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.

lthough emerging immuno-oncology products have been able to elicit unprecedented responses in cancers that are easily accessible to immune cells (eg. leukemia), solid tumors may be resistant to such therapies. 7 Hills is developing cost effective, safe therapeutics to overcome such resistance. Our lead compounds have the potential to increase the antitumor activity of numerous emerging cell-based immunotherapies, and enable the use of recently approved drugs to treat solid tumors that are currently refractory to therapy.

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7HP compounds target validated cell adhesion pathways that are critical for T cell homing to specific tissues. They are the only known activators of both the VLA-4/VCAM-1 and LFA-1/ICAM-1 cell adhesion axes. Activation of these adhesion pathways could significantly increase the trafficking of endogenous effector lymphocytes (targets of checkpoint blockade therapeutics) or adoptively transferred effectors (like CAR-T cells) into solid tumors.

Pre-clinical studies have shown that 7HP lead compounds:

Increase the adhesion of activated T-cells to simulated tumor endothelium by 100 fold,
Increase the penetration of activated T-cells into simulated tumor stroma.

On February 9, 2018 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported that the company will present a company overview at the upcoming 2018 RBC Capital Markets Global Healthcare Conference on Thursday, February 22nd at 2:35 pm ET (Press release, PTC Therapeutics, FEB 9, 2018, View Source [SID1234523882]).

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The presentation will be webcast live on the Events and Presentations page under the investor relations section of PTC Therapeutics’ website at www.ptcbio.com. The presentation will be archived for two weeks following the presentation. It is recommended that users connect to PTC’s website several minutes prior to the start of the webcast to ensure a timely connection.

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 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported financial results for its fiscal 2018 first quarter ended December 31, 2017 (Press release, Arrowhead Research Corporation, FEB 9, 2018, View Source [SID1234523890]). The company is hosting a conference call at 4:30 p.m. EST to discuss results.

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Conference Call and Webcast Details

Investors may access a live audio webcast on the Company’s website at View Source For analysts that wish to participate in the conference call, please dial 855-215-6159 or 315-625-6887 and provide Conference ID 4788374.

A replay of the webcast will be available on the company’s website approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 3 days. To access the audio replay, dial 855-859-2056 or 404-537-3406 and provide Conference ID 4788374.

Selected Fiscal 2018 First Quarter and Recent Events

Filed a Clinical Trial Application for ARO-AAT, a second generation subcutaneously administered clinical candidate for the treatment of alpha-1 antitrypsin deficiency liver disease

Filed a Clinical Trial Application for ARO-HBV, a third generation subcutaneously administered clinical candidate for the treatment of chronic hepatitis B virus infection

Presented new clinical data at HEP DART 2017 demonstrating up to 5.0 log10 reduction in HBV s-antigen and a Sustained Host Response in 50% of hepatitis B patients following RNAi therapy, ARC-520, in the 2001 open-label extension study

Made continued progress on a two-product cardiovascular collaboration with Amgen, in which one that was previously called ARO-LPA against the target lipoprotein(a) has been formally nominated as a potential clinical candidate and which is now referred to as AMG 890 by Amgen

Expanded Arrowhead’s cardiometabolic pipeline, which now includes ARO-APOC3, targeting apolipoprotein C-III, and ARO-ANG3, targeting angiopoietin-like protein 3 (ANGPTL3); with CTA filings planned around the end of 2018

Achieved continued progress with the Company’s extra-hepatic platform and pipeline, including:

ARO-Lung1, Arrowhead’s first candidate against an undisclosed gene target in the lung, which achieved nearly 90% target knockdown following inhaled administration in rodents

ARO-HIF2, the Company’s candidate targeting renal cell carcinoma, which achieved 85% target gene knockdown in a rodent tumor model