Year: 2017

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 Pharmaceuticals Announces Bayer Terminates its Option to License Vantictumab or Ipafricept

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 that Bayer Pharma has notified OncoMed of its decision not to exercise its option to license the first-in-class Wnt pathway inhibitors vantictumab (anti-Fzd, OMP-18R5) and ipafricept (Fzd8-Fc, OMP-54F28) for strategic reasons (Press release, OncoMed, APR 10, 2017, View Source [SID1234518520]). Effective June 2017, OncoMed will retain worldwide development and commercialization rights to vantictumab, ipafricept and all other Wnt pathway biologics under the collaboration. The small molecule program under the companies’ collaboration continues without change.

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"Under our collaboration with Bayer, we have received over $90 million in upfront and milestone payments that have fully funded the development of vantictumab and ipafricept. While we had looked forward to collaborating with the Bayer team on the late-stage development of these biotherapeutics, we are very pleased to have worldwide rights to two promising Phase 2-ready assets," said Paul J. Hastings, Chairman and CEO of OncoMed. "We will be conducting an internal portfolio review and prioritization as we determine next steps for all our programs, including vantictumab and ipafricept.

Vantictumab and ipafricept are selective inhibitors of the Wnt pathway. In Phase 1a and Phase 1b clinical trials, vantictumab and ipafricept have each demonstrated safety and tolerability alone and in combination with standard-of-care chemotherapies in several solid tumors.. The company is completing two Phase 1b combination clinical trials of vantictumab — one in HER2-negative breast cancer (vantictumab + paclitaxel) and one in advanced pancreatic cancer (vantictumab + gemcitabine + Abraxane) — and two Phase 1b combination clinical trials of ipafricept — one in ovarian cancer (ipafricept + carboplatin + paclitaxel) and one in pancreatic cancer (ipafricept + gemcitabine + Abraxane). Interim data presented from each of these trials during the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting and the ESMO (Free ESMO Whitepaper) 2016 Congress showed early indications of anti-tumor activity. In preclinical studies, OncoMed researchers have observed evidence of synergies when these Wnt inhibitor compounds are administered sequentially following the use of taxane-based chemotherapies. Published preclinical studies also point to the Wnt pathway as being a possible potentiator of immune response in tumors.

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.

Geron Announces Completion of Second Internal Data Reviews for Imetelstat Trials Being Conducted by Janssen

On April 10, 2017 Geron Corporation (Nasdaq:GERN) reported that Janssen Research & Development, LLC has completed the second internal data reviews of IMerge and IMbark, the clinical trials of the telomerase inhibitor imetelstat in lower risk myelodysplastic syndromes (MDS) and relapsed or refractory myelofibrosis (MF), respectively (Press release, Geron, APR 10, 2017, View Source [SID1234518518]). For IMerge, the benefit/risk profile of imetelstat in the treated patients supports continued development in lower risk myelodysplastic syndromes. A data package and proposed trial design refinements are planned to be provided to the FDA. For IMbark, the current results suggest clinical benefit and a potential overall survival benefit associated with imetelstat treatment in relapsed or refractory myelofibrosis; the trial will continue unchanged to evaluate maturing efficacy and safety data, including an assessment of overall survival.

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IMerge

IMerge (NCT02598661) is a Phase 2/3 clinical trial evaluating imetelstat in transfusion dependent patients with Low or Intermediate-1 risk MDS who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The clinical trial is in two parts: Part 1 is a Phase 2, open-label, single-arm design in approximately 30 patients and Part 2 is designed to be a Phase 3, randomized, controlled trial in approximately 170 patients. The primary efficacy endpoint is the rate of red blood cell transfusion independence lasting at least 8 weeks. Key secondary endpoints include the rates of red blood cell transfusion independence lasting at least 24 weeks and hematologic improvement. Part 1 of the trial is fully enrolled.

The second internal review of IMerge included data from the approximately 30 patients enrolled in Part 1. Based on this second internal review, the Collaboration’s Joint Steering Committee has determined the following:

The safety profile was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified.

The benefit/risk profile of imetelstat, including assessments of 8-week and 24-week transfusion independence and hematologic improvement by erythroid (HI-E) response, across multiple MDS sub-types, supports continued development in lower risk MDS.

Part 1 of the trial will continue unmodified, and patients remaining in the treatment phase may continue to receive imetelstat.

A data package, as well as proposed refinements to the trial design for Part 2 of IMerge, is planned to be provided to the FDA.

Data from Part 1 are expected to be submitted for consideration for presentation at a medical conference in the future.
Geron expects that FDA feedback and the totality of imetelstat program information, including an assessment of the evolving treatment landscape in MDS and the potential application of imetelstat in multiple hematologic malignancies, will inform Janssen’s decision to initiate Part 2 of IMerge. If Part 2 of IMerge is initiated, Geron expects this Phase 3 stage of IMerge to be opened for patient enrollment in the fourth quarter of 2017.

IMbark

IMbark (NCT02426086) was originally designed as a Phase 2 clinical trial to evaluate two dose levels of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered every three weeks) in approximately 200 patients with Intermediate-2 or High risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor. The co-primary efficacy endpoints for the trial are spleen response rate (≥35% reduction of spleen volume assessed by imaging) and symptom response rate (³50% reduction in Total Symptom Score) at 24 weeks.

The second internal review of IMbark included data from the approximately 100 patients who were enrolled in the trial, with each dosing arm analyzed separately. Based on this second internal review, the Collaboration’s Joint Steering Committee has determined the following:

The safety profile was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified.

The data support 9.4 mg/kg as an appropriate starting dose for the relapsed or refractory MF patient population.

In these relapsed or refractory MF patients treated in the 9.4 mg/kg dosing arm, the spleen volume response rate observed to date was less than that reported in front-line MF patients treated in trials with other drugs. However, activity within multiple outcome measures was observed with imetelstat treatment, which suggests clinical benefit in this relapsed or refractory MF patient population. These outcome measures included a range of spleen volume reductions, decreases in Total Symptoms Score, and improvements in hematologic parameters, such as anemia and peripheral blood counts. In addition, the data suggest a potential overall survival benefit associated with imetelstat treatment in these patients.

The trial will continue without any modifications, including conduct of all safety and efficacy assessments as planned in the protocol, including overall survival. Patients remaining in the treatment phase may continue to receive imetelstat.

Enrollment of new patients to the trial will remain suspended because the total number of patients enrolled to date is adequate to assess longer-term outcome measures when the data are fully matured.
During the next year, Geron expects Janssen to evaluate maturing efficacy and safety data from the trial, including an assessment of overall survival. Geron expects the longer-term data from the trial, potential health authority feedback, and the totality of imetelstat program information, including an assessment of the evolving treatment landscape in MF and the potential application of imetelstat in multiple hematologic malignancies, including MDS, will inform Janssen’s decision whether to continue development of imetelstat in relapsed or refractory MF.

About Imetelstat

Imetelstat (GRN163L; JNJ-63935937) is a potent and specific inhibitor of telomerase that is administered by intravenous infusion. This first-in-class compound, discovered by Geron, is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Preliminary clinical data suggest imetelstat has disease-modifying activity by inhibiting the progenitor cells of the malignant clones associated with hematologic malignancies in a relatively select manner. Most commonly reported adverse events in imetelstat clinical studies include fatigue, gastrointestinal symptoms and cytopenias. Imetelstat has not been approved for marketing by any regulatory authority.

FORMA Therapeutics Delivers Two Key Objectives in Collaboration with Celgene Corporation to Advance Protein Homeostasis Medicines to Benefit Patients

On April 10, 2017 FORMA Therapeutics announced today that it has successfully completed two additional objectives under its strategic collaboration agreement with Celgene Corporation, triggering two undisclosed payments from Celgene (Press release, Forma Therapeutics, APR 10, 2017, View Source [SID1234518517]). Previously, FORMA and Celgene entered a collaboration in the promising area of protein homeostasis to discover, develop and commercialize innovative drug candidates. This collaboration enables Celgene to evaluate select therapeutic candidates and programs in protein homeostasis during preclinical development.

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John Hohneker, M.D., Executive Vice President and Head of Research and Development at FORMA Therapeutics said, "FORMA’s integrated approach to drug discovery, bringing together distinctly novel and proprietary compound collections with clinically-meaningful biological assays across protein families, continues to deliver a promising pipeline. We have successfully identified several additional candidate compounds from our protein homeostasis programs, each with a compelling mechanism of action and potential to represent first in class therapeutic options for patients."

About Protein Homeostasis

Protein homeostasis, which is important in oncology, neurodegenerative and other disorders, involves a tightly regulated network of pathways controlling the biogenesis, folding, transport and degradation of proteins. Exploring the maintenance and regulation of such competing, yet integrated, biological pathways using a chemical biology approach, should directly contribute to the understanding of diseases associated with excessive protein misfolding, aggregation and degradation.