PureTech Health Advances New Program Targeting Immunosuppressive Gamma Delta T Cells and Related Mechanisms

On April 11, 2019 PureTech Health plc ("PureTech Health" or the "Company", LSE: PRTC), an advanced, clinical-stage biopharmaceutical company, reported the launch of a new immuno-oncology program developing monoclonal antibodies to target newly discovered immunosuppressive mechanisms in pancreatic cancer and other solid tumors (Press release, PureTech Health, APR 11, 2017, View Source [SID1234533948]).

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The approach is based on the work of Dr. George Miller, Director of S. Arthur Localio Laboratories and Director of the Cancer Immunology Program at NYU School of Medicine. Part of the body of data supporting this approach was published recently in Nature Medicine and builds upon his work previously published in Cell.

"Most solid, malignant tumors establish an immunosuppressive environment to ward off the body’s natural defenses. Dr. Miller’s work in pancreatic ductal carcinoma has revealed that inflammatory processes drive the immunosuppression through certain gamma delta T cells and macrophages," said Dr. Joseph Bolen, Chief Scientific Officer of PureTech Health. "Our novel approach builds on this finding and selectively disrupts the immunosuppression to potentially have a therapeutic effect on cancer."

This technology, exclusively licensed from the NYU School of Medicine, is being developed in a new subsidiary of PureTech Health called Nybo Therapeutics. Nybo builds on PureTech’s strength in immunology and joins PureTech’s advanced pipeline of immunology and T cell biology programs that includes a Phase IIB immunosenescence program, microbiome-based T cell mediated therapies, and CAR-T therapies.

"Pancreatic cancer is the only major cancer with a five-year survival rate in the single digits, and there has been far too little progress towards meaningful treatments," said Dr. Diane Simeone, Director of the Pancreatic Cancer Center at NYU School of Medicine and a member of Nybo’s Scientific Advisory Board. "Novel therapeutic approaches are important to pursue, and I look forward to helping advance this promising technology."

Dr. Miller commented on this announcement, "I am excited to translate our findings into first-in-class therapies for patients who desperately need new treatment options. Our work on immunosuppressive mechanisms in pancreatic cancer has shed light on new therapeutic approaches that form the foundation for Nybo, and we look forward to a great partnership with PureTech Health with whom to advance these findings."

PureTech Health has gathered a group of leading expert collaborators and advisors around this platform, including:

Erin Adams, Ph.D., is the Joseph Regenstein Professor at the Department of Biochemistry and Molecular Biology, and on the Committees of Immunology and Cancer Biology at the University of Chicago. Dr. Adams’ research is focused on understanding how events at the molecular level allow the immune system to differentiate between self and non-self with particular attention given to nonconventional T cell recognition, such as that of gamma delta T cells. The scientific approach she undertakes to tackle these questions spans multiple levels including genetics, protein biochemistry, structure, biophysics, function and cell biology and imaging. Dr. Adams is one of the pioneer researchers discovering how gamma delta T cells recognize antigens and how this recognition process regulates their activity in various tissues in which they reside.

Elizabeth Jaffee, M.D., currently serves as Deputy Director for the Johns Hopkins Kimmel Cancer Center, Associate Director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy; Associate Director for Translational Research, Co-Director of Gastrointestinal cancer and diseases program, and Co-Director of the Skip Viragh Center for Pancreatic Cancer Clinical Research and Patient Care. Dr. Jaffee is chair and member of the National Cancer Advisory Board, and served as co-chair of the NCI Blue Ribbon Panel for the National Moonshot Initiative. Dr. Jaffee is an active member of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), and has just been named President-Elect of AACR (Free AACR Whitepaper) (2017-2018). She will assume the presidency in April, 2018.

Steven Leach, M.D., is the Director of the David M. Rubenstein Center for Pancreatic Cancer Research of Memorial Sloan-Kettering. Prior to this, Dr. Leach served as Professor of Surgery, Oncology and Cell Biology, and the Paul K. Neumann Professor in Pancreatic Cancer at Johns Hopkins Medicine. Dr. Leach received his undergraduate degree from Princeton University, where he currently serves on the Board of Trustees. He then pursued his MD degree at Emory University, followed by postdoctoral training at Yale University and at M.D. Anderson. Dr. Leach is also the current Chair of the Pancreatic Cancer Action Network’s Scientific and Medical Advisory Board.

George Miller, M.D., is the Director of S. Arthur Localio Laboratories, vice chair for research in NYU, Langone’s Department of Surgery and the leader of Perlmutter Cancer Center’s Immunology Program, as well as the director of the only training program in the country in gastrointestinal oncology that is funded by the National Institutes of Health. In addition to his laboratory research, Dr. Miller is a highly experienced pancreatic and hepatobiliary surgeon with an extensive background in the evaluation and treatment of pancreatic tumors, as well as liver, bile duct cancers.

Diane M. Simeone, M.D., is currently the director of the Pancreatic Cancer Center at the NYU School of Medicine and the Associate Director of Translational Research, Perlmutter Cancer Center, NYU Langone Medical Center. She is the chair-elect of the Scientific and Medical Advisory Board of the Pancreatic Cancer Action Network, one of the country’s leading organizations advancing the battle against the disease through research funding, community engagement and government advocacy. She is a member of the Institute of Medicine of the National Academy of Sciences, serves on the National Cancer Institute’s Pancreatic Cancer Task Force, and previously was president of the Society of University Surgeons and the American Pancreatic Association.

"We will be exploring both pancreatic cancer and other solid tumor types such as colorectal cancer. In addition to monotherapy, Dr. Miller’s work suggests that this approach may enhance the effect of checkpoint inhibitors that have historically not worked in pancreatic cancer opening up the possibility of combination therapy," commented Dr. Aleksandra Filipovic, Therapeutic Lead for Oncology at PureTech.

The underlying research described above has been supported by the NYU School of Medicine’s drug discovery accelerator, the Office of Therapeutics Alliances.

About NYU Office of Therapeutics Alliances and Office of Industrial Liaison
The NYU Office of Therapeutics Alliances (OTA) was created in 2013 to accelerate and de-risk drug discovery projects developed at NYU School of Medicine towards partnerships with investors, biopharma, and non-profits. The NYU Office of Industrial Liaison (OIL) promotes the commercial development of NYU discoveries and actively seeks commercial partners for licensing and research collaborations. Over the past ten years NYU has ranked first among all universities in income from technology licensing. For more information, please visit View Source and View Source

PureTech Health Advances New Program Targeting Immunosuppressive Gamma Delta T Cells and Related Mechanisms

On April 11, 2017 PureTech Health plc ("PureTech Health" or the "Company", LSE: PRTC), an advanced, clinical-stage biopharmaceutical company, reported the launch of a new immuno-oncology program developing monoclonal antibodies to target newly discovered immunosuppressive mechanisms in pancreatic cancer and other solid tumors (Press release, PureTech Health, APR 11, 2017, View Source [SID1234535429]).

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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

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"Pancreatic cancer is the only major cancer with a five-year survival rate in the single digits, and there has been far too little progress towards meaningful treatments"
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The approach is based on the work of Dr. George Miller, Director of S. Arthur Localio Laboratories and Director of the Cancer Immunology Program at NYU School of Medicine. Part of the body of data supporting this approach was published recently in Nature Medicine and builds upon his work previously published in Cell.

"Most solid, malignant tumors establish an immunosuppressive environment to ward off the body’s natural defenses. Dr. Miller’s work in pancreatic ductal carcinoma has revealed that inflammatory processes drive the immunosuppression through certain gamma delta T cells and macrophages," said Dr. Joseph Bolen, Chief Scientific Officer of PureTech Health. "Our novel approach builds on this finding and selectively disrupts the immunosuppression to potentially have a therapeutic effect on cancer."

This technology, exclusively licensed from the NYU School of Medicine, is being developed in a new subsidiary of PureTech Health called Nybo Therapeutics. Nybo builds on PureTech’s strength in immunology and joins PureTech’s advanced pipeline of immunology and T cell biology programs that includes a Phase IIB immunosenescence program, microbiome-based T cell mediated therapies, and CAR-T therapies.

"Pancreatic cancer is the only major cancer with a five-year survival rate in the single digits, and there has been far too little progress towards meaningful treatments," said Dr. Diane Simeone, Director of the Pancreatic Cancer Center at NYU School of Medicine and a member of Nybo’s Scientific Advisory Board. "Novel therapeutic approaches are important to pursue, and I look forward to helping advance this promising technology."

Dr. Miller commented on this announcement, "I am excited to translate our findings into first-in-class therapies for patients who desperately need new treatment options. Our work on immunosuppressive mechanisms in pancreatic cancer has shed light on new therapeutic approaches that form the foundation for Nybo, and we look forward to a great partnership with PureTech Health with whom to advance these findings."

PureTech Health has gathered a group of leading expert collaborators and advisors around this platform, including:

Erin Adams, Ph.D., is the Joseph Regenstein Professor at the Department of Biochemistry and Molecular Biology, and on the Committees of Immunology and Cancer Biology at the University of Chicago. Dr. Adams’ research is focused on understanding how events at the molecular level allow the immune system to differentiate between self and non-self with particular attention given to nonconventional T cell recognition, such as that of gamma delta T cells. The scientific approach she undertakes to tackle these questions spans multiple levels including genetics, protein biochemistry, structure, biophysics, function and cell biology and imaging. Dr. Adams is one of the pioneer researchers discovering how gamma delta T cells recognize antigens and how this recognition process regulates their activity in various tissues in which they reside.

Elizabeth Jaffee, M.D., currently serves as Deputy Director for the Johns Hopkins Kimmel Cancer Center, Associate Director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy; Associate Director for Translational Research, Co-Director of Gastrointestinal cancer and diseases program, and Co-Director of the Skip Viragh Center for Pancreatic Cancer Clinical Research and Patient Care. Dr. Jaffee is chair and member of the National Cancer Advisory Board, and served as co-chair of the NCI Blue Ribbon Panel for the National Moonshot Initiative. Dr. Jaffee is an active member of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), and has just been named President-Elect of AACR (Free AACR Whitepaper) (2017-2018). She will assume the presidency in April, 2018.

Steven Leach, M.D., is the Director of the David M. Rubenstein Center for Pancreatic Cancer Research of Memorial Sloan-Kettering. Prior to this, Dr. Leach served as Professor of Surgery, Oncology and Cell Biology, and the Paul K. Neumann Professor in Pancreatic Cancer at Johns Hopkins Medicine. Dr. Leach received his undergraduate degree from Princeton University, where he currently serves on the Board of Trustees. He then pursued his MD degree at Emory University, followed by postdoctoral training at Yale University and at M.D. Anderson. Dr. Leach is also the current Chair of the Pancreatic Cancer Action Network’s Scientific and Medical Advisory Board.

George Miller, M.D., is the Director of S. Arthur Localio Laboratories, vice chair for research in NYU, Langone’s Department of Surgery and the leader of Perlmutter Cancer Center’s Immunology Program, as well as the director of the only training program in the country in gastrointestinal oncology that is funded by the National Institutes of Health. In addition to his laboratory research, Dr. Miller is a highly experienced pancreatic and hepatobiliary surgeon with an extensive background in the evaluation and treatment of pancreatic tumors, as well as liver, bile duct cancers.

Diane M. Simeone, M.D., is currently the director of the Pancreatic Cancer Center at the NYU School of Medicine and the Associate Director of Translational Research, Perlmutter Cancer Center, NYU Langone Medical Center. She is the chair-elect of the Scientific and Medical Advisory Board of the Pancreatic Cancer Action Network, one of the country’s leading organizations advancing the battle against the disease through research funding, community engagement and government advocacy. She is a member of the Institute of Medicine of the National Academy of Sciences, serves on the National Cancer Institute’s Pancreatic Cancer Task Force, and previously was president of the Society of University Surgeons and the American Pancreatic Association.

"We will be exploring both pancreatic cancer and other solid tumor types such as colorectal cancer. In addition to monotherapy, Dr. Miller’s work suggests that this approach may enhance the effect of checkpoint inhibitors that have historically not worked in pancreatic cancer opening up the possibility of combination therapy," commented Dr. Aleksandra Filipovic, Therapeutic Lead for Oncology at PureTech.

The underlying research described above has been supported by the NYU School of Medicine’s drug discovery accelerator, the Office of Therapeutics Alliances.

About NYU Office of Therapeutics Alliances and Office of Industrial Liaison
The NYU Office of Therapeutics Alliances (OTA) was created in 2013 to accelerate and de-risk drug discovery projects developed at NYU School of Medicine towards partnerships with investors, biopharma, and non-profits. The NYU Office of Industrial Liaison (OIL) promotes the commercial development of NYU discoveries and actively seeks commercial partners for licensing and research collaborations. Over the past ten years NYU has ranked first among all universities in income from technology licensing. For more information, please visit View Source and View Source

About Nybo Therapeutics
Nybo Therapeutics, a subsidiary of PureTech Health (LSE: PRTC), is developing first-in-class immuno-oncology programs dedicated to the targeting of immune-suppressive gamma delta T cells and other related mechanisms in pancreatic cancer and other solid tumors. It aims to address the great unmet need in malignancies with dismal prognoses that derive little benefit from current standards of care.

PureTech Health plc (PRTC.L) owns approximately 93.5% of the company on a diluted basis as of 11 April 2017. This calculation includes issued and outstanding shares as well as options to purchase shares and written commitments to issue shares or options, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans.

About PureTech Health
PureTech Health (PureTech Health plc, PRTC.L) is an advanced, clinical-stage biopharmaceutical Company developing novel medicines that modulate the adaptive human systems. PureTech’s therapies target the dysfunctions in the immune, nervous, and gastro-intestinal systems by addressing the underlying pathophysiology of disease from a systems perspective rather than through a single receptor or pathway. The Company is advancing a rich pipeline that includes multiple human proof-of-concept studies and pivotal or registration studies expected to read out over the next 12-18 months. PureTech Health’s growing research and development pipeline has been developed in collaboration with some of the world’s leading scientific experts, who along with PureTech’s experienced team and a stellar Board identify, analyses and advance very selectively the opportunities the Company believes hold the most promise for patients. This experienced and engaged team places PureTech Health at the forefront of ground-breaking science and technological innovation and leads the Company between and beyond existing disciplines. For more information, visit www.puretechhealth.com or connect with us on Twitter @puretechh.

Apogenix Announces Initiation of Clinical Development for ABBV-621 to Treat Solid and Hematologic Tumors by Partner AbbVie

On April 11, 2017 Apogenix AG, a biopharmaceutical company developing next-generation immuno-oncology therapeutics, reported that a clinical phase I study with ABBV-621 has been initiated by its partner AbbVie (Press release, Apogenix, APR 11, 2017, View Source [SID1234524574]). In this study, 92 patients suffering from solid tumors, non-Hodgkins’s lymphoma (NHL) or acute myeloid leukemia (AML) will be recruited. The study ("An Open-Label, Phase 1, First-In-Human Study of Safety and Tolerability of TRAIL Receptor Agonist ABBV-621 in Subjects With Previously Treated Solid Tumors and Hematologic Malignancies"; Clinicaltrials.gov ID: NCT03082209) will be recruiting in the US, EU and Japan. The phase I objectives will be to establish the safety and tolerability of ABBV-621, as well as to understand its pharmacokinetic properties.

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ABBV-621 is a novel, second-generation TRAIL-receptor agonist consisting of six receptor binding domains of TRAIL (TRAIL: TNF-related apoptosis inducing ligand), fused to the Fc-domain of a human IgG1 antibody. This novel protein was engineered by Apogenix employing its proprietary HERA technology platform (HERA: hexavalent receptor agonists; Gieffers et al., Mol. Cancer Ther. 2013, 2735-2747). The substance acts as a pure agonist by binding to TRAIL-receptors on tumor cells, thereby inducing their apoptosis (programmed cell death). ABBV-621 is designed to maximize receptor clustering but does not require Fc?-receptor-mediated crosslinking for optimal efficacy. This has been deemed an activity-limiting step for competitor antibodies in the clinic. ABBV-621 induces dose-dependent apoptotic cell death at sub- to single-digit nanomolar potencies across a large panel of human hematologic and solid tumor cell lines in vitro. In tumor xenograft models, ABBV-621 exhibits potent antitumor activity in vivo as a monotherapy and in combination with targeted agents or chemotherapy using xenograft tumors derived from colorectal, lung, leukemia, and lymphoma cell lines. In toxicity studies, ABBV-621 was well tolerated with no adverse drug-related findings.

"We are excited to see our first HERA-ligand enter clinical development. The unique mechanism of action has the potential to induce apoptosis, thereby eliminating cancer cells, and offers a new treatment option in the fight against cancer," Thomas Hoeger, Ph.D., Chief Executive Officer of Apogenix, said. "We are looking forward to see first results of the recently initiated clinical study."

In summer 2014, AbbVie acquired the worldwide rights for all TRAIL-receptor agonists developed by Apogenix. AbbVie is responsible for preclinical and clinical development of these compounds.

About HERA

Apogenix has developed a proprietary technology platform for the construction of novel hexavalent TNF superfamily receptor agonists (HERA). The specific molecular structure of HERA induces a well-defined clustering of functional TNF receptors on the surface of target immune cells. By stimulating different TNF signaling pathways, HERA-ligands can increase the anti-tumor immune response. In contrast to agonistic antibodies, the fusion proteins are pure agonists whose potent signaling capacity is independent of secondary Fc?-receptor mediated crosslinking. In addition, HERA-ligands cause neither antibody dependent cellular cytotoxicity (ADCC) nor complement-dependent cytotoxicity (CDC) and exhibit a shorter half-life than antibodies. It is therefore expected that HERA-ligands will cause less side effects in clinical development. Apogenix is utilizing its HERA technology platform to develop GITR, CD40, CD27, 4-1BB, HVEM, and OX40 receptor agonists for cancer immunotherapy. The TRAIL program was licensed to AbbVie in 2014.

MorphoSys to Present at Upcoming Conferences

On April 11, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that it will present at the following conferences (Press release, MorphoSys, APR 11, 2017, View Source [SID1234556344]):

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10th Kempen Life Sciences Conference
Date: April 19, 2017
Venue: Amsterdam, Netherlands
Presenter: Jens Holstein, Chief Financial Officer of MorphoSys AG

UBS Global Healthcare Conference
Date: May 22/23, 2017
Venue: New York, NY, USA
Presenter: Dr. Simon Moroney, Chief Executive Officer of MorphoSys AG

Berenberg European Conference
Date: May 24, 2017
Venue: Tarrytown, NY, USA
Presenter: Dr. Simon Moroney, Chief Executive Officer of MorphoSys AG

A PDF version of the presentation will be provided at www.morphosys.com.

The Annual General Meeting of MorphoSys AG will take place on May 17, 2017 in Munich. A live webcast of the event and all related information are available on www.morphosys.com/agm.

Redx Pharma presents data in oncology and fibrosis at two key scientific congresses

On April 10, 2017 Redx Pharma recently presented scientific posters in oncology and fibrosis at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 1-5, 2017, in Washington D.C., USA and the Keystone Symposia (Keystone) focused on Injury, Inflammation and Fibrosis, on March 26-30, 2017, in Snowbird, Utah, USA, respectively (Press release, Redx Pharma, APR 10, 2017, View Source [SID1234524748]).

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Dr Neil Murray, Chief Executive Officer of Redx Pharma, said: The posters recently presented at key scientific congresses demonstrate that our discovery engine continues to produce the next potential therapies for high value unmet needs in oncology and immunology.

We have previously seen that Porcupine inhibitors have shown potential applications in oncology, however we are pleased that we are now able to present validated preclinical data demonstrating that they could also be efficacious against fibrosis. As a result of this we now believe there are many development opportunities in an area that has seen little meaningful therapeutic progress for patients.

Posters
Keystone
Title: Porcupine inhibitors demonstrate suitability for use as novel anti-fibrotic therapeutics
Author: Peter Bunyard
Summary: REDX06109 demonstrated a robust anti-fibrotic response when dosed therapeutically in an animal model of kidney fibrosis at levels that are expected to be well tolerated. Preliminary data also showed that Wnt ligand is a potent stimulator of human lung fibroblast proliferation and is likely to synergise with other pro-fibrotic mediators to induce an aggressive fibrotic response to tissue injury
Download the Porcupine inhibitors presentation poster

AACR
Title: Development of REDX05358, a novel highly selective and potent pan RAF inhibitor and a potential therapeutic for BRAF and RAS tumors
Author: Helen Mason
Summary: REDX05358 is a highly potent and selective inhibitor targeting all RAF isoforms, which demonstrates anti-proliferative activity across a range of mutant cancer cell lines. Unlike the first generation RAF inhibitor, vemurafenib, which only shows transient inhibitory effects in mutant RAF colorectal cancer, REDX05358 sustains inhibition of this pathway and overcomes the resistance seen with vemurafenib both in vitro and in vivo. REDX05358 presents a potential therapeutic opportunity for the treatment of mutant cancers
Download the Development of REDX05358 presentation poster

AACR
Title: Development of 2nd generation indoleamine 2,3-dioxygenase 1 (IDO-1) selective inhibitors
Author: Caroline Phillips
Summary: A novel chemical series was identified via an in silico virtual screening method with potent cellular activity against the IDO-1 enzyme, both in cancer cell lines and human dendritic cells. Experiments in dendritic cells have revealed differences between the Redx compound series and reference compounds in their inhibitory responses to varying stimulating conditions