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: BIO Investor Forum (OncoMed) - "Tarextumab Phase 1b PINNACLE SCLC Interim Response Data"

P1 data • Oncology

OncoMed: Jefferies Healthcare Conference (OncoMed) - “Tarextumab Phase 1b PINNACLE, Response Rates"; "Extensive-stage SCLC (N=26), Tarextumab + Etoposide + Cisplatin/Carboplatin”

P1 data • Oncology • Small Cell Lung Cancer

Phase 1b trial of anti-notch 2/3 antibody OMP-59R5 in combination with etoposide and cisplatin (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC): The PINNACLE study (ESMO 2014) - Presentation time: 29.09.2014, 12:45 - 13:45, Abstract #1473P; P1, N=11; "OMP-59R5 with EP is well tolerated. The MTD has not been reached. Encouraging anti-tumor activity is observed."

P1 data • Oncology

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

P1 data • Oncology • Pancreatic Cancer

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

Anticipated regulatory • 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

OncoMed: Clinical Trial Update (OncoMed) - “OMP-59R5 in combination with Nab-P+GEM was well tolerated up to 12.5 mg/kg every other week. No DLT was observed in any of the 27 pts treated”; “Following the data cutoff point, dose escalation proceeded to 15 mg/kg (the highest dose to be tested in Phase 1b) and enrollment is ongoing”; “Diarrhea, fatigue and nausea were the most common OMP-59R5 treatment-related toxicities, and the events were mostly Grade 1 or 2, and easily managed with supportive care”; “Incidences of cytopenias seem to be similar to what has been reported with Nab-P +GEM and do not seem to be OMP-59R5 dose-dependent”; “Grade 2 infusion reactions were reported from 3 of 27 subjects”; “Concomitant chemotherapy did not appear to influence the pharmacokinetics of OMP-59R5”; “Pharmacodynamic evidence of notch pathway inhibition was observed in patient surrogate tissue (hair follicles) at OMP-59R5 doses of 7.5 mg/kg and above”

P1 data • Oncology • Pancreatic Cancer

A Phase 1b/2 study of OMP-59R5 in combination with gemcitabine in subjects with previously untreated stage iv pancreatic cancer (ALPINE) (clinicaltrials.gov) - P1/2, N=154; Sponsor: OncoMed Pharmaceuticals; Not yet recruiting -> Recruiting

Enrollment open • Pancreatic Cancer

OncoMed's tarextumab flunks mid-stage lung cancer study; shares plummet 26% premarket (SeekingAlpha) - "Thinly traded micro cap OncoMed Pharmaceuticals (NASDAQ:OMED) slumps 26% premarket on average volume in response to its announcement that its Phase 2 PINNACLE study assessing tarextumab, in combination with etoposide plus either cisplatin or carboplatin, in patients with extensive-stage small cell lung cancer failed to achieve its primary endpoint of progression-free survival or secondary endpoints of overall survival and biomarkers indicative of Notch pathway gene activation."

P2 data • Stock price • Oncology • Small Cell Lung Cancer

OncoMed: R&D Day (OncoMed) - Anticipated updated clinical and biomarker data from P1b PINNACLE trial (NCT01859741) in SCLC at ASCO (May 29 – Jun 2, 2015); Anticipated data readout from P1b/2 PINNACLE (NCT01859741) trial in first-line SCLC in 2017

Anticipated P1 data • Anticipated P1/2 data • Oncology

Final results of phase Ib of tarextumab (TRXT, OMP-59R5, anti-Notch2/3) in combination with etoposide and platinum (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC) (ASCO 2015) - Presentation time: Monday, Jun 1, 8:00 AM - 11:30 AM; Abstract #7508; P1, N=27; NCT01859741; "The MTD was not reached and TRXT 15 mg/kg was determined to be the Phase 2 dose...The overall response rate was 84%. The median duration of treatment was 128 days (6 cycles) with mPFS and mOS of 124 and 228 days, respectively. The median follow-up for PFS and OS was of 86 and 107 days respectively."

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