On April 20, 2016 The University of Chicago and AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported that they have entered into a five-year collaboration agreement designed to improve the pace of discovery and advance medical research in oncology at both organizations (Press release, AbbVie, APR 20, 2016, View Source [SID:1234511313]). Schedule your 30 min Free 1stOncology Demo! The joint strategic research agreement between AbbVie and the University of Chicago is designed to encourage and strengthen collaboration among researchers. Initially, both organizations will work together to advance research in several areas of oncology, which could include, among others, breast, lung, prostate, colorectal and hematological cancer. Research projects are chosen by a joint steering committee, comprised of representatives from each organization. AbbVie also gains an option for an exclusive license to certain University of Chicago discoveries made under the agreement.
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"University of Chicago researchers and clinicians have worked closely with AbbVie scientists in areas such as immunology and oncology for some time," said Kenneth S. Polonsky, MD, executive vice president for medical affairs at the University of Chicago and dean of the Biological Sciences Division and Pritzker School of Medicine. "This agreement adds depth to that established and productive collaboration. The increased level of interaction should speed progress in medical care, beginning with cancer patients."
As part of the agreement, AbbVie will provide funding for the collaboration that may be used for purposes including preclinical research, clinical trials and possible future programs at the University resulting from this partnership. The overall collaborative efforts will provide University of Chicago physicians and scientists with the opportunity to participate in AbbVie-sponsored clinical trials, access to new therapies developed by AbbVie for use in preclinical research funded under the collaboration, as well as opportunities to work closely with AbbVie’s research and development teams to promote scientific knowledge exchange.
"Advancements in oncology – both at the basic science and clinical levels – are happening faster and more broadly every day," said Gary Gordon, M.D., Ph.D., vice president, oncology clinical development, AbbVie. "Collaborating closely with the scientists and clinicians at the University of Chicago allows us to expand our own research efforts even further to benefit patients."
As part of the collaborative agreement, researchers from the University of Chicago and AbbVie will participate in an annual symposium that brings together scientists from both institutions to discuss research and evaluate potential new projects.
"This is a wonderful opportunity for our investigators to join forces with a leader in oncology and new drug development, accelerate the pace of discovery and deliver clinical benefits to our patients," said cancer specialist Everett Vokes, MD, professor and chairman of medicine at the University of Chicago. "This will support pre-clinical research, give our physician-scientists earlier access to drugs in the AbbVie pipeline and lay the groundwork for further interaction and collaboration."
AbbVie also holds a membership to the Chicago Innovation Exchange, a hub for multidisciplinary collaborations and support for business startup activities and an observer seat at meetings of the University of Chicago Innovation Fund Advisory Committee, which provides guidance to the Innovation Fund, a $20 million investment fund focusing on commercializing early stage research and supporting emerging companies at the University. The Innovation Fund is managed by the Chicago Innovation Exchange in partnership with UChicagoTech and the Polsky Center for Entrepreneurship & Innovation.
Collaborative efforts also provide AbbVie researchers with access to data commons technology developed by the Center for Data Intensive Science at the University of Chicago and the core technical team that is developing the technology. This novel platform powers several large-scale resources for the research community, including the National Cancer Institute Genomic Data Commons – one of the world’s largest storage, analysis and distribution systems for cancer genomics data.
Author: [email protected]
AbbVie and argenx to Collaborate on ARGX-115 Against Novel Immuno-Oncology Target
On April 21, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, and argenx (Euronext Brussels: ARGX), a clinical-stage biopharmaceutical company focused on creating and developing differentiated therapeutic antibodies to treat cancer and severe autoimmune diseases reported that they will collaborate to develop and commercialize ARGX-115 (Press release, AbbVie, APR 20, 2016, View Source [SID:1234511222]). Schedule your 30 min Free 1stOncology Demo! ARGX-115 is argenx’ preclinical-stage human antibody program targeting the novel immuno-oncology target GARP, a protein believed to contribute to immuno-suppressive effects of T-cells.
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"ARGX-115 has been developed in collaboration with an outstanding team of academics at the de Duve Institute / Université Catholique de Louvain through our Innovative Access Program, which gives argenx rights to novel, exciting targets in our areas of therapeutic focus. We believe ARGX-115 has the potential to advance immuno-oncology by selectively targeting tumor immune escape pathways," said Tim van Hauwermeiren, Chief Executive Officer of argenx. "We are proud to develop and commercialize ARGX-115 through collaboration with AbbVie, a global leader in oncology. In addition to the attractive financial elements of this transaction, our shared interest in the commercial potential of ARGX-115, including the right to co-promote the drug in Europe, makes this a highly strategic collaboration for argenx."
"The ability to modulate the body’s own immune system to fight cancer is one of the most promising scientific advancements over the past decade," said Anil Singhal, Vice President, Early Oncology Development, AbbVie. "We believe that the ARGX-115 program is a unique opportunity to explore the potential to block certain immune-suppressive pathways that allow cancers to grow."
Under the terms of the agreement, argenx will conduct research and development through IND-enabling studies. Upon successful completion of these studies, AbbVie may exercise an exclusive option to license the ARGX-115 program and assume responsibility for further clinical development and commercialization. argenx will receive an upfront payment of $40 million from AbbVie for the exclusive option to license ARGX-115 and near-term preclinical milestones of $20 million. argenx is also eligible to receive additional development, regulatory and commercial payments up to $625 million upon achievement of pre-determined milestones as well as tiered, up to double-digit royalties on net sales upon commercialization. argenx has the right to co-promote ARGX-115-based products in the European Union and Swiss Economic Area and combine the product with its own future immuno-oncology programs. Should AbbVie not exercise its option to license ARGX-115, argenx retains the right to pursue development of ARGX-115 alone.
In addition to the ARGX-115 program, and upon reaching a predetermined preclinical stage milestone, AbbVie will fund further GARP-related research by argenx for an initial period of two years. AbbVie will have the right to license additional therapeutic programs emerging from this research, for which argenx could receive associated milestone and royalty payments.
About ARGX-115/GARP
Tumors grow and progress as they escape from immune surveillance, owing to their ability to suppress the immune system by co-opting different immunosuppressive cells such as regulatory T-cells (Tregs), which can inhibit other immune effector cells through the production of active TGF-β. The membrane protein GARP play a key role in the regulation of production of active TGF-β by Tregs. Preclinical studies completed at de Duve Institute/UCL/WELBIO show ARGX-115 can inhibit the immunosuppressive activity of human Tregs by binding to GARP-inactive TGF-β complex and preventing release of active TGF-β.
ARGX-115 was discovered under argenx’ Innovative Access Program with the de Duve Institute / Université Catholique de Louvain /WELBIO.
About the Innovative Access Program
Through the Innovative Access Program argenx collaborates closely with academic experts, bringing our cutting edge antibody discovery technologies to the heart of novel target research. The extraordinary diversity of argenx’ SIMPLE AntibodyTM immune repertoires streamlines target validation, transforming novel proteins into next generation therapeutic antibody programs.
Immune Design Presents New Preclinical Data on Advances of Two Separate Intratumoral Approaches at the American Association for Cancer Research (AACR) Annual Meeting 2016
On April 20, 2016 Immune Design (Nasdaq:IMDZ), a clinical-stage immunotherapy company focused on oncology, reported the presentation of new preclinical data demonstrating broad anti-tumor activity of its ZVexTM platform and further evidence of the anti-tumor activity of G100, both via intratumoral administration (Press release, Immune Design, APR 20, 2016, View Source [SID:1234511120]). Results were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans. Schedule your 30 min Free 1stOncology Demo! "These AACR (Free AACR Whitepaper) data highlight the multi-faceted approaches that Immune Design is employing to generate a therapeutic anti-tumor immune response," said Jan ter Meulen, MD, PhD, Chief Scientific Officer at Immune Design. "The results presented support for the first time the potential intratumoral applicability of Immune Design’s dendritic-cell targeting platform, ZVex, beyond its current use to generate an antigen-specific immune response via systemic administration. Moreover, we presented additional data supporting the ongoing clinical development of G100 as a novel approach to intratumoral immunization."
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Immune Design presented data describing the intratumoral administration of a ZVex Interleukin-12 (IL-12) vector to generate localized, intratumoral expression of IL-12. IL-12 is one of the most potent modulators of innate and adaptive immune response, but its use in the clinical setting has been limited due to toxicity when administered systemically. Results presented demonstrate strong local and systemic anti-tumor efficacy of the ZVex/IL-12 across multiple pre-clinical tumor models, including synergy when co-administrated with anti-CTLA-4 and GLA, Immune Design’s synthetic TLR4 agonist, Glucopyranosyl Lipid A, the core of Immune Design’s GLAASTM platform. The AACR (Free AACR Whitepaper) presentation was titled "Intratumoral expression of IL-12 from a dendritic cell-targeting chimeric lentiviral vector from the ZVex platform cures established tumors in multiple models and induces systemic anti-tumor responses" (Abstract #4884).
In addition, Immune Design presented data highlighting the ability of its G100 product candidate, comprised of GLA in a stable emulsion, to modulate the tumor microenvironment and trigger local and systemic immune responses following its direct injection in a murine lymphoma model. G100 induced broad pro-inflammatory cytokine and chemokine responses, while also upregulating activating genes in immune cells, leading to the switch from a "cold" to a "hot" tumor state. In addition, the upregulation of checkpoints such as PD-L1 in the G100-treated tumors suggests potential synergy with immune checkpoint inhibitors. These data support IMDZ’s ongoing trial of G100 in follicular non-Hodgkin lymphoma in combination with local radiation therapy and KEYTRUDA (pembrolizumab), further described below. The AACR (Free AACR Whitepaper) presentation was titled "Intratumoral Injection of G100 (TLR4 agonist Glycopyranosyl lipid A) modulates tumor microenvironment and induces CD8 T cell-dependent, systemic anti-tumor immunity" (Abstract #4885).
About ZVex
ZVex is Immune Design’s discovery platform designed to activate and expand the immune system’s natural ability to create tumor-specific cytotoxic T cells (CTLs) in vivo. The ZVex delivery system uses a re-engineered virus to carry genetic information of a tumor antigen selectively to dendritic cells (DCs) in the skin or lymph nodes. This ultimately results in the creation of CTLs designed to kill tumor cells bearing that same specific tumor antigen. ZVex is also designed to carry the genetic information for, and therefore potentially cause dendritic cells to express, multiple antigens and/or selected epitopes of interest (including neoantigens), as well as cytokines or other immunomodulatory molecules.
About G100
G100 is a product candidate generated from the company’s GLAASTM discovery platform, and includes a specific formulation of Glucopyranosyl Lipid A (GLA), a synthetic, toll-like receptor-4 (TLR-4) agonist. G100 is part of Immune Design’s intratumoral immune activation, or ‘Endogenous Antigen,’ approach to treating cancer, which leverages the activation of dendritic and other immune cells in the tumor microenvironment to potentially create a robust immune response against the tumor’s preexisting diverse set of antigens. Preclinical and clinical data have demonstrated the ability of G100 to activate dendritic cells in tumors and to increase antigen-dependent systemic humoral and cellular Th1 immune responses. A Phase 1 study of G100 in patients with Merkel cell carcinoma (MCC) completed enrollment and preliminary data presented on the first eight patients demonstrated that G100 had an acceptable safety profile and resulted in an objective response rate (ORR) of 50% per protocol. The data presented today represent the potential expansion of the intratumoral immune activation approach to include the ZVex platform, as well.
G100 Study in Patients with Follicular Non-Hodgkin’s Lymphoma
A Phase 1b/2 study evaluating intratumoral G100 in patients with follicular non-Hodgkin’s lymphoma is currently enrolling patients (NCT: 02501473). The study is evaluating the intratumoral administration of G100 with intravenous administration of KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with follicular non-Hodgkin’s lymphoma receiving local radiation, pursuant to a collaboration with Merck. The study is designed to evaluate G100 plus local radiation and KEYTRUDA compared to G100 plus local radiation alone. In addition to an evaluation of the safety of the combination, the study will assess the response in both injected and non-injected lesions.
SignalRx Presents at AACR Annual Meeting on First-In-Class Dual PI3K/BRD4 Inhibitors for Treating Cancer
On April 19, 2016 SignalRx Pharmaceuticals Inc., focused on developing more effective oncology drugs through molecular design imparting multiple target-selected inhibition, reported the presentation of scientific data on the company’s dual small-molecule PI3K/BRD4 inhibitor program in oncology (Press release, SignalRx, APR 19, 2016, http://www.ireachcontent.com/news-releases/signalrx-presents-at-aacr-annual-meeting-on-first-in-class-dual-pi3kbrd4-inhibitors-for-treating-cancer-576189881.html [SID1234517422]). The presentation by Dr. Donald L. Durden, MD, PhD, senior scientific advisor for SignalRx, was made at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, LA.
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The presentation highlighted advancements in the development of SF2523, SF2535 and SF2558HA, all single small molecules that inhibit both PI3 kinase (PI3K) and the new epigenetic cancer target BRD4. Key breakthroughs are:
New crystal structures obtained for SF2523, SF2535 and SF2558HA with BRD4 protein providing insights on key dual inhibitor binding interactions.
First-time proof of MYC inhibition by enhancing MYC degradation via PI3K inhibition AND blocking MYC production via MYC transcription inhibition (BRD4 inhibition).
SF2523 exhibits desired in vivo anti-tumor effects with no toxicity in several mouse cancer models.
Inhibition of PI3K-gamma and delta isoforms by SF2523 function as checkpoint inhibitors and enhance immune-therapeutics.
BRD4 inhibition blocks tumor-specific super-enhancers activating the innate and adaptive immune response providing a novel strategy to treat cancer.
The company also demonstrated that SF2523 is safer to normal cells over the combination of single PI3K and BRD4 inhibitors making SF2523 an attractive anti-cancer candidate that can potentially overcome traditional toxicity issues associated with most combinations of oncology drugs.
SignalRx is also announcing that it is seeking a partner to accelerate the development of these novel small molecules into first-in-man clinical trials based on the promising profile of its PI3K/BRD4 inhibitors shown so far. Since these are single molecules with a single PK/PD and toxicity profile, there is a great opportunity to develop them as single therapeutics and streamline their development in combination therapies focused on companion diagnostics built around synthetic lethality discoveries in human cancers, e.g., kinome adaptation mediated by BRD4.
Galena Biopharma Presents GALE-301/GALE-302 Clinical Booster Data at the American Association for Cancer Research (AACR) Annual Meeting
On April 19, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of targeted oncology therapeutics that address major unmet medical needs, reported that data from the booster phase of the Company’s GALE-301/GALE-302 Phase 1/2a clinical trial was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Galena Biopharma, APR 19, 2016, View Source [SID:SID1234515197]).
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The poster, entitled, "Comparing an attenuated booster (E39’) vs. E39 booster to potentiate the clinical benefit of the folate binding protein (FBP)-derived vaccine (E39 + GM-CSF) in a phase I/IIa trial to prevent recurrence in endometrial (EC) and ovarian cancer (OC) patients," was presented today by Dr. Doreen Jackson from the San Antonio Military Medical Center. In the Phase 2a portion of the trial, patients were randomized to two different boosters: E39 (GALE-301), versus E39’ (GALE-302). The purpose of the study was to evaluate the immune responses and determine which booster, if either, would provide a sustained immune response and potentially longer disease free survival (DFS) rates.
The use of the wildtype peptide (GALE-301/E39) demonstrated the same tolerable safety profile as the attenuated peptide (GALE-302/E39’) with only Grade 1 local reactions and minimal Grade 2 toxicities. Importantly, the percentage of patients who received two booster inoculations and remained disease free was significantly better in the drug treatment arm, versus the control arm (p=0.02), regardless of which booster was used. At median follow up of 16 months, the boosters demonstrated equivalent efficacy after two booster inoculations with an estimated, two-year DFS rate of 66.7% (GALE-301 n=7, GALE-302 n=7) in each booster arm versus 36% (n=22) in the control arm.
"In our GALE-301 Phase 2a trial, we randomized patients to determine an optimal boosting strategy and to see if there was an observable difference between boosting patients with GALE-301 versus the attenuated version of the peptide, GALE-302," stated Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer. "The results show that both boosters were effective with no measurable difference between them, and we will consider this as we continue to evaluate the best path forward for our compounds targeting FBP. The primary analysis of this trial will be presented at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting in June."
A total of 51 patients were enrolled in the Phase 1/2a trial with 29 HLA-A2-positive patients in the vaccine group (VG) and 22 HLA-A2-negative patients in the control group (CG). Six monthly intradermal inoculations of GALE-301 plus 250mcg GM-CSF were administered to the VG to complete the primary vaccine series (PVS). Patients were then randomized to receive two booster inoculations of 500mcg of GALE-301 or GALE-302 plus 250mcg GM-CSF at six and twelve months post-PVS. Seventeen patients continued onto the booster series and were randomized with 14 receiving two boosters. There were no significant demographic or baseline differences between groups, no difference in toxicities were observed, and there were no Grade 3 or 4 toxicities in either group.
About GALE-301 and GALE-302
GALE-301 and GALE-302 are cancer immunotherapies that consist of a peptide derived from Folate Binding Protein (FBP) combined with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF) for the prevention of cancer recurrence in the adjuvant setting. GALE-301 is the E39 peptide, while GALE-302 is an attenuated version of this peptide, known as E39’. FBP is a well-validated therapeutic target that is highly over-expressed in ovarian, endometrial and breast cancers, and is the source of immunogenic peptides that can stimulate cytotoxic T lymphocytes (CTLs) to recognize and destroy FBP-expressing cancer cells. Two trials are ongoing with FBP peptides in gynecological cancers: the GALE-301 Phase 2a portion of the Phase 1/2a clinical trial is ongoing in ovarian and endometrial adenocarcinomas (ClinicalTrials.gov Identifier: NCT01580696); the GALE-301 plus GALE-302 Phase 1b clinical trial is ongoing in breast and ovarian cancers (ClinicalTrials.gov Identifier: NCT02019524).
About Ovarian/Endometrial Cancers
New cases of ovarian cancer occur at an annual rate of 12.1 per 100,000 women in the U.S., with an estimated 21,290 cases for 2015. Although ovarian cancer represents about 1.3% of all cancers, it represents about 2.4% of all cancer deaths, or an estimated 14,180 deaths in 2015. Approximately 1.3% of women will be diagnosed with ovarian cancer at some point during their lifetime (2010 – 2012 data). The prevalence of ovarian cancer in the U.S. is about 192,000 women, and the five-year survivorship for women with ovarian cancer is 45.6%.
Due to the lack of specific symptoms, the majority of ovarian cancer patients are diagnosed at later stages of the disease, with an estimated 75% of women presenting with advanced-stage (III or IV) disease. These patients have their tumors routinely surgically debulked to minimal residual disease, and then are treated with platinum- and/or taxane-based chemotherapy. While many patients respond to this treatment regimen and become clinically free-of-disease, the majority of these patients will relapse. Depending upon their level of residual disease, the risk for recurrence after completion of primary therapy ranges from 60% to 85%. Unfortunately for these women, once the disease recurs, treatment options are limited and the disease remains incurable.
New cases of endometrial cancer occur at an annual rate of 25.1 per 100,000 women in the U.S., with an estimated 54,870 cases for 2015. Although endometrial cancer represents about 3.3% of all cancers, it represents about 1.7% of all cancer deaths, or an estimated 10,170 deaths in 2015. Approximately 2.8% of women will be diagnosed with endometrial cancer at some point during their lifetime (2010 – 2012 data). The prevalence of endometrial cancer in the U.S. is about 620,000 women, and the five-year survivorship for women with endometrial cancer is 81.7%.