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.

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 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, reported financial results for the third quarter ended September 30, 2019 and provided an update on recent operational and business progress (Press release, RAPT Therapeutics, DEC 11, 2019, View Source [SID1234552256]).

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"We are pleased to report significant progress as a public company following our initial public offering," said Brian Wong, M.D., Ph.D., President and CEO of RAPT Therapeutics. "This includes clinical and operational advancement of our two lead compounds, FLX475 for oncology and RPT193 for allergic inflammatory disease. We recently announced a collaboration with Hanmi for FLX475 in Asia, a region with a high prevalence of ‘charged’ tumors. As we look toward 2020, we expect to report clinical proof of concept data for each program as we reach milestone events in our ongoing clinical trials."

Recent Highlights

Signed a license and collaboration agreement with Hanmi Pharmaceutical Co., LTD for the development and commercialization of FLX475 in Korea and China, including Taiwan and Hong Kong. RAPT will receive $10 million in an upfront payment and near-term milestone payment, and will receive up to $48 million in success-based development milestones and up to $60 million in potential sales milestones, as well as double-digit royalties on any future sales of FLX475 in the specified territories. In addition to leveraging its clinical trial infrastructure in Korea and China to augment RAPT’s ongoing Phase 1/2 clinical study of FLX475, Hanmi will conduct a Phase 2 clinical trial in Korea and China to evaluate FLX475 in patients with gastric cancer.

Continued enrolling patients with "charged" tumors in a Phase 1/2 study of FLX475 as a monotherapy and in combination with pembrolizumab.

Initiated a first-in-human Phase 1 study of RPT193, a CCR4 antagonist to treat allergic inflammatory diseases, including atopic dermatitis.

Completed its initial public offering (IPO), raising $33.8 million in net proceeds, which includes the underwriters’ exercise of their overallotment option to purchase additional shares at the IPO price. The Company’s stock commenced trading on the Nasdaq Global Select Market under the ticker symbol "RAPT."

Appointed Rodney Young as Chief Financial Officer.

Appointed Wendye Robbins, M.D., President and CEO of Blade Therapeutics, and Mary Ann Gray, Ph.D., President of Gray Strategic Advisors, LLC, to the Board of Directors.

Financial Results for the Third Quarter and Nine Months Ended September 30, 2019

Third Quarter ended September 30, 2019

Net loss for the third quarter of 2019 was $10.0 million, compared to $10.3 million for the third quarter of 2018.

Research and development expenses for the third quarter of 2019 were $8.6 million, compared to $9.2 million for the same period in 2018. The decrease was primarily due to decreases in costs relating to the clinical development of FLX475, outsourced research and development, and lab supplies, offset by increases in costs relating to the clinical development of RPT193 and personnel.

General and administrative expenses for the third quarter of 2019 were $1.7 million, compared to $1.4 million for the same period in 2018.

Nine Months Ended September 30, 2019

Net loss for the nine months ended September 30, 2019 was $29.8 million, compared to $26.7 million for the same period in 2018.

Research and development expenses for the nine months ended September 30, 2019 were $24.7 million, compared to $23.4 million for the same period in 2018. The increase was primarily due to increases in costs relating to the clinical development of RPT193, facilities and personnel, offset by decreases in costs relating to the clinical development of FLX475, lab supplies and outsourced research and development.

General and administrative expenses for the nine months ended September 30, 2019 were $6.1 million, compared to $3.9 million for the same period in 2018. The increase was primarily due to increases in professional service fees related to the Company’s preparation of its initial public offering.

As of September 30, 2019, the Company had cash and cash equivalents of $48.3 million. The Company completed its initial public offering on November 4, 2019 and received net proceeds of approximately $33.8 million, which includes the underwriters’ exercise of the overallotment option.

On December 11, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that results from an ongoing Phase II clinical trial of Puma’s drug neratinib are being presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 11, 2019, View Source [SID1234552255]). The presentation entitled, "Neratinib + trastuzumab + fulvestrant for HER2-mutant, hormone receptor-positive, metastatic breast cancer: updated results from the phase 2 SUMMIT ‘basket’ trial," are being presented at a poster Session by Hans Wildiers, M.D., Ph.D., University Hospitals Leuven, Belgium, an investigator of the trial. A copy of this poster presentation is available on the Puma website

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Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy and is marketed in the United States as NERLYNX (neratinib) tablets. NERLYNX was granted marketing authorization by the European Commission for the extended adjuvant treatment of hormone receptor-positive HER2-positive early stage breast cancer in August 2018.

The Phase II SUMMIT basket trial is an open-label, multicenter, multinational study to evaluate the safety and efficacy of neratinib administered daily to patients who have solid tumors with activating HER2 or HER3 mutations. In the HER2-mutant, HR-positive breast cancer cohort, 28 patients received 240 mg of neratinib daily in combination with trastuzumab and fulvestrant. In this cohort, patients had received a median of 4 prior lines of therapy in the metastatic setting (range 0-10 prior regimens) before entering the trial. All patients had been previously treated with an endocrine agent prior to entering the study, including 17 patients (61%) who had received prior fulvestrant. Further, 15 patients (54%) received prior cyclin-dependent kinase 4/6 (CDK4/6) -inhibitor therapy. Twenty-one patients (75%) had received prior chemotherapy.

The interim efficacy summary of the breast cohort that received neratinib in combination with trastuzumab and fulvestrant showed that for the 17 efficacy evaluable patients, 9 patients (53%) experienced a confirmed objective response, all of which were classified as partial responses, and 10 patients (59%) experienced clinical benefit (clinical benefit is defined as confirmed complete response or partial response or stable disease for at least 24 weeks). The median duration of response has not been reached and the median progression-free survival was 9.8 months. At the time of data cut-off, five patients continued to receive treatment.

The safety profile observed in patients treated with the combination of neratinib plus trastuzumab plus fulvestrant in the SUMMIT study was consistent with that observed previously in metastatic patients with HER2 amplified tumors. All patients received anti-diarrheal prophylaxis with loperamide alone. The interim safety results of the study showed that the most frequently observed adverse event was diarrhea. For the 28 safety evaluable patients enrolled in this cohort, 10 patients (36%) reported grade 3 diarrhea. The median duration of grade 3 diarrhea for those patients was 5.5 days. No patient permanently discontinued neratinib due to diarrhea.

Prof. Dr. Hans Wildiers said, "The combination of neratinib plus trastuzumab plus fulvestrant therapy demonstrates encouraging clinical activity with durable responses in this heavily pretreated metastatic breast cancer patient population with activating HER2 mutations and hormone receptor-positive disease. We look forward to continuing to enroll this cohort of SUMMIT."

Alan H. Auerbach, CEO and President of Puma Biotechnology, added, "We are very pleased with the activity seen with neratinib in combination with trastuzumab and fulvestrant in this cohort of patients with HER2-mutated breast cancer. We are in the process of expanding this HR-positive breast cancer cohort in SUMMIT with the intent of using this data to support future registration. We look forward to enrolling additional patients into this HR-positive breast cancer cohort in order to generate the additional data required to support approval of this combination therapy."

On December 11, 2019 MONALEESA-3 data reported that published in The New England Journal of Medicine (NEJM) shows Kisqali (ribociclib) plus fulvestrant demonstrated a statistically significant improvement in overall survival, with an almost 30% reduction in risk of death compared to fulvestrant alone, in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer1 (Press release, Novartis, DEC 11, 2019, View Source [SID1234552254]). MONALEESA-3 overall survival data were first presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September 2019 (see media release). The NEJM publication includes new analyses confirming overall survival benefit across all patient sub-groups treated with Kisqali plus fulvestrant.

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"These data show that treatment with Kisqali gives women with HR+/HER2- advanced breast cancer a chance for more life – whether they are treatment naïve or have had prior therapy," said Jeff Engelman, MD, PhD, Global Head of Oncology Research, Novartis Institutes for BioMedical Research. "Pre-clinical data show that Kisqali is distinct from other CDK4/6 inhibitors in its ability to more selectively target and inhibit CDK4."

The NEJM publication includes subgroup analyses according to line of therapy:

At 42 months, estimated survival rates among patients who received first-line therapy were 66.9% (95% CI, 58.7 to 73.9) with Kisqali plus fulvestrant vs. 56.3% (95% CI, 44.2 to 66.8) with fulvestrant alone (hazard ratio 0.70; 95% CI, 0.48 to 1.02)
Median overall survival among patients in the early-relapse and second-line subgroup was 40.2 months with Kisqali plus fulvestrant and 32.5 months with fulvestrant alone (hazard ratio, 0.73; 95% CI, 0.53 to 1.00)

A new post-hoc overall survival analysis based on prior endocrine therapy demonstrated that Kisqali plus fulvestrant had a:

36% reduction in risk of death in those who did not receive any previous endocrine therapy in any setting (HR= 0.64);
30% reduction in risk of death in those who were endocrine resistant, defined as progressive disease within the first 6 months of first-line endocrine therapy for advanced breast cancer while on endocrine therapy, or relapse within the first two years of (neo)adjuvant therapy (HR=0.70);
26% reduction in risk of death in those who were endocrine sensitive (HR=0.74).
No new safety signals were observed. The most common grade 3/4 adverse events of special interest observed in patients who received Kisqali plus fulvestrant compared to fulvestrant alone were neutropenia (57.1% vs 0.8%), hepatobiliary toxicity (13.7% vs 5.8%), QTc prolongation (3.1% vs 1.2%), respiratory disorders (2.3% vs 3.3%) and interstitial lung disease (0.2% vs 0%).

The publication of the full data results is available online.

About Kisqali (ribociclib)
Novartis is continuing to reimagine cancer by investigating Kisqali in early breast cancer. The NATALEE study is a Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO)2.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

Kisqali (ribociclib) Important Safety Information
KISQALI (ribociclib) is a prescription medicine used in combination with an aromatase inhibitor as the first hormonal-based therapy to treat pre/perimenopausal and postmenopausal women and in combination with fulvestrant as the first hormonal-based therapy or following disease progression on hormonal therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if KISQALI is safe and effective in children. KISQALI can cause severe or life-threatening inflammation of the lungs. Patients should tell their health care provider right away if they experience breathing problems or chest pains. KISQALI can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. KISQALI is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. KISQALI can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking KISQALI and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking KISQALI, patients should tell their health care provider if they are pregnant, or plan to become pregnant as KISQALI can harm an unborn baby. Females who are able to become pregnant and who take KISQALI should use effective birth control during treatment and for at least 3 weeks after the last dose of KISQALI. Do not breastfeed during treatment with KISQALI and for at least 3 weeks after the last dose of KISQALI. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with KISQALI. Patients should avoid grapefruit or grapefruit juice while taking KISQALI. The most common side effects (incidence ≥20%) include white blood cell count decreases, nausea, infections, tiredness, diarrhea, vomiting, hair loss, headache, constipation, rash, and cough. The most common grade 3/4 side effects (incidence >5%) were low neutrophils, low leukocytes, abnormal liver function tests, and low lymphocytes. Abnormalities were observed in hematology and clinical chemistry laboratory tests.