On November 20, 2017 Eleven Biotherapeutics, Inc. (NASDAQ:EBIO), a late-stage clinical oncology company advancing novel product candidates based on its Targeted Protein Therapeutics (TPTs) platform, reported financial results for the quarter ended September 30, 2017 (Press release, Eleven Biotherapeutics, NOV 20, 2017, View Source [SID1234522156]).

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"I am very pleased with our progress this quarter. In addition to strengthening our balance sheet with a successful public offering in November, we also made strong progress during this quarter on our Phase 3 clinical trial examining Vicinium in patients with non-muscle invasive bladder cancer (NMIBC)," said Stephen Hurly, President and Chief Executive Officer of Eleven Biotherapeutics. "We are driving our Phase 3 enrollment forward and expect to achieve full enrollment in Q1 2018. The Company also remains on track to report top-line three-month data from our registration trial in mid-2018 with sufficient capital to carry us through this critical milestone. Also, we are excited that the combination trial of Vicinium and durvalumab, Astra Zeneca’s checkpoint inhibitor, has opened at the National Cancer Institute and we will be gathering immune biomarker data that we believe will provide insight into the complementary mechanism of action between checkpoint inhibitors and our TPT platform."

Third Quarter Results, Recent Business Highlights and Anticipated Upcoming Milestones:

Vicinium is a single protein anti-epithelial cell adhesion molecule (anti-EpCAM) antibody fragment fused with Pseudomonas Exotoxin A (ETA) that is designed to specifically target and deliver a potent anti-cancer payload directly into tumor cells. Vicinium is currently in a Phase 3 registration clinical trial for the treatment of high-grade NMIBC in subjects who have previously received two courses of Bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. The company also has a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) evaluating Vicinium in combination with AstraZeneca’s checkpoint inhibitor, durvalumab.

In September, the Company announced completion of the manufacturing of Vicinium necessary for the ongoing Phase 3 registration trial in patients with NMIBC, and the CRADA trial with the NCI.
Completion of enrollment for the Phase 3 registration clinical trial of Vicinium is expected in the first quarter of 2018.
Topline three-month data from the Phase 3 registration clinical trial of Vicinium is expected mid-2018 and topline twelve-month data is expected in the second quarter of 2019.
Initiation of a Phase 1 trial of Vicinium and durvalumab through the NCI CRADA will collect immune response biomarker data in patients with NMIBC and is expected to commence in the fourth quarter of 2017, with initial biomarker data expected in the third quarter of 2018.
Corporate:

In October, the Company announced the appointment of Richard F. Fitzgerald as Interim Chief Financial Officer, adding extensive capital raising and transaction execution experience to Eleven’s management team.
In November, the Company completed a public offering of 5,525,000 shares of its common stock, pre-funded warrants to purchase an aggregate of 4,475,000 shares of common stock, and common warrants to purchase up to an aggregate of 10,000,000 shares of common stock, raising approximately $8.0 million in gross proceeds and $7.0 million in net proceeds, after deducting underwriting discounts and commissions and estimated expenses payable by the Company.
TPT Pipeline:

Eleven’s pipeline includes additional locally delivered product candidates, as well as a systemic TPT platform.

Proxinium is a single protein anti-EpCAM antibody fragment fused with ETA for the treatment of late-stage, EpCAM-expressing, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). In Phase 1 and 2 clinical trials, Proxinium demonstrated anti-tumor activity in both injected as well as un-injected tumors. The Company plans to evaluate Proxinium in a Phase 1/2a clinical trial in combination with a checkpoint inhibitor and is actively seeking partners for a combination program.
VB6-845d is a systemically-administered TPT utilizing a proprietary, highly potent, de-immunized plant toxin, deBouganin, for the treatment of solid tumors. The Company plans to file an investigational new drug (IND) application for VB6-845d and initiate a Phase 1 trial, once funding or a partner is secured for this program.
The Company has deferred further development of Proxinium and VB6-84d in order to focus its efforts and resources on the advancement of its Phase 3 registration trial of Vicinium. The Company is also exploring partnering and collaboration strategies to move these additional product candidates forward.

Third Quarter 2017 Financial Results:

Cash Position: Cash and cash equivalents were $11.3 million as of September 30, 2017, compared to $25.3 million as of December 31, 2016. These amounts do not include the approximately $7.0 million of net proceeds from the Company’s November 2017 public offering.
Revenue: Eleven did not record any revenue for the three months ended September 30, 2017, compared to revenue of $28.7 million for the same period in 2016. This decrease was due to revenue recognized in 2016 from the Company’s License Agreement with Roche. The next licensing milestone payment expected from Roche, if any, will be triggered upon commencement of a Phase 2 clinical trial by Roche.
R&D Expenses: Research and development expenses were $3.6 million for the three months ended September 30, 2017, compared to $2.8 million for the same period in 2016. This increase was primarily due to higher costs incurred for the Company’s ongoing Phase 3 clinical trial for NMIBC that were partially offset by the absence of costs associated with the product candidate licensed to Roche in 2016 and lower compensation related costs.
G&A Expenses: General and administrative expenses were $1.6 million for the three months ended September 30, 2017, compared to $6.4 million for the same period in 2016. This decrease was driven primarily by a reduction in severance, retention and stock-based compensation and professional fees related to the Company’s 2016 review of strategic alternatives and the acquisition of Viventia Bio, Inc.
Net Loss: Net loss was $9.1 million, or $0.37 per basic and diluted share, for the three months ended September 30, 2017, compared to net income of $19.5 million, or $0.95 per basic share and $0.91 per diluted share, for the same period in 2016. The change was primarily the result of revenue recognized in 2016 from the Company’s License Agreement with Roche.
Financial Guidance: Based on current operating plans, the Company anticipates that cash at September 30, 2017, plus the net $7.0 million raised in November 2017, will fund research and development programs and operations into mid-2018.

On November 20, 2017 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that new preclinical data for its novel covalent EGFR inhibitor were presented at the Society for Neuro-Oncology 22nd Annual Meeting, November 16-19, in San Francisco (Press release, Trillium Therapeutics, NOV 20, 2017, View Source [SID1234522151]).

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Poster Presentation: TTI-2341: A novel, orally bioavailable, brain-penetrant, covalent epidermal growth factor receptor (EGFR) inhibitor for treatment of glioblastoma multiforme (GBM) and brain metastases of non-small cell lung cancer (NSCLC).

This poster presentation highlighted preclinical data for TTI-2341, a novel covalent EGFR inhibitor. TTI-2341 had potent activity against a broad range of EGFR variants, including disease-relevant mutants T790M and C797S. TTI-2341 was shown to penetrate the blood brain barrier and demonstrated superior ADME properties and oral bioavailability relative to benchmark drugs afatinib and osimertinib. Notably, TTI-2341 achieved greater than 20-fold higher free drug brain exposure compared to osimertinib and was well tolerated at levels expected to be efficacious.

"Aberrant EGFR activity is clearly implicated in CNS tumors, particularly glioblastoma multiforme and brain metastases of non-small cell lung cancer," said Trillium CEO Dr. Niclas Stiernholm. "Currently available EGFR inhibitors have demonstrated limited efficacy due to poor penetration of the blood brain barrier and low activity against resistance-associated EGFR mutations. Our emerging preclinical data suggests that TTI-2341 can overcome these limitations."

On November 20, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported the presentation of data from a Phase 1 study of indoximod, in combination with radiation, for children with progressive brain tumors (Press release, NewLink Genetics, NOV 20, 2017, View Source [SID1234522177]). These data were presented at the Society for NeuroOncology, 22nd Annual Meeting, in San Francisco, CA, on November 19, 2017, by Theodore S. Johnson, M.D., Ph.D., Associate Professor of Pediatrics at Augusta University.

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The presentation entitled, "Radio-chemo-immunotherapy using the IDO-inhibitor indoximod for children with progressive brain tumors in the phase 1 setting" showed the combination of indoximod plus radiation was well-tolerated.

"We are very pleased with early study data combining salvage radiation therapy with indoximod. This combination seems to be well-tolerated in children with recurrent brain tumors, despite their previous treatment with high-dose radiation plans," said Theodore S. Johnson, M.D., Ph.D., Associate Professor of Pediatrics at Augusta University. "We applaud NewLink Genetics for providing access to indoximod for the children enrolling in this first-in-children study."

A link to the presentation slides can be accessed through the NewLink Genetics website at www.NewLinkGenetics.com in the "Investors & Media" section under "Events & Presentations." A second presentation, complete with scan images, given by Dr. Johnson at the Texas Children’s Neuro-oncology Conference on November 10, 2017 can be found listed in the same location on NewLink’s website. Additional information for this study, NLG2105 for pediatric patients with refractory malignant brain tumors, may be found here.

On November 20, 2017 Glactone Pharma reporrted that in strong competition and after external examination, it has been awarded a SEK 886,500 grant (approx. USD 106,000) from Vinnova (Sweden’s Innovation Agency) in the second phase of a program aimed at innovative startup companies (Press release, Glactone Pharma, NOV 20, 2017, View Source [SID1234522150]). The funded project will be used to characterize Glactone Pharma’s lead STAT3 inhibitor, a potential new drug for the treatment of cancers. A STAT3 inhibitor has great potential to address large unmet medical needs and help patients.

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Glactone Pharma’s objective for this project is to generate data on dosing and efficacy in relevant models and to obtain a correlation between pharmacokinetics and pharmacodynamics of the company’s lead compound. Having this data is important for predicting safe and efficacious doses both for non-clinical and clinical studies, thereby increasing the chances of success. STAT3 is a highly promising target in cancer with both preclinical and clinical data supporting the important roles that STAT3 plays in cancer occurrence and progression. Furthermore, STAT3 is involved in mechanisms that enable tumors and cancer cells to evade the immune system. The company’s lead compound has demonstrated the ability to modulate the immune system through STAT3 blockade in a disease model, and thereby acting as a cancer immunotherapy agent.

Immunotherapy is a treatment modality that activates and utilizes the body’s own immune system to recognize and attack tumors and is today the fastest growing and most promising area of cancer research.

Martin Johansson, CEO of Glactone Pharma, says: "The continued development of Glactone Pharma’s STAT3 inhibitor is greatly helped by this funding awarded by Vinnova and we can continue with our focus of bringing a novel drug to the clinic that potentially can help many patients. In addition, the grant is a recognition of the quality of the research that we are conducting at Glactone Pharma."

About STAT3
STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor/signaling protein that is frequently activated in many forms of cancer.

STAT3 plays crucial roles in both tumor cells and in the tumor microenvironment and is a highly promising target for cancer therapy. Direct STAT3 inhibitors have the potential to prevent metastasis, reverse drug resistance and induce apoptosis in cancer cells. Furthermore, STAT3 inhibitors can be combined with immunotherapies to increase response rates and efficacy and with targeted drugs and chemotherapy to reverse and overcome resistance and provide efficacious and safe cancer treatments.

STAT3 is an intractable drug target as it is an intracellular protein with no enzymatic activity and is activated by multiple upstream factors. Despite it not being a "classic drug target", Glactone Pharma has developed orally bioavailable small molecule inhibitors that can directly inhibit the function of STAT3.

On November 20, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the Phase III IMpower150 study met its co-primary endpoint of progression-free survival (PFS) and demonstrated that the combination of TECENTRIQ (atezolizumab) and Avastin (bevacizumab) plus chemotherapy (paclitaxel and carboplatin) provided a statistically significant and clinically meaningful reduction in the risk of disease worsening or death (PFS) compared to Avastin plus chemotherapy in the first-line treatment of people with advanced non-squamous non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, NOV 20, 2017, View Source [SID1234522149]). Initial observations for the co-primary endpoint of overall survival (OS) are encouraging. These data are not fully mature and the next OS analysis is expected in the first half of 2018. Safety for the TECENTRIQ and Avastin plus chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.

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These data will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno Oncology Congress in Geneva, Switzerland in December 2017.

"We are extremely encouraged by these results and will submit these data to health authorities globally with the goal of bringing a potential new standard of care for the initial treatment of lung cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "In addition to first-line NSCLC, we are testing the ability of TECENTRIQ and Avastin to enhance the potential of the immune system to combat a broad range of other cancers."
About the IMpower150 study

IMpower150 is a multicentre, open-label, randomised, controlled Phase III study evaluating the efficacy and safety of TECENTRIQ in combination with chemotherapy (carboplatin and paclitaxel) with or without Avastin in people with stage IV non-squamous NSCLC who had not been treated with chemotherapy for their advanced disease. It enrolled 1,202 people of which those with ALK* and EGFR mutations were excluded from the primary ITT analysis. People were randomised (1:1:1) to receive:

TECENTRIQ plus carboplatin and paclitaxel (Arm A), or
TECENTRIQ and Avastin plus carboplatin and paclitaxel (Arm B), or
Avastin plus carboplatin and paclitaxel (Arm C, control arm).

During the treatment-induction phase, people in Arm A received TECENTRIQ administered intravenously at 1200 mg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. Following the induction phase, people received maintenance treatment with TECENTRIQ (1200 mg every 3 weeks) until loss of clinical benefit or disease progression.

People in Arm B received induction treatment with TECENTRIQ (1200 mg) and Avastin administered intravenously at 15 mg/kg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. People then received maintenance treatment with the TECENTRIQ Avastin regimen until disease progression (Avastin) or loss of clinical benefit/disease progression (TECENTRIQ).

People in Arm C received induction treatment with Avastin administered intravenously at 15 mg/kg plus intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. This was followed by maintenance treatment with Avastin alone until disease progression.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1), and OS. This analysis of the IMpower150 PFS endpoint was only statistically powered to demonstrate a comparison between Arm B versus Arm C.

The primary analysis of the co-primary PFS endpoint in IMpower150 was assessed in two populations: all randomised people without an ALK or EGFR genetic mutation (intention-to-treat wild-type**) and in a subgroup of people who had a specific biomarker (T-effector "Teff" gene signature expression). IMpower150 met its PFS co-primary endpoint per study protocol for both populations assessed.

About NSCLC
Despite recent advances in the treatment of NSCLC, there is still a need for new treatment options. Lung cancer is the leading cause of cancer death globally.1 Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.2 Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.2

About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.
Currently, Roche has eight Phase III lung cancer studies underway, evaluating TECENTRIQ alone or in combination with other medicines.

TECENTRIQ is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Avastin (bevacizumab)
Avastin is a biologic cancer treatment approved in combination with chemotherapy for the first-line treatment of advanced NSCLC and, to-date, has helped over 500,000 patients lead longer lives. Avastin is considered a standard of care for the first-line treatment of advanced NSCLC and has been proven to significantly extend overall survival (OS). Avastin is currently approved in combination with any platinum-based chemotherapy in Europe, and with paclitaxel/carboplatin in the US, in first-line non-squamous NSCLC, based on results of the pivotal Phase III E4599 study. Avastin was the first medicine to help people with previously untreated advanced, non-squamous NSCLC live longer (OS) than one year when added to chemotherapy.
About the TECENTRIQ (atezolizumab) and Avastin (bevacizumab) combination
There is a strong scientific rationale to support the use of TECENTRIQ plus Avastin in combination. The TECENTRIQ and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers, including first-line advanced NSCLC. Avastin, in addition to its established anti-angiogenic effects, may further enhance TECENTRIQ’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.
About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.
By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with TECENTRIQ to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.