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Oncolytics Biotech® and PrECOG Announce Collaboration for BRACELET-1 (PrE0113) Study in Metastatic Breast Cancer

On October 22, 2019 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, and PrECOG LLC, a leading cancer research network, reported their collaboration in which PrECOG will run the BRACELET-1 (PrE0113) study (Press release, Oncolytics Biotech, OCT 22, 2019, View Source [SID1234542410]). The principal investigator will be Kathy Miller, MD, Ballve-Lantero Professor of Oncology at Indiana University School of Medicine and Associate Director of Clinical Research at Indiana University Melvin and Bren Simon Cancer Center, and PrECOG member. The study will take place in 15 centers in the United States and will evaluate the ability of pelareorep to make tumors immunologically visible to checkpoint inhibitors.

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"We’re very excited to be working with PrECOG on the BRACELET-1 study focused on hormone receptor-positive metastatic breast cancer patients, our target patient population," said Rita Laeufle, Chief Medical Officer at Oncolytics Biotech. "Our goal in this study is to confirm our biomarker of T cell clonality in order to predictively and prognostically select patients for the phase three study, as well as to demonstrate that pelareorep sensitizes the tumor to immunotherapy and improves clinical outcomes. By creating an immunogenic tumor environment with pelareorep, we can potentially increase the efficacy of checkpoint blockade and treat more patients with this novel treatment combination. This important study, along with our ongoing AWARE-1 trial, will help determine the design of the phase three registrational program for pelareorep in metastatic breast cancer, which we expect may involve combination therapy with a checkpoint inhibitor."

"We in PrECOG are excited to be investigating this novel approach to breast cancer treatment, and to bring cutting edge options to our patients," said Peter O’ Dwyer, MD, Chief Executive Officer, PrECOG, and Co-Chair, ECOG-ACRIN Cancer Research Group. "Approaches to increase the activity of these immunologically active agents are a focus of our research and studies like this have the potential to be relevant to these mechanisms across many tumor types."

PrECOG has multiple trials in the immuno-oncology space. "Immunotherapy remains in its infancy in the treatment of breast cancer. The potential for pelareorep to extend the benefits of immunotherapy to patients with hormone-sensitive disease could be a real advantage for patients," said Dr. Miller.

The BRACELET-1 (PrE0113) study seeks to replicate a previous trial that supported an advantage in overall survival through the use of pelareorep in patients with hormone receptor-positive (HR+) metastatic breast cancer. It is being designed as a phase 2, three-arm, 48-patient open-label study for second-line treatment in these patients. The first arm will be paclitaxel alone, the second arm will be paclitaxel plus pelareorep, and the third arm will be paclitaxel plus pelareorep, plus the PD-L1 checkpoint inhibitor, avelumab.

The design is expected to be finalized in the coming weeks with input from Oncolytics’ co-development partners Pfizer and Merck KGaA. It will then go to the FDA for review. The study is anticipated to begin enrollment in Q1 2020.

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 PrECOG
PrECOG, LLC is a cancer research group formed as a not-for-profit limited liability company in 2006 by the ECOG Research and Education Foundation, Inc. A central focus of PrECOG is to support the overall purpose of the ECOG-ACRIN Cancer Research Group. Its goal is to achieve research advances in all aspects of cancer care, reduce the burden of cancer, and improve the quality of life and survival in patients with cancer. PrECOG’s current portfolio includes exploratory phase 1 and 2 studies as well as phase 3 registration studies conducted in the US and the EU. For further information, please visit www.precogllc.org and www.ecog-acrin.org.

Nurix Therapeutics Announces Upcoming Scientific Presentation for its CBL-B Program at the Society for Immunotherapy of Cancer 34th Annual Meeting (SITC 2019)

On October 22, 2019 Nurix Therapeutics, Inc., a company developing therapies that control disease-causing proteins, reported that it will present data on its wholly-owned, CBL-B small molecule drug development program at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting (SITC 2019) (Press release, Nurix Therapeutics, OCT 22, 2019, View Source [SID1234542409]). SITC (Free SITC Whitepaper) is being held on November 6-10, 2019 at the Gaylord National Hotel and Convention Center in National Harbor, Maryland.

Presentation Details:
Title: Pharmacological evaluation of the ubiquitin ligase CBL-B as a small molecule, tumor immunotherapy target
Poster #: P669
Date: Friday, November 8, 2019
Time: 7:00 a.m. – 8:00 p.m. EST

Moleculin Increases Annamycin Production Due to Positive Clinical Trial Activity and Expanded Potential Indications

On October 22, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported the expansion of Annamycin production commitments in response to management’s assessment of positive AML clinical trial activity and the potential expansion of indications for use to include lung-localized tumors (Press release, Moleculin, OCT 22, 2019, View Source [SID1234542408]). The purchase commitment arranged through Davos Pharmaceuticals includes moving final production of Annamycin to a larger-scale suite within BSP Pharmaceuticals S.p.A. ("BSP") in Latina, Italy. Until now, BSP has been producing the clinical supplies of Annamycin in a smaller pilot-scale suite.

Moleculin Biotech, Inc. is a clinical stage pharmaceutical company focused on the development of a broad portfolio of oncology drug candidates for the treatment of highly resistant tumors.

"Our clinical trials of Annamycin in relapsed and refractory acute myeloid leukemia ("AML") have been going better than expected, as it now appears we will be able to reach a higher maximum tolerable dose than what was established in previous clinical trials," commented Walter Klemp, Moleculin’s Chairman and CEO. "That not only increases our chances for improved patient outcomes, it places a higher demand on drug supply. Coupled with the recent discovery in animal models that Annamycin may be well suited to treat lung-localized tumors because of its ability in such models to accumulate in the lungs at nearly 6 times the level of the current standard of care anthracycline, we are clearly going to need more drug."

Dr. Donald Picker, Moleculin’s Chief Science Officer added: "With management’s view of success in clinic and the expectation of wider demand resulting from additional clinical trials in lung-localized tumors, it’s time for Moleculin to start preparing for an eventual drug approval process. That requires the development and validation of commercial scale methods and this move with BSP marks the beginning of that process. In addition to increasing the scale of clinical supply production, we will be working with BSP and with our manufacturer of API to develop the commercial scale synthesis and drug production methods we will need to ultimately prepare for New Drug Approval."

MacroGenics Announces Second Interim Overall Survival Data from Phase 3 SOPHIA Study of Margetuximab in Patients with HER2-Positive Metastatic Breast Cancer

On October 22, 2019 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported topline results from the second pre-specified interim overall survival (OS) analysis for the Phase 3 SOPHIA study of margetuximab in patients with HER2-positive metastatic breast cancer who have previously been treated with anti-HER2-targeted therapies (Press release, MacroGenics, OCT 22, 2019, View Source [SID1234542407]). Margetuximab is an investigational, immune-enhancing monoclonal antibody derived from the Company’s proprietary Fc Optimization technology platform.

The second interim OS analysis was based on 270 events. In the intent-to-treat (ITT) population, the median OS of patients treated with margetuximab and chemotherapy was prolonged by 1.8 months compared to that of patients who received trastuzumab and chemotherapy (21.6 months versus 19.8 months; hazard ratio [HR]=0.885; 95% CI: 0.693-1.130; p=0.326). A pre-specified exploratory objective was to evaluate the effect of CD16A allelic variation on margetuximab activity. Among the approximately 85% of patients carrying a CD16A 158F allele, the median OS was prolonged by 4.3 months in the margetuximab arm compared to the trastuzumab arm (23.7 months versus 19.4 months; HR=0.793; 95% CI: 0.607-1.035; p=0.087). Among the approximately 15% of patients who were homozygous for the CD16A 158V allele, the trastuzumab arm performed better than the margetuximab arm. The final pre-specified OS analysis is planned after 385 events have accrued, which is projected to occur in 2020. The first sequential primary endpoint of progression-free survival (PFS) in the ITT population was achieved, with statistical significance as previously reported.

Margetuximab plus chemotherapy had a generally comparable safety profile overall to that of trastuzumab plus chemotherapy, consistent with data previously reported from the study. Grade 3 or greater adverse events occurred in 145 (55%) patients on the margetuximab arm compared to 140 (53%) patients on the trastuzumab arm. Serious adverse events occurred in 45 (17%) patients on the margetuximab arm compared to 50 (19%) patients on the trastuzumab arm. Infusion-related reactions were more common with margetuximab treatment than with trastuzumab (13% versus 3%) and were mostly Grade 1 or 2 and associated with the first dose.

Detailed results from the second interim OS analysis from the SOPHIA study are scheduled to be presented during an oral session at the upcoming San Antonio Breast Cancer Symposium (SABCS) in December. MacroGenics expects to submit a Biologics License Application (BLA) to the FDA before the end of 2019.

About the SOPHIA Study

The SOPHIA study (NCT02492711) is a randomized, open-label Phase 3 clinical trial evaluating margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer. To be eligible for the study, patients must have received at least two prior lines of anti-HER2-directed therapy in the metastatic setting, or in the case of having received (neo)adjuvant pertuzumab, at least one prior line of anti-HER2-directed therapy in the metastatic setting; and who have received at least one and no more than three prior lines of therapy overall in the metastatic setting. All study patients had previously received trastuzumab and pertuzumab, and approximately 90% had previously received ado-trastuzumab emtansine, or T-DM1.

The study enrolled 536 patients who were randomized 1:1 to receive either margetuximab (n=266) given intravenously at 15 mg/kg every three weeks or trastuzumab (n=270) given intravenously at 6 mg/kg (or

Exhbit 99.1
8 mg/kg for loading dose) every three weeks in combination with one of four chemotherapy agents (capecitabine, eribulin, gemcitabine or vinorelbine) given at the standard dose. Patients were stratified by the number of metastatic sites (≤2 or >2), number of lines of prior therapy for metastatic disease (≤2 or >2) and choice of chemotherapy. Intent-to-treat analysis occurred after 265 PFS events.

Primary endpoints are sequentially-assessed PFS, determined by centrally-blinded radiological review, and OS. Key secondary endpoints are PFS by investigator assessment and objective response rate (ORR). PFS and ORR were assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

About HER2-positive Breast Cancer

Human epidermal growth factor receptor 2 (HER2) is a protein found on the surface of some cancer cells that promotes growth and is associated with aggressive disease and poor prognosis. Approximately 15-20% of breast cancer cases are HER2-positive. Monoclonal antibodies (mAbs) targeting HER2 have greatly improved outcomes of patients with HER2-positive breast cancer and are now standard of care in both early-and late-stage disease. However, metastatic breast cancer remains an unmet need that eventually advances to the point where no currently approved HER2-targeting therapy continues to control the disease. Ongoing HER2 blockade is recommended for relapsed or refractory patients, but there is no approved therapy in the third line and beyond setting, or established standard of care after progression with trastuzumab, pertuzumab and ado-trastuzumab emtansine.

About Margetuximab

Margetuximab is an investigational monoclonal antibody that targets the HER2 oncoprotein. HER2 is expressed by tumor cells in breast, gastroesophageal and other solid tumors. Margetuximab was designed to provide HER2 blockade and has similar HER2 binding and antiproliferative effects as trastuzumab. In addition, margetuximab has been engineered with MacroGenics’ Fc Optimization technology to enhance the engagement of the immune system. Margetuximab is also being evaluated in combination with anti-PD-1 therapy for the treatment of patients with HER2-positive gastroesophageal cancer and the registration-directed Phase 2/3 MAHOGANY trial (NCT04082364) has recently opened to patient enrollment.

About MacroGenics’ Fc Optimization Technology

MacroGenics’ Fc Optimization platform is designed to modulate an antibody’s interaction with immune effector cells. The Fc region of certain antibodies binds activating and inhibitory receptors, referred to as FcγRs, on immune cells found within the innate immune system. Such interactions affect killing of cancer cells through antibody dependent cellular cytotoxicity (ADCC), among other Fc-dependent functions.

The activating CD16A FcγR occurs in two variants, or alleles, with high (158V) or low (158F) affinity for the Fc domain of IgG1. A majority (approximately 85%) of the population carries the 158F allele, either in the homozygous form or as heterozygous with 158V. Patients that carry the 158F allele have been reported to show diminished clinical responses to certain therapeutic antibodies, including trastuzumab.

MacroGenics’ optimized Fc region binds with increased affinity to CD16A, including the 158F low-affinity allele, and, unique to MacroGenics’ technology, with reduced affinity to CD32B, the inhibitory FcγR. MacroGenics’ optimized Fc mediates improved effector functions, such as ADCC. To date, MacroGenics has incorporated its proprietary Fc Optimization technology in margetuximab, as well as enoblituzumab, an anti-B7-H3 monoclonal antibody currently in development in combination with anti-PD-1 therapy for cancer treatment.

Lineage Cell Therapeutics to Present at Dawson James Securities 5th Annual Small Cap Growth Conference on October 29, 2019

On October 22, 2019 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs, reported that Brandi L. Roberts, Chief Financial Officer, will be presenting at the Dawson James Securities 5th Annual Small Cap Growth Conference on October 29th, 2019 at 4:05pm Eastern Time at the Wyndham Grand Hotel in the Preserve Ballroom in Jupiter, Florida (Press release, Lineage Cell Therapeutics, OCT 22, 2019, View Source [SID1234542406]).

Interested parties can access a live audio webcast on the Events and Presentations section of Lineage’s website and an archived presentation will be available for 30 days.