On December 11, 2019 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for a Phase 1b adaptive dose-finding clinical study of ARO-HIF2, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with clear cell renal cell carcinoma (ccRCC) (Press release, Arrowhead Pharmaceuticals, DEC 11, 2019, View Source [SID1234552261]).

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Javier San Martin, M.D., chief medical officer at Arrowhead, said: "ARO-HIF2 is Arrowhead’s first TRiM enabled investigational RNAi therapeutic to target a cell type outside of the liver. Clear cell renal cell carcinoma, or ccRCC, is one of the most common forms of kidney cancer. Most patients with ccRCC have a mutation in the Von Hippel-Lindau gene, rendering them unable to degrade HIF-2α, which leads to accumulation during tumor hypoxia and promotes tumor growth. We believe this makes HIF-2α an attractive target for an RNAi-based intervention."

Pending regulatory review, the company intends to initiate AROHIF21001 (NCT04169711), a Phase 1b adaptive design dose-finding clinical study in patients with advanced ccRCC to evaluate the safety of ARO-HIF2 and to determine the recommended Phase 2 dose. Additional secondary objectives include the assessment of pharmacokinetics and efficacy, based on Response Evaluation Criteria in Solid Tumors (RECIST). An exploratory objective for AROHIF21001 will be gene target knockdown using tumor biopsy.

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."