On February 5, 2015 Biota Pharmaceuticals, Inc. (NASDAQ: BOTA) reported its financial results for the three month period ended December 31, 2015, which is the second quarter of the Company’s 2016 fiscal year, and also provided an update on recent corporate developments (Filing, 8-K, Nabi Biopharmaceuticals, FEB 5, 2016, View Source [SID:1234508985]).

"I am very pleased today to report that significant progress is being made with our antiviral pipeline for respiratory indications and we remain on track to have Phase 2 data readouts in the second half of the year from both the HRV and RSV programs. Our oral RSV fusion inhibitor, BTA585, successfully completed a robust Phase 1 single ascending dose study showing a favorable safety and pharmacokinetic profile. We are nearing completion of the Phase 1 multiple ascending dose study and plan to initiate the Phase 2 RSV challenge study next quarter. Additionally we are progressing with enrollment in the Phase 2b SPIRITUS trial of vapendavir and anticipate top-line data in the second half of this year. Not only is this our lead program but it is the most advanced direct-acting antiviral in the field targeting HRV and has the potential to treat problematic upper respiratory infections in the almost 11 million moderate-to-severe asthmatics in the U.S.," stated Joseph M. Patti, PhD, president and chief executive officer at Biota Pharmaceuticals.

"I am glad to report that we have begun screening patients for the Phase 2 study of BTA074, our first-in-class direct-acting antiviral for the treatment of condyloma caused by HPV types 6 & 11, which is the most common manifestation of HPV infection and also the most common sexually-transmitted viral disease worldwide. Current topical treatments do not act on the virus directly so there is a need for a therapy with improved efficacy and reduced local skin reactions to address this contagious infection."

Recent Highlights
Announced positive Phase 1 data for BTA585. The top-line results were from a blinded, placebo-controlled single ascending dose study, which tested doses of up to 800 mg of BTA585, an oral fusion inhibitor in development for the treatment and prevention of respiratory syncytial virus (RSV) infections. Findings included:

● No serious or severe adverse events

● Low incidence of adverse events

● Pharmacokinetic (PK) data demonstrated that all doses of 100 mg or greater achieved BTA585 plasma levels that exceeded the mean EC50 of RSV clinical isolates for 24 hours. The EC50 represents the concentration of drug that is required for 50% inhibition of viral replication in vitro

● BTA585 plasma Cmax was rapidly achieved at approximately one hour following oral dosing and the half-life (T1/2) was approximately five to six hours across the dose range

● Dosing of BTA585 with a high fat meal did not adversely affect the PK

Commenced dosing in Phase 1 multiple ascending dose (MAD) study of BTA585. This study will evaluate the safety and PK of BTA585 in healthy volunteers following seven days of oral dosing. Top-line data is anticipated to be available in the first quarter of 2016.

Enrollment on track for Phase 2b SPIRITUS trial for vapendavir. Top-line data are expected in the second half of 2016 from the multi-center, randomized, double-blind, placebo-controlled dose-ranging study in moderate-to-severe adult asthmatics with symptomatic human rhinovirus (HRV) and a history of asthma exacerbation from colds.

Corporate Updates

Appointed Mark P. Colonnese as Executive Vice President and Chief Financial Officer on November 2, 2015. The Company announced the appointment of Mark Colonnese as Executive Vice President and Chief Financial Officer. Mr. Colonnese has held a number of senior executive positions in the pharmaceutical industry and, most recently, was Chief Financial Officer of Stealth BioTherapeutics, Inc.

Financial Results for the Three Month Period Ended December 31, 2015

The Company reported a net loss of $6.5 million for the three month period ended December 31, 2015, as compared to net income of $6.5 million in the same quarter of the prior fiscal year. Basic and diluted net loss per share was $0.17 for the three month period ended December 31, 2015, as compared to a basic and diluted net income per share of $0.19 in the same period of 2014.

Revenue decreased to $1.7 million for the three month period ended December 31, 2015 from $13.9 million in the same period in 2014 due to a $4.8 million decrease in royalty revenues, related to a larger Relenza government stockpile order received in the prior year, as well as lower seasonal sales of Relenza and Inavir reflecting an earlier than normal flu season in 2014, and $7.4 million decrease in revenue from services as a result of the termination of the Company’s contract with BARDA in 2014.

Cost of revenue decreased to zero for the three month period ended December 31, 2015 from $1.6 million in the same period last year due to the termination of the Company’s contract with BARDA in 2014.

Research and development expense increased to $6.3 million for the three month period ended December 31, 2015 from $4.8 million in the same period in 2014. The $1.5 million increase was the result of a $2.8 million increase in clinical costs related to the ongoing Phase 2b SPIRITUS trial for vapendavir; the Phase 1 SAD and MAD trials for BTA585; and startup expenses for the Phase 2 trial for BTA074. These costs were offset in part by a $0.8 million decrease in compensation expenses and a decrease of $0.5 million in depreciation and facility related expenses associated with the closure of the Company’s early-stage research facility in March 2015.

General and administrative expense decreased to $2.1 million for the three month period ended December 31, 2015 from $2.6 million in the same period in 2014, due largely to lower compensation expenses as a result of administrative staff reductions related to the facility closure in March 2015.

The Company held $57.2 million in cash, cash equivalents, and short and long-term investments as of December 31, 2015.

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(Filing, 10-Q, ImmunoGen, FEB 4, 2016, View Source [SID:1234508974])

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Summary
The formation of new blood vessels by angiogenesis is a key feature of number of diseases including Age-related Macular Degeneration (AMD), Proliferative Diabetic Retinopathy (PDR), atherosclerosis, rheumatoid arthritis and cancer (Press release, UCLB, FEB 4, 2016, View Source [SID:1234508995]). Vascular Endothelial Growth Factors (VEGFs) and their receptors have been previously identified as targets for therapy of these diseases but their success in human therapy is limited with adverse side effects upon long term use.
Researchers at UCL Institute of Ophthalmology have now identified a novel protein Lrg1 which acts in the pathogenic angiogenesis pathway. An antibody therapy has been developed against Lrg1 and is currently in pre-clinical development.

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The Technology and its Advantages
Researchers at UCL Institute of Ophthalmology have identified Lrg1 (leucine-rich alpha-2-glycoprotein-1) as a player in angiogenesis, tumour development, migration and aberrant scaring. Lrg1 is a secreted glycoprotein that stimulates angiogenesis by modulating the activity of TGFß. UCL researchers showed that antibodies against Lrg1 block lesion formation in the mouse model of laser-induced choroidal neovascularisation (CNV) (Wang et al., 2013, Nature, 499(7458):306-11). Significantly, in the mouse model of oxygen-induced retinopathy they observed that Lrg1 is involved specifically in the development of pathological vascular tufts, but not the normal vessel growth that occurs during the revascularisation phase. Collectively, these data revealed that Lrg1 is required for pathological angiogenesis, identifying Lrg1 as a therapeutic target for diseases such as wet AMD and cancer, in which aberrant blood vessel growth occurs.

The team developed a series of monoclonal antibodies against Lrg1. The lead candidate has been humanised and de-immunised and funding has been secured to develop the CMC process to GMP standards, perform pre-clinical toxicology studies and Phase IIa trial.

Targeting Lrg1 offers an alternative over currently used anti-VEGFs. These compounds have efficacy in wet AMD, diabetic retinopathy and cancer, but there is a significant fraction of patients who either fail to respond to VEGF blockade or who become refractory. The currently used VEGF blockers are known to have adverse effects in ocular indications, most likely because VEGF has a homeostatic role in neuronal cells, and this may limit long-term drug administration. In cancer, systemic administration of Avastin is associated with an increased risk of cardiovascular events, haemorrhage and stroke.

Market Opportunity
Currently the anti-angiogenic therapeutic market is dominated by the anti-VEGFs, in particular Avastin, Lucentis and Eylea.
Although Wet AMD, which results from the abnormal growth of blood vessels accounts for only 10-15% of all AMD cases, it is responsible for more than 80% of AMD-related vision loss. Datamonitor Healthcare estimates that sales of drugs for wet AMD across the US and five major EU markets (France, Germany, Italy, Spain, and the UK) will reach almost $5.8bn by 2023.
Diabetic retinopathy is the leading cause of blindness in adults of working age affecting 11.5M people in the seven major markets in 2010. According to Grand View Research Inc, global DR market is expected to reach $10.11bn by 2022.
Global cancer prevalence is driven by the aging population and even though cancer is not a single, homogenous disease, TGFß has been implicated in many cancer types – making this therapeutic approach suitable for many cancer indications. The global market for cancer is expected to reach $147bn by 2018, according to a report by the IMS Institute for Healthcare Informatics.
Collectively these three main indications for which Lrg1 antagonists could be used can be estimated to achieve ca. $160bn market potential.

On February 3, 2016 Advaxis, Inc. (NASDAQ: ADXS), a clinical stage biotechnology company developing cancer immunotherapies, reported that it has entered into a co-development and commercialization agreement with Especificos Stendhal SA de CV ("Stendhal"), for Advaxis’ lead Lm Technology immunotherapy, axalimogene filolisbac (ADXS-HPV), in HPV-associated cancers (Filing, 8-K, Advaxis, FEB 4, 2016, View Source [SID:1234508970]). Stendhal is a privately held Latin American specialty pharmaceutical company that partners with leading drug companies to deliver effective solutions for life-threatening diseases in Latin American markets.

Under the terms of the Agreement, Stendhal will pay $10 million toward the expenses of AIM2CERV, a planned global Phase 3 clinical trial in women with high-risk, locally advanced cervical cancer. This payment covers a significant portion of the total planned study costs. Stendhal will also work with Advaxis to complete the clinical trial of axalimogene filolisbac in Mexico, Brazil, Colombia, and other investigational sites in Latin American countries. Additionally, Stendhal will manage the regulatory approval process, promotion, commercialization and market access for axalimogene filolisbac in these markets. Advaxis and Stendhal will share profits on a pre-determined basis.

Stendhal has a long history of partnering with leading pharmaceutical companies to bring therapies for HIV, infectious disease, and neurologic and cardiovascular disease to its Latin American markets. This new partnership with Advaxis will expand its growing portfolio in oncology and is one of the first of its kind in Latin America to make cancer immunotherapies available in the region.

HPV-related cancer is a looming public health issue in Latin America. According to the World Health Organization, cervical cancer mortality rates are three times higher in Latin America and the Caribbean than in North America. More than 83,000 women are diagnosed annually and, without intervention, mortality is projected to increase to 45 percent by 2030. HPV is also prevalent in 90.4 percent of anal cancer in Latin America and the Caribbean.

"We’re pleased to announce our agreement with Stendhal, which enables us to greatly expand the clinical program for, and the potential impact of, axalimogene filolisbac in HPV-related cancers," said Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. "We now have the potential to address an important unmet medical need in an area of the world where the rate of HPV-associated cancers is unfortunately extremely high."

"Our mission is to bring new treatments to Latin America and ensure that patients have access to therapies that have the potential to save their lives. Women throughout our region are facing increasing rates of HPV and the burden of cervical cancer," said Carlos Arenas, Chief Executive Officer of Stendhal. "It is through partnerships such as this one that we can alter the course of disease and address the health inequalities many in Latin America face."

About Cervical Cancer

Cervical cancer is the fourth most common cancer in women worldwide. In the U.S., nearly 13,000 new cases are diagnosed annually and approximately 4,100 deaths are reported because of cervical cancer. According to the WHO/ICO Information Centre on HPV and Cervical Cancer, about 3.9 percent of women in the U.S. are estimated to harbor high-risk cervical HPV infection at a given time, and 71.7 percent of invasive cervical cancers are attributed to high-risk HPV strains.

About Anal Cancer

Anal cancer is a fairly rare form of cancer in the United States, but the number of new anal cancer cases has been rising for years. The risk of being diagnosed with anal cancer in one’s lifetime is about 1 in 500. According to the American Cancer Society, approximately 7,270 new cases of anal cancer were diagnosed and about 1,010 people died of the disease in 2014.

HPV-Associated Head and Neck Cancers

More than 90 percent of head and neck squamous cell oropharyngeal cancers originate from the mucosal linings of the oral cavity, pharynx, or larynx. Currently, 60 to 80 percent of these cancers are caused by HPV. Head and neck cancers are treated by surgical removal of the cancer and lymph nodes, often followed by radiation and chemotherapy based on the extent of the disease. While patients may achieve good long-term survival, standard treatments can change their physical appearance and are associated with significant short and long-term toxicities which may interfere with salivary gland function, taste, smell, and the ability to swallow.

The incidence of HPV-associated head and neck cancers has been increasing at an epidemic rate, while head and neck cancers from other causes have been decreasing. According to the WHO, approximately 15 to 20 percent of the 400,000 new cases of head and neck cancer are HPV-related. In the US, there are about 12,000 new cases of HPV-associated head and neck cancer per year and it affects men about 3 times more frequently than women. HPV-associated head and neck cancer is growing fastest in developed countries like the U.S.

About Axalimogene Filolisbac

Axalimogene filolisbac (ADXS-HPV) is Advaxis’ lead Lm Technology immunotherapy candidate for the treatment of HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, axalimogene filolisbac showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology. Axalimogene filolisbac has Orphan Drug Designation in the U.S. for the treatment of anal cancer.

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