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Onxeo Announces Positive Interim Results from Phase 1 Study of AsiDNATM, a First-In-Class DNA Damage Response Inhibitor

On November 5, 2018 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), a clinical-stage biotechnology company specializing in the development of innovative drugs in oncology targeting tumor DNA Damage Response (DDR) to fight resistant cancers, reported positive interim results from the first three dose levels already evaluated out of six planned in its Phase 1 DRIIV-1 study of AsiDNA, the Company’s first-in-class DNA Damage Response inhibitor (Press release, Onxeo, NOV 5, 2018, View Source [SID1234530739]).

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A total of 10 patients with advanced solid tumors received 112 infusions of AsiDNA ranging from 200mg (DL1) to 600mg (DL3). The administration of DL4 (900mg) is ongoing and the full data set from DRIIV-1 is expected to be available in the first half of 2019.

Judith Greciet, Chief Executive Officer of Onxeo, said: "We are very pleased to report highly compelling interim results from our DRIIV-1 study. Beyond the safety endpoints of all phase 1 studies, DRIIV-1 was foremost designed to demonstrate that AsiDNA administered intravenously activates in patients’ tumors cells the intended DNA Damage Response biological targets. Midway through the study, data show that robust target engagement was demonstrated as early as the second dose level, which represents a meaningful proof-of-mechanism of AsiDNA in man. In addition, the results indicate a favorable safety profile for AsiDNA in a difficult-to-treat patient population. These proof-of-mechanism and activity results further support the clinical potential of AsiDNA in solid tumors and represent a major value catalyst in the development of our first-in-class drug candidate."

Pharmacokinetic parameters

Both Cmax (maximal concentration) & AUC (area under the curve) data show dose proportionality from dose level 1 to dose level 3, with systemic exposure rising proportionally to the dose.

Pharmacodynamic parameters (activity data)

In accordance with the study protocol, biopsies were performed during cycle 2 of treatment with AsiDNA and analyzed by comparison with baseline biopsies. Target engagement by AsiDNA was measured by quantifying through immuno-histochemistry two established biomarkers of the activation of DNA-PK, a major target for AsiDNA, gH2AX and pHSP90.

Post-treatment biopsies were available and analyzed for four patients (two post-DL2 and two post-DL3), showing a robust activation of DNA-PKA as evidenced by a significant post-treatment increase in the quantification of these activity biomarkers in patients’ tumor tissue. These data confirmed strong target engagement and activity in tumors at these two AsiDNA dosages.

Furthermore, the quantification of a well-known tumor proliferation biomarker, Ki67, showed a clear decrease of the proliferation rate in tumors of three patients and stabilization in one patient.

Safety data

Intravenous administration of AsiDNA was generally well-tolerated at DL1, DL2 and DL3, with no drug- related serious adverse event and no dose-limiting toxicity.

Olivier de Beaumont, Chief Medical Officer of Onxeo, concluded: "We are very encouraged by these first safety and proof-of-mechanism data, which confirm the activity and tolerability of AsiDNA via systemic administration. AsiDNA is now ready to enter the next stage of its clinical development. Our translational work on the combination of AsiDNA with PARP inhibitors is indicative of the unique properties of this combination, such as the prevention, and even reversal, of the resistance to PARP inhibitors. Promising data have also been obtained in combination with DNA-damaging agents such as platins or taxanes. Combining AsiDNA with these agents will therefore be our first priority as we expand its clinical development to Phase1b/2 efficacy studies in combination in 2019. In parallel, the DRIIV-1 study is progressing to plan and we are on track to deliver full results in the first half of 2019."

Onxeo will host a conference call in English with a Q&A session for analysts and investors at 5:30 pm CET / 11:30 pm ET today to discuss this announcement

Location

Phone number

France +33 1 72 72 74 03
United States +1 646 722 4916
United Kingdom +44 20 7194 3759
Denmark +45 8233 3187

Participation code: 33251686#

Access to the management presentation prior to the call

An audio replay file will be made available after the session on Onxeo’s website.
About the DRIIV-1 study

DRIIV-1 (DNA Repair Inhibitor administered IntraVenously) is an open-label, dose escalation, Phase 1 study evaluating the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNA via systemic (IV) administration in patients with advanced solid tumors. The study is being conducted at leading oncology centers in France and Belgium.

Six dose levels (DLs) are planned (DL1 to DL6): 200mg, 400mg, 600mg, 900mg, 1,300mg and 1,800mg. All patients receive a loading dose of AsiDNA for 3 consecutive days (1-hour IV infusion at day 1, day 2 and day 3), followed by a one-hour IV infusion once a week (at day 8 and day 15) of a 21 days treatment period (1 cycle = 21 days). In each subsequent cycle, AsiDNA is administered on a weekly basis (day 1, day 8 and day 15) of a 21 days treatment period. Patients are continuing study treatment until disease progression, unacceptable toxicity or patient’s refusal to continue.

Each dose level is stepped up following validation by a Data Safety Monitoring Board.

The primary objective is to determine dose-limiting toxicities and maximum tolerated dose of IV infusion of AsiDNA. Secondary objectives are to assess the safety profile, PK parameters and target engagement of AsiDNA based on the quantification of activity biomarkers in tumor tissue (YH2AX, pHSP90). In addition, proliferation tumor status as measured by KI67 immunostaining, and preliminary efficacy of AsiDNA, are also being evaluated.

Audentes Therapeutics Board of Directors Appoints Co-Founder and Chief Executive Officer Matthew R. Patterson as Chairman

On November 5, 2018 Audentes Therapeutics, Inc. (Nasdaq: BOLD), a biotechnology company focused on developing and commercializing innovative gene therapy products for patients living with serious, life-threatening rare diseases, reported that Co-Founder and Chief Executive Officer (CEO) Matthew R. Patterson has been appointed Chairman of the Board of Directors (Press release, Audentes Therapeutics, NOV 5, 2018, View Source [SID1234530738]). The Board of Directors also appointed Louis G. Lange, M.D., Ph.D. as Lead Independent Director. Mr. Patterson and Dr. Lange have held board member roles since 2012 and 2015, respectively.

"It is a great privilege for me to serve our company as Chairman of the Board of Directors," stated Matthew R. Patterson, Chairman and CEO. "Audentes is at an exciting inflection point, and I look forward to working closely with the board and management team to deliver on important milestones that advance our mission of developing innovative gene therapy products for patients living with serious, life-threatening rare diseases."

Mr. Patterson continued, "I am also pleased to announce the appointment of Dr. Lange to the position of Lead Independent Director. Lou is a recognized leader in the biotechnology industry who brings a unique and valued perspective to our organization. We’re fortunate to benefit from Lou’s deep experience gained over a successful career as a physician and founder and CEO of innovative public biotechnology companies, and I look forward to partnering with him in the leadership of our board."

Mr. Patterson has more than 25 years of experience in the research, development, and commercialization of innovative treatments for rare diseases and has held positions of senior management in both private and public biotechnology companies. Previously Mr. Patterson worked for Genzyme Corporation, BioMarin Pharmaceutical, and Amicus Therapeutics. Prior to Audentes he was an Entrepreneur-In-Residence with OrbiMed, one of the world’s largest healthcare dedicated investment firms. Mr. Patterson currently serves as Chairman of the Alliance for Regenerative Medicine (ARM), the international advocacy organization representing the gene and cell therapy and broader regenerative medicine sector. He is a member of the Board of Directors for Homology Medicines, Inc., Modis Therapeutics, Inc., and Gilda’s Club of New York City, which provides support for people living with cancer. Mr. Patterson received his Bachelor’s degree in Biochemistry from Bowdoin College.

Dr. Lange was the founder of CV Therapeutics, and as the Chairman, CEO, and Chief Scientific Officer, led the company through an IPO, the approval of two first-in-class cardiovascular drugs, RANEXA and LEXISCAN, and the sale of the company to Gilead Sciences, Inc. Prior to joining industry, Dr. Lange spent 22 years in academic medicine at Harvard and Washington University, where he served as Chief of Cardiology and Professor of Medicine at Jewish Hospital and was one of the first academicians in molecular cardiology. Dr. Lange is currently a General Partner at Asset Management Ventures, serves as a senior advisor to Gilead Sciences, Inc., and has served on numerous other public and private boards in both the non-profit and for-profit sectors. Dr. Lange holds a Doctorate degree in Biochemistry from Harvard University and a Medical Doctor degree from Harvard Medical School. He earned a Bachelor’s degree from the University of Rochester.

Seattle Genetics Submits Supplemental Biologics License Application for ADCETRIS® (Brentuximab Vedotin) in Frontline Treatment of CD30-Expressing Peripheral T-Cell Lymphomas

On November 5, 2018 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that it has submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ECHELON-2 trial evaluating ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the frontline treatment of patients with CD30-expressing peripheral T-cell lymphoma (PTCL) (Press release, Seattle Genetics, NOV 5, 2018, View Source [SID1234530737]). The positive topline results of the phase 3 ECHELON-2 clinical trial were announced in October 2018 and full data will be presented at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, December 1-4, 2018 in San Diego, Calif. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of several types of PTCL. ADCETRIS is currently not approved for the frontline treatment of PTCL.

"CD30 is expressed in several subtypes of peripheral T-cell lymphoma, an aggressive type of non-Hodgkin lymphoma, and the current standard of care for frontline treatment consisting of a multi-agent chemotherapy regimen called CHOP has not changed in several decades," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "Results from the ECHELON-2 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival and importantly, overall survival, in patients with previously untreated CD30-expressing PTCL who were treated with ADCETRIS in combination with CHP chemotherapy over standard of care CHOP chemotherapy. We believe these superior results over standard of care represent a significant advance for patients with CD30-expressing PTCL and for the medical community, and we look forward to working with the FDA during the review process of this application to bring this potential new treatment regimen to patients as quickly as possible."

The phase 3 ECHELON-2 clinical trial evaluated the combination of ADCETRIS plus CHP (cyclophosphamide, doxorubicin, prednisone) compared to a recognized standard of care chemotherapy regimen, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in previously untreated CD30-expressing PTCL. The ECHELON-2 study met its primary endpoint demonstrating a statistically significant improvement in progression-free survival (PFS) as assessed by an Independent Review Facility (IRF; hazard ratio=0.71; p-value=0.0110). The ADCETRIS plus CHP arm also demonstrated superior overall survival (OS), a key secondary endpoint, compared to CHOP (hazard ratio=0.66; p-value=0.0244). All other key secondary endpoints, including PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate and objective response rate were statistically significant in favor of the ADCETRIS plus CHP arm. The safety profile of ADCETRIS plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of ADCETRIS in combination with chemotherapy. Full data will be presented at the ASH (Free ASH Whitepaper) Annual Meeting in the following session:

Oral Session: Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: T-Cell Lymphoma: Chemotherapy and Targeted Approaches (Abstract #997)
Date/Location: Monday, December 3, 2018 at 6:15 p.m. PT, San Diego Convention Center, Room 6F
Presenter: Steven Horwitz, M.D., Department of Medicine, Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York
ECHELON-2 Phase 3 Clinical Trial Design

The randomized, double-blind, placebo-controlled phase 3 trial is investigating ADCETRIS plus CHP (cyclophosphamide, doxorubicin, prednisone) versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as frontline therapy in patients with CD30-expressing peripheral T-cell lymphoma, also known as mature T-cell lymphoma. The primary endpoint is progression-free survival (PFS) per Independent Review Facility assessment, with events defined as progression, death, or receipt of chemotherapy for residual or progressive disease. Secondary endpoints include PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate, overall survival and objective response rate, in addition to safety. The multi-center trial was conducted at sites across North America, Europe and Asia and was designed to enroll 450 patients, approximately 75 percent of whom were to be diagnosed with sALCL. The ECHELON-2 trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) and the trial also received European Medicines Agency (EMA) scientific advice.

Please see Important Safety Information at the end of this press release.

About T-Cell Lymphomas

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. There are more than 60 subtypes of non-Hodgkin lymphomas which are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing). PTCL accounts for approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and Europe and may be as high as 24 percent in parts of Asia.

About ADCETRIS (brentuximab vedotin)

ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include the recently completed phase 3 ECHELON-2 trial in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), the completed phase 3 ECHELON-1 trial in previously untreated Hodgkin lymphoma, the completed phase 3 ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for five indications in adult patients with: (1) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy, (2) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (3) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (4) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has received marketing authorization by regulatory authorities in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

US FDA GRANTS PV-10 ORPHAN DRUG DESIGNATION FOR NEUROBLASTOMA

On November 5, 2018 Provectus (OTCQB: PVCT) reported that the Company was granted orphan drug designation (ODD) by the U.S. Food and Drug Administration (FDA) for small molecule oncolytic immunotherapy PV-10 for the treatment of neuroblastoma, a non-central nervous system (CNS) pediatric solid tumor (Press release, Provectus Biopharmaceuticals, NOV 5, 2018, View Source [SID1234530736]). Intratumoral injection of PV-10 can yield immunogenic cell death (ICD) in solid tumor cancers and stimulate tumor-specific reactivity in circulating T cells.1-4

Neuroblastoma forms from immature nerve cells and usually begins in the adrenal glands. It may also begin in the abdomen, chest, or near the spine. Neuroblastoma most often occurs in children younger than 5 years of age, and presents when the tumor grows and causes symptoms. According to the National Cancer Institute SEER Cancer Statistics Review 1975-2015, the 5-year survival among children 0 to 19 years of age is 75.2%.5

Initial non-clinical testing of PV-10 in treatment-refractory neuroblastoma has closely paralleled previous non-clinical and clinical study of PV-10 for murine and human adult solid tumors, at both the tumor (selective destruction of injected tumors) and cellular (ICD) levels.6 Non-clinical investigation by member institutions of the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC) has confirmed that ICD also occurs in neuroblastoma.

The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US. ODD status qualifies companies for benefits that include seven years of market exclusivity following marketing approval, tax credits on U.S. clinical trials, eligibility for orphan drug grants, and waiver of certain administrative fees.

ODD status previously was granted to PV-10 for the treatments of metastatic melanoma in 2007 and hepatocellular carcinoma (HCC) in 2013.

About Neuroblastoma

If detected at an early stage, surgery is the definitive treatment. Once neuroblastoma has recurred or spread from the primary site, therapeutic options are limited principally to chemotherapy or clinical trial.7 A recent review of emerging treatment options for neuroblastoma noted that "less than 50% of patients with high-risk neuroblastoma will survive long-term with current therapies, and survivors are at risk for serious treatment-related late toxicities."8

Therapeutic options include high-dose systemic chemotherapy with alkylating agents, radiation therapy, experimental treatments like regional therapy, or immunotherapy. Unlike many adult solid tumor types, pediatric solid tumors have largely proven unresponsive to immune checkpoint inhibitors such as anti-PD-1 antibodies. A recent Phase 2 study of pembrolizumab in pediatric solid tumors showed that less than 20% of patients tested were candidates for anti-PD-1 therapy based on low expression of the PD-L1 biomarker, and no candidates achieved an objective response.9

About PV-10

Provectus’ lead investigational oncology drug, PV-10, the first small molecule oncolytic immunotherapy, can induce immunogenic cell death. PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver, and preclinical study for pediatric cancers.

About the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium

The Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC) was founded in February 2003 by Dr. Tanya Trippett at Memorial Sloan Kettering Cancer Center and Dr. Lia Gore at the University of Colorado Cancer Center. POETIC is composed of ten large academic medical centers in North America with a major emphasis on comprehensive cancer care and research that provide the collaborative and research strength needed to complete intensive phase I and II studies. Each of the institutions is uniquely suited to complete early studies in the pediatric and adolescent populations. POETIC’s assets include membership in NCI-designated Comprehensive Cancer Centers, on-site NIH-funded pediatric and/or general clinical translational research centers (CTRCs/CTSAs), and active collaborations with developmental therapeutics programs for adults at a majority of its member institutions. The availability of strong basic science and translational research programs at the institutions allows focus on the development and evaluation of new therapeutic strategies for patients with cancer and related disorders. POETIC’s pediatric oncology studies focus on the biologic basis for anti-cancer therapy, and in particular, attempt to explore and evaluate novel agents and/or combinations of therapies early in clinical development as well as new approaches to targeted delivery. For additional information about POETIC, please visit the Consortium’s website at www.poeticphase1.org.

Omeros Corporation to Announce Third Quarter 2018 Financial Results on November 9, 2018

On November 5, 2018 Omeros Corporation (NASDAQ: OMER) reported that the company will issue its third quarter 2018 financial results for the period ended September 30, 2018, on Friday, November 9, 2018, before the market opens (Press release, Omeros, NOV 5, 2018, View Source;p=RssLanding&cat=news&id=2375238 [SID1234530735]). Omeros management will host a conference call and webcast that day at 8:30 a.m. Eastern Time (5:30 a.m. Pacific Time) to discuss the financial results.

Conference Call Details

To access the live conference call via phone, please dial (844) 831-4029 from the United States and Canada or (920) 663-6278 internationally. The participant passcode is 7771247. Please dial in approximately 10 minutes prior to the start of the call. A telephone replay will be available for one week following the call and may be accessed by dialing (855) 859-2056 from the United States and Canada or (404) 537-3406 internationally. The replay passcode is 7771247.

To access the live and subsequently archived webcast of the conference call, go to Omeros’ website at www.omeros.com and go to "Events" under the Investors section of the website. Please connect to the website at least 15 minutes prior to the call to allow for any software download that may be necessary.