On October 10, 2018 Epizyme, Inc. (Nasdaq: EPZM), a clinical-stage company developing novel epigenetic therapies, reported that updated efficacy and safety data from the fully enrolled cohort of epithelioid sarcoma (ES) patients in its ongoing Phase 2 trial of tazemetostat will be presented in a poster discussion session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress to be held October 19-23 in Munich, Germany (Press release, Epizyme, OCT 10, 2018, View Source [SID1234529845]). Tazemetostat is the company’s potent, selective, orally available, first-in-class EZH2 inhibitor.

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The Phase 2 study ES cohort completed enrollment in 2017 with a total of 62 patients. Detailed data will be presented at the Congress, including objective response rate (ORR), the study’s primary endpoint, and other important endpoints in this disease including duration of response, overall survival (OS), disease control rate and safety. For the first time, an analysis of ORR, durability and OS will be presented in both treatment-naive patients and in relapsed and/or refractory patients from the fully enrolled study cohort. Data will be presented by the study’s primary investigator, Mrinal Gounder, M.D., attending physician, Sarcoma Medical Oncology and Early Drug Development Service, and assistant professor, Memorial Sloan Kettering Cancer Center.

"We are excited to share these updated efficacy and safety data on tazemetostat in patients with epithelioid sarcoma, a rare and deadly cancer," said Robert Bazemore, president and chief executive officer of Epizyme. "We remain committed to bringing this potential therapy to patients living with ES, and are confident as we progress towards our first NDA submission in the first half of 2019."

In addition to the ES data, Epizyme will present data from the company’s Phase 2 study of tazemetostat in adult patients with INI1-negative tumors in two additional poster discussions and during one oral session at ESMO (Free ESMO Whitepaper). A complete list of the tazemetostat presentations at ESMO (Free ESMO Whitepaper) are listed below:

Epithelioid Sarcoma Poster Discussion Session
Title: A phase 2, multicenter study of the EZH2 inhibitor tazemetostat in adults: (epithelioid sarcoma cohort)
Abstract No.: 1615PD
Date: Monday, October 22, 2018; 11:50 a.m. CEST
Location: Hall B3 – Room 23
Presenter: Mrinal Gounder, M.D.

Proffered Paper (Oral Presentation) Session
Title: Molecular characterization of epithelioid sarcoma (ES) tumors derived from patients enrolled in a phase 2 study of tazemetostat
Abstract No.: 1892O
Date: Saturday, October 20, 2018; 11:12 a.m. – 11:24 a.m. CEST
Location: Hall B3 – Room 21
Presenter: Mrinal Gounder, M.D.

Poster Discussion Sessions
Title: A phase 2, multicenter study of the EZH2 inhibitor tazemetostat in adults (INI1-negative tumors cohort)
Abstract No.: 1611PD
Date: Monday, October 22, 2018; 11:50 a.m. CEST
Location: Hall B3 – Room 23
Presenter: Silvia Stacchiotti, M.D.

Title: A phase 2, multicenter study of the EZH2 inhibitor tazemetostat in adults (rhabdoid tumor cohort)
Abstract No.: 1612PD
Date: Monday, October 22, 2018; 11:50 a.m. CEST
Location: Hall B3 – Room 23
Presenter: Robin L. Jones, MRCP, M.D.

Conference Call Information
Epizyme Management will host a conference call on Monday, October 22, 2018 at 8:30am EDT. To participate in the conference call, please dial 877-844-6886 (domestic) or 970-315-0315 (international) and refer to conference ID 8780088. The webcast can be accessed in the Investor Relations section of the company’s website at www.epizyme.com. The replay of the webcast will be available in the investor section of the company’s website for 60 days.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a potent, selective, orally available, first-in-class EZH2 inhibitor, is currently being studied as a monotherapy in ongoing Phase 2 programs in certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors; follicular lymphoma (FL); and combination studies in diffuse large B-cell lymphoma (DLBCL) and non–small cell lung cancer (NSCLC).

On October 10, 2018 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported the publication of a peer-reviewed scientific paper on the mechanism of action for VAL-083, the Company’s product candidate, in Cell Death and Disease by Nature Publishing Group (Press release, DelMar Pharmaceuticals, OCT 10, 2018, View Source [SID1234530251]).

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The paper, entitled "Dianhydrogalactitol induces replication-dependent DNA damage in tumor cells preferentially resolved by homologous recombination," details the mechanism of action for VAL-083 (dianhydrogalactitol) involving S-phase dependent DNA double stand breaks (DSB) and homologous recombination (HR) DNA repair. This peer-reviewed publication further validates VAL-083’s unique anti-tumor mechanism and differentiates it from the standard-of-care. In addition, this research supports the use of VAL-083 in combination with drugs targeting cancer cells in S-phase, including topoisomerase inhibitors. Furthermore, the results suggest VAL-083 as a potential treatment option for tumors with impaired HR DNA repair, such as high-grade ovarian carcinomas, or tumors treated with PARP inhibitors.

The research was conducted in the laboratory of Dr. Mads Daugaard at the Vancouver Prostate Center, one of the world’s most respected cancer research institutes. Using non-small cell lung cancer (NSCLC) as a model system for cancer cells, the research group showed that VAL-083-induced cytotoxicity materialized when the cells entered the S-phase of the cell cycle. The resulting DNA damage subsequently triggered irreversible cell cycle arrest and ultimately cancer cell death. Further analysis revealed that cancer cells attempted to use their HR DNA repair pathway to reverse VAL-083-induced DNA damage and cancer cells with an impaired HR repair pathway were therefore particularly sensitive to VAL-083.

DelMar is currently studying VAL-083 in two collaborator-supported, biomarker driven, Phase 2 clinical trials for MGMT-unmethylated glioblastoma multiforme (GBM). As demonstrated in prior publications, the DNA repair protein MGMT is overexpressed in over 60% of GBM patients which causes resistance to the standard-of-care (temozolomide). In contrast to temozolomide, which targets the O6-position of guanine vulnerable to MGMT repair, VAL-083 targets the N7-position of guanine. This distinct mechanism-of-action differentiates VAL-083 from temozolomide and nitrosoureas, allowing VAL-083 to overcome MGMT-related chemoresistance, thereby addressing a significant unmet medical need.

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class," bifunctional DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institute (NCI). DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance, including MGMT, in cancer cell models and animal studies. Further details regarding these studies can be found at:

View Source

VAL-083 has been granted orphan drug designations by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas. VAL-083 has been granted fast-track status for the treatment of recurrent GBM by the US FDA.

On October 10, 2018 Helix BioPharma Corp. (TSX: HBP), (FSE: HBP) ("Helix" or the "Company"), an immuno-oncology company developing innovative drug candidates for the prevention and treatment of cancer, reported that it has extended its collaboration agreement with Moffitt Cancer Center for an additional year (Press release, Helix BioPharma, OCT 10, 2018, View Source [SID1234530409]).

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During the first year of the collaboration, a new pancreatic adenocarcinoma mouse model suitable for testing L-DOS47 in combination with immunotherapy was developed. Preliminary studies in this model showed that L-DOS47 may increase the activity of a PD-1/PD-L1 inhibitor in treating pancreatic cancer. In addition, work was initiated to demonstrate that certain imaging techniques may be useful in directly measuring tumor acidity. Helix is hoping to use this non-invasive technique in the clinic soon.

In year two of the project, work will include not only the study of L-DOS47 in combination with PD-1/PDL1 inhibitors, but also in combination with other drugs in the pancreatic model. Analysis of the immune response that is occurring in the tumor upon L-DOS47 combination treatment will also be characterised. Results from these studies will add to the current understanding of how tumor acidity affects the tumor immune response. Data from these studies will also support Helix’s plan to increase the clinical application of L-DOS47 with various combination treatments, including immunotherapies with checkpoint inhibitors.

"We are strongly encouraged by our preliminary data that this may be an effective approach to improving outcomes to a variety of therapies" said Dr. Robert Gillies, Martin Silbiger Endowed Chair, Moffitt Cancer Center. "We know that tumor acidity is an important contributor to therapy resistance, and thus neutralizing acidity with L-DOS47 should have a positive effect in combination with chemotherapies and immune checkpoint blockade".

"This years’ Nobel prize in Physiology or Medicine was awarded for the discovery of cancer therapy by inhibition of negative immune regulation." said Heman Chao, Ph.D., Chief Executive & Scientific Officer of Helix. "We are very excited to work with the Moffitt team in applying L-DOS47 in immunotherapy and we look forward to using L-DOS47 with PD-1/PD-L1 inhibitors in the clinic which could result in significant benefits to patients."

On October 10, 2018 Incyte (Nasdaq: INCY) has reported that the Phase 2 intermediate data of its selective inhibitor of FGFR1 / 2/3 in the clinical research phase, pemigatinib (INCB54828), will be will present at the next European Congress of Oncology (ESMO) (Free ESMO Whitepaper) 2018 that will take place in Munich, Germany, from October 19 to 23, 2018 (Press release, Incyte, OCT 10, 2018, View Source [SID1234529846]).

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The information that will be announced in ESMO (Free ESMO Whitepaper) 2018 includes poster presentations on the FIGHT-202 study of pemigatinib in patients with advanced cholangiocarcinoma (cancer of the bile duct) and previously treated / metastatic or surgically unresectable with a genetic alteration of the factor of fibroblastic growth (FGF) / FGFR, as well as the FIGHT-201 study of pemigatinib in patients with metastatic or surgically unresectable urothelial carcinoma (cancer of the bladder) carrying an alteration of the FGF / FGFR gene.

"We are pleased that pemigatinib data – part of our portfolio of targeted treatments – have been selected for presentation at this year’s ESMO (Free ESMO Whitepaper) conference," said Steven Stein, MD, medical director, Incyte. "We are keen to share the latest intermediate data from the ongoing FIGHT-202 trial for pemigatinib in patients with cholangiocarcinoma, who continue to support our project to submit the new drug registration request in 2019 for this indication, as well as updated data from the FIGHT-201 study of pemigatinib in patients with urothelial carcinoma, which supports the recruitment for the continuous administration cohort of this trial ».

The summaries were made public today on the ESMO (Free ESMO Whitepaper) congress website, at View Source .

Poster details:

Intermediate results of FIGHT-202, an open and multicenter Phase 2 study of INCB054828 in patients (pts) with advanced and previously treated / metastatic or surgically unresectable cholangiocarcinoma (CCA) with / without alterations of the fibroblast growth factor (FGF) gene / FGF receptor (FGFR) (summary No. 756P, poster presentation session)

Sunday, October 21, 2018 from 12:45 pm Spanish Peninsular Time until 1:45 pm Spanish Peninsular Time (6:45 am East Coast Time at 7:45 am Eastern Time) in the Pavilion A3 – Poster Area Networking Hub
Intermediate results of FIGHT-202, an open-label multicentre study in Phase 2 of INCB054828 in patients (pts) with metastatic or surgically unresectable urothelial carcinoma (UC) carrying the genetic alterations (GA) of fibroblast growth factor (FGF) / FGF receptor (FGFR) (summary No. 900P, poster presentation session)

Monday, October 22, 2018 from 12:45 pm Spanish Peninsular Time at 1:45 pm Spanish Peninsular Time (6:45 am East Coast Time at 7:45 am Eastern Time) in Hall A3 – Poster Area Networking Hub
The details of the full session and the data submission lists for ESMO (Free ESMO Whitepaper) 2018 can be found at:

View Source .

About the FGFR and Pemigatinib (INCB54828)

Fibroblast growth factor receptors (FGFR) play an important role in the proliferation of tumor cells and in survival, migration and angiogenesis (formation of new blood vessels). The mutations, translocations and activating gene amplifications of the FGFRs are closely correlated with the development of various types of cancer.

Pemigatinib is a potent selective inhibitor of isoforms 1, 2 and 3 of FGFR that, in preclinical studies, has shown a selective pharmacological activity against cancer cells with alterations in FGFR. Phase 2 studies investigating the safety and efficacy of pemigatinib monotherapy for various neoplasms due to FGFR are underway. The FIGHT clinical trial program (FIbroblast Growth factor receptor in oncology and Hematology Trials) currently comprises the FIGHT-201 study in patients with metastatic or surgically unresectable bladder cancer, including activating alterations of FGFR3; the FIGHT-202 study in patients with metastatic or surgically unresectable cholangiocarcinoma who did not respond to previous treatment, including activating translocations of FGFR2; and the FIGHT-203 study in patients with myeloproliferative neoplasms with activating translocations of FGFR1.

On October 10, 2018 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported that its acquisition of Vernalis plc has successfully closed and Vernalis will now operate as a subsidiary of Ligand (Press release, Ligand, OCT 10, 2018, View Source [SID1234529847]). Vernalis is a structure-based drug discovery biotechnology company with a broad pipeline of partnered programs and ongoing collaborations. In conjunction with this event, Ligand announced that its portfolio now contains more than 178 shots on goal.

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"We welcome the Vernalis team into the Ligand family and are pleased to add its expertise in structure-based drug discovery to our discovery technology platforms that we offer partners. The Vernalis team has proven its ability to generate novel drug candidates for its partners, including the leading partnerships with Verona and Corvus for COPD and oncology," said John Higgins, Chief Executive Officer of Ligand. "As we advance the Ligand business model, we will continue to evaluate a variety of business, royalty and technology acquisitions, all with the objective of adding shots on goal to our portfolio and creating potential for long-term, diversified and sustainable cash flows for our investors."

Under the terms of the acquisition, Ligand paid Vernalis shareholders approximately $42.3 million, offset by approximately $32 million of net cash on hand at Vernalis, after deal costs.

As previously announced, the acquisition of Vernalis provides Ligand with the following:

A portfolio of more than 8 fully-funded partnered programs, or shots on goal, including:
RPL554, a Phase 2, novel treatment for COPD, which is partnered with Verona Pharma;
CPI-444, a Phase 1, adenosine A2A receptor antagonist for treatment of solid tumors, which is partnered with Corvus Pharmaceuticals.
A 70-person R&D team based in Cambridge, England focused on fragment- and structure-based drug discovery and partnering, with an active portfolio of collaboration agreements generating over $8 million per year of service revenue matched by a comparable level of costs, and partnerships that have the potential to generate additional near-term shots on goal. Ongoing collaboration partners include Servier, Daiichi Sankyo, Asahi Kasei and others.
An established compound library and additional early-stage, unpartnered programs in oncology, CNS and other areas that will provide business development out-licensing and corporate formation opportunities.
England-based operations that provide a platform to more efficiently pursue investment and acquisition opportunities in Europe and the United Kingdom.
Ligand 2018 Financial Outlook

As previously announced, revenue and operating expense impact from Vernalis in 2018 is currently expected to be small and mostly offset each other. Beyond 2018, research business revenue is expected to approximate expenses with longer-term milestones and royalties being accretive to future Ligand earnings.

Advisors

MTS Securities, LLC and finnCap Ltd. served as financial advisors and Latham Watkins LLP served as legal advisor to Ligand in this transaction.