On November 9, 2020 AVEO Oncology (Nasdaq: AVEO) reported financial results for the third quarter ended September 30, 2020 and provided a business update (Press release, AVEO, NOV 9, 2020, View Source [SID1234570441]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In advance of the Food and Drug Administration’s (FDA) March 31, 2021 Prescription Drug User Fee Act (PDUFA) target action date for our tivozanib New Drug Application, we are actively building out AVEO’s U.S. commercial infrastructure to support the FDA-pending U.S. launch of tivozanib in relapsed or refractory renal cell carcinoma (RCC)," said Michael Bailey, president and chief executive officer of AVEO. "Market data suggests that a significant and growing demand exists for effective and better tolerated treatment options for these patients. These data also suggest that roughly half of patients currently forego treatment in the third- and fourth-line of treatment.1 We believe tivozanib has the potential to help address some of these challenges and provide patients with a new option for continuing their fight against cancer."

Mr. Bailey added, "Beyond our ongoing development of tivozanib as a potential monotherapy treatment, we are continuing our work in the immunotherapy combination setting as a key area of focus, given tivozanib’s tolerability profile and effects on reducing regulatory T-cells2 to potentially enhance activity of the immune system. In addition, we further enhanced our pipeline by regaining full global rights to our second late-stage asset, ficlatuzumab, and have secured additional manufacturing capacity to enable a potential registrational Phase 3 trial in head and neck squamous cell cancer (HNSCC) in 2022. Finally, we remain on track to file an Investigational New Drug (IND) application by the end of the year for AV-380 for the treatment of cancer cachexia, with a potential Phase 1 study in the first quarter of 2021, following the IND safe to proceed letter."

Tivozanib Updates

Announced Publication of Results from Phase 1b/2 TiNivo Study of Tivozanib in Combination with OPDIVO (nivolumab) in RCC in Annals of Oncology. In November 2020, AVEO announced that previously reported results from the Phase 1b/2 TiNivo study of oral (PO) tivozanib (FOTIVDA), AVEO’s next-generation vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (TKI) drug candidate, in combination with intravenous (IV) nivolumab (OPDIVO, Bristol-Myers Squibb), an immune checkpoint, or PD-1, inhibitor, for the treatment of advanced RCC, were published in Annals of Oncology. The article, titled "TiNivo: Safety and Efficacy of Tivozanib-Nivolumab Combination Therapy in Patients with Metastatic Renal Cell Carcinoma", is available online first via this link.

AVEO is also studying tivozanib in combination with IMFINZI (durvalumab), AstraZeneca’s human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with first-line metastatic hepatocellular carcinoma (HCC) in the Phase 1b/2 DEDUCTIVE clinical trial, which is currently in Phase 2.
Published Final Overall Survival Results from Phase 3 TIVO-3 Study of Tivozanib in RCC in European Urology. In September 2020, AVEO announced that final overall survival (OS) results from its pivotal Phase 3 TIVO-3 study comparing tivozanib to sorafenib in third- and fourth-line RCC were published in the journal European Urology. The article, titled "Final Overall Survival Results from a Phase 3 Study to Compare Tivozanib to Sorafenib as Third- or Fourth-line Therapy in Subjects with Metastatic Renal Cell Carcinoma," is available online via this link.
Preparations Ongoing to Support Commercial Launch of Tivozanib in the U.S. Following the PDUFA Date (March 31, 2021). In preparation for the potential commercial launch of tivozanib in the U.S., the Company continues to expand its sales, marketing, market access and medical affairs teams, and is working to put in place its U.S. distribution capabilities by the end of the year. In connection with these preparations, in October 2020, AVEO announced the appointment of David W. Crist as vice president of sales. Mr. Crist, who brings to AVEO over twenty years of oncology sales experience in both launch-stage and late-stage companies, will be responsible for building out AVEO’s sales force in anticipation of the potential marketing approval and launch of tivozanib in the U.S.
Tivozanib Non-Oncology Partnership Update

$2.8 Million Development Milestone from Kyowa Kirin Co., Ltd. In August 2020, the Company announced that it earned a $2.8 million development milestone payment from partner Kyowa Kirin. The milestone relates to acceptance by the Japanese Pharmaceuticals and Medical Devices Agency of an IND application for a new formulation of tivozanib in a non-oncology indication being developed by Kyowa Kirin.

Under the terms of AVEO’s agreement with Kyowa Kirin, in addition to the 2019 upfront payment of $25 million to AVEO, waiver of AVEO’s obligation to make an $18 million milestone payment upon AVEO gaining U.S. marketing approval of tivozanib for RCC, and the $2.8 million IND development milestone, Kyowa Kirin has also agreed to pay AVEO up to an additional $388 million in potential milestone payments upon the successful achievement of certain development, regulatory, and commercial objectives in non-oncology indications of tivozanib. Kyowa Kirin will also be obligated to make tiered royalty payments on the net sales of a product for these indications, ranging from a high single-digit to low double-digit percent.
Ficlatuzumab Update

Regained Full Global Rights to Ficlatuzumab. In September 2020, AVEO regained full global rights to ficlatuzumab, the Company’s potent hepatocyte growth factor (HGF) inhibitor antibody which binds to the HGF ligand with high affinity and specificity to inhibit HGF/c-Met biological activities. The Company announced plans to fund the clinical manufacture of ficlatuzumab to enable a potential registrational Phase 3 clinical trial in HNSCC, as well as additional potential development in Phase 2 studies in pancreatic cancer and acute myeloid leukemia. Ficlatuzumab is being studied in an ongoing randomized confirmatory Phase 2 study in combination with cetuximab, an EGFR-targeted antibody, in metastatic HNSCC, which is expected to conclude enrollment in the fourth quarter of 2020, with results from the study expected in the middle of 2021. In that timeframe, the Company plans to provide an update on its pivotal program for ficlatuzumab.
AV-380 Update

Company on Track for IND Application Submission by Year-end, with Phase 1 Clinical Study Planned for the First Quarter of 2021. AVEO plans to submit an IND application to the FDA for AV-380, its first-in-class, potent, humanized inhibitory antibody targeting GDF15, for the treatment of cancer cachexia by year-end. Cachexia, a common complication in patients with advanced cancer and other chronic diseases, is a complex metabolic syndrome characterized by malnutrition and severe involuntary weight loss due to the loss of muscle and fat tissue, as well as the clinical manifestation of anemia, inflammation and suppression of immune functions. Preparations for a Phase 1 trial are currently underway.
Corporate Updates

Announced Restructuring of Existing Term Loan with Closing of New Tranched, $35 Million Debt Facility, Potentially Providing for Working Capital into 2022. In August 2020, The Company announced the closing of a tranched, $35 million debt facility with Hercules Capital, Inc. and its affiliates. Under the terms of the agreement, the initial tranche of $15 million fully refinanced AVEO’s existing Hercules term loan facility, which had an outstanding principal amount of approximately $9.7 million, providing net new proceeds of $5.3 million. A second $10 million tranche is contingent upon the approval of the tivozanib New Drug Application by the FDA as a treatment for RCC, and certain other terms and conditions. An additional two $5 million tranches would potentially become available after that time – one if net product revenues of tivozanib reach $20.0 million within a specified time frame, and the other upon the lender’s consent.
A current summary of the Company’s activities and corporate updates is available in AVEO’s corporate presentation available on the investor relations portion of the Company’s website at investor.aveooncology.com.

Third Quarter 2020 Financial Results

AVEO ended Q3 2020 with $68.8 million in cash, cash equivalents and marketable securities as compared with $47.7 million at December 31, 2019.
Total revenue was approximately $3.6 million for Q3 2020 compared with $25.7 million for Q3 2019. The third quarter of 2019 included the $25.0 million upfront payment pursuant to AVEO’s agreement with Kyowa Kirin for non-oncology indications of tivozanib.
Research and development expense for Q3 2020 was $5.9 million compared with $4.0 million for Q3 2019.
General and administrative expense for Q3 2020 was $5.8 million compared with $2.9 million for Q3 2019.
Net loss for Q3 2020 was $8.4 million, or net loss of $0.33 per basic and diluted share, compared with net income of $16.4 million for Q3 2019, or net income of $1.02 per basic and diluted share, respectively.
Financial Guidance

AVEO believes that its $68.8 million in cash, cash equivalents and marketable securities as of September 30, 2020, along with anticipated partnership cost sharing reimbursements, royalties from EUSA’s FOTIVDA sales and, if the pending marketing application for FOTIVDA is approved by the FDA, resulting product revenues upon commercial launch and the potential additional $20 million in credit under the Hercules loan, would allow the Company to fund planned operations into 2022.

In accordance with Accounting Standards Update No. 2014-15, Disclosure of Uncertainties about an Entity’s Ability to Continue as a Going Concern (Accounting Standards Codification Subtopic 205-40), cash flows that are contingent on FDA approval, such as product revenues, cannot be reflected in the going concern assessment. As a result, Hercules loan funding contingent on such approval and revenue is also excluded from the Company’s going concern assessment. Accordingly, the Company continues to have a going concern opinion.

About Tivozanib (FOTIVDA)

Tivozanib is an oral, once-daily, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved as FOTIVDA for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union and other countries in the EUSA territory. 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.3,4 Tivozanib is being studied in the TIVO-3 trial, which is supporting a regulatory submission of tivozanib in the U.S. seeking marketing approval as a treatment for adult patients with relapsed or refractory advanced RCC. Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models2 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC.5 Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers. Tivozanib is also being studied by partner Kyowa Kirin in non-oncology indications.