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 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus"), reported data discussing the immunologic effects of PV-10 on colon cancer cells were presented yesterday at the 11th Annual Academic Surgical Congress in Jacksonville, Florida (Press release, Provectus Pharmaceuticals, FEB 3, 2016, http://www.pvct.com/pressrelease.html?article=20160203.1 [SID:1234508954]).

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The abstract, titled "PV-10 Induces Potent Immunogenic Apoptosis in Colon Cancer Cells," was presented by N. M. Kunda of the University of Illinois at Chicago, Division of Surgical Oncology, Department of Surgery, College of Medicine, Chicago, IL, USA. The research team is led by Dr. A.V. Maker, and co-authors in addition to Drs. Kunda and Maker are: J. Qin, G. Qiao also of UIC, Division of Surgical Oncology, Department of Surgery. The team of authors also includes B. Prabhakarof the University of Illinois at Chicago, Department of Microbiology & Immunology, College of Medicine, Chicago, IL, USA. Dr. Maker belongs to both Departments.

In the presentation, Dr. Kunda noted that in vitro testing of PV-10 on colon cancer (murine CT-26 cells) showed cytotoxicity consistent with immunogenic apoptosis. Further, he stated that the researchers observed cell arrest, apoptosis, autophagy and endoplasmic reticulum (ER) stress. He concluded that these results are consistent with immunologic cell death caused by PV-10.

Dr. Eric Wachter, CTO of Provectus, said, "The work reported in Dr. Kunda’s presentation further expands our understanding of the mechanism of action of PV-10 as an ablative immunotherapy for solid tumors, and parallels immunologic signaling noted upon ablation of melanoma with PV-10."

On February 3, 2016 MabVax Therapeutics Holdings, Inc. (OTCQB: MBVX), a clinical-stage immuno-oncology drug development company, reported that President and Chief Executive Officer David Hansen is scheduled to present a corporate overview at the 18th Annual BIO CEO & Investor Conference on Tuesday, February 9, 2016, at 10:30 a.m. Eastern time (7:30 a.m. Pacific time) (Press release, MabVax, FEB 3, 2016, View Source [SID:1234508957]). The conference is being held at The Waldorf Astoria New York hotel in New York City.

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"This is an exciting time at MabVax with preparations underway to begin Phase I clinical trials with our fully human antibody product HuMab-5B1 as both a therapeutic agent and a new generation PET scan cancer imaging agent," said David Hansen, MabVax’s President and Chief Executive Officer. "We anticipate reporting an interim safety assessment and determination of a maximum tolerated dose in the therapeutics trial and an initial set of disease images in the imaging trial by mid-year 2016. These near-term interim data could provide additional validation for our proprietary approach to immune-oncology. We look forward to updating investors on our progress and upcoming milestones at this well-attended conference."

A live webcast of the presentation will be available on Company’s website at View Source A replay of the presentation will be available for 90 days.

On February 03, 2016 Immunomedics, Inc., (Nasdaq:IMMU) reported financial results for the second quarter ended December 31, 2015 (Filing, 8-K, Immunomedics, FEB 3, 2016, View Source [SID:1234508963]). The Company also highlighted recent key developments and planned activities for its clinical pipeline.

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Second Quarter Fiscal 2016 Results

Total revenues for the second quarter of fiscal year 2016, which ended on December 31, 2015, were $0.7 million, as compared to total revenues of $1.0 million for the same quarter last fiscal year. The decrease of $0.3 million in total revenues this quarter was primarily the result of $0.2 million lower LeukoScan product sales, due equally to unfavorable currency fluctuations and lower sales volume in Europe, and a $0.1 million decline in research and development revenues from fewer number of government funded research grants.

Total costs and expenses for the current quarter were $16.4 million, as compared to $12.5 million for the same period in 2014, representing an increase of $3.9 million or 31%. This increase was driven primarily by $3.9 million increased research and development expenses from higher product development expenses related to the Phase 3 PANCRIT-1 registration study of yttrium-90-labeled clivatuzumab tetraxetan for the therapy of patients with advanced pancreatic cancer and the Phase 2 antibody-drug conjugates’ clinical trials. The increase in research and development expenses was partially offset by a $0.2 million lowered legal and professional expenses, principally related to the arbitration proceedings with Takeda-Nycomed, which concluded during the 2015 fiscal year.

Interest expense this quarter related to the 4.75% Convertible Senior Notes due 2020 was $1.4 million, which included the amortization of $0.2 million debt issuance costs. There was no interest expense for the same quarter last fiscal year.

An income tax benefit of $3.2 million was recorded during the current quarter, the result of cash proceeds received for the sale of a portion of our New Jersey State tax net operating losses and research and development tax credits. There were no similar tax benefits during the previous quarter.

Net loss attributable to our stockholders this quarter was $13.7 million, or $0.15 per share, compared with a net loss attributable to our stockholders of $11.4 million, or $0.12 per share, for the same quarter in fiscal 2015. The $2.3 million increase in net loss this quarter was primarily due to the increase in research and development expenses and interest expense for the Convertible Senior Notes, which was partially offset by the $3.2 million tax benefits received.

First Half Fiscal 2016 Results

For the first half of fiscal year 2016, total revenues were $1.4 million, as compared to total revenues of $2.1 million for the same period last fiscal year. The decrease of $0.7 million in total revenues was primarily due to a $0.4 million reduction in research and development revenue from a decline in the number of government funded research grants and $0.3 million lowered LeukoScan sales, due to unfavorable currency fluctuations and lower sales volume in Europe.

Total costs and expenses for the six-month period ended December 31, 2015 were $31.2 million, as compared to $26.0 million for the same period in 2014, representing an increase of $5.2 million or 20%. This increase was driven primarily by $7.4 million higher research and development expenses for product development expenses related to the Phase 3 PANCRIT-1 and the Phase 2 antibody-drug conjugates’ clinical trials. The increase in research and development expenses this period was partially offset by the $2.4 million decrease in general and administrative expenses attributable primarily to reduced legal and professional fees related to the arbitration proceedings with Takeda-Nycomed.

Interest expense this period related to the 4.75% Convertible Senior Notes was $2.8 million and included the amortization of $0.4 million debt issuance costs. There was no interest expense for the same period last fiscal year.

An income tax benefit of $3.2 million was recorded for the current period, the result of cash proceeds received for the sale of a portion of our New Jersey State tax net operating losses and research and development tax credits. No tax benefits were received during the previous period.

Net loss attributable to our stockholders this period was $29.1 million, or $0.31 per share. This compares to net loss attributable to our stockholders of $23.8 million, or $0.26 per share, for the same period last fiscal year. The $5.3 million increase in net loss this period was primarily due to increased research and development costs related to clinical trials and interest expense for the Convertible Senior Notes, partially offset by the income tax benefits received and lower legal and professional fees, as described above.

As of December 31, 2015, cash, cash equivalents and marketable securities totaled $76.0 million. On January 21, 2016, the Company received another $1.9 million in proceeds as a result of a second sale of our New Jersey State net operating losses and research and development tax credits.

"The $5.1 million total cash proceeds that the Company received from the State of New Jersey’s Technology Business Tax Certificate Transfer Program has allowed us to continue to advance our key clinical programs according to plan, as exemplified by the recent Special Protocol Assessment for a future Phase 3 trial for sacituzumab govitecan in patients with triple-negative breast cancer," commented Peter P. Pfreundschuh, Vice President Finance and Chief Financial Officer. "We are pleased with the current enrollment into the ongoing pivotal Phase 3 PANCRIT-1 study in patients with advanced pancreatic cancer, which is expected to complete enrollment this calendar year," added Mr. Pfreundschuh.

The Company’s key clinical developments and future planned activities:

Sacituzumab Govitecan (IMMU-132)

The Company has reached agreement with the U.S. Food and Drug Administration regarding a Special Protocol Assessment (SPA) on the design of a Phase 3 trial of sacituzumab govitecan for the treatment of patients with metastatic triple-negative breast cancer.

Improved progression-free survival (PFS) with an interim median PFS of 7.0 months was reported at the 2015 AACR (Free AACR Whitepaper)-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference in patients with triple-negative breast cancer (TNBC) treated with sacituzumab govitecan. (View Source)

Continuing positive results in heavily pretreated, metastatic TNBC were presented in a poster discussion session at the 2015 San Antonio Breast Cancer Symposium in San Antonio, Texas. Interim results included an objective response rate of 31% by RECIST 1.1 in 58 evaluable patients, with 78% of these responding patients confirmed with a follow-up computed tomography scan, including 2 patients with a complete response. (View Source).
IMMU-114

At the 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Orlando, Florida, the Company reported initial results of a Phase 1, first-in-man clinical study of subcutaneous injections of IMMU-114 in patients with relapsed non-Hodgkin lymphoma and chronic lymphocytic leukemia, which showed 50% of patients having objective evidence of treatment activity, including one patient with a complete response. (More information on the results can be assessed at View Source)

On February 3, 2016 Trillium Therapeutics Inc. (NASDAQ:TRIL)(TSX:TR) a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer,reported that it has initiated dosing in its Phase 1 clinical trial of TTI-621 (SIRPaFc), a novel checkpoint inhibitor of the innate immune system, in relapsed or refractory hematologic malignancies (Press release, Trillium Therapeutics, FEB 3, 2016, View Source [SID:1234508969]).

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TTI-621 is an antibody-like fusion protein that blocks the inhibitory activity of CD47, a molecule that is overexpressed by a wide variety of tumors. CD47 binds to SIRPa on macrophages and delivers a "do not eat" signal that inhibits the ability of macrophages to engulf and destroy cancer cells. Preclinical studies have shown that TTI-621 has anti-tumor activity across a range of hematologic tumors.

"This is an exciting time for Trillium as we now emerge as a clinical stage oncology company evaluating a novel immune checkpoint inhibitor," commented Dr. Eric Sievers, Trillium’s Chief Medical Officer. "At a fundamental level, a cancer patient’s ineffective immune response allows the tumor to propagate unchecked. By blocking CD47, a key cell-surface protein that inhibits phagocytosis, we hope to summon a durable anti-tumor response in patients who are beset by cancer."

The two-part clinical trial is designed as a multi-center, open-label Phase 1a/1b trial, evaluating TTI-621 as a single-agent in patients with relapsed or refractory hematologic malignancies. During the dose escalation phase set to enroll up to 36 subjects, the safety, tolerability, pharmacokinetics and pharmacodynamics will be characterized to determine the optimal dose for subsequent enrollment in the expansion phase. In this second part of the trial, the safety and preliminary antitumor activity of TTI-621 at the optimal dose identified in the escalation phase will be explored in 12-15 subjects per hematologic malignancy type: indolent B-cell lymphoma, aggressive B-cell lymphoma, T-cell lymphoma, Hodgkin lymphoma, chronic lymphocytic leukemia, multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome.

Trillium has proposed five trial sites including the Mayo Clinic, Columbia University Medical Center, City of Hope National Medical Center, The Colorado Blood Cancer Institute, and Tennessee Oncology.