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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"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.

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

OncoMed’s Phase 2 Demcizumab Pancreatic Cancer Trial Misses Primary Endpoint

On April 10, 2017 OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported top-line results from the company’s Phase 2 YOSEMITE clinical trial of demcizumab (anti-DLL4, OMP-21M18) in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in previously untreated patients with metastatic pancreatic cancer (Press release, OncoMed, APR 10, 2017, View Source [SID1234518519]). The randomized Phase 2 "YOSEMITE" trial was designed to assess the efficacy and safety of demcizumab plus standard-of-care chemotherapy in first-line metastatic pancreatic cancer with the primary endpoint of progression-free survival and a secondary endpoint of overall survival. The trial did not meet the primary endpoint of progression-free survival. Additionally, the interim median overall survival analysis did not show a benefit for demcizumab in combination with Abraxane plus gemcitabine compared to the Abraxane, gemcitabine plus placebo arm in patients with first-line metastatic pancreatic cancer.

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"Patients in all three arms of the Phase 2 YOSEMITE trial surpassed the published median overall survival rates for Abraxane plus gemcitabine in first-line metastatic pancreatic patients. While the interim median overall survival was 13.2 months in the pooled demcizumab arms, the interim median overall survival of Abraxane plus gemcitabine was not reached at the time of these analyses. Based on the lack of benefit over standard-of-care, which performed remarkably well, we will be discontinuing this trial. We will conduct additional analyses, together with our partner, Celgene, to understand these outcomes. We will also discontinue any additional enrollment in our other ongoing demcizumab trials and conduct analyses of the data from those trials as planned," said Paul J. Hastings, Chairman and CEO of OncoMed Pharmaceuticals. "OncoMed remains focused on completing and analyzing the results of the two randomized Phase 2 clinical trials, PINNACLE and DENALI, that are anticipated in the first half of this year and in continuing the advancement of our portfolio of biotherapeutic candidates."

OncoMed management will host a conference call today at 8:30 a.m. ET/5:30 a.m. PT to discuss the YOSEMITE clinical trial data.

Summary of Key Findings

Progression-Free Survival: The median progression-free survival (mPFS) was essentially the same across all arms of the study. For patients receiving demcizumab (either one or two truncated courses) in combination with Abraxane plus gemcitabine the mPFS was 5.5 months compared to a mPFS of 5.5 months for those in the Abraxane, gemcitabine plus placebo group (HR=0.93). In addition, no significant differences were observed when the individual treatment arms were compared to the Abraxane, gemcitabine plus placebo arm: in patients receiving a single truncated course of demcizumab the mPFS was 5.4 months (HR=1.03), and the mPFS was 5.5 months (HR=0.83) in patients receiving two truncated courses of demcizumab.

Interim Overall Survival: The interim median overall survival (mOS) for patients receiving either one or two truncated courses of demcizumab in combination with Abraxane plus gemcitabine (n =136) was 13.2 months, while a mOS was not reached for the Abraxane, gemcitabine plus placebo arm (HR=1.02). No significant differences were observed when the individual treatment arms were compared: an interim mOS of 10.6 months was observed with a single course of demcizumab (n=71) (HR=1.2) and an interim mOS of 13.3 months was seen among patients receiving two courses of demcizumab (n=65) (HR=0.87). These results are based on an analysis that occurred at the 125th PFS event at which time there were 75 deaths.

Response and Clinical Benefit Rates: Overall response rate (defined as complete responses and partial responses) was 33.1% (45 of 136 patients) in the combined demcizumab, Abraxane plus gemcitabine groups and 41.2% (28 of 68 patients) in the Abraxane, gemcitabine plus placebo group. The overall clinical benefit rate (defined as complete responses, partial responses and stable disease) was slightly higher in the pooled demcizumab arms at 74.3% (101 of 136 patients) compared to 70.6% (48 of 68 patients) in the Abraxane, gemcitabine plus placebo group. Response was measured using the RECIST 1.1 criteria and is based on unconfirmed investigator assessment.

Safety and tolerability: Demcizumab, Abraxane plus gemcitabine were generally well tolerated with nausea, diarrhea, anemia and fatigue being the most common reported toxicities. The incidence of Grade 3 or greater heart failure, pulmonary hypertension and bleeding were (3.7% vs. 0%), (0.7% vs 0%) and (8.1% vs. 1.5%) in the pooled demcizumab, Abraxane plus gemcitabine arms and the Abraxane, gemcitabine plus placebo arm, respectively.
"Pancreatic cancer has proven to be a uniquely challenging disease, and these data appear to reflect some of those disease and treatment complexities. The safety data seen in the YOSEMITE trial were generally consistent and in line with our expectations. We continue to analyze these data, and look forward to presenting the full study findings at a future scientific congress," said Robert Stagg, PharmD, Senior Vice President of Clinical Research and Development. "We would like to sincerely thank the patients and their families, investigators and staff for their support and participation in this study."

About the Phase 2 YOSEMITE Trial
The randomized Phase 2 "YOSEMITE" trial was designed to assess the efficacy and safety of demcizumab in combination with Abraxane plus gemcitabine, compared to Abraxane, gemcitabine plus placebo in first-line pancreatic cancer patients with metastatic disease. Two-hundred and seven patients were randomized and 204 patients were treated in one of three study arms: 1) Abraxane, gemcitabine plus placebo, 2) Abraxane, gemcitabine plus one 70-day truncated course of demcizumab (given once every 2 weeks with the last dose given on Day 70) or 3) Abraxane, gemcitabine plus two 70-day truncated courses of demcizumab (separated by a 98 day period without demcizumab) with the last demcizumab dose given on day 238.

The primary endpoint of YOSEMITE was progression-free survival. Secondary and exploratory endpoints were overall survival, response rate, pharmacokinetics, immunogenicity, safety and biomarker analyses. The YOSEMITE Phase 2 trial was conducted at 49 clinical sites in the U.S., Canada, Europe and Australia. OncoMed initiated YOSEMITE in April 2015 and completed enrollment of patients in September 2016.

Conference Call Today
OncoMed management will host a conference call today beginning at 8:30 a.m. ET/5:30 a.m. PT to review top-line results from the Phase 2 YOSEMITE clinical trial.

Analysts and investors can participate in the conference call by dialing 1-855-420-0692 (domestic) and
1-484-756-4194 (international) using the conference ID# 5625895. A webcast of the conference call will be accessible through a link in the Investor Relations section of the OncoMed website: View Source An audio replay of the conference call can be accessed by dialing 1-855-859-2056 (domestic) or 1-404-537-3406 utilizing the conference ID number listed above. The web broadcast of the conference call will be available for replay through 90 days via the OncoMed website.

About Pancreatic Cancer
Pancreatic cancer is the third leading cause of cancer-related deaths. According to the American Cancer Society, each year in the United States there are approximately 54,000 new cases of pancreatic cancer and 43,000 deaths. The majority of patients with pancreatic cancer are diagnosed after their cancer has spread locally and/or metastasized to distant organs. The average life expectancy after the diagnosis of metastatic pancreatic cancer is less than one year.

About Demcizumab
Demcizumab is a humanized monoclonal antibody targeting Delta-like Ligand 4 (DLL4), a key member of the Notch signaling pathway. Based on preclinical studies, demcizumab may have a multi-pronged mechanism of action: halting cancer stem cell growth and reducing cancer stem cell frequency, disrupting angiogenesis in the tumor and augmenting anti-tumor immune responses by decreasing tumor myeloid-derived suppressor cells (MDSCs).

Demcizumab is currently being studied in two randomized Phase 2 clinical trials. The YOSEMITE trial is testing demcizumab with Abraxane plus gemcitabine versus Abraxane plus gemcitabine alone in first-line advanced pancreatic cancer patients. The DENALI trial is testing demcizumab with pemetrexed and carboplatin versus pemetrexed and carboplatin alone in first-line advanced non-small cell lung cancer patients. A Phase 1b trial combining demcizumab with the anti-PD1 antibody pembrolizumab in solid tumor patients was also initiated in early 2016. Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.

REGiMMUNE Completes $6 Million Series E Financing

On April 7, 2017 REGiMMUNE Corporation reported the closing of a Series E financing on April 7th (Press release, REGimmune, APR 7, 2017, View Source [SID1234642231]). The company raised 6 million US in this new round, which was led by SMBC Venture Capital Co., Ltd., the VC arm of Sumitomo Mitsui Banking Corporation(SMBC) and Japan Asia Investment Corporation (JAIC). Additional investors participating in this round are new investors Miyako Capital,Iyo-Gin Capital, Oita Venture Capital, Kyoritsu Captal,Hiroshima Venture Capital and several individual investors. Existing investors, and Mitsubishi UFJ Bank Capital also invested in this financing. Proceeds from this funding will be used clinical study in US.

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REGiMMUNE successfully completed a Phase I/2a study of RGI-2001 for Graft versus Host Disease (GvHD) . Data from the Phase I/2a study showed no safety concerns up to the highest dose and some preliminary signs of efficacy were observed.

Kenzo Kosuda, President and Chief Executive Officer, said "We now have positive human clinical data that validates the usefulness of our immune-regulating technology platform. The financing announced today will allow us to start an addinotal clinical study to gain the more human data."