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Aviragen Therapeutics and Vaxart Enter into Merger Agreement

On October 30, 2017 Aviragen Therapeutics, Inc. (NASDAQ:AVIR), a company focused on the discovery and development of direct-acting antivirals to treat infections that have limited therapeutic options, and Vaxart, Inc., a privately-held, clinical-stage company focused on developing oral recombinant vaccines based on its proprietary delivery platform that allows for administration by tablet rather than by injection, reported that the companies have entered into a definitive merger agreement (Press release, Aviragen Therapeutics, OCT 30, 2017, View Source [SID1234639795]). The merger will result in a combined company, Vaxart, Inc., focused on developing orally-delivered therapeutics and prophylactics to address a variety of viral infections.

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"We are thrilled with the prospect of combining forces with Aviragen, which will create a deep pipeline of antiviral products and allow Vaxart to accelerate development of the promising vaccine candidates that are based on our proprietary oral delivery platform," said Wouter Latour, M.D., Chief Executive Officer of Vaxart. "This transaction gives us the opportunity to build on the positive Phase 2 challenge study results we announced recently for our influenza oral tablet vaccine, as well as the excellent results we obtained in the safety and immunogenicity studies with our norovirus vaccine. Additionally, it will provide us access to Aviragen’s antiviral assets, including their BTA074 Phase 2 program for the treatment of condyloma caused by HPV, which is on track to complete enrollment this quarter and to report top-line safety and efficacy data in the second quarter of 2018."

"We believe our oral vaccine programs are significantly de-risked based on the positive clinical outcome of the BARDA-funded H1N1 influenza Phase 2 challenge study which serves as proof of concept for our technology platform as a whole," continued Latour, "and we look forward to taking our norovirus vaccine into a Phase 2 challenge study next. Norovirus is the leading cause of acute viral gastroenteritis in the United States, causing frequent outbreaks across the population, and we believe our oral tablet vaccine would be the optimal approach to address this unmet medical need."

The Vaxart technology platform has been engineered for the delivery of a wide range of oral vaccines, initially targeting norovirus, human papilloma virus (HPV), respiratory syncytial virus, and influenza, using a convenient and room temperature-stable tablet, which eliminates the need for injection. In clinical studies to date, Vaxart vaccines consistently generated broad systemic and local immune responses that could provide important advantages in preventing infection, as well as robust T cell responses that we believe are essential to obtain a therapeutic benefit in chronic viral infection and cancer.

"After a comprehensive review of strategic alternatives, we are delighted to announce this transaction with Vaxart, which will complement Aviragen’s focus on infectious diseases and position us to create both near and long-term value for our stockholders," said Joseph M. Patti, Ph.D., President and Chief Executive Officer of Aviragen Therapeutics. "Vaxart is well-funded to advance its norovirus and HPV antiviral vaccine programs, and together with BTA074, the combined companies are poised to provide meaningful value-creating data readouts."

Today, Vaxart will be announcing positive results from the company’s Phase 1b open-label, dose-ranging study assessing the safety and immunogenicity of VXA-G1.1-NN, Vaxart’s norovirus oral tablet vaccine, in 60 healthy adult volunteers. VXA-G1.1-NN met both the primary and secondary endpoints for safety and immunogenicity in the clinical trial. Based on the favorable clinical data, a Phase 2 norovirus challenge study is expected to begin in the second half of 2018. To date, Vaxart has dosed more than 300 adult volunteers with its vaccines for norovirus, respiratory syncytial virus and influenza.

About the Transaction

The exchange ratio in the merger agreement was determined by assigning $60 million in value to Aviragen for its financial and clinical assets and $90 million in value for Vaxart’s assets. On a pro forma basis, after giving effect to the number of shares of Aviragen common stock issued in the merger, Vaxart’s securityholders will own approximately 60% of the combined company and Aviragen securityholders will own approximately 40% of the combined company, subject to certain potential adjustments as described in the merger agreement. The transaction has been approved by the board of directors of both companies. The merger is expected to close in the first quarter of 2018, subject to the approval of the stockholders of each company as well as other customary conditions. Wouter Latour, M.D., will serve as Chief Executive Officer of the combined company.

Upon the closing of the transaction, the name of the combined company will become Vaxart, Inc. and shares of the combined are expected to continue trading on NASDAQ under the proposed ticker symbol "VXRT."

Stifel, Nicolaus & Company, Incorporated is acting as financial advisor to Aviragen, and Dechert LLP is serving as legal counsel to Aviragen. Cooley LLP is serving as legal counsel to Vaxart.

Aviragen will reduce its workforce by six to a total of 10 full-time employees, who will remain on board to complete the BTA074 Phase 2 clinical trial and assist with the transition of duties to the Vaxart management team.

Aviragen and Vaxart management will host a conference call this morning, Monday, October 30, 2017 at 8:30 a.m. EDT to discuss the planned merger. To participate in the conference call, please dial (877) 312-5422 (United States) or (253) 237-1122 (international) and refer to conference ID number 6295889. A replay of the conference call can be accessed under the Investors section of Aviragen’s website at www.aviragentherapeutics.com and on the Vaxart website at www.vaxart.com.

10-K/A [Amend] – Annual report [Section 13 and 15(d), not S-K Item 405]

10-Q – Quarterly report [Sections 13 or 15(d)]

Vertex Pharmaceuticals has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Vertex Pharmaceuticals, 2017, OCT 30, 2017, View Source [SID1234521308]).

Xynomic Pharma Acquires Global Rights of Boehringer Ingelheim’s BI 882370, a Novel and Potent RAF Inhibitor against Solid Tumors

On October 30, 2018 Xynomic Pharma, a clinical stage US oncology drug development company, reported that it has acquired exclusive global rights to develop, manufacture and commercialize BI 882370, a 2nd-generation RAF inhibitor, from Boehringer Ingelheim, a top-20 global pharmaceutical company (Press release, Xynomic Pharmaceuticals, OCT 30, 2017, View Source [SID1234527683]). Under the terms of the agreement Xynomic will pay upfront, milestone and royalty payments up to approximately $502 million.

BI 882370 is a potent and selective RAF inhibitor uniquely binding to the DFG-out conformation, whereas marketed BRAF inhibitors occupy the DFG-in conformation. BI 882370 inhibited proliferation of BRAFmut melanoma cell lines with 100x higher potency (EC50 1 – 10 nM) than vemurafenib (VEM), a marketed BRAF inhibitor.

In the colorectal cancer (CRC) animal models, BI 882370 was superior to VEM in both the Colo-205V600V/E model and HT-29V600V/E model. BI 882370 in combination with cetuximab induced tumor regressions in the less sensitive HT-29 model.

In melanoma’s G-361V600V/E model, BI 882370 was superior to VEM, marketed BRAF inhibitor dabrafenib (DAB), marketed MEK inhibitor trametinib (TRA) and DAB-TRA combination. In a second melanoma model A375V600E in which tumors developed resistance to VEM, the TRA-BI 882370 combination demonstrated superior efficacy over TRA-DAB combination.

There were no relevant findings in exploratory toxicology studies at exposures delivering efficacy superior to VEM, DAB and TRA.

"BI 882370, with an impressive efficacy and safety profile demonstrated in animal models, is well positioned to become a best-in-class 2nd-generation Pan-RAF inhibitor for the treatment of B-RAF mutant cancers including CRC and melanoma. We are honored to partner with BI, a global leader in oncology, and will move this asset into clinical testing expeditiously," said Y. Mark Xu, Chairman, CEO and President of Xynomic.

RAF inhibitors have attracted resurged and strong interest in oncology. Compared to 1st-generation, BI 882370 may provide an improved therapeutic window, enabling more pronounced and longer-lasting pathway suppression and thus resulting in improved efficacy.

Xynomic’s pipeline also includes Abexinostat, a potentially best-in-class HDAC inhibitor entering global pivotal Ph 3 trials against Non-Hodgkin’s lymphoma and renal cell carcinoma.

Clinical Data for X4P-001-IO in Combination with Inlyta® (Axitinib) Demonstrated Encouraging Overall Response Rates (Including a Complete Response) and Disease Control Rates in Patients with Clear Cell Renal Cell Carcinoma

On October 30, 2017 X4 Pharmaceuticals, a clinical stage biotechnology company developing a novel CXCR4 inhibitor to improve immune cell trafficking to treat cancer and rare diseases, reported updated results from the Phase 1 part of an ongoing Phase 1/2 study of X4P-001-IO in combination with Inlyta (axitinib) in patients with clear cell renal cell carcinoma (ccRCC) (Press release, X4 Pharmaceuticals, OCT 30, 2017, View Source [SID1234521340]).

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The results in patients with ccRCC who received the combination treatment of X4P-001-IO, a CXCR4 inhibitor, and Inlyta, Pfizer’s VEGFR kinase inhibitor, showed an objective response rate (ORR) of 29%, including 1 patient achieving a confirmed complete response (CR), with an encouraging disease control rate (DCR) of 93%. 31% of patients entering the study had received one prior line of therapy while the majority of patients (69%) had received at least two prior lines of therapy. The data were presented at the 2017 AACR (Free AACR Whitepaper)-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference on October 29 in Philadelphia.

"The combination of CXCR4 inhibition and VEGFR inhibition shows promising clinical results in this very difficult to treat population of patients with ccRCC. These results suggest that X4P-001-IO may address some of the limitations and augment the clinical utility of axitinib, which is a clinically meaningful drug in the treatment of patients with advanced metastatic ccRCC," said Michael Atkins, MD, Deputy Director, Georgetown Lombardi Comprehensive Cancer Center, William M. Scholl Professor of Oncology at Georgetown University School of Medicine, and lead investigator of the study. "These results, while early, are very promising with a strong disease control rate and a manageable safety profile."

Results from the 16 patients with advanced ccRCC enrolled in the dose escalation part of the ongoing Phase 1/2 study as of the data cutoff date of October 2, 2017 were presented and highlights of the poster presentation include:

The combination of X4P-001-IO and Inlyta showed one confirmed complete response (CR) and produced a DCR and ORR of 93 percent (13/14) and 29 percent (4/14), respectively, in the evaluable patient population.
The median duration on treatment at the data cutoff was 22.1 weeks and 44 percent of patients had been exposed to study treatment for at least 24 weeks.
X4P-001-IO in combination with Inlyta was considered to be safe and generally well tolerated. The most frequent treatment-related adverse events (AEs) were hypertension, diarrhea, fatigue, nausea, decreased appetite, headache and dry eye. No grade 4 or 5 AEs were observed.
Pharmacodynamic (PD) measurements demonstrated that the 400 mg dose inhibited the intended target chemokine receptor CXCR4.
Based on the study results, a dose of 400 mg X4P-001-IO once daily with 5 mg Inlyta twice daily has been selected for the Phase 2 portion of the ongoing Phase 1/2 study.
"We are encouraged by the results to date in this first cohort of patients, many of whom have been on study for over six months and have seen early signs of clinical efficacy with manageable side effects," said Sudha Parasuraman, MD, Chief Medical Officer of X4. "We look forward to sharing a comprehensive update on the ongoing Phase 2a clinical trial, as well as the path forward for further development, in 2018."

The Phase 2 portion of the study continues to enroll patients to evaluate the clinical efficacy of X4P-001-IO as measured by objective response rate (ORR), duration of response (DOR), and progression free survival (PFS), as well as explore the correlation of biomarkers with efficacy. (View Source)

About X4P-001-IO in Cancer

X4P-001-IO is an investigational selective, oral, small molecule inhibitor of CXCR4 (C-X-C receptor type 4) that regulates the tumor microenvironment thereby enhancing endogenous anti-tumor responses. CXCR4 is a chemokine receptor that modulates immune function and angiogenesis through the trafficking of key immune cells such as T- cells, dendritic cells, and myeloid derived suppressor cells. CXCR4 signaling is disrupted in a broad range of cancers, facilitating tumor growth by allowing cancer cells to evade immune detection and creating a pro-tumor microenvironment.

About Renal Cell Carcinoma

Kidney cancer is among the ten most common cancers in both men and women with more than 60,000 new diagnoses each year in the United States.1 Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, and advanced ccRCC accounts for approximately 20% of the patient population. Therapies for advanced ccRCC include immunotherapies, mammalian target of rapamycin (mTOR) kinase inhibitors, and angiogenesis inhibitors, such as vascular endothelial growth factor (VEGF) inhibitors.2 There continue to be unmet medical needs with advanced ccRCC because durable responses remain a serious clinical challenge for patients with advanced disease.