On February 12, 2018 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported that data from an earlier Phase 2 clinical study of axalimogene filolisbac (ADXS11-001) as a treatment for persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC) was accepted for publication in the May edition of peer-reviewed International Journal of Gynecological Cancer (Press release, Advaxis, FEB 12, 2018, View Source [SID1234523905]). The article is titled, "A Randomized Phase 2 Study of ADXS11-001 Listeria monocytogenes-Listeriolysin O Immunotherapy With or Without Cisplatin in Treatment of Advanced Cervical Cancer."

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This multicenter, randomized Phase 2 study conducted in India compared axalimogene filolisbac as a monotherapy with axalimogene filolisbac in combination with chemotherapy (cisplatin) in 110 patients with PRmCC. The primary endpoint was overall survival (OS), and patients were followed every three months for up to 18 months for tumor response and survival status.

The 12-month OS rate was approximately 35% (n = 38/109). Median OS was 8.28 months in the axalimogene filolisbac monotherapy arm and 8.78 months in the combination arm (p=non-significant). Overall, approximately 25% of patients (n = 27/109) reached the 18-month survival milestone. There were 3 confirmed complete responses (RECIST 1.1) and 1 confirmed partial response.

The most commonly reported treatment related adverse events were mild-to-moderate and related to cytokine release symptoms (chills, fever, vomiting and nausea), consistent with the observed safety profile in later clinical studies.

"These compelling results led to the conduct of the Phase 2 GOG-0265 study, where the 12-month OS rate with axalimogene filolisbac was subsequently replicated in a more heavily-pretreated PRmCC population in the U.S. In addition, these data are supportive of our upcoming planned submission of a conditional Marketing Authorization Application with the European Medicines Agency for axalimogene filolisbac for the treatment for metastatic cervical cancer, and give us added confidence in our immunotherapy as a treatment for these patients with limited treatment options," stated Anthony Lombardo, interim Chief Executive Officer of Advaxis.

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack. In a Phase 2 trial evaluating axalimogene filolisbac for the treatment of PRmCC, the product candidate showed a 12-month overall survival rate of 38% observed in 50 patients in the trial. This is a 55% improvement over an expected, model-predicted, 12-month survival rate of 24.5%.

Axalimogene filolisbac has achieved multiple regulatory milestones, including classification as an EMA advanced therapy-medicinal product for the treatment of cervical cancer, receipt of the U.S. Food and Drug Administration (FDA) Fast Track Designation as an adjuvant therapy for treating high-risk, locally advanced cervical cancer (HRLACC), receipt of a Special Protocol Assessment agreement with the FDA for the Phase 3 AIM2CERV trial, and orphan drug designations in three HPV-associated indications (PRmCC, head and neck, and anal cancer).

On February 12, 2018 Clovis Oncology, Inc. (NASDAQ: CLVS) reported its fourth quarter and full year 2017 financial results on Monday, February 26, 2018, after the close of the U.S. financial markets (Press release, Clovis Oncology, FEB 12, 2018, View Source;p=RssLanding&cat=news&id=2331932 [SID1234523909]). Clovis’ senior management will host a conference call and live audio webcast at 4:30 p.m. ET to discuss the company’s results in greater detail.

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The conference call is being webcast and can be accessed from the Clovis Oncology website at www.clovisoncology.com. A replay of the webcast will be available for 30 days.

Conference Call Details

Clovis will hold a conference call to discuss fourth quarter and full year 2017 results on February 26 at 4:30 p.m. ET. The conference call will be simultaneously webcast on the Company’s web site at www.clovisoncology.com, and archived for future review. Dial-in numbers for the conference call are as follows: US participants 866.489.9022, International participants 678.509.7575, conference ID: 3097118.

On February 12, 2018 AVEO Oncology (NASDAQ:AVEO) reported that the United Kingdom’s National Institute for Health and Care Excellence (NICE) has published a Final Appraisal Determination (FAD) recommending FOTIVDA (tivozanib) for the first line treatment of adult patients with advanced renal cell carcinoma (aRCC) (Press release, AVEO, FEB 12, 2018, View Source;p=RssLanding&cat=news&id=2331779 [SID1234523907]). In the European Union, Norway and Iceland, tivozanib is indicated for the first line treatment of adult patients with aRCC and for adult patients who are vascular endothelial growth factor receptor (VEGFR) and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for aRCC.1 Tivozanib is an oral, once-daily, potent and highly-selective vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI).

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EUSA Pharma is the licensee for tivozanib in Europe, North and South Africa, Latin America and Australasia. The positive recommendation triggers a $2M milestone payment to AVEO from EUSA Pharma.

"The recommendation from NICE marks the first European Union reimbursement approval for FOTIVDA, helping ensure broadening patient access to FOTIVDA in key European markets following its launch in Germany in the fall of 2017," said Michael Bailey, president and chief executive officer of AVEO. "This recommendation underscores the strength and commercial-stage value of our partnership with EUSA Pharma, and triggers a $2 million milestone payment to AVEO. We continue to execute on our strategic plans, and we have had a very productive 2018 thus far, with the recent presentation of positive preliminary data from our tivozanib and nivolumab combination TiNivo study in RCC and an investigator sponsored study of tivozanib in liver cancer. We look forward to several potential additional key milestones in 2018, including further EU reimbursement decisions as well as topline data in the second quarter from our Phase 3 TIVO-3 study."

Under the terms of their December 2015 agreement, EUSA Pharma has agreed to pay AVEO up to $386 million in future research and development funding and milestone payments, assuming successful achievement of specified development, regulatory and commercialization objectives, as well as a tiered royalty ranging from a low double-digit up to mid-twenty percent on net sales of tivozanib in the agreement’s territories. Thirty percent of milestone and royalty payments received by AVEO, excluding research and development funding, are due to Kyowa Hakko Kirin (KHK) as a sublicensing fee in Europe. In the United States, the royalty obligation to KHK ranges from the low- to mid-teens on net sales.

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 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.