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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 [SID1234527257]).

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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.

CytomX Therapeutics Announces FDA Clearance of Investigational New Drug Application for CX-2029, a CD71-Directed Probody Therapeutic

On May 22, 2018 CytomX Therapeutics, Inc. (Nasdaq:CTMX) a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, reported that the U.S. Food and Drug Administration has cleared its Investigational New Drug (IND) application for CX-2029, a first-in-class CD71-directed Probody drug conjugate being co-developed by CytomX and its partner AbbVie (Press release, CytomX Therapeutics, MAY 22, 2018, View Source [SID1234527069]). CD71, also known as the transferrin receptor 1, is a highly expressed protein present in a number of solid and hematologic cancers that possess attractive molecular properties for the efficient delivery of cytotoxic payloads to tumor cells. The achievement of this milestone triggers a $25 million payment to CytomX from AbbVie.

"CD71 has long been considered a high potential but challenging target for antibody drug conjugates given its high expression in tumors but ubiquitous expression in normal tissues. However, we see CD71 is an attractive candidate for a Probody drug conjugate approach, since our technology can potentially localize treatment directly to tumor tissue," said Sean McCarthy, D.Phil., president and chief executive officer of CytomX Therapeutics. "With CX-2029 now clear to advance into Phase 1, CytomX and our partners now have four clinical-stage Probody programs with anticipated initial data readouts later this year from our two wholly-owned programs, CX-072 and CX-2009. It is also noteworthy that this milestone comes just two years following the signing of our agreements with AbbVie, reflecting the efficiency of this collaboration."

"The IND clearance of CX-2029 marks an important step in our partnership with CytomX," said Steve Davidsen, Ph.D., vice president, oncology drug discovery, AbbVie. "Our partnership has the potential to advance emerging areas of science with the hope of providing additional options for people living with cancer."

About the Collaboration
AbbVie and CytomX are co-developing CX-2029, a Probody drug conjugate against CD71, with CytomX leading pre-clinical and early clinical development. AbbVie will lead later development and commercialization, with global late-stage development costs shared between the two companies. CytomX is eligible to receive up to $470 million in development, regulatory and commercial milestones, pending the achievement of pre-determined outcomes. AbbVie will lead global commercial activities with CytomX eligible to receive a profit share in the U.S. and tiered double-digit royalties on net product sales outside of the U.S. CytomX retains an option to co-promote in the U.S.

AbbVie also received exclusive worldwide rights to develop and commercialize Probody drug conjugates against up to two additional, undisclosed targets. Should AbbVie ultimately pursue these targets, CytomX is eligible to receive additional milestone and royalty payments per target on any resulting products.

Aileron Therapeutics Announces Publication of ALRN-6924 Nonclinical Data in T-cell Lymphomas by Researchers at Dana-Farber Cancer Institute

On May 22, 2018 Aileron Therapeutics (Nasdaq:ALRN), the leader in the field of stapled peptide therapeutics for cancers and other diseases, reported the publication of nonclinical results in Nature Communications demonstrating the anti-cancer potential of ALRN-6924 in models of T-cell lymphoma (TCL) (Press release, Aileron Therapeutics, MAY 22, 2018, View Source;p=RssLanding&cat=news&id=2350149 [SID1234526844]). ALRN-6924 is designed to reactivate p53-mediated tumor suppression by targeting the two primary p53 suppressor proteins, MDM2 and MDMX. ALRN-6924 is being evaluated in Phase 1 and Phase 2 clinical trials in patients with peripheral T-cell lymphoma (PTCL) and acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

As reported in the study, ALRN-6924 showed potent in vitro activity and superior in vivo activity across eight different patient-derived xenograft models, compared to the standard-of-care agent. Separately, it was noted in the publication that ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from preclinical models.

"These data independently confirm previous preclinical and clinical results that the stapled peptide ALRN-6924 possesses anti-cancer activity based on a novel mechanism of action—the dual inhibition of MDMX and MDM2, instead of the inhibition of MDM2 alone. In addition, these data further demonstrate that stapled peptides represent a new treatment modality with unique properties that enable the targeting of previously ‘undruggable’ targets," said Manuel Aivado, MD, PhD, Chief Medical and Scientific Officer of Aileron.

"We were very gratified by these results," said David Weinstock, MD, Principal Investigator and Associate Professor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School. "The xenograft models we created and tested provide significant insight into the activity of a drug like ALRN-6924 and how well it will work in patients. We’re excited to see this drug move forward in clinical trials and hope to better understand the best way to use it as either a single agent or in combinations."

The study in Nature Communications is titled, "Targetable Vulnerabilities in T- and NK-cell Lymphomas Identified Through Preclinical Models."

About ALRN-6924
ALRN-6924 is a first-in-class product candidate designed to reactivate wild type p53 tumor suppression by disrupting the interactions between the two primary p53 suppressor proteins, MDMX and MDM2. Aileron believes ALRN-6924 is the first and only product candidate in clinical development that can equipotently bind to and disrupt the interaction of MDMX and MDM2 with p53. Based on preclinical data and preliminary evidence of safety and anti-tumor activity in its ongoing clinical trials, there may be a significant opportunity to develop ALRN-6924 as a monotherapy or combination therapy for a wide variety of solid and liquid tumors. ALRN-6924 is currently being evaluated in multiple clinical trials for the treatment of acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS) and peripheral T-cell lymphoma (PTCL). For information about its clinical trials, please visit www.clinicaltrials.gov.

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

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

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).