On February 10, 2018 AVEO Oncology (NASDAQ: AVEO) and EUSA Pharma reported the presentation of preliminary results from the Phase 2 portion of the TiNivo study, a Phase 1b/2 multicenter trial of oral (PO) tivozanib (FOTIVDA) in combination with intravenous (IV) nivolumab (OPDIVO, Bristol-Myers Squibb), an immune checkpoint, or PD-1, inhibitor, for the treatment of metastatic renal cell carcinoma (mRCC) (Press release, AVEO, FEB 10, 2018, View Source;p=RssLanding&cat=news&id=2331694 [SID1234523891]). The results were presented today at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Genitourinary Cancers Symposium (ASCO GU), in a poster presentation titled "Tivozanib combined with nivolumab: Phase Ib/II study in metastatic renal cell carcinoma (mRCC)" (Abstract 618). A copy of the presentation is available at www.aveooncology.com or further information can be obtained via EUSA Pharma Medical Information.

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The Phase 1/2 study has enrolled a total of 27 patients. The Phase 2 portion of the study (n=21) was designed to assess the safety, tolerability, and anti-tumor activity of the full dose and schedule of PO tivozanib (1.5 mg/QD for 21 days followed by a 7-day rest period), as established in the Phase 1 portion of the study (n=6), in combination with IV nivolumab (240 mg every 2 weeks). The combination was generally well tolerated. Treatment-related Grade 3/4 adverse events occurred in 44% of patients, the most common of which was hypertension.

Preliminary efficacy was assessed in 14 patients treated with the full dose and schedule of PO tivozanib in combination with IV nivolumab and enrolled at least 4 months prior to the data cutoff date. Of these, seven had received at least one prior systemic therapy. An objective response rate was observed in 64% of patients (partial responses), and a disease control rate (partial response + stable disease) was observed in 100% of patients. At the time of data collection, 11 of 14 evaluable patients remained on study.

"These preliminary data continue to support the rationale for choosing a high-specificity VEGF inhibitor TKI, such as tivozanib, in building upon the benefit of immune checkpoint therapy in renal cancer," said Doctor Bernard Escudier, MD, ex-Chairman of the Genitourinary Oncology Committee, Gustave Roussy, and lead investigator of the study. "Combining VEGF TKIs and immune checkpoint inhibitors has been hampered by toxicity, potentially emerging with the use of other TKIs, while minimal off-target toxicities have been observed with tivozanib in this combination. These results open the possibility for triple-combination therapy using tivozanib, nivolumab and ipilimumab, an immune system activator targeting CTLA-4."

"We believe that VEGF TKI-immunotherapy combinations are the obvious next step in the evolution of treatment within mRCC, which underscores the need for a VEGF therapy with best-in-class safety," said Michael Needle, M.D., chief medical officer of AVEO. "The preliminary activity and favorable safety profile observed thus far in the TiNivo study are encouraging and support the further exploration of tivozanib combinations with immuno-oncology therapies. In addition to the TiNivo study, we continue to look forward to topline data in the second quarter of 2018 from our Phase 3 TIVO-3 study, which, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of mRCC, is designed to support a request for regulatory approval of tivozanib in North America as a first and third line treatment for mRCC."

Lee Morley, EUSA Pharma’s Chief Executive Officer said, "We are excited by the continued development potential for tivozanib and the data arising from initial studies in combination with checkpoint inhibitors. As an effective TKI with a favorable tolerability profile, we are already launching tivozanib across the EU in line with its recent approval as monotherapy in the first line setting, and on the basis of the TiNivo study, we look forward to the potential to develop new innovative treatment options for patients in the future."

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models, enabling potentially enhanced activity when used in combination with immune modulating therapy. As part of a North American registration plan, Tivozanib is currently being studied in the Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced RCC. Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal and breast cancers.

On February 9, 2019 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that Susan M. Molineaux, Ph.D, the company’s Founder, President and Chief Executive Officer, will participate in a fireside chat at the Leerink Partners Global Healthcare Conference at 10:00 a.m. ET on Thursday, February 15, 2018 in New York City (Press release, Calithera Biosciences, FEB 9, 2018, View Source [SID1234535246]). The presentation will be webcast live and available for replay for up to 30 days at www.calithera.com in the Investor Relations section

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On February 9, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported preliminary clinical data from patients with urothelial carcinoma (UC) enrolled in an ongoing Phase 1 clinical trial of tislelizumab, an investigational anti-PD-1 antibody, at the 2018 Genitourinary Cancers Symposium in San Francisco (Press release, BeiGene, FEB 9, 2018, View Source;p=RssLanding&cat=news&id=2331663 [SID1234523892]). The preliminary Phase 1 data suggest that tislelizumab was generally well tolerated and exhibited objective responses in patients with UC.

"Tislelizumab administration resulted in objective responses, including a complete response, and a disease-control rate of 53 percent. Tislelizumab was generally well-tolerated in patients with urothelial carcinoma," said Shahneen Sandhu, M.D., medical oncologist at the Peter MacCallum Cancer Center in Melbourne, Australia and lead author. "We are highly encouraged by these results and that further study of tislelizumab may lead to a new treatment for patients with urothelial cancer."

"Tislelizumab is currently being evaluated in five pivotal trials globally and in China, including a pivotal trial in patients with previously treated, PD-L1-positive, locally advanced or metastatic urothelial carcinoma in China. This is the first presentation of tislelizumab data in the population with urothelial cancer, an area of unmet need. We are pleased by these preliminary results, which we believe provide an important foundation for our clinical understanding of tislelizumab’s efficacy and safety in specific patient populations both as a single agent and in combination," commented Amy Peterson, M.D., Chief Medical Officer, Immuno-Oncology, at BeiGene.

Summary of Results from the Ongoing Phase 1 Trial

The multi-center, open-label Phase 1 trial (NCT02407990) of tislelizumab as monotherapy in advanced solid tumors is being conducted in Australia, New Zealand, the United States, Taiwan, and South Korea and consists of dose escalation, schedule expansion, fixed dose expansion, and indication expansion in disease-specific cohorts.

Data presented at the Genitourinary Cancers Symposium included 16 patients with urothelial carcinoma. Of these, 12 had one or more prior systemic anticancer treatment for metastatic disease and the remaining four had progressed after receiving platinum-based regimen in the neoadjuvant or adjuvant setting. In addition, five patients had prior radiotherapy. At the time of the data cutoff on August 28, 2017, median treatment duration was 4.3 months (range of 0.7 to 18.3 months). A total of six patients remained on treatment.

Adverse events (AEs) assessed by the investigator to be related to treatment occurred in 14 patients (88%). Of those, fatigue (31%), rash (19%), infusion related reactions (13%), nausea (13%), pain in extremity (13%), and proteinuria (13%) occurred in more than one patient. All of the treatment-related AEs were grade 1 or 2 except one case each of fatigue, hyperglycemia, and diabetes mellitus. One adverse event of muscle weakness, which was associated with disease progression and occurred more than one month after the last dose of the study drug, had a fatal outcome; this event was considered not related to treatment.

At the time of the data cutoff, 15 patients were evaluable, defined as having a measurable baseline tumor assessment and at least one evaluable post-baseline tumor response assessment, or had progressed or died prior to the initial tumor assessment. One patient had a confirmed complete response (CR), four achieved a confirmed partial response (PR), and three achieved stable disease (SD). Nine evaluable patients had PD-L1 status determined. There was one CR, two PR and one SD among six PD-L1 high patients, and one PR among three PD-L1 low or negative patients.

About Urothelial Carcinoma

Cancer that begins in cells that line the urethra, bladder, ureters, renal pelvis, and some other organs are referred to as urothelial carcinoma.i Urothelial carcinoma is the most common type of bladder cancer and the fifth most common cancer in the United States.ii In 2017, it was estimated that there were 79,030 new cases of bladder cancer and 16,870 deaths.iii

About Tislelizumab

Tislelizumab is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).

On February 9, 2018 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or the "Company"), reported that the Database Safety Monitoring Board ("DSMB") confirmed that the combination of eftilagimod alpha ("efti", "LAG-3Ig", or "IMP321") with pembrolizumab (KEYTRUDA) is safe and well tolerated at doses up to 30 mg per subcutaneous injection (Filing, 6-K, Immutep, FEB 9, 2018, View Source [SID1234523880]).

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In this first-in-man TACTI-mel (Two ACTive Immunotherapies in melanoma) Phase I clinical trial in Australia, efti is combined with pembrolizumab in unresectable or metastatic melanoma patients. The data to date shows no safety concerns from the combination with doses of efti at 1 mg, 6 mg, and 30 mg. No drug related serious adverse events have been reported and the DSMB concluded repeated injections of efti are safe and well tolerated.

The patients eligible to participate in the TACTI-mel Phase I clinical trial are those that have either had a suboptimal response or had disease progression with pembrolizumab monotherapy. In this clinical trial, the combination starts at cycle five of pembrolizumab and is limited to six months of treatment.

Encouraged by the TACTI-mel Phase I clinical trial interim results presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2017 Annual Meeting in November 2017, Immutep now plans to expand the TACTI-mel study by six patients at 30 mg of efti in combination with pembrolizumab starting at cycle one and with a treatment duration of 12 months.

"There is limited clinical experience with combining an APC activator such as efti with an immune checkpoint inhibitor such as pembrolizumab, analogous to pushing the accelerator and also releasing the brakes on cancer-fighting T cells", said Dr. Frédéric Triebel, Immutep’s Chief Scientific and Medical Officer. "Therefore, the TACTI-mel trial design included certain key safety measures such as starting with a low dose and at cycle five, which excludes patients with early severe adverse events to pembrolizumab, and limiting treatment to six months. The positive results now provide the basis to safely extend the clinical trial to start at cycle one with the recommended Phase II dose and for a 12-month duration, meaning patients could benefit earlier and for longer from the combination."

As previously disclosed, all three cohorts of the TACTI-mel Phase I clinical trial totalling 18 patients have been fully recruited and the data from these three cohorts is expected in H1 2018.

On February 9, 2018 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for cancer, respiratory and other diseases, and Seattle Genetics, Inc. (NASDAQ: SGEN), a global biotechnology company developing innovative, targeted therapies for cancer, reported they have entered into a collaboration and license agreement with the goal of developing multiple targeted bispecific immuno-oncology treatments for solid tumors and blood cancers (Press release, Seattle Genetics, FEB 9, 2018, View Source;p=RssLanding&cat=news&id=2331570 [SID1234523875]).

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The collaboration leverages the expertise and core technologies of both companies to develop novel Antibody-Anticalin fusion proteins. Pieris’ proprietary suite of agonistic costimulatory Anticalin proteins, when fused to a tumor-targeting antibody, can activate the immune system preferentially in the tumor microenvironment. Seattle Genetics, through its industry-leading work in the field of antibody-drug conjugates (ADCs), has a substantial portfolio of cancer targets and tumor-specific monoclonal antibodies from which programs will be selected for the collaboration. The bispecific drug candidates in this alliance will be designed to enable the patient’s immune cells to specifically attack tumors.

"As the industry leader in ADCs, we bring deep expertise in targeted cancer therapy development to this collaboration with Pieris," said Dennis Benjamin, Ph.D., Senior Vice President of Research at Seattle Genetics. "Pieris’ Anticalin technology and Antibody-Anticalin bispecific approach are intended to overcome the limitations of currently available immuno-oncology products. This partnership leverages our cancer targets and tumor-specific antibodies to explore multiple novel bispecific combinations, with the goal of developing targeted therapies that improve outcomes for people with cancer."

Under the terms of the agreement, Seattle Genetics will pay Pieris a $30 million upfront fee, tiered royalties on net sales up to low double-digits, and up to $1.2 billion in total success-based payments across three product candidates. The companies will pursue multiple Antibody-Anticalin fusion proteins during the research phase, and Seattle Genetics has the option to select up to three therapeutic programs for further development. Prior to the initiation of a pivotal trial, Pieris may opt into global co-development and US commercialization of the second program and share in global costs and profits on a 50/50 basis. Seattle Genetics will solely develop, fund and commercialize the other two programs.

"Pieris was the first company to bring a tumor-targeted costimulatory bispecific to patients with PRS-343, and we are looking forward to broadening our bispecific pipeline through this alliance. Seattle Genetics is a compelling partner for Pieris with a long-standing commitment to oncology," said Stephen S. Yoder, President and CEO of Pieris. "The collaboration combines the excellent protein engineering and translational capabilities of both companies, utilizing Seattle Genetics’ tumor-targeted monoclonal antibodies and Pieris’ Anticalin proteins to create novel bispecifics. This is our third significant alliance since January 2017 and is in alignment with our goal to create a respiratory- and oncology-focused commercial company."

About Anticalin Therapeutics:

Anticalin proteins are derived from lipocalins, small human proteins that naturally bind, store and transport a wide spectrum of molecules. Anticalin proteins feature the typical four-loop variable region and a rigidly conserved beta-barrel backbone of lipocalins, which, together, form a shapeable cup-like binding pocket. Proprietary to Pieris, Anticalin proteins are a novel class of protein therapeutics validated in the clinic and by partnerships with leading pharmaceutical companies. Anticalin is a registered trademark of Pieris.