ipafricept (OMP-54F28) / Mereo Biopharma - LARVOL DELTA

Phase Ib study of WNT inhibitor ipafricept (IPA) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (mPC). (ASCO-GI 2019) - P1b; "IPA can be safely administered with Nab-P and G in pts with mPC. Additional studies targeting the WNT pathway in pancreatic cancer are warranted."

Clinical • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Phase Ib study of WNT inhibitor ipafricept (IPA) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (mPC). (ASCO-GI 2019) - P1b; "IPA can be safely administered with Nab-P and G in pts with mPC. Additional studies targeting the WNT pathway in pancreatic cancer are warranted."

Clinical • P1 data

[VIRTUAL] Analysis of clinical trials targeting the Wnt signaling pathway for cancer therapy (ASHP 2020) - "The most commonly used drugs, investigated in 3 or more clinical trials included DKN-01 [DKK1 neutralizing monoclonal antibody] (9.9%), PRI-724 [CBP/ β-catenin complex inhibitor] (4%), OMP-54F28 [Decoy Receptor for Wnt lignads] (4%), Vantictumab [monoclonal antibody against Frizzled receptors] (4%), Cirmtuzumab [monoclonal antibody against ROR1] (4%), and BHQ880 [monoclonal antibody against DKK1] (3%). Based on our analysis, we reckon that DKK1 is the most investigated Wnt pathway target in cancer clinical trials, with DKN-01 being the most explored drug. Out of the 91 studies, the highest number of trials were carried out in colorectal cancer, followed by multiple myeloma. The preponderance of the clinical trials in early phases and active status could be the possible reasons for the deficit of Wnt pathway modifiers for cancer therapy in clinical practice."

Clinical • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Hepatology • Leukemia • Multiple Myeloma • Oncology • Pancreatic Cancer • Solid Tumor • DKK1 • ROR1 • SPON1

Wnt antagonists synergize with immune checkpoint inhibitors to enhance anti-tumor responses (AACR 2018) - "Here, we show that in various syngeneic murine tumor models, targeting Wnt signaling using the Fzd receptor monoclonal antagonist antibody, OMP-18R5 (vantictumab) or the pan-Wnt decoy receptor Fc fusion protein OMP-Fzd8-Fc (ipafricept) in combination with immune checkpoint inhibitors anti-CTLA-4 or anti-PD1 induce synergistic anti-tumor responses leading to decreased tumor volume and increased infiltration of activated CD8+ T cells into the tumor microenvironment. More importantly, we demonstrate that anti-PD1 and the Wnt antagonists decrease immune suppressive myeloid cell populations, which may enhance therapeutic efficacy and anti-tumor responses. Therefore, these results suggest that co-targeting Wnt and immune checkpoint proteins may provide valuable opportunities for novel combination strategies for immunotherapeutic clinical development."

Checkpoint inhibition • IO Biomarker • PD(L)-1 Biomarker • Oncology

Frizzled receptors in tumors, focusing on signaling, roles, modulation mechanisms, and targeted therapies. (PubMed, Oncol Res) - "However, the occurrence of fragility fractures in patients treated with Fzd-targeted agents such as OMP-54F28 and OMP-18R5 limits the development of this combination. Along with new insights on signaling, roles, and modulation mechanisms of Fzds in human tumors, more Fzd-related therapeutic targets will be developed."

Journal • Musculoskeletal Diseases • Oncology

Phase 1b study of Wnt inhibitor ipafricept (IPA) with gemcitabine and nab-paclitaxel in patients with previously untreated stage IV pancreatic cancer (mPDAC). (PubMed, Clin Cancer Res) - "IPA can be administered with Nab-P+G with reasonable tolerance. Wnt pathway remains a therapeutic target of interest in mPDAC."

Clinical • Journal • P1 data • Anorexia • Fatigue • Gastrointestinal Cancer • Leukopenia • Musculoskeletal Diseases • Oncology • Orthopedics • Pancreatic Cancer • Solid Tumor

Phase 1b study of WNT inhibitor ipafricept (IPA, decoy receptor for WNT ligands) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (PC) (ESMO 2016) - Ambassador: Heinz-Josef Lenz; Presentation time: Oct 9, 2016, 15:00 - 16:00; Abstract #367PD; P1, N=19; NCT02050178; Sponsor: OncoMed Pharmaceuticals, Inc.; "IPA can be safely administered in combination with Nab-P and G in pts with stage IV PC. No fragility fractures were observed. Updated results, including biomarker analysis in pt tumors, with PFS and overall survival, will be presented."

P1 data • GI (CRC, Pancreatic cancer) KOL Tracker

Dose Escalation Study of OMP-54F28 in Combination With Nab-Paclitaxel and Gemcitabine in Patients With Previously Untreated Stage IV Pancreatic Cancer (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: OncoMed Pharmaceuticals, Inc.; Trial primary completion date: Dec 2014 ->Dec 2016

Trial primary completion date • Biosimilar • Inflammation • Oncology • Pancreatic Cancer

A Dose Escalation Study of OMP-54F28 in Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=26; Completed; Sponsor: OncoMed Pharmaceuticals, Inc.; Active, not recruiting ➔ Completed; N=36 ➔ 26; Trial primary completion date: Dec 2015 ➔ Aug 2016

Enrollment change • Trial completion • Trial primary completion date • Biosimilar • Oncology

OncoMed: BIO Investor Forum (OncoMed) - "Phase 1a Summary"; "Tolerability profile distinct from vantictumab. Taste changes, muscle cramps, alopecia"; "On-target mild-to-moderate bone related adverse events. Risk mitigation implemented"; "Modulation of WNT pathway in patient samples"; "Nine patients stable disease >112 days" 

P1 data • Oncology

OncoMed: Annual Report 2015 (OncoMed) - Anticipated expiry of patents in US and ex-US related to composition of matter and methods of use in 2031; Anticipated expiry of composition of matter patent in US in 2034; Anticipated expiry of patents in US related to certain Fzd-Fc biologics and uses of Fzd-Fc biologics in the treatment of cancer 2026 or 2027; Anticipated expiry of patents in US related to polynucleotides in 2026; Anticipated expiry of patents US, PCT and ex-US related to ipafricept, certain uses of ipafricept and/or related biomarkers between 2026 and 2036

Anticipated patent expiry • Oncology

OncoMed: Q2 FY 2016 Results (OncoMed) - Anticipated initial data presentation from P1b trial (NCT02050178) of ipafricept in combination with nab-paclitaxel and gemcitabine for pancreatic cancer at ESMO (October 7-11, 2016)

Anticipated P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Ipafricept: Anticipated expiry of patents in US and ex-US related to composition of matter and methods of use in 2031 (OncoMed) - Annual Report 2016: Anticipated expiry of composition of matter patent in US in 2034; Anticipated expiry of patents in US related to certain Fzd-Fc biologics and uses of Fzd-Fc biologics in the treatment of cancer 2026 or 2027; Anticipated expiry of patents in US related to polynucleotides in 2026; Anticipated expiry of patents US, PCT and ex-US related to ipafricept, certain uses of ipafricept and/or related biomarkers between 2032 and 2036

Anticipated patent expiry • Oncology

OncoMed: Cantor Fitzgerald Healthcare Conference 2016 (OncoMed) - Anticipated data from P1b trial (NCT02050178) of ipafricept in combination with nab-paclitaxel and gemcitabine for pancreatic cancer in H2 2017

Anticipated P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

A first-in-human phase 1 study of anticancer stem cell agent OMP-54F28 (FZD8-Fc), decoy receptor for WNT ligands, in patients with advanced solid tumors (ASCO 2014) - Presentation time: Saturday, May 31; 2:39 PM - 2:51 PM; Abstract #2505; P1, N=25; NCT01608867; Sponsor: OncoMed Pharmaceuticals; "OMP-54F28 is well tolerated up to 20 mg/kg, double the target efficacious dose. PD modulation in bone and hair follicles was observed. Several patients experienced prolonged SD"

P1 data • Oncology

OncoMed: Cowen & Company Healthcare Conference (OncoMed) - "Phase 1a study"; "N=22 (Dose levels: 0.5 to 15 mg/kg"; "Safety: Fzd8-Fc is well tolerated in refractory solid tumor patients"; "Biomarker: WNT pathway modulation"; "Efficacy: Potential early activity in 2/2 Desmoid tumor pts; RCC and pancreatic"

P1 data • Oncology

OncoMed: BIO CEO & Investor Conference (OncoMed) - Anticipated data from P1b trials in HCC (NCT02069145), ovarian cancer (NCT02092363) and pancreatic cancer (NCT02050178) in 2016

Anticipated P1 data • Hepatocellular Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer

Oncomed: Biocentury's NewsMakers In The Biotech Industry Conference (OncoMed) - Anticipated data from P1a trial for solid tumors in 2013; Anticipated initiation of P1b trial for solid tumors (indication #1) in 2013-2014; Anticipated results from P1b trial for solid tumors (indication #1) in 2013-2016; Anticipated initiation of P1b trial for solid tumors (indication #2) in 2013-2014; Anticipated results from P1b trial for solid tumors (indication #2) in 2013-2016; Anticipated initiation of P1b trial for solid tumors (indication #3) in 2013-2014; Anticipated results from P1b trial for solid tumors (indication #3) in 2013-2016

Anticipated new P1 trial • Anticipated P1 data • Oncology

OncoMed: Q1 2014 Results (OncoMed) - Anticipated presentation of P1a data for advanced solid tumors at ASCO (May 30-June 3, 2014)

Anticipated P1 data • Oncology

OncoMed: ASCO 2016 (OncoMed) - "Ipafricept in combination with paclitaxel and carboplatin was well tolerated in patients with recurrent platinum-sensitive ovarian cancer"; "Nausea and fatigue were the most commonly reported toxicities. Grade 3 or higher ipafricept-related toxicities reported were neutropenia and hypophosphatemia. Ipafricept did not appear to enhance chemotherapy related toxicities"; "No fragility fractures were observed with the revised bone safety plan"; "Chemotherapy did not appear to influence the PK of ipafricept. IPA has a low rate of immunogenicity with no impact on drug exposure"; "Encouraging anti-tumor activity was seen in patients, both for the original regimen and the revised regimen with sequential dosing, with an overall response rate of 84%"

P1 data • Oncology • Ovarian Cancer

A phase 1b dose escalation study of ipafricept (OMP54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer. (PubMed, Gynecol Oncol) - "IPA is well tolerated in combination with sequential C/P. ORR, PFS and OS are comparable to historical data but bone toxicity at efficacy doses of this particular Wnt inhibitor limit further development in EOC."

Clinical • Combination therapy • Journal • P1 data

Wnt signaling dynamics in head and neck squamous cell cancer tumor-stroma interactions. (PubMed, Mol Carcinog) - "Wnt inhibitors, OMP-18R5 and OMP-54F28, significantly reduced growth of HNSCC patient-derived xenografts and suppressed Wnt activation at the tumor epithelial-stromal boundary. Taken together, our findings suggest that Wnt signaling is initiated in cancer cells which then activate CAFs, and in turn perpetuate a paracrine signaling loop. This suggests that targeting Wnt signaling in the TME is essential."

Journal

WNT antagonists exhibit unique combinatorial antitumor activity with taxanes by potentiating mitotic cell death. (PubMed, Sci Adv) - "By blocking WNT/β-catenin signaling before mitotic blockade by paclitaxel, we found that this treatment effectively sensitizes cancer stem cells to taxanes. This combination strategy and treatment regimen has been incorporated into ongoing clinical testing for vantictumab and ipafricept."

Journal

Phase Ib study of WNT inhibitor ipafricept (IPA) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (mPC). (ASCO-GI 2019) - No abstract available.

Clinical • P1 data