On December 11, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported the presentation of new data that suggests treatment with TAVO (tavokinogene telseplasmid) has the ability to improve immune responses in heavily pretreated, inoperable and locally advanced triple negative breast cancers by increasing tumor infiltrating lymphocyte (TIL) density, increasing effector cytokines, and upregulating immune-related gene expression, factors associated with long-term response to anti-PD1 antibodies (Press release, OncoSec Medical, DEC 11, 2018, View Source [SID1234532009]).

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The now completed Pilot TNBC study, OMS-140 (NCT02531425), was designed to determine whether a single cycle of TAVO monotherapy could enhance anti-tumor immune responses in a TNBC salvage setting. Specifically, a comparative analysis of patient’s pre-TAVO tumor and blood samples to the post-TAVO tumor and blood samples demonstrated that, with only a single cycle of TAVO, a treatment-related increase of CD8+ TIL was observed in four of 10 patients, while also demonstrating a relative decrease in immune suppressive cells.

Nanostring analysis (a novel platform for quantification of gene expression) of the tumor microenvironment revealed a meaningful increase of immune-related transcripts while on treatment. The investigator also evaluated the peripheral blood through a longitudinal analysis of PBMCs (peripheral blood mononuclear cells), and, in doing so, noted an increase of both effector and partially exhausted T cells, which complements the reduced frequency of immune-suppressive MDSC (myeloid-derived suppressor cells) reported earlier this year at AACR (Free AACR Whitepaper).

These data, along with increased effector cytokines noted in serum, demonstrate both local and systemic immune responses with only one cycle of TAVO in this difficult to treat patient population. Additionally, as observed in other clinical trials with TAVO, this study showed that TAVO is safe and well tolerated in this patient population.

These data, as well as other clinical and immunological data, were presented at the 2018 San Antonio Breast Cancer Symposium (SABCS) taking place December 4-8 in San Antonio, Texas.

"The immunological signatures described here, including conversion of non-immunogenic tumors into immunologically active lesions, are very encouraging, especially when considering that patients with very advanced disease received only one cycle of TAVO," said Dr. Christopher Twitty, Chief Scientific Officer of OncoSec. "Late-stage triple negative breast cancer patients have very few treatment options, and those that are available, come with serious toxicities and limited effectiveness. Recent data suggest that some patients with triple negative tumors will benefit from treatment with PD-1 checkpoint inhibitors, but only if the patient’s tumor is immunologically active," continued Dr. Twitty. "This study represents the potential of a safe and effective immunotherapy to turn non-immunogenic tumors into an immunologically active tissue, expanding the benefits of PD-1 checkpoint inhibitors to a much broader subset of women with triple negative breast cancer, which would be an important advance for the treatment of these patients."

As previously reported, a subset of patients that completed a single cycle of TAVO in this study, were sequentially treated with an anti-PD-1 checkpoint therapy (nivolumab). Importantly, some of these patients, one with prior disease progression on anti-PD-L1 antibody monotherapy, experienced robust clinical responses beyond the TAVO treated lesions. One of these patients continues to be treated with TAVO under a compassionate use protocol.

Based on these findings, OncoSec and Merck initiated a second TAVO Phase 2 study in TNBC, KEYNOTE-890, to evaluate the combination of TAVO with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in approximately 25 patients with treatment-refractory, inoperable or metastatic triple negative breast cancer (NCT03567720).

Since KEYNOTE-890 opened in October, investigators have already enrolled five patients into the trial. The KEYNOTE-890 study is testing the combination in patients with inoperable locally advanced or metastatic TNBC who have progressed on more than one line of prior therapy. Patients will be treated with the combination of TAVO with pembrolizumab. The primary endpoint is to assess efficacy as measured by objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

On December 11, 2018 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported the initiation of the triple combination arm of the Phase 2a COMBAT/KEYNOTE-202 study in patients with metastatic pancreatic cancer (PDAC) under its immuno-oncology collaboration with Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada) (Press release, BioLineRx, DEC 11, 2018, View Source;p=irol-newsArticle&ID=2380207 [SID1234532008]). As previously announced, the triple combination arm will investigate the safety, tolerability and efficacy of BL-8040, KEYTRUDA and chemotherapy.

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The triple combination arm will focus on second-line pancreatic cancer patients, and will include approximately 40 patients with unresectable metastatic pancreatic adenocarcinoma who have progressed following first-line therapy prior to enrollment. Patients will receive BL-8040 monotherapy priming treatment for 5 days, followed by ongoing cycles of the combination of chemotherapy (Onivyde/5-fluorouracil/leucovorin – 5-FU/LV), KEYTRUDA and BL-8040 until progression. The primary endpoint of the study is the objective response rate (ORR) assessed by RECIST v1.1 criteria. Secondary endpoints will include overall survival, progression free survival, and the disease control rate.

"We are pleased to commence this triple combination arm of our Phase 2a pancreatic study, under the framework of our immuno-oncology collaboration with MSD," stated Philip Serlin, Chief Executive Officer of BioLineRx. "We believe that the addition of chemotherapy may be synergistic with BL-8040 and KEYTRUDA, as chemotherapy has been shown to reduce overall tumor burden while inducing immunogenic cell death, leading to activation and expansion of new tumor-reactive T-cells. Based on its mechanism of action, we believe that BL-8040 may facilitate the infiltration of these T-cells into the tumor core, alongside the restoration of T-cell activity within the tumor by KEYTRUDA. We look forward to results of the study expected in the second half of 2019."

At the recent European Society for Medical Oncology 2018 Congress in Munich, Germany, BioLineRx disclosed top-line results from the dual combination arm of the Phase 2a COMBAT/KEYNOTE-202 study, evaluating PDAC patients treated with BL-8040 in combination with KEYTRUDA. The results show encouraging disease control and extended overall survival, particularly in patients undergoing second-line treatment. In addition, the data also demonstrate that BL-8040 significantly improves T-cell infiltration into the tumor and reduces immunosuppression in the tumor microenvironment.

About the COMBAT/KEYNOTE-202 Study

The Phase 2a COMBAT/KEYNOTE-202 study was originally designed as an open-label, multicenter, single-arm trial to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), in over 30 subjects with metastatic pancreatic adenocarcinoma. The study was primarily designed to evaluate the clinical response, safety and tolerability of the combination of these therapies, and was carried out in the US, Israel and additional territories. The study is being conducted by BioLineRx under a collaboration agreement signed in 2016 between BioLineRx and MSD, through a subsidiary.

In July 2018, the Company announced the expansion of its immuno-oncology collaboration with MSD to include a triple combination arm investigating the safety, tolerability and efficacy of BL-8040, KEYTRUDA and chemotherapy as part of the Phase 2a COMBAT/KEYNOTE-202 study. The triple combination arm will focus on second-line pancreatic cancer patients.

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells to peripheral blood and to be effective at inducing direct tumor cell death. In addition, clinical findings have demonstrated the ability of BL-8040 to mediate infiltration of T-cells into tumors that were previously immunologically "cold" and devoid of immune cell infiltrate. Immune checkpoint inhibitors (such as KEYTRUDA) produce anti-cancer effects by increasing the activity of T-cells through blockade of the interaction between the immune checkpoint receptor PD-1, on T-cells, and its ligand PD-L1, on tumor cells. Pancreatic cancers have very little T-cell infiltrate, making them less susceptive to checkpoint blockade than other tumors that are infiltrated by T-cells. Therefore, combining BL-8040 with immune checkpoint blockade is predicted to increase the responsiveness of pancreatic cancer patients to immunotherapy. Further increase in the sensitivity of pancreatic cancer cells to BL-8040 and KEYTRUDA may be achieved by chemotherapy-mediated immunogenic cell death and exposure of new tumor antigens, resulting in activation of new anti-cancer T cell clones.

About BL-8040

BL-8040 is a short synthetic peptide for the treatment of hematological malignancies, solid tumors, and stem cell mobilization. It functions as a high-affinity best-in-class antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells and immune-cells, sensitization of cancer cells to chemo- and bio-based anti-cancer therapies, and direct anti-cancer effect by inducing programmed cell death (apoptosis). BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On December 11, 2018 PharmaMar (MSE:PHM) reported the Australian Regulatory Agency (TGA) has informed STA that Aplidin (plitidepsin) has been approved for the treatment of multiple myeloma in combination with dexamethasone (Press release, PharmaMar, DEC 11, 2018, View Source [SID1234532007]).

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Aplidin will be available to patients who have failed or are resistant to other therapies, after the TGA decision to approve Aplidin before any other country.

The indication has been approved for the treatment of patients that relapse after three lines of treatment, including proteasome inhibitors or immunomodulators. It can also be administered as 3rd line treatment, when the patient has already received two prior lines and is refractory or intolerant to proteasome inhibitors or immunomodulators.

This approval opens the door to many other markets in South America, Mexico, Canada, Asia Pacific, Middle East and North Africa, among others, that will review Aplidin after TGA’s decision, and where PharmaMar has partners for this product.

PharmaMar signed a licensing agreement with Specialised Therapeutics Asia Pte, Ltd (STA), established in Singapore, to market Aplidin in Australia and New Zealand in August 2015, along with a new agreement for 12 other Asian countries in February 2016.

Professor Andrew Spencer, Head of the Malignant Haematology and Stem Cell Transplantation Service at The Alfred Hospital, said: "Aplidin provides a chance for some myeloma patients to extend their lives. We now have another drug to offer patients who have relapsed after being treated with existing therapies. This is important, because once patients become resistant to standard therapies, there have been very limited treatment options."

Professor Jeff Szer, Peter MacCallum Cancer Centre and Royal Melbourne Hospital haematologist, who was the Australian principal investigator on the pivotal Aplidin registration study, said Aplidin had been shown to be effective and well tolerated. He commented: "More Australian myeloma patients were enrolled into the pivotal international trial of Aplidin than anywhere else in the world. These patients in the Phase 3 study known as ADMYRE have now paved the way for others to have access to a new and novel therapy. This really means that some patients with advanced myeloma have the possibility of improved outcomes, when previous therapies have failed."

Carlo Montagner, Chief Executive Officer of Specialised Therapeutics Asia, said Australian regulatory authorities should be commended for ensuring Australian myeloma patients have the first opportunity to access this cutting-edge therapy. He commented: "It is not often that Australian patients are the first in the world to access new medicines. In this case, the TGA is at the forefront, with decision-makers recognizing the great need that exists in multiple myeloma. This disease remains incurable and patients eventually run out of treatment options."

José María Fernández Sousa-Faro, President of PharmaMar, said: "This approval for an incurable disease, corroborates the work that the PharmaMar team has done over the years with Aplidin. Patients and the medical community will now have a new therapeutic alternative with a new mechanism of action, that is different from the products currently in use."

Luis Mora, Managing Director of PharmaMar´s Oncology Business Unit, added: "The approval of Aplidin is a very important step forward for the company. This increases PharmaMar’s presence with a second drug on the Australian market and, together with our partners, we are initiating procedures for other markets, such as South America, Mexico, Canada, Asia and Israel."
In Europe, as already announced, the decision of the European Medicines Agency (EMA) is being appealed to the Luxembourg Court.

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On December 11, 2018 THERADIAG (ISIN: FR0004197747, Ticker: ALTER), a company specializing in in vitro diagnostics and theranostics, reported the appointment by its Board of Directors of Bertrand de Castelnau as its Chief Executive Officer (Directeur Général) (Press release, Theradiag, DEC 11, 2018, View Source;utm_medium=rss&utm_campaign=appointment-of-bertrand-de-castelnau-as-chief-executive-officer-of-theradiag [SID1234532002]).

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Bertrand de Castelnau will replace Michel Finance, whose term expires on December 31, 2018, and will take up his post from January 21, 2019. To this end, the Board of Directors appointed Fabienne François, currently Chief Financial and Administrative Officer at Theradiag, as interim Chief Executive Officer for the period from January 1 to January 20, 2019.

Aged 58, Bertrand de Castelnau has more than 25 years’ experience in the field of diagnostics. He began his career as a Commercial Attaché in Islamabad, Pakistan. He then joined Roche in Switzerland, as a Corporate Auditor before moving to the Diagnostics division and then taking charge of the Asia-Pacific region for Roche Diagnostics, based in Singapore. Bertrand went on to become Operations Manager at Guerbet for four years, before spending 10 years running the Horiba ABX Group and its Horiba Medical division. Finally he joined DiaSys as head of Marketing, Sales and Finance.

A fluent speaker of several languages, he holds an MBA from the Ecole des Hautes Etudes Commerciales (HEC) and a law degree from Paris.

Pierre Morgon, Chairman of the Board of Directors of Theradiag commented: "We are delighted to welcome Bertrand as Chief Executive Officer of Theradiag. His 25 years’ experience in the field of diagnostics and his track record of creating partnerships and developing international businesses will be key advantages for the expansion of Theradiag."

Bertrand de Castelnau, incoming Chief Executive Officer of Theradiag, added, "I am joining the Theradiag team with great enthusiasm and look forward to contributing my skills and experience to the growth and the expansion of the international reach of Theradiag and of biotherapy monitoring."

Changes to the Board of Directors

Following the resignation of Dominique Costantini from her position as Director, the Board of Directors is now as follows:

Pierre Morgon, Chairman of the Board of Directors
Sylvie Bratel, Independent Director
Vincent Fert, Independent Director
John Li, Director
Dominique Takizawa, Independent Director

On December 1, 2018 BiomX Ltd., a microbiome company developing customized phage therapies, reported that it has appointed Dr. Sailaja Puttagunta, M.D., as its Chief Medical Officer (CMO) (Press release, BiomX, DEC 11, 2018, View Source [SID1234532001]). With her extensive experience in conducting Phase I to IV clinical trials, contributing to NDA submissions in anti-microbial disease areas and product launch preparations, Dr. Puttagunta will oversee BiomX’s clinical development and strategy as the company prepares to enter the clinic with its Acne and Irritable Bowel Disease (IBD) programs. The company’s Acne program is expected to enter the clinic in mid 2019, and the IBD program is expected to commence clinical trials in 2020. Dr. Puttagunta will be based in United States’ East Coast and will work closely with BiomX’s Israeli management.

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"Sailaja’s broad experience and knowledge of the U.S. and global drug development field will accelerate our phage therapeutics advancement toward the clinic," stated Jonathan Solomon, CEO of BiomX. "BiomX is also establishing a presence in the U.S. with Sailaja’s appointment. Her clinical expertise and extensive contacts in the medical community will help build a strong foundation for our global footprint."

"BiomX’s novel approach to targeting harmful bacteria in our microbiome, harnessing bacteria’s natural enemies, bacteriophages, bodes great promise not only due to the phages’ lethality, but also due to their high specificity, which enables not harming the beneficial bacteria," added Dr. Puttagunta. "I am looking forward to bringing this technology to the clinic where it has the potential to help patients with chronic and sometimes life-threatening diseases."

Dr. Sailaja Puttagunta, M.D., was most recently Vice President, Development at Iterum Therapeutics, a clinical-stage pharmaceutical company developing antibiotics against multi-drug resistant pathogens. Prior to Iterum, Dr. Puttagunta served as VP, Medical Affairs for Anti-infectives at Allergan from early 2015 and was the VP of Development and Medical Affairs at Durata Therapeutics, Inc. prior to its acquisition by Actavis plc. From 2006 to 2012, Dr. Puttagunta led teams within clinical development and medical affairs on various antibiotic compounds at Pfizer Inc. Dr. Puttagunta has 20 years of clinical, academic and research experience in medicine and in the sub-specialty of infectious diseases. She graduated from Gandhi Medical College in Hyderabad, India and completed her residency in Internal Medicine and a fellowship in Infectious Diseases at Yale University School of Medicine. She also holds an M.S. in Biochemistry from the New York University School of Medicine.