tarextumab (OMP-59R5) / Mereo Biopharma, Novartis - LARVOL DELTA

Results of a randomized, placebo-controlled, phase 2 study of tarextumab (TRXT, anti-Notch2/3) in combination with etoposide and platinum (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC) (ESMO 2017) - P1b/2; "Pts were randomized 1:1 to platinum (cisplatin 75 mg/m2 or carboplatin AUC of 5 mg/ml*min on day 1, investigator’s choice) + etoposide (EP) 100 mg/m2 on days 1-3 + TRXT 15 mg/kg on day 1 or EP + placebo (pbo) every 21 days. Tarextumab in combination with platinum-based therapy did not improve PFS, OS, ORR in previously untreated SCLC. Biomarker analysis failed to establish a predictive marker for TRXT efficacy. Pts treated with TRXT experienced more toxicity."

Combination therapy • P2 data • Small Cell Lung Cancer

Results of a randomized phase II trial of an anti-notch 2/3, tarextumab (OMP-59R5, TRXT, anti-Notch2/3), in combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) in patients (pts) with untreated metastatic pancreatic cancer (mPC). (ASCO-GI 2017) - P1b/2; "Addition of TRXT to Nab-P+Gem did not improve OS in 1st line mPC. A potential detrimental effect on PFS and ORR was seen in subjects with N3 < 25%ile.nBackground: Tarextumab (TRXT), fully human IgG2 antibody inhibits signaling of Notch2/ 3 receptors."

Clinical • P2 data • Biliary Cancer • Biosimilar • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Circulating Tumor Cells (CTCs) in patients with extensive stage small cell lung cancer and their association with clinical outcome (AACR 2017) - P1b/2; "...Tarextumab (TRXT, anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. PINNACLE is a Phase 1b/2 trial of TRXT in combination with etoposide and platinum therapy (EP) in patients with untreated extensive stage small cell lung cancer (ES-SCLC)... Our findings suggest that CTCs are frequently detectable in patients and are a prognostic factor in ES-SCLC. CTCs decrease with TRXT and platinum-based chemotherapy. Updated results will be presented."

Biomarker • Clinical • Biosimilar • Lung Cancer • Oncology • Small Cell Lung Cancer

A Review on the Efficacy and Safety of Nab-Paclitaxel with Gemcitabine in Combination with Other Therapeutic Agents as New Treatment Strategies in Pancreatic Cancer. (PubMed, Life (Basel)) - "The seven therapeutic agents were ibrutinib, necuparanib, tarextumab, apatorsen, cisplatin, enzalutamide, and momelotinib. The triple regimen is emerging as the first-line option for patients with pancreatic cancer, albeit with some limitations. Thus, further studies of this regimen are recommended."

Combination therapy • Journal • Review • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer. (PubMed, Cancer Med) - P1b/2 | "The addition of tarextumab to nab-paclitaxel and gemcitabine did not improve OS, PFS, or ORR in first-line metastatic PDAC, and PFS was specifically statistically worse in the tarextumab-treated patients."

Biomarker • Clinical • Journal • P2 data • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Thrombocytopenia

OncoMed achieves $72.5 million in milestone payments from Celgene; Announces year-end cash balance (GlobeNewswire) - "OncoMed achieved the $70 million safety milestone from Celgene based on an analysis of available Phase 1b and blinded interim Phase 2 clinical trial safety data associated with the demcizumab..."; Anticipated survival data of P1b pancreatic cancer study of demcizumab and Abraxane combination in ASCO GI 2016; Anticipated intiation of P1b of demcizumab in combination with pembrolizumab in Q1 2016; Anticpated enrollment Completion of P2 YOSEMITE trial; Anticipated results from P1b ovarian cancer trial of demcizumab plus paclitaxel; Anticipated P1b data of tarextumab plus chemotherapy in SCLC at 16th IASLC conference; Anticipated top-line results from the Phase 2 'ALPINE' trial; Anticipated initiation of P1b trial of Brontictuzumab in colorectal cancer; Anticipated initiation of P1a data of OMP-305B83."

Anticipated conference • Anticipated enrollment status • Anticipated new P1 trial • Anticipated P1 data • Anticipated P2 data • Commercial • Gastrointestinal Cancer • Hematological Malignancies • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer

EGFR/Notch Antagonists Enhance the Response to Inhibitors of the PI3K-Akt Pathway by Decreasing Tumour-Initiating Cell Frequency. (PubMed, Clin Cancer Res) - "These findings suggest that the co-blockade of EGFR and Notch signalling has the potential to increase the response to PI3K inhibition and PTG12 may gain clinical efficacy when combined with PI3K blockage in cancer treatment."

Journal • Oncology • Transplantation • Triple Negative Breast Cancer

OncoMed's phase 2 trial of tarextumab in small cell lung cancer does not meet endpoints (OncoMed Press Release) - P2, N=145; NCT01859741; "OncoMed Pharmaceuticals...today reported top-line results from...PINNACLE clinical trial of tarextumab...in previously untreated patients with extensive-stage small cell lung cancer...the trial did not meet its primary endpoint of progression-free survival or secondary endpoints of overall survival and biomarkers reflective of Notch pathway gene activation...it will discontinue enrollment in the Phase 1b clinical trial of brontictuzumab...in combination with trifluridine/tipiracil (Lonsurf®) in third-line colorectal cancer patients."

Enrollment closed • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Small Cell Lung Cancer

MorphoSys: Leerink Partners Annual Emerging Biotech Conference (Morphosys) - Anticipated data from P2 ALPINE trial (NCT01647828) for pancreatic cancer in 2016

Anticipated P2 data • Oncology • Pancreatic Cancer

OncoMed announces abstracts accepted for presentation at the 2015 ASCO Annual Meeting (OncoMed Press Release) - "OncoMed will present new clinical data from clinical trials of its lead anti-cancer stem cell therapeutics, demcizumab and tarextumab. Final data from OncoMed's Phase 1b clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) in small cell lung cancer...[and] New data from the company's Phase 1b clinical trials of demcizumab (OMP-21M18, anti-DLL4) in pancreatic cancer and non-small cell lung cancer (NSCLC) will be presented in posters during the meeting."

Anticipated conference • Anticipated P1 data • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer

Morphosys: J.P. Morgan Healthcare Conference (Morphosys) - Anticipated data from P2 trial in pancreatic cancer in 2016

Anticipated P2 data • Oncology • Pancreatic Cancer

"$OMED phase 2 PINNACLE SCLC trial completed enrollment. Data by EOY or early 2017." - @bradloncar

Anticipated P2 data • Enrollment closed • Oncology • Small Cell Lung Cancer

A Dose Escalation Study of OMP-59R5 in Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=42; Completed; Sponsor: OncoMed Pharmaceuticals, Inc.; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Oncology

OncoMed: Leerink Immuno-Oncology Roundtable Conference (OncoMed) - "Tarextumab Phase 1B PINNACLE: Biomarker and Survival Analysis"; "Dose response and biomarker trends observed"; "Potentially longer survival noted in patients who received higher doses of tarextumab + platinum therapy and among Notch3 high patients"

P1 data • Oncology

Oncomed: Biocentury's NewsMakers In The Biotech Industry Conference (OncoMed) - "Anti-Notch2/3 (OMR-59R5) summary"; "Potential GSK Opt-In Program"; "Ph1a study completed: Oral Plenary Presentation: Mol Targets and Cancer Therapeutics 2012"; "Safety: Well tolerated in refractory solid tumor patients"; "Toxicity: On-target diarrhea"; "Maximum tolerated dose (MTD) established for 3 dosing schedules (QW, Q2W,Q3W)"; "Efficacy: Prolonged stable disease"; "Triple Negative BC (JAG1 amplification), Liposarcoma, Adeniod Cystic Carcinoma, Rectal Cancer, Kaposi Sarcoma"

P1 data • Oncology • Pancreatic Cancer

OncoMed: Q1 2014 Results (OncoMed) - Anticipated presentation of interim data from P1b PINNACLE trial in combination with etoposide and cisplatin for extensive-stage small cell lung cancer at ASCO (May 30-June 3, 2014); Anticipated initiation of P2 portion of P1/2 ALPINE trial for pancreatic cancer in 2014; Anticipated initiation of P2 portion of P1/2 PINNACLE trial for small cell lung cancer in 2014

Anticipated new P1/2 trial • Anticipated P1/2 data • Oncology • Pancreatic Cancer

Oncomed: Q3 FY 2014 Results (OncoMed) - Anticipated presentation of biomarker analysis of tarextumab Notch pathway modulation from the ALPINE P1b trial for pancreatic cancer at EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics Meeting (Nov 18-21, 2014)

Anticipated P1 data • Oncology • Pancreatic Cancer

A first-in-human phase I study to evaluate the fully human monoclonal antibody OMP-59R5 (anti-Notch2/3) administered intravenously to patients with advanced solid tumors (ASCO 2012) - Presentation time: Sat, Jun 2, 1:15 PM - 5:15 PM; Anticipated presentation at ASCO 2012

Anticipated P1 data presentation • Oncology

A first-in-human phase I study to evaluate the fully human monoclonal antibody OMP-59R5 (anti-Notch2/3) administered intravenously to patients with advanced solid tumors (ASCO 2012) - Presentation time: Saturday June 2, 1:15 PM to 5:15 PM; P1, N=24; PK of OMP-59R5 was characterized by fast and dose-dependent clearance; Two patients (Kaposi’s sarcoma at 5mg/kg and adenoid cystic carcinoma at 2.5mg/kg) had prolonged stable disease for ≥110 days; PD analyses for Notch pathway modulation are ongoing

P1 pharmacokinetic data • Oncology

OncoMed: Jefferies Global Healthcare Conference (OncoMed) - Anticipated initiation of P2 portion of P1/2 ALPINE trial for pancreatic cancer in H2 2014; Anticipated initiation of P2 portion of P1/2 PINNACLE trial for small cell lung cancer in H2 2014 

Anticipated new P2 trial • Oncology • Pancreatic Cancer

GSK: R&D Event (GSK) - Anticipated regulatory submission in SCLC and pancreatic cancer in 2020

Anticipated regulatory • Oncology • Pancreatic Cancer

OncoMed: BIO Investor Forum (OncoMed) - "Tarextumab Phase 1b ALPINE Pancreatic Cancer Response Data"

P1 data • Oncology • Pancreatic Cancer

OncoMed Pharmaceuticals completes enrollment of phase 2 PINNACLE clinical trial of tarextumab in small cell lung cancer (OncoMed Press Release) - P1/2, N=145; NCT01859741; Sponsor: OncoMed Pharmaceuticals, Inc; "OncoMed...today announced the completion of patient enrollment in the Phase 2 'PINNACLE' clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) for the treatment of small cell lung cancer (SCLC)...Topline data from the Phase 2 trial are expected to be reported at the end of 2016 or in early 2017."

Anticipated P2 data • Enrollment closed • Oncology • Small Cell Lung Cancer

Tarextumab: "The addition of tarextumab to Nab-P+Gem did not improve OS… (OncoMed) - ASCO GI 2017: "The addition of tarextumab to Nab-P+Gem did not improve OS in subjects with untreated metastatic pancreas adenocarcinoma in overall intent to treat population as well as in each of the Notch 3 subgroups"

P2 data • Oncology • Pancreatic Cancer

Oncomed: Biocentury's NewsMakers In The Biotech Industry Conference (OncoMed) - "ALPINE Ph1b: Best Radiographic Response"; "Waterfall Plot (First N=12 Evaluable Pts)"

P1 data • Oncology • Pancreatic Cancer