On November 9, 2020 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) and SOLTI-Innovative Breast Cancer Research reported the publication of an electronic poster with clinical data from the AWARE-1 window-of-opportunity breast cancer study at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting (Press release, Oncolytics Biotech, NOV 9, 2020, View Source [SID1234570364]).

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The AWARE-1 study, a collaboration between Oncolytics Biotech and SOLTI, combines the appropriate intervention for each patient’s breast cancer sub-type, plus pelareorep, with or without atezolizumab (Tecentriq), followed by surgery in early-stage breast cancer patients. Data presented in the electronic poster were from the ten HR+/HER2- breast cancer patients that make up the study’s first cohort. These data demonstrate the ability of pelareorep to promote a pro-inflammatory tumor microenvironment (TME) and provide a basis for the findings of a prior successful phase 2 trial (IND-213) that showed a near doubling of overall survival with pelareorep treatment in HR+/HER2- breast cancer patients (link to PR, link to poster).

"AWARE-1’s elegant paired-biopsy design allows us to assess the impact of pelareorep on each patient’s tumor immune environment, and the results to date have been very promising," said Dr. Aleix Prat, M.D., PhD., Translational Investigator of the Study, SOLTI President and Head of the Medical Oncology Department at Hospital Clinic in Barcelona. "These data continue to support pelareorep’s ability to train the immune system to target cancer and highlight its potential to address a critical unmet need by increasing the number of patients responding to checkpoint inhibitor therapies. Data presented at SITC (Free SITC Whitepaper) showing pelareorep-induced generation and expansion of anti-tumor and anti-viral T cell clones are also noteworthy, as they suggest the induction of a durable anti-cancer immune memory effect. These data, together with previously reported AWARE-1 results, provide strong support for the observed survival benefit in a prior randomized phase 2 study evaluating pelareorep in metastatic breast cancer patients."

Key data and conclusions from the electronic poster include:

•Tumor-cell specific pelareorep replication was observed in all cohort-1 patients following systemic pelareorep administration

•70% of cohort 1 patients saw an increase in CelTIL, the study’s primary endpoint and a measure of tumor-associated cellularity and tumor-infiltrating lymphocytes that is associated with favorable clinical outcomes

•On average, there was a 14-fold increase in intratumoral CD8+ T cells from baseline (pre-pelareorep administration) to surgery (21-days post-administration), with increases observed in all cohort-1 patients

•Pelareorep administration led to the generation and expansion of new T cell clones in the tumor and periphery, which included both anti-tumor and anti-viral clones

Thomas Heineman, M.D., Ph.D., Global Head of Clinical Development and Operations at Oncolytics, commented, "These newly announced AWARE-1 results add to the promising clinical dataset supporting pelareorep’s immunotherapeutic mechanism of action and to the proposed registration pathway in our lead metastatic breast cancer program. The observed 70% CelTIL response rate in cohort-1 patients is highly encouraging, as CelTIL is associated with favorable patient outcomes, and this response rate was achieved despite the absence of checkpoint blockade therapy. Further, previously announced data have shown that CelTIL scores correlate with high peripheral T cell clonality, underscoring T cell clonality’s potential as a predictive biomarker that may facilitate the design of future registrational trials and improve their chances of success. We look forward to presenting additional AWARE-1 data later this year and to the continued progress of the trial, which will be key as we move our lead breast cancer program towards a registrational study."

The electronic poster, titled, "Changes in T cell clonality in AWARE-1 study, a window-of-opportunity study with atezolizumab and the oncolytic virus pelareorep in early breast cancer" is being presented at SITC (Free SITC Whitepaper) by Dr. Prat. As of the SITC (Free SITC Whitepaper) data cut-off, AWARE-1 has enrolled 23 out of 38 patients, including all patients in the study’s first two cohorts.

Details on the AWARE-1 electronic poster, which are available on the SITC (Free SITC Whitepaper) 2020 website and on the Posters & Publications page of Oncolytics’ website (LINK), are shown below.

Poster Number: 806
Title: Changes in T cell clonality in AWARE-1 study, a window-of-opportunity study with atezolizumab and the oncolytic virus pelareorep in early breast cancer
Presentation Date and Time: Thursday, November 12 from 4:50-5:20 p.m. EST and Saturday, November 14 from 1:00-1:30 p.m. EST
Presenter: Dr. Aleix Prat

About AWARE-1
AWARE-1 is an open label window-of-opportunity study in early-stage breast cancer enrolling 38 patients into five cohorts:
•Cohort 1 (n=10), HR+ / HER2- (pelareorep + letrozole)

•Cohort 2 (n=10), HR+ / HER2- (pelareorep + letrozole + atezolizumab)

•Cohort 3 (n=6), TNBC (pelareorep + atezolizumab)

•Cohort 4 (n=6), HR+ / HER2+ (pelareorep + trastuzumab + atezolizumab)

•Cohort 5 (n=6), HR- / HER2+ (pelareorep + trastuzumab + atezolizumab)

The study combines pelareorep with the standard of care according to breast cancer subtype and atezolizumab. Patients are biopsied on day one followed immediately by treatment, then again on day three, and a final biopsy after three weeks, on the day of their mastectomy. Data generated from this study is intended to confirm that the virus is acting as a novel immunotherapy and to provide comprehensive biomarker data by breast cancer subtype. The primary endpoint of the study is overall CelTIL (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study include CelTIL by breast cancer subtype, safety and tumor, and blood-based biomarkers.
For more information about the AWARE-1 study, refer to View Source

About Breast Cancer
Breast cancer is the most common cancer in women worldwide, with over two million new cases diagnosed in 2018, representing about 25 percent of all cancers in women. Incidence rates vary widely across the world, from 27 per 100,000 in Middle Africa and Eastern Asia to 85 per 100,000 in Northern America. It is the fifth most common cause of death from cancer in women globally, with an estimated 522,000 deaths.

Breast cancer starts when cells in the breast begin to grow out of control. These cells usually form a tumor that can often be seen on an x-ray or felt as a lump. The malignant tumor (cancer) is getting worse when the cells grow into (invade) surrounding tissues or spread (metastasize) to distant areas of the body.

About Pelareorep
Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

About SOLTI
SOLTI is a leading cooperative group in the field of clinical cancer research. With its academic and translational core, the group is committed to designing and executing clinical trials based on the molecular biology of tumors. Its focus is on breast cancer, but it also explores other kinds of tumors. The main goal of SOLTI is to promote through disruptive means the development of innovative research that will improve the well-being and future outcomes of cancer patients. Since its creation in 1995, SOLTI’s purpose has been to bring about a paradigm shift in clinical and translational cancer research from within academia. With 77 clinical trials under their belt and more than 30 ongoing investigations, SOLTI counts on the work of more than 400 researchers from a network comprising more than 100 hospitals in Spain and Portugal, all coordinated by the team of 50 workers from the head office. SOLTI is a member of the Spanish Society of Medical Oncology (SEOM).
To find out more about SOLTI, visit www.gruposolti.org / Twitter: @SOLTI / LinkedIn / Youtube

On November 9, 2020 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported the presentation of clinical data from its Phase 1b/2a clinical trial of DKN-01 in patients with advanced esophagogastric cancer (EGC) at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 35th Anniversary Annual Meeting (Press release, Leap Therapeutics, NOV 9, 2020, View Source [SID1234570363]). DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein.

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In the study, high levels of tumoral DKK1 expression correlated with improved clinical outcomes in heterogeneous EGC patients treated with DKN-01 as monotherapy or in combination with pembrolizumab or paclitaxel. Pooled data for the 69 patients in the study for whom tumoral DKK1 expression data is available demonstrated that DKK1-high patients experienced higher overall response rates (ORR), a doubling of median progression-free survival (PFS), and longer median overall survival (OS) as compared to DKK1-low patients. Additionally, DKK1-high anti-PD-1/PD-L1 refractory patients treated with DKN-01 plus pembrolizumab experienced longer PFS and OS compared to DKK1-low patients, suggesting that DKK1 tumoral expression may serve as a predictive biomarker to identify patients for treatment with DKN-01 in combination with anti-PD-1 antibodies. No notable differences were found in baseline MSS, TMB, or PD-L1 expression between DKK1-high versus DKK1-low groups.

"We continue to observe clinically meaningful activity of DKN-01 in patients with advanced previously treated esophagogastric cancer that reinforces our belief that elevated tumoral DKK1 expression is a predictive biomarker for improved outcomes, particularly for those patients treated with DKN-01 in combination with an anti-PD-1 antibody," said Samuel J. Klempner, MD, Assistant Professor, Massachusetts General Hospital Cancer Center and Harvard Medical School.

"We believe that the totality of the results from this study provides strong support for the ongoing study of DKN-01 in combination with tislelizumab, an anti-PD-1 antibody, in DKK1-high second line gastroesophageal junction and gastric cancer (GEJ/GC) patients and in combination with tislelizumab, capecitabine, and oxaliplatin in first-line GEJ/GC patients," continued Dr. Klempner.

The P102 Study in Relapsed or Refractory Esophagogastric Cancer

The P102 study (KEYNOTE-731) is a multi-part Phase 1/2 study of DKN-01 as a monotherapy and in combination with paclitaxel or KEYTRUDA (pembrolizumab) in advanced EGC patients, with a median of two previous treatments with standard therapies, representing a difficult to treat population. The study is intended to establish the safety and activity of DKN-01 as a monotherapy and in combination with paclitaxel or pembrolizumab, with efficacy endpoints of ORR, PFS, and OS. Tumoral DKK1 expression was determined retrospectively by RNAscope chromogenic in situ hybridization and correlated with clinical outcomes. Pembrolizumab was provided for the study through a clinical trial collaboration agreement with Merck (known as MSD outside the United States and Canada).

Key DKN-01/Pembrolizumab Findings from the P102 Study

·Anti-PD-1/PD-L1 refractory patients (all): The four DKK1-high patients had a significantly longer PFS of 12.8 weeks and OS of 46 weeks as compared to the five DKK1-low patients who experienced PFS of 6 weeks and OS of 16 weeks.

·Anti-PD1/PD-L1 refractory GEJ/GC patients: The three DKK1-high patients had a best response of stable disease (SD) and a longer PFS of 13.4 weeks and OS of 37.4 weeks, as compared to the two DKK1-low patients who both had progressive disease (PD) with a PFS of 3.6 weeks and OS of 11.7 weeks.

·Anti-PD-1/PD-L1 naïve GEJ/GC patients: As previously reported, DKK1-high patients experienced over 22 weeks PFS and nearly 32 weeks OS, with a 50% overall response rate and 80% disease control rate (DCR) in ten evaluable patients. DKK1-low patients experienced nearly 6 weeks PFS and over 17 weeks OS, with a 20% DCR in fifteen evaluable patients. PD-L1 Combined Positive Scores (CPS) did not predict efficacy on the combination of DKN-01 plus pembrolizumab. In multi-variate analysis, DKK1-high status correlated with longer PFS independent of PD-L1 CPS scores.

About DKN-01

DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein, a modulator of Wnt/Beta-catenin signaling, a signaling pathway frequently implicated in tumorigenesis and suppressing the immune system. DKK1 has an important role in tumor cell signaling and in mediating an immuno-suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK ligands on tumor cells. The U.S. Food and Drug Administration has granted Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and Fast Track Designation in combination with tislelizumab for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high DKK1 protein, following disease progression on or after prior fluoropyrimidine- and platinum- containing chemotherapy and if appropriate, human epidermal receptor growth factor (HER2)/neu-targeted therapy.

On November 9, 2020 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage biopharmaceutical company pioneering a novel class of immunotherapies, reported that the Company’s T cell therapy demonstrates an 86% objective response rate in combination with Merck’s Keytruda (pembrolizumab) in patients with Program Death Ligand 1 (PD-L1) positive relapsed / refractory diffuse large B-cell lymphoma (r/r DLBCL) (Press release, IMV, NOV 9, 2020, View Source [SID1234570362]). Detailed results will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting, to be held virtually Nov. 9-14, 2020 and during a webcast hosted by IMV on November 12, 2020.

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"Biomarkers are critical for the development of precision medicine in oncology. Not only can they improve the outcome of cancer patients receiving treatments, but they also can greatly reduce the risk inherent in late-stage clinical trials and facilitate the path to market for new treatments such as our new T cell therapy," said Joanne Schindler, Chief Medical Officer at IMV. "DLBCL is the most common form of Non-Hodgkin lymphoma and relapsed/refractory patients need more accessible and better treatment options. Identifying a biomarker predictive of response for these patients was an important objective of our clinical plan and path to approval."

All clinical responses are associated with expression of the PD-L1 biomarker

All clinical responses observed so far in the study have been in PD-L1 positive subjects defined as a percentage of PD-L1+ cells scored in the tumor region of 10% or more. No benefits have been observed in the PD-L1 negative population (n=11) where all subjects experienced Progressive Disease (PD) (n=9) or a Stable Disease (SD) (n=2).

The difference between the two populations is statistically significant and indicates that PD-L1 has the potential to become a predictive biomarker and a companion diagnostic for DLBCL

treatment with the combination, to identify and recruit the patients that are the most likely to respond.

As of the data cut-off date for the presentation at SITC (Free SITC Whitepaper), 18 pre-treatment samples from patients enrolled in the SPiReL study were available for biomarker analysis. Thirty nine percent (7/18) of subjects demonstrated a positive pre-treatment tumor PD-L1 expression. Key findings for this population include:

100% of subjects with Disease Control Rate (DCR) defined as Stable Disease (SD) or Complete or Partial Response (CR or PR)

86% (6/7) of subjects with Objective Response Rate (ORR) (3 CR, and 3 PR)

The PD-L1 pathway regulates T-cell responses allowing tumors to evade detection by the immune system. PD-L1 expression has been extensively studied in relation to the prognosis of various cancers and is approved in multiple tumor types as a predictive biomarker for treatment with checkpoint inhibitors targeting the PD-1/PD-L1 pathway. In DLBCL, PD-L1 has been shown to be expressed in 26% to 75% of patients and is generally thought to be associated with a poor prognosis and shorter survival1,2.

Checkpoint inhibitors such as Keytruda and Opdivo are not approved in DLBCL and have demonstrated limited activity including in PD-L1 positive patients.1,3

Poster Presentation Details

Poster Title

Baseline PD-L1 expression and tumor immune infiltration is associated with clinical response in patients with r/r DLBCL treated with DPX-Survivac, low-dose cyclophosphamide and pembrolizumab

Presenter: Neil Berinstein, MD, FRCPC, ABIM
Hematologist at the Sunnybrook Health Science Centre, Toronto.

Poster is available on Company’s website and on the SITC (Free SITC Whitepaper) conference platform since November 9 at 8.00am EST. The final poster presentation will include additional data collected between the date of the abstract submission and the presentation itself. The poster is available under the Scientific Publications & Posters section on IMV’s website.

Company will discuss the data during a live webcast on November 12 at 8.00am EST with a presentation of the results by Neil Berinstein, MD, FRCPC, ABIM, Principal Investigator of the SPiReL study. Webcast registration will be available under "Events, Webcasts and Presentations" in the Investors section of IMV’s website. The video recording will be available for replay shortly thereafter.

About the SPiReL Study

1 Xu-Monette, Zijun Y et al. "PD-1 expression and clinical PD-1 blockade in B-cell lymphomas" Blood vol. 131,1 (2018): 68-83. doi:10.1182/blood-2017-07-740993
2 Suzuki Y, Kohno K, Matsue K, et al. PD-L1 (SP142) expression in neoplastic cells predicts a poor prognosis for patients with intravascular large B-cell lymphoma treated with rituximab-based multi-agent chemotherapy. Cancer Med. 2020;9(13):4768-4776. doi:10.1002/cam4.3104
3 Ansell SM, et al. Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study. J Clin Oncol. 2019 Feb 20;37(6):481-489. doi: 10.1200/JCO.18.00766

"SPiReL" is a Phase 2 non-randomized, open label, efficacy, and safety study of a novel immunotherapy combination with DPX-Survivac and pembrolizumab. Intermittent low dose cyclophosphamide is given as an immune modulator. Subjects with r/r incurable DLBCL and survivin expression are eligible for participation. The primary outcome is to document the objective response rate using modified Cheson criteria to the combination treatment. Secondary objectives include safety, duration of response and time to next treatment. Exploratory endpoints include T cell response, tumour immune cell infiltration, and biomarker analysis. To date, 24 subjects have been enrolled.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapy that generates targeted and sustained cancer cell killing capabilities in vivo. Treatments with the DPX-Survivac T cell therapy have demonstrated a favorable safety profile across all clinical studies.

IMV’s T cell therapy, DPX-Survivac, consists of survivin-based peptides formulated in IMV’s proprietary delivery platform (DPX). IMV’s lead compound is designed to generate a sustained cytotoxic T cell response against cancer cells presenting survivin peptides on their surface.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to chemotherapies. IMV has identified over 20 cancer indications in which survivin can be targeted by DPX-Survivac.

DPX-Survivac has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer, as well as Orphan Drug designation status from the U.S. FDA and the European Medicines Agency (EMA) in the ovarian cancer indication.

On November 9, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing oncolytic viruses to target hard-to-treat solid tumors, reported that the poster "A randomised open-label phase I/II study adding ONCOS-102 to pemetrexed/cisplatin in patients with unresectable malignant pleural mesothelioma – 12-month analysis of biomarkers and clinical outcomes" are now available at the Company’s website (Press release, Targovax, NOV 9, 2020, View Source [SID1234570361]).

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The abstract presents the 12-month analysis of biomarkers and clinical outcome from the phase I/II trial in malignant pleural mesothelioma where ONCOS-102 is added to standard of care chemotherapy (pemetrexed / cisplatin). This analysis supports the data presented in June.

Title (361): A randomised open-label phase I/II study adding ONCOS-102 to pemetrexed/cisplatin in patients with unresectable malignant pleural mesothelioma – 12-month analysis of biomarkers and clinical outcomes
Presenter:

Prof. Luis Paz-Ares, Principal Investigator of the trial and Chair of the Medical Oncology Department at the Hospital Doce de Octubre, Madrid

Poster session:

Location:

Wednesday 11. November 23:15-23:45 CET (17:15–17:45 EST)

Friday 13. November 22:40-23:10 CET (16:40-17:10 EST)

Virtual Poster Hall

The poster is also available on Targovax’s website.

On November 9, 2020 Ambrx Inc., a clinical-stage biopharmaceutical company focused on developing Precision Biologics using an expanded genetic code reported the successful closing of an oversubscribed US$200 million crossover financing round (Press release, Ambrx, NOV 9, 2020, View Source [SID1234570360]).

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New investors include Fidelity Management & Research Company LLC, funds and accounts managed by BlackRock, Cormorant Asset Management, HBM Healthcare Investments, Invus, Adage Capital Partners and Suvretta Capital Management. BofA Securities acted as the sole placement agent for the offering.

"This financing represents our most significant capital raise to date and includes several leading global and US based healthcare funds. Since mid-2018, our new management team, set on a new long term vision, has committed to building company fundamentals and transforming Ambrx from a technology developer to a full-fledged biopharmaceutical company," said Dr. Feng Tian, CEO and Chairman of Ambrx. "The conclusion of this financing and the strong data emerging from our ongoing clinical programs, as well as our deep preclinical pipeline of proprietary drug candidates, positions the company for rapid growth."

Ambrx technology uses an expanded genetic code to incorporate synthetic amino acids into protein, all completed within a living cell. These synthetic amino acids enable the creation of Precision Biologics, an exciting new class of therapeutics with broad application and potential. This includes next generation antibody drug conjugates (ADCs), bispecifics, and targeted immuno-oncology therapies for cancer as well as smart cytokines to modulate the immune system, and long acting therapeutic peptides for metabolic and cardiovascular disease.

The company’s innovation engine continues to expand the clinical and preclinical pipeline by discovering new and valuable programs that take full advantage of the Ambrx technologies. These novel programs have the potential to address a wide range of diseases with new or improved mechanisms of action, providing the company with a rich set of programs to develop internally or in partnership with leading pharmaceutical companies.