triple combination was well tolerated, with immune mediated toxicities not appearing above what would be expected with either umbralisib or pembrolizumab alone

In this heavily pre-treated cohort with a median of 2 (1-9) prior lines of therapy:

91% (10 of 11) Overall Response Rate (ORR) in patients with relapsed/refractory CLL

83% (5 of 6) ORR in BTK refractory CLL patients, with 4 of 5 responders achieving a response to U2 alone at the patient’s first efficacy assessment, prior to the addition of pembrolizumab

38% (3 of 8) ORR in RT, with two durable complete responses; 1 subject relapsed post-CAR-T in CR for 12 months and 1 subject progressed post-transplant continuing on study in CR now 20+ months. Two additional subjects were in stable disease, one with a 49% reduction in tumor burden.

The data presentations are now available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On September 23, 2019 Oragenics, Inc. (NYSE American:OGEN), a leader in the development of new antibiotics against infectious diseases and effective treatments for oral mucositis ("OM"), reported that an abstract from its ongoing double-blind, randomized, placebo-controlled Phase 2 trial of AG013 in severe oral mucositis, will be presented as a poster at the upcoming European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress ("ESMO") on September 27 – October 1, 2019, in Barcelona, Spain (Press release, Oragenics, SEP 23, 2019, View Source [SID1234539711]),.

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The abstract, titled "Severe Oral Mucositis Mitigation by Genetically Modified Lactococcus Lactis Bacteria (LLB) Producing Human Trefoil Factor 1 (hTFF1; AG013) In Patients Being Treated with Concomitant Chemoradiation (CRT) for Oral and Oralpharyngeal Cancers (OCOCPC)," can be viewed at www.oragenics.com and will be presented at the ESMO (Free ESMO Whitepaper) Congress on September 30, 2019.