On November 11, 2020 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported that it will today present an updated clinical & translational analysis from its Phase II bemcentinib and pembrolizumab combination study (BGBC008) in advanced non-small cell lung cancer (NSCLC), at an oral presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Annual Meeting (Press release, BerGenBio, NOV 11, 2020, View Source [SID1234570621]).

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The presentation will provide updated data from Cohort B of the study, assessing the safety and efficacy of bemcentinib in combination with anti-PD-1 therapy pembrolizumab, in 16 refractory NSCLC patients previously treated with a PD-L1 or PD-1 checkpoint inhibitor (CPI) as a monotherapy.

"AXL is implicated in resistance to immunotherapy and this study is based around the hypothesis that blocking AXL signalling represents a novel approach to prevent cancer survival mechanisms and to improve the efficacy of immuno-oncology drugs," commented Professor James Spicer, PhD, who will give the presentation at SITC (Free SITC Whitepaper). "Our findings from this interim analysis suggest that bemcentinib has potential to reverse acquired resistance to checkpoint inhibitors among previously treated NSCLC patients by targeting AXL expressing macrophages and regulatory dendritic cells. These encouraging results support the further development of AXL inhibition as a means to extend the efficacy of immunotherapy in biomarker-selected NSCLC patients."

The combination of bemcentinib and pembrolizumab was overall shown to be well tolerated and clinically active in CPI-refractory composite AXL (cAXL) positive NSCLC. Of the evaluable patients in Cohort B 58% were cAXL-positive, 25% were PD-L1 negative (<1%TPS), and 42% patients were PD-L1 low positive (1-49% TPS). 86% of cAXL-positive patients achieved clinical benefit (one partial response, five stable disease) while none was observed in cAXL negative patients.

The study demonstrated a median progression-free survival among cAXL positive patients in Cohort B patients of 4.73 months, compared with 1.87 months among cAXL-negative patients.

Full details of the presentation are as follows:

Title: A PhII study of bemcentinib, a first-in-class selective AXL kinase inhibitor, in combination with pembrolizumab in pts with previously-treated advanced NSCLC: Updated clinical & translational analysis

Author: Professor James Spicer, Professor of Experimental Cancer Medicine at King’s College London

Session/Abstract ID: Combinatorial Therapies, 362

Date/Time: 11 November 2020, 11.40am EST

The presentation will be made available on BerGenBio’s website, under `Presentations’.

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

On November 11, 2020 tar Therapeutics (Nasdaq: NKTR) reported four data presentations for its I-O pipeline from three separate clinical-stage investigational agents at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Nektar Therapeutics, NOV 11, 2020, View Source [SID1234570620]).

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New clinical results were presented for bempegaldesleukin (BEMPEG; NKTR-214), NKTR-262 and NKTR-255. Data for BEMPEG and NKTR-262 were featured in two oral presentation sessions presented by Adi Diab, MD, Associate Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center during, respectively, the Concurrent Rapid Oral Abstract Presentation Session and the Combinatorial Therapies Session on Wednesday, November 11th. Clinical data for NKTR-255 and preclinical data for NKTR-262 were also featured in poster presentations by Dr. Nina Shah, Associate Professor, Department of Medicine, at the University of California San Francisco and Dr. Annah Rolig, Earle A. Chiles Research Institute, Providence Cancer Institute on Monday, November 9th.

Adi Diab, MD, lead investigator of the PIVOT-02 study noted: "These updated PIVOT-02 clinical data further validate our prior results that BEMPEG plus nivolumab provides both deep and durable responses in first-line metastatic Stage IV melanoma patients. We observed a total overall response rate of 53%, with 34% achieving a complete response, and now we have also observed a median depth of response of 78.5%, as well as a median progression free survival for the entire cohort of 30.9 months."

"The data presented at this year’s SITC (Free SITC Whitepaper) Meeting highlight that, by targeting key immunological processes, we have the opportunity to more effectively harness the body’s immune system to fight cancer," said Jonathan Zalevsky, Ph.D., Head of Research and Development at Nektar Therapeutics. "In the PIVOT-02 study of BEMPEG plus nivolumab, we observed that 90% or 18 of the 20 metastatic melanoma patients who responded went on to achieve a 100% reduction in their RECIST target lesions, and, importantly for the first time, we reported a two year survival rate of 77% from this study, and median OS has not yet been reached."

"For our TLR agonist candidate, we presented data demonstrating that the combination of NKTR-262 and bempegaldesleukin alters the tumor micro-environment through activation of both the innate and adaptive arms of the immune system," continued Zalevsky. "Data presented for NKTR-255 demonstrated this novel IL-15 agonist was biologically active in patients. We observed durable and sustained increases in Natural Killer and CD8+ T cells as well as disease stabilization in the first patients who were treated in the lowest dose cohorts, which included patients with highly-refractory and heavily pre-treated multiple myeloma and Non-Hodgkin’s lymphoma."

Clinical presentations at 2020 SITC (Free SITC Whitepaper) are available for download at View Source

Highlights from the presentations are as follows:

Abstract 420: "Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study", Diab, A., et al. (Concurrent Rapid Oral Abstract Presentation Session: Clinical):

Confirmed best overall response rate (ORR) was 53% (20/38) in efficacy-evaluable patients, with a 34% (13/38) complete response (CR) rate. 47% (18/38) of patients achieved 100% reduction in RECIST target lesions. 80% (16/20) of patients had ongoing responses and median duration of response was not reached at a 29-month follow-up. (Response was measured per RECIST 1.1 by blinded independent central radiology review for efficacy-evaluable patients treated. Data cut as of September 1, 2020).
Median progression-free survival (PFS) observed was 30.9 months. Median overall survival (OS) was not reached. Based upon a Kaplan-Meier Estimate of OS, the OS rates at 12 months, 24 months and 36 months are 82%, 77%, and 71%, respectively.
New biomarker translational data presented show non-invasive, on-treatment biomarkers (CD8+ PSD* and eosinophils) predicted response to the combination.
BEMPEG plus NIVO was well tolerated; treatment-related AEs are predictable and consistent with previous reports.
In July of 2019, this novel combination was awarded US FDA Breakthrough Therapy Designation for the treatment of patients with previously untreated unresectable or metastatic melanoma.
In melanoma, registrational Phase 3 trials evaluating BEMPEG plus NIVO are enrolling patients in the first-line metastatic setting (PIVOT IO 001; NCT03635983) and in the adjuvant setting (PIVOT-12; NCT04410445).
Abstract 368: "REVEAL: Phase 1 dose-escalation study of NKTR-262, a novel TLR7/8 agonist, plus bempegaldesleukin: local innate immune activation and systemic adaptive immune expansion for treating solid tumors", Diab, A., et al. (Combinatorial Therapies):

Safety, pharmacokinetics (PK), pharmacodynamics (PD) and biomarker data supported selection of NKTR-262 3.84 mg Intra-Tumoral (IT) plus BEMPEG 0.006 mg IV q3w as the RP2D. A maximum-tolerated dose was not reached.
Robust TLR 7/8 engagement was observed upon administration of NKTR-262 IT.
NKTR-262 plus BEMPEG induced systemic activation of T cells and Natural Killer (NK) cells demonstrating engagement of the entire immune activation cascade required for systemic tumor clearance.
Induction of TLR7/8-responsive genes significantly correlated with CD11c+ baseline density. CD11c+ target cells are significantly more abundant in baseline melanoma biopsies vs other tumor types.
NKTR-262 IT, as monotherapy or in combination with BEMPEG, showed early signs of clinical activity and an acceptable safety profile in a highly relapsed/refractory, heavily pre-treated melanoma patient population.
Abstract 355: "First-in-human phase I study of NKTR-255 in patients with relapsed/refractory hematologic malignancies," Shah, N., et al.

NKTR-255 was biologically active and demonstrated consistent expansion of lymphocytes, with durable and sustained increases in NK and CD8+ T cells in this highly refractory population of patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).
NKTR-255 was well tolerated with low-grade, cytokine-related AEs that were transient and easily managed.
NKTR-255 exhibited a long half-life with no evidence of accumulation.
These data support continued dose escalation of NKTR-255 and subsequent evaluation in combination with other anticancer agents.
Abstract 451: "Combining Bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) pairs local innate activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity", Rolig, A., et al.

BEMPEG/NKTR-262 treatment produces a higher fraction of activated tumor antigen-specific cytotoxic CD8 T cells systemically, correlating with superior anti-tumor efficacy relative to BEMPEG combined with radiotherapy (RT).
BEMPEG/NKTR-262 combination therapy depends on CD8 T cells and NK cells.
BEMPEG/NKTR-262 combination therapy induces intra-tumoral CD8+ T cells that have increased activity as demonstrated by increased granzyme expression and increased tumor killing, and reduced conversion to an exhausted phenotype (PD-1, Tim3, Lag3).
Loss of NK cells reduces CD8+T cell percentages and function in the peripheral blood and in the tumor, suggesting a connection between early NK cell function and anti-tumor adaptive immune responses.
Analyst Call with Panel of Oncology Experts:

Nektar will webcast an analyst and investor conference call that will include SITC (Free SITC Whitepaper) authors and presenters, Dr. Adi Diab, Associate Professor, Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center; Dr. Brendan Curti, Director of the Melanoma Program, Cytokine and Adoptive Immunotherapy and Genitourinary Oncology Research at Providence Cancer Institute; Dr. Nina Shah, Associate Professor, Department of Medicine, at the University of California San Francisco; and Dr. Alan Tan, Assistant Professor, Department of Internal Medicine, Division of Hematology, Oncology and Cell Therapy at Rush Medical College.

Date and Time: Wednesday, November 11, 2020, at 4:15 p.m. EST

Dial-in: 877-881-2183 (toll-free) or 970-315-0453 (enter access code 2090614)

Investors and analysts can also view slides and listen to the live audio webcast of the presentation at View Source The event will also be available for replay for two weeks on the company’s website, www.nektar.com.

Dr. Adi Diab

Adi Diab, M.D., serves as Associate Professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center. Dr. Diab is one of the lead investigators in PIVOT-02, the Phase 1/2 study of BEMPEG plus nivolumab, and in REVEAL, the Phase 1/2 study of NKTR-262 and BEMPEG. He is also on the steering committee for the BMS-sponsored Phase 3 registrational study, PIVOT IO 001, which is ongoing, in patients with previously untreated metastatic melanoma. His research is focused on developing new immunotherapeutic strategies that will improve clinical outcomes in patients. He has authored or co-authored over thirty scientific publications and abstracts and serves as a reviewer for Cancer Discovery, Journal of Clinical Oncology, Nature Reviews Journal of Immunotherapy and Journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).

Dr. Brendan D. Curti

Brendan D. Curti, M.D., is the Robert W. Franz Chair for Clinic Research and Member in the Earle A. Chiles Research Institute at Providence Cancer Institute. He serves as the Director of Cytokine and Adoptive Immunotherapy, Melanoma Program and Genitourinary Oncology Research. His clinical research focuses on developing new immunotherapies for melanoma, renal cell carcinoma, prostate cancer and bladder cancer. He previously served as a Senior Investigator in the Biological Response Modifiers Program at the National Cancer Institute and was an Associate Professor at the Penn State College of Medicine before joining the Earle A. Chiles Research Institute at Providence Cancer Institute.

Dr. Nina Shah

Nina Shah, M.D., is an Associate Professor in the Department of Medicine at the University of California San Francisco and a specialist in blood diseases who focuses on treating multiple myeloma, a type of cancer affecting certain cells in the bone marrow. Her areas of professional interest include the intersection of immunology and oncology as well as helping patients fight multiple myeloma by boosting their immune systems. She is an investigator in the NKTR-255 Phase 1/2 study in hematological malignancies. She belongs to the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), American Society of Hematology (ASH) (Free ASH Whitepaper) and American Society for Transplantation and Cellular Therapy.

Dr. Alan Tan

Alan Tan, MD, is an Assistant Professor in the Division of Hematology, Oncology and Cell Therapy at Rush Medical College. He specializes in kidney cancer, bladder cancer, prostate cancer and melanoma. He also has an extensive background in hematologic malignancies. Dr. Tan has clinical research interest in designing and implementing clinical trials to test novel immunotherapies and targeted therapies for renal cell carcinoma and GU malignancies. He is an investigator in the NKTR-255 Phase 1/2 study in hematological malignancies. He also has interest in precision genomic cancer medicine, identifying molecular alterations that will serve as targets for individualized treatment strategies.

About Bempegaldesleukin (NKTR-214)

Bempegaldesleukin (BEMPEG: NKTR-214) is an investigational CD122-preferential IL-2–pathway agonist that leverages the clinically validated IL-2 pathway to stimulate an antitumor immune response.1 BEMPEG was engineered to deliver a controlled, sustained, and preferential IL-2 pathway signal, with the goals of stimulating an antitumor immune response while minimizing toxicity, thereby allowing for outpatient administration.1,2 In a phase 1 trial of BEMPEG in combination with the checkpoint inhibitor nivolumab (NIVO; PIVOT-02), the combination was well tolerated and produced durable responses that deepened over time in multiple advanced solid tumor types.3

In July of 2019, Bristol-Myers Squibb and Nektar Therapeutics announced that the U.S. Food and Drug Administration granted Breakthrough Therapy Designation for investigational agent bempegaldesleukin in combination with nivolumab for the treatment of patients with previously untreated unresectable or metastatic melanoma.

The Nektar-Bristol-Myers Squibb joint clinical development program for BEMPEG+NIVO includes registrational and other studies of BEMPEG plus NIVO in select tumor types (melanoma, renal cell carcinoma or RCC, and bladder cancer). This includes a Phase 3 trial in first-line advanced melanoma (NCT03635983), a Phase 3 trial in adjuvant melanoma (NCT04410445), a Phase 3 trial in advanced RCC (NCT03729245), a Phase 3 trial in muscle-invasive bladder cancer (NCT04209114), a Phase 2 trial in cisplatin-ineligible urothelial carcinoma (NCT03785925) and a Phase 1/2 trial in combination with a tyrosine kinase inhibitor in advanced RCC (NCT04540705).

BEMPEG is also being evaluated by Nektar in the PROPEL study in combination with pembrolizumab in non-small cell lung cancer (NCT03138889) and in collaboration with Vaccibody in the DIRECT-01 study in combination with VB10.NEO in squamous cell carcinoma of the head and neck (NCT03548467).

About NKTR-255

NKTR-255 is an IL-15 receptor agonist designed to activate the IL-15 pathway, expand NK cells and promote the survival and expansion of memory CD8+ T cells. Through optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances formation of long-term immunological memory, which may lead to sustained anti-tumor immune response. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which is rapidly cleared from the body and must be administered frequently and in high doses, limiting its utility due to toxicity and convenience of use.

About NKTR-262

NKTR-262 is a novel small molecule agonist designed to activate toll-like receptors (TLRs). Intratumoral delivery of NKTR-262 promotes TLR activation to induce the development of antigen-specific immunity by initiating the process by which the immune system generates antigen-specific cytotoxic T cells to the patient’s specific tumor.4 NKTR-214 targets CD122 specific receptors found on the surface of these cancer-killing immune cells, known as CD8+ effector T cells.

On November 11, 2020 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported its financial results and operational highlights for the quarter ended September 30, 2020 (Press release, Oncolytics Biotech, NOV 11, 2020, View Source [SID1234570618]). All dollar amounts are expressed in Canadian currency unless otherwise noted.

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"We continue to execute on our clinical and corporate milestones to expand the understanding and clinical benefit of pelareorep," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech Inc. "Clinical AWARE-1 data presented at SITC (Free SITC Whitepaper) 2020 demonstrated the ability of pelareorep to reverse immunosuppressive tumor microenvironments and generate the anti-tumor T cell clones needed for a durable anti-cancer immune memory effect. These findings reinforce the survival benefit observed in a prior phase 2 study and bode well for a successful outcome of our BRACELET-1 trial, which rapidly completed its safety run-in phase and continues to enroll patients. We look forward to delivering additional mechanistic, biomarker, and efficacy data before the end of this year to inform the design of our phase 3 registrational program."

Dr. Coffey continued, "Data from the AWARE-1 and BRACELET-1 trials expand the commercial opportunity of pelareorep into additional indications and breast cancer subtypes, and the IRENE trial will answer if pelareorep can bolster the effectiveness of an anti-PD-1 combination treatment in triple-negative breast cancer patients. Likewise, our collaboration with Roche and AIO will drive the GOBLET phase 1/2 trial to determine if pelareorep can boost the effectiveness of Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab in patients with difficult-to-treat GI cancers. Together, these trials will define the potential of pelareorep to synergistically combine with checkpoint inhibitors and increase the number of patients responding to such therapies, as well as validate blood-based biomarkers that may facilitate the patient selection process. Finally, the addition of Dr. Richard Vile, a world-renowned expert in oncolytic viruses and immuno-oncology, to our Scientific Advisory Board, positions Oncolytics to expand the clinical applicability of pelareorep within breast cancer and across multiple cancer indications."

Third Quarter and Subsequent Highlights

Clinical Highlights

Presented new AWARE-1 Findings of Pelareorep-Induced Increases in CelTIL and Generation of Anti-tumor T Cell Clones in HR+/HER2- Breast Cancer Patients
Newly announced AWARE-1 data presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Annual Meeting showed that systemic pelareorep administration led to the generation of new anti-viral and anti-tumor T cell clones and an average 14-fold increase in intratumoral CD8 T cells. Data also showed that 70% of patients saw an increase in CelTIL (the study’s primary endpoint), a measure of tumor-associated cellularity and tumor-infiltrating lymphocytes that is associated with favorable clinical response. These data support the results of a prior successful phase 2 trial (IND-213) that showed a near doubling of overall survival with pelareorep treatment by demonstrating pelareorep’s ability to induce a robust and potentially long-lasting anti-tumor T cell response in patients with HR+/HER2- breast cancer (link to PR, link to poster). Oncolytics recently completed enrollment of AWARE-1’s first two cohorts and expects to present additional data from the study by year-end.

Initiation of Dosing in Phase 2 IRENE Study
The investigator-sponsored study, which represents an expansion of Oncolytics’ lead breast cancer program into a new disease subtype, will investigate the use of pelareorep in combination with Incyte’s anti-PD-1 checkpoint inhibitor retifanlimab (INCMGA00012) in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). In addition to investigating the safety and efficacy of pelareorep-anti-PD-1 combination treatment in TNBC patients, IRENE will also evaluate changes in PD-L1 expression and correlations between treatment outcomes and peripheral T cell clonality, a previously identified biomarker of pelareorep response.

Initiated Phase 1/2 GOBLET Study in Collaboration with Roche and AIO
The recently announced multi-center trial will be managed by AIO, a leading academic cooperative medical oncology group based in Germany, and will investigate the use of pelareorep in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab (Tecentriq) in patients with metastatic pancreatic, metastatic colorectal and advanced anal cancers. The study builds on previously reported early clinical data showing that pelareorep-based combination treatments stimulated an adaptive immune response and led to a greater than 90% clinical benefit rate in KRAS mutated colorectal cancer patients (link to PR, link to study), as well as a greater than 80% increase in progression-free survival in pancreatic cancer patients with low levels of CEACAM6 expression (link to PR, link to poster). In addition to evaluating the safety and efficacy of pelareorep-atezolizumab treatment, the trial also seeks to validate CEACAM6 and T cell clonality as predictive blood-based biomarkers, which may improve the patient selection process in future registration studies and increase their likelihood of success.

Corporate Highlights

Appointed Richard Vile, Ph.D., to Scientific Advisory Board (SAB)
Dr. Vile, a Professor of Immunology at the Mayo Clinic, is a world-renowned scientist and long-time collaborator of Oncolytics with extensive experience studying pelareorep. Dr. Vile is a recognized key opinion leader whose research focuses on several areas of immuno-oncology, including oncolytic viruses, adoptive cell therapies (ACTs) such as chimeric antigen receptor (CAR) T cells, and potential synergistic interactions between oncolytic viruses and ACTs. In addition to his role as a professor at the Mayo Clinic ("Mayo"), Dr. Vile is the Director of Mayo’s Immuno-oncology and Gene and Virus Therapy programs and Co-Director of the Cancer Immunology and Immunotherapy program. He also serves on the editorial board of several prestigious scientific journals, including Molecular Therapy, Gene Therapy, The Journal of Gene Medicine, and OncoImmunology.

Appointed Thomas C. Heineman, M.D., Ph.D., as Global Head of Clinical Development and Operations
Dr. Heineman has extensive experience leading clinical development at biotech companies, most recently serving as Senior Vice President and Head of Clinical Development at Denovo Biopharma. Prior to his time at Denovo, Dr. Heineman served as Vice President and Head of Clinical Development at Genocea Biosciences and Halozyme Therapeutics, where he was also the Head of Translational Medicine. Dr. Heineman’s experience further extends into big pharma and academia, as he has previously held roles as Senior Director, Global Clinical Research and Development at GlaxoSmithKline and as an Associate Professor at the Saint Louis University School of Medicine.

Financial Highlights

As of September 30, 2020, the Company reported $26.7 million in cash and cash equivalents. The Company raised $3.6 million during the third quarter through the issuing of common stock through our ATM facility.

Operating expense for the third quarter of 2020 was $2.5 million, compared to $1.8 million in the third quarter of 2019.

R&D expense for the third quarter of 2020 was $3.9 million, compared to $1.7 million in the third quarter of 2019.

Net cash used in operating activities for the third quarter of 2020 was $6.1 million, compared to $4.5 million for the third quarter of 2019.

The net loss for the third quarter of 2020 was $6.7 million, compared to a net loss of $3.5 million in the third quarter of 2019. The basic and diluted loss per share was $0.16 in the third quarter of 2020, compared to a basic and diluted loss per share of $0.16 in the third quarter of 2019.
Anticipated Milestones & Catalysts

Presentation of new AWARE-1 data and analyses: Q4 2020

Announcement of final data from phase 2 NU 18I01 second-line pancreatic cancer study*: H1 2021

Dosing of the first patient in GOBLET study in gastrointestinal cancer: H1 2021
Oncolytics expects to provide updates on the timing of the following milestones over the coming months:

Announcement of interim data from phase 1 WINSHIP 4398-18 multiple myeloma study

Interim safety update for phase 2 BRACELET-1 metastatic breast cancer study

Final biomarker data for AWARE-1 breast cancer study

Complete enrollment in phase 2 BRACELET-1 metastatic breast cancer study

Final data for phase 2 BRACELET-1 metastatic breast cancer study
*Guidance provided by clinical investigators

Update on COVID-19

Company Continues to Efficiently Execute Business Continuity Plan
Oncolytics has developed a robust business continuity plan to ensure the safety of patients, employees, and investigators, as well as the productivity of our clinical programs. We expect that the continued execution of this plan will allow the Company to build on the positive momentum of the past two quarters, despite any COVID-19-related challenges that may arise. Moving forward, we plan to remain in contact with relevant stakeholders and keep the market apprised of any new information that may impact clinical timelines.

Webcast and Conference Call
Management will host a conference call for Analysts and Institutional Investors at 5 pm ET today, November 11, 2020. To access the call, please dial (888) 231-8191 (North America) or (647) 427-7450 (International) and, if needed, provide confirmation number: 678-8931. A live webcast of the call will also be available by clicking here or on the Investor Relations page of Oncolytics’ website (LINK) and will be archived for three months. A dial-in replay will be available for one week and can be accessed by dialing (855) 859-2056 (North America) or (416) 849-0833 (International) and using reference code: 678-8931.View Source;tp_key=fb7d246153

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 IRENE
The IRENE (INCMGA00012 and the oncolytic virus pelareorep in metastatic triple-negative breast cancer) study is a single-arm, open-label, phase 2 study evaluating the combination of pelareorep and INCMGA00012 for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer. The study will enroll 25 patients and will be conducted at the Rutgers Cancer Institute of New Jersey and The Ohio State University Comprehensive Cancer Center.

Study participants will receive pelareorep intravenously on days 1, 2, 15, and 16 of 28-day treatment cycles. INCMGA00012 will be administered on day 3 of each cycle, with treatment cycles continuing until disease progression is observed. The co-primary endpoints of the study are safety and objective response rate. Secondary endpoints include progression-free survival, overall survival, and duration of response. Exploratory endpoints include peripheral T cell clonality and pre- vs. post-treatment change in tumor PD-L1 expression.

For more information on the IRENE study, refer to View Source

About GOBLET
The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication biomarker, safety, and efficacy study in advanced or metastatic GI tumors. The study will be conducted at 25 centers in Germany. The primary endpoint of the study is safety, with overall response rate and blood-based biomarkers (T cell clonality and CEACAM6) as exploratory endpoints. Approximately 55 patients are planned for enrollment across four separate cohorts:

Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line metastatic Pancreatic cancer patients (n=12);
Pelareorep in combination with atezolizumab in 2nd and 3rd line metastatic colorectal cancer patients that are diagnosed as MSI high (microsatellite instability) (n=19);
Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients (n=14); and
Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients (n=10).
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 Gastrointestinal Cancer
Excluding skin cancers, colorectal cancer is the third most common cancer, with an estimated 104,610 new cases of colon cancer and 43,340 new cases of rectal cancer diagnosed in the U.S. in 20201. Also, for the 2020 year, the American Cancer Society estimates there will be 57,600 new cases of pancreatic cancer2 and 8,590 new cases of anal cancer 3 in the U.S.

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.

On November 11, 2020 Inhibrx, Inc. (Nasdaq: INBX), a biotechnology company with four clinical programs in development, reported updated interim results today from a Phase 1 clinical trial evaluating the efficacy and safety of INBRX-109 in patients with chondrosarcoma (Press release, Inhibrx, NOV 11, 2020, View Source [SID1234570617]). This data will be presented to attendees of the Annual Connective Tissue Oncology Society ("CTOS") Conference on November 20, 2020 (Paper #16). Chondrosarcoma is an orphan disease and bone cancer with approximately 2,800 new patients diagnosed annually in the United States and the European Union. There are currently no therapeutics approved for the treatment of chondrosarcoma.

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Inhibrx’s most advanced program, INBRX-109, is a precision-engineered, tetravalent DR5 agonist antibody designed to exploit the tumor-biased cell death induced by DR5 activation.

Of the 12 patients evaluable for efficacy within the ongoing chondrosarcoma expansion cohort to date, disease control was observed in 11 of 12 patients (92%) and 8 of 12 patients (67%) had a decrease in their tumor burden by RECIST.
Two of the patients achieved partial responses with reductions in tumor size of 60% and 32% as of October 2020.
Based on these preliminary results, the observed disease control rate at the four-month follow-up was 8 of 12 subjects (67%) with 7 of 12 patients continuing on study. The longest disease control duration observed to date for a patient in this cohort was 33 weeks, or approximately eight months.
The safety and tolerability profile continued to be favorable with most patients, approximately 90%, experiencing no signs of hepatotoxicity. There have been no new serious or severe adverse events since Inhibrx’s last safety update in July 2020.
The trial is ongoing and an additional 10 patient slots were added, per investigator requests, to the chondrosarcoma cohort.
"I am quite pleased to see prolonged progression free survival in a disease that has been unresponsive to conventional therapies," notes Dr. Sant P. Chawla, one of the principal investigators conducting the Phase 1 trial at the Sarcoma Oncology Center in Santa Monica, California.

"We believe the results in chondrosarcoma, a disease with a significant unmet need, are very promising. We are meeting with the Food and Drug Administration in the near future to discuss the design of a registration-enabling study that we anticipate initiating in the second quarter of next year," said Mark Lappe, CEO for Inhibrx. "Additionally, this month, we will initiate dosing in patients with synovial sarcoma, as well as our first chemotherapy combination cohorts with INBRX-109 in pancreatic adenocarcinoma and epithelioid subtype malignant pleural mesothelioma."

Conference Call Details
Inhibrx will hold a conference call to discuss these results today at 2:30 p.m. PT. Investors may join via the web: View Source or may listen to the call by dialing (1-877-870-4263) from locations in the United States or (1-412-317-0790) from outside the United States. Please refer to Inhibrx, Inc. when calling in. Following the webcast, the presentation may be accessed through a link on the investors section of Inhibrx’s website at View Source The webcast will be available for 60 days following the event. Inhibrx has also updated its corporate presentation which is available on the "Investors" section of its website at www.inhibrx.com.

About INBRX-109
INBRX-109 is a precisely engineered tetravalent single domain antibody (sdAb) based therapeutic candidate that agonizes DR5 to induce tumor selective programmed cell death. A three-part, Phase 1 clinical trial was initiated in November 2018. Part 1, dose escalation, was completed in August 2019 with enrollment of 20 patients. INBRX-109 was well-tolerated, with no significant toxicities observed at doses up to and including the maximum administered dose of 30 mg/kg. No maximum tolerated dose was reached. Part 2, single agent dose expansion, commenced in September 2019, while Part 3, chemotherapy combination cohorts, initiated this month in epithelioid subtype malignant pleural mesothelioma and pancreatic adenocarcinoma.

About the Inhibrx sdAb Platform
Inhibrx utilizes diverse methods of protein engineering in the construction of therapeutic candidates that can address the specific requirements of complex target and disease biology. A key tool for this effort is the Inhibrx proprietary sdAb platform, which enables the development of therapeutic candidates with attributes superior to other monoclonal antibody and fusion protein approaches. This platform allows for the combination of multiple binding units in a single molecule, enabling therapeutic candidates with precisely defined valency or multiple specificities that can achieve enhanced cell signaling or conditional target activation. An additional benefit of this platform is that these optimized, multi-functional entities can be manufactured using established processes that are commonly used to produce therapeutic proteins.

On November 11, 2020 Protagonist Therapeutics, Inc. (NASDAQ:PTGX) reported that Dinesh V. Patel, Ph.D., President and Chief Executive Officer, will participate in a fireside chat at the upcoming Jefferies Virtual 2020 London Healthcare Conference (Press release, Protagonist, NOV 11, 2020, View Source [SID1234570616]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Presentation details:
Date: Tuesday, Nov. 17, 2020
Time: 5:35 p.m. GMT (12:35 p.m. EST)

A live and archived webcast of the event will be available at View Source and in the Investors section of the Protagonist Therapeutics website at View Source