On December 11, 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 updated results from the Phase 3 SOPHIA study comparing margetuximab plus chemotherapy versus trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer who have previously been treated with anti-HER2-targeted therapies (Press release, MacroGenics, DEC 11, 2019, View Source [SID1234553173]). Margetuximab is an investigational, immune-enhancing monoclonal antibody derived from the Company’s proprietary Fc-engineering technology platform. The data were presented today during an oral session at the San Antonio Breast Cancer Symposium (SABCS) by Dr. Hope Rugo, M.D., Director, Breast Oncology and Clinical Trials Education, University of California San Francisco Helen Diller Family Comprehensive Cancer Center.

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"Patients with later stage HER2-positive metastatic breast cancer need access to new therapies. The updated SOPHIA study results presented today at the second interim survival analysis showed a trend in overall survival favoring margetuximab and are encouraging. Furthermore, margetuximab is the only HER2-targeted agent to show PFS superiority versus trastuzumab in a head-to-head Phase 3 clinical trial," said Dr. Rugo. "The SOPHIA study also includes a pre-specified analysis of CD16A genotype as a predictor of anti-HER2 antibody efficacy, which although exploratory, is the first such prospective clinical analysis and suggests differential benefit in this population."

Overall survival (OS) results favored margetuximab plus chemotherapy compared with trastuzumab and chemotherapy in the intention-to-treat (ITT) population; however, these data did not reach statistical significance at this second interim analysis as of a September 2019 cut-off after 270 events (median OS=21.6 months versus 19.8 months; hazard ratio [HR]=0.89; 95% CI: 0.69-1.13; P=0.326). The final pre-specified OS analysis is planned after 385 events have accrued, which is projected to occur in the second half of 2020. A pre-specified exploratory objective of the study was to evaluate the effect of CD16A (Fcγ receptor) allelic variation on margetuximab activity. Among the genetically defined subpopulation of patients carrying a CD16A 158F allele, who represent approximately 85% of the human (and SOPHIA study) population, the median OS at the second interim analysis was prolonged by 4.3 months in the margetuximab arm compared to the trastuzumab arm (23.7 months versus 19.4 months; HR=0.79; 95% CI: 0.61-1.04; nominal 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.

As previously reported, margetuximab plus chemotherapy showed a statistically significant improvement in independently-assessed progression-free survival (PFS) compared to trastuzumab plus chemotherapy in this study as of an October 2018 cut-off after 256 events (median PFS=5.8 months versus 4.9 months; HR=0.76; 95% CI: 0.59-0.98; P=0.033). An updated investigator-assessed analysis as of a September 2019 cut-off showed consistent results after 430 PFS events (median PFS=5.7 months in the margetuximab arm versus 4.4 in the trastuzumab arm; HR=0.71; nominal P=0.0006). Similarly, at the time of this updated analysis, additional patients were evaluable for response in the ITT population. Investigator-assessed objective response rate (ORR) was 25.2% (95% CI: 20.1-30.9%) in the margetuximab arm compared to 13.7% (95% CI: 9.8–18.4%) in the trastuzumab (nominal P=0.0006). The clinical benefit rate (CBR, which includes CR+PR+SD>6 months, was 48.1% (95% CI: 42.0-54.3%) in the margetuximab arm versus 35.6% (95% CI: 29.9-41.6%) in the trastuzumab arm (nominal P=0.0025).

"MacroGenics is focused on developing novel antibody-based therapies for patients who face unmet medical needs. We believe that margetuximab, if approved by regulators, will address an important unmet need and could become a valuable treatment option for patients living with this devastating disease," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We are grateful for the patients who participated in this study, as well as their families, and look forward to submitting a BLA to the FDA, which we expect to occur before the end of the year."

Margetuximab plus chemotherapy has shown a safety profile generally comparable to that of trastuzumab plus chemotherapy in this study. As of the April 2019 cut-off for safety, Grade 3 or greater adverse events occurred in 142 (54%) patients on the margetuximab arm compared to 140 (53%) patients on the trastuzumab arm. Serious adverse events occurred in 43 (16%) patients on the margetuximab arm compared to 49 (18%) patients on the trastuzumab arm. Infusion-related reactions (IRR) 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. A substudy evaluating shorter, 30-minute infusions of margetuximab in Cycle 2 and beyond showed no effect on safety outcomes, as well as risk or severity of IRR. These data will be presented at the SABCS during Poster Session 1, today from 5:00 – 7:00 p.m. CT (P1-18-04: Gradishar, et al. "Phase 3 SOPHIA study of margetuximab + chemotherapy vs trastuzumab + chemotherapy in patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies: infusion time substudy results").

The presentations are available on the Events & Presentations page on MacroGenics’ website at View Source

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, who have previously been treated with anti-HER2-targeted therapies. 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 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. Intent-to-treat PFS 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 ORR. Tertiary endpoints include ORR by investigator assessment and safety. 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 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, the Fc region of 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. The company has initiated the registration-directed Phase 2/3 MAHOGANY trial (NCT04082364).

On December 11, 2019 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB), a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that positive frontline data for naxitamab will be presented at the Company’s R&D event, which takes place in New York City today at 12 p.m. Eastern (Press release, Y-mAbs Therapeutics, DEC 11, 2019, View Source [SID1234552257]). Key opinion leaders, including Dr. Shakeel Modak, M.D., MRCP and Dr. Kim Kramer, M.D., both from Memorial Sloan Kettering Cancer Center ("MSK") and Dr. Jaume Mora, M.D., Ph.D. from SJD Barcelona Children’s Hospital, will discuss the current treatment landscape and unmet medical needs for high-risk neuroblastoma and other solid tumors. Members of the media and public may access the event via a live webcast.

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Dr. Mora, who has experience treating frontline neuroblastoma patients with both naxitamab and a competing anti-GD2 antibody, will present clinical data from both antibodies. Data from an investigator sponsored frontline study of 34 patients with high-risk stage 4 neuroblastoma in first complete remission showed a 72% event free survival at 24 months for naxitamab patients, which compared favorably to the 63% reported at 24 months for a population of 89 patients treated with a competing anti-GD2 antibody. In addition, it was noted that only 20% of the patients treated with naxitamab received bone marrow transplant, as was the case for all patients treated with the competing anti-GD2 antibody. In terms of overall survival ("OS"), the naxitamab patients achieved an 86% OS at 24 months, compared to 84% OS for the competing anti-GD2 antibody.

The naxitamab treatment was well-tolerated, and the infusion related pain generally associated with anti-GD2 antibodies required significantly less opioids for naxitamab than for the competing anti-GD2 antibody. The use of morphica generally declined significantly after the first treatment cycle, and naxitamab required less than 15% of the morphine dose required by the competing anti-GD2 antibody. A second frontline study with naxitamab is currently ongoing at MSK in New York City, and Y-mAbs expects data from this study to be published in the first half of 2020. Y-mAbs is also planning a multicenter frontline study, which we expect to initiate in 2020.

"I am delighted and excited to welcome this excellent group of key opinion leaders to our R&D Event. It will be a great opportunity to learn more about the clinical experience of both naxitamab and omburtamab, also noting that SJD Barcelona Children’s Hospital, a major pediatric center located in Barcelona, Spain, has produced very encouraging frontline naxitmab data," said Thomas Gad, Founder, Chairman, President and Head of Business Development and Strategy.

Dr. Claus Moller, Chief Executive Officer further notes, "We are excited to share the first ever frontline data from naxitamab, and believe this to be class leading clinical results. The reduced use of morphica and the convenience of giving naxitamab in an outpatient setting, shows the important role naxitamab has in addressing the clear unmet medical needs of children waiting for new treatment options."

MSK has institutional financial interests with Y-mAbs in the form of equity and intellectual property interests through licensing agreements.

On December 11, 2019 Omega Funds, a leading international investment firm focused on delivering impactful medicines to patients, reported the closing of Omega Fund VI, L.P. ("Fund VI"), with $438 million in capital commitments (Press release, Omega Fund Management, DEC 11, 2019, View Source [SID1234552274]). With Fund VI, the firm will continue to execute on its strategy of creating and investing in life sciences companies that target the most urgent medical needs. Since its inception in 2004, Omega Funds has raised more than $1 billion to invest in exceptional entrepreneurs developing innovative products across multiple therapeutic areas, including oncology, immunology, rare diseases, precision medicine and others.

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Omega Funds has a strong track record of identifying and supporting great management teams and companies by providing domain knowledge and perspective, network connectivity, and capital. Omega Funds’ portfolio companies have brought 37 new products to market and the firm’s investments have contributed to 24 successful portfolio company IPOs and 35 portfolio company exits via M&A.

"We appreciate the trust from our limited partners and their support of our distinctive investment style, which is guided by our conviction in people, products and breakthrough ideas, not by conventional categories," said Otello Stampacchia, Ph.D., Managing Director of Omega Funds. "Fund VI builds on our modus operandi aimed at investing in and, in many cases, actively combining innovative science with exceptional founders and company builders."

Fund VI is stage-agnostic and is expected to be deployed across companies in the U.S. and Europe. Similar to past funds, Fund VI investments will include a variety of investment approaches, from company founding and creation to early venture rounds and late-stage public investing, as well as direct secondary transactions.

"We believe this is the most exciting time to be investing in life sciences in a generation, but it requires diverse skills to capture the opportunity set," added Dr. Stampacchia. "At Omega, we have thoughtfully assembled a team that has the experience, insights and connections needed to successfully identify and harvest innovation from both sides of the Atlantic."

Omega Funds also announced today that industry veteran Bernard Davitian will be joining the firm as a Partner, beginning January 2020. Recent additions to the Omega Funds team also include Deirdre Cunnane, J.D., who joined as Chief Operating Officer and General Counsel in October 2019, as well as Paulina Hill, Ph.D., who joined as Principal, and Katie Kerfoot, who joined as head of Investor Relations, both of whom joined in January 2019.

Mr. Davitian has extensive experience in the life sciences and biotech industry, marked by a number of successful transactions involving financings and M&A. He previously served as SVP and Managing Director at Sanofi Ventures, having first joined Sanofi in 2010 as Vice President, Deputy Global Head, Business Development. Prior to Sanofi, Mr. Davitian held leadership roles at Fovea Pharmaceuticals, which was sold to Sanofi in 2009 in a €370 million cash transaction, Neurotech Pharmaceuticals, Transgene, which successfully raised $100 million in a 1998 IPO on the NASDAQ and EuroNext, as well as Institut Mérieux (now Sanofi Pasteur).

Ms. Cunnane, COO & GC, has held similar roles both in venture funds and within a biotech company. She joins Omega Funds from Catabasis Pharmaceuticals, a publicly traded biotech company where she held various leadership positions over the past four years. Prior to joining Catabasis, Ms. Cunnane served as General Counsel at Advanced Technology Ventures and Lightstone Ventures.

Prior to joining Omega Funds, Dr. Hill was on the healthcare team at Polaris Partners since 2012. She completed her postdoctoral fellowship in Robert Langer’s lab in the Chemical Engineering department at the Massachusetts Institute of Technology and earned her Ph.D. in Molecular Medicine from the Wake Forest University School of Medicine.

Ms. Kerfoot joined Omega Funds to lead the firm’s communications strategy and investor relations initiatives, including marketing and fundraising. Prior to joining Omega Funds, she covered specialty pharmaceutical companies as an equity research analyst at Wells Fargo Securities and BMO Capital Markets in New York. Ms. Kerfoot has an extensive journalism background, including on-air reporting with an NBC-affiliate local news station and a national online news network.

On December 11, 2019 Kite, a Gilead Company (Nasdaq: GILD), reported that it has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for the investigational chimeric antigen receptor (CAR) T cell therapy, KTE-X19, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) (Press release, Kite Pharma, DEC 11, 2019, View Source [SID1234552275]).

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The BLA submission is based on data from the Phase 2 ZUMA-2 trial, which demonstrated an overall response rate of 93 percent, including 67 percent with complete response, as assessed by an Independent Radiologic Review Committee (IRRC) following a single infusion of KTE-X19. In the safety analysis, Grade 3 or higher cytokine release syndrome (CRS) and neurologic events were seen in 15 percent and 31 percent of patients, respectively. No Grade 5 CRS or neurologic events occurred. Detailed findings from this trial were recently presented at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in Orlando.

"There remains a significant need for new treatments for patients with relapsed/refractory MCL despite recent advances, so this regulatory filing is an especially important milestone for the MCL community," said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. "We look forward to working with the FDA to bring KTE-X19 to appropriate patients as quickly as possible and continuing to deliver on the promise of our industry-leading cell therapy development program with a second CAR T therapy."

Kite plans to submit a Marketing Authorization Application for KTE-X19 in the European Union in early 2020. KTE-X19 has been granted Breakthrough Therapy Designation (BTD) by the FDA and Priority Medicines (PRIME) by the European Medicines Agency (EMA) for relapsed or refractory MCL.

KTE-X19 is investigational and not approved anywhere globally. Its efficacy and safety have not been established. More information about clinical trials with KTE-X19 is available at www.clinicaltrials.gov.

About MCL

MCL is a rare form of non-Hodgkin lymphoma (NHL) that arises from cells originating in the "mantle zone" of the lymph node and typically affects men over the age of 60.

About ZUMA-2

ZUMA-2 is a single-arm, multicenter, open-label Phase 2 study involving 74 enrolled/leukapheresed adult patients (≥18 years old) with MCL whose disease is refractory to or has relapsed following up to five prior lines of therapy, including anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy and the BTK inhibitors ibrutinib or acalabrutinib. The objectives of the study are to evaluate the efficacy (60 patients) and safety (68 patients) after a single infusion of KTE-X19 in this patient population. The primary endpoint for the study is objective response rate (ORR). ORR in this trial is defined as the combined rate of complete responses and partial responses as assessed by an IRRC.

Secondary endpoints include duration of response, progression-free survival, overall survival, incidence of adverse events, incidence of anti-CD19 CAR antibodies, levels of anti-CD19 CAR T cells in blood, levels of cytokines in serum, and changes over time in the EQ-5D scale score and visual analogue scale score. The study is ongoing.

About KTE-X19

KTE-X19 is an investigational, autologous, anti-CD19 CAR T cell therapy. KTE-X19 uses the XLP manufacturing process that includes T-cell selection and lymphocyte enrichment. Lymphocyte enrichment is a necessary step in certain B-cell malignancies with evidence of circulating lymphoblasts. KTE-X19 is currently in Phase 1/2 trials in acute lymphoblastic leukemia (ALL), mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).

On December 11, 2019 BioInvent International AB (publ) (OMXS: BINV), a biotech company focused on the discovery and development of novel and first-in-class immuno-modulatory antibodies for cancer immunotherapy, and Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, reported compelling results from extensive in vitro and in vivo preclinical studies with BT-001, an oncolytic virus (OV) expressing an anti-CTLA4 antibody and the cytokine GM-CSF (Press release, BioInvent, DEC 11, 2019, View Source [SID1234552260]).

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BT-001 is a multifunctional OV being co-developed by Transgene and BioInvent. It was generated using Transgene’s Invir.IO platform and its patented large capacity VVcopTK-RR- oncolytic virus, which has been designed to encode for a Treg-depleting anti-CTLA4 antibody derived from BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms as well as the cytokine GM-CSF.

The therapeutic activity was assessed in several immunocompetent preclinical models, showing outstanding antitumoral activity for BT-001 murine surrogate antibody-encoding viruses conferring cures in a majority of mice transplanted with different solid cancer tumors (> 70% in all tested models).

– The new preclinical data also confirmed that the anti-CTLA4 antibody expressed by BT-001 in mouse tumor cells retained biochemical integrity and folding, functionality, and biological activity.

– In addition, BT-001’s biodistribution profile demonstrated higher concentration and prolonged activity of the anti-CTLA4 antibodies in tumors compared to intravenous anti-CTLA-4 antibody therapy.

A comprehensive and detailed package of preclinical data on BT-001 will be presented at scientific meetings in the coming months.

BioInvent and Transgene confirm that they intend to submit a clinical trial application in the first half of 2020 to conduct a first-in-human trial with BT-001 in Europe and in the USA.

"With BT-001, we build on the success of three clinically validated axes of activating patients own immune defense to combat cancer – anti-CTLA-4, anti-PD-1/PD-L1, and oncoviral immunotherapy. We are excited to bring forward to clinical testing our antibody-encoding oncolytic virus, which has indicated synergistic activity and potential for significantly improved tolerability compared to available anti-PD-1/anti-CTLA-4 combination therapy," said Björn Frendéus, Ph.D., Chief Scientific Officer of BioInvent.

"Thanks to the fruitful collaboration between Transgene and BioInvent, we have been able to generate these exciting preclinical data with BT-001. We have confirmed that BT-001 is able to replicate within cancer cells in immunocompetent models, and locally produce high and long-lasting concentrations of both anti-CTLA4 antibody and GM-CSF, leading to the destruction of the tumor. Based on these data, we are optimistic that upcoming clinical trials with BT-001 will deliver improved efficacy while minimizing the adverse events that have been associated with this class of immune checkpoint inhibitor," said Éric Quéméneur, Pharm.D., Ph.D., Executive VP, Chief Scientific Officer of Transgene.