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GamaMabs Pharma to present at 2018 ASCO annual meeting results from the First-In-Human clinical study of GM102 in advanced gynecological cancers

On May 22, 2018 GamaMabs Pharma, a biotechnology company developing optimized therapeutic antibodies targeting the Anti-Müllerian Hormone Receptor II (AMHRII) for the treatment of cancer, reported the upcoming presentation of clinical data from the First-In-Human C101 phase Ia/Ib study of its GM102 antibody during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, on June 4 in Chicago, USA (Press release, GamaMabs Pharma, MAY 22, 2018, View Source [SID1234526865]).

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Data will be reported on 27 patients with advanced or recurrent AMHRII-positive epithelial ovarian (EOC), granulosa ovarian (GCT), cervical and endometrial cancers, treated with GM102 monotherapy in eight successive escalation cohorts at five major European cancer centers.

No safety signal was reported at all doses tested. Two clinical objective partial responses according to RECIST criteria were observed among four GCT patients. Peripheral blood pharmacodynamic changes observed under GM102 treatment suggested an immune cell recruitment to the tumor site. In paired tumor biopsies before and under GM102 treatment, enhanced CD16 and Granzyme B biomarker expression was observed in the tumor micro-environment, suggesting GM102-induced cellular cytotoxicity or phagocytosis.

Expansion cohorts in EOC and GCT at the recommended GM102 dose are currently ongoing, with first results anticipated early 2019.

GM102 is a first-in-class glyco-engineered (low-fucose) monoclonal antibody selectively targeting AMHRII-expressing tumors. AMHRII, an embryonic receptor involved in the regression of the Müllerian ducts in the male embryo, is constitutively expressed in ovarian granulosa tumors (GCT) and re-expressed in approximately 70% of gynecological tumors. GM102 exerts its anti-tumor activity through NK cell and macrophage engagement in the tumor microenvironment, resulting in enhanced tumor phagocytosis and ADCC (Antibody Dependent Cell Cytotoxicity).

"These first results are really encouraging, especially for patients with granulosa ovarian cancers who do not have therapeutic alternatives at this stage," said Pr. Alexandra Leary, Gustave Roussy Institute (France), principal investigator of the study. "We are gathering experience with additional patients in the expansion part of the study; should these first results be confirmed, we will move forward with a larger phase 2 study in this indication with great enthusiasm, given the unmet medical need."

"We are happy to share such exciting data with the medical community, which confirm the unique immunological mode of action of GM102 and shows its translation into clinical activity," said Stéphane Degove, CEO at GamaMabs Pharma. "We are expanding our GM102 clinical development program beyond the field of gynecological cancers in other tumor types that also express AMHRII," he added.

Results will be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago, during the Gynecologic Cancer session, on June 4, 2018, 1:15 PM-4:45 PM.
Abstract #5542; Poster ID 214461, ‘A first-in-human study of monoclonal antibody GM102 in patients with Anti-Mullerian-Hormone-Receptor II (AMHRII) positive gynecological cancers’ by A Leary and co-authors.
Following the presentation, the poster will be available on the Publication page of GamaMabs’ website1.

Bexion Pharmaceuticals, Inc. To Present Clinical Data at 2018 ASCO Annual Meeting

On May 22, 2018 Bexion Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on rare brain and solid tumors, reported that it will feature one clinical poster presentation and three online publications at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held June 1-5 in Chicago, IL.

The ASCO (Free ASCO Whitepaper) Annual Meeting brings together more than 32,000 oncology professionals from around the world to discuss state-of-the-art treatment modalities, new therapies, and ongoing controversies in the field.

Bexion’s representation:

Abstract # 2517: First-in-class Phase Ia Study of BXQ-350 for Solid Tumors and Gliomas

Olivier Rixe, MD, PhD, will participate in a Q&A panel presenting data from this study during a Poster Discussion Session on Monday 4 June 2018 from 3:00-4:15 pm. Dr. Rixe’s comments will include that BXQ-350 met its Phase I Safety endpoint with no significant DLT or SAE attributed to drug at the highest planned dose. In addition, it was observed that BXQ-350 showed promising clinical activity in heavily pre-treated patients with recurrent brain cancer and advanced solid tumors.

The following three abstracts will be included online in the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting Proceedings, a Journal of Clinical Oncology supplement, publicly released on May 16, 2018.

Absence of Indicators of Hypercoagulability and Anti-Phospholipid Syndrome in BXQ-350 First in Human Study

Therapeutic BXQ-350 nanovesicles, comprised of a lysosomal activator protein and a phosphor- lipid, did not cause anti-phospholipid syndrome (APS) or clinically significant hypercoagulability in humans.

Allometric Scaling of Preclinical Pharmacokinetic and Toxicokinetic Parameters to Predict Clinical Pharmacokinetics of BXQ-350 Saposin C Protein-Phosphatidylserine Nanovesicles

Allometric scaling of animal PK/TK data provided reasonable estimates of human PK and exposure for BXQ-350 and can be expected to have good predictive utility for extrapolating drug dose and pharmacokinetic parameters.

Combined Effect of Gemcitabine (GEM) and SapC-DOPS Nanovesicles on Pancreatic Ductal Adenocarcinoma (PDAC) in Mice

The combination of Gemcitabine and SapC-DOPS demonstrated enhanced antitumor activity in Pancreatic Ductal Adenocarcinoma (PDAC) in mice.

"These abstracts highlight the excitement we have on the potential of BXQ-350 to treat brain and multiple solid tumors; and potentially opening new avenues to treat CNS tumors" stated Dr. Ray Takigiku, Founder and CEO of Bexion.

"The University of New Mexico Comprehensive Cancer Center is pleased to take part in these Phase 1A clinical trials," said Rixe, who is the Principal Investigator at that site and author of the Phase I protocol. "I am honored to present the preliminary results to the scientific community on Bexion’s BXQ-350 and share these exciting new developments."

About BXQ-350

BXQ-350 is a unique formulation of a synthetically produced, human lysosomal protein, Saposin C (sphingolipid activator protein, or SapC), and the phospholipid dioleoylphosphatidylserine (DOPS).

BIOGEN TO PRESENT AT THE BERNSTEIN 34TH ANNUAL STRATEGIC DECISIONS CONFERENCE

On May 22, 2018 Biogen Inc. (NASDAQ: BIIB) reported that it will present at the Bernstein 34th Annual Strategic Decisions Conference (Press release, Biogen, MAY 22, 2018, View Source [SID1234526855]). The webcast will be live on Wednesday, May 30, 2018 at 9:00 a.m. ET. To access the live webcast, please visit Biogen’s Investors section at www.biogen.com/investors. An archived version of the webcast will be available following the presentation.

Genoscience Pharma extends its first clinical trial of GN561 in patients with advanced liver cancers to France

On May 22, 2018 Genoscience Pharma, a clinical-stage biotechnology company dedicated to discovering and developing anticancer drugs, reported the extension to France of its first-in-human Phase 1b/2a clinical study using the oral small molecule GNS561 in advanced liver cancers (cholangiocarcinoma and hepatocellular carcinoma) (Press release, GenoScience, MAY 22, 2018, View Source [SID1234526852]). GNS561 received an IND for a two-year international clinical trial involving up to 50 patients with liver cancer. It is small molecule, administered orally, with a new mechanism of action which works primarily by dysregulating zinc homeostasis in cancer cells and by inducing cancer cell death.

This international Phase 1/2a study, which began in April 2018 at the Jules Bordet Institute in Brussels, Belgium, will be performed in several European countries and the United States. It will evaluate the safety, activity, pharmacokinetic and pharmacodynamic properties of escalating doses of GNS561. Professor Ghassan Abu Alfa of Memorial Sloan Kettering in New York is co-principal investigator in the United States. Professor Ahmad Awada, head of the Department of Medical Oncology at the Jules Bordet Institute is the lead investigator in Belgium. The French study is led by Professor Philippe Merle, head of the Medical Oncology Department and principal investigator at Croix Rousse Hospital, Lyon, France.

Up to 36 patients will be enrolled in six cohorts during the escalation phase. Additional patients will be included in the continuous treatment phase to obtain a total of 20 evaluable subjects at the recommended dose.

"This approval from the French regulatory authorities (ANSM) for our clinical program represents a paradigm shift for our company. It expands our international clinical capacity and offers the opportunity to investigate GNS561’s potential for patients in France," said Professor Philippe Halfon, president and CEO of Genoscience Pharma.

"We are pleased that our clinical program was quickly approved by the regulatory authorities in Belgium and France and by the institutional review boards and ethics committees in both countries. The first cohort of patients having been initiated in Belgium, we are now excited to continue our international evaluation of GNS561 by opening new centers in France. The enrollment and treatment of patients with advanced cholangiocarcinoma represents a new milestone for Genoscience Pharma," said Professor Eric Raymond, chief medical officer.

"We are excited to be enrolling our first patient with GNS561. The mechanism of action of this novel anticancer agent offers great promise. We are hopeful that GNS561 will prove to be a significant and effective weapon against liver cancer, specifically for patients with cholangiocarcinoma for whom there are limited options beyond gemcitabine-platinum based therapy," said Professor Philippe Merle, principal investigator.

About Cholangiocarcinoma
Cholangiocarcinoma (CCAs) is a heterogeneous group of bile duct cancers that arise from cholangiocytes that line the biliary tree. CCAs are classified based on their anatomic location, as follows: (1) intrahepatic CCA (iCCA), (2) perihilar CCA (pCCA) or (3) distal CCA (dCCA). iCCA represents 15% of CCA and is the second most common primary hepatic cancer, after hepatocellular carcinoma, with about 12,000 new cases every year in the US and in five combined European countries (France, UK, Italy, Germany, Spain, Belgium). In past decades, differing from overall cancer trends, iCCA incidence has more than doubled worldwide and its mortality rates have been escalating with a 39% increase. It is predicted to keep dramatically progressing due to a sedentary lifestyle, exposure to chemicals and an ageing population. Due to the late appearance of symptoms and late diagnosis, the tumour is unresectable in 60 to 70% of cases; patients are only eligible for chemotherapy.
Systemic chemotherapy options are critically limited: the standard practice is the first-line use of platinum and gemcitabine combinations, which leads to on average only a moderate overall survival benefit of 11.7 months. To date, despite numerous studies, no second-line treatment is recommended in clinical guidelines as no benefit from the further use of chemotherapy, targeted therapy and immunotherapy was observed.

About GNS561
GNS561 is a novel Solute Carrier Transporter (SLCT) inhibitor demonstrating potent antitumor activity against a range of human cancer cell lines, including HCC. It also shows activity in cell lines resistant to current standard-of-care treatment options for HCC. GNS561 is an orally bioavailable compound initially being developed for the treatment of
primary liver cancer, including advanced HCC. It is also being investigated preclinically in other solid tumors.

Approval of UCART123 Amendment in AML to Accelerate Clinical Development

On May 22, 2018 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported the approval of an amendment to the protocol for the Phase 1 clinical trial of Cellectis’ UCART123 product candidate in patients with acute myeloid leukemia (AML) (Press release, Cellectis, MAY 22, 2018, file:///C:/Users/LENOVO/Downloads/20180522_PR_UCART123_Protocol_Amendment_addendum%20(1).pdf [SID1234526851]).

The main changes to the protocol include:

Dose level 1 to be administered increases from 6.25×104 to 2.5×105 UCART123 cells per kilogram. Dose levels 2 and 3 are now respectively at 6.25×105 and 5.05×106. Dose level -1 is now at 1.25×105. The product’s safety and tolerability profile allowed Cellectis to increase dose levels with a capping at 80kg equivalent.
The dose limiting toxicities (DLT) observation period decreases from 42 to 28 days post-UCART123 infusion, except for patients with aplastic bone marrow at Day 28 for whom the DLT observation period remains 42 days.
The time interval between the first and the second patient for UCART123 infusion at each new dose level tested shortens from 42 days to 28 days (42 days in case of aplastic anemia) then to 14 days for subsequent patients.
A potential second UCART123 infusion is implemented.
In addition, a new AML clinical center has been opened at MD Anderson Cancer Center in Houston, Texas, aiming at increasing the patient enrollment pace. The study is led by Prof. Hagop Kantarjian, MD, Department Chair, Department of Leukemia, Division of Cancer Medicine, and Dr. Naveen Pemmaraju, MD, Assistant Professor, being Principal Investigator.

"This amendment approval for Cellectis’ UCART123 protocol is an important step in the progression of our study, and opening another clinical site at MD Anderson – one of the world’s most premier cancer centers – puts the Company on solid ground to help as many AML patients as possible with this innovative new therapy," said Prof. Stéphane Depil, Senior Vice President, R&D, and Chief Medical Officer at Cellectis. "Off-the-shelf gene editing immunotherapy is continuing to revolutionize the landscape of modern medicine, and we hope that this approach leads to a lifesaving treatment for AML patients in the near future."

"As Cellectis has been working very closely with the concerned parties to review the details of UCART123 study to date, we are eager to hit the ground running with the new protocol in an effort to find a truly effective treatment for AML patients with high unmet medical needs," added Stéphan Reynier, Chief Regulatory and Compliance Officer at Cellectis. "We look forward to obtaining additional data so that we can address such a rare and devastating disease."

The FDA review period for this protocol amendment has passed and Cellectis obtained IRB’s approval.

More information about this trial is available at ClinicalTrials.gov.

About UCART123 clinical trial

Our first wholly controlled product candidate, UCART123, is a gene edited T-cell investigational drug that targets CD123, an antigen expressed at the surface of leukemic cells in AML. Cellectis received in February 2017 an Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) to conduct Phase 1 clinical trial with UCART123 in patients with AML. This marks the first allogeneic, "off-the-shelf" gene-edited CAR T-cell product candidate that the FDA has approved for clinical trial.

UCART123 clinical trial in AML is a Phase 1, open label dose-escalation and dose-expansion study to evaluate the safety, expansion, persistence and clinical activity of UCART123 (allogeneic engineered T-cells expressing anti-CD123 chimeric antigen receptor), administered in patients with relapsed/refractory AML, and patients with newly diagnosed high-risk AML.

The clinical research is coordinated by principal investigator Prof. Gail J. Roboz, MD, at Weill Cornell, Professor of Medicine at Weill Cornell Medicine and Director of the Clinical and Translational Leukemia Programs at Weill Cornell Medicine and NewYork-Presbyterian.

AML is a devastating clonal hematopoietic stem cell neoplasm that is characterized by uncontrolled proliferation and accumulation of leukemic blasts in bone marrow, peripheral blood and, occasionally, in other tissues. These cells disrupt normal hematopoiesis and rapidly cause bone marrow failure and death. In the U.S. alone, there are in 2017 an estimated 21,000 new AML cases per year, with 10,000 estimated deaths per year

About UCART123 clinical trial
Our first wholly controlled product candidate, UCART123, is a gene edited T-cell investigational drug that targets CD123, an antigen expressed at the surface of leukemic cells in AML. Cellectis received in February 2017 an Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) to conduct Phase 1 clinical trial with UCART123 in patients with AML. This marks the first allogeneic, "off-the-shelf"
gene-edited CAR T-cell product candidate that the FDA has approved for clinical trial.

UCART123 clinical trial in AML is a Phase 1, open label dose-escalation and doseexpansion study to evaluate the safety, expansion, persistence and clinical activity of UCART123 (allogeneic engineered T-cells expressing anti-CD123 chimeric antigen receptor), administered in patients with relapsed/refractory AML, and patients with newly
diagnosed high-risk AML.

AML is a devastating clonal hematopoietic stem cell neoplasm that is characterized by uncontrolled proliferation and accumulation of leukemic blasts in bone marrow, peripheral blood and, occasionally, in other tissues. These cells disrupt normal hematopoiesis and rapidly cause bone marrow failure and death. In the U.S. alone, there
are in 2017 an estimated 21,000 new AML cases per year, with 10,000 estimated deaths per year.