On June 28, 2016 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer as well as autoimmune disorders and infectious diseases, reported the closing of the global collaboration and license agreement for MGD015 with Janssen Biotech, Inc (Press release, MacroGenics, JUN 28, 2016, View Source [SID:1234513583]). The agreement was announced on May 18, 2016 and was subject to a waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended. Such waiting period has since expired.

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Under the terms of the agreement, MacroGenics will receive a $75 million upfront license fee. Janssen will be responsible for developing MGD015, a product candidate that incorporates MacroGenics’ proprietary Dual-Affinity Re-Targeting, or DART, platform to simultaneously target CD3 and an undisclosed tumor target for the potential treatment of various hematological malignancies and solid tumors. Assuming successful development and commercialization of MGD015, MacroGenics could receive up to an additional $665 million in clinical, regulatory and commercialization milestone payments. If commercialized, MacroGenics would be eligible to receive double-digit royalties on any global net sales and has the option to co-promote MGD015 with Janssen in the U.S. In addition, MacroGenics may elect to fund a portion of late-stage clinical development to receive a profit share in the U.S. and Canada in lieu of royalties with respect to these territories.

About MGD015

MGD015 is designed to redirect T cells, via their CD3 component, to eliminate cells that overexpress an undisclosed antigen in various hematological malignancies and solid tumors. MacroGenics has demonstrated that MGD015 is able to kill these targeted cells both in vitro and in vivo, with high response rates in several mouse tumor xenograft models. In addition, this product candidate and the Company’s other DART molecules that redirect T cells against cancer targets are manufactured using a conventional antibody platform without the complexity of having to genetically modify T cells from individual patients as required by approaches such as chimeric antigen receptor (CAR) T-cells.

On June 28, 2016 Xencor, Inc. (Xencor) (NASDAQ:XNCR) reported that it has entered into a collaboration and license agreement with Novartis to develop and commercialize novel therapeutics, including XmAb14045 expected to begin clinical development for acute myeloid leukemia in 2016; and XmAb13676 also expected to begin clinical development for B-cell malignancies in 2016 (Press release, Xencor, JUN 28, 2016, View Source [SID:1234513582]).

“We are excited to move forward in collaboration with Novartis on the development of XmAb14045 and XmAb13676, while maintaining our rights in the U.S.,” said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. “This opportunity to work with and learn from a world leader in the late-stage development and commercialization of immune-oncology drugs gives us the opportunity to take our lead drugs through clinical development and into commercialization in the U.S. and, with the other molecules to be developed, continues to expand the reach of our technology.”

Under the terms of the agreement, the parties will collaborate and share development costs for the worldwide development of XmAb14045 and XmAb13676, with Xencor maintaining U.S. commercialization rights and Novartis having commercialization rights in the rest of the world. Novartis will receive worldwide rights to Xencor’s bispecific technology to develop and commercialize four additional targets selected by Novartis, one of which Xencor may elect to co-detail in the U.S. The bispecific collaboration will include molecular engineering by Xencor. Additionally, Novartis will receive a worldwide non-exclusive license to use Xencor’s XmAb Fc technologies in up to ten molecules.

Xencor will receive a $150 million upfront payment and is eligible to receive clinical, regulatory and sales milestone payments for successful programs. Xencor is also eligible to receive tiered, low double-digit royalties for sales of XmAb14045 and XmAb13676 outside of the U.S., mid single-digit tiered royalties for worldwide sales of the four proprietary Novartis bi-specific molecules, unless Xencor exercises its right to co-detail one of these molecules and share in the costs and U.S. profit, and low single-digit royalties on Novartis molecules incorporating Xencor’s XmAb Fc technology.

Xencor will discuss this collaboration and licensing agreement among additional items today, Tuesday, June 28, 2016, at the Company’s Analyst Day from 8:30 a.m. – 11:30 a.m. ET in New York City. A live audio webcast of the presentation will be available under the “Events & Presentations” section in the Investors section of the Xencor’s website located at View Source

About Xencor’s XmAb Bispecific Technology

As opposed to traditional monoclonal antibodies that target and bind to a single antigen, bispecific antibodies are designed to elicit multiple biological effects that require simultaneous binding to two different antigen targets. Xencor’s XmAb bispecific Fc domain technology is designed to maintain full-length antibody properties in a bispecific antibody, potentially enabling favorable in vivo half-life and simplified manufacturing.

Efforts at bispecific antibody design are typically frustrated by poor molecular stability, difficulties in production and short in vivo half-life. Xencor has engineered a series of Fc domain variants that spontaneously form stable, heterodimeric bispecific antibodies and that can be made and purified with standard antibody production methods. These bispecific Fc domains are used to generate a broad array of novel drug candidates in a range of molecule formats.

Xencor’s initial bispecific programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3 binding domain). These bispecific antibodies activate T cells at the site of the tumor for highly potent killing of malignant cells. The XmAb Fc domain format allows Xencor to tune the potency of the T-cell killing, potentially improving the tolerability of tumor immunotherapy.

About Xencor’s XmAb Fc Technologies

Xencor’s proprietary XmAb antibody engineering platform creates subtle, precise alterations to the antibody’s Fc domain — the stem of the structure that is responsible for antibodies’ natural immune functions and highly stable structure. These subtle changes elicit dramatically enhanced performance. XmAb Fc domains are plug-and-play and can be substituted into nearly any antibody. The resulting engineered antibodies retain the beneficial stability, pharmacokinetics and ease of development of natural antibodies, and are produced with standard methods for antibody manufacturing. We have created four lead XmAb Fc domains, each enhancing a key property for antibody therapeutics: our Bispecific, Immune Inhibitor, Cytotoxic and Xtend Fc domains.

On June 28, 2016 Xencor, Inc. (Xencor) (NASDAQ:XNCR) reported that it has entered into a collaboration and license agreement with Novartis to develop and commercialize novel therapeutics, including XmAb14045 expected to begin clinical development for acute myeloid leukemia in 2016; and XmAb13676 also expected to begin clinical development for B-cell malignancies in 2016 (Press release, Xencor, JUN 28, 2016, View Source [SID:1234513582]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"We are excited to move forward in collaboration with Novartis on the development of XmAb14045 and XmAb13676, while maintaining our rights in the U.S.," said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. "This opportunity to work with and learn from a world leader in the late-stage development and commercialization of immune-oncology drugs gives us the opportunity to take our lead drugs through clinical development and into commercialization in the U.S. and, with the other molecules to be developed, continues to expand the reach of our technology."

Under the terms of the agreement, the parties will collaborate and share development costs for the worldwide development of XmAb14045 and XmAb13676, with Xencor maintaining U.S. commercialization rights and Novartis having commercialization rights in the rest of the world. Novartis will receive worldwide rights to Xencor’s bispecific technology to develop and commercialize four additional targets selected by Novartis, one of which Xencor may elect to co-detail in the U.S. The bispecific collaboration will include molecular engineering by Xencor. Additionally, Novartis will receive a worldwide non-exclusive license to use Xencor’s XmAb Fc technologies in up to ten molecules.

Xencor will receive a $150 million upfront payment and is eligible to receive clinical, regulatory and sales milestone payments for successful programs. Xencor is also eligible to receive tiered, low double-digit royalties for sales of XmAb14045 and XmAb13676 outside of the U.S., mid single-digit tiered royalties for worldwide sales of the four proprietary Novartis bi-specific molecules, unless Xencor exercises its right to co-detail one of these molecules and share in the costs and U.S. profit, and low single-digit royalties on Novartis molecules incorporating Xencor’s XmAb Fc technology.

Xencor will discuss this collaboration and licensing agreement among additional items today, Tuesday, June 28, 2016, at the Company’s Analyst Day from 8:30 a.m. – 11:30 a.m. ET in New York City. A live audio webcast of the presentation will be available under the "Events & Presentations" section in the Investors section of the Xencor’s website located at View Source

About Xencor’s XmAb Bispecific Technology

As opposed to traditional monoclonal antibodies that target and bind to a single antigen, bispecific antibodies are designed to elicit multiple biological effects that require simultaneous binding to two different antigen targets. Xencor’s XmAb bispecific Fc domain technology is designed to maintain full-length antibody properties in a bispecific antibody, potentially enabling favorable in vivo half-life and simplified manufacturing.

Efforts at bispecific antibody design are typically frustrated by poor molecular stability, difficulties in production and short in vivo half-life. Xencor has engineered a series of Fc domain variants that spontaneously form stable, heterodimeric bispecific antibodies and that can be made and purified with standard antibody production methods. These bispecific Fc domains are used to generate a broad array of novel drug candidates in a range of molecule formats.

Xencor’s initial bispecific programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3 binding domain). These bispecific antibodies activate T cells at the site of the tumor for highly potent killing of malignant cells. The XmAb Fc domain format allows Xencor to tune the potency of the T-cell killing, potentially improving the tolerability of tumor immunotherapy.

About Xencor’s XmAb Fc Technologies

Xencor’s proprietary XmAb antibody engineering platform creates subtle, precise alterations to the antibody’s Fc domain — the stem of the structure that is responsible for antibodies’ natural immune functions and highly stable structure. These subtle changes elicit dramatically enhanced performance. XmAb Fc domains are plug-and-play and can be substituted into nearly any antibody. The resulting engineered antibodies retain the beneficial stability, pharmacokinetics and ease of development of natural antibodies, and are produced with standard methods for antibody manufacturing. We have created four lead XmAb Fc domains, each enhancing a key property for antibody therapeutics: our Bispecific, Immune Inhibitor, Cytotoxic and Xtend Fc domains.

On June 28, 2016 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported the filing of regulatory submissions required to commence a Phase 2a trial for BL-8040 in combination with KEYTRUDA (pembrolizumab) for the treatment of patients with pancreatic cancer (Press release, BioLineRx, JUN 28, 2016, View Source [SID:1234513580]). The study is expected to commence shortly after receipt of regulatory approval, anticipated in the third quarter of 2016.

The Phase 2a study, named the COMBAT study, is an open-label, multicenter, single-arm trial designed to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, in up to 30 subjects with metastatic pancreatic adenocarcinoma. The study is designed to evaluate the clinical response, safety and tolerability of the combination of these therapies as well as multiple pharmacodynamic parameters, including the ability to improve infiltration of T cells into the tumor and their reactivity. It is expected to take place in the US, Israel and additional territories.

In January 2016, BioLineRx entered into a collaboration with MSD, known as Merck in the US and Canada, to support a Phase 2 study investigating BioLineRx’s BL-8040 in combination with KEYTRUDA in patients with metastatic pancreatic cancer. BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells and to be effective at inducing direct tumor cell death. Additional findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the infiltration of anti-tumor T cells into the tumor. Therefore, when combined with KEYTRUDA, which blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells, BL-8040 has the potential to enable activated T cells to better reach tumor cells in the fight against pancreatic cancer.

“We are looking forward to commencing this combination study of our lead oncology product and Merck’s immune checkpoint inhibitor, which marks the entrance of BL-8040 into the exciting and promising field of cancer immunotherapy,” stated Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx. “Over the past few months, we have worked closely with Merck’s clinical team on the design and finalization of the study protocol. We believe that the combination of BL-8040 with KEYTRUDA has the potential to expand the benefit of immunotherapy to cancer types currently resistant to immuno-oncology treatments, such as pancreatic cancer, which represent a significant unmet medical need. Furthermore, we view BL-8040’s inhibition of CXCR4, which effects a change in the protective tumor micro-environment, as potentially synergistic with immune checkpoint inhibitors in additional oncological indications.”

About Pancreatic Cancer

Pancreatic cancers of all types are the seventh most common cause of cancer deaths. According to the American Cancer Society, in 2015, nearly 50,000 were diagnosed with pancreatic cancer and an estimated 40,000 will die from the disease. The most common type of pancreatic cancer is pancreatic adenocarcinoma, which accounts for about 85 percent of cases. These adenocarcinomas start within the part of the pancreas that makes digestive enzymes. There are usually no symptoms in the early stages of the disease and symptoms that are specific enough to suggest the onset of pancreatic cancer typically do not develop until the disease has reached an advanced stage. The five-year survival rate of pancreatic adenocarcinoma is around 7 percent.

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On June 28, 2016 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported the filing of regulatory submissions required to commence a Phase 2a trial for BL-8040 in combination with KEYTRUDA (pembrolizumab) for the treatment of patients with pancreatic cancer (Press release, BioLineRx, JUN 28, 2016, View Source [SID:1234513580]).The study is expected to commence shortly after receipt of regulatory approval, anticipated in the third quarter of 2016.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase 2a study, named the COMBAT study, is an open-label, multicenter, single-arm trial designed to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, in up to 30 subjects with metastatic pancreatic adenocarcinoma. The study is designed to evaluate the clinical response, safety and tolerability of the combination of these therapies as well as multiple pharmacodynamic parameters, including the ability to improve infiltration of T cells into the tumor and their reactivity. It is expected to take place in the US, Israel and additional territories.

In January 2016, BioLineRx entered into a collaboration with MSD, known as Merck in the US and Canada, to support a Phase 2 study investigating BioLineRx’s BL-8040 in combination with KEYTRUDA in patients with metastatic pancreatic cancer. BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells and to be effective at inducing direct tumor cell death. Additional findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the infiltration of anti-tumor T cells into the tumor. Therefore, when combined with KEYTRUDA, which blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells, BL-8040 has the potential to enable activated T cells to better reach tumor cells in the fight against pancreatic cancer.

"We are looking forward to commencing this combination study of our lead oncology product and Merck’s immune checkpoint inhibitor, which marks the entrance of BL-8040 into the exciting and promising field of cancer immunotherapy," stated Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx. "Over the past few months, we have worked closely with Merck’s clinical team on the design and finalization of the study protocol. We believe that the combination of BL-8040 with KEYTRUDA has the potential to expand the benefit of immunotherapy to cancer types currently resistant to immuno-oncology treatments, such as pancreatic cancer, which represent a significant unmet medical need. Furthermore, we view BL-8040’s inhibition of CXCR4, which effects a change in the protective tumor micro-environment, as potentially synergistic with immune checkpoint inhibitors in additional oncological indications."

About Pancreatic Cancer

Pancreatic cancers of all types are the seventh most common cause of cancer deaths. According to the American Cancer Society, in 2015, nearly 50,000 were diagnosed with pancreatic cancer and an estimated 40,000 will die from the disease. The most common type of pancreatic cancer is pancreatic adenocarcinoma, which accounts for about 85 percent of cases. These adenocarcinomas start within the part of the pancreas that makes digestive enzymes. There are usually no symptoms in the early stages of the disease and symptoms that are specific enough to suggest the onset of pancreatic cancer typically do not develop until the disease has reached an advanced stage. The five-year survival rate of pancreatic adenocarcinoma is around 7 percent.

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.